sMAdCAM:IL-6 (sMIL Index): A novel signature associated with COVID-19 disease progression and development of anti-SARS-CoV-2 antibodies

ABSTRACT

Recent studies positing the gut as a sanctuary site for viral persistence in SARS-CoV-2 infection highlight the importance of assimilating profiles of systemic as well as gut inflammatory mediators to understand the pathology of COVID-19. Also, the role of these markers in governing virus specific immunity following infection remains largely unexplored. A cohort (n=84) of SARS-C0V-2 infected individuals included a group of in-patients (n=60) at various stages of disease progression together with convalescent individuals (n=24) recruited between April and June 2020 from Mumbai, India. Follow-up of 35 in-patients at day 7 post diagnosis was carried out. Th1/Th2/Th17 cytokines along with soluble MAdCAM (sMAdCAM) levels in plasma were measured. Also, anti-viral humoral response as measured by rapid antibody test (IgG, IgM), Chemiluminescent Immunoassay (IgG) and antibodies binding to SARS-CoV-2 proteins were measured by Surface Plasmon Resonance (SPR) from plasma.IL-6 and sMAdCAM levels among in-patients inversely correlated with one another. When expressed as a novel integrated marker -sMIL index (sMAdCAM/IL-6 ratio), these levels were incrementally and significantly higher in various disease states with convalescents exhibiting the highest values. Importantly, sMAdCAM levels as well as sMIL index (fold change) correlated with peak association rates of receptor binding domain and fold change in binding to spike respectively as measured by SPR. Our results highlight key systemic and gutassociated parameters that need to be monitored and investigated further to optimally guide therapeutic and prophylactic interventions for COVID-19.