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
. 2023 Feb 16;15(2):553.
doi: 10.3390/v15020553.

Hyperinflammatory Response in COVID-19: A Systematic Review

Marcos Jessé Abrahão Silva  1   2 , Layana Rufino Ribeiro  2 , Maria Isabel Montoril Gouveia  2 , Beatriz Dos Reis Marcelino  3 , Carolynne Silva Dos Santos  4 , Karla Valéria Batista Lima  2 , Luana Nepomuceno Gondim Costa Lima  1   2
Affiliations

Hyperinflammatory Response in COVID-19: A Systematic Review

Marcos Jessé Abrahão Silva et al. Viruses. .

Abstract

COVID-19 is a multisystemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The immunopathogenic conditions of the hyperinflammatory response that cause systemic inflammation are extremely linked to its severity. This research sought to review the immunopathological elements that contribute to its progression. This is a systematic review using the PUBMED, LILACS, MEDLINE, and SCIELO databases using articles between May 2020 and July 2022 with the following search terms in conjunction with "AND": "SARS-CoV-2"; "COVID-19"; "ARDS" and "Cytokine Storm". The quality appraisal and risk of bias were assessed by the JBI checklists and the Cochrane Collaboration's RoB 2.0 and ROBINS-I tools, respectively, and the risk of bias for in vitro studies by a pre-defined standard in the literature. The search resulted in 39 articles. The main actors in this response denote SARS-CoV-2 Spike proteins, cellular proteases, leukocytes, cytokines, and proteolytic cascades. The "cytokine storm" itself brings several complications to the host through cytokines such as IL-6 and chemokines (such as CCL2), which influence tissue inflammation through apoptosis and pyroptosis. The hyperinflammatory response causes several unfavorable outcomes in patients, and systemic inflammation caused largely by the dysregulation of the immune response should be controlled for their recovery.

Keywords: ARDS; COVID-19; SARS-CoV-2; cytokine storm; immunity.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart of the procedures for the identification, selection, eligibility, and inclusion of studies for analysis. Belém, PA, Brazil (2022).
Figure 2
Figure 2
Risk of bias in randomized controlled studies. Overall results (A). Categories are presented as percentages (B).
Figure 3
Figure 3
Overall risk of bias in non-randomized studies. Categories are presented as percentages.
Figure 4
Figure 4
Hyperinflammatory response in patients with COVID-19. It describes the stages of immune processes in the human body from viral entry into the alveolar epithelial cell, the processes of adhesion and recognition by APCs, the activation of cell signaling pathways, secretion of inflammatory mediators by immune cells responsible for the generation of cytokine storms, the recruitment of co-stimulatory molecules of this inflammation, activation of proteases, inflammasomes, and coagulation factors, as well as the elevation of the patient’s clinical parameters that reflect pathological complications, which can be related to either local or systemic damage and lead to death. This didactic illustrative scheme for the hyperinflammatory response to COVID-19 is based on the results of this review. They are represented in chronological order of events by letters (A–Z).
See this image and copyright information in PMC

References

    1. Sethi B.A., Sethi A., Ali S., Aamir H.S. Impact of Coronavirus disease (COVID-19) pandemic on health professionals. Pak. J. Med. Sci. 2020;36:S6–S11. doi: 10.12669/pjms.36.COVID19-S4.2779. - DOI - PMC - PubMed
    1. Graham R.L., Donaldson E.F., Baric R.S. A decade after SARS: Strategies for controlling emerging coronaviruses. Nat. Rev. Microbiol. 2013;11:836–848. doi: 10.1038/nrmicro3143. - DOI - PMC - PubMed
    1. Yan R., Zhang Y., Li Y., Xia L., Guo Y., Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science. 2020;367:1444–1448. doi: 10.1126/science.abb2762. - DOI - PMC - PubMed
    1. Tabassum A., Iqbal M.S., Sultan S., Alhuthali R.A., Alshubaili D.I., Sayyam R.S., Abyad L.M., Qasem A.H., Arbaeen A.F. Dysregulated Bradykinin: Mystery in the Pathogenesis of COVID-19. Mediat. Inflamm. 2022;2022:e7423537. doi: 10.1155/2022/7423537. - DOI - PMC - PubMed
    1. Hoffmann M., Kleine-Weber H., Schroeder S., Krüger N., Herrler T., Erichsen S., Schiergens T.S., Herrler G., Wu N.H., Nitsche A., et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181:271–280.e8. doi: 10.1016/j.cell.2020.02.052. - DOI - PMC - PubMed

Publication types