Does vitamin D reduce the severity of COVID-19?

Does vitamin D reduce the severity of COVID-19?

A recent review published in the Research position* The preprint server examined published studies for a consistent association between vitamin D levels and the severity of coronavirus disease 2019 (COVID-19).

Study: What is the impact of vitamin D levels on the severity of COVID-19?: A systematic review.  Image Credit: FotoHelin/Shutterstock
To study: What is the impact of vitamin D levels on the severity of COVID-19?: a systematic review. Image Credit: FotoHelin/Shutterstock


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the body through the respiratory system, where the SARS-CoV-2 spike protein binds to angiotensin-converting enzyme 2 (ACE-2) receptors. in the bronchial and nasal passages. epithelium

The entry and rapid replication of the virus alter the epithelial-endothelial barrier, causing a deregulation of the inflammatory response and triggering a cytokine storm. The increased immune response during the cytokine storm can damage tissues and organs and has been linked to long-term fatigue and systemic complications experienced after recovery.

Cytokine storm is an imbalance in the levels of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interferon gamma (INF-γ), and interleukin 6 (IL-6) and 1 beta (IL- 1β). ), and anti-inflammatory factors such as IL-10. Vitamin D regulates the balance between proinflammatory and anti-inflammatory cytokines, with studies showing significant protective effects of vitamin D supplementation against acute respiratory infections. The active form of vitamin D, calcitriol, is also known to activate antiviral peptides. Understanding the association between vitamin D levels and COVID-19 severity could provide methods to proactively protect people against severe outcomes.

About the study

In the current study, the researchers conducted a systematic review of studies that examined the progression of COVID-19 severity based on patients’ vitamin D levels. The review included prospective, cross-sectional, case-controlled, cross-sectional, and observational cohort studies comparing mean serum vitamin D levels with COVID-19 positivity rates, hospitalizations, COVID-19 severity, and survivors and non-survivors. .

The study analyzed the means and standard deviations of vitamin D levels in COVID-19 positive and negative people using a meta-analysis effect size calculator. In addition, p-value and 95% confidence intervals were also calculated. The researchers also used t-tests to determine differences in vitamin D levels between severe and moderate cases of COVID-19 and between COVID-19 survivors and those who succumbed to the disease. In addition, they explored studies that examined vitamin D levels in relation to length of hospitalization.


The results were nearly significant when the mean serum vitamin D levels in COVID-19-positive people were compared to those in COVID-19-negative people. However, when vitamin D levels were compared with progression of COVID-19 severity, the results were not statistically significant. Serum vitamin D levels were also not significantly different when compared between COVID-19 survivors and deaths.

The mean median serum vitamin D values ​​for COVID-19 positive patients was 27.08 nmol/L, compared to 48.67 nmol/L for COVID-19 negative patients. At a p value of 0.059, this difference was considered almost significant.

The review examined a study that evaluated the impact of vitamin D on inflammatory cytokine levels and found significantly higher levels of the pro-inflammatory cytokine IL-6 in people with vitamin D deficiency. Patients whose vitamin D levels were greater than 75 nmol/L showed lower inflammatory markers, such as C-reactive protein. However, the studies did not show a significant direct association between C-reactive protein and vitamin D levels. The study also reported a lower probability of survival from COVID-19 among patients with vitamin D levels below 30 nmol/ L.

A study comparing vitamin D levels between hospitalized patients presenting with severe symptoms of COVID-19 and outpatients with milder symptoms of the disease found that patients with severe symptoms had significantly lower mean vitamin D levels (less than 12 ng/mL). Although the difference was not statistically significant, the review found that people with higher vitamin D levels had fewer average hospital days. However, three contrasting studies also found that patients with higher levels of vitamin D stayed hospitalized longer.

Furthermore, no statistically significant difference was found in the vitamin D levels of people with moderate and severe symptoms of COVID-19. The t-test results also reported no significant difference in vitamin D levels from COVID-19 survivals and mortalities.


To summarize, the review examined several studies that compared mean serum vitamin D levels with factors such as COVID-19 positive cases, severity of infection, disease survivors, deaths, inflammatory cytokine levels, and markers such as C-reactive protein, and the number of days spent in the hospital.

Overall, the results reported no significant associations between vitamin D levels and COVID-19 severity, mortality, or length of hospitalization. Vitamin D deficiency appeared to be associated with the likelihood of being COVID-19 positive, but the near-significant association decreased when examined on a larger scale.

*Important news

Research Square publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice or health-related behavior, or be treated as established information.

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