Pulmonary Inflammatory Response in Lethal COVID-19 Reveals Potential Therapeutic Targets and Drugs in Phases III/IV Clinical Trials

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), etiological agent of the coronavirus disease 2019 (COVID-19), has led to more than 425 million cases and more than 5.9 million deaths globally (WHO, 2021). Since the World Health Organization (WHO) declared the outbreak of COVID-19 as a pandemic, the novel coronavirus has been acquiring several mutations that not only increase its transmissibility rate but also mediates evasion of the host immune response and vaccination surveillance. Positive selection maintains amino-acid variants that increase virus fitness, whereas negative selection generally removes changes that reduce virus fitness (Lo Presti et al., 2020). For instance, some of the most predominant variants are capable of escaping monoclonal antibodies, partially eluding the polyclonal immune responses induced by previous infection or even allowing re-infections. It should be noted that recent improvements in immune escape are linked to mutations that alter the N-terminal domain (NTD) rather than the receptor-binding domain (RBD) of the spike (S) protein, where early and functionally important alterations predominated (Burioni and Topol, 2021).