LAUSR

The COVID-19 pandemic has been coupled worldwide with an explosion of information about the virus. In its present form, COVID-19 seems to have two very challenging characteristics [1]: it is highly infectious and, despite having a benign course in the vast majority of patients, it requires hospital admission and even intensive care for a far from negligible proportion of infected. This has generated a lot of publications at a rapid pace, addressing and investigating different aspects of the epidemic [see, e.g., 2– 7] and, sadly, also an increase in misinformation, that is of course not all malevolent, although its impact can be devastating [8, 9]. Across all the huge literature on the possible determinants leading to a reduction of the infection, fatality, and mortality rates, our attention has been attracted by the work of Ilie et al. on the role of vitamin D in the prevention of COVID19 infection and mortality [10]. Vitamin D is known to play an important role in bone metabolism through regulation of calcium and phosphate homeostasis, and may also play an important role in immune system regulation. Vitamin D is produced by the body during exposure to sunlight, but is also found in oily fish, eggs, and fortified food products. In addition to causing rickets, vitamin D deficiency has been linked to respiratory infections [10, 11]. Some studies have suggested that vitamin D supplementation can decrease the frequency and severity of respiratory infections; however, further research is needed before specific recommendations can be made [12–14]. According to these general premises, the work of Ilie et al. may play a fundamental role in limiting the spread of COVID-19 and reducing the number of deaths [15]. The authors clearly state that the crude association observed in the present study may be explained by the role of vitamin D in the prevention of COVID-19 infection or more probably by a potential protection of vitamin D from the more negative consequences of the infection. This is a rather neat and important statement, that may strongly contribute to handle the pandemic outcomes properly. Unfortunately, however, we cast some doubts on the statistical methods employed on which this statement is based. The fundamental statement above is based on a correlation test, though it implicitly implies a cause–effect relationship. However, correlation does not imply causation, that can be investigated, e.g., in a regression setting. We reproduced the analysis published in the work of Ilie et al. [15]. We noticed the following: