Sex-specific differences in nutritional status as risk factors for cognitive decline amongst older adults with Post-COVID Syndrome

Sex-specific differences in nutritional status as risk factors for cognitive decline amongst older adults with Post-COVID Syndrome | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Sex-specific differences in nutritional status as risk factors for cognitive decline amongst older adults with Post-COVID Syndrome Alma L. Guzmán-Gurrola, Laura González-López, Jonathan S. Chávez-Íñiguez, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7520208/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background/Objectives : Post-COVID syndrome (PCS) emerged as a significant public health concern, is characterized by persistent symptoms following SARS-CoV-2 infection. Cognitive impairment is a common sequela, particularly among older adults (OA). Although olfactory dysfunction and malnutrition have been previously associated to cognitive decline, it remains to be elusive to what extent sex-specific variations in these and additional factors will be pivotal to guide targeted interventions in a sex specific manner. This study seeks to identify clinical and biological correlates for cognitive decline in older adults, with emphasis in gender specificity. Methods : We underwent a cross-sectional study among older adults hospitalized at a geriatric care unit. Olfactory function was assessed using the Sniffin' Stick Test. Cognitive impairment was evaluated by the Mini-Mental State Examination, and nutritional status was assessed with the Mini Nutritional Assessment. Statistical analyses included linear regression. Results : A total of 45 patients with PCS were included. Cognitive impairment was observed in 66.7% of participants and was significantly associated with olfactory dysfunction, no direct association was found with nutritional status. However, on a multiple regression analysis, the nutritional status was significantly associated to cognitive decline. Conclusions : Olfactory dysfunction is a potential biomarker for cognitive impairment in older adults with PCS. In our study nutritional status emerged as a crucial factor associated to olfactory dysfunction and cognitive decline with a higher impact on women. Further research is needed to elucidate the underlying mechanisms related to a nutritional decline in older women with olfactory dysfunction and develop targeted interventions to mitigate cognitive decline in this vulnerable population, through improvement in nutrition and olfactory training. olfactory capacity nutritional risk mini nutritional assessment cognitive impairment post-COVID syndrome older adults Figures Figure 1 Figure 2 1. Introduction Post-COVID syndrome (PCS) has emerged as a health problem worldwide, defined by the persistence in symptoms after the acute confirmed infection with SARS-CoV-2 for at least 3 months as a continuous, relapsing/remitting, or progressive disease state [ 1 ] ; it is considered a systemic condition [ 2 ], with an incidence and prevalence of 50% and 45% respectively [ 2 , 3 ]. Common signs and symptoms include fatigue, loss of memory, cognitive impairment, difficulty breathing, thoracic pain, anosmia, ageusia, arthralgias, myalgias and functional impairment [ 4 ]. One of the most distinctive symptoms of SARS-CoV2 infection and the consequent PCS, is the loss in olfactory capacity, affecting 85 to 98% of infected individuals [ 5 – 7 ]. The prevalence of olfactory changes in older adults (OA) is 27%, and occurs more frequently in men [ 8 ]. OA are a vulnerable population due to defects in immune response, typically associated to a high prevalence in cardiorenal metabolic, and geriatric comorbidities; as a result, OA have increased risk for cognitive decline [ 9 ] and malnutrition [ 10 ]. The development of cognitive impairment is of special interest in OA, since it has been a common neuropsychiatric consequence of COVID infection [ 11 – 13 ], believed to appear as result of increased permeability in the encephalic barrier and irreversible neuronal damage [ 14 ], with deterioration in memory function, microvascular endothelial dysfunction, the presence of inflammatory metabolites and beta-amyloid within the brain [ 15 ]. During PCS the development of cognitive impairment is not entirely clear, and the presence of additional sex specific risk factors needs to be addressed [ 16 ]. Multiple investigations regarding sex varieties in post COVID syndrome have shown sex specific risk factors. A large prospective study from the RECOVER consortium (NIH) found that women have a substantially higher risk compared to men, with a relative risk of 1.31; this association was evident across almost all age groups except the youngest (18–39 years) [ 17 ]. Similarly, a systematic review and meta-analysis confirmed that women are 48% more likely to experience persistent symptoms after infection (OR 1.48; 95% CI 1.17–1.86) [ 18 ]. Furthermore, in a Spanish multicenter study, the average number of post-COVID symptoms was higher in women compared to men, and female sex was associated with greater risk of fatigue, dyspnea, physical pain, hair loss, ocular disturbances, depression, and/or sleep disorders [ 19 ]. This gender bias is also reflected in neurological and psychiatric manifestations, with women more frequently reporting headache, sleep disturbances, and cognitive complaints compared to men [ 20 ]. In general, the study of the PCS in OA has been scarcely explored in the literature [ 21 ]. To fill this gap in knowledge, we underwent a cross-sectional study with the purpose of investigating the contribution of sex specific risk factors for the development of cognitive decline during PCS in a cohort of OA hospitalized patients. 2. Materials and Methods 2.1. Study participants. Participants that met the following criteria were included in the study: (1) older adults (OA) hospitalized in a tertiary referral hospital at the geriatric clinic, during the period comprised between August 2023 - August 2024 (2) a confirmed positive test and diagnosis of COVID-19 at least 3 months before the inclusion in our study, and (3) a diagnosis of post-COVID syndrome. OA were excluded if they had a psychiatric condition such as bipolar disorder, schizophrenia, a neurological diagnosis of dementia or an important cognitive impairment to answer questionnaires or impeded to stablish study measurements. The study protocol was designed according to the STROBE [ 22 ] and RECORD guidelines for observational studies [ 23 ] and submitted for IRB approval before patient recruitment. The study was conducted according to the Declaration of Helsinki [ 24 ]. With participants willingly accepting to participate in our study, after signature of the informed consent. 2.2. Study Design. This was a cross-sectional study, performed in a geriatric clinic of a tertiary referral hospital. For all participants, data were collected immediately after hospital admission. 2.3. Study measurements: 2.3.1. Demographic and clinical variables: Demographic and clinical information related to COVID-19 infection and PCS was obtained by automated retrieval from the institutional electronic medical records system. Physical examination, olfactory function, cognitive evaluation, and nutritional evaluation were performed within the first 48 hours of patient hospitalization. 2.3.2. Olfactory functions: To measure olfactory function in our patients, we used the Sniffin’ Stick Test II, which has been previously validated for this purpose [ 25 ]. The capacity for odor identification was evaluated using 12 common odors; the identification of < 9 odors was defined as functional hyposmia and < 6 as anosmia. In each participant, olfactory tests, nutritional status, and cognitive abilities were performed during the same session in a well-ventilated room. First, we evaluated olfactory function, then cognitive abilities, and finally nutritional status. 2.3.3. Cognitive Evaluation: A geriatric cognitive function evaluation, was assessed clinicians attending at the geriatric clinic, with validated instruments available from the National Institute of Geriatrics website [ 26 ]. Cognitive evaluation included the following domains: orientation to time, memory, attention and executive function, assessed with the adapted Spanish version [ 27 ] from the previously published Folstein Mini-Mental State Examination (MMSE) [ 28 ]. Scores ranged from 0 to 30, with lower scores indicating increasing severity of cognitive impairment. Subjects with a score between 0 to 24 were considered at risk for cognitive impairment and individuals who scored > 24 were considered without cognitive impairment. 2.3.4. Nutritional Assessment: Measurements were obtained by a certified geriatric nutritionist, and included, the Mini Nutritional Assessment (MNA®), which has been validated for OA [ 10 ]. The MNA includes anthropometric measurements, a global assessment, a dietary questionnaire and a subjective assessment. According to the developers’ instructions, the MNA administration utilizes a two-step approach: screening and a global assessment. Subsequently, based on the MNA total score, patients are classified as ‘‘malnourished’’ (score 24). The ‘‘global assessment step’’ of the MNA should only be administered to patients not reaching the screening threshold. Additionally, other measurements were added to the nutritional status including height, weight, mid-arm circumference (MAC) and calf circumference (CC). Weight was measured in kilograms, with participants standing up, using a Tanita BC-558 Ironman scale. Height was measured in centimeters with participants placed under the stadiometer, head facing forward, without shoes, and feet together, using a Seca 213 portable stadiometer. Calf circumference CC was measured in centimeters with Lufkin anthropometric tape, at the point where the calf acquires greater volume between the ankle and knee. The mid-arm circumference (MAC) was measured in centimeters with Lufkin's anthropometric tape, performed on the arm bent in a 90º position and with a tape measure at the midpoint between the bony points of the acromion and olecranon. 2.3.5. Statistical Analysis: Categorical variables were presented as frequencies and percentages; continuous variables were expressed as mean ± standard deviation (SD). Inferences for categorical variables were established with the chi squared test. For continuous dependent variables we used single and multiple linear regression models, to establish the association of risk factors for cognitive impairment in post-COVID Syndrome. A p value of < 0.05 was considered significant, we used the software STATA 17 for calculations. 3. Results During the study period a total of 90 patients were hospitalized in our clinic with PCS, main reasons for hospitalization were: upper respiratory tract affection (38%), cerebrovascular or neurological affections (29%), general malaise/fever of unknown origin (15%), GI tract affection/dehydration (13%), and anemia or cardiometabolic alterations (4%). For all hospitalized patients, eligibility was assessed, subjects that met the inclusion criteria were invited to participate in the study (Fig. 1 ). The sociodemographic characteristics of OA are described in Table 1 , divided by the presence of risk for cognitive impairment or cognitive impairment (MMSE < 24); overall, the studied population had an age range from 65 to 89 years old, and 51% of the studied population were female. The more frequent comorbidities included hypertension in 55.6%, Type 2 diabetes (T2D) in 40%, chronic obstructive pulmonary disease (COPD) in 35.6% and chronic kidney disease (CKD) in 22.2%; more than 50% of the studied population had more than 3 comorbidities at the time of the assessment. Table 1 Demographic characteristics of older adults (OS) with Post-COVID syndrome (PCS) divided by the presence of cognitive impairment. Parameter Mean (SD) P value No risk for CI (n = 15) Risk for CI or CI (n = 30) Age, y 75.6 (5.9) 75.9 (6.7) 0.862 Males, No. (%) 9 (60) 13 (43.3) 0.292 Weight, Kg 60.8 (18.4) 67.6 (13.7) 0.169 Height, mt 1.6 (0.09) 1.6 (0.9) 0.212 BMI 23.2 (18.1-26.07) 26.82 (21.8–31.2) 0.057 CC 29.09 (25.7–32.5) 31.45 (28.4–35.0) 0.109 MAC 26.72 (21.3–34) 28.21 (24-30.7) 0.295 Obesity, No. (%) 5 (33.3) 17 (56.7) 0.140 Comorbidities, No. (%) Basic education, 13 (86.7) 20 (80) 0.771 Diabetes 5 (33.3) 13 (43.3) 0.519 Hypertension 8 (53.3) 17 (56.7) 0.832 Kidney Disease 3 (20.0) 7 (23.3) 0.800 COPD 5 (33.3) 11 (36.7) 0.826 > 3 comorbilities 8 (53.3) 18 (60.0) 0.670 Smoker 2 (13.3) 4 (13.3) 1.000 Ex Smoker 4 (26.7) 7 (23.3) 0.806 COVID Symptoms, No. (%) Anosmia 13 (86.7) 26 (86.7) 1.000 Ageusia 9 (60.0) 16 (53.3) 0.671 Fatigue 15 (100) 26 (86.7) 0.138 Memory Problems 6 (40.0) 27 (90.0) < 0.001* Insomnia 12 (80.0) 23 (76.7) 0.800 COVID Severity, No. (%) Hospitalization 9 (60) 15 (50) 0.526 Suplementary 02 8 (53.3) 16 (53.3) 0.920 Intubation 1 (6.7) 1 (3.3) 0.920 Hospital stays days median (ICR) 8 (0–60) 4 (0–15) 0.252 Reinfection COVID 1 (6.7) 2 (6.7) 1.000 Post-COVID Syndrome, days m(SD) 125.8 (77.9) 231.3 (216.1) 0.0751 Tests, Median (ICR) MNA 15.7 (12–17) 20.0 (16.5–24) 0.004* MMSE 26 (25–29) 19 (15–22) < 0.001* SNIFFIN TEST 9 (7–10) 8 (5–10) 0.5124 BMI: Body mass index; CC: calf circumference; MAC: Mean arm circumference; COPD: Chronic Obstructive Pulmonary Disease MNA: Mini-Nutritional Assessment MMSE: Mini-Mental State Examination, ICR interquartile range. With respect to the nutritional status, a total of 23 patients (51%) were in the normal/risk group, and 22 (49%) had malnutrition. Compared to those with a normal/risk nutritional status, those with malnutrition had significantly lower weight (57.0 vs. 73.2 kg), a lower BMI (21.3 vs. 28.1), smaller calf circumference (26.9 vs. 34.0), mid-arm circumference (23.4 vs. 28.8), and a lower MNA score (14.5 vs. 22.4) (p for all < 0.05). The malnutrition group also had a higher frequency of diabetes (22.7% vs. 56.5%). During the acute COVID infection, up to 53.3% required hospitalization during the acute phase of the disease, with a median (ICR) of 5 (0–15) hospital days. Therapy with supplementary oxygen was required by 75.5% and 4% assisted mechanical ventilation. In the post-COVID stage, 77.8% were unable to wean off supplemental oxygen, 86% presented anosmia, 91.1% fatigue, 55.5% ageusia, 73.3% memory problems, and 77.7% insomnia. The average duration of these symptoms was 99.48 ± 128.15 days. With respect to sex specific analysis, the prevalence of cognitive decline was lower in women 13 (59.1%) than in men 17 (73.9%), while the risk of malnutrition was slightly higher for women 12 (52.2%) compared to men 10 (45.5%) (p = 0.652). Even though the MNA was not significantly different in women (18.7 + 4.8) compared to men (18.4 + 4.7) (p = 0.865), we observed that men with cognitive decline had significantly lower BMI (23.3 ± 4.5) compared to women (29.5 ± 6.3) (p < 0.0051), smaller calf circumference (29.4 ± 4.1) in comparison to women (33.0 ± 3.9) (p = 0.0204) and smaller middle upper arm circumference (25.5 ± 3.8) compared to women (30.2 ± 5.5) (p = 0.0177). In women, a wider calf circumference and middle arm circumference, probable associated to the presence of obesity, as well as a lower MNA score were significantly associated with cognitive decline. In men, anthropometric measurements were not found in association with cognitive decline, only a lower MNA score was significantly associated to cognitive decline (Table 2 ) (Located at the end of the manuscript due to its length). Table 2 Gender-specific clinical parameters associated with cognitive decline assessed with mini mental state examination (MMSE). Variable Female (n = 23) P value Male (n = 22) P value No risk for CI (n = 6) Risk for CI or CI (n = 17) No risk for CI (n = 9) Risk for CI or CI (n = 13) Age, y 73.1 ± 3.7 74.7 ± 6.2 0.574 77.3 ± 6.7 77.8 ± 7.1 0.889 Weight, Kg 55.8 ± 22.2 69.5 ± 14.0 0.091 64.1 ± 16.0 65.1 ± 13.3 0.8789 Height, mt 1.5 ± .08 1.5 ± .08 0.776 1.7 ± .05 1.7 ± .04 0.801 BMI 23.3 ± 9.3 29.5 ± 6.3 0.080 23.2 ± 5.7 23.3 ± 4.5 0.959 CC 28.8 ± 4.4 33.0 ± 3.9 0.039* 29.3 ± 5.6 29.4 ± 4.1 0.9607 MAC 24.3 ± 4.8 30.2 ± 5.5 0.031* 28.4 ± 8.0 25.7 ± 3.8 0.3035 Obesity, No. (%) 1 (7) 12 (92) 0.022* 4 (44) 5 (55) 0.779 Comorbidities, No. (%) Basic education 6 (30) 14 (70) 0.270 7 (39) 11 (61) 0.683 Diabetes 2 (17) 10 (83) 0.283 3 (50) 3 (50) 0.595 Hypertension 3 (50) 11 (64.7) 0.526 5 (55.5) 6 (46.1) 0.665 Kidney Disease 3 (50) 2 (11.7) 0.051 0 (0) 5 (38.4) 0.034* COPD 3 (50) 5 (29.4) 0.363 2 (22.2) 6 (46.1) 0.251 > 3 comorbilities Smoker 3 (50) 13 (76.4) 0.420 1 (11.1) 3 (23.0) 0.474 Ex Smoker 1 (16.6) 2 (11.7) 0.759 3 (33.3) 5 (38.4) 0.806 Cardiovascular 3 (50) 13 (76.4) 0.226 7 (77.7) 12 (92.3) 0.329 Autoimmunity 1 (16.6) 3 (17.6) 0.957 0 (0) 3 (23) 0.121 PCS Symptoms, No. (%) Anosmia 6 (32) 13 (68) 0.191 7 (35) 13 (65) 0.075 Ageusia 4 (30) 9 (70) 0.560 5 (42) 7 (58) 0.937 Fatigue 6 (32) 13 (68) 0.191 9 (41) 13 (59) Memory Problems 2 (12) 15 (88) 0.008* 4 (25) 12 (75) 0.013* Insomnia 4 (25) 12 (75) 0.858 8 (42) 11 (58) 0.774 Cough 1 (16.6) 10 (58.8) 0.076 7 (77.7) 8 (61.5) 0.421 Dispnoea 4 (66.6) 5 (29.4) 0.108 8 (88.8) 7 (53.8) 0.083 Palpitations 5 (55.5) 1 (7.6) 0.003* Brainfog 2 (33.3) 3 (17.6) 0.423 2 (22.2) 3 (23) 0 .013* Dizziness 0 (0.0) 3 (17.6) 0.270 1 (11.1) 2 (15.3) 0.774 Depresion 4 (66.6) 6 (35.2) 0.183 2 (22.2) 4 (30.7) 0.658 Myalgias 3 (50) 5 (29.4) 0.363 3 (33.3) 2 (15.3) 0.323 COVID Severity, No. (%) Hospitalization 5 (42) 7 (58) 0.076 4 (33) 8 (66) 0.429 Suplementary 02 5 (33) 10 (67) 0.278 8 (42) 11 (58) 0.774 Intubation 1 (50) 1 (50) 0.420 0 0 - In-hospital, days 34.3 ± 48.6 5.5 ± 6.3 0.021* 27 ± 43.8 13.9 ± 18.5 0.345 COVID reinfection 1 (33) 2 (66) 0.759 0 0 - PCS,days 152.8 ± 113.5 200.4 ± 215.0 0.614 107.8 ± 40.6 271.8 ± 219.3 0.039* Tests MNA 18.7 (4.8) 0.8(0.5) < 0.0001* 18.4 (4.7) 0.5 (0.5) < 0.0001* MMSE 27.1 (1.9) 18.1 (3.9) < 0.0001* 26.3 (2.1) 19.3 (4.4) 0.0003* SNIFFIN TEST 0.7 (1.8) 0.7 (3.1) 1.0 8.1 (3.2) 6.6 (2.2) 0.2163 Older adults syndromes Frialty 2 (33.3) 11 (64.7) 0.183 5 (55.5) 11 (84.6) 0.132 Sarcopenia 1 (16.6) 3 (17.6) 0.957 2 (22) 6 (46) 0.251 Biochemical parameters Hb 12.0 (4.3) 12.1 (2.8) 0.9609 12.2 (2.2) 11.1 (4.0) 0.4527 Leukocytes 12.5 (9.0) 9.4 (5.9) 0.3501 9.4 (4.1) 9.8 (4.7) 0.8417 Lymphocytes 1.7 (0.9) 1.5 (0.9) 0.6157 1.8 (0.8) 1.2 (0.5) 0.0646 Neutrophiles 10.8 (9.6) 7.2 (6.2) 0.3348 6.5 (4.3) 7.1 (4) 0.7497 Platelets 365.4 (132.5) 207.3 (61) 0.0007 226.4 (91.8) 274.6 (135.4) 0.3647 Creatinin 0.7 (0.2) 1.1 (0.9) 0.3294 1.5 (1.6) 1 (0.6) 0.3337 Urea 42.8 (14.7) 60.5 (56.2) 0.4611 63.4 (64.9) 56.8 (36.8) 0.7641 LDH 250 (73.5) 206 (110.4) 0.6125 181.8 (77.7) 220 (138) 0.5973 AST 30.8 (8.7) 31.3 (26.3) 0.4659 21 (9.8) 17.4 (11.1) 0.5138 ALT 24.8 (8.6) 19.4 (8.9) 0.2680 32.8 (40.7) 12.5 (7.2) 0.1038 BMI: Body mass index; CC: calf circumference; MAC: Mean arm circumference; COPD: Chronic Obstructive Pulmonary Disease; PCS: post-COVID syndrome; MNA: Mini-Nutritional Assessment; MMSE: Mini-Mental State Examination, ICR interquartile range. With respect to PCS, we found that symptoms such as ageusia, memory problems, depression and myalgias were more frequent in women compared to men, although only the presence of memory problems was significantly associated with cognitive decline for both sexes, additionally palpitations and brain fog were significantly associated with cognitive decline only in men, also a larger number of days with PCS was significantly associated with cognitive decline exclusively in men (Table 2 ). During the acute infection, men appear to experience a more severe COVID-19, with higher number of hospitalizations and higher need for supplementary O2, compared to women. A smaller number of hospitalization days was found to be a risk factor for women but not for men (Table 2 ). With respect to biochemical parameters, we found that lower platelet count was significantly associated with cognitive decline, exclusively in women. The remaining parameters were non-significantly associated with cognitive decline in a sex-specific manner. With respect to olfactory capacity, 53.3% of the population included in our study had hyposmia and 33.3% had anosmia. We found that the olfactory capacity, assessed by the sniffing test, had a positive correlation with MMSE (p = 0.012) (Fig. 2 ), and a negative correlation with increased age (p = 0.005) and the number of days with PCS (p = 0.018). We did not find differences in the olfactory capacity when we analyzed sex-specific comparisons. Interestingly, the sniffing test was not significantly associated with MNA, but it showed a significant association with CC, MAC, BMI, and obesity (Table 3 ). Table 3 Coefficients of variation in univariate analysis for altered sense of smell, assessed with mini nutritional assessment (MNA). Variable Coefficient R 2 P (95% CI) MNA 0.133 0.051 0.135 -0.043–0.309 BMI 0.142 0.120 0.020* 0.024–0.261 Obesity 1.895 0.121 0.019* 0.322–3.468 CC 0.272 0.212 0.001* 0.111–0.435 MAC 0.229 0.238 0.001* 0.103–0.356 Age, yr -0.178 0.168 0.005* -0.299–0.056- Male -0.773 0.020 0.353 -2.433–0.888 Days with PCS -0.005 0.123 0.018* -0.009 – -0.001 COVID reinfection -1.381 0.016 0.408 -4.716–1.954 MNA Mini Nutritional Assessment, BMI Body Mass Index, CC Calf Circumference, MAC Middle Arm Circumference, PCS Post-COVID Syndrome. 4. Discussion In this cohort of OA with Post-COVID syndrome, decline in olfactory capacity was common, this complication was associated to cognitive impairment and nutritional status. Both associations maintain a gradient of severity, as the olfactory capacity worsens, the cognitive state declines assessed by the MMSE. Of notice a decline in the sniffing test was associated with several measurements of the nutritional state such as BMI, CC and MAC but not with the MNA test. Which might reflect some important considerations for the routine use of MNA in the hospital setting, where other measurements or tools could be more useful, such as the BMI, CC, and MAC for isolated measurements and the NRS-2002, MUST and SGA as tools to evaluate nutritional status in hospitalized OA [ 29 ]. MNA test has been very useful in identifying the risk for malnourishment but does not consider other abnormalities such as obesity or overweight which have been important factors associated to COVID infection [ 30 ]. In our analyzed patients for example, obesity was a risk factor for cognitive decline exclusively in women. Cognitive impairment was identified in more than two-thirds of older adults in our study. In previous studies, persistent inflammation during post-COVID syndrome has been associated with fatigue, cognitive decline, and behavioral disorders [ 11 , 31 ]. We observed a significant association between reduced olfactory function and cognitive decline. This event may be bidirectional and can be explained by the pathophysiological mechanism of immune hyperactivation, neuroinflammation, direct viral encephalitis, blood-brain barrier integrity damage, hypoxia, and cerebrovascular disease [ 32 ]. In a meta-analysis performed by Ceban et al., brain neurodegeneration was observed in COVID-19 patients, with microvascular damage and metabolic alterations such as hypometabolism in the dorsolateral prefrontal cortex [ 11 ]. In our study, another important factor for cognitive decline was increased age; aging plays a fundamental role in olfactory capacity, reaching its peak at age 40 and afterwards progressively declining [ 21 ]. Recent studies have consistently highlighted sex-related differences in the prevalence and clinical expression of post-COVID syndrome, with women being disproportionately more affected compared to men [ 17 ]. Additionally, women are significantly more likely to present fatigue, dyspnea, and neurocognitive complaints compared to men [ 20 ]. In our study, women presented more frequently ageusia, memory problems, depression, and myalgias. Such data reinforce the hypothesis that hormonal and immunological factors, particularly estrogen-mediated immune modulation, may contribute to the heightened vulnerability of women to long post-COVID syndrome, although further mechanistic studies are required to confirm this relationship [ 33 ]. In contrast, men appear to experience a more severe acute COVID-19, as reflected in our study with higher number of hospitalizations, higher need for supplementary O2; previous studies also reported higher mortality rates in men [ 18 ]. Importantly, the consistency of these systematic results across diverse populations suggests that sex differences in post-COVID risk are not fundamentally due to cultural or healthcare-access disparities, but rather reflect an underlying biological and pathophysiological mechanisms contributing to the outcome [ 19 ]. Collectively, the reviewed international evidence emphasizes the necessity of integrating sex as an independent determinant factor in both clinical assessment and research design for post-COVID care and post-COVID syndrome understanding. In the Muccioli et al. study, brain magnetic resonance imaging examined the integrity of the olfactory system and the neuropsychological profile in patients with persistent olfactory dysfunction related to COVID-19 infection and healthy controls. There was a correlation between alterations in the olfactory network and the severity of olfactory dysfunction and neuropsychological tests, without morphological changes. However, no evidence in this study suggested neurodegeneration in patients with PCS [ 34 ]. The sense of smell is essential as it stimulates appetite, promotes food intake, protects from poisoning, and is associated with better quality of life [ 32 , 35 ]. Anosmia is considered a common and cardinal symptom of COVID-19, particularly in the early stages of infection, sometimes being the only symptom in an otherwise asymptomatic patient. SARS-CoV-2 primarily targets cells expressing the angiotensin-converting enzyme 2 (ACE2) receptor, which is abundantly present in the nasal epithelium, particularly on non-neuronal cells. Key cells involved in the loss of olfactory function are the sustentacular cells that support the function of olfactory neurons [ 36 ]. Currently the development of anosmia in COVID-19 is considered to have a heritable component of up to 48% [ 37 ]. SARS-CoV-2 infection reduces olfactory capacity through multiple pathways, including endothelial dysfunction, autoimmunity, latent viral reactivation, hyperinflammation, and autonomic nervous system dysfunction [ 38 ] (Supplementary Fig. 1). Importantly, as olfactory capacity decreases, the risk of malnutrition increases [ 39 ]. In our study, more than two-thirds of patients had hyposmia or anosmia, a similar finding was previously reported by Lechien et al. in a sample of 417 patients where 85.6% presented olfactory alterations [ 40 ]. Malnutrition in OA with post-COVID syndrome is one of the most common complications. In our study a positive correlation was observed with better nutrition (higher MNA) and higher cognition, which can be translated into a clinical need for screening in OA of malnutrition, frailty and loss of smell; since altogether may contribute to the deterioration of nutritional status, and consequently to cognitive impairment [ 41 ]. Previous studies discuss olfactory capacity and its impact on nutritional status [ 42 , 43 ]; however, only one recent study showed a correlation between olfactory function and the subjective global assessment (SGA) score in patients with chronic kidney disease [ 44 ]. While others have not been able to corroborate a true association between loss of olfactory function and nutritional status in OA [ 45 ]. Furthermore, it has been estimated that olfactory impairment could be more common in men compared to women [ 46 ]. In our study, olfactory impairment was slightly more frequent in men, but it was not significantly associated with cognitive decline nor MNA score. A similar study to ours evaluated the relationship between olfactory dysfunction, nutritional status, and cognitive function. It assessed 45 geriatric patients with neurodegenerative diseases and found that olfactory function had no association with nutritional status [ 47 ]. This cohort differs from ours as it was conducted in 2016, before the emergence of COVID-19, therefore distinct pathophysiological mechanism for olfactory decline were involved. Some of the limitations of our study include the cross-sectional design which is not suitable to imply causality but rather to generates hypotheses. The sample size is small, and there are multiple confounders that can participate in the generation of cognitive decline. We did not measure inflammatory biomarkers, nor included information about treatments during the acute infection or for PCS. The strengths of our study lie in its population; older adults with post-COVID syndrome, which have been an understudied population despite suffering from severe sequels. We evaluated, together, the risk of malnutrition, olfactory capacity, and cognitive impairment, metrics that require a qualified personnel, are not often performed on a routine basis. 5. Conclusions In conclusion, our study presents suggestive risk factors for cognitive involvement in a sex specific manner, including self-reported memory problems for both sexes, and brain fog, palpitations and dyspnea for men. We observed that OA with post-COVID syndrome frequently presented a decline in olfactory capacity and this complication was associated to cognitive impairment. Nutritional status measured by the MNA is importantly associated in the development of cognitive impairment irrespective of the sex, while changes in anthropometric measurements related to obesity where only associated to cognitive decline in women. Our findings should be confirmed in larger, longer-term, multicenter studies with measurements of inflammatory biomarkers and other comorbidities previously associated to cognitive impairment. Furthermore, the research around post-COVID syndrome should be enhanced to define better treatments that can help this population to resolve their situation and prevent more serious or threatening outcomes for OA. Declarations Informed Consent Statement Informed consent was obtained from all subjects involved in the study. Conflicts of Interest The authors declare no conflicts of interest. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author Contribution Conceptualization, ALGG, LGL and MGZC; methodology, ALGG, LGL, EIFH, and MGZC; formal analysis, EIFH and MGZC.; investigation, ALGG, JCI, and MVV; resources, ALG, LGL and MGZC; data obtention, ALGG; data curation, ALGG and MGZC; writing—original draft preparation, ALGG, JCI, MVV, and MGZC; writing—review and editing ALGG, LGL, JCI, MVV, EIFH, and MGZC; supervision, LGL, JCI, and MGZC. All authors have read and agreed to the published version of the manuscript.” Acknowledgement Upon acceptance APC will be covered by Fondo Semilla from Universidad Autónoma de Guadalajara. Data Availability The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. References Batiha GE, Al-Kuraishy HM, Al-Gareeb AI, Welson NN. Pathophysiology of Post-COVID syndromes: a new perspective. Virol J. 2022;19(1):158. 10.1186/s12985-022-01891-2 . Carrillo-Esper R. Post-COVID-19 syndrome. Gac Med Mex. 2022;158(3):115–7. 10.24875/GMM.M22000652 . Carfi A, Bernabei R, Landi F, Gemelli Against C-P-ACSG. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020;324(6):603–5. 10.1001/jama.2020.12603 . Cabrera Martimbianco AL, Pacheco RL, Bagattini AM, Riera R. Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review. Int J Clin Pract. 2021;75(10):e14357. 10.1111/ijcp.14357 . Arikawa E, Kaneko N, Nohara K, Yamaguchi T, Mitsuyama M, Sakai T. Influence of Olfactory Function on Appetite and Nutritional Status in the Elderly Requiring Nursing Care. J Nutr Health Aging. 2020;24(4):398–403. 10.1007/s12603-020-1334-3 . Borsetto D, Hopkins C, Philips V, Obholzer R, Tirelli G, Polesel J, et al. Self-reported alteration of sense of smell or taste in patients with COVID-19: a systematic review and meta-analysis on 3563 patients. Rhinology. 2020;58(5):430–6. 10.4193/Rhin20.185 . Wanga V, Chevinsky JR, Dimitrov LV, Gerdes ME, Whitfield GP, Bonacci RA, et al. Long-Term Symptoms Among Adults Tested for SARS-CoV-2 - United States, January 2020-April 2021. MMWR Morb Mortal Wkly Rep. 2021;70(36):1235–41. 10.15585/mmwr.mm7036a1 . Murphy C, Schubert CR, Cruickshanks KJ, Klein BE, Klein R, Nondahl DM. Prevalence of olfactory impairment in older adults. JAMA. 2002;288(18):2307–12. 10.1001/jama.288.18.2307 . Chang JY, Chou KR, Chang YL, Lin WY, Chiu HL, Liao YC et al. Enhancing Cognitive Function and Well-being in Older Adults With Cognitive and Physical Decline: A Meta-analysis of Randomized Controlled Trials Examining Physical Activity Interventions. J Phys Act Health. 2025:1–12. 10.1123/jpah.2025-0401 Cereda E, Pedrolli C, Klersy C, Bonardi C, Quarleri L, Cappello S, et al. Nutritional status in older persons according to healthcare setting: A systematic review and meta-analysis of prevalence data using MNA((R)). Clin Nutr. 2016;35(6):1282–90. 10.1016/j.clnu.2016.03.008 . Ceban F, Ling S, Lui LMW, Lee Y, Gill H, Teopiz KM, et al. Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis. Brain Behav Immun. 2022;101:93–135. 10.1016/j.bbi.2021.12.020 . He D, Yuan M, Dang W, Bai L, Yang R, Wang J, et al. Long term neuropsychiatric consequences in COVID-19 survivors: Cognitive impairment and inflammatory underpinnings fifteen months after discharge. Asian J Psychiatr. 2023;80:103409. 10.1016/j.ajp.2022.103409 . Mansell V, Hall Dykgraaf S, Kidd M, Goodyear-Smith F. Long COVID and older people. Lancet Healthy Longev. 2022;3(12):e849–54. 10.1016/S2666-7568(22)00245-8 . Chen Y, Yang W, Chen F, Cui L. COVID-19 and cognitive impairment: neuroinvasive and blood–brain barrier dysfunction. J Neuroinflammation. 2022;19(1):222. 10.1186/s12974-022-02579-8 . Tavares-Junior JWL, de Souza ACC, Borges JWP, Oliveira DN, Siqueira-Neto JI, Sobreira-Neto MA, et al. COVID-19 associated cognitive impairment: A systematic review. Cortex. 2022;152:77–97. 10.1016/j.cortex.2022.04.006 . Rothenberg E. Coronavirus Disease 19 from the Perspective of Ageing with Focus on Nutritional Status and Nutrition Management-A Narrative Review. Nutrients. 2021;13(4). 10.3390/nu13041294 . Shah DP, Thaweethai T, Karlson EW, Bonilla H, Horne BD, Mullington JM, et al. Sex Differences in Long COVID. JAMA Netw Open. 2025;8(1):e2455430. 10.1001/jamanetworkopen.2024.55430 . Fernandez-de-Las-Penas C, Martin-Guerrero JD, Pellicer-Valero OJ, Navarro-Pardo E, Gomez-Mayordomo V, Cuadrado ML, et al. Female Sex Is a Risk Factor Associated with Long-Term Post-COVID Related-Symptoms but Not with COVID-19 Symptoms: The LONG-COVID-EXP-CM Multicenter Study. J Clin Med. 2022;11(2). 10.3390/jcm11020413 . Muley A, Mitra S, Bhaliya B, Soni S, Joshi A. A Systematic Review and Meta-analysis to Identify Risk Factors for Developing Long COVID-19. J Assoc Phys India. 2024;72(5):68–74. Notarte KI, de Oliveira MHS, Peligro PJ, Velasco JV, Macaranas I, Ver AT, et al. Age, Sex and Previous Comorbidities as Risk Factors Not Associated with SARS-CoV-2 Infection for Long COVID-19: A Systematic Review and Meta-Analysis. J Clin Med. 2022;11(24). 10.3390/jcm11247314 . Fatuzzo I, Niccolini GF, Zoccali F, Cavalcanti L, Bellizzi MG, Riccardi G, et al. Neurons, Nose, and Neurodegenerative Diseases: Olfactory Function and Cognitive Impairment. Int J Mol Sci. 2023;24(3). 10.3390/ijms24032117 . von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies. Int J Surg. 2014;12(12):1495–9. 10.1016/j.ijsu.2014.07.013 . Benchimol EI, Smeeth L, Guttmann A, Harron K, Moher D, Petersen I, et al. The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement. PLoS Med. 2015;12(10):e1001885. 10.1371/journal.pmed.1001885 . Resneck JS. Jr. Revisions to the Declaration of Helsinki on Its 60th Anniversary: A Modernized Set of Ethical Principles to Promote and Ensure Respect for Participants in a Rapidly Innovating Medical Research Ecosystem. JAMA. 2025;333(1):15–7. 10.1001/jama.2024.21902 . Cho JH, Jeong YS, Lee YJ, Hong SC, Yoon JH, Kim JK. The Korean version of the Sniffin' stick (KVSS) test and its validity in comparison with the cross-cultural smell identification test (CC-SIT). Auris Nasus Larynx. 2009;36(3):280–6. 10.1016/j.anl.2008.07.005 . Instituto Nacional de G. Guía de instrumentos de evaluación geriátrica integral. https://www.gob.mx/inger/documentos/guia-de-instrumentos-de-evaluacion-geriatrica-integral Beaman SRd, Beaman PE, Garcia-Peña C, Villa MA, Heres J, Córdova A, Aging, et al. Neuropsychol Cognition. 2004;11(1):1–11. 10.1076/anec.11.1.1.29366 . Folstein MF, Folstein SE, McHugh PR. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98. 10.1016/0022-3956(75)90026-6 . Kroc L, Fife E, Piechocka-Wochniak E, Soltysik B, Kostka T. Comparison of Nutrition Risk Screening 2002 and Subjective Global Assessment Form as Short Nutrition Assessment Tools in Older Hospitalized Adults. Nutrients. 2021;13(1). 10.3390/nu13010225 . Silva DFO, Lima S, Sena-Evangelista KCM, Marchioni DM, Cobucci RN, Andrade FB. Nutritional Risk Screening Tools for Older Adults with COVID-19: A Systematic Review. Nutrients. 2020;12(10). 10.3390/nu12102956 . Xiong J, Lipsitz O, Nasri F, Lui LMW, Gill H, Phan L, et al. Impact of COVID-19 pandemic on mental health in the general population: A systematic review. J Affect Disord. 2020;277:55–64. 10.1016/j.jad.2020.08.001 . Doty RL. Olfactory dysfunction in COVID-19: pathology and long-term implications for brain health. Trends Mol Med. 2022;28(9):781–94. 10.1016/j.molmed.2022.06.005 . Sylvester SV, Rusu R, Chan B, Bellows M, O'Keefe C, Nicholson S. Sex differences in sequelae from COVID-19 infection and in long COVID syndrome: a review. Curr Med Res Opin. 2022;38(8):1391–9. 10.1080/03007995.2022.2081454 . Muccioli L, Sighinolfi G, Mitolo M, Ferri L, Jane Rochat M, Pensato U, et al. Cognitive and functional connectivity impairment in post-COVID-19 olfactory dysfunction. Neuroimage Clin. 2023;38:103410. 10.1016/j.nicl.2023.103410 . Winter AL, Henecke S, Lundstrom JN, Thunell E. Impairment of quality of life due to COVID-19-induced long-term olfactory dysfunction. Front Psychol. 2023;14:1165911. 10.3389/fpsyg.2023.1165911 . Butowt R, von Bartheld CS. Anosmia in COVID-19: Underlying Mechanisms and Assessment of an Olfactory Route to Brain Infection. Neuroscientist. 2021;27(6):582–603. 10.1177/1073858420956905 . Williams FMK, Freidin MB, Mangino M, Couvreur S, Visconti A, Bowyer RCE, et al. Self-Reported Symptoms of COVID-19, Including Symptoms Most Predictive of SARS-CoV-2 Infection, Are Heritable. Twin Res Hum Genet. 2020;23(6):316–21. 10.1017/thg.2020.85 . Hopkins C, Surda P, Whitehead E, Kumar BN. Early recovery following new onset anosmia during the COVID-19 pandemic - an observational cohort study. J Otolaryngol Head Neck Surg. 2020;49(1):26. 10.1186/s40463-020-00423-8 . Gunzer W. Changes of Olfactory Performance during the Process of Aging - Psychophysical Testing and Its Relevance in the Fight against Malnutrition. J Nutr Health Aging. 2017;21(9):1010–5. 10.1007/s12603-017-0873-8 . Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020;277(8):2251–61. 10.1007/s00405-020-05965-1 . Grund S, Bauer JM. Malnutrition and Sarcopenia in COVID-19 Survivors. Clin Geriatr Med. 2022;38(3):559–64. 10.1016/j.cger.2022.04.001 . Hummel T, Nordin S. Olfactory disorders and their consequences for quality of life. Acta Otolaryngol. 2005;125(2):116–21. 10.1080/00016480410022787 . Toller SV. Assessing the impact of anosmia: review of a questionnaire's findings. Chem Senses. 1999;24(6):705–12. 10.1093/chemse/24.6.705 . Raff AC, Lieu S, Melamed ML, Quan Z, Ponda M, Meyer TW, et al. Relationship of impaired olfactory function in ESRD to malnutrition and retained uremic molecules. Am J Kidney Dis. 2008;52(1):102–10. 10.1053/j.ajkd.2008.02.301 . Toussaint N, de Roon M, van Campen JP, Kremer S, Boesveldt S. Loss of olfactory function and nutritional status in vital older adults and geriatric patients. Chem Senses. 2015;40(3):197–203. 10.1093/chemse/bju113 . Schubert CR, Cruickshanks KJ, Fischer ME, Huang GH, Klein BE, Klein R, et al. Olfactory impairment in an adult population: the Beaver Dam Offspring Study. Chem Senses. 2012;37(4):325–34. 10.1093/chemse/bjr102 . Jin SY, Jeong HS, Lee JW, Kwon KR, Rha KS, Kim YM. Effects of nutritional status and cognitive ability on olfactory function in geriatric patients. Auris Nasus Larynx. 2016;43(1):56–61. 10.1016/j.anl.2015.06.009 . Additional Declarations No competing interests reported. Supplementary Files floatimage1.jpeg Graphical abstract. Created in BioRender. Zavala, M. (2025) https://BioRender.com/1nptejd SuplementaryFig1.jpeg Supplementary Materials: Supplementary Figure 1. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7520208","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":540057130,"identity":"d6771a55-bb57-493b-b1c8-d6bb6506ffd2","order_by":0,"name":"Alma L. Guzmán-Gurrola","email":"","orcid":"","institution":"Hospital Civil de Gudadalajara Fray Antonio Alcalde","correspondingAuthor":false,"prefix":"","firstName":"Alma","middleName":"L.","lastName":"Guzmán-Gurrola","suffix":""},{"id":540057131,"identity":"b85948c1-819f-4f36-84e6-d860e5409ed0","order_by":1,"name":"Laura González-López","email":"","orcid":"","institution":"Universidad del Valle de Atemajac Campus Guadalajara","correspondingAuthor":false,"prefix":"","firstName":"Laura","middleName":"","lastName":"González-López","suffix":""},{"id":540057132,"identity":"1266a5df-6564-4ca9-b01f-993ae423332c","order_by":2,"name":"Jonathan S. Chávez-Íñiguez","email":"","orcid":"","institution":"Hospital Civil de Gudadalajara Fray Antonio Alcalde","correspondingAuthor":false,"prefix":"","firstName":"Jonathan","middleName":"S.","lastName":"Chávez-Íñiguez","suffix":""},{"id":540057133,"identity":"6cc29b22-2fd7-414b-94bd-a3233d8ad1f2","order_by":3,"name":"Mariana Verduzco Vázquez","email":"","orcid":"","institution":"Universidad Autónoma de Guadalajara","correspondingAuthor":false,"prefix":"","firstName":"Mariana","middleName":"Verduzco","lastName":"Vázquez","suffix":""},{"id":540057134,"identity":"4fef0a3a-f92a-4a46-b442-757807988589","order_by":4,"name":"Efraín I Flores-Hernández","email":"","orcid":"","institution":"Universidad Autónoma de Guadalajara","correspondingAuthor":false,"prefix":"","firstName":"Efraín","middleName":"I","lastName":"Flores-Hernández","suffix":""},{"id":540057135,"identity":"88e24889-2be2-4ede-a753-164042455886","order_by":5,"name":"Maria G. Zavala-Cerna","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8ElEQVRIiWNgGAWjYJCCA1Ca8QEDG4lamA2I1gIDbBJEadFtP/vwwA8GOznz2c3PKj6UHWYwOH78AtPNNtxazM6kGxzsYUg2lrlzzOzmjHNALWdyCphzzuDRciCN4QAPw4HEGRIJZrd524BaDuQkMOdU4NFy/hnDwT8MB+pnSKR/K/4L0nL+DVCLAR4tN9IYDgNtSZCQyDFjZgRpuZF+AL8tN54xHJYxSDacIZFTLNlzLp1H8sYbhsN4/XI+jfnjmwo7eQmJ9I0ffpRZy/GdT3/4OBdPiEEAkst5gMjgACEN6ID9Aak6RsEoGAWjYHgDAMWUUzqBaHzNAAAAAElFTkSuQmCC","orcid":"","institution":"Universidad Autónoma de Guadalajara","correspondingAuthor":true,"prefix":"","firstName":"Maria","middleName":"G.","lastName":"Zavala-Cerna","suffix":""}],"badges":[],"createdAt":"2025-09-02 17:38:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7520208/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7520208/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":95197631,"identity":"03c5c461-ed72-4313-9595-009628c0ada0","added_by":"auto","created_at":"2025-11-05 11:41:11","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2244982,"visible":true,"origin":"","legend":"","description":"","filename":"SEP15.docx","url":"https://assets-eu.researchsquare.com/files/rs-7520208/v1/8939f1cb0e97d93cfe133095.docx"},{"id":95197620,"identity":"eb342847-1762-4a4f-bade-3a9be5d40a72","added_by":"auto","created_at":"2025-11-05 11:41:11","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":8133,"visible":true,"origin":"","legend":"","description":"","filename":"45b27ea45f4c408a924a07000ee331fa.json","url":"https://assets-eu.researchsquare.com/files/rs-7520208/v1/8c0ae7421329e7167fadbe24.json"},{"id":95197626,"identity":"a4fc40f7-cf0b-4eea-b5eb-bfcd075be0cb","added_by":"auto","created_at":"2025-11-05 11:41:11","extension":"jpeg","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":3174929,"visible":true,"origin":"","legend":"","description":"","filename":"SuplementaryFig1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7520208/v1/7508cd7d5a9b2850ddc75385.jpeg"},{"id":95197629,"identity":"440192d1-bcdd-4525-9ee2-fd1d32e01300","added_by":"auto","created_at":"2025-11-05 11:41:11","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":163743,"visible":true,"origin":"","legend":"","description":"","filename":"45b27ea45f4c408a924a07000ee331fa1enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7520208/v1/c7e89f063f6d9a99ba935620.xml"},{"id":95197625,"identity":"bdc1ac31-e374-417b-9dfc-50b5526ee834","added_by":"auto","created_at":"2025-11-05 11:41:11","extension":"png","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":189376,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7520208/v1/139ca2a652d572ecf982431e.png"},{"id":95197621,"identity":"442d4fe8-cf2b-4ed8-a671-9de24f7909dc","added_by":"auto","created_at":"2025-11-05 11:41:11","extension":"png","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":93617,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7520208/v1/9e9035bcdce4937d82ceb70f.png"},{"id":95227652,"identity":"13600b95-5a3a-4450-b752-57e74173188d","added_by":"auto","created_at":"2025-11-05 16:32:41","extension":"png","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":83161,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7520208/v1/8373fd9fd1ac94c4e0744247.png"},{"id":95227623,"identity":"951a9bd4-89fc-4ef5-8425-701ed705f537","added_by":"auto","created_at":"2025-11-05 16:32:40","extension":"xml","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":159578,"visible":true,"origin":"","legend":"","description":"","filename":"45b27ea45f4c408a924a07000ee331fa1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7520208/v1/cee58243ca876788c378721a.xml"},{"id":95197630,"identity":"9ffcb0c9-e145-4f00-ac6f-9e9f9c266ed7","added_by":"auto","created_at":"2025-11-05 11:41:11","extension":"html","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":170855,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7520208/v1/6cedd3ffbf3cf755e1b16066.html"},{"id":95229034,"identity":"49fb015e-9d6f-4485-8d77-ec11442ea978","added_by":"auto","created_at":"2025-11-05 16:34:23","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":175154,"visible":true,"origin":"","legend":"\u003cp\u003eStudy Flow Diagram. CI cognitive impairment.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7520208/v1/cff1195c3f9dc2fda8bd12aa.jpeg"},{"id":95197618,"identity":"68f56b51-383a-4ebc-9b0e-e88c7ea35cf6","added_by":"auto","created_at":"2025-11-05 11:41:11","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":420785,"visible":true,"origin":"","legend":"\u003cp\u003eFitted Graphs for regressions between sniffing test and continues variables related to nutritional status, age and days with post-COVID syndrome (PCS). MNA mini nutritional assessment, BMI body mass index, CC calf circumference, and MAC mid-arm circumference.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7520208/v1/5ba5fa55746f560891c3370f.jpeg"},{"id":100373892,"identity":"002e4342-f519-4141-840c-2f811ad669d1","added_by":"auto","created_at":"2026-01-16 08:20:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1841788,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7520208/v1/891ee7b9-891c-41da-ae85-89675f46eca3.pdf"},{"id":95227328,"identity":"724bafdc-7429-4752-9e74-008127215d4e","added_by":"auto","created_at":"2025-11-05 16:32:23","extension":"jpeg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1210441,"visible":true,"origin":"","legend":"\u003cp\u003eGraphical abstract.\u003c/p\u003e\n\u003cp\u003eCreated in BioRender. Zavala, M. (2025) https://BioRender.com/1nptejd\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7520208/v1/a0d15085b3c06b1f48b482ed.jpeg"},{"id":95228802,"identity":"37024d3b-6418-485b-b59d-dface0958caf","added_by":"auto","created_at":"2025-11-05 16:34:09","extension":"jpeg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":3174929,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Materials: \u003c/strong\u003eSupplementary\u003cstrong\u003e \u003c/strong\u003eFigure 1.\u003c/p\u003e","description":"","filename":"SuplementaryFig1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7520208/v1/3938f3601f7947c8f8a74058.jpeg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sex-specific differences in nutritional status as risk factors for cognitive decline amongst older adults with Post-COVID Syndrome","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003ePost-COVID syndrome (PCS) has emerged as a health problem worldwide, defined by the persistence in symptoms after the acute confirmed infection with SARS-CoV-2 for at least 3 months as a continuous, relapsing/remitting, or progressive disease state [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] ; it is considered a systemic condition [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], with an incidence and prevalence of 50% and 45% respectively [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Common signs and symptoms include fatigue, loss of memory, cognitive impairment, difficulty breathing, thoracic pain, anosmia, ageusia, arthralgias, myalgias and functional impairment [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOne of the most distinctive symptoms of SARS-CoV2 infection and the consequent PCS, is the loss in olfactory capacity, affecting 85 to 98% of infected individuals [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The prevalence of olfactory changes in older adults (OA) is 27%, and occurs more frequently in men [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOA are a vulnerable population due to defects in immune response, typically associated to a high prevalence in cardiorenal metabolic, and geriatric comorbidities; as a result, OA have increased risk for cognitive decline [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] and malnutrition [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe development of cognitive impairment is of special interest in OA, since it has been a common neuropsychiatric consequence of COVID infection [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], believed to appear as result of increased permeability in the encephalic barrier and irreversible neuronal damage [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], with deterioration in memory function, microvascular endothelial dysfunction, the presence of inflammatory metabolites and beta-amyloid within the brain [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. During PCS the development of cognitive impairment is not entirely clear, and the presence of additional sex specific risk factors needs to be addressed [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMultiple investigations regarding sex varieties in post COVID syndrome have shown sex specific risk factors. A large prospective study from the RECOVER consortium (NIH) found that women have a substantially higher risk compared to men, with a relative risk of 1.31; this association was evident across almost all age groups except the youngest (18\u0026ndash;39 years) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Similarly, a systematic review and meta-analysis confirmed that women are 48% more likely to experience persistent symptoms after infection (OR 1.48; 95% CI 1.17\u0026ndash;1.86) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Furthermore, in a Spanish multicenter study, the average number of post-COVID symptoms was higher in women compared to men, and female sex was associated with greater risk of fatigue, dyspnea, physical pain, hair loss, ocular disturbances, depression, and/or sleep disorders [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. This gender bias is also reflected in neurological and psychiatric manifestations, with women more frequently reporting headache, sleep disturbances, and cognitive complaints compared to men [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In general, the study of the PCS in OA has been scarcely explored in the literature [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. To fill this gap in knowledge, we underwent a cross-sectional study with the purpose of investigating the contribution of sex specific risk factors for the development of cognitive decline during PCS in a cohort of OA hospitalized patients.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1. Study participants.\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eParticipants that met the following criteria were included in the study: (1) older adults (OA) hospitalized in a tertiary referral hospital at the geriatric clinic, during the period comprised between August 2023 - August 2024 (2) a confirmed positive test and diagnosis of COVID-19 at least 3 months before the inclusion in our study, and (3) a diagnosis of post-COVID syndrome.\u003c/p\u003e\u003cp\u003eOA were excluded if they had a psychiatric condition such as bipolar disorder, schizophrenia, a neurological diagnosis of dementia or an important cognitive impairment to answer questionnaires or impeded to stablish study measurements.\u003c/p\u003e\u003cp\u003eThe study protocol was designed according to the STROBE [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] and RECORD guidelines for observational studies [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] and submitted for IRB approval before patient recruitment. The study was conducted according to the Declaration of Helsinki [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. With participants willingly accepting to participate in our study, after signature of the informed consent.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2. Study Design.\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThis was a cross-sectional study, performed in a geriatric clinic of a tertiary referral hospital. For all participants, data were collected immediately after hospital admission.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3. Study measurements:\u003c/h2\u003e\u003cdiv id=\"Sec6\" class=\"Section3\"\u003e\u003ch2\u003e2.3.1. Demographic and clinical variables:\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eDemographic and clinical information related to COVID-19 infection and PCS was obtained by automated retrieval from the institutional electronic medical records system. Physical examination, olfactory function, cognitive evaluation, and nutritional evaluation were performed within the first 48 hours of patient hospitalization.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section3\"\u003e\u003ch2\u003e2.3.2. Olfactory functions:\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eTo measure olfactory function in our patients, we used the Sniffin\u0026rsquo; Stick Test II, which has been previously validated for this purpose [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The capacity for odor identification was evaluated using 12 common odors; the identification of \u0026lt;\u0026thinsp;9 odors was defined as functional hyposmia and \u0026lt;\u0026thinsp;6 as anosmia. In each participant, olfactory tests, nutritional status, and cognitive abilities were performed during the same session in a well-ventilated room. First, we evaluated olfactory function, then cognitive abilities, and finally nutritional status.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section3\"\u003e\u003ch2\u003e2.3.3. Cognitive Evaluation:\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eA geriatric cognitive function evaluation, was assessed clinicians attending at the geriatric clinic, with validated instruments available from the National Institute of Geriatrics website [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Cognitive evaluation included the following domains: orientation to time, memory, attention and executive function, assessed with the adapted Spanish version [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] from the previously published Folstein Mini-Mental State Examination (MMSE) [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Scores ranged from 0 to 30, with lower scores indicating increasing severity of cognitive impairment. Subjects with a score between 0 to 24 were considered at risk for cognitive impairment and individuals who scored\u0026thinsp;\u0026gt;\u0026thinsp;24 were considered without cognitive impairment.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section3\"\u003e\u003ch2\u003e2.3.4. Nutritional Assessment:\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eMeasurements were obtained by a certified geriatric nutritionist, and included, the Mini Nutritional Assessment (MNA\u0026reg;), which has been validated for OA [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The MNA includes anthropometric measurements, a global assessment, a dietary questionnaire and a subjective assessment. According to the developers\u0026rsquo; instructions, the MNA administration utilizes a two-step approach: screening and a global assessment. Subsequently, based on the MNA total score, patients are classified as \u0026lsquo;\u0026lsquo;malnourished\u0026rsquo;\u0026rsquo; (score\u0026thinsp;\u0026lt;\u0026thinsp;17), \u0026lsquo;\u0026lsquo;at risk of malnutrition\u0026rsquo;\u0026rsquo; (scores 17.5\u0026ndash;23.5) or as having a \u0026lsquo;\u0026lsquo;normal nutritional status\u0026rdquo; (score\u0026thinsp;\u0026gt;\u0026thinsp;24). The \u0026lsquo;\u0026lsquo;global assessment step\u0026rsquo;\u0026rsquo; of the MNA should only be administered to patients not reaching the screening threshold. Additionally, other measurements were added to the nutritional status including height, weight, mid-arm circumference (MAC) and calf circumference (CC). Weight was measured in kilograms, with participants standing up, using a Tanita BC-558 Ironman scale. Height was measured in centimeters with participants placed under the stadiometer, head facing forward, without shoes, and feet together, using a Seca 213 portable stadiometer. Calf circumference CC was measured in centimeters with Lufkin anthropometric tape, at the point where the calf acquires greater volume between the ankle and knee. The mid-arm circumference (MAC) was measured in centimeters with Lufkin's anthropometric tape, performed on the arm bent in a 90\u0026ordm; position and with a tape measure at the midpoint between the bony points of the acromion and olecranon.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section3\"\u003e\u003ch2\u003e2.3.5. Statistical Analysis:\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eCategorical variables were presented as frequencies and percentages; continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). Inferences for categorical variables were established with the chi squared test. For continuous dependent variables we used single and multiple linear regression models, to establish the association of risk factors for cognitive impairment in post-COVID Syndrome. A p value of \u0026lt;\u0026thinsp;0.05 was considered significant, we used the software STATA 17 for calculations.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eDuring the study period a total of 90 patients were hospitalized in our clinic with PCS, main reasons for hospitalization were: upper respiratory tract affection (38%), cerebrovascular or neurological affections (29%), general malaise/fever of unknown origin (15%), GI tract affection/dehydration (13%), and anemia or cardiometabolic alterations (4%).\u003c/p\u003e\u003cp\u003eFor all hospitalized patients, eligibility was assessed, subjects that met the inclusion criteria were invited to participate in the study (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThe sociodemographic characteristics of OA are described in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, divided by the presence of risk for cognitive impairment or cognitive impairment (MMSE\u0026thinsp;\u0026lt;\u0026thinsp;24); overall, the studied population had an age range from 65 to 89 years old, and 51% of the studied population were female. The more frequent comorbidities included hypertension in 55.6%, Type 2 diabetes (T2D) in 40%, chronic obstructive pulmonary disease (COPD) in 35.6% and chronic kidney disease (CKD) in 22.2%; more than 50% of the studied population had more than 3 comorbidities at the time of the assessment.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic characteristics of older adults (OS) with Post-COVID syndrome (PCS) divided by the presence of cognitive impairment.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameter\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eMean (SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo risk for CI\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRisk for CI or CI\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e75.6 (5.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e75.9 (6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.862\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMales, No. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (43.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.292\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight, Kg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60.8 (18.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e67.6 (13.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.169\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeight, mt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.6 (0.09)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.6 (0.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.212\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23.2 (18.1-26.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26.82 (21.8\u0026ndash;31.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.057\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29.09 (25.7\u0026ndash;32.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31.45 (28.4\u0026ndash;35.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.109\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMAC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26.72 (21.3\u0026ndash;34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28.21 (24-30.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.295\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eObesity, No. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (56.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.140\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eComorbidities, No. (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBasic education,\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (86.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.771\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (43.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.519\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (53.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (56.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.832\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKidney Disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (20.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (23.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.800\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCOPD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (36.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.826\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;3 comorbilities\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (53.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 (60.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.670\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoker\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (13.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (13.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEx Smoker\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (26.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (23.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.806\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCOVID Symptoms, No. (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnosmia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (86.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26 (86.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAgeusia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (60.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (53.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.671\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFatigue\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26 (86.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.138\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMemory Problems\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27 (90.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInsomnia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (80.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23 (76.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.800\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCOVID Severity, No. (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHospitalization\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.526\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSuplementary 02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (53.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (53.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.920\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntubation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (3.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.920\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHospital stays days median (ICR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (0\u0026ndash;60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (0\u0026ndash;15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.252\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReinfection COVID\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePost-COVID Syndrome, days m(SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e125.8 (77.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e231.3 (216.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0751\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTests, Median (ICR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15.7 (12\u0026ndash;17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20.0 (16.5\u0026ndash;24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.004*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMMSE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (25\u0026ndash;29)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (15\u0026ndash;22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSNIFFIN TEST\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (7\u0026ndash;10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (5\u0026ndash;10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.5124\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eBMI: Body mass index; CC: calf circumference; MAC: Mean arm circumference; COPD: Chronic Obstructive Pulmonary Disease MNA: Mini-Nutritional Assessment MMSE: Mini-Mental State Examination, ICR interquartile range.\u003c/p\u003e\u003cp\u003eWith respect to the nutritional status, a total of 23 patients (51%) were in the normal/risk group, and 22 (49%) had malnutrition. Compared to those with a normal/risk nutritional status, those with malnutrition had significantly lower weight (57.0 vs. 73.2 kg), a lower BMI (21.3 vs. 28.1), smaller calf circumference (26.9 vs. 34.0), mid-arm circumference (23.4 vs. 28.8), and a lower MNA score (14.5 vs. 22.4) (p for all \u0026lt;\u0026thinsp;0.05). The malnutrition group also had a higher frequency of diabetes (22.7% vs. 56.5%).\u003c/p\u003e\u003cp\u003eDuring the acute COVID infection, up to 53.3% required hospitalization during the acute phase of the disease, with a median (ICR) of 5 (0\u0026ndash;15) hospital days. Therapy with supplementary oxygen was required by 75.5% and 4% assisted mechanical ventilation.\u003c/p\u003e\u003cp\u003eIn the post-COVID stage, 77.8% were unable to wean off supplemental oxygen, 86% presented anosmia, 91.1% fatigue, 55.5% ageusia, 73.3% memory problems, and 77.7% insomnia. The average duration of these symptoms was 99.48\u0026thinsp;\u0026plusmn;\u0026thinsp;128.15 days.\u003c/p\u003e\u003cp\u003eWith respect to sex specific analysis, the prevalence of cognitive decline was lower in women 13 (59.1%) than in men 17 (73.9%), while the risk of malnutrition was slightly higher for women 12 (52.2%) compared to men 10 (45.5%) (p\u0026thinsp;=\u0026thinsp;0.652). Even though the MNA was not significantly different in women (18.7\u0026thinsp;+\u0026thinsp;4.8) compared to men (18.4\u0026thinsp;+\u0026thinsp;4.7) (p\u0026thinsp;=\u0026thinsp;0.865), we observed that men with cognitive decline had significantly lower BMI (23.3 \u0026plusmn; 4.5) compared to women (29.5 \u0026plusmn; 6.3) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0051), smaller calf circumference (29.4 \u0026plusmn; 4.1) in comparison to women (33.0 \u0026plusmn; 3.9) (p\u0026thinsp;=\u0026thinsp;0.0204) and smaller middle upper arm circumference (25.5 \u0026plusmn; 3.8) compared to women (30.2 \u0026plusmn; 5.5) (p\u0026thinsp;=\u0026thinsp;0.0177). In women, a wider calf circumference and middle arm circumference, probable associated to the presence of obesity, as well as a lower MNA score were significantly associated with cognitive decline. In men, anthropometric measurements were not found in association with cognitive decline, only a lower MNA score was significantly associated to cognitive decline (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) (Located at the end of the manuscript due to its length).\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eGender-specific clinical parameters associated with cognitive decline assessed with mini mental state examination (MMSE).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eFemale (n\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eMale (n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo risk for CI\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRisk for CI or CI (n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNo risk for CI\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eRisk for CI or CI (n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e73.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e74.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.574\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e77.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e77.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.889\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight, Kg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55.8\u0026thinsp;\u0026plusmn;\u0026thinsp;22.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e69.5\u0026thinsp;\u0026plusmn;\u0026thinsp;14.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.091\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e64.1\u0026thinsp;\u0026plusmn;\u0026thinsp;16.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e65.1\u0026thinsp;\u0026plusmn;\u0026thinsp;13.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.8789\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeight, mt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.776\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.801\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.080\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e23.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.959\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.039*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e29.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e29.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.9607\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMAC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.031*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e28.4\u0026thinsp;\u0026plusmn;\u0026thinsp;8.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e25.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.3035\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eObesity, No. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (92)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.022*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4 (44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5 (55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.779\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eComorbidities, No. (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBasic education\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.270\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7 (39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11 (61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.683\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.283\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.595\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (64.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.526\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5 (55.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6 (46.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.665\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKidney Disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (11.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.051\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5 (38.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.034*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCOPD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (29.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.363\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (22.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6 (46.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.251\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;3 comorbilities\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoker\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (76.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.420\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 (11.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 (23.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.474\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEx Smoker\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (16.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (11.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.759\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3 (33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5 (38.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.806\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiovascular\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (76.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.226\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7 (77.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12 (92.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.329\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAutoimmunity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (16.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (17.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.957\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 (23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.121\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePCS Symptoms, No. (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnosmia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (68)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.191\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7 (35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13 (65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.075\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAgeusia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.560\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5 (42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7 (58)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.937\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFatigue\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (68)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.191\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9 (41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13 (59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMemory Problems\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15 (88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.008*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12 (75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.013*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInsomnia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.858\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8 (42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11 (58)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.774\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCough\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (16.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (58.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.076\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7 (77.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8 (61.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.421\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDispnoea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (66.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (29.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.108\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8 (88.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7 (53.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.083\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePalpitations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5 (55.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (7.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.003*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBrainfog\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (17.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.423\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (22.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 (23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0\u003cb\u003e.013*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDizziness\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (17.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.270\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 (11.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2 (15.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.774\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDepresion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (66.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (35.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.183\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (22.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4 (30.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.658\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMyalgias\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (29.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.363\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3 (33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2 (15.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.323\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCOVID Severity, No. (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHospitalization\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (58)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.076\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4 (33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8 (66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.429\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSuplementary 02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.278\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8 (42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11 (58)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.774\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntubation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.420\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIn-hospital, days\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34.3\u0026thinsp;\u0026plusmn;\u0026thinsp;48.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.021*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e27\u0026thinsp;\u0026plusmn;\u0026thinsp;43.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13.9\u0026thinsp;\u0026plusmn;\u0026thinsp;18.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.345\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCOVID reinfection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.759\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePCS,days\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e152.8\u0026thinsp;\u0026plusmn;\u0026thinsp;113.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e200.4\u0026thinsp;\u0026plusmn;\u0026thinsp;215.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.614\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e107.8\u0026thinsp;\u0026plusmn;\u0026thinsp;40.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e271.8\u0026thinsp;\u0026plusmn;\u0026thinsp;219.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.039*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTests\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18.7 (4.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.8(0.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e18.4 (4.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.5 (0.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMMSE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27.1 (1.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18.1 (3.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e26.3 (2.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e19.3 (4.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.0003*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSNIFFIN TEST\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.7 (1.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.7 (3.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8.1 (3.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6.6 (2.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.2163\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOlder adults syndromes\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFrialty\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (64.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.183\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5 (55.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11 (84.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.132\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSarcopenia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (16.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (17.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.957\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6 (46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.251\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBiochemical parameters\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.0 (4.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12.1 (2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.9609\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12.2 (2.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11.1 (4.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.4527\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLeukocytes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.5 (9.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.4 (5.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.3501\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9.4 (4.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9.8 (4.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.8417\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphocytes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.7 (0.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.5 (0.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.6157\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.8 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.2 (0.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.0646\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeutrophiles\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.8 (9.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.2 (6.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.3348\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6.5 (4.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7.1 (4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.7497\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelets\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e365.4 (132.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e207.3 (61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0007\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e226.4 (91.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e274.6 (135.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.3647\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatinin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.7 (0.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.1 (0.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.3294\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.5 (1.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (0.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.3337\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42.8 (14.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60.5 (56.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.4611\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e63.4 (64.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e56.8 (36.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.7641\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLDH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e250 (73.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e206 (110.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.6125\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e181.8 (77.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e220 (138)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.5973\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30.8 (8.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31.3 (26.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.4659\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e21 (9.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e17.4 (11.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.5138\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.8 (8.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19.4 (8.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.2680\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e32.8 (40.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12.5 (7.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.1038\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eBMI: Body mass index; CC: calf circumference; MAC: Mean arm circumference; COPD: Chronic Obstructive Pulmonary Disease; PCS: post-COVID syndrome; MNA: Mini-Nutritional Assessment; MMSE: Mini-Mental State Examination, ICR interquartile range.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eWith respect to PCS, we found that symptoms such as ageusia, memory problems, depression and myalgias were more frequent in women compared to men, although only the presence of memory problems was significantly associated with cognitive decline for both sexes, additionally palpitations and brain fog were significantly associated with cognitive decline only in men, also a larger number of days with PCS was significantly associated with cognitive decline exclusively in men (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eDuring the acute infection, men appear to experience a more severe COVID-19, with higher number of hospitalizations and higher need for supplementary O2, compared to women. A smaller number of hospitalization days was found to be a risk factor for women but not for men (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eWith respect to biochemical parameters, we found that lower platelet count was significantly associated with cognitive decline, exclusively in women. The remaining parameters were non-significantly associated with cognitive decline in a sex-specific manner.\u003c/p\u003e\u003cp\u003eWith respect to olfactory capacity, 53.3% of the population included in our study had hyposmia and 33.3% had anosmia. We found that the olfactory capacity, assessed by the sniffing test, had a positive correlation with MMSE (p\u0026thinsp;=\u0026thinsp;0.012) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), and a negative correlation with increased age (p\u0026thinsp;=\u0026thinsp;0.005) and the number of days with PCS (p\u0026thinsp;=\u0026thinsp;0.018). We did not find differences in the olfactory capacity when we analyzed sex-specific comparisons. Interestingly, the sniffing test was not significantly associated with MNA, but it showed a significant association with CC, MAC, BMI, and obesity (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCoefficients of variation in univariate analysis for altered sense of smell, assessed with mini nutritional assessment (MNA).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCoefficient\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eR\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e(95% CI)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.133\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.051\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.135\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.043\u0026ndash;0.309\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.142\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.120\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.020*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.024\u0026ndash;0.261\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eObesity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.895\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.121\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.019*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.322\u0026ndash;3.468\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.272\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.212\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.001*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.111\u0026ndash;0.435\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMAC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.229\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.238\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.001*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.103\u0026ndash;0.356\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, yr\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.178\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.168\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.005*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.299\u0026ndash;0.056-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.773\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.020\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.353\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-2.433\u0026ndash;0.888\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDays with PCS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.123\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.018*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.009 \u0026ndash; -0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCOVID reinfection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-1.381\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.408\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-4.716\u0026ndash;1.954\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eMNA Mini Nutritional Assessment, BMI Body Mass Index, CC Calf Circumference, MAC Middle Arm Circumference, PCS Post-COVID Syndrome.\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eIn this cohort of OA with Post-COVID syndrome, decline in olfactory capacity was common, this complication was associated to cognitive impairment and nutritional status. Both associations maintain a gradient of severity, as the olfactory capacity worsens, the cognitive state declines assessed by the MMSE. Of notice a decline in the sniffing test was associated with several measurements of the nutritional state such as BMI, CC and MAC but not with the MNA test. Which might reflect some important considerations for the routine use of MNA in the hospital setting, where other measurements or tools could be more useful, such as the BMI, CC, and MAC for isolated measurements and the NRS-2002, MUST and SGA as tools to evaluate nutritional status in hospitalized OA [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. MNA test has been very useful in identifying the risk for malnourishment but does not consider other abnormalities such as obesity or overweight which have been important factors associated to COVID infection [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In our analyzed patients for example, obesity was a risk factor for cognitive decline exclusively in women.\u003c/p\u003e\u003cp\u003eCognitive impairment was identified in more than two-thirds of older adults in our study. In previous studies, persistent inflammation during post-COVID syndrome has been associated with fatigue, cognitive decline, and behavioral disorders [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. We observed a significant association between reduced olfactory function and cognitive decline. This event may be bidirectional and can be explained by the pathophysiological mechanism of immune hyperactivation, neuroinflammation, direct viral encephalitis, blood-brain barrier integrity damage, hypoxia, and cerebrovascular disease [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In a meta-analysis performed by Ceban et al., brain neurodegeneration was observed in COVID-19 patients, with microvascular damage and metabolic alterations such as hypometabolism in the dorsolateral prefrontal cortex [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn our study, another important factor for cognitive decline was increased age; aging plays a fundamental role in olfactory capacity, reaching its peak at age 40 and afterwards progressively declining [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRecent studies have consistently highlighted sex-related differences in the prevalence and clinical expression of post-COVID syndrome, with women being disproportionately more affected compared to men [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Additionally, women are significantly more likely to present fatigue, dyspnea, and neurocognitive complaints compared to men [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In our study, women presented more frequently ageusia, memory problems, depression, and myalgias. Such data reinforce the hypothesis that hormonal and immunological factors, particularly estrogen-mediated immune modulation, may contribute to the heightened vulnerability of women to long post-COVID syndrome, although further mechanistic studies are required to confirm this relationship [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn contrast, men appear to experience a more severe acute COVID-19, as reflected in our study with higher number of hospitalizations, higher need for supplementary O2; previous studies also reported higher mortality rates in men [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Importantly, the consistency of these systematic results across diverse populations suggests that sex differences in post-COVID risk are not fundamentally due to cultural or healthcare-access disparities, but rather reflect an underlying biological and pathophysiological mechanisms contributing to the outcome [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Collectively, the reviewed international evidence emphasizes the necessity of integrating sex as an independent determinant factor in both clinical assessment and research design for post-COVID care and post-COVID syndrome understanding.\u003c/p\u003e\u003cp\u003eIn the Muccioli et al. study, brain magnetic resonance imaging examined the integrity of the olfactory system and the neuropsychological profile in patients with persistent olfactory dysfunction related to COVID-19 infection and healthy controls. There was a correlation between alterations in the olfactory network and the severity of olfactory dysfunction and neuropsychological tests, without morphological changes. However, no evidence in this study suggested neurodegeneration in patients with PCS [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe sense of smell is essential as it stimulates appetite, promotes food intake, protects from poisoning, and is associated with better quality of life [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Anosmia is considered a common and cardinal symptom of COVID-19, particularly in the early stages of infection, sometimes being the only symptom in an otherwise asymptomatic patient. SARS-CoV-2 primarily targets cells expressing the angiotensin-converting enzyme 2 (ACE2) receptor, which is abundantly present in the nasal epithelium, particularly on non-neuronal cells. Key cells involved in the loss of olfactory function are the sustentacular cells that support the function of olfactory neurons [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Currently the development of anosmia in COVID-19 is considered to have a heritable component of up to 48% [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. SARS-CoV-2 infection reduces olfactory capacity through multiple pathways, including endothelial dysfunction, autoimmunity, latent viral reactivation, hyperinflammation, and autonomic nervous system dysfunction [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e] (Supplementary Fig.\u0026nbsp;1). Importantly, as olfactory capacity decreases, the risk of malnutrition increases [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. In our study, more than two-thirds of patients had hyposmia or anosmia, a similar finding was previously reported by Lechien et al. in a sample of 417 patients where 85.6% presented olfactory alterations [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMalnutrition in OA with post-COVID syndrome is one of the most common complications.\u003c/p\u003e\u003cp\u003eIn our study a positive correlation was observed with better nutrition (higher MNA) and higher cognition, which can be translated into a clinical need for screening in OA of malnutrition, frailty and loss of smell; since altogether may contribute to the deterioration of nutritional status, and consequently to cognitive impairment [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Previous studies discuss olfactory capacity and its impact on nutritional status [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]; however, only one recent study showed a correlation between olfactory function and the subjective global assessment (SGA) score in patients with chronic kidney disease [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. While others have not been able to corroborate a true association between loss of olfactory function and nutritional status in OA [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. Furthermore, it has been estimated that olfactory impairment could be more common in men compared to women [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. In our study, olfactory impairment was slightly more frequent in men, but it was not significantly associated with cognitive decline nor MNA score.\u003c/p\u003e\u003cp\u003eA similar study to ours evaluated the relationship between olfactory dysfunction, nutritional status, and cognitive function. It assessed 45 geriatric patients with neurodegenerative diseases and found that olfactory function had no association with nutritional status [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. This cohort differs from ours as it was conducted in 2016, before the emergence of COVID-19, therefore distinct pathophysiological mechanism for olfactory decline were involved.\u003c/p\u003e\u003cp\u003eSome of the limitations of our study include the cross-sectional design which is not suitable to imply causality but rather to generates hypotheses. The sample size is small, and there are multiple confounders that can participate in the generation of cognitive decline. We did not measure inflammatory biomarkers, nor included information about treatments during the acute infection or for PCS.\u003c/p\u003e\u003cp\u003eThe strengths of our study lie in its population; older adults with post-COVID syndrome, which have been an understudied population despite suffering from severe sequels. We evaluated, together, the risk of malnutrition, olfactory capacity, and cognitive impairment, metrics that require a qualified personnel, are not often performed on a routine basis.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eIn conclusion, our study presents suggestive risk factors for cognitive involvement in a sex specific manner, including self-reported memory problems for both sexes, and brain fog, palpitations and dyspnea for men. We observed that OA with post-COVID syndrome frequently presented a decline in olfactory capacity and this complication was associated to cognitive impairment. Nutritional status measured by the MNA is importantly associated in the development of cognitive impairment irrespective of the sex, while changes in anthropometric measurements related to obesity where only associated to cognitive decline in women. Our findings should be confirmed in larger, longer-term, multicenter studies with measurements of inflammatory biomarkers and other comorbidities previously associated to cognitive impairment. Furthermore, the research around post-COVID syndrome should be enhanced to define better treatments that can help this population to resolve their situation and prevent more serious or threatening outcomes for OA.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eInformed Consent Statement\u003c/h2\u003e\u003cp\u003e\u003cb\u003e\u003c/b\u003eInformed consent was obtained from all subjects involved in the study.\u003c/p\u003e\u003ch2\u003eConflicts of Interest\u003c/h2\u003e\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization, ALGG, LGL and MGZC; methodology, ALGG, LGL, EIFH, and MGZC; formal analysis, EIFH and MGZC.; investigation, ALGG, JCI, and MVV; resources, ALG, LGL and MGZC; data obtention, ALGG; data curation, ALGG and MGZC; writing\u0026mdash;original draft preparation, ALGG, JCI, MVV, and MGZC; writing\u0026mdash;review and editing ALGG, LGL, JCI, MVV, EIFH, and MGZC; supervision, LGL, JCI, and MGZC. All authors have read and agreed to the published version of the manuscript.\u0026rdquo;\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eUpon acceptance APC will be covered by Fondo Semilla from Universidad Aut\u0026oacute;noma de Guadalajara.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBatiha GE, Al-Kuraishy HM, Al-Gareeb AI, Welson NN. Pathophysiology of Post-COVID syndromes: a new perspective. Virol J. 2022;19(1):158. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12985-022-01891-2\u003c/span\u003e\u003cspan address=\"10.1186/s12985-022-01891-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCarrillo-Esper R. Post-COVID-19 syndrome. Gac Med Mex. 2022;158(3):115\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.24875/GMM.M22000652\u003c/span\u003e\u003cspan address=\"10.24875/GMM.M22000652\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCarfi A, Bernabei R, Landi F, Gemelli Against C-P-ACSG. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020;324(6):603\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jama.2020.12603\u003c/span\u003e\u003cspan address=\"10.1001/jama.2020.12603\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCabrera Martimbianco AL, Pacheco RL, Bagattini AM, Riera R. Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review. Int J Clin Pract. 2021;75(10):e14357. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/ijcp.14357\u003c/span\u003e\u003cspan address=\"10.1111/ijcp.14357\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eArikawa E, Kaneko N, Nohara K, Yamaguchi T, Mitsuyama M, Sakai T. Influence of Olfactory Function on Appetite and Nutritional Status in the Elderly Requiring Nursing Care. J Nutr Health Aging. 2020;24(4):398\u0026ndash;403. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s12603-020-1334-3\u003c/span\u003e\u003cspan address=\"10.1007/s12603-020-1334-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBorsetto D, Hopkins C, Philips V, Obholzer R, Tirelli G, Polesel J, et al. Self-reported alteration of sense of smell or taste in patients with COVID-19: a systematic review and meta-analysis on 3563 patients. Rhinology. 2020;58(5):430\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4193/Rhin20.185\u003c/span\u003e\u003cspan address=\"10.4193/Rhin20.185\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWanga V, Chevinsky JR, Dimitrov LV, Gerdes ME, Whitfield GP, Bonacci RA, et al. Long-Term Symptoms Among Adults Tested for SARS-CoV-2 - United States, January 2020-April 2021. MMWR Morb Mortal Wkly Rep. 2021;70(36):1235\u0026ndash;41. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.15585/mmwr.mm7036a1\u003c/span\u003e\u003cspan address=\"10.15585/mmwr.mm7036a1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMurphy C, Schubert CR, Cruickshanks KJ, Klein BE, Klein R, Nondahl DM. Prevalence of olfactory impairment in older adults. JAMA. 2002;288(18):2307\u0026ndash;12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jama.288.18.2307\u003c/span\u003e\u003cspan address=\"10.1001/jama.288.18.2307\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChang JY, Chou KR, Chang YL, Lin WY, Chiu HL, Liao YC et al. Enhancing Cognitive Function and Well-being in Older Adults With Cognitive and Physical Decline: A Meta-analysis of Randomized Controlled Trials Examining Physical Activity Interventions. J Phys Act Health. 2025:1\u0026ndash;12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1123/jpah.2025-0401\u003c/span\u003e\u003cspan address=\"10.1123/jpah.2025-0401\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCereda E, Pedrolli C, Klersy C, Bonardi C, Quarleri L, Cappello S, et al. Nutritional status in older persons according to healthcare setting: A systematic review and meta-analysis of prevalence data using MNA((R)). Clin Nutr. 2016;35(6):1282\u0026ndash;90. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.clnu.2016.03.008\u003c/span\u003e\u003cspan address=\"10.1016/j.clnu.2016.03.008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCeban F, Ling S, Lui LMW, Lee Y, Gill H, Teopiz KM, et al. Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis. Brain Behav Immun. 2022;101:93\u0026ndash;135. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.bbi.2021.12.020\u003c/span\u003e\u003cspan address=\"10.1016/j.bbi.2021.12.020\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHe D, Yuan M, Dang W, Bai L, Yang R, Wang J, et al. Long term neuropsychiatric consequences in COVID-19 survivors: Cognitive impairment and inflammatory underpinnings fifteen months after discharge. Asian J Psychiatr. 2023;80:103409. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ajp.2022.103409\u003c/span\u003e\u003cspan address=\"10.1016/j.ajp.2022.103409\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMansell V, Hall Dykgraaf S, Kidd M, Goodyear-Smith F. Long COVID and older people. Lancet Healthy Longev. 2022;3(12):e849\u0026ndash;54. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S2666-7568(22)00245-8\u003c/span\u003e\u003cspan address=\"10.1016/S2666-7568(22)00245-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen Y, Yang W, Chen F, Cui L. COVID-19 and cognitive impairment: neuroinvasive and blood\u0026ndash;brain barrier dysfunction. J Neuroinflammation. 2022;19(1):222. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12974-022-02579-8\u003c/span\u003e\u003cspan address=\"10.1186/s12974-022-02579-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTavares-Junior JWL, de Souza ACC, Borges JWP, Oliveira DN, Siqueira-Neto JI, Sobreira-Neto MA, et al. COVID-19 associated cognitive impairment: A systematic review. Cortex. 2022;152:77\u0026ndash;97. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.cortex.2022.04.006\u003c/span\u003e\u003cspan address=\"10.1016/j.cortex.2022.04.006\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRothenberg E. Coronavirus Disease 19 from the Perspective of Ageing with Focus on Nutritional Status and Nutrition Management-A Narrative Review. Nutrients. 2021;13(4). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/nu13041294\u003c/span\u003e\u003cspan address=\"10.3390/nu13041294\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShah DP, Thaweethai T, Karlson EW, Bonilla H, Horne BD, Mullington JM, et al. Sex Differences in Long COVID. JAMA Netw Open. 2025;8(1):e2455430. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamanetworkopen.2024.55430\u003c/span\u003e\u003cspan address=\"10.1001/jamanetworkopen.2024.55430\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFernandez-de-Las-Penas C, Martin-Guerrero JD, Pellicer-Valero OJ, Navarro-Pardo E, Gomez-Mayordomo V, Cuadrado ML, et al. Female Sex Is a Risk Factor Associated with Long-Term Post-COVID Related-Symptoms but Not with COVID-19 Symptoms: The LONG-COVID-EXP-CM Multicenter Study. J Clin Med. 2022;11(2). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/jcm11020413\u003c/span\u003e\u003cspan address=\"10.3390/jcm11020413\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMuley A, Mitra S, Bhaliya B, Soni S, Joshi A. A Systematic Review and Meta-analysis to Identify Risk Factors for Developing Long COVID-19. J Assoc Phys India. 2024;72(5):68\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNotarte KI, de Oliveira MHS, Peligro PJ, Velasco JV, Macaranas I, Ver AT, et al. Age, Sex and Previous Comorbidities as Risk Factors Not Associated with SARS-CoV-2 Infection for Long COVID-19: A Systematic Review and Meta-Analysis. J Clin Med. 2022;11(24). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/jcm11247314\u003c/span\u003e\u003cspan address=\"10.3390/jcm11247314\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFatuzzo I, Niccolini GF, Zoccali F, Cavalcanti L, Bellizzi MG, Riccardi G, et al. Neurons, Nose, and Neurodegenerative Diseases: Olfactory Function and Cognitive Impairment. Int J Mol Sci. 2023;24(3). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/ijms24032117\u003c/span\u003e\u003cspan address=\"10.3390/ijms24032117\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evon Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies. Int J Surg. 2014;12(12):1495\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ijsu.2014.07.013\u003c/span\u003e\u003cspan address=\"10.1016/j.ijsu.2014.07.013\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBenchimol EI, Smeeth L, Guttmann A, Harron K, Moher D, Petersen I, et al. The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement. PLoS Med. 2015;12(10):e1001885. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pmed.1001885\u003c/span\u003e\u003cspan address=\"10.1371/journal.pmed.1001885\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eResneck JS. Jr. Revisions to the Declaration of Helsinki on Its 60th Anniversary: A Modernized Set of Ethical Principles to Promote and Ensure Respect for Participants in a Rapidly Innovating Medical Research Ecosystem. JAMA. 2025;333(1):15\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jama.2024.21902\u003c/span\u003e\u003cspan address=\"10.1001/jama.2024.21902\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCho JH, Jeong YS, Lee YJ, Hong SC, Yoon JH, Kim JK. The Korean version of the Sniffin' stick (KVSS) test and its validity in comparison with the cross-cultural smell identification test (CC-SIT). Auris Nasus Larynx. 2009;36(3):280\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.anl.2008.07.005\u003c/span\u003e\u003cspan address=\"10.1016/j.anl.2008.07.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eInstituto Nacional de G. Gu\u0026iacute;a de instrumentos de evaluaci\u0026oacute;n geri\u0026aacute;trica integral. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.gob.mx/inger/documentos/guia-de-instrumentos-de-evaluacion-geriatrica-integral\u003c/span\u003e\u003cspan address=\"https://www.gob.mx/inger/documentos/guia-de-instrumentos-de-evaluacion-geriatrica-integral\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBeaman SRd, Beaman PE, Garcia-Pe\u0026ntilde;a C, Villa MA, Heres J, C\u0026oacute;rdova A, Aging, et al. Neuropsychol Cognition. 2004;11(1):1\u0026ndash;11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1076/anec.11.1.1.29366\u003c/span\u003e\u003cspan address=\"10.1076/anec.11.1.1.29366\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFolstein MF, Folstein SE, McHugh PR. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189\u0026ndash;98. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/0022-3956(75)90026-6\u003c/span\u003e\u003cspan address=\"10.1016/0022-3956(75)90026-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKroc L, Fife E, Piechocka-Wochniak E, Soltysik B, Kostka T. Comparison of Nutrition Risk Screening 2002 and Subjective Global Assessment Form as Short Nutrition Assessment Tools in Older Hospitalized Adults. Nutrients. 2021;13(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/nu13010225\u003c/span\u003e\u003cspan address=\"10.3390/nu13010225\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSilva DFO, Lima S, Sena-Evangelista KCM, Marchioni DM, Cobucci RN, Andrade FB. Nutritional Risk Screening Tools for Older Adults with COVID-19: A Systematic Review. Nutrients. 2020;12(10). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/nu12102956\u003c/span\u003e\u003cspan address=\"10.3390/nu12102956\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXiong J, Lipsitz O, Nasri F, Lui LMW, Gill H, Phan L, et al. Impact of COVID-19 pandemic on mental health in the general population: A systematic review. J Affect Disord. 2020;277:55\u0026ndash;64. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jad.2020.08.001\u003c/span\u003e\u003cspan address=\"10.1016/j.jad.2020.08.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDoty RL. Olfactory dysfunction in COVID-19: pathology and long-term implications for brain health. Trends Mol Med. 2022;28(9):781\u0026ndash;94. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.molmed.2022.06.005\u003c/span\u003e\u003cspan address=\"10.1016/j.molmed.2022.06.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSylvester SV, Rusu R, Chan B, Bellows M, O'Keefe C, Nicholson S. Sex differences in sequelae from COVID-19 infection and in long COVID syndrome: a review. Curr Med Res Opin. 2022;38(8):1391\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/03007995.2022.2081454\u003c/span\u003e\u003cspan address=\"10.1080/03007995.2022.2081454\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMuccioli L, Sighinolfi G, Mitolo M, Ferri L, Jane Rochat M, Pensato U, et al. Cognitive and functional connectivity impairment in post-COVID-19 olfactory dysfunction. Neuroimage Clin. 2023;38:103410. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.nicl.2023.103410\u003c/span\u003e\u003cspan address=\"10.1016/j.nicl.2023.103410\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWinter AL, Henecke S, Lundstrom JN, Thunell E. Impairment of quality of life due to COVID-19-induced long-term olfactory dysfunction. Front Psychol. 2023;14:1165911. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fpsyg.2023.1165911\u003c/span\u003e\u003cspan address=\"10.3389/fpsyg.2023.1165911\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eButowt R, von Bartheld CS. Anosmia in COVID-19: Underlying Mechanisms and Assessment of an Olfactory Route to Brain Infection. Neuroscientist. 2021;27(6):582\u0026ndash;603. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/1073858420956905\u003c/span\u003e\u003cspan address=\"10.1177/1073858420956905\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWilliams FMK, Freidin MB, Mangino M, Couvreur S, Visconti A, Bowyer RCE, et al. Self-Reported Symptoms of COVID-19, Including Symptoms Most Predictive of SARS-CoV-2 Infection, Are Heritable. Twin Res Hum Genet. 2020;23(6):316\u0026ndash;21. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1017/thg.2020.85\u003c/span\u003e\u003cspan address=\"10.1017/thg.2020.85\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHopkins C, Surda P, Whitehead E, Kumar BN. Early recovery following new onset anosmia during the COVID-19 pandemic - an observational cohort study. J Otolaryngol Head Neck Surg. 2020;49(1):26. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s40463-020-00423-8\u003c/span\u003e\u003cspan address=\"10.1186/s40463-020-00423-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGunzer W. Changes of Olfactory Performance during the Process of Aging - Psychophysical Testing and Its Relevance in the Fight against Malnutrition. J Nutr Health Aging. 2017;21(9):1010\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s12603-017-0873-8\u003c/span\u003e\u003cspan address=\"10.1007/s12603-017-0873-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020;277(8):2251\u0026ndash;61. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00405-020-05965-1\u003c/span\u003e\u003cspan address=\"10.1007/s00405-020-05965-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGrund S, Bauer JM. Malnutrition and Sarcopenia in COVID-19 Survivors. Clin Geriatr Med. 2022;38(3):559\u0026ndash;64. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.cger.2022.04.001\u003c/span\u003e\u003cspan address=\"10.1016/j.cger.2022.04.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHummel T, Nordin S. Olfactory disorders and their consequences for quality of life. Acta Otolaryngol. 2005;125(2):116\u0026ndash;21. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/00016480410022787\u003c/span\u003e\u003cspan address=\"10.1080/00016480410022787\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eToller SV. Assessing the impact of anosmia: review of a questionnaire's findings. Chem Senses. 1999;24(6):705\u0026ndash;12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/chemse/24.6.705\u003c/span\u003e\u003cspan address=\"10.1093/chemse/24.6.705\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRaff AC, Lieu S, Melamed ML, Quan Z, Ponda M, Meyer TW, et al. Relationship of impaired olfactory function in ESRD to malnutrition and retained uremic molecules. Am J Kidney Dis. 2008;52(1):102\u0026ndash;10. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1053/j.ajkd.2008.02.301\u003c/span\u003e\u003cspan address=\"10.1053/j.ajkd.2008.02.301\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eToussaint N, de Roon M, van Campen JP, Kremer S, Boesveldt S. Loss of olfactory function and nutritional status in vital older adults and geriatric patients. Chem Senses. 2015;40(3):197\u0026ndash;203. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/chemse/bju113\u003c/span\u003e\u003cspan address=\"10.1093/chemse/bju113\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchubert CR, Cruickshanks KJ, Fischer ME, Huang GH, Klein BE, Klein R, et al. Olfactory impairment in an adult population: the Beaver Dam Offspring Study. Chem Senses. 2012;37(4):325\u0026ndash;34. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/chemse/bjr102\u003c/span\u003e\u003cspan address=\"10.1093/chemse/bjr102\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJin SY, Jeong HS, Lee JW, Kwon KR, Rha KS, Kim YM. Effects of nutritional status and cognitive ability on olfactory function in geriatric patients. Auris Nasus Larynx. 2016;43(1):56\u0026ndash;61. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.anl.2015.06.009\u003c/span\u003e\u003cspan address=\"10.1016/j.anl.2015.06.009\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"olfactory capacity, nutritional risk, mini nutritional assessment, cognitive impairment, post-COVID syndrome, older adults","lastPublishedDoi":"10.21203/rs.3.rs-7520208/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7520208/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground/Objectives\u003c/strong\u003e: Post-COVID syndrome (PCS) emerged as a significant public health concern, is characterized by persistent symptoms following SARS-CoV-2 infection. Cognitive impairment is a common sequela, particularly among older adults (OA). Although olfactory dysfunction and malnutrition have been previously associated to cognitive decline, it remains to be elusive to what extent sex-specific variations in these and additional factors will be pivotal to guide targeted interventions in a sex specific manner. This study seeks to identify clinical and biological correlates for cognitive decline in older adults, with emphasis in gender specificity.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: We underwent a cross-sectional study among older adults hospitalized at a geriatric care unit. Olfactory function was assessed using the Sniffin' Stick Test. Cognitive impairment was evaluated by the Mini-Mental State Examination, and nutritional status was assessed with the Mini Nutritional Assessment. Statistical analyses included linear regression.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: A total of 45 patients with PCS were included. Cognitive impairment was observed in 66.7% of participants and was significantly associated with olfactory dysfunction, no direct association was found with nutritional status. However, on a multiple regression analysis, the nutritional status was significantly associated to cognitive decline.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: Olfactory dysfunction is a potential biomarker for cognitive impairment in older adults with PCS. In our study nutritional status emerged as a crucial factor associated to olfactory dysfunction and cognitive decline with a higher impact on women. Further research is needed to elucidate the underlying mechanisms related to a nutritional decline in older women with olfactory dysfunction and develop targeted interventions to mitigate cognitive decline in this vulnerable population, through improvement in nutrition and olfactory training.\u003c/p\u003e","manuscriptTitle":"Sex-specific differences in nutritional status as risk factors for cognitive decline amongst older adults with Post-COVID Syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-05 11:41:06","doi":"10.21203/rs.3.rs-7520208/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"34194aa2-e695-43dd-87db-122f150a7e73","owner":[],"postedDate":"November 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-15T17:53:55+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-05 11:41:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7520208","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7520208","identity":"rs-7520208","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}