key: cord-0913708-6eludrj4 authors: Verma, Anil; Hawes, Chase E.; Lakshmanappa, Yashavanth Shaan; Schmidt, Brian A.; Roh, Jamin W.; Dutra, Joseph; Louie, William; Liu, Hongwei; Ma, Zhong-Min; Watanabe, Jennifer K.; Usachenko, Jodie L.; Immareddy, Ramya; Sammak, Rebecca L.; Pollard, Rachel; Reader, J. Rachel; Olstad, Katherine J.; Coffey, Lark L.; Kozlowski, Pamela A.; Hartigan-O’Connor, Dennis J.; Nussenzweig, Michel; Van Rompay, Koen K.A.; Morrison, John H.; Iyer, Smita S. title: Monoclonal antibodies protect aged rhesus macaques from SARS-CoV-2 induced immune activation and neuroinflammation date: 2021-10-19 journal: Cell Rep DOI: 10.1016/j.celrep.2021.109942 sha: a59f7477da82695e25aac8eb6dd3e4a8f35d62e6 doc_id: 913708 cord_uid: 6eludrj4 Anti-viral monoclonal antibody (mAb) treatments may provide immediate but short-term immunity from COVID-19 in high-risk populations such as people with diabetes and the elderly, however, data on their efficacy in these populations is limited. We demonstrate that prophylactic mAb treatment blocks viral replication in both the upper and lower respiratory tract in aged, type-2-diabetic rhesus macaques. mAb infusion dramatically curtails SARS-CoV-2-mediated stimulation of interferon-induced chemokines and T cell activation, significantly reducing development of interstitial pneumonia. Furthermore, mAb infusion significantly dampens the greater than three-fold increase in SARS-CoV-2-induced effector CD4 T cell influx into the cerebrospinal fluid. Our data show that neutralizing mAbs administered preventatively to high-risk populations may mitigate the adverse inflammatory consequences of SARS-CoV-2 exposure. Effective deployment of multiple SARS-CoV-2 vaccines combined with aggressive vaccination campaigns have led to marked reductions in severe disease, hospitalizations, and death interstitial pneumonia, and prevent T cell activation. 170 indicative of disparity in viral replication across the respiratory tract. Indeed, we also observed 171 differential impact of mAb efficacy on viral replication in the airways versus the lung 172 parenchyma, suggesting that tissue-specific factors and/or neutralizing activity may be variably regulated across the airways. Altogether, the data are in line with a recent study demonstrating 174 that neutralizing mAb reduced incidence of COVID-19 in a nursing and assisted living facility of interstitial pneumonia. In affected areas alveolar septae were variably expanded by inflammatory cells often accompanied by perivascular cuffing of small and medium sized blood 184 vessels with mixed inflammation as previously described (Shaan Lakshmanappa et al., 2021) . In 3/4 animals the disease was considered moderate while one animal had mild disease. The 186 animals given the RBD mAb treatment had minimal to no evidence of interstitial pneumonia. The visual difference between the groups was striking and readily apparent without further semi-188 quantitative scoring, indicating that RBD mAb treatment prior to SARS-CoV-2 infection prevents 189 the development of any significant interstitial pneumonia ( Figure 1I ). To identify immune activation in the lower respiratory tract, we analyzed inflammatory We studied tissue-specific indices of T cell activation focusing on the spleen and liver as non- Materials Availability. This study did not generate new unique reagents. Data Availability and Code Availability. The published article includes all data generated 505 during this study. This paper does not report original code. Any additional information required to reanalyze the data reported in this paper is available from 507 the lead contact upon request. 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