Association between low serum vitamin D and increased mortality and severity due to COVID-19: reverse causality?

We are very close to completing two years since the start of the COVID-19 pandemic. Even though vaccines have been developed and applied to more than 4 billion people in the world, SARS-CoV-2 continues to be a challenge for humanity. Therefore, it is important to study modifiable risk factors that may increase the severity of COVID-19, and one of the most discussed has been vitamin D. Currently, there is some evidence of association between low serum 25-hydroxyvitamin D [25(OH)D3] and increased mortality and severity due to SARS-CoV-2 infection. Before the pandemic, experimental evidence in animal and human studies had reported that an acute inflammatory process can cause a secondary decrease in 25(OH)D3. COVID-19 can be associated with a severe inflammatory process with an elevation of inflammatory markers; in this light, the reported association between low 25(OH)D3 and COVID-19 severity and/or mortality may be an epiphenomenon of the inflammatory process induced by SARS-CoV-2 and be an example of reverse causality.