Does vitamin D cause atopy? (preprint)

Due to the Covid-19 pandemic, the intake of vitamin D (VD) has increased. Vitamin D has multiple regulatory effects in the human body, including immunological. Evidence accentuates the generation of a pro-tolerogenic T helper (Th) 2 cell state with VD, suppressing a Th1 inflammatory response. Th2 cell polarization is characteristic of atopy. However, VD promotes a balanced state through the action of regulatory T cells, controlling cytokines, both pro-inflammatory and anti-inflammatory, and by reducing B cell proliferation and differentiation, thus preventing the development of atopy.

Technical note: The use and misuse of threshold diagnostic criteria in paleopathology.

Weighted threshold diagnostic criteria approaches have emerged for diseases that involve skeletal/bony tissue that are readily diagnosed in the field of paleopathology such as Vitamin C deficiency (scurvy), Vitamin D deficiency (rickets) and treponemal disease. These criteria differ from traditional differential diagnosis in that they involve standardized inclusion criteria based on the lesion's specificity to the disease. Here I discuss the limitations and benefits of threshold criteria. I argue that while these criteria will benefit from further revision such as inclusion of lesion severity, and the incorporation of exclusion criteria, threshold diagnostic approaches have considerable value in the future of diagnosis in the field.

The Vitamin D Serum Levels in Pregnant Women Affected by COVID-19: A Systematic Review and Meta-Analysis.

Vitamin D can modulate immune responses, and its deficiency is linked to increased autoimmunity and susceptibility to infection. In the general population, it has been observed that serum vitamin D levels are connected with the risk of COVID-19 and its severity. Our study aims to examine reported findings on the effect of vitamin D serum levels on infection of COVID-19 during pregnancy. PubMed, Web of Science, Embase, and Cochrane Library were searched for relevant studies. Serum vitamin D serum levels in COVID-19-positive and COVID-19-negative pregnant women were 24.61 ± 20.86 ng/mL and 24.12 ± 17.33 ng/mL, respectively. In mild vs. moderate to critical COVID-19 pregnant women, vitamin D serum levels were 16.71 ± 9.04 ng/mL vs. 10.7 ± 9.37 ng/mL and severe vs. non-severe were 13.21 ± 11.47 ng/mL vs. 15.76 ± 10.0 ng/mL. Only one study reported vitamin D serum levels in the placenta of COVID-19-positive pregnant women compared with the control and results varied and amounted to 14.06 ± 0.51 ng/mL vs. 12.45 ± 0.58 ng/mL, respectively. Vitamin D deficiency tends to be common in pregnant women who have COVID-19, and the level of this vitamin has been demonstrated to have a strong correlation with the severity of the illness. As vitamin D serum levels correlate with COVID-19 symptoms and even with its occurrence, appropriate vitamin D supplementation in the prenatal period is suggested.

SARS-CoV-2 in Mexico: An Association Among Geography, Comorbidities, and Vitamin D Deficiency.

Objective: The aim of this study was to determine the association among temperature, relative humidity, latitude, vitamin D content and comorbidities in the spread of SAR-CoV-2 in Mexico in 2 different waves. Methods: The data on SARS-CoV-2 infections and comorbidities were obtained from the Mexican entities with the highest number of positive cases and deaths in the 2 waves that have most damaged the population. Results: Low temperature, high relative humidity, vitamin D deficiency and high percentage of comorbidities were factors that correlated with a high spread of SARS-CoV-2. Interestingly, 73.8% of the population had one of the most common comorbidities that favor the spread of the virus. Conclusion: The high percentage of comorbidities and the deficient concentration of vitamin D were determining factors in the high number of infections and deaths in Mexico. Furthermore, weather conditions could contribute to and alert to the spread of SARS-CoV-2.

COVID-19 and Other Pleiotropic Actions of Vitamin D: Proceedings from the Fifth International Conference "Vitamin D-Minimum, Maximum, Optimum" under the Auspices of the European Vitamin D Association (EVIDAS).

Vitamin D deficiency appeared as a worldwide pandemic markedly earlier than the COVID-19 pandemic was announced in global media [...].

A Retrospective Chart Review Evaluating Changes in 25-Hydroxyvitamin D Levels among Patients Attending the University Healthcare Centre during the COVID-19 Pandemic.

COVID-19-pandemic-related home confinement aids in limiting the spread of the virus but restricts exposure to sunlight, thereby possibly affecting 25(OH)D concentrations. This study aimed to investigate the effect of lockdown measures on 25(OH)D levels in outpatients visiting the healthcare centre over a period of two years. In this retrospective chart review, outpatients who visited a university healthcare centre for a health check-up over a period of two years were included. The patients' 25(OH)D serum levels and status were compared before, during, and after the lockdown periods. A total of 7234 patients were included in this study, with a mean age of 34.66 ± 16.78. The overall prevalence of 25(OH)D insufficiency, deficiency and sufficiency was 33.8%, 30.7% and 35.4%, respectively. The proportion of individuals with 25-(OH) D deficiency prior to lockdown was 29% and this proportion increased in the lockdown and post-lockdown periods to 31.1% and 32%, respectively. Although gender was less likely to have an impact on the 25 (OH) D level during the lockdown period (p = 0.630), we found an association between gender and 25 (OH) D status in the pre-lockdown and post-lockdown periods (p < 0.001 and p < 0.001, respectively). Another association between nationality and 25 (OH)D levels was found before, during and after the lockdown periods (p < 0.001). In addition, the youngest population, aged between 1 and 14, was strongly affected by the home confinement. Age had a positive and significant (p < 0.05) effect on 25 (OH) D status regardless of the different periods. Moreover, in the pre-lockdown period, male outpatients had 1.56 chance of having a sufficient level of 25 (OH)D. However, during the lockdown period, this chance decreased to 0.85 and then increased to 0.99 after the lockdown period. We found no statistically significant difference in the mean serum concentrations or in the prevalence of vitamin D insufficiency when we compared values from before, during and immediately after the COVID-19 lockdown period. However, there was a generally increased prevalence of vitamin D insufficiency in our study population. Another association between gender, nationality and age groups with 25(OH) D was found. Regular exposure to UVR is recommended for maintaining adequate vitamin D levels and to prevent vitamin D deficiency. Further research is needed to determine the best indications for vitamin D supplementation if confinement periods are extended and to consider the potential health consequences of prolonged confinement periods not only on vitamin D status but also on overall public health. The findings of this study may be considered by stakeholders for a targeted supplementation approach for risk groups.

The Effect of Weekly 50,000 IU Vitamin D3 Supplements on the Serum Levels of Selected Cytokines Involved in Cytokine Storm: A Randomized Clinical Trial in Adults with Vitamin D Deficiency.

This research aimed to evaluate the effects of high-dose cholecalciferol (VD3) supplements (50,000 IU/week) on selected circulating cytokines associated with cytokine storms in adults with vitamin D deficiency. This clinical trial, based in Jordan, included 50 participants receiving vitamin D3 supplements (50,000 IU/week) for 8 weeks; the exact number was assigned to the control group. Interleukin-6 (IL-6), interleukin-1ß (IL-1ß), interleukin-10 (IL-10), tumor necrotic factor-α (TNF-α), and leptin were measured in serum at baseline and 10 weeks (wash out: 2 weeks). Our results revealed that vitamin D3 supplementation significantly increased the serum levels of 25OHD, IL-6, IL-10, IL-1ß, and leptin compared with baseline. In contrast, the serum level of TNF-α insignificantly increased in the group receiving vitamin D3 supplementation. Although the observations of this trial may refer to a potential negative effect of VD3 supplementation during cytokine storms, further trials are required to clarify the potential benefits of VD3 supplement during cytokine storms.

Evaluation of 25-hydroxyvitamin D (25(OH)D) levels before and during the COVID-19 pandemic: A cross-sectional study and trend analysis involving 86,772 samples.

BACKGROUND: The aim of this paper was to evaluate the change in 25-hidroxyvitamin D (25(OH)D) levels before and during the COVID-19 pandemic. METHODS: In this retrospective, cross-sectional and methodological study included 86,772 patients (18-75 years) samples who were admitted to the Izmir Dokuz Eylul University Hospital (latitude and longitude (Turkey): 27 E 09; 38 N 25, respectively) for various reasons and whose 25(OH)D levels were measured in the biochemistry unit between 2019-2020 and 2020-2021 (before and during the COVID-19 outbreak). A time series analysis of monthly averages for 25(OH)D was performed. For the purpose of seasonal study, the mean levels of 25(OH)D are grouped by years. Data were modeled in terms of 25(OH)D levels using the MATLAB Curve Fitting Toolbox. RESULTS: There was no significant difference between the sexes according to 25(OH)D levels (p>0.05). 25(OH)D levels were significantly higher in the summer months and lower in the winter months (p<0.001). When comparing the spring months, 25(OH)D levels in 2020 (18 ± 10) were found to be significantly lower than in 2019 (22 ± 12) (p<0.001); on the contrary, when examined based on the summer, autumn, and winter months, it was determined that 25(OH)D levels increased in 2020 (summer: 25 ± 13, autumn: 25 ± 14, and winter: 19 ± 10) compared to 2019 (summer: 23 ± 11, autumn: 22 ± 10, and winter: 19 ± 11) (p<0.001). In the estimates curve obtained with an error margin of 11% in the time series analysis, it was estimated that the 25(OH)D averages after the pandemic would be similar to those before the pandemic. CONCLUSIONS: Restrictions, partial or complete closures, and curfews can significantly affect individuals' 25(OH)D levels during the COVID-19 outbreak. There is a need for multicenter studies with larger populations covering different regions to strengthen and support our results.

Vitamin D Levels in the Pre- and Post-COVID-19 Pandemic Periods and Related Confinement at Pediatric Age.

Coronavirus disease 2019 (COVID-19) restrictions have been correlated with vitamin D deficiency in children, but some uncertainties remain. We retrospectively studied vitamin 25-(OH) D blood levels in 2182 Italian children/adolescents hospitalized for various chronic diseases in the year before (n = 1052) and after (n = 1130) the nationwide lockdown. The type of underlying disease, gender, and mean age (91 ± 55 and 91 ± 61 months, respectively) of patients included in the two periods were comparable. Although mean levels were the same (p = 0.24), deficiency status affected a significantly higher number of subjects during the lockdown period than in the pre-COVID period (p = 0.03), particularly in summer (p = 0.02), and there was also a smoothing of seasonal variations in vitamin D levels. Particularly at risk were males (OR = 1.22; p = 0.03), the 1-5 year age group (OR = 1.57; p < 0.01) and the 6-12 year age group (OR = 1.30; p = 0.04). Infants appeared not to be affected (p = 1.00). In the post-COVID period, the risk of vitamin D deficiency was unchanged in disease-specific groups. However, the proportion of deficiency or severe deficiency differed significantly in the subgroup with endocrinopathy (higher; Chi-square p = 0.04), and with respiratory problems and obesity (lower; Chi-square p = 0.01 and p < 0.01, respectively). Conflicting/opposite literature results advocate for further studies to clearly indicate the need for supplementation during possible future periods of confinement.

Association of Vitamin D levels on the Clinical Outcomes of Patients Hospitalized for COVID-19 in a Tertiary Hospital.

Objectives: This study aimed to compare the severity of COVID-19, inflammatory parameters and clinical outcomes among patients with normal and subnormal levels of Vitamin D. Methodology: This is a retrospective cohort study of 135 patients admitted in a tertiary hospital for COVID-19. Patients were grouped according to their Vitamin D level. Primary outcome measure was the composite of all-cause mortality and morbidity. Other outcome measures determined were the comparison among the groups on the severity of COVID-19 infection, changes in inflammatory parameters, length of hospital stay and duration of respiratory support. Results: There was a significant trend of higher ICU admission (p=0.024), mortality (p=0.006) and poor clinical outcome (p=0.009) among the Vitamin D deficient group. No significant difference was found for most of the inflammatory parameters, duration of hospital stay and respiratory support. Overall, patients with deficient, but not insufficient Vitamin D level had 6 times higher odds of composite poor outcome than those with normal Vitamin D (crude OR=5.18, p=0.003; adjusted OR=6.3, p=0.043). Conclusion: The inverse relationship between Vitamin D level and poor composite outcome observed in our study suggests that low Vitamin D may be a risk factor for poor prognosis among patients admitted for COVID-19.

Reasons to avoid vitamin D deficiency during COVID-19 pandemic.

The effects of vitamin D on the musculoskeletal system are well established. Its deficiency causes osteomalacia, secondary hyperparathyroidism, and an increased risk for fractures and falls. However, clinical and experimental evidence points to extra-skeletal actions of vitamin D, including on immune and respiratory systems. Thus, during this COVID-19 pandemic, a possible deleterious role of vitamin D deficiency has been questioned. This paper aims to present a brief review of the literature and discuss, based on evidence, the role of vitamin D in the lung function and in the prevention of respiratory infections. Relevant articles were searched in the databases MEDLINE/PubMed and SciELO/LILACS. The mechanisms of vitamin D action in the immune system response will be discussed. Clinical data from systematic reviews and meta-analyses show benefits in the prevention of respiratory infections and improvement of pulmonary function when vitamin D-deficient patients are supplemented. At the time of writing this paper, no published data on vitamin D supplementation for patients with COVID-19 have been found. Vitamin D supplementation is recommended during this period of social isolation to avoid any deficiency, especially in the context of bone outcomes, aiming to achieve normal values of 25(OH)D. The prevention of respiratory infections and improvement of pulmonary function are additional benefits observed when vitamin D deficiency is treated. Thus far, any protective effect of vitamin D specifically against severe COVID-19 remains unclear. We also emphasize avoiding bolus or extremely high doses of vitamin D, which can increase the risk of intoxication without evidence of benefits.

Vitamin D as a prognostic biomarker in COVID-19: single-center study and meta-analyses.

Vitamin D was investigated as a prognostic biomarker in COVID-19, in relation to both disease susceptibility and outcomes in infected individuals. Patients admitted to the hospital with a confirmed COVID-19 diagnosis were included if they had a vitamin D measurement prior to hospitalization. Using age- and sex-matched controls, vitamin D levels were investigated for an association with COVID-19 related hospitalizations. Further, vitamin D levels were investigated for an association with 30-day mortality in hospitalized COVID-19 patients. Additionally, three meta-analyses were conducted, investigating the association of vitamin D with the following outcomes: Having a positive SARS-CoV-2 test, hospitalization with COVID-19, and mortality in COVID-19 patients. A total of 685 hospitalized COVID-19 patients were included in the single-center study. Compared to controls, they had higher vitamin D levels. Unadjusted analysis of these 685 cases found higher vitamin D levels associated with increased 30-day mortality. This association disappeared after adjusting for age. In the fully adjusted model, no association between vitamin D and 30-day mortality was found. The meta-analyses found significant associations between lower vitamin D and having a positive SARS-CoV-2 test, and mortality among hospital-admitted COVID-19 patients. The relationship between lower vitamin D and COVID-19 related hospital admissions trended towards being positive but was not statistically significant. Many factors seem to influence the associations between vitamin D and COVID-19 related outcomes. Consequently, we do not believe that vitamin D in and of itself is likely to be a clinically useful and widely applicable predictor for the susceptibility and severity of COVID-19 infections.

Highlights from the 24th workshop on vitamin D in Austin, September 2022.

The 24th Workshop on Vitamin D was held September 7-9, 2022 in Austin, Texas and covered a wide diversity of research in the vitamin D field from across the globe. Here, we summarize the meeting, individual sessions, awards and presentations given.

Serum 25-Hydroxy Vitamin D Levels in Children with Acute Respiratory Infections Caused by Respiratory Virus or Atypical Pathogen Infection.

We aimed to clarify the involvement of vitamin D status in virus or atypical pathogens infection in children with acute respiratory infections (ARIs). In this retrospective study, 295 patients with ARIs were attacked by a respiratory virus or a single atypical pathogen; 17 patients with ARIs induced by two pathogens, and 636 healthy children were included. Serum 25(OH)D levels of all children were measured. Oropharyngeal samples of the patients for viruses or atypical pathogens were studied by polymerase chain reaction (PCR) or reverse transcription-polymerase chain reaction (RT-PCR). In our studies, 58.98% of the 295 single-infected subjects and 76.47% of the 17 co-infected subjects had 25(OH)D levels below the recommended 50.0 nmol/L; the mean 25(OH)D levels were 48.48 ± 19.91 nmol/L and 44.12 ± 12.78 nmol/L. Low serum 25(OH)D levels were remarkable in patients with one of seven viruses or atypical pathogens infected. These results were significantly different from those in the healthy group. There were no significant differences in 25(OH)D levels between single infection and co-infection groups. There were no differences in severity among means of 25(OH)D levels. Female or >6-year-old children patients with low serum 25(OH)D levels were more vulnerable to pathogenic respiratory pathogens. However, serum 25(OH)D levels may be related to the recovery of ARIs. These findings provide additional evidence for the development of strategies to prevent ARIs in children.

A Scoping Review of Vitamin D for Nonskeletal Health: A Framework for Evidence-based Clinical Practice.

BACKGROUND: Low serum 25-hydroxy-vitamin D [25(OH)D] levels are prevalent worldwide. Although the benefits of vitamin D supplementation have focused on skeletal disorders (eg, rickets, osteomalacia, osteoporosis), emerging evidence for nonskeletal health merits further discussion. PURPOSE: The purpose of this review was to critically examine the vitamin D supplementation literature pertaining to nonskeletal health to help guide clinicians. METHODS: A scoping review that included observational studies and randomized clinical trials (RCTs) was performed. Evidence from meta-analyses and individual RCTs are discussed, and controversies and future directions are considered. FINDINGS: 25(OH)D deficiency is a ubiquitous condition associated with multiple nonskeletal diseases, including cardiometabolic (heart disease, diabetes, and kidney disease), immune (HIV/AIDS and cancer), lung (from traditional chronic disorders to coronavirus disease 2019), and gut diseases. Vitamin D deficiency also affects health across the life span (children, pregnant, and elderly), mental illness, and reproduction in both men and women. In contrast, vitamin D supplementation does not necessarily improve major medical outcomes, even when low 25(OH)D levels are treated. Screening for 25(OH)D status remains an important practice, primarily for high-risk patients (eg, elderly, women with osteoporosis, people with low exposure to sunlight). It is reasonable to supplement with vitamin D to treat 25(OH)D deficiency, such that if beneficial nonskeletal health occurs, this may be considered as a coadjutant instead of the central tenet of the disease. Furthermore, optimizing dosing regimens is an important clinical consideration. IMPLICATIONS: Although 25(OH)D deficiency is prevalent in nonskeletal diseases, there is no uniform evidence that vitamin D supplementation improves major medical outcomes, even when low 25(OH)D levels are corrected. Findings from RCTs warrant caution due to possible selection bias. Overall, vitamin D supplementation must be guided by circulating levels as a reasonable medical practice to correct 25(OH)D deficiency.

Correlation of Plasma 25(OH)D3 and Vitamin D Binding Protein Levels with COVID-19 Severity and Outcome in Hospitalized Patients.

BACKGROUND: The Coronavirus Disease-19 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been declared a worldwide pandemic. The severity of COVID-19 varies greatly across infected individuals. Possible factors may include plasma levels of 25(OH)D and vitamin D binding protein (DBP), as both are involved in the host immune response. Other possible nutrition-related factors include malnutrition and/or obesity which disrupt the optimal host immune response to infections. Current literature shows inconsistent evidence about the association of plasma 25(OH)D3 and DBP on infection severity and clinical outcomes. OBJECTIVES: This study aimed to measure plasma 25(OH)D3 and DBP in hospitalized COVID-19 cases and assess their correlation with infection severity, inflammatory markers, and clinical outcome. METHODS: 167 patients were included in this analytical cross-sectional study, of which 81 were critical and 86 were non-critical hospitalized COVID-19 patients. Plasma levels of 25(OH)D3, DBP, and the inflammatory cytokines, IL-6, IL-8, IL-10, and TNF-α were assessed using the Enzyme-linked Immunosorbent Assay (ELISA). Information regarding biochemical and anthropometrical indices, hospital length of stay (LoS), and illness outcome was obtained from the medical records. RESULTS: Plasma 25(OH)D3 level was found to be significantly lower in critical compared to non-critical patients (Median = 8.38 (IQR = 2.33) vs. 9.83 (IQR = 3.03) nmol/L, respectively; p < 0.001), and it positively correlated with hospital LoS. However, plasma 25(OH)D3 did not correlate with mortality or any of the inflammatory markers. DBP on the other hand correlated positively with mortality (rs = 0.188, p = 0.015) and hospital LoS (rs = 0.233, p = 0.002). DBP was significantly higher in critical than non-critical patients (Median = 1262.18 (IQR = 463.66) vs. 1153.35 (IQR = 418.46) ng/mL, respectively; p < 0.001). Furthermore, IL-6 and IL-8 were significantly higher in critical than non-critical patients. However, no differences were found in IL-10, TNF-α, IL-10/TNF-α, TNF-α/IL-10, IL-6/IL-10, or CRP between groups. CONCLUSION: The current study found that critical COVID-19 patients had lower 25(OH)D3 than non-critical patients, yet, levels were found to be suboptimal in both groups. Further, critical patients had higher DBP levels as compared to non-critical patients. This finding may encourage future research to unravel the effects of this understudied protein that appears to have significant associations with inflammation, even though the precise mechanism is unknown.

Influence of Strict Lockdown on Vitamin D Deficiency in Pregnant Women: A Word of Caution.

The main source of vitamin D results from skin sunlight exposure. Vitamin D deficiency (VDD) is linked to several adverse events during pregnancy. While performing a cross-sectional study with 886 pregnant women in Elda (Spain) from September 2019 to July 2020 to determine the association of VDD with gestational diabetes mellitus in relation to body mass index, a strict lockdown (SL) due to the COVID-19 pandemic was declared from 15 March 2020 to 15 May 2020. To determine if VDD prevalence in the local population of pregnant women was influenced by SL, a retrospective cross-sectional study was conducted to estimate the prevalence odds ratio (POR) for the association of VDD and SL. A crude logistic regression model was calculated, and then further adjusted by the biweekly measured vitamin D-specific UVB dose in our geographical area. The POR during SL was 4.0 (95%CI = 2.7-5.7), with a VDD prevalence of 77.8% in the quarantine period. Our results revealed that VDD prevalence in pregnant women was influenced by SL. This valuable information could guide us in future if public officials order the population to stay indoors for any given reason.

Vitamin D: 100 years of discoveries, yet controversy continues.

Over the past 100 years, many major breakthroughs and discoveries have occurred in relation to vitamin D research. These developments include the cure of rickets in 1919, the discovery of vitamin D compounds, advances in vitamin D molecular biology, and improvements in our understanding of endocrine control of vitamin D metabolism. Furthermore, recommended daily allowances for vitamin D have been established and large clinical trials of vitamin D, aimed at clarifying the effect of Vitamin D in the prevention of multiple diseases, have been completed. However, disappointingly, these clinical trials have not fulfilled the expectations many had 10 years ago. In almost every trial, various doses and routes of administration did not show efficacy of vitamin D in preventing fractures, falls, cancer, cardiovascular diseases, type 2 diabetes, asthma, and respiratory infections. Although concerns about side-effects of long-term high-dose treatments, such as hypercalcaemia and nephrocalcinosis, have been around for four decades, some trials from the past 5 years have had new and unexpected adverse events. These adverse events include increased fractures, falls, and hospitalisations in older people (aged >65 years). Several of these clinical trials were powered appropriately for a primary outcome but did not include dose response studies and were underpowered for secondary analyses. Furthermore, more attention should be paid to the safety of high doses of vitamin D supplementation, particularly in older people. In addition, despite universal recommendations by osteoporosis societies for combining calcium supplements with vitamin D there remains insufficient data about their efficacy and effect on fracture risk in the highest risk groups. More trials are needed for people with severe vitamin D deficiency (ie, serum 25-hydroxyvitamin D <25nmol/L [10ng/mL]). In this Personal View, we summarise and discuss some of the major discoveries and controversies in the field of vitamin D.

Vitamin D and SARS-CoV-2.

The single-stranded RNA virus, SARS-CoV-2, causing the COVID-19 pandemic, has severely impacted daily life globally. It has been suggested to supplement the general population with vitamin D to reduce the impact of COVID-19. Nevertheless, no clear consensus can be found as to whether vitamin D affects COVID-19 disease burden. Some studies found that vitamin D levels and/or vitamin D supplementation alleviated COVID-19 disease severity and mortality. Contrarily, other studies found no such effects of vitamin D. To understand this lack of consensus, it is relevant to investigate molecular studies of the vitamin D receptor (VDR), as such studies might explain apparent controversies. We have investigated recent studies of how transcriptional regulation by the VDR affects the immune response against SARS-CoV-2. One study found that cells from severe COVID-19 patients displayed a dysregulated vitamin D response. Contrarily, another study observed a normal immune response towards SARS-CoV-2 in a patient with a non-functional VDR. These observations indicate that hypovitaminosis D is not a prerequisite for an efficient immune response against SARS-CoV-2 and therefore not a driving factor for developing severe COVID-19. However, should a patient develop severe COVID-19, vitamin D seems to be beneficial potentially by dampening the cytokine storm.