![]() ![]() It should be noted that day 4 after infection likely does not represent the peak of viremia in the BAL, and previous studies indicate that peak viral loads are reached at day 1 after infection in the BAL ( 42). Viral RNA was also found in the BAL of all animals at day 4 after infection and was mostly cleared by days 7 to 10. Total genomic Nucleocapsid (gN) and subgenomic Nucleocapsid (sgN) RNA levels from nasal and throat swabs peaked 1 to 2 days after infection and decreased to undetectable levels by days 7 to 10 ( Fig. 1, A and C) in the lungs of five of six animals at day 3 after infection, which resolved by day 9. ![]() 18FDG-PET/CT imaging showed evidence of heterogeneous inflammatory foci with increased 18FDG uptake ( Fig. Six male rhesus macaques were infected with 1 × 10 6 tissue culture infectious dose (TCID) 50 intranasally (i.n.) and 1 × 10 6 TCID 50 intratracheally (i.t.), for a total dose of 2 × 10 6 TCID 50 of SARS-CoV-2/USA-WA1 (table S1). Thus, current NHP models are suitable for the study of protective host immune responses associated with mild SARS-CoV-2 infection, but not the mechanisms of pathogenesis during severe disease. SARS-CoV-2–immune and SARS-CoV-2–vaccinated rhesus macaques are protected from reinfection primarily by neutralizing antibodies and, to a lesser extent, anamnestic T cell responses ( 53– 64). Rhesus macaques, cynomolgus macaques, and African green monkeys typically develop mild symptoms after SARS-CoV-2 infection ( 42– 52). Several nonhuman primate (NHP) species can be experimentally infected with SARS-CoV-2. On the other hand, species more resistant to SARS-CoV-2 induced disease are useful tools in examining mechanisms of efficient control of viral replication. Syrian hamsters and ferrets are also moderately susceptible and shed infectious virus ( 37– 41). For example, transgenic mouse strains expressing human angiotensin converting enzyme 2 (ACE2) (K18-hACE2), and mice induced to express hACE2 with viral vectors, are highly susceptible to SARS-CoV-2 infection ( 32– 36). Studies in SARS-CoV-2–susceptible species provide insights into COVID-19 disease pathogenesis. Whereas neutralizing antibodies are clearly protective in immune hosts, T cell responses may also contribute to the protection provided by vaccination and natural infection ( 21– 24).Īnimal models can be used to obtain a detailed understanding of the host response in infected tissues. Coordinated activation of CD8 + and CD4 + T cells, T cell activation state, and antigen (Ag) specificity have all been linked to favorable outcomes of SARS-CoV-2 infection ( 15– 20). Increased proinflammatory cytokines ( 1– 3), deficient type I interferon (IFN) responses ( 4– 6), and activation of inflammasomes ( 7), neutrophils ( 8– 10), and monocytes/macrophages ( 3, 10– 14) have all been associated with severe COVID-19. There is a need to parse out the role of individual immune cell types and molecular pathways that contribute to effective control of viral infection in asymptomatic/mild disease and those leading to organ failure during severe coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a spectrum of clinical outcomes, ranging from asymptomatic to fatal. Thus, SARS-CoV-2 replication wanes in the lungs, as well as the nasal and oral mucosa, of rhesus macaques before antigen-specific effector T cells arrive at those sites, suggesting that innate immunity efficiently restricts viral replication during mild COVID-19. SARS-CoV-2–specific T cells were not detectable in the nasal turbinates, salivary glands, and tonsils on day 10 after infection. Virus-specific effector CD8 + and CD4 + T cells became detectable in the BAL and lung tissue on days 7 to 10 after viral RNA, radiologic evidence of lung inflammation, and IFN-activated myeloid cells had substantially declined. 18F-fluorodeoxyglucose ( 18FDG)–avid lung abnormalities and interferon (IFN)–activated monocytes and macrophages in the bronchoalveolar lavage (BAL) were found on days 3 to 4 after infection. Viral RNA levels were highest on days 1 to 2 after infection and fell precipitously thereafter. ![]() Here, we used rhesus macaques to model protective primary immune responses in tissues during mild coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily replicates in mucosal sites, and more information is needed about immune responses in infected tissues. Barber +19 authors +17 authors +12 authors fewer Authors Info & Affiliations ![]() Johnson, Mario Roederer, Alan Sher, Daniela Weiskopf, Alessandro Sette, Emmie de Wit, Heather D. Lora, NIAID/DIR Tuberculosis Imaging Program, Kelsie Brooks, , E. Kauffman, , Shunsuke Sakai, Danielle E. Nelson, Sivaranjani Namasivayam, , Taylor W. ![]()
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