Understanding the outcomes of COVID-19 - does the current model of an acute respiratory infection really fit?

J Gen Virol. 2021 Mar;102(3):001545. doi: 10.1099/jgv.0.001545. Epub 2020 Dec 15.

Abstract

Although coronavirus disease 2019 (COVID-19) is regarded as an acute, resolving infection followed by the development of protective immunity, recent systematic literature review documents evidence for often highly prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory and faecal samples, periodic recurrence of PCR positivity in a substantial proportion of individuals and increasingly documented instances of reinfection associated with a lack of protective immunity. This pattern of infection is quite distinct from the acute/resolving nature of other human pathogenic respiratory viruses, such as influenza A virus and respiratory syncytial virus. Prolonged shedding of SARS-CoV-2 furthermore occurs irrespective of disease severity or development of virus-neutralizing antibodies. SARS-CoV-2 possesses an intensely structured RNA genome, an attribute shared with other human and veterinary coronaviruses and with other mammalian RNA viruses such as hepatitis C virus. These are capable of long-term persistence, possibly through poorly understood RNA structure-mediated effects on innate and adaptive host immune responses. The assumption that resolution of COVID-19 and the appearance of anti-SARS-CoV-2 IgG antibodies represents virus clearance and protection from reinfection, implicit for example in the susceptible-infected-recovered (SIR) model used for epidemic prediction, should be rigorously re-evaluated.

Keywords: COVID-19; SARS-CoV-2; coronavirus; persistence; respiratory syncytial virus influenza A virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral / immunology*
  • COVID-19 / immunology*
  • Hepatitis C / immunology
  • Humans
  • Immunity, Humoral
  • Immunoglobulin G / immunology
  • Influenza, Human / immunology
  • Models, Biological
  • Reinfection
  • Respiratory Tract Infections / immunology*
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / isolation & purification

Substances

  • Antibodies, Viral
  • Immunoglobulin G