Pathogenesis, Treatment and Prevention of Emerging Infectious Diseases

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

Research in this project is currently focused on six areas. These are: characterization of the survivors of the anthrax attacks of 2001; characterization of emerging respiratory infections including SARS, COVID-19, and influenza; evaluation of experimental vaccines and treatments for Ebola virus; characterizing the long-term sequelae of Ebola virus infection; evaluating experimental therapeutics for COVID-19; characterizing the long-term sequelae of SARS-CoV-2 infection. The anthrax study has enrolled a cohort of volunteers who are currently undergoing an extensive diagnostic evaluation. The COVID-19 therapeutic trial ACTIV-3, followed its placebo-controlled study of bamlanivimab (a monoclonal antibody directed toward the spike protein of SARS CoV-2) with studies of the Brii monoclonal antibody cocktail (amubarvimab-romlusevimab), the Vir antibody sotrovimab, the Astra-Zeneca combination of antibodies (tixagevimab-cilgavimab) and the Molecular Partners/Novartis darpins (ensovibep). While none of these showed benefit for the primary endpoint of time to recovery, the Astra-Zeneca arm showed an overall improvement in survival in a secondary endpoint. Separating patients into groups based upon baseline levels of antibody to SARS-CoV-2 and plasma levels of SARS-CoV-2 nucleocapsid antigen demonstrated a potential benefit for bamlanivimab in the group that was antibody negative and strongly antigen positive. A randomized, placebo-controlled trial of COVID-19 immune immunoglobulin in hospitalized patients failed to show benefit. A longitudinal study of COVID-19 survivors and controls demonstrated that symptoms consistent with post-acute sequelae of SARS-CoV-2 infection (PASC) were reported by 55% of the COVID-19 cohort and 13% of control participants. Increased risk for PASC was noted in women and those with a history of anxiety disorder. Abnormal findings on physical examination and diagnostic testing were uncommon. Exploratory studies found no evidence of persistent viral infection, autoimmunity, or abnormal immune activation in participants with PASC.