Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis

The COVID-19 outbreak has rapidly expanded to a global pandemic; however, our knowledge is limited with regards to the protective factors against this infection. The aim of this systematic literature review and meta-analysis was to evaluate the impact of vitamin D supplementation on COVID-19 related outcomes. A systematic search of relevant papers published until January 2022 was conducted to identify randomized controlled trials (RCTs) and non-randomized studies of intervention (NRISs). The primary outcomes included the risk of COVID-19 infection (primary prevention studies on uninfected individuals), hospital admission (secondary prevention studies on mild COVID-19 cases), and ICU admission and mortality rate (tertiary prevention studies on hospitalized COVID-19 patients). We identified five studies (one RCT, four NRISs) on primary prevention, with five (two RCTs, three NRISs) on secondary prevention, and 13 (six RCTs, seven NRISs) on tertiary prevention. Pooled analysis showed no significant effect on the risk of COVID-19 infection. No meta-analysis was possible on hospitalization risk due to paucity of data. Vitamin D supplementation was significantly associated with a reduced risk of ICU admission (RR = 0.35, 95% CI: 0.20, 0.62) and mortality (RR = 0.46, 95% CI: 0.30, 0.70). Vitamin D supplementation had no significant impact on the risk of COVID-19 infection, whereas it showed protective effects against mortality and ICU admission in COVID-19 patients.     

Algorithm for Individual Prediction of COVID-19–Related Hospitalization Based on Symptoms: Development and Implementation Study

BackgroundThe COVID-19 pandemic has placed a huge strain on the health care system globally. The metropolitan area of Milan, Italy, was one of the regions most impacted by the COVID-19 pandemic worldwide. Risk prediction models developed by combining administrative databases and basic clinical data are needed to stratify individual patient risk for public health purposes.ObjectiveThis study aims to develop a stratification tool aimed at improving COVID-19 patient management and health care organization.MethodsA predictive algorithm was developed and applied to 36,834 patients with COVID-19 in Italy between March 8 and the October 9, 2020, in order to foresee their risk of hospitalization. Exposures considered were age, sex, comorbidities, and symptoms associated with COVID-19 (eg, vomiting, cough, fever, diarrhea, myalgia, asthenia, headache, anosmia, ageusia, and dyspnea). The outcome was hospitalizations and emergency department admissions for COVID-19. Discrimination and calibration of the model were also assessed.ResultsThe predictive model showed a good fit for predicting COVID-19 hospitalization (C-index 0.79) and a good overall prediction accuracy (Brier score 0.14). The model was well calibrated (intercept –0.0028, slope 0.9970). Based on these results, 118,804 patients diagnosed with COVID-19 from October 25 to December 11, 2020, were stratified into low, medium, and high risk for COVID-19 severity. Among the overall study population, 67,030 (56.42%) were classified as low-risk patients; 43,886 (36.94%), as medium-risk patients; and 7888 (6.64%), as high-risk patients. In all, 89.37% (106,179/118,804) of the overall study population was being assisted at home, 9% (10,695/118,804) was hospitalized, and 1.62% (1930/118,804) died. Among those assisted at home, most people (63,983/106,179, 60.26%) were classified as low risk, whereas only 3.63% (3858/106,179) were classified at high risk. According to ordinal logistic regression, the odds ratio (OR) of being hospitalized or dead was 5.0 (95% CI 4.6-5.4) among high-risk patients and 2.7 (95% CI 2.6-2.9) among medium-risk patients, as compared to low-risk patients.ConclusionsA simple monitoring system, based on primary care data sets linked to COVID-19 testing results, hospital admissions data, and death records may assist in the proper planning and allocation of patients and resources during the ongoing COVID-19 pandemic.     

The Effectiveness of Pfizer-BioNTech and Oxford-AstraZeneca Vaccines to Prevent Severe COVID-19 in Costa Rica: Nationwide,Ecological Study of Hospitalization Prevalence

BackgroundThe Costa Rican COVID-19 vaccination program has used Pfizer-BioNTech and Oxford-AstraZeneca vaccines. Real-world estimates of the effectiveness of these vaccines to prevent hospitalizations range from 90%-98% for two doses and from 70%-91% for a single dose. Almost all of these estimates predate the Delta variant.ObjectiveThe aim of this study is to estimate the dose-dependent effectiveness of COVID-19 vaccines to prevent severe illness in real-world conditions in Costa Rica, after the Delta variant became dominant.MethodsThis observational study is a secondary analysis of hospitalization prevalence. The sample is all 3.67 million adult residents living in Costa Rica by mid-2021. The study is based on public aggregated data of 5978 COVID-19–related hospital records from September 14, 2021, to October 20, 2021, and 6.1 million vaccination doses administered to determine hospitalization prevalence by dose-specific vaccination status. The intervention retrospectively evaluated is vaccination with Pfizer-BioNTech (78%) and Oxford-AstraZeneca (22%). The main outcome studied is being hospitalized.ResultsVaccine effectiveness against hospitalization (VEH) was estimated as 93.4% (95% CI 93.0-93.9) for complete vaccination and 76.7% (95% CI 75.0-78.3) for single-dose vaccination among adults of all ages. VEH was lower and more uncertain among older adults aged ≥58 years: 92% (95% CI 91%-93%) for those who had received full vaccination and 64% (95% CI 58%-69%) for those who had received partial vaccination. Single-dose VEH declined over time during the study period, especially in the older age group. Estimates were sensitive to possible errors in the population count used to determine the residual number of unvaccinated people when vaccine coverage is high.ConclusionsThe Costa Rican COVID-19 vaccination program that administered Pfizer-BioNTech and Oxford-AstraZeneca vaccines seems to be highly effective at preventing COVID-19–related hospitalization after the Delta variant became dominant. Even a single dose seems to provide some degree of protection, which is good news for people whose second dose of the Pfizer-BioNTech vaccine was postponed several weeks to more rapidly increase the number of people vaccinated with a first dose. Timely monitoring of vaccine effectiveness is important to detect eventual failures and motivate the public to get vaccinated by providing information regarding the effectiveness of the vaccines.     

Vitamin D Supplementation and COVID-19 Outcomes: Mounting Evidence and Fewer Doubts

The coronavirus disease 2019 (COVID-19) has already killed more than 6 million people around the world. A growing body of epidemiological evidence suggests that low 25-hydroxy vitamin D (25-OH-vitamin D) plasma levels are associated with an increased risk of developing COVID-19 and —most importantly—with a higher risk of developing more severe COVID-19 and dying. On the other hand, vitamin D supplementation during the early phases of COVID-19 has been related to a decreased length of hospital stay, less frequent need for oxygen, and a reduced mortality rate in inpatients. This seems to be particularly true when high dosages are used. In light of this evidence, further studies are needed to define the best timing for vitamin D supplementation and the most effective dosage schedule.     

Mental Health Conditions and Severe COVID-19 Outcomes after Hospitalization,United States

Among 664,956 hospitalized COVID-19 patients during March 2020–July 2021 in the United States, select mental health conditions (i.e., anxiety, depression, bipolar, schizophrenia) were associated with increased risk for same-hospital readmission and longer length of stay. Anxiety was also associated with increased risk for intensive care unit admission, invasive mechanical ventilation, and death.     

Estimating and Characterizing COVID-19 Deaths,Puerto Rico,March–July 2020

ObjectivesUsing the Council of State and Territorial Epidemiologists (CSTE) classification guidelines, we characterized coronavirus disease 2019 (COVID-19)–associated confirmed and probable deaths in Puerto Rico during March–July 2020. We also estimated the total number of possible deaths due to COVID-19 in Puerto Rico during the same period.MethodsWe described data on COVID-19–associated mortality, in which the lower bound was the sum of confirmed and probable COVID-19 deaths and the upper bound was excess mortality, estimated as the difference between observed deaths and average expected deaths. We obtained data from the Puerto Rico Department of Health COVID-19 Mortality Surveillance System, the Centers for Disease Control and Prevention’s National Electronic Disease Surveillance System Base System, and the National Center for Health Statistics.ResultsDuring March–July 2020, 225 COVID-19–associated deaths were identified in Puerto Rico (119 confirmed deaths and 106 probable deaths). The median age of decedents was 73 (interquartile range, 59-83); 60 (26.7%) deaths occurred in the Metropolitana region, and 140 (62.2%) deaths occurred among men. Of the 225 decedents, 180 (83.6%) had been hospitalized and 93 (41.3%) had required mechanical ventilation. Influenza and pneumonia (48.0%), sepsis (28.9%), and respiratory failure (27.1%) were the most common conditions contributing to COVID-19 deaths based on death certificates. Based on excess mortality calculations, as many as 638 COVID-19–associated deaths could have occurred during the study period, up to 413 more COVID-19–associated deaths than originally reported.ConclusionsIncluding probable deaths per the CSTE guidelines and monitoring all-cause excess mortality can lead to a better estimation of COVID-19–associated deaths and serve as a model to enhance mortality surveillance in other US jurisdictions.     

Decreased Mortality Over Time During the First Wave in Patients With COVID-19 in Geriatric Care: Data From the Stockholm GeroCovid Study

ObjectiveTo describe temporal changes in treatment, care, and short-term mortality outcomes of geriatric patients during the first wave of the COVID-19 pandemic.DesignObservational study.Setting and ParticipantsAltogether 1785 patients diagnosed with COVID-19 and 6744 hospitalized for non–COVID-19 causes at 7 geriatric clinics in Stockholm from March 6 to July 31, 2020, were included.MethodsAcross admission month, patient vital signs and pharmacological treatment in relationship to risk for in-hospital death were analyzed using the Poisson regression model. Incidence rates (IRs) and incidence rate ratios (IRRs) of death are presented.ResultsIn patients with COVID-19, the IR of mortality were 27%, 17%, 10%, 8%, and 2% from March to July, respectively, after standardization for demographics and vital signs. Compared with patients admitted in March, the risk of in-hospital death decreased by 29% [IRR 0.71, 95% confidence interval (CI) 0.51-0.99] in April, 61% (0.39, 0.26-0.58) in May, 68% (0.32, 0.19-0.55) in June, and 86% (0.14, 0.03-0.58) in July. The proportion of patients admitted for geriatric care with oxygen saturation <90% decreased from 13% to 1%, which partly explains the improvement of COVID-19 patient survival. In non–COVID-19 patients during the pandemic, mortality rates remained relatively stable (IR 1.3%-2.3%). Compared with non–COVID-19 geriatric patients, the IRR of death declined from 11 times higher (IRR 11.7, 95% CI 6.11-22.3) to 1.6 times (2.61, 0.50-13.7) between March and July in patients with COVID-19.Conclusions and ImplicationsMortality risk in geriatric patients from the Stockholm region declined over time throughout the first pandemic wave of COVID-19. The improved survival rate over time was only partly related to improvement in saturation status at the admission of the patients hospitalized later throughout the pandemic. Lower incidence during the later months could have led to less severe hospitalized cases driving down mortality.     

Risk Factors of COVID-19 Critical Outcomes in the Eastern Mediterranean Region: Multicountry Retrospective Study

BackgroundThe establishment of empirical evidence in the Eastern Mediterranean Region necessitates the implementation of wide-scale studies to describe the demographic, clinical features, and severity profile of patients with COVID-19.ObjectiveThis study aims to assess the patterns of COVID-19 severity and mortality in seven countries, and to determine the risk factors of COVID-19 severity and mortality.MethodsThis multicountry study was based on a retrospective review of medical records of hospitalized patients confirmed to have COVID-19. This study includes data from Iraq, Pakistan, Sudan, Somalia, Morocco, Egypt, and Yemen. All demographic and clinical data were extracted from hospital records (paper files) by trained data collectors.ResultsA total of 4141 patients were included in this study from seven countries. Comorbidities were reported by nearly half of the patients, with hypertension (n=1021, 24.7%) and diabetes (n=939, 22.7%) being the most common. Older age, diabetes mellitus, hypertension, and heart diseases were significantly associated with COVID-19 severity and mortality. Ever smoking and renal diseases were significantly associated with severity but not mortality, while male gender, respiratory diseases, and malignancy were significantly associated with mortality but not severity.ConclusionsThe study confirms the role of comorbidities and demographic features on the severity and mortality of COVID-19. Understanding the contributing factors ensures attentive care and informs clinical management of patients with poorer prognoses in the early stages of diseases.     

Multinational Observational Cohort Study of COVID-19–Associated Pulmonary Aspergillosis

We performed an observational study to investigate intensive care unit incidence, risk factors, and outcomes of coronavirus disease–associated pulmonary aspergillosis (CAPA). We found 10%–15% CAPA incidence among 823 patients in 2 cohorts. Several factors were independently associated with CAPA in 1 cohort and mortality rates were 43%–52%.     

Social Determinants in Self-Protective Behavior Related to COVID-19: Association Rule–Mining Study

BackgroundHuman behavior is crucial in health outcomes. Particularly, individual behavior is a determinant of the success of measures to overcome critical conditions, such as a pandemic. In addition to intrinsic public health challenges associated with COVID-19, in many countries, some individuals decided not to get vaccinated, streets were crowded, parties were happening, and businesses struggling to survive were partially open, despite lockdown or stay-at-home instructions. These behaviors contrast with the instructions for potential benefits associated with social distancing, use of masks, and vaccination to manage collective and individual risks.ObjectiveConsidering that human behavior is a result of individuals'' social and economic conditions, we investigated the social and working characteristics associated with reports of appropriate protective behavior in Brazil.MethodsWe analyzed data from a large web survey of individuals reporting their behavior during the pandemic. We selected 3 common self-care measures: use of protective masks, distancing by at least 1 m when out of the house, and handwashing or use of alcohol, combined with assessment of the social context of respondents. We measured the frequency of the use of these self-protective measures. Using a frequent pattern–mining perspective, we generated association rules from a set of answers to questions that co-occur with at least a given frequency, identifying the pattern of characteristics of the groups divided according to protective behavior reports.ResultsThe rationale was to identify a pool of working and social characteristics that might have better adhesion to behaviors and self-care measures, showing these are more socially determined than previously thought. We identified common patterns of socioeconomic and working determinants of compliance with protective self-care measures. Data mining showed that social determinants might be important to shape behavior in different stages of the pandemic.ConclusionsIdentification of context determinants might be helpful to identify unexpected facilitators and constraints to fully follow public policies. The context of diseases contributes to psychological and physical health outcomes, and context understanding might change the approach to a disease. Hidden social determinants might change protective behavior, and social determinants of protective behavior related to COVID-19 are related to work and economic conditions.Trial RegistrationNot applicable.     

Vitamin D Supplementation to Prevent COVID-19 Infections and Deaths—Accumulating Evidence from Epidemiological and Intervention Studies Calls for Immediate Action

The COVID-19 pandemic poses an unprecedented threat to human health, health care systems, public life, and economy around the globe. The repertoire of effective therapies for severe courses of the disease has remained limited. A large proportion of the world population suffers from vitamin D insufficiency or deficiency, with prevalence being particularly high among the COVID-19 high-risk populations. Vitamin D supplementation has been suggested as a potential option to prevent COVID-19 infections, severe courses, and deaths from the disease, but is not widely practiced. This article provides an up-to-date summary of recent epidemiological and intervention studies on a possible role of vitamin D supplementation for preventing severe COVID-19 cases and deaths. Despite limitations and remaining uncertainties, accumulating evidence strongly supports widespread vitamin D supplementation, in particular of high-risk populations, as well as high-dose supplementation of those infected. Given the dynamics of the COVID-19 pandemic, the benefit–risk ratio of such supplementation calls for immediate action even before results of ongoing large-scale randomized trials become available.     

Surveillance of COVID-19–Associated Multisystem Inflammatory Syndrome in Children,South Korea

A concerning development during the coronavirus disease pandemic has been multisystem inflammatory syndrome in children. Reports of this condition in East Asia have been limited. In South Korea, 3 cases were reported to the national surveillance system for multisystem inflammatory syndrome in children. All case-patients were hospitalized and survived with no major disease sequelae.     

Presenting Characteristics,Comorbidities, and Outcomes Among Patients With COVID-19 Hospitalized in Pakistan: Retrospective Observational Study

BackgroundCOVID-19 became a pandemic rapidly after its emergence in December 2019. It belongs to the coronavirus family of viruses, which have struck a few times before in history. Data based on previous research regarding etiology and epidemiology of other viruses from this family helped played a vital role in formulating prevention and precaution strategies during the initial stages of this pandemic. Data related to COVID-19 in Pakistan were not initially documented on a large scale. In addition, due to a weak health care system and low economic conditions, Pakistan’s population, in general, already suffers from many comorbidities, which can severely affect the outcome of patients infected with COVID-19.ObjectiveCOVID-19 infections are coupled with a manifestation of various notable outcomes that can be documented and characterized clinically. The aim of this study was to examine these clinical manifestations, which can serve as indicators for early detection as well as severity prognosis for COVID-19 infections, especially in high-risk groups.MethodsA retrospective observational study involving abstraction of demographic features, presenting symptoms, and adverse clinical outcomes for 1812 patients with COVID-19 was conducted. Patients were admitted to the four major hospitals in the Rawalpindi-Islamabad region of Pakistan, and the study was conducted from February to August 2020. Multivariate regression analysis was carried out to identify significant indicators of COVID-19 severity, intensive care unit (ICU) admission, ventilator aid, and mortality. The study not only relates COVID-19 infection with comorbidities, but also examines other related factors, such as age and gender.ResultsThis study identified fever (1592/1812, 87.9%), cough (1433/1812, 79.1%), and shortness of breath (998/1812, 55.1%) at the time of hospital admission as the most prevalent symptoms for patients with COVID-19. These symptoms were common but not conclusive of the outcome of infection. Out of 1812 patients, 24.4% (n=443) required ICU admission and 21.5% (n=390) required ventilator aid at some point of disease progression during their stay at the hospital; 25.9% (n=469) of the patients died. Further analysis revealed the relationship of the presented symptoms and comorbidities with the progression of disease severity in these patients. Older adult patients with comorbidities, such as hypertension, diabetes, chronic kidney disease, and asthma, were significantly affected in higher proportions, resulting in requirement of ICU admission and ventilator aid in some cases and, in many cases, even mortality.ConclusionsOlder adult patients with comorbidities, such as hypertension, diabetes, asthma, chronic obstructive pulmonary disorder, and chronic kidney disease, are at increased risk of developing severe COVID-19 infections, with an increased likelihood of adverse clinical outcomes.     

Effectiveness of In-Hospital Cholecalciferol Use on Clinical Outcomes in Comorbid COVID-19 Patients: A Hypothesis-Generating Study

Little information is available on the beneficial effects of cholecalciferol treatment in comorbid patients hospitalized for COVID-19. The aim of this study was to retrospectively examine the clinical outcome of patients receiving in-hospital high-dose bolus cholecalciferol. Patients with a positive diagnosis of SARS-CoV-2 and overt COVID-19, hospitalized from 15 March to 20 April 2020, were considered. Based on clinical characteristics, they were supplemented (or not) with 400,000 IU bolus oral cholecalciferol (200,000 IU administered in two consecutive days) and the composite outcome (transfer to intensive care unit; ICU and/or death) was recorded. Ninety-one patients (aged 74 ± 13 years) with COVID-19 were included in this retrospective study. Fifty (54.9%) patients presented with two or more comorbid diseases. Based on the decision of the referring physician, 36 (39.6%) patients were treated with vitamin D. Receiver operating characteristic curve analysis revealed a significant predictive power of the four variables: (a) low (<50 nmol/L) 25(OH) vitamin D levels, (b) current cigarette smoking, (c) elevated D-dimer levels (d) and the presence of comorbid diseases, to explain the decision to administer vitamin D (area under the curve = 0.77, 95% CI: 0.67–0.87, p < 0.0001). Over the follow-up period (14 ± 10 days), 27 (29.7%) patients were transferred to the ICU and 22 (24.2%) died (16 prior to ICU and six in ICU). Overall, 43 (47.3%) patients experienced the combined endpoint of transfer to ICU and/or death. Logistic regression analyses revealed that the comorbidity burden significantly modified the effect of vitamin D treatment on the study outcome, both in crude (p = 0.033) and propensity score-adjusted analyses (p = 0.039), so the positive effect of high-dose cholecalciferol on the combined endpoint was significantly amplified with increasing comorbidity burden. This hypothesis-generating study warrants the formal evaluation (i.e., clinical trial) of the potential benefit that cholecalciferol can offer in these comorbid COVID-19 patients.