Dendritic cells in COVID-19 immunopathogenesis: insights for a possible role in determining disease outcome.

Abstract

SARS-CoV-2 is the causative agent of the COVID-19 pandemic. This novel coronavirus emerged in China, quickly spreading to more than 200 countries worldwide. Although most patients are only mildly ill or even asymptomatic, some develop severe pneumonia and become critically ill. One of the biggest unanswered questions is why some develop severe disease, whilst others do not. Insight on the interaction between SARS-CoV-2 and the immune system and the contribution of dysfunctional immune responses to disease progression will be instrumental to the understanding of COVID-19 pathogenesis, risk factors for worst outcome, and rational design of effective therapies and vaccines. In this review we have gathered the knowledge available thus far on the epidemiology of SARS-COV-2 infection, focusing on the susceptibility of older individuals, SARS-CoV-2-host cell interaction during infection and the immune response directed at SARS-CoV-2. Dendritic cells act as crucial messengers linking innate and adaptative immunity against viral infections. Thus, this review also brings a focused discussion on the role of dendritic cells and their immune functions during SARS-CoV-2 infection and how immune evasion strategies of SARS-CoV-2 and advancing age mediate dendritic cell dysfunctions that contribute to COVID-19 pathogenesis and increased susceptibility to worst outcomes. This review brings to light the hypothesis that concomitant occurrence of dendritic cell dysfunction/cytopathic effects induced by SARS-CoV-2 and/or aging may influence disease outcome in the elderly. Lastly, a detailed discussion on the effects and mechanisms of action of drugs currently being tested for COVID-19 on the function of dendritic cells is also provided.