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 10 5 or 10 6 TCID 50 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. Author summary SARS-CoV-2 infection presents a wide spectrum of clinical manifestations ranging from asymptomatic to fatal respiratory failure. The determinants for failure in viral control and/or fatal disease progression have not been elucidated fully. Both acquired immune effectors, antibodies and CD8 + T cells, are considered to contribute to viral control. However, it remains unknown whether a deficiency in either of these two arms is directly linked to failure in the control of SARS-CoV-2 replication. In the present study, to know the requirement of CD8 + T cells for viral control after the establishment of infection, we examined the effect of CD8 + cell depletion by monoclonal anti-CD8 antibody administration in the subacute phase on SARS-CoV-2 replication in cynomolgus macaques. Unexpectedly, our analysis revealed no significant impact of CD8 + cell depletion on viral replication, indicating that subacute SARS-CoV-2 replication can be controlled in the absence of CD8 + T cells. CD8 + T-cell responses may contribute to viral control in SARS-CoV-2 infection, but this study suggests that CD8 + T-cell dysfunction may not solely lead to viral control failure or fatal disease progression.
【초록키워드】 SARS-CoV-2, Respiratory failure, antibody, T cells, SARS-COV-2 infection, T-cell Response, Infection, progression, CD8, immune, RNA, clinical manifestations, Nasopharyngeal swab, Kinetics, T cell, Viral, Asymptomatic, nasopharyngeal swabs, viral replication, plasma, macaque, SARS-CoV-2 RNA, Viral RNA, determinants, SARS-CoV-2 replication, Antibody titers, T-cell responses, cynomolgus macaques, Neutralizing antibody titer, monoclonal, macaques, administration, Analysis, Lymph node, lead, clinical manifestation, determinant, Pharyngeal swab, deficiency, Post-infection, retropharyngeal lymph node, failure, necropsy, viral control, convalescent individuals, T-cell dysfunction, TCID, effectors, fatal disease, anti-CD8, pharyngeal mucosa, Arm, FIVE, Cell, examined, intranasally, inoculated, eight, treated, functional, contribute, absence, in viral, comparable, days post-infection, undetectable, 【제목키워드】 Subacute, Cell, absence,