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
Review
. 2020 Sep 24:11:558898.
doi: 10.3389/fimmu.2020.558898. eCollection 2020.

COVID-19: In the Eye of the Cytokine Storm

Roberto de la Rica  1 , Marcio Borges  1 , Marta Gonzalez-Freire  2
Affiliations
Review

COVID-19: In the Eye of the Cytokine Storm

Roberto de la Rica et al. Front Immunol. .

Abstract

The dysregulated release of cytokines has been identified as one of the key factors behind poorer outcomes in COVID-19. This "cytokine storm" produces an excessive inflammatory and immune response, especially in the lungs, leading to acute respiratory distress (ARDS), pulmonary edema and multi-organ failure. Alleviating this inflammatory state is crucial to improve prognosis. Pro-inflammatory factors play a central role in COVID-19 severity, especially in patients with comorbidities. In these situations, an overactive, untreated immune response can be deadly, suggesting that mortality in COVID-19 cases is likely due to this virally driven hyperinflammation. Administering immunomodulators has not yielded conclusive improvements in other pathologies characterized by dysregulated inflammation such as sepsis, SARS-CoV-1, and MERS. The success of these drugs at reducing COVID-19-driven inflammation is still anecdotal and comes with serious risks. It is also imperative to screen the elderly for risk factors that predispose them to severe COVID-19. Immunosenescence and comorbidities should be taken into consideration. In this review, we summarize the latest data available about the role of the cytokine storm in COVID-19 disease severity as well as potential therapeutic approaches to ameliorate it. We also examine the role of inflammation in other diseases and conditions often comorbid with COVID-19, such as aging, sepsis, and pulmonary disorders. Finally, we identify gaps in our knowledge and suggest priorities for future research aimed at stratifying patients according to risk as well as personalizing therapies in the context of COVID19-driven hyperinflammation.

Keywords: COVID-19; SARS-CoV-2; aging; immunosenecence; inflammation; sepsis.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Schematic representation of the origin and repercussions of COVID-19 cytokine storm. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into entry epithelial lung cells, binding to angiotensin-converting enzyme 2 receptor (ACE2). Th rapid viral replication in the first stages of the infection results in high proinflammatory state that attenuate and delay the IFN responses, which provokes an accumulation of pathogenic inflammatory macrophages. This, in turn, results in an even higher production of cytokines. This cytokine storm produces an excessive inflammatory and immune response, especially in the lungs, leading to ARDS, pulmonary edema, apoptosis of epithelial cells, vascular damage and multi-organ failure.
Figure 2
Figure 2
Prevention and management COVID-19. (A) There is an urgent need to improve our understanding on the phenotype profiles behind the progress from mild to severe or critical COVID-19. This includes analyzing the different risk factors as well as circulating biomarkers. In turn, this could lead to personalized therapies with reduced side effects. It is also imperative to screen the elderly for risk factors that predispose them to severe COVID-19. Immunosenescence and comorbidities should be taken into consideration (B) An operative classification to screen COVID-19 patients is showed in this panel. Age is a risk factor specially in the severe and critically ill patients.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bektas A, Schurman SH, Gonzalez-Freire M, Dunn CA, Singh AK, Macian F, et al. . Age-associated changes in human CD4(+) T cells point to mitochondrial dysfunction consequent to impaired autophagy. Aging. (2019) 11:9234–63. 10.18632/aging.102438 - DOI - PMC - PubMed
    1. Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. (2018) 14:576–90. 10.1038/s41574-018-0059-4 - DOI - PubMed
    1. Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. (2018) 15:505–22. 10.1038/s41569-018-0064-2 - DOI - PMC - PubMed
    1. Fabbri E, An Y, Zoli M, Simonsick EM, Guralnik JM, Bandinelli S, et al. . Aging and the burden of multimorbidity: associations with inflammatory and anabolic hormonal biomarkers. J Gerontol A Biol Sci Med Sci. (2015) 70:63–70. 10.1093/gerona/glu127 - DOI - PMC - PubMed
    1. Heinrich PC, Castell JV, Andus T. Interleukin-6 and the acute phase response. Biochem J. (1990) 265:621–36. 10.1042/bj2650621 - DOI - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources