Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated coronavirus disease 2019 (COVID-19) pandemic has been the subject of a large number of studies in recent times. Here, starting from the evidence that in Italy, the areas with the lowest number of COVID-19 cases were those with the highest incidence of malaria in the early 1900's, we explore possible inverse relationships between malaria and COVID-19. Indeed, some genetic variants, which have been demonstrated to give an advantage against malaria, can also play a role in the incidence and severity of SARS-CoV-2 infections (e.g., the ACE2 receptor). To verify this scientific hypothesis, we here use public data from whole-genome sequencing (WGS) experiments to extrapolate the genetic information of 46 world populations with matched COVID-19 data. In particular, we focus on 47 genes, including ACE2 and genes which have previously been reported to play a role in malaria. Only common variants (>5%) in at least 30% of the selected populations were considered, and, for this subset, we correlate the intra-population allele frequency with the COVID-19 data (cases/million inhabitants), eventually pinpointing meaningful variants in 6 genes. This study allows us to distinguish between positive and negative correlations, i.e., variants whose frequency significantly increases with increasing or decreasing COVID-19 cases. Finally, we discuss the possible molecular mechanisms associated with these variants and advance potential therapeutic options, which may help fight and/or prevent COVID-19.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated coronavirus disease 2019 (COVID-19) has gripped the world in a pandemic, challenging its healthcare infrastructure, economy, and culture
A possible confounding factor could derive from the fact that the spread of SARS-CoV-2 is slightly greater in the northern Italian regions, while the malaria was endemic especially in the coasts of central and southern Italy
The present study demonstrates that some genetic variants selected to be protective against malaria may play a role in the severity of SARS-CoV-2 infections
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated coronavirus disease 2019 (COVID-19) has gripped the world in a pandemic, challenging its healthcare infrastructure, economy, and culture. COVID-19 immune-response and symptoms, including fever, fatigue, headache, gastrointestinal issues, etc., are very similar to those of malaria and other infections, which are endemic in many sub-Saharan areas. This may lead to a delayed diagnosis and make the access to health facilities. Despite the fear and the alert about sub-Saharan countries, SARS-CoV-2 has not hit malariaendemic regions so strongly as everyone would have expected [2]. These observations prompted us to analyze from the epidemiological and genetic standpoints possible links between malaria and COVID-19
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