Pathophysiology of acute respiratory syndrome coronavirus 2 infection: a systematic literature review to inform EULAR points to consider

Najm, A. , Alunno, A., Mariette, X., Terrier, B., De Marco, G., Emmel, J., Mason, L., McGonagle, D. G. and Machado, P. M. (2021) Pathophysiology of acute respiratory syndrome coronavirus 2 infection: a systematic literature review to inform EULAR points to consider. RMD Open, 7, e001549. (doi: 10.1136/rmdopen-2020-001549) (PMID:33574116) (PMCID:PMC7880117)

Abstract

Background: The SARS-CoV-2 pandemic is a global health problem. Beside the specific pathogenic effect of SARS-CoV-2, incompletely understood deleterious and aberrant host immune responses play critical roles in severe disease. Our objective was to summarise the available information on the pathophysiology of COVID-19. Methods: Two reviewers independently identified eligible studies according to the following PICO framework: P (population): patients with SARS-CoV-2 infection; I (intervention): any intervention/no intervention; C (comparator): any comparator; O (outcome) any clinical or serological outcome including but not limited to immune cell phenotype and function and serum cytokine concentration. Results: Of the 55 496 records yielded, 84 articles were eligible for inclusion according to question-specific research criteria. Proinflammatory cytokine expression, including interleukin-6 (IL-6), was increased, especially in severe COVID-19, although not as high as other states with severe systemic inflammation. The myeloid and lymphoid compartments were differentially affected by SARS-CoV-2 infection depending on disease phenotype. Failure to maintain high interferon (IFN) levels was characteristic of severe forms of COVID-19 and could be related to loss-of-function mutations in the IFN pathway and/or the presence of anti-IFN antibodies. Antibody response to SARS-CoV-2 infection showed a high variability across individuals and disease spectrum. Multiparametric algorithms showed variable diagnostic performances in predicting survival, hospitalisation, disease progression or severity, and mortality. Conclusions: SARS-CoV-2 infection affects both humoral and cellular immunity depending on both disease severity and individual parameters. This systematic literature review informed the EULAR ‘points to consider’ on COVID-19 pathophysiology and immunomodulatory therapies.

• Item Type: Articles
• Additional Information: Funding: This work was funded by the European League Against Rheumatism (CLI122). PMM is supported by the National Institute for Health Research (NIHR), University College London Hospitals (UCLH), Biomedical Research Centre (BRC).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Najm, Dr Aurelie
• Authors: Najm, A., Alunno, A., Mariette, X., Terrier, B., De Marco, G., Emmel, J., Mason, L., McGonagle, D. G., and Machado, P. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: RMD Open
• Publisher: BMJ Publishing Group
• ISSN: 2056-5933
• Published Online: 11 February 2021
• Copyright Holders: Copyright © Author(s) (or their employer(s)) 2021
• First Published: First published in RMD Open 7: e001549
• Publisher Policy: Reproduced under a Creative Commons licence