SARS-CoV-2 and Influenza Infection in the Syrian Hamster

PROJECT SUMMARYIn a few months, a potential second wave of CoVID-19 will be superimposed on theinfluenza season, which starts in the fall and typically peaks between December andFebruary in the United States. By then, the majority of Americans are unlikely to beimmune to SARS-CoV-2. An effective SARS-CoV-2 vaccine is likely to take months toyears to achieve widespread protection. In addition, reduced social distancing is likely toelicit regional surges in CoVID-19. Potential synergy between these two respiratorypathogens could result in significant morbidity in the short-term. In the long term, we facethe reality that SARS-CoV-2 may assume endemic status and may interact with otherseasonal respiratory pathogens for the foreseeable future. The overall goal of thisproposal is to determine whether prior influenza infection worsens CoVID-19- likedisease in the SARS-CoV-2 Syrian hamster model. Recent studies indicate that ACE2may be upregulated by influenza infection. The Syrian hamster supports infection withhuman influenza A H1N1 subtypes as well as contemporary H3N2 subtypes that cannotreplicate in mice. Additionally, the Syrian hamster is a faithful spontaneous animal modelof CoVID-19. We will pursue two aims: 1) to characterize interferon-driven immuneresponses and ACE2 expression in hamsters infected intranasally with contemporaryH3N2 and H1N1 influenza strains and 2) to characterize clinical disease course, immuneresponses and translationally relevant biomarker alterations following SARS-CoV-2infection of acutely infected and recovered influenza-infected hamsters. We will use afactorial design to assess the effects of controllable variables (influenza virus infectionalone, combined influenza/ SARS-CoV-2, acute/recovered status and sex) on clinicallyrelevant outcome measures (body weight, duration/severity of clinical illness andpulmonary injury scoring). Cytokine, immune and ACE2 responses will allow us toassess association of these variables with infection status and clinical phenotype. Theseapproaches will provide direct and translationally relevant data regarding impact ofinfluenza on SARS-CoV-2 clinical phenotype, as well as advance understanding ofunderlying immune responses.