ABSTRACT
Abstract: Background: Epidemiological evidence for decreased prevalence and/or mortality due to SARS-CoV-2 infections in countries endemic for malaria have been reported. However, such associational studies in human population are limited by known and several unknown confounding factors. The current study, the first of its kind, was designed to seek experimental evidence to test the hypothesis if prior exposure to Plasmodial infections cross-protect against SARS-CoV-2 challenge infection in a murine model, K-18 human ACE2 transgenic mice. Methods: Mice that had recovered from Plasmodium chabaudi infection 40 days earlier were challenged with a virulent strain of SARS-CoV-2 and viral load in lungs as well as mortality were scored and compared with K18 hACE2 mice that had not experienced prior malaria. Results: The viral load in lungs 6 days post challenge were comparable in malaria recovered mice and controls suggesting no significant generation of anti-viral immunity. However, mice with prior malaria exposure were significantly protected against SARS-CoV-2 induced mortality. Significant differences were observed in several host immune responses between the two groups when cytokines, chemokines and transcription factors were quantified in lungs. The plasma levels of several cytokines and chemokines were also significantly different between the two groups. Conclusion: The results of the study suggest that prior exposure to malaria protects mice against viral induced mortality in K18 hACE2 transgenic mice challenged with a virulent isolate of SARS- CoV-2 in the absence of demonstrable host immunity inhibiting viral growth in lungs.