Monoclonal antibodies protect aged rhesus macaques from SARS-CoV-2 induced immune activation and neuroinflammation

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.

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.