SARS-CoV-2 vaccination and risk of infectious diseases in hospitalized older patients

SARS-CoV-2 vaccination and risk of infectious diseases in hospitalized older patients | 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 SARS-CoV-2 vaccination and risk of infectious diseases in hospitalized older patients Marco Balducci, Edoardo Locatelli, Maria Giorgia Barbieri, Elena Ferrighi, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3327002/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Jan, 2024 Read the published version in European Geriatric Medicine → Version 1 posted 6 You are reading this latest preprint version Abstract Purpose. Vaccinations, for example flu vaccine, may be a cause of cross-reactive immunostimulation that prevents a larger spectrum of infections. However, whether SARS-CoV-2 vaccinations may also determine this effect is unclear. This study aims, first, to assess the incidence of infections at hospital admission and during the hospitalization in older inpatients vaccinated and unvaccinated against SARS-CoV-2; second, to compare length of hospital stay and in-hospital mortality between vaccinated and unvaccinated individuals. Methods . This retrospective study included 754 older inpatients admitted to the Geriatrics and Orthogeriatrics Units of the University Hospital of Ferrara (Italy) between March 2021 and November 2021. Sociodemographic and health-related data, and the diagnosis of infections at hospital admission and during hospitalization were collected from medical records. Results. The sample’s mean age was 87.2 years, 59.2% were females, and 75.5% were vaccinated against SARS-CoV-2. Vaccinated individuals had a 33% lower odds of intra-hospital infections (OR = 0.67, 95%CI:0.46–0.98) and 40% lower in-hospital death (HR = 0.60, 95%CI:0.39–0.94), also after adjusting for potential confounders, while no significant results emerged about infections at hospital admission. Considering the hospitalization’s endpoints, SARS-CoV-2 vaccination was associated with a lower probability of being transferred to long-term care or other hospital departments than returning home (OR = 0.63, 95%CI:0.40–0.99). Conclusions. In older inpatients, SARS-CoV-2 vaccination may reduce the risk of intra-hospital infectious diseases not caused by SARS-CoV-2 and all-cause in-hospital mortality. The vaccination coverage in the older population could limit not only the onset and severity of COVID-19 but also the occurrence of other infectious diseases. SARS-CoV-2 vaccination intra-hospital infections aged hospitalization mortality Figures Figure 1 Key summary points Aim. To evaluate the incidence of infections and the in-hospital mortality rate in older inpatients vaccinated and unvaccinated against SARS-CoV-2. Findings. SARS-CoV-2 vaccination reduced the risk of non-SARS-CoV-2 intra-hospital infections and in-hospital mortality. Cross-reactive immunostimulation may explain these findings. Message. This research showed the importance of guaranteeing appropriate SARS-CoV-2 vaccination coverage in older population, which could limit not only the incidence and severity of COVID-19 but also the onset of other acute infectious diseases and the risk of in-hospital mortality. Background Acute infections are one of the leading causes of hospitalization and death in older people.[ 1 – 5 ] Infections acquired in healthcare settings, in particular, are associated with several adverse outcomes, and recent Italian data showed that, in the pre-pandemic period, their incidence among inpatients aged 65 years and older was around 9.1%.[ 6 , 7 ] Interestingly, a slight deflection in the intra-hospital and community-acquired infections caused by non-SARS-CoV-2 pathogens was observed in the general population in the last two years.[ 8 , 9 ] Beyond the stricter prevention and control measures implemented since the pandemic started, one could argue that, as reported on influenza and pneumococcal vaccinations, also SARS-CoV-2 vaccines may play a protective role against other microorganisms. Indeed, previous studies and meta-analyses demonstrated that the influenza vaccine could significantly prevent the onset of influenza-related pneumonia and reduce the risk of hospitalization in patients over 65 years.[ 10 – 13 ] Similar results emerged regarding the pneumococcal vaccine, whose cross-reactivity was supported by some immunological investigations.[ 14 – 17 ] In this study, we hypothesized that SARS-CoV-2 vaccination in older patients could reduce the incidence of infections leading to hospital admission and those occurring during hospitalization, even if caused by different pathogens from coronaviruses. Therefore, the primary aim of this study was to assess the incidence of infectious diseases diagnosed at admission and during the hospital stay among older inpatients who were vs. those who were not vaccinated against SARS-CoV-2. The secondary aim was to evaluate whether having been vaccinated for SARS-CoV-2 infection might positively impact some hospitalization endpoints, such as the length of hospital stay, the discharge setting, and in-hospital mortality. Methods Study design and population This is an observational retrospective study involving patients ≥ 65 years admitted to the Geriatrics and Orthogeriatrics Units of the University Hospital of Ferrara (Italy) between March 2021 and November 2021. The study protocol was approved by the local ethical committee (Independent Ethics Committee of the Area Vasta Emilia Centro, protocol number: 881/2022/Oss/AOUFe). All the patients consecutively admitted during the study period were assessed for recruitment. Inclusion criteria were: a) having received two-doses SARS-CoV-2 vaccination at least three weeks before hospital admission; b) having received a single dose of SARS-CoV-2 vaccine because of a previous (or subsequent) SARS-CoV-2 infection, confirmed by clinical records; c) having not been vaccinated against SARS-CoV-2 and not reporting a previous SARS-CoV-2 infection. Exclusion criteria were: d) having received two-doses SARS-CoV-2 vaccination since lesser than three weeks before hospital admission; e) having received only a single dose of SARS-CoV-2 vaccine with no previous (or subsequent) SARS-CoV-2 infection. Therefore, enrolled patients were classified into two groups: vaccinated (inclusion criteria a or b ) vs unvaccinated patients (inclusion criteria c ). From the 962 patients who accessed the Geriatrics and Orthogeriatrics Units of the University Hospital of Ferrara (Italy) between March 2021 and November 2021, we excluded those with exclusion criteria d (n = 52) and e (n = 156), obtaining asample of 754 patients. Data collection The patients’ data were obtained from the hospital database system (software SAP®) and digitized clinical records (software CUP 2000®). For each patient, we collected information on socio-demographic (age, sex), pre-hospital setting (home, nursing home, long-term care, other hospital units), medical history (arterial hypertension, diabetes, cerebrovascular diseases, cardiovascular diseases, chronic lung diseases, gastrointestinal disorders, chronic kidney failure, osteoarticular and rheumatic diseases, dementia and other neurodegenerative diseases, neoplasia, and psychiatric disorders), polypharmacy (defined as the use of 5 or more chronic medications per day, before admission),[ 18 , 19 ] use of immunosuppressive drugs and corticosteroids, acute illness and laboratory data at hospital admission (hemoglobin, leukocytes, neutrophils, lymphocytes, total protein, albumin, creatinine, electrolytes, C-reactive protein, procalcitonin), and some in-hospital therapies (number of antibiotics, the necessity of oxygen support). Data on SARS-CoV-2 vaccination status (type of vaccine performed, number of doses received, date of the last vaccine dose) were obtained by hospital medical records. Moreover, we recorded information from the multidimensional geriatric assessment performed routinely at ward admission, including the evaluation of functional status through the Basic Activities of Daily Living (BADL) and Instrumental Activities of Daily Living (IADL) scales, and cognitive performance using the Short Portable Mental Status Questionnaire (SPMSQ). Study outcomes Acute infectious diseases at hospital admission and during the hospital stay were identified from medical records and coded according to the International Classification of Diseases, 9th revision, as reported in Supplementary Table 1. As secondary outcomes, we considered the length of hospital stay, in-hospital all-cause mortality, and discharge destination (home, long-term care [LTC], nursing home [NH], transfer to another hospital ward). Statistical Analysis Participants’ demographic and clinical characteristics were described through mean and standard deviation or median and interquartile range (IQR) for the quantitative variables and frequency and percentage for the categorical variables. The characteristics of vaccinated and unvaccinated patients were compared by Student’s t-test for quantitative variables with normal distribution, Kruskal-Wallis test for quantitative variables without normal distribution, and Chi-squared test for categorical variables. The associations of SARS-CoV-2 vaccination status with intra-hospital infections and discharge destination were evaluated by binary and multinomial logistic regression analysis, respectively. The strength of these associations was expressed by odds ratio (OR) and 95% confidence interval (95%CI). Regarding the discharge destination, coming back to the pre-admission setting (home or NH) was considered as the reference outcome, while alternative outcomes included discharge to an LTC or other acute wards, new admission to a NH, and in-hospital death. The association between SARS-CoV-2 vaccination status and in-hospital mortality was assessed through Cox regression analysis and expressed as hazard ratio (HR) and 95%CI after checking the proportionality hazard assumption. The models obtained by both logistic and Cox regressions were adjusted for potential confounders in the studied associations. In particular, Model 1 was corrected for age, sex, and pre-hospital setting. Model 2 also included the number of chronic diseases, polypharmacy, chronic use of immunosuppressive or corticosteroid drugs, and BADL. Model 3 was further adjusted for specific acute illnesses diagnosed at hospital admission that could have substantially impacted the study outcomes: anaemia, falls/fractures, stroke/transient ischemic attack, and infections. Results As shown in Table 1 , the mean age of the 754 patients was 87.2 years, 59.2% were females, and 71.8% were admitted from home. The mean number of chronic diseases was 5.2, and 78.5% of patients reported polypharmacy. Overall, the median pre-hospital BADL and IADL were 2 (IQR: 0–4) and 0 (IQR: 0–2), respectively. Of the total sample, 569 (75.5%) were vaccinated against SARS-CoV-2; of these, 96% received two doses of vaccine, 1.9% were administered a single dose of the vaccine because they had a previous or subsequent COVID-19, and 2.1% got a two-doses vaccination plus a booster dose. Most of the participants were vaccinated with a messenger RNA vaccine (73.1% Pfizer-BioNtech and 24.6% Spikevax), while the minority with a viral vector vaccine (2.1% Vaxzevria and 0.2% Janssen). Table 1 Demographic and clinical characteristics of the study population according to SARS-CoV-2 vaccination status Overall (N = 754) Unvaccinated (N = 185) Vaccinated (N = 569) p -value Demographic characteristics Sex (female), n (%) 446 (59.2) 115 (62.2) 331 (58.2) 0.383 Age (years), mean (SD) 87.2 (5.6) 86.4 (6.2) 87.5 (5.4) 0.021 Pre-hospital setting Home, n (%) 541 (71.8) 133 (72.3) 408 (71.7) 0.006 Nursing home, n (%) 91 (12.1) 19 (10.3) 72 (12.7) LTC, n (%) 9 (1.2) 5 (2.7) 4 (0.7) Family home, n (%) 53 (7.0) 6 (3.3) 47 (8.3) Other hospital units, n (%) 59 (7.8) 21 (11.4) 38 (6.7) Cognitive and functional status SPMSQ, median (IQR) 6 (2–8) 6 (2–8) 6 (2–8) 0.903 BADL, median (IQR) 2 (0–4) 1 (0–2) 1 (0–4) 0.209 IADL, median (IQR) 0 (0–2) 0 (0-1.25) 0 (0–3) 0.323 Chronic diseases Arterial hypertension, n (%) 651 (86.3) 163 (88.1) 488 (85.8) 0.495 Diabetes, n (%) 195 (25.9) 53 (28.6) 142 (25) 0.368 Cerebrovascular diseases, n (%) 414 (54.9) 88 (47.6) 326 (57.3) 0.026 Cardiovascular diseases, n (%) 507 (67.2) 126 (68.1) 381 (67) 0.842 Chronic lung diseases, n (%) 173 (22.9) 40 (21.6) 133 (23.4) 0.695 Gastrointestinal diseases, n (%) 382 (50.7) 97 (52.4) 285 (50.1) 0.639 Chronic kidney failure, n (%) 277 (36.7) 71 (38.4) 206 (36.2) 0.656 Osteoarticular diseases, n (%) 337 (44.7) 88 (47.6) 249 (43.8) 0.412 Rheumatic diseases, n (%) 55 (7.3) 17 (9.2) 38 (6,7) 0.328 Dementia, n (%) 374 (49.6) 95 (51.4) 279 (49) 0.643 Other neurodegenerative diseases, n (%) 86 (11.4) 19 (10.3) 67 (11.8) 0.670 Neoplasia, n (%) 275 (36.5) 66 (35.7) 209 (36.7) 0.864 Psychiatric diseases, n (%) 203 (26.9) 50 (27) 153 (26.9) 1.000 Number of chronic diseases, mean (SD) 5.21 (1.82) 5.26 (1.84) 5.20 (1.81) 0.675 Previous COVID-19 infection, n (%) 38 (5.0) 15 (8.2) 23 (4.0) 0.043 Chronic medications Medications number, mean (SD) 7.09 (2.99) 6.95 (2.9) 7.14 (3.02) 0.438 Polypharmacy ( ≥ 5 drugs), n (%) 591 (78.5) 147 (79.5) 444 (78.2) 0.789 Corticosteroids, n (%) 94 (12.5) 26 (14.1) 68 (12) 0.538 Immunosuppressor, n (%) 18 (2.4) 8 (4.3) 10 (1.8) 0.089 BADL, Basic activities of Daily Living; IADL, Instrumental Activities of Daily Living; SPMSQ, Short Portable Mental Status Questionnaire; SD, Standard Deviation. Bold values indicate p-values < 0.05. Compared with unvaccinated individuals, those vaccinated were significantly older (86.4 vs 87.5 years) and more likely to come from residential facilities (21.7% vs 16.3%) and have cerebrovascular diseases (57.3% vs 47.6%) (Table 1 ). Considering the causes of hospital admission (Supplementary Table 2), we found that anemia, falls and fractures were presented more frequently in unvaccinated patients, and pneumonia was slightly more common in those vaccinated (22.0% vs 14.6%, p = 0.039). No differences between groups emerged for other causes of admission, and when considering the presence of any kind of infection at hospital admission (49.9% vs 49.2%, respectively, p = 0.931). About biochemical parameters (Table 2 ), unvaccinated patients had significantly lower serum hemoglobin, total protein, and albumin levels and higher C-reactive protein than those vaccinated. No substantial differences were observed concerning the need for oxygen support and the number of antibiotics administrated during the hospitalization. Table 2 Hospital-related data of the study population according to SARS-CoV-2 vaccination status Overall (N = 754) Unvaccinated (N = 185) Vaccinated (N = 569) p-value Blood tests Hemoglobin (g/dL) 11.30 (2.35) 10.89 (2.44) 11.44 (2.31) 0.006 White blood cells (x10 3 /mm 3 ) 10.8 (6.9) 10.4 (6.0) 10.9 (7.1) 0.414 Neutrophils (x10 3 /mm 3 ) 8.2 (5.2) 8.1 (4.9) 8.3 (5.4) 0.719 Lymphocytes (x10 3 /mm 3 ) 1.5 (2.1) 1.5 (2.4) 1.5 (1.9) 0.890 Total protein (g/dL) 6.05 (0.79) 5.89 (0.74) 6.1 (0.8) 0.003 Albumin (g/dL) 50.41 (7.12) 49.12 (8.77) 50.82 (6.47) 0.011 Creatinine (mg/dL) 1.58 (1.43) 1.64 (1.59) 1.57 (1.37) 0.522 CRP (mg/dL) 6.47 (7.61) 7.72 (8.73) 6.06 (7.17) 0.011 Procalcitonin (ng/mL) 7.03 (25.95) 3.23 (8.59) 8.28 (29.42) 0.092 In-hospital therapy Oxygen therapy, n (%) 276 (36.6) 67 (36.2) 209 (36.7) 0.969 Antibiotics 0.88 (0.93) 0.91 (0.99) 0.87 (0.91) 0.595 Notes : all reported variables except “Oxygen therapy” are expressed as mean (SD) Abbreviations : CRP, C-Reactive Protein; SD: Standard Deviation. Bold values indicate p-values <0.05. While there were no differences in the frequency of vaccinated and unvaccinated patients presenting with infections at hospital admission, the incidence of intra-hospital infectious diseases was significantly lower in the former group (33.2% vs 45.4%, p = 0.004). In particular, as shown in Fig. 1 , during the hospitalization vaccinated individuals reported less frequently respiratory tract infections and gastroduodenitis (5.1% vs 10.8%, p = 0.010 and 2.5% vs 9.7%. p < 0.001, respectively). Similar results were found considering only patients with acute infections on admission (n = 375). The cumulative incidence of intra-hospital infectious diseases in this subsample was lower in vaccinated than unvaccinated patients (32.3% vs 61.5%, p = 0.002), especially as concerns infectious gastroduodenitis (3.5% vs 13.2%, p = 0.002) and urinary tract infections (19.7% vs 29.7%, p = 0.065). These results were confirmed in the logistic regression after adjusting for potential confounders (Table 3 ). A total of 375 (49.7%) of the patients were admitted for acute infectious diseases, and 274 (36.3%) developed an intra-hospital infection during the hospital stay. Indeed, SARS-CoV-2 vaccination resulted independently associated with a 41% lower risk of developing intra-hospital infections (OR = 0.59, 95%CI: 0.41–0.85, p = 0.005). This association was further confirmed, albeit slightly attenuated, correcting for the main causes (infectious and non-infectious) of hospitalization (OR = 0.67, 95%CI: 0.46–0.98, p = 0.041). Table 3 Logistic regression for the association between SARS-CoV-2 vaccination and intra-hospital infections OR (95%CI) of intra-hospital infections p -value Model 1 Model 2 Model 3 SARS-CoV-2 vaccination (vs non-vaccination) 0.59 (0.42–0.84) p = 0.003 0.59 (0.41–0.85) p = 0.005 0.67 (0.46–0.98) p = 0.038 Model 1 is adjusted for age, sex, and pre-admission setting; Model 2 is also adjusted for the number of chronic diseases, polypharmacy, use of corticosteroid or immunosuppressant drugs, and BADL; Model 3 includes the variables in Model 2 and also the presence of acute cerebrovascular diseases, falls/fractures, anemia and infections at hospital admission. Abbreviations : BADL, Basic Activities of Daily Living; OR, Odds Ratio; 95% CI, 95% Confidence Intervals. During the hospital stay, 114 (15.1%) patients died, and higher mortality was observed among the unvaccinated than the vaccinated ones (24.3% vs 12.1%, p < 0.001). At the fully-adjusted Cox regression (Table 4 ), SARS-CoV-2 vaccination significantly reduced the likelihood of in-hospital death by 40% (HR = 0.60, 95%CI: 0.39–0.94, p = 0.041). Table 4 Cox regression for the association between SARS-CoV-2 vaccination and in-hospital mortality HR (95%CI) of in-hospital mortality p -value Model 1 Model 2 Model 3 SARS-CoV-2 vaccination (ref: non-vaccination) 0.64 (0.43–0.96) p = 0.029 0.63 (0.41–0.97) p = 0.036 0.60 (0.39–0.93) p = 0.024 Model 1 is adjusted for age, sex, and pre-admission setting; Model 2 is also adjusted for the number of chronic diseases, polypharmacy, use of corticosteroid or immunosuppressant drugs, and BADL; Model 3 includes the variables in Model 2 and also the presence of acute cerebrovascular diseases, falls/fractures, anemia and infections at hospital admission. Abbreviations : BADL, Basic Activities of Daily Living; HR, Hazard Ratio; 95% CI, 95% Confidence Intervals. Regarding the length of hospital stay, unvaccinated individuals reported an almost 2-day longer hospitalization than the vaccinated ones (12.5 [SD 10.4] vs 10.9 [SD 7.3] days, p = 0.017). Moreover, they were less likely to return to their pre-admission setting at discharge (41.1% vs 52.9% vs p = 0.007) but tended to be transferred more frequently to LTC or other hospital wards (23.8% vs 19.2%, p = 0.205). In the logistic regression (Supplementary Table 3), SARS-CoV-2 vaccination was associated with a lower probability of being transferred to LTC or other hospital departments (OR = 0.63, 95%CI: 0.40–0.99, p = 0.043), but the results were attenuated after adjustment for the cause of hospitalization (OR = 0.64, 95% CI: 0.41–1.02, p = 0.059). No significant associations emerged on the new transfer to a NH. Discussion Our study showed that older inpatients vaccinated against SARS-CoV-2 were less likely to develop infectious diseases and die during the hospital stay than those not vaccinated. Moreover, vaccinated patients had, on average, a shorter hospital stay compared with their unvaccinated counterparts. The frequency of acute infections at hospital admission and during hospitalization in our sample was noteworthy, affecting 49% and 36% of patients, respectively. These data align with the current literature, which reports that infections caused 48% of hospital admissions in older people[ 20 ] and occurred in around 40% of older inpatients during hospitalization.[ 21 ] When looking at the likelihood of developing an infection during the hospital stay, we found that SARS-CoV-2 vaccinated patients had a 33% lower risk than the unvaccinated ones. A possible explanation of this result may be that vaccinated patients had a better health status at hospital admission, making them less vulnerable to intra-hospital infections. Accordingly, comparing clinical data at hospital admission, vaccinated participants had higher hemoglobin, total protein, and albumin levels than unvaccinated. However, no significant differences emerged in other laboratory parameters or the type and number of comorbidities, except for cerebrovascular diseases (more frequent in vaccinated participants). Furthermore, vaccinated patients were older than the unvaccinated ones; therefore, they may have presented a greater impairment in the immune response linked to immunosenescence.[ 22 , 23 ] In addition to the above considerations, when adjusting the association for the potential confounders, the reduction in the risk of intra-hospital infections among vaccinated patients was only slightly attenuated and consistent with the main analysis. Although residual confounding cannot be ruled out, these findings suggest that SARS-CoV-2 vaccination may protect against other infectious diseases. This effect could be related to the development of a cross-reactive antibody response against different pathogens beyond SARS-CoV-2, or a general stimulation of the immune response. Such an issue has already been demonstrated for other vaccines recommended to the older population. For instance, through these mechanisms, the influenza vaccine can also prevent influenza-related pneumonia,[ 11 – 13 ] and the pneumococcal vaccine protects from pneumonia caused by serotypes of Streptococcus pneumoniae [ 16 , 17 ] that are not the specific targets of the vaccine. As concerns the SARS-CoV-2 vaccines, previous studies suggest that they lead to produce cross-reactive antibodies against other common human coronaviruses.[ 24 – 26 ] Moreover, as previously mentioned, the protective effect of SARS-CoV-2 against a larger spectrum of infectious diseases may involve an immunostimulatory effect both on the innate and acquired responses.[ 27 – 29 ] Indeed, previous research underlined that some components of SARS-CoV-2 mRNA vaccines could act as adjuvants and boost immunity. In particular, recent studies by Alameh et. al and Kobiyama et al, suggest an intrinsic adjuvant activity of the lipid nanoparticle (LNP)-encapsulated nucleoside-modified in mRNA vaccines, that stimulates the immune response.[ 30 , 31 ] Interestingly, in our sample, we did not find any difference between vaccinated and unvaccinated patients regarding the overall frequency of infectious diseases at hospital admission. When focusing on the specific infections at hospital admission, however, a slightly increased prevalence of pneumonia emerged among the vaccinated patients. This issue is not of clear explanation; one hypothesis is that unvaccinated patients may could be less prone to access hospital in case of respiratory infections of mild or medium severity. Conversely, the lower odds of intra-hospital infections among vaccinated patients supports the hypothesis that SARS-CoV-2 vaccination might be more protective in conditions of greater vulnerability, such as during hospitalization with other ongoing acute illnesses. Another possible explanation is that the cross-reactivity of SARS-CoV-2 vaccines may be mainly directed to pathogens causing intra-hospital rather than community-acquired infections. In this regard, exploring which specific microorganisms may be hit by cross-reactive antibodies induced by SARS-CoV-2 vaccines in future investigations would be interesting. Likely because of the above-described effects and immunostimulation, older inpatients who got the vaccination against SARS-CoV-2 reported better hospitalization-related outcomes, including shorter hospital stay and lower in-hospital mortality, even when analyses were adjusted for potential confounders. Moreover, in the same way, vaccinated older adults showed a lower probability of being transferred to another ward or LTC rather than returning to their pre-admission setting, supporting the positive influence of vaccination on the patient’s prognosis.[ 32 , 33 ] Limitations of our study include the lack of available data about the specific microorganisms causing the infections detected at hospital admission or during the hospital stay. Furthermore, the incidence of non-infectious in-hospital complications, which could have influenced the patient’s prognosis, was not investigated. However, we believe that having collected extensive data about health, functional and cognitive status, and the need for oxygen supplementation during the hospitalization, allowed us to capture the patients’ vulnerability and prognosis. Moreover, the negligible frequency of patients who got a viral vector vaccine did not allow us to perform appropriate subgroup analyses by type of vaccine administered. Finally, as in all observational studies, we may not have completely controlled the confounding effects of other variables in the tested associations. However, the inclusion of several possible confounders in the analyses supports our results. Conversely, the strengths of our study concern the large sample size and the wide set of information collected for each patient. Furthermore, the real-world setting of our study allows us to generalize the observed results to the general older population. Lastly, we investigated an issue novel and of current interest, contributing to the available scientific literature. In conclusion, our study suggests that SARS-CoV-2 vaccination in older hospitalized patients reduces the risk of intra-hospital infections, even caused by non-SARS-CoV-2 microorganisms, and in-hospital mortality. These findings highlight the importance of guaranteeing appropriate vaccination coverage in older population, which could limit not only the incidence and severity of COVID-19 but also the onset of other infectious diseases. Declarations Conflict of Interest. The authors declare no conflict of interest. Ethical approval. The study protocol was approved by the local ethical committee (Independent Ethics Committee of the Area Vasta Emilia Centro, protocol number: 881/2022/Oss/AOUFe). Funding: None. Author Contributions: Study conceptualization and design: MB, EL, MGB, EF, SS, GB, FS, IM, FR, SM, SV, and CT; acquisition of subjects and/or data: MB, EL, MGB, EF, SS, GB, IM; analysis and interpretation of data: FR, and CT; writing - original draft preparation: MB, EL, MGB, EF, SS, GB, FS, IM, FR, and CT; writing - review and editing: FS, FR, SM, SV, and CT. References Goto T, Yoshida K, Tsugawa Y, Camargo CA, Hasegawa K. Infectious Disease-Related Emergency Department Visits of Elderly Adults in the United States, 2011-2012. J Am Geriatr Soc 2016;64:31–6. https://doi.org/10.1111/jgs.13836. Levant S, Chari K, DeFrances CJ. Hospitalizations for patients aged 85 and over in the United States, 2000-2010. NCHS Data Brief 2015:1–8. Curns AT, Steiner CA, Sejvar JJ, Schonberger LB. Hospital Charges Attributable to a Primary Diagnosis of Infectious Diseases in Older Adults in the United States, 1998 to 2004. J Am Geriatr Soc 2008;56:969–75. https://doi.org/10.1111/j.1532-5415.2008.01712.x. Liang SY. Sepsis and Other Infectious Disease Emergencies in the Elderly. Emerg Med Clin North Am 2016;34:501–22. https://doi.org/10.1016/j.emc.2016.04.005. Alves VP, Casemiro FG, Araujo BG de, Lima MA de S, Oliveira RS de, Fernandes FT de S, et al. Factors Associated with Mortality among Elderly People in the COVID-19 Pandemic (SARS-CoV-2): A Systematic Review and Meta-Analysis. Int J Environ Res Public Health 2021;18:8008. https://doi.org/10.3390/ijerph18158008. WHO. World Report on Ageing and Health. WHO: Geneva, Switzerland 2015:260. Studio di prevalenza italiano sulle infezioni correlate all’assistenza e sull’uso di antibiotici negli ospedali per acuti-Protocollo ECDC. n.d. Su C, Zhang Z, Zhao X, Peng H, Hong Y, Huang L, et al. Changes in prevalence of nosocomial infection pre- and post-COVID-19 pandemic from a tertiary Hospital in China. BMC Infect Dis 2021;21:693. https://doi.org/10.1186/s12879-021-06396-x. Chow EJ, Uyeki TM, Chu HY. The effects of the COVID-19 pandemic on community respiratory virus activity. Nat Rev Microbiol 2022. https://doi.org/10.1038/s41579-022-00807-9. Heo JY, Song JY, Noh JY, Choi MJ, Yoon JG, Lee SN, et al. Effects of influenza immunization on pneumonia in the elderly. Hum Vaccin Immunother 2018;14:744–9. https://doi.org/10.1080/21645515.2017.1405200. Grijalva CG, Zhu Y, Williams DJ, Self WH, Ampofo K, Pavia AT, et al. Association Between Hospitalization With Community-Acquired Laboratory-Confirmed Influenza Pneumonia and Prior Receipt of Influenza Vaccination. JAMA 2015;314:1488. https://doi.org/10.1001/jama.2015.12160. Suzuki M, Katsurada N, Le MN, Kaneko N, Yaegashi M, Hosokawa N, et al. Effectiveness of inactivated influenza vaccine against laboratory-confirmed influenza pneumonia among adults aged ≥65 years in Japan. Vaccine 2018;36:2960–7. https://doi.org/10.1016/j.vaccine.2018.04.037. Fallani E, Orsi A, Signori A, Icardi G, Domnich A. An exploratory study to assess patterns of influenza- and pneumonia-related mortality among the Italian elderly. Hum Vaccin Immunother 2021;17:5514–21. https://doi.org/10.1080/21645515.2021.2005381. Eggenhuizen PJ, Ng BH, Chang J, Fell AL, Cheong RMY, Wong WY, et al. BCG Vaccine Derived Peptides Induce SARS-CoV-2 T Cell Cross-Reactivity. Front Immunol 2021;12. https://doi.org/10.3389/fimmu.2021.692729. Vojdani A, Vojdani E, Melgar AL, Redd J. Reaction of SARS-CoV-2 antibodies with other pathogens, vaccines, and food antigens. Front Immunol 2022;13. https://doi.org/10.3389/fimmu.2022.1003094. Braconier JH, Myhre EB, Odeberg H. Cross-reacting opsonic antibodies to clinically important pneumococcal serotypes after pneumococcal vaccination. Eur J Clin Microbiol 1983;2:453–8. https://doi.org/10.1007/BF02013903. Cunningham AL, McIntyre P, Subbarao K, Booy R, Levin MJ. Vaccines for older adults. BMJ 2021:n188. https://doi.org/10.1136/bmj.n188. Gnjidic D, Hilmer SN, Blyth FM, Naganathan V, Waite L, Seibel MJ, et al. Polypharmacy cutoff and outcomes: five or more medicines were used to identify community-dwelling older men at risk of different adverse outcomes. J Clin Epidemiol 2012;65:989–95. https://doi.org/10.1016/j.jclinepi.2012.02.018. Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr 2017;17:230. https://doi.org/10.1186/s12877-017-0621-2. Curns AT, Holman RC, Sejvar JJ, Owings MF, Schonberger LB. Infectious Disease Hospitalizations Among Older Adults in the United States From 1990 Through 2002. Arch Intern Med 2005;165:2514. https://doi.org/10.1001/archinte.165.21.2514. Coudert M, Pépin M, de Thezy A, Fercot E, Laycuras M, Coudert A-L, et al. Présentation clinique et performance de la bandelette urinaire pour le diagnostic d’infection urinaire en population gériatrique. Rev Med Interne 2019;40:714–21. https://doi.org/10.1016/j.revmed.2019.06.010. Pawelec G. Age and immunity: What is “immunosenescence”? Exp Gerontol 2018;105:4–9. https://doi.org/10.1016/j.exger.2017.10.024. Frasca D, Diaz A, Romero M, Garcia D, Blomberg BB. B Cell Immunosenescence. Annu Rev Cell Dev Biol 2020;36:551–74. https://doi.org/10.1146/annurev-cellbio-011620-034148. Grobben M, van der Straten K, Brouwer PJ, Brinkkemper M, Maisonnasse P, Dereuddre-Bosquet N, et al. Cross-reactive antibodies after SARS-CoV-2 infection and vaccination. Elife 2021;10. https://doi.org/10.7554/eLife.70330. Narowski TM, Raphel K, Adams LE, Huang J, Vielot NA, Jadi R, et al. SARS-CoV-2 mRNA vaccine induces robust specific and cross-reactive IgG and unequal neutralizing antibodies in naive and previously infected people. Cell Rep 2022;38:110336. https://doi.org/10.1016/j.celrep.2022.110336. Sampson AT, Heeney J, Cantoni D, Ferrari M, Sans MS, George C, et al. Coronavirus Pseudotypes for All Circulating Human Coronaviruses for Quantification of Cross-Neutralizing Antibody Responses. Viruses 2021;13:1579. https://doi.org/10.3390/v13081579. Loyal L, Braun J, Henze L, Kruse B, Dingeldey M, Reimer U, et al. Cross-reactive CD4 + T cells enhance SARS-CoV-2 immune responses upon infection and vaccination. Science (1979) 2021;374. https://doi.org/10.1126/science.abh1823. Mateus J, Grifoni A, Tarke A, Sidney J, Ramirez SI, Dan JM, et al. Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science (1979) 2020;370:89–94. https://doi.org/10.1126/science.abd3871. Saunders KO, Lee E, Parks R, Martinez DR, Li D, Chen H, et al. Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses. Nature 2021;594:553–9. https://doi.org/10.1038/s41586-021-03594-0. Kobiyama K, Ishii KJ. Making innate sense of mRNA vaccine adjuvanticity. Nat Immunol 2022;23:474–6. https://doi.org/10.1038/s41590-022-01168-4. Alameh M-G, Tombácz I, Bettini E, Lederer K, Ndeupen S, Sittplangkoon C, et al. Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses. Immunity 2021;54:2877-2892.e7. https://doi.org/10.1016/j.immuni.2021.11.001. Lopez Bernal J, Andrews N, Gower C, Robertson C, Stowe J, Tessier E, et al. Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study. BMJ 2021:n1088. https://doi.org/10.1136/bmj.n1088. Liu Y, Mao B, Liang S, Yang J-W, Lu H-W, Chai Y-H, et al. Association between age and clinical characteristics and outcomes of COVID-19. European Respiratory Journal 2020;55:2001112. https://doi.org/10.1183/13993003.01112-2020. Supplementary Files SUPPLEMENTARYMATERIALS.pdf Cite Share Download PDF Status: Published Journal Publication published 05 Jan, 2024 Read the published version in European Geriatric Medicine → Version 1 posted Editorial decision: Major revisions 26 Sep, 2023 Reviewers agreed at journal 21 Sep, 2023 Reviewers invited by journal 14 Sep, 2023 Editor invited by journal 13 Sep, 2023 Editor assigned by journal 09 Sep, 2023 First submitted to journal 05 Sep, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3327002","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":233171060,"identity":"7d7bb1fa-9b07-4210-a7bd-84bcb8bc89f7","order_by":0,"name":"Marco Balducci","email":"","orcid":"","institution":"University of Ferrara: Universita degli Studi di Ferrara","correspondingAuthor":false,"prefix":"","firstName":"Marco","middleName":"","lastName":"Balducci","suffix":""},{"id":233171061,"identity":"84b321c3-f4c5-438f-8f12-82171e9ad739","order_by":1,"name":"Edoardo Locatelli","email":"","orcid":"","institution":"University of Ferrara: Universita degli Studi di Ferrara","correspondingAuthor":false,"prefix":"","firstName":"Edoardo","middleName":"","lastName":"Locatelli","suffix":""},{"id":233171062,"identity":"d92a327b-0055-4346-a7f8-d03a272e7b0d","order_by":2,"name":"Maria Giorgia Barbieri","email":"","orcid":"","institution":"University of Ferrara: Universita degli Studi di Ferrara","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"Giorgia","lastName":"Barbieri","suffix":""},{"id":233171063,"identity":"ae36ef34-2ee9-4c40-90d5-330f345bc5ec","order_by":3,"name":"Elena Ferrighi","email":"","orcid":"","institution":"University of Ferrara: Universita degli Studi di Ferrara","correspondingAuthor":false,"prefix":"","firstName":"Elena","middleName":"","lastName":"Ferrighi","suffix":""},{"id":233171064,"identity":"47ae7e64-dc6b-470b-b4d0-c7d890630a2b","order_by":4,"name":"Serena Scardina","email":"","orcid":"","institution":"University of Ferrara: Universita degli Studi di Ferrara","correspondingAuthor":false,"prefix":"","firstName":"Serena","middleName":"","lastName":"Scardina","suffix":""},{"id":233171065,"identity":"ef40c898-3450-4c6b-aaf0-85a0bdaf59aa","order_by":5,"name":"Giulia Barrile","email":"","orcid":"","institution":"University of Ferrara: Universita degli Studi di Ferrara","correspondingAuthor":false,"prefix":"","firstName":"Giulia","middleName":"","lastName":"Barrile","suffix":""},{"id":233171066,"identity":"23543ebf-56d3-48c6-b1a0-7639c5279208","order_by":6,"name":"Federica Sganga","email":"","orcid":"","institution":"University Hospital Arcispedale Sant'Anna of Ferrara: Azienda Ospedaliero Universitaria di Ferrara Arcispedale Sant'Anna","correspondingAuthor":false,"prefix":"","firstName":"Federica","middleName":"","lastName":"Sganga","suffix":""},{"id":233171067,"identity":"a050478b-a104-47b2-8438-712d6e0d061f","order_by":7,"name":"Irene Mattioli","email":"","orcid":"","institution":"University Hospital Arcispedale Sant'Anna of Ferrara: Azienda Ospedaliero Universitaria di Ferrara Arcispedale Sant'Anna","correspondingAuthor":false,"prefix":"","firstName":"Irene","middleName":"","lastName":"Mattioli","suffix":""},{"id":233171068,"identity":"c659dcf3-85fc-455e-a2be-3f11bfbbc77c","order_by":8,"name":"Francesca Remelli","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEUlEQVRIiWNgGAWjYBAC9gZUvoUMG1jIwAKnFp4DqHwJHjawkIEECVoYJBLADNxapA8/e/Cjok6ev4H34aMbFRI8fJLPr274USDBwN/enYBVC1+auWHPmcOGMw6wGxvnnAE6TDqn7GYP0GESZ85uwKbFnofBTJqx7UACwwE2NuncNrCWtBs8QC0GErlYtfDwsH+TZvxXlyB/gI39d+4/oBbJM2k3/+DVwgO0pYE5wQBoC3NuA1CLBPux2/ht4SmT7Dl22HDjYTZm6ZxjoEDOYbstYyDBg8svQIdtk/hRUycvd7yN8XNOjY2cfPvxZzff/LGR42/vxaoFAZgRxhiASfzKUQH7A1JUj4JRMApGwfAHAGSRUhEI3BHnAAAAAElFTkSuQmCC","orcid":"","institution":"Azienda Ospedaliero Universitaria di Ferrara","correspondingAuthor":true,"prefix":"","firstName":"Francesca","middleName":"","lastName":"Remelli","suffix":""},{"id":233171069,"identity":"96ee332a-9db3-40e3-9847-02b4bed43bd7","order_by":9,"name":"Stefania Maggi","email":"","orcid":"","institution":"IN CNR Padova: Istituto di Neuroscienze Consiglio Nazionale delle Ricerche Sede di Padova","correspondingAuthor":false,"prefix":"","firstName":"Stefania","middleName":"","lastName":"Maggi","suffix":""},{"id":233171070,"identity":"a61ad132-ec16-4f89-a4a7-371bef0ca2f4","order_by":10,"name":"Stefano Volpato","email":"","orcid":"","institution":"University of Ferrara: Universita degli Studi di Ferrara","correspondingAuthor":false,"prefix":"","firstName":"Stefano","middleName":"","lastName":"Volpato","suffix":""},{"id":233171071,"identity":"6ca2d39d-3f12-4832-a3ab-5cea18aedfe7","order_by":11,"name":"Caterina Trevisan","email":"","orcid":"","institution":"University of Ferrara: Universita degli Studi di Ferrara","correspondingAuthor":false,"prefix":"","firstName":"Caterina","middleName":"","lastName":"Trevisan","suffix":""}],"badges":[],"createdAt":"2023-09-05 09:17:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3327002/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3327002/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s41999-023-00902-x","type":"published","date":"2024-01-05T11:36:30+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":43378239,"identity":"ab981e52-1a84-4d96-ad11-562b2a2be963","added_by":"auto","created_at":"2023-09-19 16:36:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":159453,"visible":true,"origin":"","legend":"\u003cp\u003eCumulative incidence of intra-hospital infections in vaccinated and unvaccinated patients.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3327002/v1/95547b6c09f07fb783e59f11.png"},{"id":54154302,"identity":"3e2aca1f-40a9-4ae0-8c45-7eeffc7fc6c2","added_by":"auto","created_at":"2024-04-05 11:36:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":520849,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3327002/v1/910f5204-a017-4c06-bdd7-a73c304e39a0.pdf"},{"id":43378240,"identity":"b06db344-877a-461a-9a94-5245845259ae","added_by":"auto","created_at":"2023-09-19 16:36:15","extension":"pdf","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":195540,"visible":true,"origin":"","legend":"","description":"","filename":"SUPPLEMENTARYMATERIALS.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3327002/v1/f74282a7e20bd2486f7de48a.pdf"}],"financialInterests":"","formattedTitle":"SARS-CoV-2 vaccination and risk of infectious diseases in hospitalized older patients","fulltext":[{"header":"Key summary points","content":"\u003cp\u003e\u003cstrong\u003eAim.\u0026nbsp;\u003c/strong\u003eTo evaluate the incidence of infections and the in-hospital mortality rate in older inpatients vaccinated and unvaccinated against SARS-CoV-2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFindings.\u003c/strong\u003e SARS-CoV-2 vaccination reduced the risk of non-SARS-CoV-2 intra-hospital infections and in-hospital mortality. Cross-reactive immunostimulation may explain these findings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMessage.\u0026nbsp;\u003c/strong\u003eThis research showed the importance of guaranteeing appropriate SARS-CoV-2 vaccination coverage in older population, which could limit not only the incidence and severity of COVID-19 but also the onset of other acute infectious diseases and the risk of in-hospital mortality.\u003c/p\u003e"},{"header":"Background","content":"\u003cp\u003eAcute infections are one of the leading causes of hospitalization and death in older people.[\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] Infections acquired in healthcare settings, in particular, are associated with several adverse outcomes, and recent Italian data showed that, in the pre-pandemic period, their incidence among inpatients aged 65 years and older was around 9.1%.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eInterestingly, a slight deflection in the intra-hospital and community-acquired infections caused by non-SARS-CoV-2 pathogens was observed in the general population in the last two years.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Beyond the stricter prevention and control measures implemented since the pandemic started, one could argue that, as reported on influenza and pneumococcal vaccinations, also SARS-CoV-2 vaccines may play a protective role against other microorganisms. Indeed, previous studies and meta-analyses demonstrated that the influenza vaccine could significantly prevent the onset of influenza-related pneumonia and reduce the risk of hospitalization in patients over 65 years.[\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] Similar results emerged regarding the pneumococcal vaccine, whose cross-reactivity was supported by some immunological investigations.[\u003cspan additionalcitationids=\"CR15 CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn this study, we hypothesized that SARS-CoV-2 vaccination in older patients could reduce the incidence of infections leading to hospital admission and those occurring during hospitalization, even if caused by different pathogens from coronaviruses.\u003c/p\u003e \u003cp\u003eTherefore, the primary aim of this study was to assess the incidence of infectious diseases diagnosed at admission and during the hospital stay among older inpatients who were vs. those who were not vaccinated against SARS-CoV-2. The secondary aim was to evaluate whether having been vaccinated for SARS-CoV-2 infection might positively impact some hospitalization endpoints, such as the length of hospital stay, the discharge setting, and in-hospital mortality.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and population\u003c/h2\u003e \u003cp\u003eThis is an observational retrospective study involving patients\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;65 years admitted to the Geriatrics and Orthogeriatrics Units of the University Hospital of Ferrara (Italy) between March 2021 and November 2021. The study protocol was approved by the local ethical committee (Independent Ethics Committee of the Area Vasta Emilia Centro, protocol number: 881/2022/Oss/AOUFe).\u003c/p\u003e \u003cp\u003eAll the patients consecutively admitted during the study period were assessed for recruitment. Inclusion criteria were: \u003cem\u003ea)\u003c/em\u003e having received two-doses SARS-CoV-2 vaccination at least three weeks before hospital admission; \u003cem\u003eb)\u003c/em\u003e having received a single dose of SARS-CoV-2 vaccine because of a previous (or subsequent) SARS-CoV-2 infection, confirmed by clinical records; \u003cem\u003ec)\u003c/em\u003e having not been vaccinated against SARS-CoV-2 and not reporting a previous SARS-CoV-2 infection.\u003c/p\u003e \u003cp\u003eExclusion criteria were: \u003cem\u003ed)\u003c/em\u003e having received two-doses SARS-CoV-2 vaccination since lesser than three weeks before hospital admission; \u003cem\u003ee)\u003c/em\u003e having received only a single dose of SARS-CoV-2 vaccine with no previous (or subsequent) SARS-CoV-2 infection.\u003c/p\u003e \u003cp\u003eTherefore, enrolled patients were classified into two groups: vaccinated (inclusion criteria \u003cem\u003ea\u003c/em\u003e or \u003cem\u003eb\u003c/em\u003e) \u003cem\u003evs\u003c/em\u003e unvaccinated patients (inclusion criteria \u003cem\u003ec\u003c/em\u003e).\u003c/p\u003e \u003cp\u003eFrom the 962 patients who accessed the Geriatrics and Orthogeriatrics Units of the University Hospital of Ferrara (Italy) between March 2021 and November 2021, we excluded those with exclusion criteria \u003cem\u003ed\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;52) and \u003cem\u003ee\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;156), obtaining asample of 754 patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003eThe patients\u0026rsquo; data were obtained from the hospital database system (software SAP\u0026reg;) and digitized clinical records (software CUP 2000\u0026reg;). For each patient, we collected information on socio-demographic (age, sex), pre-hospital setting (home, nursing home, long-term care, other hospital units), medical history (arterial hypertension, diabetes, cerebrovascular diseases, cardiovascular diseases, chronic lung diseases, gastrointestinal disorders, chronic kidney failure, osteoarticular and rheumatic diseases, dementia and other neurodegenerative diseases, neoplasia, and psychiatric disorders), polypharmacy (defined as the use of 5 or more chronic medications per day, before admission),[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] use of immunosuppressive drugs and corticosteroids, acute illness and laboratory data at hospital admission (hemoglobin, leukocytes, neutrophils, lymphocytes, total protein, albumin, creatinine, electrolytes, C-reactive protein, procalcitonin), and some in-hospital therapies (number of antibiotics, the necessity of oxygen support). Data on SARS-CoV-2 vaccination status (type of vaccine performed, number of doses received, date of the last vaccine dose) were obtained by hospital medical records. Moreover, we recorded information from the multidimensional geriatric assessment performed routinely at ward admission, including the evaluation of functional status through the Basic Activities of Daily Living (BADL) and Instrumental Activities of Daily Living (IADL) scales, and cognitive performance using the Short Portable Mental Status Questionnaire (SPMSQ).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy outcomes\u003c/h3\u003e\n\u003cp\u003eAcute infectious diseases at hospital admission and during the hospital stay were identified from medical records and coded according to the International Classification of Diseases, 9th revision, as reported in Supplementary Table\u0026nbsp;1.\u003c/p\u003e \u003cp\u003eAs secondary outcomes, we considered the length of hospital stay, in-hospital all-cause mortality, and discharge destination (home, long-term care [LTC], nursing home [NH], transfer to another hospital ward).\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eParticipants\u0026rsquo; demographic and clinical characteristics were described through mean and standard deviation or median and interquartile range (IQR) for the quantitative variables and frequency and percentage for the categorical variables. The characteristics of vaccinated and unvaccinated patients were compared by Student\u0026rsquo;s t-test for quantitative variables with normal distribution, Kruskal-Wallis test for quantitative variables without normal distribution, and Chi-squared test for categorical variables.\u003c/p\u003e \u003cp\u003eThe associations of SARS-CoV-2 vaccination status with intra-hospital infections and discharge destination were evaluated by binary and multinomial logistic regression analysis, respectively. The strength of these associations was expressed by odds ratio (OR) and 95% confidence interval (95%CI). Regarding the discharge destination, coming back to the pre-admission setting (home or NH) was considered as the reference outcome, while alternative outcomes included discharge to an LTC or other acute wards, new admission to a NH, and in-hospital death.\u003c/p\u003e \u003cp\u003eThe association between SARS-CoV-2 vaccination status and in-hospital mortality was assessed through Cox regression analysis and expressed as hazard ratio (HR) and 95%CI after checking the proportionality hazard assumption.\u003c/p\u003e \u003cp\u003eThe models obtained by both logistic and Cox regressions were adjusted for potential confounders in the studied associations. In particular, Model 1 was corrected for age, sex, and pre-hospital setting. Model 2 also included the number of chronic diseases, polypharmacy, chronic use of immunosuppressive or corticosteroid drugs, and BADL. Model 3 was further adjusted for specific acute illnesses diagnosed at hospital admission that could have substantially impacted the study outcomes: anaemia, falls/fractures, stroke/transient ischemic attack, and infections.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eAs shown in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, the mean age of the 754 patients was 87.2 years, 59.2% were females, and 71.8% were admitted from home. The mean number of chronic diseases was 5.2, and 78.5% of patients reported polypharmacy. Overall, the median pre-hospital BADL and IADL were 2 (IQR: 0\u0026ndash;4) and 0 (IQR: 0\u0026ndash;2), respectively. Of the total sample, 569 (75.5%) were vaccinated against SARS-CoV-2; of these, 96% received two doses of vaccine, 1.9% were administered a single dose of the vaccine because they had a previous or subsequent COVID-19, and 2.1% got a two-doses vaccination plus a booster dose. Most of the participants were vaccinated with a messenger RNA vaccine (73.1% Pfizer-BioNtech and 24.6% Spikevax), while the minority with a viral vector vaccine (2.1% Vaxzevria and 0.2% Janssen).\u0026nbsp;\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003e\u003cstrong\u003eDemographic and clinical characteristics of the study population according to SARS-CoV-2 vaccination status\u003c/strong\u003e\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\u003eOverall\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;754)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eUnvaccinated\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;185)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVaccinated\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;569)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-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\u003e\u003cem\u003eDemographic characteristics\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex (female), n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e446 (59.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e115 (62.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e331 (58.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.383\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (years), mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87.2 (5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86.4 (6.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87.5 (5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.021\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ePre-hospital setting\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHome, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e541 (71.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e133 (72.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e408 (71.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNursing home, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e91 (12.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 (10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72 (12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLTC, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFamily home, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53 (7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther hospital units, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59 (7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38 (6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eCognitive and functional status\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSPMSQ, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (2\u0026ndash;8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (2\u0026ndash;8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (2\u0026ndash;8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.903\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBADL, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (0\u0026ndash;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0\u0026ndash;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0\u0026ndash;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.209\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIADL, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0\u0026ndash;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0-1.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0\u0026ndash;3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.323\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eChronic diseases\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eArterial hypertension, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e651 (86.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e163 (88.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e488 (85.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.495\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e195 (25.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53 (28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e142 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.368\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCerebrovascular diseases, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e414 (54.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88 (47.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e326 (57.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.026\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCardiovascular diseases, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e507 (67.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e126 (68.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e381 (67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.842\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic lung diseases, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e173 (22.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40 (21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e133 (23.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.695\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGastrointestinal diseases, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e382 (50.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97 (52.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e285 (50.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.639\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic kidney failure, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e277 (36.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71 (38.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e206 (36.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.656\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOsteoarticular diseases, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e337 (44.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88 (47.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e249 (43.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.412\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRheumatic diseases, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55 (7.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (9.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38 (6,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.328\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDementia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e374 (49.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95 (51.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e279 (49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.643\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther neurodegenerative diseases, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 (10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.670\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNeoplasia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e275 (36.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66 (35.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e209 (36.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.864\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePsychiatric diseases, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e203 (26.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e153 (26.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of chronic diseases, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.21 (1.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.26 (1.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.20 (1.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.675\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrevious COVID-19 infection, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (8.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23 (4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.043\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eChronic medications\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedications number, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.09 (2.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.95 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.14 (3.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.438\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePolypharmacy (\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;5 drugs), n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e591 (78.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e147 (79.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e444 (78.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.789\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCorticosteroids, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e94 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26 (14.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.538\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eImmunosuppressor, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18 (2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (4.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.089\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\"\u003eBADL, Basic activities of Daily Living; IADL, Instrumental Activities of Daily Living; SPMSQ, Short Portable Mental Status Questionnaire; SD, Standard Deviation. Bold values indicate p-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eCompared with unvaccinated individuals, those vaccinated were significantly older (86.4 vs 87.5 years) and more likely to come from residential facilities (21.7% vs 16.3%) and have cerebrovascular diseases (57.3% vs 47.6%) (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Considering the causes of hospital admission (Supplementary Table 2), we found that anemia, falls and fractures were presented more frequently in unvaccinated patients, and pneumonia was slightly more common in those vaccinated (22.0% vs 14.6%, p\u0026thinsp;=\u0026thinsp;0.039). No differences between groups emerged for other causes of admission, and when considering the presence of any kind of infection at hospital admission (49.9% vs 49.2%, respectively, p\u0026thinsp;=\u0026thinsp;0.931). About biochemical parameters (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e), unvaccinated patients had significantly lower serum hemoglobin, total protein, and albumin levels and higher C-reactive protein than those vaccinated. No substantial differences were observed concerning the need for oxygen support and the number of antibiotics administrated during the hospitalization.\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eHospital-related data of the study population according to SARS-CoV-2 vaccination status\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\u003eOverall\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;754)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eUnvaccinated\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;185)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVaccinated\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;569)\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\u003e\u003cem\u003eBlood tests\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.30 (2.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.89 (2.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.44 (2.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWhite blood cells (x10\u003csup\u003e3\u003c/sup\u003e/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.8 (6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.4 (6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.9 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.414\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNeutrophils (x10\u003csup\u003e3\u003c/sup\u003e/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.2 (5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.1 (4.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.3 (5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.719\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLymphocytes (x10\u003csup\u003e3\u003c/sup\u003e/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.5 (2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.5 (2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.5 (1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.890\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal protein (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.05 (0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.89 (0.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.1 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlbumin (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e50.41 (7.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e49.12 (8.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e50.82 (6.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCreatinine (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.58 (1.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.64 (1.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.57 (1.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.522\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRP (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.47 (7.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.72 (8.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.06 (7.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProcalcitonin (ng/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.03 (25.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.23 (8.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.28 (29.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.092\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eIn-hospital therapy\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOxygen therapy, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e276 (36.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e67 (36.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e209 (36.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.969\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAntibiotics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.88 (0.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.91 (0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.87 (0.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.595\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eNotes\u003c/em\u003e: all reported variables except \u0026ldquo;Oxygen therapy\u0026rdquo; are expressed as mean (SD)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations\u003c/em\u003e: CRP, C-Reactive Protein; SD: Standard Deviation. Bold values indicate p-values \u0026lt;0.05.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eWhile there were no differences in the frequency of vaccinated and unvaccinated patients presenting with infections at hospital admission, the incidence of intra-hospital infectious diseases was significantly lower in the former group (33.2% vs 45.4%, p\u0026thinsp;=\u0026thinsp;0.004). In particular, as shown in Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, during the hospitalization vaccinated individuals reported less frequently respiratory tract infections and gastroduodenitis (5.1% vs 10.8%, p\u0026thinsp;=\u0026thinsp;0.010 and 2.5% vs 9.7%. p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, respectively). Similar results were found considering only patients with acute infections on admission (n\u0026thinsp;=\u0026thinsp;375). The cumulative incidence of intra-hospital infectious diseases in this subsample was lower in vaccinated than unvaccinated patients (32.3% vs 61.5%, p\u0026thinsp;=\u0026thinsp;0.002), especially as concerns infectious gastroduodenitis (3.5% vs 13.2%, p\u0026thinsp;=\u0026thinsp;0.002) and urinary tract infections (19.7% vs 29.7%, p\u0026thinsp;=\u0026thinsp;0.065).\u003c/p\u003e\n\u003cp\u003eThese results were confirmed in the logistic regression after adjusting for potential confounders (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). A total of 375 (49.7%) of the patients were admitted for acute infectious diseases, and 274 (36.3%) developed an intra-hospital infection during the hospital stay. Indeed, SARS-CoV-2 vaccination resulted independently associated with a 41% lower risk of developing intra-hospital infections (OR\u0026thinsp;=\u0026thinsp;0.59, 95%CI: 0.41\u0026ndash;0.85, p\u0026thinsp;=\u0026thinsp;0.005). This association was further confirmed, albeit slightly attenuated, correcting for the main causes (infectious and non-infectious) of hospitalization (OR\u0026thinsp;=\u0026thinsp;0.67, 95%CI: 0.46\u0026ndash;0.98, p\u0026thinsp;=\u0026thinsp;0.041).\u0026nbsp;\u003c/p\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003e\u003cstrong\u003eLogistic regression for the association between SARS-CoV-2 vaccination and intra-hospital infections\u003c/strong\u003e\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\" colspan=\"3\"\u003e\n \u003cp\u003eOR (95%CI) of intra-hospital infections\u003c/p\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-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\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSARS-CoV-2 vaccination\u003c/p\u003e\n \u003cp\u003e(vs non-vaccination)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.59 (0.42\u0026ndash;0.84)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.59 (0.41\u0026ndash;0.85) \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.67 (0.46\u0026ndash;0.98) \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.038\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eModel 1 is adjusted for age, sex, and pre-admission setting; Model 2 is also adjusted for the number of chronic diseases, polypharmacy, use of corticosteroid or immunosuppressant drugs, and BADL; Model 3 includes the variables in Model 2 and also the presence of acute cerebrovascular diseases, falls/fractures, anemia and infections at hospital admission. \u003cem\u003eAbbreviations\u003c/em\u003e: BADL, Basic Activities of Daily Living; OR, Odds Ratio; 95% CI, 95% Confidence Intervals.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eDuring the hospital stay, 114 (15.1%) patients died, and higher mortality was observed among the unvaccinated than the vaccinated ones (24.3% vs 12.1%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). At the fully-adjusted Cox regression (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e), SARS-CoV-2 vaccination significantly reduced the likelihood of in-hospital death by 40% (HR\u0026thinsp;=\u0026thinsp;0.60, 95%CI: 0.39\u0026ndash;0.94, p\u0026thinsp;=\u0026thinsp;0.041).\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003e\u003cstrong\u003eCox regression for the association between SARS-CoV-2 vaccination and in-hospital mortality\u003c/strong\u003e\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\" colspan=\"3\"\u003e\n \u003cp\u003eHR (95%CI) of in-hospital mortality\u003c/p\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-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\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSARS-CoV-2 vaccination\u003c/p\u003e\n \u003cp\u003e(ref: non-vaccination)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.64 (0.43\u0026ndash;0.96) \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.029\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.63 (0.41\u0026ndash;0.97) \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.60 (0.39\u0026ndash;0.93) \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eModel 1 is adjusted for age, sex, and pre-admission setting; Model 2 is also adjusted for the number of chronic diseases, polypharmacy, use of corticosteroid or immunosuppressant drugs, and BADL; Model 3 includes the variables in Model 2 and also the presence of acute cerebrovascular diseases, falls/fractures, anemia and infections at hospital admission. \u003cem\u003eAbbreviations\u003c/em\u003e: BADL, Basic Activities of Daily Living; HR, Hazard Ratio; 95% CI, 95% Confidence Intervals.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eRegarding the length of hospital stay, unvaccinated individuals reported an almost 2-day longer hospitalization than the vaccinated ones (12.5 [SD 10.4] vs 10.9 [SD 7.3] days, p\u0026thinsp;=\u0026thinsp;0.017). Moreover, they were less likely to return to their pre-admission setting at discharge (41.1% vs 52.9% vs p\u0026thinsp;=\u0026thinsp;0.007) but tended to be transferred more frequently to LTC or other hospital wards (23.8% vs 19.2%, p\u0026thinsp;=\u0026thinsp;0.205). In the logistic regression (Supplementary Table 3), SARS-CoV-2 vaccination was associated with a lower probability of being transferred to LTC or other hospital departments (OR\u0026thinsp;=\u0026thinsp;0.63, 95%CI: 0.40\u0026ndash;0.99, p\u0026thinsp;=\u0026thinsp;0.043), but the results were attenuated after adjustment for the cause of hospitalization (OR\u0026thinsp;=\u0026thinsp;0.64, 95% CI: 0.41\u0026ndash;1.02, p\u0026thinsp;=\u0026thinsp;0.059). No significant associations emerged on the new transfer to a NH.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study showed that older inpatients vaccinated against SARS-CoV-2 were less likely to develop infectious diseases and die during the hospital stay than those not vaccinated. Moreover, vaccinated patients had, on average, a shorter hospital stay compared with their unvaccinated counterparts.\u003c/p\u003e \u003cp\u003eThe frequency of acute infections at hospital admission and during hospitalization in our sample was noteworthy, affecting 49% and 36% of patients, respectively. These data align with the current literature, which reports that infections caused 48% of hospital admissions in older people[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] and occurred in around 40% of older inpatients during hospitalization.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eWhen looking at the likelihood of developing an infection during the hospital stay, we found that SARS-CoV-2 vaccinated patients had a 33% lower risk than the unvaccinated ones. A possible explanation of this result may be that vaccinated patients had a better health status at hospital admission, making them less vulnerable to intra-hospital infections. Accordingly, comparing clinical data at hospital admission, vaccinated participants had higher hemoglobin, total protein, and albumin levels than unvaccinated. However, no significant differences emerged in other laboratory parameters or the type and number of comorbidities, except for cerebrovascular diseases (more frequent in vaccinated participants). Furthermore, vaccinated patients were older than the unvaccinated ones; therefore, they may have presented a greater impairment in the immune response linked to immunosenescence.[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] In addition to the above considerations, when adjusting the association for the potential confounders, the reduction in the risk of intra-hospital infections among vaccinated patients was only slightly attenuated and consistent with the main analysis. Although residual confounding cannot be ruled out, these findings suggest that SARS-CoV-2 vaccination may protect against other infectious diseases. This effect could be related to the development of a cross-reactive antibody response against different pathogens beyond SARS-CoV-2, or a general stimulation of the immune response. Such an issue has already been demonstrated for other vaccines recommended to the older population. For instance, through these mechanisms, the influenza vaccine can also prevent influenza-related pneumonia,[\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] and the pneumococcal vaccine protects from pneumonia caused by serotypes of \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] that are not the specific targets of the vaccine. As concerns the SARS-CoV-2 vaccines, previous studies suggest that they lead to produce cross-reactive antibodies against other common human coronaviruses.[\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] Moreover, as previously mentioned, the protective effect of SARS-CoV-2 against a larger spectrum of infectious diseases may involve an immunostimulatory effect both on the innate and acquired responses.[\u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] Indeed, previous research underlined that some components of SARS-CoV-2 mRNA vaccines could act as adjuvants and boost immunity. In particular, recent studies by Alameh et. al and Kobiyama et al, suggest an intrinsic adjuvant activity of the lipid nanoparticle (LNP)-encapsulated nucleoside-modified in mRNA vaccines, that stimulates the immune response.[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] Interestingly, in our sample, we did not find any difference between vaccinated and unvaccinated patients regarding the overall frequency of infectious diseases at hospital admission. When focusing on the specific infections at hospital admission, however, a slightly increased prevalence of pneumonia emerged among the vaccinated patients. This issue is not of clear explanation; one hypothesis is that unvaccinated patients may could be less prone to access hospital in case of respiratory infections of mild or medium severity. Conversely, the lower odds of intra-hospital infections among vaccinated patients supports the hypothesis that SARS-CoV-2 vaccination might be more protective in conditions of greater vulnerability, such as during hospitalization with other ongoing acute illnesses. Another possible explanation is that the cross-reactivity of SARS-CoV-2 vaccines may be mainly directed to pathogens causing intra-hospital rather than community-acquired infections. In this regard, exploring which specific microorganisms may be hit by cross-reactive antibodies induced by SARS-CoV-2 vaccines in future investigations would be interesting.\u003c/p\u003e \u003cp\u003eLikely because of the above-described effects and immunostimulation, older inpatients who got the vaccination against SARS-CoV-2 reported better hospitalization-related outcomes, including shorter hospital stay and lower in-hospital mortality, even when analyses were adjusted for potential confounders. Moreover, in the same way, vaccinated older adults showed a lower probability of being transferred to another ward or LTC rather than returning to their pre-admission setting, supporting the positive influence of vaccination on the patient\u0026rsquo;s prognosis.[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eLimitations of our study include the lack of available data about the specific microorganisms causing the infections detected at hospital admission or during the hospital stay. Furthermore, the incidence of non-infectious in-hospital complications, which could have influenced the patient\u0026rsquo;s prognosis, was not investigated. However, we believe that having collected extensive data about health, functional and cognitive status, and the need for oxygen supplementation during the hospitalization, allowed us to capture the patients\u0026rsquo; vulnerability and prognosis. Moreover, the negligible frequency of patients who got a viral vector vaccine did not allow us to perform appropriate subgroup analyses by type of vaccine administered. Finally, as in all observational studies, we may not have completely controlled the confounding effects of other variables in the tested associations. However, the inclusion of several possible confounders in the analyses supports our results.\u003c/p\u003e \u003cp\u003eConversely, the strengths of our study concern the large sample size and the wide set of information collected for each patient. Furthermore, the real-world setting of our study allows us to generalize the observed results to the general older population. Lastly, we investigated an issue novel and of current interest, contributing to the available scientific literature.\u003c/p\u003e \u003cp\u003eIn conclusion, our study suggests that SARS-CoV-2 vaccination in older hospitalized patients reduces the risk of intra-hospital infections, even caused by non-SARS-CoV-2 microorganisms, and in-hospital mortality. These findings highlight the importance of guaranteeing appropriate vaccination coverage in older population, which could limit not only the incidence and severity of COVID-19 but also the onset of other infectious diseases.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest.\u0026nbsp;\u003c/strong\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval.\u0026nbsp;\u003c/strong\u003eThe study protocol was approved by the local ethical committee (Independent Ethics Committee of the Area Vasta Emilia Centro, protocol number: 881/2022/Oss/AOUFe).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e None.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u0026nbsp;\u003c/strong\u003eStudy conceptualization and design: MB, EL, MGB, EF, SS, GB, FS, IM, FR, SM, SV, and CT; acquisition of subjects and/or data: MB, EL, MGB, EF, SS, GB, IM; analysis and interpretation of data: FR, and CT; writing - original draft preparation: MB, EL, MGB, EF, SS, GB, FS, IM, FR, and CT; writing - review and editing: FS, FR, SM, SV, and CT.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGoto T, Yoshida K, Tsugawa Y, Camargo CA, Hasegawa K. Infectious Disease-Related Emergency Department Visits of Elderly Adults in the United States, 2011-2012. J Am Geriatr Soc 2016;64:31\u0026ndash;6. https://doi.org/10.1111/jgs.13836.\u003c/li\u003e\n\u003cli\u003eLevant S, Chari K, DeFrances CJ. Hospitalizations for patients aged 85 and over in the United States, 2000-2010. NCHS Data Brief 2015:1\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eCurns AT, Steiner CA, Sejvar JJ, Schonberger LB. Hospital Charges Attributable to a Primary Diagnosis of Infectious Diseases in Older Adults in the United States, 1998 to 2004. J Am Geriatr Soc 2008;56:969\u0026ndash;75. https://doi.org/10.1111/j.1532-5415.2008.01712.x.\u003c/li\u003e\n\u003cli\u003eLiang SY. Sepsis and Other Infectious Disease Emergencies in the Elderly. Emerg Med Clin North Am 2016;34:501\u0026ndash;22. https://doi.org/10.1016/j.emc.2016.04.005.\u003c/li\u003e\n\u003cli\u003eAlves VP, Casemiro FG, Araujo BG de, Lima MA de S, Oliveira RS de, Fernandes FT de S, et al. Factors Associated with Mortality among Elderly People in the COVID-19 Pandemic (SARS-CoV-2): A Systematic Review and Meta-Analysis. Int J Environ Res Public Health 2021;18:8008. https://doi.org/10.3390/ijerph18158008.\u003c/li\u003e\n\u003cli\u003eWHO. World Report on Ageing and Health. WHO: Geneva, Switzerland 2015:260.\u003c/li\u003e\n\u003cli\u003eStudio di prevalenza italiano sulle infezioni correlate all\u0026rsquo;assistenza e sull\u0026rsquo;uso di antibiotici negli ospedali per acuti-Protocollo ECDC. n.d.\u003c/li\u003e\n\u003cli\u003eSu C, Zhang Z, Zhao X, Peng H, Hong Y, Huang L, et al. Changes in prevalence of nosocomial infection pre- and post-COVID-19 pandemic from a tertiary Hospital in China. BMC Infect Dis 2021;21:693. https://doi.org/10.1186/s12879-021-06396-x.\u003c/li\u003e\n\u003cli\u003eChow EJ, Uyeki TM, Chu HY. The effects of the COVID-19 pandemic on community respiratory virus activity. Nat Rev Microbiol 2022. https://doi.org/10.1038/s41579-022-00807-9.\u003c/li\u003e\n\u003cli\u003eHeo JY, Song JY, Noh JY, Choi MJ, Yoon JG, Lee SN, et al. Effects of influenza immunization on pneumonia in the elderly. Hum Vaccin Immunother 2018;14:744\u0026ndash;9. https://doi.org/10.1080/21645515.2017.1405200.\u003c/li\u003e\n\u003cli\u003eGrijalva CG, Zhu Y, Williams DJ, Self WH, Ampofo K, Pavia AT, et al. Association Between Hospitalization With Community-Acquired Laboratory-Confirmed Influenza Pneumonia and Prior Receipt of Influenza Vaccination. JAMA 2015;314:1488. https://doi.org/10.1001/jama.2015.12160.\u003c/li\u003e\n\u003cli\u003eSuzuki M, Katsurada N, Le MN, Kaneko N, Yaegashi M, Hosokawa N, et al. Effectiveness of inactivated influenza vaccine against laboratory-confirmed influenza pneumonia among adults aged \u0026ge;65 years in Japan. Vaccine 2018;36:2960\u0026ndash;7. https://doi.org/10.1016/j.vaccine.2018.04.037.\u003c/li\u003e\n\u003cli\u003eFallani E, Orsi A, Signori A, Icardi G, Domnich A. An exploratory study to assess patterns of influenza- and pneumonia-related mortality among the Italian elderly. Hum Vaccin Immunother 2021;17:5514\u0026ndash;21. https://doi.org/10.1080/21645515.2021.2005381.\u003c/li\u003e\n\u003cli\u003eEggenhuizen PJ, Ng BH, Chang J, Fell AL, Cheong RMY, Wong WY, et al. BCG Vaccine Derived Peptides Induce SARS-CoV-2 T Cell Cross-Reactivity. Front Immunol 2021;12. https://doi.org/10.3389/fimmu.2021.692729.\u003c/li\u003e\n\u003cli\u003eVojdani A, Vojdani E, Melgar AL, Redd J. Reaction of SARS-CoV-2 antibodies with other pathogens, vaccines, and food antigens. Front Immunol 2022;13. https://doi.org/10.3389/fimmu.2022.1003094.\u003c/li\u003e\n\u003cli\u003eBraconier JH, Myhre EB, Odeberg H. Cross-reacting opsonic antibodies to clinically important pneumococcal serotypes after pneumococcal vaccination. Eur J Clin Microbiol 1983;2:453\u0026ndash;8. https://doi.org/10.1007/BF02013903.\u003c/li\u003e\n\u003cli\u003eCunningham AL, McIntyre P, Subbarao K, Booy R, Levin MJ. Vaccines for older adults. BMJ 2021:n188. https://doi.org/10.1136/bmj.n188.\u003c/li\u003e\n\u003cli\u003eGnjidic D, Hilmer SN, Blyth FM, Naganathan V, Waite L, Seibel MJ, et al. Polypharmacy cutoff and outcomes: five or more medicines were used to identify community-dwelling older men at risk of different adverse outcomes. J Clin Epidemiol 2012;65:989\u0026ndash;95. https://doi.org/10.1016/j.jclinepi.2012.02.018.\u003c/li\u003e\n\u003cli\u003eMasnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr 2017;17:230. https://doi.org/10.1186/s12877-017-0621-2.\u003c/li\u003e\n\u003cli\u003eCurns AT, Holman RC, Sejvar JJ, Owings MF, Schonberger LB. Infectious Disease Hospitalizations Among Older Adults in the United States From 1990 Through 2002. Arch Intern Med 2005;165:2514. https://doi.org/10.1001/archinte.165.21.2514.\u003c/li\u003e\n\u003cli\u003eCoudert M, P\u0026eacute;pin M, de Thezy A, Fercot E, Laycuras M, Coudert A-L, et al. Pr\u0026eacute;sentation clinique et performance de la bandelette urinaire pour le diagnostic d\u0026rsquo;infection urinaire en population g\u0026eacute;riatrique. Rev Med Interne 2019;40:714\u0026ndash;21. https://doi.org/10.1016/j.revmed.2019.06.010.\u003c/li\u003e\n\u003cli\u003ePawelec G. Age and immunity: What is \u0026ldquo;immunosenescence\u0026rdquo;? Exp Gerontol 2018;105:4\u0026ndash;9. https://doi.org/10.1016/j.exger.2017.10.024.\u003c/li\u003e\n\u003cli\u003eFrasca D, Diaz A, Romero M, Garcia D, Blomberg BB. B Cell Immunosenescence. Annu Rev Cell Dev Biol 2020;36:551\u0026ndash;74. https://doi.org/10.1146/annurev-cellbio-011620-034148.\u003c/li\u003e\n\u003cli\u003eGrobben M, van der Straten K, Brouwer PJ, Brinkkemper M, Maisonnasse P, Dereuddre-Bosquet N, et al. Cross-reactive antibodies after SARS-CoV-2 infection and vaccination. Elife 2021;10. https://doi.org/10.7554/eLife.70330.\u003c/li\u003e\n\u003cli\u003eNarowski TM, Raphel K, Adams LE, Huang J, Vielot NA, Jadi R, et al. SARS-CoV-2 mRNA vaccine induces robust specific and cross-reactive IgG and unequal neutralizing antibodies in naive and previously infected people. Cell Rep 2022;38:110336. https://doi.org/10.1016/j.celrep.2022.110336.\u003c/li\u003e\n\u003cli\u003eSampson AT, Heeney J, Cantoni D, Ferrari M, Sans MS, George C, et al. Coronavirus Pseudotypes for All Circulating Human Coronaviruses for Quantification of Cross-Neutralizing Antibody Responses. Viruses 2021;13:1579. https://doi.org/10.3390/v13081579.\u003c/li\u003e\n\u003cli\u003eLoyal L, Braun J, Henze L, Kruse B, Dingeldey M, Reimer U, et al. Cross-reactive CD4 \u003csup\u003e+\u003c/sup\u003e T cells enhance SARS-CoV-2 immune responses upon infection and vaccination. Science (1979) 2021;374. https://doi.org/10.1126/science.abh1823.\u003c/li\u003e\n\u003cli\u003eMateus J, Grifoni A, Tarke A, Sidney J, Ramirez SI, Dan JM, et al. Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science (1979) 2020;370:89\u0026ndash;94. https://doi.org/10.1126/science.abd3871.\u003c/li\u003e\n\u003cli\u003eSaunders KO, Lee E, Parks R, Martinez DR, Li D, Chen H, et al. Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses. Nature 2021;594:553\u0026ndash;9. https://doi.org/10.1038/s41586-021-03594-0.\u003c/li\u003e\n\u003cli\u003eKobiyama K, Ishii KJ. Making innate sense of mRNA vaccine adjuvanticity. Nat Immunol 2022;23:474\u0026ndash;6. https://doi.org/10.1038/s41590-022-01168-4.\u003c/li\u003e\n\u003cli\u003eAlameh M-G, Tomb\u0026aacute;cz I, Bettini E, Lederer K, Ndeupen S, Sittplangkoon C, et al. Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses. Immunity 2021;54:2877-2892.e7. https://doi.org/10.1016/j.immuni.2021.11.001.\u003c/li\u003e\n\u003cli\u003eLopez Bernal J, Andrews N, Gower C, Robertson C, Stowe J, Tessier E, et al. Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study. BMJ 2021:n1088. https://doi.org/10.1136/bmj.n1088.\u003c/li\u003e\n\u003cli\u003eLiu Y, Mao B, Liang S, Yang J-W, Lu H-W, Chai Y-H, et al. Association between age and clinical characteristics and outcomes of COVID-19. European Respiratory Journal 2020;55:2001112. https://doi.org/10.1183/13993003.01112-2020.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-geriatric-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"EGEM","sideBox":"Learn more about [European Geriatric Medicine](https://www.springer.com/journal/41999)","snPcode":"41999","submissionUrl":"https://www.editorialmanager.com/egem/default2.aspx","title":"European Geriatric Medicine","twitterHandle":"","acdcEnabled":false,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"SARS-CoV-2 vaccination, intra-hospital infections, aged, hospitalization, mortality","lastPublishedDoi":"10.21203/rs.3.rs-3327002/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3327002/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose.\u003c/h2\u003e \u003cp\u003eVaccinations, for example flu vaccine, may be a cause of cross-reactive immunostimulation that prevents a larger spectrum of infections. However, whether SARS-CoV-2 vaccinations may also determine this effect is unclear. This study aims, first, to assess the incidence of infections at hospital admission and during the hospitalization in older inpatients vaccinated and unvaccinated against SARS-CoV-2; second, to compare length of hospital stay and in-hospital mortality between vaccinated and unvaccinated individuals.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e. This retrospective study included 754 older inpatients admitted to the Geriatrics and Orthogeriatrics Units of the University Hospital of Ferrara (Italy) between March 2021 and November 2021. Sociodemographic and health-related data, and the diagnosis of infections at hospital admission and during hospitalization were collected from medical records.\u003c/p\u003e\u003ch2\u003eResults.\u003c/h2\u003e \u003cp\u003eThe sample\u0026rsquo;s mean age was 87.2 years, 59.2% were females, and 75.5% were vaccinated against SARS-CoV-2. Vaccinated individuals had a 33% lower odds of intra-hospital infections (OR\u0026thinsp;=\u0026thinsp;0.67, 95%CI:0.46\u0026ndash;0.98) and 40% lower in-hospital death (HR\u0026thinsp;=\u0026thinsp;0.60, 95%CI:0.39\u0026ndash;0.94), also after adjusting for potential confounders, while no significant results emerged about infections at hospital admission. Considering the hospitalization\u0026rsquo;s endpoints, SARS-CoV-2 vaccination was associated with a lower probability of being transferred to long-term care or other hospital departments than returning home (OR\u0026thinsp;=\u0026thinsp;0.63, 95%CI:0.40\u0026ndash;0.99).\u003c/p\u003e\u003ch2\u003eConclusions.\u003c/h2\u003e \u003cp\u003eIn older inpatients, SARS-CoV-2 vaccination may reduce the risk of intra-hospital infectious diseases not caused by SARS-CoV-2 and all-cause in-hospital mortality. The vaccination coverage in the older population could limit not only the onset and severity of COVID-19 but also the occurrence of other infectious diseases.\u003c/p\u003e","manuscriptTitle":"SARS-CoV-2 vaccination and risk of infectious diseases in hospitalized older patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-09-19 16:36:10","doi":"10.21203/rs.3.rs-3327002/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revisions","date":"2023-09-26T14:48:37+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2023-09-21T06:35:05+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-09-14T06:59:58+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"European Geriatric Medicine","date":"2023-09-13T09:27:27+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-09-09T14:39:14+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Geriatric Medicine","date":"2023-09-05T05:17:40+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-geriatric-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"EGEM","sideBox":"Learn more about [European Geriatric Medicine](https://www.springer.com/journal/41999)","snPcode":"41999","submissionUrl":"https://www.editorialmanager.com/egem/default2.aspx","title":"European Geriatric Medicine","twitterHandle":"","acdcEnabled":false,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"8d731587-2e65-469e-88ad-2f81374dce70","owner":[],"postedDate":"September 19th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-04-05T11:36:30+00:00","versionOfRecord":{"articleIdentity":"rs-3327002","link":"https://doi.org/10.1007/s41999-023-00902-x","journal":{"identity":"european-geriatric-medicine","isVorOnly":false,"title":"European Geriatric Medicine"},"publishedOn":"2024-01-05 11:36:30","publishedOnDateReadable":"January 5th, 2024"},"versionCreatedAt":"2023-09-19 16:36:10","video":"","vorDoi":"10.1007/s41999-023-00902-x","vorDoiUrl":"https://doi.org/10.1007/s41999-023-00902-x","workflowStages":[]},"version":"v1","identity":"rs-3327002","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3327002","identity":"rs-3327002","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}