As the world battles the coronavirus disease 2019 (COVID-19) pandemic, wading through the deluge of published COVID-19 research has become a challenge for clinicians. Despite a strong push for the practice of evidence-based medicine over the past decades, a search of COVID-19 literature in recent months paints a different picture. The use of hydroxychloroquine has been the `poster child` for the importance of conducting randomized controlled trials (RCTs), initially showing promise in uncontrolled studies [ 1 ] and even being recommended by governmental leaders, only to later show no benefit in RCTs [ 2 ]. Similarly, many observational studies have reported on risk factors for COVID-19. A recent genome-wide association analysis (GWAS) has implicated that blood group A patients had a higher risk of severe COVID-19 than other blood types [ 3 ], while other studies have found associations between vitamin D levels/latitude, and Bacille de Calmette et Guérin (BCG) vaccine and mortality to COVID-19 [ 4 ]. Based on the results of these studies, shall we tell our blood group A patients to stay home or tell everyone to take vitamin D or get vaccinated with BCG? What are the mechanisms underlying these relationships? Although blood group antigens are known to play a role in infections, the results of the recent GWAS study may have been influenced by the control group comprising blood donors and the lack of adjustment for comorbidities [ 5 ]. Low vitamin D levels have often been associated with a higher risk of infections, but vitamin D supplementation has not been shown to prevent respiratory infections among adults with low vitamin D levels [ 6 ]. The BCG vaccine is thought to provide broad protection against other infections, but a recent study showed no difference in rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among vaccinated or unvaccinated adults [ 7 ]. Overall, evidence supporting a causal relationship between blood types, vitamin D and BCG vaccine and COVID-19 risk are scant.
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