Compartmental Model Suggests Importance of Innate Immune Response to COVID-19 Infection in Rhesus Macaques

Bull Math Biol. 2021 May 26;83(7):79. doi: 10.1007/s11538-021-00909-0.

Abstract

The pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has quickly spread worldwide, creating a serious health crisis. The virus is primarily associated with flu-like symptoms but can also lead to severe pathologies and death. We here present an ordinary differential equation model of the intrahost immune response to SARS-CoV-2 infection, fitted to experimental data gleaned from rhesus macaques. The model is calibrated to data from a nonlethal infection, but the model can replicate behavior from various lethal scenarios as well. We evaluate the sensitivity of the model to biologically relevant parameters governing the strength and efficacy of the immune response. We also simulate the effect of both anti-inflammatory and antiviral drugs on the host immune response and demonstrate the ability of the model to lessen the severity of a formerly lethal infection with the addition of the appropriately calibrated drug. Our model emphasizes the importance of tight control of the innate immune response for host survival and viral clearance.

Keywords: Innate immunity; Mathematical modeling of COVID-19.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptive Immunity
  • Aging / immunology
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / pharmacology
  • COVID-19 / epidemiology
  • COVID-19 / immunology*
  • COVID-19 Drug Treatment
  • Computer Simulation
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Host Microbial Interactions / drug effects
  • Host Microbial Interactions / immunology
  • Humans
  • Immunity, Innate*
  • Macaca mulatta / immunology*
  • Mathematical Concepts
  • Models, Immunological*
  • Pandemics
  • Respiratory System / immunology
  • Respiratory System / virology
  • SARS-CoV-2* / immunology
  • Viral Load / immunology

Substances

  • Anti-Inflammatory Agents
  • Antiviral Agents