Mathematical modeling of interaction between innate and adaptive immune responses in COVID‐19 and implications for viral pathogenesis

Du, Sean Quan; Yuan, Weiming

We have applied mathematical modeling to investigate the infections of the ongoing coronavirus disease‐2019 (COVID‐19) pandemic caused by SARS‐CoV‐2 virus. We first validated our model using the well‐studied influenza viruses and then compared the pathogenesis processes between the two viruses. The interaction between host innate and adaptive immune responses was found to be a potential cause for the higher severity and mortality in COVID‐19 patients. Specifically, the timing mismatch between the two immune responses has a major impact on disease progression. The adaptive immune response of the COVID‐19 patients is more likely to come before the peak of viral load, while the opposite is true for influenza patients. This difference in timing causes delayed depletion of vulnerable epithelial cells in the lungs in COVID‐19 patients while enhancing viral clearance in influenza patients. Stronger adaptive immunity in COVID‐19 patients can potentially lead to longer recovery time and more severe secondary complications. Based on our analysis, delaying the onset of adaptive immune responses during the early phase of infections may be a potential treatment option for high‐risk COVID‐19 patients. Suppressing the adaptive immune response temporarily and avoiding its interference with the innate immune response may allow the innate immunity to more efficiently clear the virus.