Recovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques

Hasenkrug, Kim J.; Feldmann, Friederike; Myers, Lara; Santiago, Mario L.; Guo, Kejun; Barrett, Bradley S.; Mickens, Kaylee L.; Carmody, Aaron; Okumura, Atsushi; Rao, Deepashri; Collins, Madison M.; Messer, Ronald J.; Lovaglio, Jamie; Shaia, Carl; Rosenke, Rebecca; van Doremalen, Neeltje; Clancy, Chad; Saturday, Greg; Hanley, Patrick; Smith, Brian J.; Meade-White, Kimberly; Shupert, W. Lesley; Hawman, David W.; Feldmann, Heinz

Severe coronavirus disease 2019 (COVID-19) has been associated with T cell lymphopenia, but no causal effect of T cell deficiency on disease severity has been established. To investigate the specific role of T cells in recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, we studied rhesus macaques that were depleted of either CD4(+), CD8(+), or both T cell subsets prior to infection. Peak virus loads were similar in all groups, but the resolution of virus in the T cell-depleted animals was slightly delayed compared to that in controls. The T cell-depleted groups developed virus-neutralizing antibody responses and class switched to IgG. When reinfected 6 weeks later, the T cell-depleted animals showed anamnestic immune responses characterized by rapid induction of high-titer virus-neutralizing antibodies, faster control of virus loads, and reduced clinical signs. These results indicate that while T cells play a role in the recovery of rhesus macaques from acute SARS-CoV-2 infections, their depletion does not induce severe disease, and T cells do not account for the natural resistance of rhesus macaques to severe COVID-19. Neither primed CD4(+) nor CD8(+) T cells appeared critical for immunoglobulin class switching, the development of immunological memory, or protection from a second infection.