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

Cell Rep. 2021 Nov 2;37(5):109942. doi: 10.1016/j.celrep.2021.109942. Epub 2021 Oct 19.

Abstract

Anti-viral monoclonal antibody (mAb) treatments may provide immediate but short-term immunity from coronavirus disease 2019 (COVID-19) in high-risk populations, such as people with diabetes and the elderly; however, data on their efficacy in these populations are limited. We demonstrate that prophylactic mAb treatment blocks viral replication in both the upper and lower respiratory tracts in aged, type 2 diabetic rhesus macaques. mAb infusion dramatically curtails severe acute respiratory syndrome coronavirus 2 (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 3-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.

Keywords: NeuroCOVID, inflammation; SARS-CoV-2; cerebrospinal fluid; effector CD4 T cells; interstitial pneumonia; lymph node; neuroinflammation; pathogenesis; rhesus macaques.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / immunology
  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • COVID-19 / cerebrospinal fluid
  • COVID-19 / complications
  • COVID-19 / immunology
  • COVID-19 / prevention & control*
  • Diabetes Complications / immunology
  • Diabetes Complications / virology
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / immunology
  • Female
  • Humans
  • Lymphocyte Activation
  • Macaca mulatta
  • Male
  • Neuritis / immunology
  • Neuritis / prevention & control
  • Pre-Exposure Prophylaxis
  • SARS-CoV-2 / immunology*
  • T-Lymphocytes / immunology
  • Virus Replication / immunology

Substances

  • Antibodies, Monoclonal