Investigation of the prevalence of vitamin D deficiency in hospitalized COVID-19 patients and its association with disease severity, outcome, and mortality

Investigation of the prevalence of vitamin D deficiency in hospitalized COVID-19 patients and its association with disease severity, outcome, and mortality | 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 Investigation of the prevalence of vitamin D deficiency in hospitalized COVID-19 patients and its association with disease severity, outcome, and mortality Abolfazl Zendehdel, SaeidReza JamaliMoghaddamsiyahkali, Ziba Aghsaeifard, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8254002/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background In this study, we aimed to assess the prevalence of vitamin D deficiency in hospitalized Covid-19 patients and demonstrate its association with severity and mortality of the disease. Methods This observational study at Ziaeian Hospital, Tehran, Iran. Of all confirmed COVID-19 patients who were admitted to this hospital 276 patients were enrolled in this study and divided into two groups; 145 patients in group1 with a serum 25(OH)D level > 20 ng/ml and 131 patients in group 2 with a serum 25 (OH)D level = < 20 ng/ml. The severity, outcome, and mortality of COVID-19 disease were compared in these two groups, based on chest CT scans findings, laboratory data, and patient' vital signs on admission day, and the duration of hospitalization, requirement to ICU admission, need for intubation, and mortality. Results The prevalence of vitamin D deficiency was 22.1%, and vitamin D insufficiency by definition of serum 25(OH)D levels 12–20 ng/ml was 25.4%. Despite, an increase in serum levels of CPK, Ferritin, LDH, CRP, D-dimer, AST, and ALT, there was not any significant relationship between serum level of 25(OH)D with laboratory tests, chest CT scan scores, and patient's vital signs on admission day by univariate and multivariate analysis. The odds of incidence of ICU admission, mechanical ventilation, and mortality were higher in group 2 which was not statistically significant by univariate and multivariate analysis. Still, the mortality was significantly higher in subgroup 2 by multivariate regression analysis. Conclusion This study showed that vitamin D deficiency was associated with a higher mortality rate, while could not show any significant association between serum 25(OH)D levels with the incidence of ICU admission, need for mechanical ventilation, and length of hospital stay, also we did not find any significant relationship with laboratory tests, radiologic findings, and patient's vital signs on admission day. COVID-19 vitamin D prevalence severity outcome mortality Figures Figure 1 Introduction Coronavirus disease (COVID-19) originated in Wuhan, China, rapidly spread around the world, due to its inherently contagious, made a pandemic on March 12, 2020, resulting in many death in every country around the world and became a big concern for global public health ( 1 ). So it is important to identify modifiable prognostic and risk factors that could affect disease outcomes and result in severity and mortality of disease in COVID-19-infected patients to have better management and control of this pandemic and help to improve its outcomes. The clinical presentation of this disease is extensive and characterized by an important clinical variability between different infected patients ( 2 ), which could suggest that there are important host-related factors that affect its severity and outcome. This fact that there is a significant difference in Covid-19 mortality among different countries, particularly when mortality is evaluated by latitude, and seen that peoples who are less exposed to sunlight to retain adequate vitamin D levels have a higher mortality rate, bring a new debate about the possible role of vitamin D in determining the clinical status and outcomes of these patients ( 3 , 4 ). Additionally, older adults with underlying diseases are at higher risk for severe illness ( 5 ). A low level of vitamin D is common in the elderly and has been associated with all-cause mortality including sepsis ( 4 ). Vitamin D deficiency is also more prevalent among individuals with darker skin than those with lighter skin color, and studies have shown that people from racial groups with darker skin are at greater risk for severe Covid-19 disease ( 6 ). Furthermore, obesity is a cause of susceptibility to severe Covid-19 infection ( 4 , 7 ), and is associated with vitamin D insufficiency due to its deposition in body fat ( 8 ). Several studies demonstrated that low vitamin D has been associated with increased risk and severity of respiratory tract infections. ( 4 , 9 ) ( 10 ), and in one of our studies, we demonstrated that vitamin D intake decreased Chronic obstructive pulmonary disease (COPD) exacerbation and improved FEV1 in the severe/very severe cases of COPD ( 11 ). Therefore, there is an interest to investigate the role of vitamin D, as its deficiency is a prevalent condition worldwide, in modulating the severity of Covid-19 infection given the complex pathophysiology of this disease, but this association may be confounded by common causal or risk factors of both low serum vitamin D levels and severe Covid-19 infections like elderly. Vitamin D (calciferol), is a generic term that refers to a group of fat-soluble compounds with a four-ringed cholesterol in base ( 4 , 12 ). 10% of vitamin D is from diet in the form of two metabolites, D2 and D3, and consumed through vitamin D-rich foods including fatty fish, eggs, and fortified foods, while the other 90%, the major source of Vit D, is provided in the skin by nonenzymatic conversion of 7-dehydrocholestrol to D3 after exposure to sunlight ( 12 , 13 ). This dermal synthesis could vary based on geographic location and latitude, season and time of day or length of daily exposure, the skin type and its pigmentation, use of sunblock lotions ( 12 ). Melanin reduces dermal synthesis of Vit D3 in darker skin. Malabsorptive syndromes and fat-malabsorption disorders associated with low serum 25(OH)D levels ( 12 ). Vitamin D2 and D3, from diet or skin, are biologically inactive and require converting enzymatically. In the first step these metabolites must be 25-hydroxylated and convert to 25(OH)D (calcidiol) in liver, which is the major circulating form of vitamin D with the highest half-life of two or three weeks, then 25(OH)D, 1-hydroxylated via 1-alpha- hydroxylase enzyme (CYP27B1) in kidneys as renal, or in other tissues as extrarenal or local pathways, to make its active form 1,25-dihydrocholecalciferol vitamin D (calcitriol) ( 12 , 14 ). The liver has also the capacity of metabolize 25(OH)D to inactive metabolites which is accomplished by the P450 system and is enhanced by alcohol, barbiturates, and phenytoin. The serum concentration of 25(OH)D is the best laboratory indicator of vitamin D adequacy and is commonly used to assess individual vit D status ( 6 , 12 ). Based on Institute of Medicine (IOM) conclusion a serum 25(OH)D level of 20 ng/ml is sufficient for most individuals ( 12 ). The active form of vitamin D, 1,25(OH)2D, binds to vitamin d receptors (VDR) which is an intracellular receptor in target tissues and is nearly universally expressed in nucleated cells, and regulate gene transcriptions. Approximately 3 percent of human/mouse genome is under the control of 1,25(OH)2D ( 15 ). Vitamin D has a known role in calcium and bone hemostasis, but the spectrum of its activity is much broader than it, and besides that potentially regulates many other cellular functions ( 15 ). Antigen presenting cells, such as macrophages, B and T cells, and dendritic cells express vitamin D receptors (VDR). Vitamin D has major effects on nearly all cells of the immune system and can modulate most aspects of the innate and acquired immune system ( 9 , 15 ) Although several clinical trials and studies have been performed to evaluate the role of vitamin D as a preventive and therapeutic option in Covid-19 infected patients, but the results remain controversial ( 16 , 17 ). Some observational studies have shown a correlation between Covid-19 severity and mortality with low serum levels of 25(OH)D ( 14 , 18 ), while others did not. ( 19 , 20 ) Therefore, further studies are required in an emergency situation like this pandemic, to demonstrate this fact, even though the incidence is starting to decline and vaccines are already available, because there have been some Covid-19 cases with severe disease and even death in patients who were fully vaccinated and a new wave of patients due to new variants of virus may emerge in the future, so it is important to keep researching. In this study, we aimed to evaluate the prevalence of vitamin D deficiency in patients with Covid-19 infection in this hospital, as a center for Covid-19 patients, and its association with mortality, outcome, and severity of Covid-19 disease by comparing two groups, based on clinical outcomes including length of hospital stay, need for ICU admission, mechanical ventilation, mortality rate and the results of lab tests, chest CT scans scores and patient's vital signs on admission day. Methods Study design This was a single center observational study, performed at Ziaeian Hospital between March 21th and September 11th, 2020. This hospital is an educational and medical center for Covid-19 infected patients at Tehran university of Medical Science, Iran. 276 inpatients with confirmed Covid-19 during almost five consecutive months, were enrolled in this study, according to their serum level of 25 (OH) D, and were assigned to two groups. Group 1 including 145 inpatients, had a serum level of 25 (OH) D > 20 ng/ml, whereas patients in group 2 including 131 inpatients had a level of vit D = < 20 ng/ml. Also, the analysis was performed as a secondary finding (sensitivity analysis), between two subgroups of patients with serum 25(OH)D levels 30 (as an optimal range, subgroup 1), to clarify the probable association in vitamin D deficient group of patients. patients who were admitted to this hospital received therapeutic regimens according to the guidelines issued by Iranian Ministry of Health and Medical Education ( 7 ), Considering the revisions happened on these protocols and guidelines during the period of study, it was tried to mitigate the effect of this therapeutic changes, on our sampling and its proportion. Study population The confirmed Covid-19 infected patients with moderate to severe disease who need hospitalization were enrolled in this study by simple random sampling without stratification, from admitted patients in this hospital. Confirmation of the diagnosis of Covid-19 was based on clinical symptoms with a radiologic change of chest computed tomography (CT) for Covid-19 or a positive diagnostic kit result (Rt-PCR) ( 21 ), aside from the approval of diagnosis and clinical requirement of hospitalization by our physicians in this hospital. ( 7 ) Patients without diseases associated with vitamin D deficiency such as parathyroid disease or history of its surgery, liver and kidney failure, malabsorption disorders such as chronic diarrhea, bile duct disorders, celiac disease, and pancreatic diseases were included in the study. Patients do not meet inclusion criteria or patients with a lack of data or written informed consent were excluded from the study. we excluded only one patient who was under chemotherapy treatment and only one pregnant patient from the sample. Also, patients treated with vitamin D drugs at the hospital were excluded from the study. Demographic information of individuals, laboratory parameters including LDH (lactate dehydrogenase), CRP (c-reactive protein), Vit D (vitamin D), D-dimer, ferritin, CPK (creatinine phosphokinase), CBC (complete blood count), AST and ALT(liver function tests), clinical features and vital signs including pulse rate, respiratory rates, blood pressure, blood oxygen saturation, the result of Covid-19 test (PCR), chest CT scans, underlying disease (diabetes, hypertension, cardiovascular problems, respiratory problems, etc.), the admission to the intensive care unit (ICU), the requirement of mechanical ventilation, the duration of hospitalization, their outcome and mortality were extracted from patient's clinical records and compared. Patient form was used to record all the information for each patient. This study was approved by the Ethical committee of Tehran University of Medical Science (Ethic number: IR.TUMS. VCR.REC.1399.262), and was conducted in accordance with the Declaration of Helsinki and in compliance with ethical guidelines. Written informed consent was obtained from all patients when admitted to the hospital. Data and identities of individuals were kept confidential. Intervention and measurement Vitamin D status of the patients was measured by their serum 25(OH)D level on admission day and classified into different classes: deficient (less than 12 ng/ml), insufficient (12–20 ng/ml), sufficient (more than 20 ng/ml) ( 22 ). The severity of patient's disease is evaluated with these criteria: clinical findings including SO2, SBP, PR, RR, and paraclinical parameters including LDH (lactate dehydrogenase), CRP (c-reactive protein), D-dimer, ferritin, CPK (creatinine phosphokinase), CBC/diff (complete blood count), AST and ALT (liver function tests) and chest CT scans score at the first day of admission. According to the guidelines issued by Iranian Ministry of Health and Medical Education (r) severe disease defined by SO2 30/min, PR > 125/min, or SBP 500 ug/l or D-dimer > 1000 ng/ml, CRP > 12 mg/l (or > = 2+), CPK > 340 U/l in women and > 390 in men, LDH > 960 U/l in patients younger than 65 years old or > 1060 in patients > = 65years, elevated ALT and AST u/l or > ULN (upper limit normal defined by our hospital laboratory), or Lymph < 20% in CBC/diff. ( 7 ) Chest CT severity score (CT-SS) was used to access the severity of the disease based on the degree of involvement of their lungs at chest CT scans and was used to compare the severity of disease between our two groups. This scoring was done with an expert radiologist in this hospital, according to this score both lungs are divided into 5 lobes and each lobe can get a score of involvement between 1 to 5 so every CT scan is scored between 1 to 25 ( 23 ). Severe disease defined by a CT-SS > 12.5 or more than 50% involvement of lungs at chest CT scans ( 7 ) . Outcome In this study, the mortality and severity of Covid-19 disease were assessed and compared in the groups with and without vitamin D deficiency to understand the association between serum level of vitamin D and outcome of Covid-19 disease. The severity of Covid-19 disease is assessed by clinical findings (SO2, SBP, PR, RR), and paraclinical parameters (LDH (lactate dehydrogenase), CRP (c-reactive protein), D-dimer, ferritin, CPK (creatinine phosphokinase), CBC/diff (complete blood count), AST and ALT (liver function tests)), and chest CT scans scores on the admission day and patient's outcomes during hospitalization. The primary endpoint was the serum level of these lab tests, clinical and vital signs and CT scans scores on the admission day, as the cross-sectional part of our study. The secondary endpoints were, the duration of hospitalization (length of hospital stay), a requirement for admission to the intensive care unit (ICU), mechanical ventilation, and patient's outcome, discharge, or mortality, as the cohort part of the study. Then by multivariate regression analysis (for age and sex), the adjusted association of serum level of vitamin D was observed on mortality and severity. Statistical analysis The data obtained were computerized and statistically analyzed using (SPSS v26). The results are expressed as frequency and percentage for qualitative variables and as mean and standard deviation (mean ± SD) quantitative variables. Confidence interval was 0.95 (Cl, 0.95). P value less than 0.05 was considered statistically significant. The power of study was 80%. Chi-square test and independent samples T-test were used to compare the baseline characteristics between two groups. Logistic regression analysis was used to investigate the relationship between binary outcomes and serum levels of vitamin D. Linear regression analysis was used to investigate the relationship between continuous outcomes and serum levels of vitamin D. Adjustment for confounding variables was performed by multiple linear and multiple logistic regression. Results Patients’ characteristics A total of 276 inpatients with confirmed Covid-19 infection after initial screening and excluding were enrolled in this study during almost five consecutive months and divided into two groups, 145 (52.5%) patients were classified into group1, who had a serum 25(OH)D level > 20 ng/ml as the sufficient group and 131(47.5%) of patients were classified in group2 with a serum 25(OH)D level of = < 20 ng/ml as the deficient and insufficient group. The baseline demographic and clinical characteristics of these identified patients are shown in Table 1 . As shown in this table, there were significant differences between two groups regarding gender and mean age which is higher in sufficient group (group 1) in comparison with group 2, but there were no significant differences between two groups in terms of underlying disease, smoking, and obesity. Table 1 patients demographic and characteristics data of two groups Total N = 276 Group 1 Serum vit D > 20)) N = 145 Group 2 (Serum vit D 30 Yes, number (%) Mean (sd) 57.4 (18.9) 169 (61.2%) 107 (38.8%) 91 (33%) 53 (19.2%) 32/137 (23.4%) 27.7 (5.9) 60.1 (18.1) 79 (54.5%) 66 (45.5%) 49 (33.8%) 24 (16.6%) 20/73 (27.4%) 28.1 ( 5 ) 54.4 (19.4) 90 (68.7%) 41 (31.3%) 42 (32.1%) 29 (22.1%) 12/64 (18.8%) 27.2 (6.9) 0.01 0.01 0.7 0.2 0.3 BMI = Body mass index, Sd = Standard deviation Overall, of these 276 patients, 107 (38.8%) patients were female and 169 (61.2%) were male and their ages ranged from 18 to 94 years old (mean = 57.4, Sd = 18.9). Vitamin D deficiency (serum 25(OH)D level 20 ng/ml). The mean quantitative serum level of 25(OH)D was 24.8 ng/ml (Sd = 16.1) in total group, 36.2 ng/ml (Sd = 13.8) in sufficient group ( 1 ), and 12.1 ng/ml (Sd = 5.3) in group 2. The percentage of ICU admission was 17.8% (49/276), mechanical ventilation 8.8% (24/274), mortality was 15.3% (42/275) and the mean of hospitalization length was 7.4 days (Sd = 5.4), in total group (276 patients). The relationship between serum 25 (OH)D level with biochemical parameters and radiologic findings on admission day (cross-sectional part of the study) The disease severity was assessed by patient's vital signs, chest CT scans findings, and the result of laboratory tests on admission day and compared between two groups. (Table 2 ) Table 2 the correlation between vitamin D status and lab tests, radiologic findings and vital signs in groups Univariate analysis Multivariate analysis Total N = 276 Group 1 N = 145 Group 2 N = 131 p- value AOR (95%CI) p-value CPK Sever Number (%)) 18 (6.5%) 8 (5.5%) 10 (7.6%) 0.4 1.43 (0.53, 3.83) 0.4 Ferritin Number (%) 102 (37%) 46 (31.7%) 56 (42.7%) 0.059 1.58 (0.94, 2.66) 0.08 LDH Number (%) 21 (7.6%) 7 (4.8%) 14 (10.7%) 0.07 2.58 (0.99, 6.75) 0.05 CRP Number (%) 154 (55.8%) 79 (54.5%) 75 (57.3%) 0.6 1.17 (0.7, 1.90) 0.5 D-dimer Number (%) 20 (7.2%) 8 (5.5%) 12 (9.2%) 0.2 2.08 (0.80, 5.39) 0.1 Lymphocyte Number (%) 126 (45.7%) 69 (47.6%) 57 (43.5%) 0.4 0.97 (0.58, 1.61) 0.9 AST Number (%) 97 (35.3%) 46 (31.7%) 51 (39.2%) 0.1 1.41 (0.85, 2.35) 0.1 ALT Number (%) 73 (26.5%) 36 (24.8%) 37 (28.5%) 0.4 1.12 (0.64, 1.96) 0.6 CT scan Number (%) 76 (27.5%) 44 (30.3%) 32 (24.4%) 0.3 0.79 (0.45, 1.37) 0.4 RR Number (%) 1 (0.4%) 0 (0%) 1 (0.8%) 0.9 SPO2 Number (%) 82 (29.7) 46 (31.7%) 36 (27.5%) 0.4 0.86 (0.50, 1.49) 0.6 SBP Number (%) 2 (0.7%) 1 (0.7%) 1 (0.8%) 0.9 0.99 (0.05, 16.90) 0.9 PR Number (%) 1 (0.4%) 0 (0%) 1 (0.8%) 0.9 AOR = Adjusted odds ratio, CI = Confidence interval, SD = Standard deviation, LDH = lactate dehydrogenase, CRP = c-reactive protein, CPK = creatinine phosphokinase Although the serum levels of CPK, Ferritin, LDH, CRP, D-dimer, AST, and ALT were higher in group 2 and we had more severe cases in group 2 and a near significant p-value for Ferritin (P = 0.05, AP = 0.08) and LDH (P = 0.07, AP = 0.05), by univariate and multivariate regression analysis there is no statistically significant differences between two groups in regard to laboratory tests. Since the age and gender had statistically significant differences between two groups (group 1, group 2), these confounding variables were adjusted in final models. Despite a little difference in a number of severe cases in PR, SBP, and RR between two groups, there was not a particular result, and could not be analyzed due to the small number of events. The number of severe cases in chest CT scans scores was a little higher in group 1 but by univariate and multivariate regression analysis there was not a significant difference between two groups in this regard and we could not show any relationship between serum level of 25(OH)D and the result of these lab tests and biochemical parameters, patient's vital signs or the degree of involvement on their chest CT scans on admission day. Also, we did a sensitivity analysis between two subgroups of serum 25(OH)D levels 30 (as an optimal range, subgroup 1), to identify the probable differences in association between serum level of vitamin D and these parameters by comparing two subgroups together to show it better but as shown in Table 3 the same results were seen in a comparison between two subgroups and there were no statistically significant differences between them in these regards. Table 3 the correlation between vitamin D status and lab tests, radiologic findings and vital signs in subgroups Univariate analysis Multivariate analysis Total N = 156 Subgroup 1 N = 91 Subgroup 2 N = 65 p- value AOR (95%CI) p-value CPK Sever Number (%) 13 (8.3%) 6 (6.6%) 7 (10.8%) 0.3 1.52 (0.44, 5.18) 0.4 Ferritin Number (%) 59 (37.8%) 29 (31.9%) 30 (46.2%) 0.07 1.59 (0.77, 3.30) 0.2 LDH Number (%) 15 (9.6%) 8 (8.8%) 7 (10.8%) 0.6 1.81 (0.56, 5.82) 0.3 CRP Number (%) 89 (57.1%) 53 (58.2%) 36 (55.4%) 0.7 0.85 (0.42, 1.70) 0.6 D-dimer Number (%) 8 (5.1%) 4 (4.4%) 4 (6.2%) 0.6 1.85 (0.41, 8.30) 0.4 Lymphocyte Number (%) 75 (48.1%) 45 (49.5%) 30 (46.2%) 0.6 0.98 (0.48, 2) 0.9 AST Number (%) 60 (38.5%) 30 (33%) 30 (46.2%) 0.09 1.98 (0.96,4.08) 0.06 ALT Number (%) 50 (32.1%) 27 (29.7%) 23 (35.4%) 0.4 1.08 (0.5,2.32) 0.8 CT scan Number (%) 37/145 (25.5%) 24/86 (27.9%) 13/59 (22%) 0.4 0.74 (0.32, 1.71) 0.4 RR Number (%) 1(0.6%) 0 (0%) 1 (1.6%) SPO2 Number (%) 46 (29.5%) 27 (29.7%) 19 (29.2%) 0.9 1.10 (0.50, 2.40) 0.8 SBP Number (%) 1 (0.6%) 0 (0%) 1 (1.5%) 0.9 PR Number (%) 0 (0%) 0 (0%) 0 (0%) AOR = Adjusted odds ratio, CI = Confidence interval, SD = Standard deviation, LDH = lactate dehydrogenase, CRP = c-reactive protein, CPK = creatinine phosphokinase The association between serum 25(OH)D level and clinical outcomes of Covid-19 disease (cohort design part of the study) As shown in Table 4 by comparison between two groups, despite higher percentages in mortality (17.6% vs 13.2%, p = o.3) and incidence of ICU admission (18.3% vs 17.2%, P = 0.8) and mechanical ventilation (10% vs 7.6%, p = 0.4), in patients with vitamin D deficiency and insufficiency (group 2), by univariate and multivariate regression analysis there is no significant differences between the two groups regarding, the incidence of mechanical ventilation (AOR = 1.52, 95%Cl = 0.63_3.66, P = 0.3), ICU admission (AOR = 1.15, 95%Cl = 0.61_2.20, P = 0.6), mortality (AOR = 1.70, 95%Cl = 0.85_3.40, P = 0.1) and the length of hospital stay (AB=-0.77, 95%Cl=-2.07_O.51, P = 0.2)(Fig. 1 ). Table 4 Clinical outcome comparison of study population for groups and subgroups Univariate analysis Multivariate analysis Group 1 N = 145 Group 2 N = 131 OR/B (95%CI) p- value AOR/B (95%CL) p-value LOHS Day(sd) Mechanical Ventilation Yes(%) ICU admission Yes(%) Mortality Yes(%) 7.9 (5.9) 11 (7.6%) 25 (17.2%) 19 (13.2%) Subgroup N = 91 6.8 (4.9) 13 (10.0%) 24 (18.3%) 23 (17.6%) Subgroup N = 65 -1.05 (-2.35, 0.24) 1.34 (0.58, 3.11) 1.07 (0.58, 1.99) 1.40 (0.72, 2.71) 0.1 0.4 0.8 0.3 -0.77 (-2.07, 0.51) 1.52 (0.63, 3.66) 1.15 (0.61, 2.20) 1.70 (0.85, 3.40) 0.2 0.3 0.6 0.1 LOHS Yes (%) Mechanical Ventilation Yes (%) ICU admission Yes (%) Mortality Yes (%) 7.9 (6.2) 6 (6.7%) 14 (15.4%) 10 (11.1%) 7.4 (4.8) 5 (7.8%) 14 (21.5%) 12 (18.5%) -4.97 (-2.32,1.32) 1.18 (0.34, 4.07) 1.51 (0.66, 3.43) 1.81 (0.73, 4.49) 0.5 0.7 0.3 0.2 -0.27 (-2.22,1.67) 1.35 (0.36, 5.08) 1.92 (0.77, 4.74) 2.93 (1.05, 8.15) 0.7 0.6 0.1 0.03 AOR = Adjusted odds ratio, CI = Confidence interval, ICU = Intensive care unit, SD = Standard deviation B = Regression coefficient, LOHS = Length of hospital stay In sensitivity analysis between two subgroups, by univariate regression analysis the comparison of the incidence of ICU admission (21.5% vs 15.4%, P = 0.3), mechanical ventilation (7.8% vs 6.7%, p = 0.7) and mortality (18.5% vs 11.1%, P = 0.2), showed a higher percentage in subgroup 2 with vitamin D deficiency which was not statistically significant, but by multivariate regression analysis the comparison of mortality between two subgroups was significantly higher in subgroup 2 ( AOR = 2.93, 95% CI = 1.05,8.15, P = 0.03) and serum level of vitamin D was negatively correlated with mortality.(Table 4 ) Discussion This pandemic has led to many death in every country around the world, has a severe burden and consecutive socioeconomic disruptions, and threatened the public health ( 24 ), So it is important to identify modifiable risk factors which could be effective and result in a poorer outcome of disease in covid-19 infected patients to have better management and controlling of the disease and its outcome. Therefore in this study, we evaluate the role of vitamin D as a protective factor, in Covid-19 severity and outcome for confirmed Covid-19 hospitalized patients, considering the fact that its deficiency is a prevalent condition worldwide. Vitamin D is a steroid hormone that has potent immunomodulatory actions and may influence the immune response to viral infections ( 25 ), and its deficiency is a risk factor for Covid-19 patients. In a large recent population-based study in Iranian children and adolescents, prevalence of vitamin D deficiency which is defined as serum 25(OH)D level < 30 ng/ml, was 71.1% ( 26 ), while in another population-based study in northeastern Iran, this prevalence (serum 25(OH)D level < 30 ng/ml) reported 62.2% ( 27 ). In our study the prevalence of serum 25(OH)D level < 30 ng/ml in Covid-19 inpatients was 67% (185/276), so according to the present study there is not much difference in prevalence of vitamin D deficiency between general population and Covid-19 hospitalized patients with moderate to severe disease, however, based on the limitations of our study's results, no scientific comment can be made, and more studies are needed in this field. In one observational study in Italy, revealed that serum 25(OH)D levels were inversely associated with IL6 levels, mortality, and need for ICU admission regardless of the confounding variables and are an independent predictor of disease severity and mortality in hospitalized patients ( 9 ). Similarly, according to the results of a systematic review and meta-analysis study, there is a strong correlation between mortality rate caused by Covid-19 infection and serum level of vitamin D, and suggested that a serum level of approximately 50 ng/ml may prevent any excess mortality and said that low D3 is a predictor rather than just a side effect of the infection ( 28 ). In this study, we showed that vitamin D deficiency (serum level 30 ng/ml in subgroup 1, P = 0,03) and also associated with an increased incidence of ICU admission and mechanical ventilation, which was not statistically significant. In some studies, the association between vitamin D deficiency with Covid-19 disease and its outcome remains controversial and further studies requirements for evaluating the role of this vitamin suggested ( 6 ) ( 16 ), Whereas, other studies showed that there was no significant association between serum level of vitamin D and Covid-19 clinical outcomes ( 19 , 20 ). In one retrospective cohort study which was similar to our study, 270 Covid-19 inpatients were enrolled and divided into two groups based on their vitamin D levels > = 20 ng/ml and < 20 ng/ml, which showed that there was no association between vitamin D level with the need for ICU admission, mechanical ventilation, mortality, and thromboembolism in COVID-19 patients ( 19 ). In our study when we compare both groups together, which were divided based on serum 25(OH)D levels of > = 20 ng/ml and < 20ng/ml, we did not see any significant association between serum levels of vitamin D with a length of hospitalization, incidence of ICU admission, mechanical ventilation, and mortality, too. So one of the reasons for controversial results of different studies may be due to this inconsistent definition of vitamin D deficiency (< 12 ng/ml or < 20 ng/ml). The results of another systematic review and meta-analysis showed that the most of studies indicated a significant association between serum 25(OH)D levels and Covid-19 severity and outcome, but the results of studies that evaluated the association between vitamin D deficiency and pulmonary complications, inflammation, hospitalization, and ICU admission were inconsistent and insufficient ( 29 ). In current study, we show that despite an increase in inflammatory biochemical parameters including the serum level of CPK, Ferritin, LDH, CRP, D-dimer, AST, and ALT, but we could not show any significant association between serum 25(OH)D levels and inflammatory lab tests. Also, there was no association between pulmonary involvement on chest CT scans and serum levels of vitamin D in this study. In another observational study in Turkey, 204 Covid-19 patients were enrolled and divided into two groups according to the severity of their disease outpatients with mild disease and patients with severe conditions, showed that there was a significantly lower serum of vitamin D and a significantly higher serum level of inflammatory lab tests including CRP, Ferritin and D-dimer and lymphocyte count, in a group of inpatients with severe disease ( 30 ). As seen, the patients in this study ( 30 ), were divided into outpatients and inpatients in comparison with our study, in which we only evaluate these inflammatory biochemical parameters in moderate to severe cases who need to hospitalization and were inpatients. So another reason for controversial results of studies may be due to the design of the studies, which could perform in hospitalized, outpatients, or population based with normal individuals in comparison with patients (according to biobank data) ( 31 ). The plasma concentration of 1,25(OH)2D, the active and functional form of vitamin D, is resulting from both, the availability of 25(OH)D and the activity of the enzymatic conversions, and also seen it has affected by genetic factors. Twin studies suggested high heritability of serum 25(OH)D levels. Also the risk of adverse health outcomes associated with low serum 25(OH)D levels may be due in part to genetic factors ( 15 ). A meta-analysis identified common polymorphisms in the vitamin D receptors (VDR) gene which significantly modified the association of serum 25(OH)D and major health outcomes ( 15 ). Also in another study showed a higher susceptibility or risk of acute lower respiratory tract infections (ALRI) due to vitamin D receptor (VDR) gen polymorphisms ( 32 ). So, the differentiation between its effects on different peoples may be due to these genotype variations and define to some extent the meaning of end-organ sensitivity to vit D metabolites. In one observational study showed that there is an identified gene cluster as a genetic susceptibility locus in severe Covid-19 patients with respiratory failure ( 33 ). So another reason for the different results of studies or mortality rate or severity of disease between individuals and countries may be due to these genetic differences in enzymatic pathways, in vitamin D receptors, or in susceptibility to Covid-19 infection and severity, in addition to other risk factors which could effect on people's health like the nutritional and socioeconomic factors or the primary health conditions of individuals or societies and other unknown risk factors which could confound these results. Another reason could be measuring serum level of vitamin D before or after developing infection and inflammation to avoid the negative effect of the illness on vitamin D levels ( 17 ), because the causal link between low vitamin D status and infections or autoimmune disease remains unclear ( 15 ). Conclusion Vitamin D deficiency (serum 25 (OH)D level 30 ng/ml in hospitalized Covid-19 patients, but we could not find any significant association between vitamin D levels with the incidence of ICU admission, need for mechanical ventilation and length of hospital stay. Also, we did not see any significant relationship between serum levels of vitamin D with biochemical lab tests, radiologic findings on chest CT scans, and patient' vital signs on admission day. Considering this fact that despite the absence of a statistically significant association between serum level of vitamin D and severity criteria on admission and first day, between two subgroups, the presence of a significant difference in mortality between them at the end, maybe we could say that vitamin D deficiency could have a causal effect on Covid-19 outcome and mortality, not only a side effect of Covid-19 disease, so maybe treatment of the people with vitamin D deficiency before infection could improve Covid-19 outcome. Maybe further studies with a better design and method could clarify and show these facts better. The limitation of our study is incomplete medical records that we had to remove several patients, human error in measuring or recording the data may be small sample size, especially for better results in some conclusions and the patients were not evaluated at the same time and were reviewed in five consecutive months, therefore, the epidemiologic and virologic changes may be an effect on our results. Although we tried to consider known confounding variables such as age, gender, comorbidities, smoking, and obesity to some extent in our results other factors like drugs and the basic health conditions of patients and other nutrients and unknown confounding variables may effect our results. Abbreviations COVID-19 Coronavirus disease VDR vitamin d receptors IOM Institute of Medicine ICU Intensive care unit LDH lactate dehydrogenase CRP c-reactive protein CPK creatinine phosphokinase CBC complete blood count COPD Chronic obstructive pulmonary disease Declarations Acknowledgment We would like to thank the Tehran University of Medical science and Ziaeian Hospital, and acknowledge its research unit for their support and facilities for conducting this study. Conflict of interest The author has no conflict of interest in any terms during the study to declare Funding This study had a research project grant from Tehran university of Medical science. Compliance with Ethical Standards Ethical approval: All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Availability of data and material: Data sharing not applicable to this article as no datasets were generated or analyzed during the current study. Contributors’ Statement Page: Dr. Abolfazl Zendehdel and Dr. Ziba Aghsaeifard and Dr. Ghasem Azimi: conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. Dr. Saeed Reza Jamali Moghaddam siyahkali and Dr. Azadeh Asoodeh: Designed the data collection instruments, collected data, carried out the initial analyses, and reviewed and revised the manuscript. Dr. Mohammad Bidkhori and Dr. Muhammad Abubakar Nuhu: Coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. References Kupferschmidt K, Cohen J. Race to find COVID-19 treatments accelerates. American Association for the Advancement of Science; 2020. Oristrell J, Oliva J, Casado E, Subirana I, Domínguez D, Toloba A, et al. Vitamin D supplementation and COVID-19 risk: A population-based, cohort study. J Endocrinol Investig. 2022;45(1):167–79. Margarucci LM, Montanari E, Gianfranceschi G, Caprara C, Valeriani F, Piccolella A et al. The role of vitamin D in prevention of COVID-19 and its severity: an umbrella review. Acta Bio Medica: Atenei Parmensis. 2021;92(Suppl 6). Xu Y, Baylink DJ, Chen C-S, Reeves ME, Xiao J, Lacy C, et al. The importance of vitamin d metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID-19. J translational Med. 2020;18(1):1–12. Zendehdel A, JamaliMoghaddamsiyahkali S, Bidkhori M, Ansari M, Asoodeh A. The Role of Underlying Diseases on Covid-19 Severity and Mortality among Hospitalized Patients: a single-center, retrospective, cohort study. Endocrine, Metabolic & Immune Disorders - Drug Targets; 2021. Thacher TD, editor. Vitamin D and COVID-19. Mayo Clinic Proceedings; 2021: Elsevier. Iranian Ministry of Health and Medical Education. Diagnostic and therapeutic flowchart of COVID 19 disease at the outpatient and inpatient service levels ed. national guidelines for novel corona virus. national guidelines for novel corona virus. 2022. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 2000;72(3):690–3. Campi I, Gennari L, Merlotti D, Mingiano C, Frosali A, Giovanelli L, et al. Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy. BMC Infect Dis. 2021;21(1):1–13. Ginde AA, Mansbach JM, Camargo CA. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009;169(4):384–90. Zendedel A, Gholami M, Anbari K, Ghanadi K, Ceneicel Bachari E, Azargon A. Effects of vitaminn D intake on FEV1 and COPD exacerbation: a randomized clinical trial study. Global J health Sci. 2015. Sassan Pazirandeh M, David L, Burns M. Overview of vitamin D 2021 [updated Sep 23, 2021. 2:[Available from: https://www3.utdos.ir/contents/vitamin-d-deficiency-in-adults-definition-clinical-manifestations-and-treatment?search=vitamin%20d§ionRank=3&usage_type=default&anchor=H20&source=machineLearning&selectedTitle=2~146&display_rank=1#H20 Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–81. Radujkovic A, Hippchen T, Tiwari-Heckler S, Dreher S, Boxberger M, Merle U. Vitamin D deficiency and outcome of COVID-19 patients. Nutrients. 2020;12(9):2757. Roger Bouillon M, PhD FRCP, Vitamin D. and extraskeletal health 2021 [updated Feb 22, 2021. 2:[Available from: https://www3.utdos.ir/contents/vitamin-d-and-extraskeletal-health?search=vitamin%20d&source=search_result&selectedTitle=5~146&usage_type=default&display_rank=4 Diabetes TL. Vitamin D and COVID-19: why the controversy? Elsevier; 2021. p. 53. Smolders J, van den Ouweland J, Geven C, Pickkers P, Kox M. Vitamin D deficiency in COVID-19: Mixing up cause and consequence. Metabolism-Clinical Experimental. 2021;115. AlSafar H, Grant WB, Hijazi R, Uddin M, Alkaabi N, Tay G, et al. COVID-19 disease severity and death in relation to vitamin D status among SARS-CoV-2-positive UAE residents. Nutrients. 2021;13(5):1714. Lohia P, Nguyen P, Patel N, Kapur S. Exploring the link between vitamin D and clinical outcomes in COVID-19. Am J Physiology-Endocrinology Metabolism. 2021;320(3):E520–6. Hastie CE, Pell JP, Sattar N. Vitamin D and COVID-19 infection and mortality in UK Biobank. Eur J Nutr. 2021;60(1):545–8. Fang Y, Zhang H, Xie J, Lin M, Ying L, Pang P, et al. Sensitivity of chest CT for COVID-19: comparison to RT-PCR. Radiology. 2020;296(2):E115–7. Bess Dawson-Hughes M. Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment 2021 [2:[Available from: https://www3.utdos.ir/contents/vitamin-d-deficiency-in-adults-definition-clinical-manifestations-and-treatment?search=vitamin%20d&source=search_result&selectedTitle=2~146&usage_type=default&display_rank =. Assistant R. COVID-19 imaging findings. Rediology Assistant. 2020. Panovska-Stavridis I, Ridova N, Stojanoska T, Demiri I, Stevanovic M, Stojanovska S et al. Insight in the Current Progress in the Largest Clinical Trials for Covid-19 Drug Management (As of January 2021). prilozi. 2021;42(1). Cannell J, Vieth R, Umhau J, Holick M, Grant W, Madronich S, et al. Epidemic influenza and vitamin D. Epidemiol Infect. 2006;134(6):1129–40. Rastad H, Mahdavi Gorabi A, Qorbani M, Seif E, Asayesh H, Motlagh ME, et al. Prevalence and determinants of vitamin D deficiency in Iranian children and adolescents: the CASPIAN-V study. J Diabetes Metabolic Disorders. 2021;20(1):383–9. Esmaeili SA, Mohammadian S, Radbakhsh S, Momtazi-Borojeni AA, Kheirmand Parizi P, Atabati H, et al. Evaluation of vitamin D(3) deficiency: A population-based study in northeastern Iran. J Cell Biochem. 2019;120(6):10337–41. Borsche L, Glauner B, Mendel Jv. COVID-19 mortality risk correlates inversely with vitamin D3 status, and a mortality rate close to zero could theoretically be achieved at 50 ng/ml 25 (OH) D3: Results of a systematic review and meta-analysis. Nutrients. 2021;13(10):3596. Kazemi A, Mohammadi V, Aghababaee SK, Golzarand M, Clark CC, Babajafari S. Association of vitamin D status with SARS-CoV-2 infection or COVID-19 severity: a systematic review and meta-analysis. Adv Nutr. 2021;12(5):1636–58. Başaran N, Adaş M, Gökden Y, Turgut N, Yıldırmak T, Güntaş G. The relationship between vitamin D and the severity of COVID-19. Bratislava Medical Journal-Bratislavske Lekarske Listy; 2021. Ali N. Role of vitamin D in preventing of COVID-19 infection, progression and severity. J Infect Public Health. 2020;13(10):1373–80. Roth DE, Jones AB, Prosser C, Robinson JL, Vohra S. Vitamin D receptor polymorphisms and the risk of acute lower respiratory tract infection in early childhood. J Infect Dis. 2008;197(5):676–80. Group SC-G. Genomewide association study of severe Covid-19 with respiratory failure. N Engl J Med. 2020;383(16):1522–34. Additional Declarations No competing interests reported. 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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-8254002","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":570986016,"identity":"ba50fd11-8bba-4563-8c92-b72f5a6fa524","order_by":0,"name":"Abolfazl Zendehdel","email":"","orcid":"","institution":"Tehran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Abolfazl","middleName":"","lastName":"Zendehdel","suffix":""},{"id":570986020,"identity":"f624a20b-c9f9-4c9e-96c5-7f4b7736a20d","order_by":1,"name":"SaeidReza JamaliMoghaddamsiyahkali","email":"","orcid":"","institution":"Tehran University of 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06:20:26","extension":"html","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":136456,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8254002/v1/d9ab8fafd780de2ffda37bfc.html"},{"id":100013411,"identity":"8e72280e-b86a-44f9-8fc0-257b675feacf","added_by":"auto","created_at":"2026-01-12 06:20:26","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":405654,"visible":true,"origin":"","legend":"\u003cp\u003eThe association between vitamin D level and mortality.\u003c/p\u003e","description":"","filename":"Figure.png","url":"https://assets-eu.researchsquare.com/files/rs-8254002/v1/fe940f2a07c54d55478f3269.png"},{"id":100381330,"identity":"5255c6d4-a53d-423d-b6f1-482441a1dd28","added_by":"auto","created_at":"2026-01-16 10:38:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1222478,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8254002/v1/edfbf091-d349-4c52-8139-6b30cc679877.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Investigation of the prevalence of vitamin D deficiency in hospitalized COVID-19 patients and its association with disease severity, outcome, and mortality","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCoronavirus disease (COVID-19) originated in Wuhan, China, rapidly spread around the world, due to its inherently contagious, made a pandemic on March 12, 2020, resulting in many death in every country around the world and became a big concern for global public health (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). So it is important to identify modifiable prognostic and risk factors that could affect disease outcomes and result in severity and mortality of disease in COVID-19-infected patients to have better management and control of this pandemic and help to improve its outcomes.\u003c/p\u003e \u003cp\u003eThe clinical presentation of this disease is extensive and characterized by an important clinical variability between different infected patients (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), which could suggest that there are important host-related factors that affect its severity and outcome.\u003c/p\u003e \u003cp\u003eThis fact that there is a significant difference in Covid-19 mortality among different countries, particularly when mortality is evaluated by latitude, and seen that peoples who are less exposed to sunlight to retain adequate vitamin D levels have a higher mortality rate, bring a new debate about the possible role of vitamin D in determining the clinical status and outcomes of these patients (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAdditionally, older adults with underlying diseases are at higher risk for severe illness (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). A low level of vitamin D is common in the elderly and has been associated with all-cause mortality including sepsis (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eVitamin D deficiency is also more prevalent among individuals with darker skin than those with lighter skin color, and studies have shown that people from racial groups with darker skin are at greater risk for severe Covid-19 disease (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFurthermore, obesity is a cause of susceptibility to severe Covid-19 infection (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e), and is associated with vitamin D insufficiency due to its deposition in body fat (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSeveral studies demonstrated that low vitamin D has been associated with increased risk and severity of respiratory tract infections. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), and in one of our studies, we demonstrated that vitamin D intake decreased Chronic obstructive pulmonary disease (COPD) exacerbation and improved FEV1 in the severe/very severe cases of COPD (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTherefore, there is an interest to investigate the role of vitamin D, as its deficiency is a prevalent condition worldwide, in modulating the severity of Covid-19 infection given the complex pathophysiology of this disease, but this association may be confounded by common causal or risk factors of both low serum vitamin D levels and severe Covid-19 infections like elderly.\u003c/p\u003e \u003cp\u003eVitamin D (calciferol), is a generic term that refers to a group of fat-soluble compounds with a four-ringed cholesterol in base (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). 10% of vitamin D is from diet in the form of two metabolites, D2 and D3, and consumed through vitamin D-rich foods including fatty fish, eggs, and fortified foods, while the other 90%, the major source of Vit D, is provided in the skin by nonenzymatic conversion of 7-dehydrocholestrol to D3 after exposure to sunlight (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). This dermal synthesis could vary based on geographic location and latitude, season and time of day or length of daily exposure, the skin type and its pigmentation, use of sunblock lotions (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMelanin reduces dermal synthesis of Vit D3 in darker skin. Malabsorptive syndromes and fat-malabsorption disorders associated with low serum 25(OH)D levels (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eVitamin D2 and D3, from diet or skin, are biologically inactive and require converting enzymatically. In the first step these metabolites must be 25-hydroxylated and convert to 25(OH)D (calcidiol) in liver, which is the major circulating form of vitamin D with the highest half-life of two or three weeks, then 25(OH)D, 1-hydroxylated via 1-alpha- hydroxylase enzyme (CYP27B1) in kidneys as renal, or in other tissues as extrarenal or local pathways, to make its active form 1,25-dihydrocholecalciferol vitamin D (calcitriol) (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe liver has also the capacity of metabolize 25(OH)D to inactive metabolites which is accomplished by the P450 system and is enhanced by alcohol, barbiturates, and phenytoin. The serum concentration of 25(OH)D is the best laboratory indicator of vitamin D adequacy and is commonly used to assess individual vit D status (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Based on Institute of Medicine (IOM) conclusion a serum 25(OH)D level of 20 ng/ml is sufficient for most individuals (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe active form of vitamin D, 1,25(OH)2D, binds to vitamin d receptors (VDR) which is an intracellular receptor in target tissues and is nearly universally expressed in nucleated cells, and regulate gene transcriptions. Approximately 3 percent of human/mouse genome is under the control of 1,25(OH)2D (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eVitamin D has a known role in calcium and bone hemostasis, but the spectrum of its activity is much broader than it, and besides that potentially regulates many other cellular functions (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAntigen presenting cells, such as macrophages, B and T cells, and dendritic cells express vitamin D receptors (VDR). Vitamin D has major effects on nearly all cells of the immune system and can modulate most aspects of the innate and acquired immune system (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eAlthough several clinical trials and studies have been performed to evaluate the role of vitamin D as a preventive and therapeutic option in Covid-19 infected patients, but the results remain controversial (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Some observational studies have shown a correlation between Covid-19 severity and mortality with low serum levels of 25(OH)D (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), while others did not. (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eTherefore, further studies are required in an emergency situation like this pandemic, to demonstrate this fact, even though the incidence is starting to decline and vaccines are already available, because there have been some Covid-19 cases with severe disease and even death in patients who were fully vaccinated and a new wave of patients due to new variants of virus may emerge in the future, so it is important to keep researching.\u003c/p\u003e \u003cp\u003eIn this study, we aimed to evaluate the prevalence of vitamin D deficiency in patients with Covid-19 infection in this hospital, as a center for Covid-19 patients, and its association with mortality, outcome, and severity of Covid-19 disease by comparing two groups, based on clinical outcomes including length of hospital stay, need for ICU admission, mechanical ventilation, mortality rate and the results of lab tests, chest CT scans scores and patient's vital signs on admission day.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis was a single center observational study, performed at Ziaeian Hospital between March 21th and September 11th, 2020. This hospital is an educational and medical center for Covid-19 infected patients at Tehran university of Medical Science, Iran.\u003c/p\u003e \u003cp\u003e276 inpatients with confirmed Covid-19 during almost five consecutive months, were enrolled in this study, according to their serum level of 25 (OH) D, and were assigned to two groups. Group 1 including 145 inpatients, had a serum level of 25 (OH) D\u0026thinsp;\u0026gt;\u0026thinsp;20 ng/ml, whereas patients in group 2 including 131 inpatients had a level of vit D\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;20 ng/ml.\u003c/p\u003e \u003cp\u003eAlso, the analysis was performed as a secondary finding (sensitivity analysis), between two subgroups of patients with serum 25(OH)D levels\u0026thinsp;\u0026lt;\u0026thinsp;12 (deficiency, subgroup 2) and serum 25(OH)D levels\u0026thinsp;\u0026gt;\u0026thinsp;30 (as an optimal range, subgroup 1), to clarify the probable association in vitamin D deficient group of patients.\u003c/p\u003e \u003cp\u003epatients who were admitted to this hospital received therapeutic regimens according to the guidelines issued by Iranian Ministry of Health and Medical Education (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e), Considering the revisions happened on these protocols and guidelines during the period of study, it was tried to mitigate the effect of this therapeutic changes, on our sampling and its proportion.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy population\u003c/h3\u003e\n\u003cp\u003eThe confirmed Covid-19 infected patients with moderate to severe disease who need hospitalization were enrolled in this study by simple random sampling without stratification, from admitted patients in this hospital. Confirmation of the diagnosis of Covid-19 was based on clinical symptoms with a radiologic change of chest computed tomography (CT) for Covid-19 or a positive diagnostic kit result (Rt-PCR) (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), aside from the approval of diagnosis and clinical requirement of hospitalization by our physicians in this hospital. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003cp\u003ePatients without diseases associated with vitamin D deficiency such as parathyroid disease or history of its surgery, liver and kidney failure, malabsorption disorders such as chronic diarrhea, bile duct disorders, celiac disease, and pancreatic diseases were included in the study. Patients do not meet inclusion criteria or patients with a lack of data or written informed consent were excluded from the study. we excluded only one patient who was under chemotherapy treatment and only one pregnant patient from the sample. Also, patients treated with vitamin D drugs at the hospital were excluded from the study.\u003c/p\u003e \u003cp\u003eDemographic information of individuals, laboratory parameters including LDH (lactate dehydrogenase), CRP (c-reactive protein), Vit D (vitamin D), D-dimer, ferritin, CPK (creatinine phosphokinase), CBC (complete blood count), AST and ALT(liver function tests), clinical features and vital signs including pulse rate, respiratory rates, blood pressure, blood oxygen saturation, the result of Covid-19 test (PCR), chest CT scans, underlying disease (diabetes, hypertension, cardiovascular problems, respiratory problems, etc.), the admission to the intensive care unit (ICU), the requirement of mechanical ventilation, the duration of hospitalization, their outcome and mortality were extracted from patient's clinical records and compared. Patient form was used to record all the information for each patient.\u003c/p\u003e \u003cp\u003e This study was approved by the Ethical committee of Tehran University of Medical Science (Ethic number: IR.TUMS. VCR.REC.1399.262), and was conducted in accordance with the Declaration of Helsinki and in compliance with ethical guidelines. Written informed consent was obtained from all patients when admitted to the hospital. Data and identities of individuals were kept confidential.\u003c/p\u003e\n\u003ch3\u003eIntervention and measurement\u003c/h3\u003e\n\u003cp\u003eVitamin D status of the patients was measured by their serum 25(OH)D level on admission day and classified into different classes: deficient (less than 12 ng/ml), insufficient (12\u0026ndash;20 ng/ml), sufficient (more than 20 ng/ml) (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe severity of patient's disease is evaluated with these criteria: clinical findings including SO2, SBP, PR, RR, and paraclinical parameters including LDH (lactate dehydrogenase), CRP (c-reactive protein), D-dimer, ferritin, CPK (creatinine phosphokinase), CBC/diff (complete blood count), AST and ALT (liver function tests) and chest CT scans score at the first day of admission. According to the guidelines issued by Iranian Ministry of Health and Medical Education (r) severe disease defined by SO2\u0026thinsp;\u0026lt;\u0026thinsp;90%, RR\u0026thinsp;\u0026gt;\u0026thinsp;30/min, PR\u0026thinsp;\u0026gt;\u0026thinsp;125/min, or SBP\u0026thinsp;\u0026lt;\u0026thinsp;90 mmHg or in lab tests a Ferritin\u0026thinsp;\u0026gt;\u0026thinsp;500 ug/l or D-dimer\u0026thinsp;\u0026gt;\u0026thinsp;1000 ng/ml, CRP\u0026thinsp;\u0026gt;\u0026thinsp;12 mg/l (or \u0026gt;\u0026thinsp;=\u0026thinsp;2+), CPK\u0026thinsp;\u0026gt;\u0026thinsp;340 U/l in women and \u0026gt;\u0026thinsp;390 in men, LDH\u0026thinsp;\u0026gt;\u0026thinsp;960 U/l in patients younger than 65 years old or \u0026gt;\u0026thinsp;1060 in patients\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;65years, elevated ALT and AST u/l or \u0026gt;\u0026thinsp;ULN (upper limit normal defined by our hospital laboratory), or Lymph\u0026thinsp;\u0026lt;\u0026thinsp;20% in CBC/diff. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eChest CT severity score (CT-SS) was used to access the severity of the disease based on the degree of involvement of their lungs at chest CT scans and was used to compare the severity of disease between our two groups. This scoring was done with an expert radiologist in this hospital, according to this score both lungs are divided into 5 lobes and each lobe can get a score of involvement between 1 to 5 so every CT scan is scored between 1 to 25 (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Severe disease defined by a CT-SS\u0026thinsp;\u0026gt;\u0026thinsp;12.5 or more than 50% involvement of lungs at chest CT scans (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) .\u003c/p\u003e\n\u003ch3\u003eOutcome\u003c/h3\u003e\n\u003cp\u003eIn this study, the mortality and severity of Covid-19 disease were assessed and compared in the groups with and without vitamin D deficiency to understand the association between serum level of vitamin D and outcome of Covid-19 disease.\u003c/p\u003e \u003cp\u003eThe severity of Covid-19 disease is assessed by clinical findings (SO2, SBP, PR, RR), and paraclinical parameters (LDH (lactate dehydrogenase), CRP (c-reactive protein), D-dimer, ferritin, CPK (creatinine phosphokinase), CBC/diff (complete blood count), AST and ALT (liver function tests)), and chest CT scans scores on the admission day and patient's outcomes during hospitalization.\u003c/p\u003e \u003cp\u003eThe primary endpoint was the serum level of these lab tests, clinical and vital signs and CT scans scores on the admission day, as the cross-sectional part of our study. The secondary endpoints were, the duration of hospitalization (length of hospital stay), a requirement for admission to the intensive care unit (ICU), mechanical ventilation, and patient's outcome, discharge, or mortality, as the cohort part of the study.\u003c/p\u003e \u003cp\u003eThen by multivariate regression analysis (for age and sex), the adjusted association of serum level of vitamin D was observed on mortality and severity.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe data obtained were computerized and statistically analyzed using (SPSS v26). The results are expressed as frequency and percentage for qualitative variables and as mean and standard deviation (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD) quantitative variables. Confidence interval was 0.95 (Cl, 0.95). P value less than 0.05 was considered statistically significant. The power of study was 80%.\u003c/p\u003e \u003cp\u003eChi-square test and independent samples T-test were used to compare the baseline characteristics between two groups.\u003c/p\u003e \u003cp\u003eLogistic regression analysis was used to investigate the relationship between binary outcomes and serum levels of vitamin D. Linear regression analysis was used to investigate the relationship between continuous outcomes and serum levels of vitamin D. Adjustment for confounding variables was performed by multiple linear and multiple logistic regression.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003ch2\u003ePatients\u0026rsquo; characteristics\u003c/h2\u003e\n\u003cp\u003eA total of 276 inpatients with confirmed Covid-19 infection after initial screening and excluding were enrolled in this study during almost five consecutive months and divided into two groups, 145 (52.5%) patients were classified into group1, who had a serum 25(OH)D level\u0026thinsp;\u0026gt;\u0026thinsp;20 ng/ml as the sufficient group and 131(47.5%) of patients were classified in group2 with a serum 25(OH)D level of =\u0026thinsp;\u0026lt;\u0026thinsp;20 ng/ml as the deficient and insufficient group.\u003c/p\u003e\n\u003cp\u003eThe baseline demographic and clinical characteristics of these identified patients are shown in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. As shown in this table, there were significant differences between two groups regarding gender and mean age which is higher in sufficient group (group 1) in comparison with group 2, but there were no significant differences between two groups in terms of underlying disease, smoking, and obesity.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003epatients demographic and characteristics data of two groups\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTotal\u003c/p\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;276\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGroup 1\u003c/p\u003e\n\u003cp\u003eSerum vit D\u0026thinsp;\u0026gt;\u0026thinsp;20))\u003c/p\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;145\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGroup 2\u003c/p\u003e\n\u003cp\u003e(Serum vit D\u0026thinsp;\u0026lt;\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;131\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep-value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge, year\u003c/p\u003e\n\u003cp\u003eMean (sd)\u003c/p\u003e\n\u003cp\u003eSex, number (%)\u003c/p\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003cp\u003eUnderlying disease\u003c/p\u003e\n\u003cp\u003eYes, number (%)\u003c/p\u003e\n\u003cp\u003eSmoking\u003c/p\u003e\n\u003cp\u003eYes, number (%)\u003c/p\u003e\n\u003cp\u003eBMI\u0026thinsp;\u0026gt;\u0026thinsp;30\u003c/p\u003e\n\u003cp\u003eYes, number (%)\u003c/p\u003e\n\u003cp\u003eMean (sd)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e57.4 (18.9)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e169 (61.2%)\u003c/p\u003e\n\u003cp\u003e107 (38.8%)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e91 (33%)\u003c/p\u003e\n\u003cp\u003e53 (19.2%)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e32/137 (23.4%)\u003c/p\u003e\n\u003cp\u003e27.7 (5.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e60.1 (18.1)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e79 (54.5%)\u003c/p\u003e\n\u003cp\u003e66 (45.5%)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e49 (33.8%)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e24 (16.6%)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e20/73 (27.4%)\u003c/p\u003e\n\u003cp\u003e28.1 (\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e54.4 (19.4)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e90 (68.7%)\u003c/p\u003e\n\u003cp\u003e41 (31.3%)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e42 (32.1%)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e29 (22.1%)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e12/64 (18.8%)\u003c/p\u003e\n\u003cp\u003e27.2 (6.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.01\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.01\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.7\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.2\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003eBMI\u0026thinsp;=\u0026thinsp;Body mass index, Sd\u0026thinsp;=\u0026thinsp;Standard deviation\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eOverall, of these 276 patients, 107 (38.8%) patients were female and 169 (61.2%) were male and their ages ranged from 18 to 94 years old (mean\u0026thinsp;=\u0026thinsp;57.4, Sd\u0026thinsp;=\u0026thinsp;18.9).\u003c/p\u003e\n\u003cp\u003eVitamin D deficiency (serum 25(OH)D level\u0026thinsp;\u0026lt;\u0026thinsp;12 ng/ml) was found in 22.1% (n\u0026thinsp;=\u0026thinsp;61) of all patients and insufficiency (12\u0026ndash;20 ng/ml) in 25.4% (n\u0026thinsp;=\u0026thinsp;70), while 52.5% (n\u0026thinsp;=\u0026thinsp;145) of patients had a normal serum 25(OH)D level (\u0026gt;\u0026thinsp;20 ng/ml). The mean quantitative serum level of 25(OH)D was 24.8 ng/ml (Sd\u0026thinsp;=\u0026thinsp;16.1) in total group, 36.2 ng/ml (Sd\u0026thinsp;=\u0026thinsp;13.8) in sufficient group (\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e), and 12.1 ng/ml (Sd\u0026thinsp;=\u0026thinsp;5.3) in group 2.\u003c/p\u003e\n\u003cp\u003eThe percentage of ICU admission was 17.8% (49/276), mechanical ventilation 8.8% (24/274), mortality was 15.3% (42/275) and the mean of hospitalization length was 7.4 days (Sd\u0026thinsp;=\u0026thinsp;5.4), in total group (276 patients).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe relationship between serum 25 (OH)D level with biochemical parameters and radiologic findings on admission day (cross-sectional part of the study)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe disease severity was assessed by patient's vital signs, chest CT scans findings, and the result of laboratory tests on admission day and compared between two groups. (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003ethe correlation between vitamin D status and lab tests, radiologic findings and vital signs in groups\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth colspan=\"8\" align=\"left\"\u003e\n\u003cp\u003eUnivariate analysis\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eMultivariate analysis\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eTotal\u003c/p\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;276\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGroup 1\u003c/p\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;145\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGroup 2\u003c/p\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;131\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003ep- value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAOR (95%CI)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003ep-value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCPK\u003c/p\u003e\n\u003cp\u003eSever Number (%))\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e18 (6.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e8 (5.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e10 (7.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e1.43 (0.53, 3.83)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.4\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eFerritin Number (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e102 (37%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e46 (31.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e56 (42.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.059\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e1.58 (0.94, 2.66)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.08\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLDH\u003c/p\u003e\n\u003cp\u003eNumber (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e21 (7.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e7 (4.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e14 (10.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.07\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e2.58 (0.99, 6.75)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCRP\u003c/p\u003e\n\u003cp\u003eNumber (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e154 (55.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e79 (54.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e75 (57.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e1.17 (0.7, 1.90)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.5\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eD-dimer Number (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e20 (7.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e8 (5.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e12 (9.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e2.08 (0.80, 5.39)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLymphocyte Number (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e126 (45.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e69 (47.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e57 (43.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.97 (0.58, 1.61)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.9\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eAST\u003c/p\u003e\n\u003cp\u003eNumber (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e97 (35.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e46 (31.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e51 (39.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e1.41 (0.85, 2.35)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eALT\u003c/p\u003e\n\u003cp\u003eNumber (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e73 (26.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e36 (24.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e37 (28.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e1.12 (0.64, 1.96)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.6\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCT scan Number (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e76 (27.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e44 (30.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e32 (24.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.79 (0.45, 1.37)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.4\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRR\u003c/p\u003e\n\u003cp\u003eNumber (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1 (0.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0 (0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1 (0.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSPO2\u003c/p\u003e\n\u003cp\u003eNumber (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e82 (29.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e46 (31.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e36 (27.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.86 (0.50, 1.49)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.6\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSBP\u003c/p\u003e\n\u003cp\u003eNumber (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e2 (0.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1 (0.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1 (0.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.99 (0.05, 16.90)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.9\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003ePR\u003c/p\u003e\n\u003cp\u003eNumber (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1 (0.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0 (0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1 (0.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"15\"\u003eAOR\u0026thinsp;=\u0026thinsp;Adjusted odds ratio, CI\u0026thinsp;=\u0026thinsp;Confidence interval, SD\u0026thinsp;=\u0026thinsp;Standard deviation, LDH\u0026thinsp;=\u0026thinsp;lactate dehydrogenase, CRP\u0026thinsp;=\u0026thinsp;c-reactive protein, CPK\u0026thinsp;=\u0026thinsp;creatinine phosphokinase\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAlthough the serum levels of CPK, Ferritin, LDH, CRP, D-dimer, AST, and ALT were higher in group 2 and we had more severe cases in group 2 and a near significant p-value for Ferritin (P\u0026thinsp;=\u0026thinsp;0.05, AP\u0026thinsp;=\u0026thinsp;0.08) and LDH (P\u0026thinsp;=\u0026thinsp;0.07, AP\u0026thinsp;=\u0026thinsp;0.05), by univariate and multivariate regression analysis there is no statistically significant differences between two groups in regard to laboratory tests.\u003c/p\u003e\n\u003cp\u003eSince the age and gender had statistically significant differences between two groups (group 1, group 2), these confounding variables were adjusted in final models.\u003c/p\u003e\n\u003cp\u003eDespite a little difference in a number of severe cases in PR, SBP, and RR between two groups, there was not a particular result, and could not be analyzed due to the small number of events.\u003c/p\u003e\n\u003cp\u003eThe number of severe cases in chest CT scans scores was a little higher in group 1 but by univariate and multivariate regression analysis there was not a significant difference between two groups in this regard and we could not show any relationship between serum level of 25(OH)D and the result of these lab tests and biochemical parameters, patient's vital signs or the degree of involvement on their chest CT scans on admission day.\u003c/p\u003e\n\u003cp\u003eAlso, we did a sensitivity analysis between two subgroups of serum 25(OH)D levels\u0026thinsp;\u0026lt;\u0026thinsp;12 (deficiency, subgroup 2) and serum 25(OH)D levels\u0026thinsp;\u0026gt;\u0026thinsp;30 (as an optimal range, subgroup 1), to identify the probable differences in association between serum level of vitamin D and these parameters by comparing two subgroups together to show it better but as shown in Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e the same results were seen in a comparison between two subgroups and there were no statistically significant differences between them in these regards.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003ethe correlation between vitamin D status and lab tests, radiologic findings and vital signs in subgroups\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth colspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eUnivariate analysis\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eMultivariate analysis\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTotal\u003c/p\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;156\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSubgroup 1\u003c/p\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;91\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSubgroup 2\u003c/p\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;65\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep- value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAOR (95%CI)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep-value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCPK\u003c/p\u003e\n\u003cp\u003eSever Number (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e13 (8.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (6.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7 (10.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.52 (0.44, 5.18)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.4\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFerritin Number (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e59 (37.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29 (31.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30 (46.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.07\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.59 (0.77, 3.30)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.2\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLDH\u003c/p\u003e\n\u003cp\u003eNumber (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e15 (9.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (8.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7 (10.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.81 (0.56, 5.82)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCRP\u003c/p\u003e\n\u003cp\u003eNumber (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e89 (57.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e53 (58.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36 (55.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.85 (0.42, 1.70)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.6\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eD-dimer Number (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e8 (5.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (4.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (6.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.85 (0.41, 8.30)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.4\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLymphocyte Number (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e75 (48.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45 (49.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30 (46.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.98 (0.48, 2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.9\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAST\u003c/p\u003e\n\u003cp\u003eNumber (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e60 (38.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30 (33%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30 (46.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.09\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.98 (0.96,4.08)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.06\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALT\u003c/p\u003e\n\u003cp\u003eNumber (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e50 (32.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27 (29.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23 (35.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.08 (0.5,2.32)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.8\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCT scan Number (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e37/145 (25.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24/86 (27.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13/59 (22%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.74 (0.32, 1.71)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.4\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRR\u003c/p\u003e\n\u003cp\u003eNumber (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1(0.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (1.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSPO2\u003c/p\u003e\n\u003cp\u003eNumber (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e46 (29.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27 (29.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19 (29.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.10 (0.50, 2.40)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.8\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSBP\u003c/p\u003e\n\u003cp\u003eNumber (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1 (0.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (1.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePR\u003c/p\u003e\n\u003cp\u003eNumber (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0 (0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"11\"\u003eAOR\u0026thinsp;=\u0026thinsp;Adjusted odds ratio, CI\u0026thinsp;=\u0026thinsp;Confidence interval, SD\u0026thinsp;=\u0026thinsp;Standard deviation, LDH\u0026thinsp;=\u0026thinsp;lactate dehydrogenase, CRP\u0026thinsp;=\u0026thinsp;c-reactive protein, CPK\u0026thinsp;=\u0026thinsp;creatinine phosphokinase\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eThe association between serum 25(OH)D level and clinical outcomes of Covid-19 disease (cohort design part of the study)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e by comparison between two groups, despite higher percentages in mortality (17.6% vs 13.2%, p\u0026thinsp;=\u0026thinsp;o.3) and incidence of ICU admission (18.3% vs 17.2%, P\u0026thinsp;=\u0026thinsp;0.8) and mechanical ventilation (10% vs 7.6%, p\u0026thinsp;=\u0026thinsp;0.4), in patients with vitamin D deficiency and insufficiency (group 2), by univariate and multivariate regression analysis there is no significant differences between the two groups regarding, the incidence of mechanical ventilation (AOR\u0026thinsp;=\u0026thinsp;1.52, 95%Cl\u0026thinsp;=\u0026thinsp;0.63_3.66, P\u0026thinsp;=\u0026thinsp;0.3), ICU admission (AOR\u0026thinsp;=\u0026thinsp;1.15, 95%Cl\u0026thinsp;=\u0026thinsp;0.61_2.20, P\u0026thinsp;=\u0026thinsp;0.6), mortality (AOR\u0026thinsp;=\u0026thinsp;1.70, 95%Cl\u0026thinsp;=\u0026thinsp;0.85_3.40, P\u0026thinsp;=\u0026thinsp;0.1) and the length of hospital stay (AB=-0.77, 95%Cl=-2.07_O.51, P\u0026thinsp;=\u0026thinsp;0.2)(Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eClinical outcome comparison of study population for groups and subgroups\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth colspan=\"8\" align=\"left\"\u003e\n\u003cp\u003eUnivariate analysis\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eMultivariate analysis\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth colspan=\"1\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGroup 1\u003c/p\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;145\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGroup 2\u003c/p\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;131\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eOR/B (95%CI)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003ep- value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAOR/B (95%CL)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep-value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"1\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eLOHS\u003c/p\u003e\n\u003cp\u003eDay(sd)\u003c/p\u003e\n\u003cp\u003eMechanical\u003c/p\u003e\n\u003cp\u003eVentilation\u003c/p\u003e\n\u003cp\u003eYes(%)\u003c/p\u003e\n\u003cp\u003eICU admission\u003c/p\u003e\n\u003cp\u003eYes(%)\u003c/p\u003e\n\u003cp\u003eMortality\u003c/p\u003e\n\u003cp\u003eYes(%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e7.9 (5.9)\u003c/p\u003e\n\u003cp\u003e11 (7.6%)\u003c/p\u003e\n\u003cp\u003e25 (17.2%)\u003c/p\u003e\n\u003cp\u003e19 (13.2%)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSubgroup\u003c/p\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;91\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e6.8 (4.9)\u003c/p\u003e\n\u003cp\u003e13 (10.0%)\u003c/p\u003e\n\u003cp\u003e24 (18.3%)\u003c/p\u003e\n\u003cp\u003e23 (17.6%)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSubgroup\u003c/p\u003e\n\u003cp\u003eN\u0026thinsp;=\u0026thinsp;65\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e-1.05 (-2.35, 0.24)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.34 (0.58, 3.11)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.07 (0.58, 1.99)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.40 (0.72, 2.71)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.1\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.4\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.8\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.77 (-2.07, 0.51)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.52 (0.63, 3.66)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.15 (0.61, 2.20)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.70 (0.85, 3.40)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.2\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.3\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.6\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eLOHS\u003c/p\u003e\n\u003cp\u003eYes (%)\u003c/p\u003e\n\u003cp\u003eMechanical\u003c/p\u003e\n\u003cp\u003eVentilation\u003c/p\u003e\n\u003cp\u003eYes (%)\u003c/p\u003e\n\u003cp\u003eICU admission\u003c/p\u003e\n\u003cp\u003eYes (%)\u003c/p\u003e\n\u003cp\u003eMortality\u003c/p\u003e\n\u003cp\u003eYes (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e7.9 (6.2)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e6 (6.7%)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e14 (15.4%)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e10 (11.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e7.4 (4.8)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e5 (7.8%)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e14 (21.5%)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e12 (18.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e-4.97 (-2.32,1.32)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.18 (0.34, 4.07)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.51 (0.66, 3.43)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.81 (0.73, 4.49)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.5\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.7\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.3\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.27 (-2.22,1.67)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.35 (0.36, 5.08)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.92 (0.77, 4.74)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.93 (1.05, 8.15)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.7\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.6\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.1\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.03\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"16\"\u003eAOR\u0026thinsp;=\u0026thinsp;Adjusted odds ratio, CI\u0026thinsp;=\u0026thinsp;Confidence interval, ICU\u0026thinsp;=\u0026thinsp;Intensive care unit, SD\u0026thinsp;=\u0026thinsp;Standard deviation B\u0026thinsp;=\u0026thinsp;Regression coefficient, LOHS\u0026thinsp;=\u0026thinsp;Length of hospital stay\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn sensitivity analysis between two subgroups, by univariate regression analysis the comparison of the incidence of ICU admission (21.5% vs 15.4%, P\u0026thinsp;=\u0026thinsp;0.3), mechanical ventilation (7.8% vs 6.7%, p\u0026thinsp;=\u0026thinsp;0.7) and mortality (18.5% vs 11.1%, P\u0026thinsp;=\u0026thinsp;0.2), showed a higher percentage in subgroup 2 with vitamin D deficiency which was not statistically significant, but by multivariate regression analysis the comparison of mortality between two subgroups was significantly higher in subgroup 2 ( AOR\u0026thinsp;=\u0026thinsp;2.93, 95% CI\u0026thinsp;=\u0026thinsp;1.05,8.15, P\u0026thinsp;=\u0026thinsp;0.03) and serum level of vitamin D was negatively correlated with mortality.(Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis pandemic has led to many death in every country around the world, has a severe burden and consecutive socioeconomic disruptions, and threatened the public health (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e), So it is important to identify modifiable risk factors which could be effective and result in a poorer outcome of disease in covid-19 infected patients to have better management and controlling of the disease and its outcome.\u003c/p\u003e \u003cp\u003eTherefore in this study, we evaluate the role of vitamin D as a protective factor, in Covid-19 severity and outcome for confirmed Covid-19 hospitalized patients, considering the fact that its deficiency is a prevalent condition worldwide.\u003c/p\u003e \u003cp\u003eVitamin D is a steroid hormone that has potent immunomodulatory actions and may influence the immune response to viral infections (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e), and its deficiency is a risk factor for Covid-19 patients.\u003c/p\u003e \u003cp\u003eIn a large recent population-based study in Iranian children and adolescents, prevalence of vitamin D deficiency which is defined as serum 25(OH)D level\u0026thinsp;\u0026lt;\u0026thinsp;30 ng/ml, was 71.1% (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e), while in another population-based study in northeastern Iran, this prevalence (serum 25(OH)D level\u0026thinsp;\u0026lt;\u0026thinsp;30 ng/ml) reported 62.2% (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our study the prevalence of serum 25(OH)D level\u0026thinsp;\u0026lt;\u0026thinsp;30 ng/ml in Covid-19 inpatients was 67% (185/276), so according to the present study there is not much difference in prevalence of vitamin D deficiency between general population and Covid-19 hospitalized patients with moderate to severe disease, however, based on the limitations of our study's results, no scientific comment can be made, and more studies are needed in this field.\u003c/p\u003e \u003cp\u003eIn one observational study in Italy, revealed that serum 25(OH)D levels were inversely associated with IL6 levels, mortality, and need for ICU admission regardless of the confounding variables and are an independent predictor of disease severity and mortality in hospitalized patients (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSimilarly, according to the results of a systematic review and meta-analysis study, there is a strong correlation between mortality rate caused by Covid-19 infection and serum level of vitamin D, and suggested that a serum level of approximately 50 ng/ml may prevent any excess mortality and said that low D3 is a predictor rather than just a side effect of the infection (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this study, we showed that vitamin D deficiency (serum level\u0026thinsp;\u0026lt;\u0026thinsp;12ng/ml in subgroup 2), was associated with a statistically significant increase in mortality rate in comparison with sufficient group (serum level\u0026thinsp;\u0026gt;\u0026thinsp;30 ng/ml in subgroup 1, P\u0026thinsp;=\u0026thinsp;0,03) and also associated with an increased incidence of ICU admission and mechanical ventilation, which was not statistically significant.\u003c/p\u003e \u003cp\u003eIn some studies, the association between vitamin D deficiency with Covid-19 disease and its outcome remains controversial and further studies requirements for evaluating the role of this vitamin suggested (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), Whereas, other studies showed that there was no significant association between serum level of vitamin D and Covid-19 clinical outcomes (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn one retrospective cohort study which was similar to our study, 270 Covid-19 inpatients were enrolled and divided into two groups based on their vitamin D levels\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;20 ng/ml and \u0026lt;\u0026thinsp;20 ng/ml, which showed that there was no association between vitamin D level with the need for ICU admission, mechanical ventilation, mortality, and thromboembolism in COVID-19 patients (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our study when we compare both groups together, which were divided based on serum 25(OH)D levels of \u0026gt;\u0026thinsp;=\u0026thinsp;20 ng/ml and \u0026lt;\u0026thinsp;20ng/ml, we did not see any significant association between serum levels of vitamin D with a length of hospitalization, incidence of ICU admission, mechanical ventilation, and mortality, too. So one of the reasons for controversial results of different studies may be due to this inconsistent definition of vitamin D deficiency (\u0026lt;\u0026thinsp;12 ng/ml or \u0026lt;\u0026thinsp;20 ng/ml).\u003c/p\u003e \u003cp\u003eThe results of another systematic review and meta-analysis showed that the most of studies indicated a significant association between serum 25(OH)D levels and Covid-19 severity and outcome, but the results of studies that evaluated the association between vitamin D deficiency and pulmonary complications, inflammation, hospitalization, and ICU admission were inconsistent and insufficient (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn current study, we show that despite an increase in inflammatory biochemical parameters including the serum level of CPK, Ferritin, LDH, CRP, D-dimer, AST, and ALT, but we could not show any significant association between serum 25(OH)D levels and inflammatory lab tests. Also, there was no association between pulmonary involvement on chest CT scans and serum levels of vitamin D in this study.\u003c/p\u003e \u003cp\u003eIn another observational study in Turkey, 204 Covid-19 patients were enrolled and divided into two groups according to the severity of their disease outpatients with mild disease and patients with severe conditions, showed that there was a significantly lower serum of vitamin D and a significantly higher serum level of inflammatory lab tests including CRP, Ferritin and D-dimer and lymphocyte count, in a group of inpatients with severe disease (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAs seen, the patients in this study (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e), were divided into outpatients and inpatients in comparison with our study, in which we only evaluate these inflammatory biochemical parameters in moderate to severe cases who need to hospitalization and were inpatients. So another reason for controversial results of studies may be due to the design of the studies, which could perform in hospitalized, outpatients, or population based with normal individuals in comparison with patients (according to biobank data) (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe plasma concentration of 1,25(OH)2D, the active and functional form of vitamin D, is resulting from both, the availability of 25(OH)D and the activity of the enzymatic conversions, and also seen it has affected by genetic factors. Twin studies suggested high heritability of serum 25(OH)D levels. Also the risk of adverse health outcomes associated with low serum 25(OH)D levels may be due in part to genetic factors (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA meta-analysis identified common polymorphisms in the vitamin D receptors (VDR) gene which significantly modified the association of serum 25(OH)D and major health outcomes (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlso in another study showed a higher susceptibility or risk of acute lower respiratory tract infections (ALRI) due to vitamin D receptor (VDR) gen polymorphisms (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). So, the differentiation between its effects on different peoples may be due to these genotype variations and define to some extent the meaning of end-organ sensitivity to vit D metabolites.\u003c/p\u003e \u003cp\u003eIn one observational study showed that there is an identified gene cluster as a genetic susceptibility locus in severe Covid-19 patients with respiratory failure (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSo another reason for the different results of studies or mortality rate or severity of disease between individuals and countries may be due to these genetic differences in enzymatic pathways, in vitamin D receptors, or in susceptibility to Covid-19 infection and severity, in addition to other risk factors which could effect on people's health like the nutritional and socioeconomic factors or the primary health conditions of individuals or societies and other unknown risk factors which could confound these results.\u003c/p\u003e \u003cp\u003eAnother reason could be measuring serum level of vitamin D before or after developing infection and inflammation to avoid the negative effect of the illness on vitamin D levels (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), because the causal link between low vitamin D status and infections or autoimmune disease remains unclear (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eVitamin D deficiency (serum 25 (OH)D level\u0026thinsp;\u0026lt;\u0026thinsp;12 ng/ml) was significantly associated with a higher mortality rate in comparison with patients with serum 25(OH)D levels\u0026thinsp;\u0026gt;\u0026thinsp;30 ng/ml in hospitalized Covid-19 patients, but we could not find any significant association between vitamin D levels with the incidence of ICU admission, need for mechanical ventilation and length of hospital stay. Also, we did not see any significant relationship between serum levels of vitamin D with biochemical lab tests, radiologic findings on chest CT scans, and patient' vital signs on admission day. Considering this fact that despite the absence of a statistically significant association between serum level of vitamin D and severity criteria on admission and first day, between two subgroups, the presence of a significant difference in mortality between them at the end, maybe we could say that vitamin D deficiency could have a causal effect on Covid-19 outcome and mortality, not only a side effect of Covid-19 disease, so maybe treatment of the people with vitamin D deficiency before infection could improve Covid-19 outcome. Maybe further studies with a better design and method could clarify and show these facts better.\u003c/p\u003e \u003cp\u003eThe limitation of our study is incomplete medical records that we had to remove several patients, human error in measuring or recording the data may be small sample size, especially for better results in some conclusions and the patients were not evaluated at the same time and were reviewed in five consecutive months, therefore, the epidemiologic and virologic changes may be an effect on our results. Although we tried to consider known confounding variables such as age, gender, comorbidities, smoking, and obesity to some extent in our results other factors like drugs and the basic health conditions of patients and other nutrients and unknown confounding variables may effect our results.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCOVID-19\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCoronavirus disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVDR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003evitamin d receptors\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIOM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInstitute of Medicine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntensive care unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLDH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003elactate dehydrogenase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ec-reactive protein\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCPK\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecreatinine phosphokinase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCBC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecomplete blood count\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCOPD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eChronic obstructive pulmonary disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgment\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank the Tehran University of Medical science and Ziaeian Hospital, and acknowledge its research unit for their support and facilities for conducting this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author has no conflict of interest in any terms during the study to declare\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study had a research project grant from Tehran university of Medical science.\u003c/p\u003e\n\u003ch1\u003e\u003cstrong\u003eCompliance with Ethical Standards\u003c/strong\u003e\u003c/h1\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval:\u003c/strong\u003e All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material:\u0026nbsp;\u003c/strong\u003eData sharing not applicable to this article as no datasets were generated or analyzed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributors’ Statement Page:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr. Abolfazl Zendehdel and Dr. Ziba Aghsaeifard and Dr. Ghasem Azimi: conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript.\u003c/p\u003e\n\u003cp\u003eDr. Saeed Reza Jamali Moghaddam siyahkali and Dr. Azadeh Asoodeh: Designed the data collection instruments, collected data, carried out the initial analyses, and reviewed and revised the manuscript.\u003c/p\u003e\n\u003cp\u003eDr. Mohammad Bidkhori and Dr. Muhammad Abubakar Nuhu: Coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKupferschmidt K, Cohen J. 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Elsevier; 2021. p. 53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmolders J, van den Ouweland J, Geven C, Pickkers P, Kox M. Vitamin D deficiency in COVID-19: Mixing up cause and consequence. Metabolism-Clinical Experimental. 2021;115.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlSafar H, Grant WB, Hijazi R, Uddin M, Alkaabi N, Tay G, et al. COVID-19 disease severity and death in relation to vitamin D status among SARS-CoV-2-positive UAE residents. Nutrients. 2021;13(5):1714.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLohia P, Nguyen P, Patel N, Kapur S. Exploring the link between vitamin D and clinical outcomes in COVID-19. Am J Physiology-Endocrinology Metabolism. 2021;320(3):E520\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHastie CE, Pell JP, Sattar N. Vitamin D and COVID-19 infection and mortality in UK Biobank. Eur J Nutr. 2021;60(1):545\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFang Y, Zhang H, Xie J, Lin M, Ying L, Pang P, et al. Sensitivity of chest CT for COVID-19: comparison to RT-PCR. Radiology. 2020;296(2):E115\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBess Dawson-Hughes M. 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J Diabetes Metabolic Disorders. 2021;20(1):383\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEsmaeili SA, Mohammadian S, Radbakhsh S, Momtazi-Borojeni AA, Kheirmand Parizi P, Atabati H, et al. Evaluation of vitamin D(3) deficiency: A population-based study in northeastern Iran. J Cell Biochem. 2019;120(6):10337\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBorsche L, Glauner B, Mendel Jv. COVID-19 mortality risk correlates inversely with vitamin D3 status, and a mortality rate close to zero could theoretically be achieved at 50 ng/ml 25 (OH) D3: Results of a systematic review and meta-analysis. Nutrients. 2021;13(10):3596.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKazemi A, Mohammadi V, Aghababaee SK, Golzarand M, Clark CC, Babajafari S. Association of vitamin D status with SARS-CoV-2 infection or COVID-19 severity: a systematic review and meta-analysis. Adv Nutr. 2021;12(5):1636\u0026ndash;58.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaşaran N, Adaş M, G\u0026ouml;kden Y, Turgut N, Yıldırmak T, G\u0026uuml;ntaş G. The relationship between vitamin D and the severity of COVID-19. Bratislava Medical Journal-Bratislavske Lekarske Listy; 2021.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAli N. Role of vitamin D in preventing of COVID-19 infection, progression and severity. J Infect Public Health. 2020;13(10):1373\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoth DE, Jones AB, Prosser C, Robinson JL, Vohra S. Vitamin D receptor polymorphisms and the risk of acute lower respiratory tract infection in early childhood. J Infect Dis. 2008;197(5):676\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGroup SC-G. Genomewide association study of severe Covid-19 with respiratory failure. N Engl J Med. 2020;383(16):1522\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"COVID-19, vitamin D, prevalence, severity, outcome, mortality","lastPublishedDoi":"10.21203/rs.3.rs-8254002/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8254002/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIn this study, we aimed to assess the prevalence of vitamin D deficiency in hospitalized Covid-19 patients and demonstrate its association with severity and mortality of the disease.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis observational study at Ziaeian Hospital, Tehran, Iran. Of all confirmed COVID-19 patients who were admitted to this hospital 276 patients were enrolled in this study and divided into two groups; 145 patients in group1 with a serum 25(OH)D level\u0026thinsp;\u0026gt;\u0026thinsp;20 ng/ml and 131 patients in group 2 with a serum 25 (OH)D level\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;20 ng/ml. The severity, outcome, and mortality of COVID-19 disease were compared in these two groups, based on chest CT scans findings, laboratory data, and patient' vital signs on admission day, and the duration of hospitalization, requirement to ICU admission, need for intubation, and mortality.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe prevalence of vitamin D deficiency was 22.1%, and vitamin D insufficiency by definition of serum 25(OH)D levels 12\u0026ndash;20 ng/ml was 25.4%. Despite, an increase in serum levels of CPK, Ferritin, LDH, CRP, D-dimer, AST, and ALT, there was not any significant relationship between serum level of 25(OH)D with laboratory tests, chest CT scan scores, and patient's vital signs on admission day by univariate and multivariate analysis. The odds of incidence of ICU admission, mechanical ventilation, and mortality were higher in group 2 which was not statistically significant by univariate and multivariate analysis. Still, the mortality was significantly higher in subgroup 2 by multivariate regression analysis.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis study showed that vitamin D deficiency was associated with a higher mortality rate, while could not show any significant association between serum 25(OH)D levels with the incidence of ICU admission, need for mechanical ventilation, and length of hospital stay, also we did not find any significant relationship with laboratory tests, radiologic findings, and patient's vital signs on admission day.\u003c/p\u003e","manuscriptTitle":"Investigation of the prevalence of vitamin D deficiency in hospitalized COVID-19 patients and its association with disease severity, outcome, and mortality","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-12 06:20:22","doi":"10.21203/rs.3.rs-8254002/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-01-19T19:43:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"191176394032445629140632192856501912876","date":"2026-01-17T15:42:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"200140258709584528300074587498930768325","date":"2026-01-09T21:27:36+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-07T15:18:32+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-18T10:43:57+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-17T03:41:09+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-17T03:40:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2025-12-01T21:15:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c3113dde-8d58-40f8-8afc-9dbb815eabe3","owner":[],"postedDate":"January 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-01-12T06:20:22+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-12 06:20:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8254002","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8254002","identity":"rs-8254002","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}