Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets

Singh, Dhiraj Kumar; Singh, Bindu; Ganatra, Shashank R.; Gazi, Michal; Cole, Journey; Thippeshappa, Rajesh; Alfson, Kendra J.; Clemmons, Elizabeth; Gonzalez, Olga; Escobedo, Ruby; Lee, Tae-Hyung; Chatterjee, Ayan; Goez-Gazi, Yenny; Sharan, Riti; Gough, Maya; Alvarez, Cynthia; Blakley, Alyssa; Ferdin, Justin; Bartley, Carmen; Staples, Hilary; Parodi, Laura; Callery, Jessica; Mannino, Amanda; Klaffke, Benjamin; Escareno, Priscilla; Platt, Roy N.; Hodara, Vida; Scordo, Julia; Gautam, Shalini; Vilanova, Andreu G.; Olmo-Fontanez, Angelica; Schami, Alyssa; Oyejide, Adelekan; Ajithdoss, Dharani K.; Copin, Richard; Baum, Alina; Kyratsous, Christos; Alvarez, Xavier; Ahmed, Mushtaq; Rosa, Bruce; Goodroe, Anna; Dutton, John; Hall-Ursone, Shannan; Frost, Patrice A.; Voges, Andra K.; Ross, Corinna N.; Sayers, Ken; Chen, Christopher; Hallam, Cory; Khader, Shabaana A.; Mitreva, Makedonka; Anderson, Timothy J. C.; Martinez-Sobrido, Luis; Patterson, Jean L.; Turner, Joanne; Torrelles, Jordi B.; Dick, Edward J.; Brasky, Kathleen; Schlesinger, Larry S.; Giavedoni, Luis D.; Carrion, Ricardo; Kaushal, Deepak

Nonhuman primate (NHP) models will expedite therapeutics and vaccines for COVID-19 into clinical trials. We compared acute SARS-CoV-2 infection in young and old rhesus macaques and baboons and old marmosets. Macaques had clinical signs of viral infection, mild-to-moderate pneumonitis and extra-pulmonary pathologies; both age groups recovered in two weeks. Baboons had prolonged viral RNA shedding and substantially more lung inflammation compared with macaques. Inflammation in bronchoalveolar lavage (BAL) was increased in old versus young baboons. Using techniques like CT imaging, immunophenotyping, alveolar/peripheral cytokine responses and immunohistochemical analyses, we delineated cellular immune responses to SARS-CoV-2 infection in macaque and baboon lungs, including innate and adaptive immune cells and a prominent Type I-interferon response. Macaques developed T cell memory phenotype/responses and bystander cytokine production. Old macaques had lower titres of SARS-CoV-2-specific IgG antibody levels compared with young. Acute respiratory distress in macaques and baboons recapitulates the progression of COVID-19 in humans, making them suitable as models to test vaccines and therapies.