Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques
Takushi Nomura, Hiroyuki Yamamoto, Masako Nishizawa, Trang Thi Thu Hau, Shigeyoshi Harada, Hiroshi Ishii, Sayuri Seki, Midori Nakamura‐Hoshi, Midori Okazaki, Sachie Daigen, Ai Kawana‐Tachikawa, Noriyo Nagata, Naoko Iwata‐Yoshikawa, Nozomi Shiwa, Shun Iida, Harutaka Katano, Tadaki Suzuki, Eun‐Sil Park, Ken Maeda, Yuriko Suzaki, Yasushi Ami, Tetsuro Matano
Abstract
SARS-CoV-2 infection presents clinical manifestations ranging from asymptomatic to fatal respiratory failure. Despite the induction of functional SARS-CoV-2-specific CD8+ T-cell responses in convalescent individuals, the role of virus-specific CD8+ T-cell responses in the control of SARS-CoV-2 replication remains unknown. In the present study, we show that subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques. Eight macaques were intranasally inoculated with 105 or 106 TCID50 of SARS-CoV-2, and three of the eight macaques were treated with a monoclonal anti-CD8 antibody on days 5 and 7 post-infection. In these three macaques, CD8+ T cells were undetectable on day 7 and thereafter, while virus-specific CD8+ T-cell responses were induced in the remaining five untreated animals. Viral RNA was detected in nasopharyngeal swabs for 10-17 days post-infection in all macaques, and the kinetics of viral RNA levels in pharyngeal swabs and plasma neutralizing antibody titers were comparable between the anti-CD8 antibody treated and untreated animals. SARS-CoV-2 RNA was detected in the pharyngeal mucosa and/or retropharyngeal lymph node obtained at necropsy on day 21 in two of the untreated group but undetectable in all macaques treated with anti-CD8 antibody. CD8+ T-cell responses may contribute to viral control in SARS-CoV-2 infection, but our results indicate possible containment of subacute viral replication in the absence of CD8+ T cells, implying that CD8+ T-cell dysfunction may not solely lead to viral control failure.