Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Feb;7(1):e001549.
doi: 10.1136/rmdopen-2020-001549.

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

Aurélie Najm #  1 , Alessia Alunno #  2 , Xavier Mariette  3   4 , Benjamin Terrier  5   6 , Gabriele De Marco  7   8 , Jenny Emmel  9 , Laura Mason  9 , Dennis G McGonagle  7   10 , Pedro M Machado  11   12   13
Affiliations

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

Aurélie Najm et al. RMD Open. 2021 Feb.

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.

Keywords: COVID-19; T-lymphocyte subsets; cytokines; genetic; inflammation; polymorphism.

PubMed Disclaimer

Conflict of interest statement

Competing interests: AA, AN, JE, LM and GDM have nothing to declare. XM has received consulting and/or speaker’s fees from BMS, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Novartis, Pfizer, Servier and UCB, all unrelated to this manuscript. BT has received consulting and/or speaker’s fees from Roche, Chugai, Vifor Pharma, GSK, AstraZeneca, Terumo BCT, LFB and Grifols. DGMG has received consulting and/or speaker’s fees from AbbVie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this manuscript. PMM has received consulting and/or speaker’s fees from AbbVie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript.

References

    1. Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature 2020;579:265–9. 10.1038/s41586-020-2008-3 - DOI - PMC - PubMed
    1. Who coronavirus disease (COVID-19) Dashboard. Available: https://covid19.who.int [Accessed 6 Dec 2020].
    1. Wiersinga WJ, Rhodes A, Cheng AC, et al. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19). JAMA 2020;324:782–93. 10.1001/jama.2020.12839 - DOI - PubMed
    1. Carsana L, Sonzogni A, Nasr A, et al. Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study. Lancet Infect Dis 2020;20:1135–40. 10.1016/S1473-3099(20)30434-5 - DOI - PMC - PubMed
    1. Alunno A, Carubbi F, Rodríguez-Carrio J. Storm, Typhoon, cyclone or Hurricane in patients with COVID-19? beware of the same storm that has a different origin. RMD Open 2020;6:e001295 10.1136/rmdopen-2020-001295 - DOI - PMC - PubMed

Publication types