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
. 2022 Oct 18;10(10):2620.
doi: 10.3390/biomedicines10102620.

From Cytokine Storm to Cytokine Breeze: Did Lessons Learned from Immunopathogenesis Improve Immunomodulatory Treatment of Moderate-to-Severe COVID-19?

Goran Rondovic  1   2 , Dragan Djordjevic  1   2 , Ivo Udovicic  1   2 , Ivan Stanojevic  2   3 , Snjezana Zeba  1   2 , Tanja Abazovic  1 , Danilo Vojvodic  2   3 , Dzihan Abazovic  4 , Wasim Khan  5 , Maja Surbatovic  1   2
Affiliations
Review

From Cytokine Storm to Cytokine Breeze: Did Lessons Learned from Immunopathogenesis Improve Immunomodulatory Treatment of Moderate-to-Severe COVID-19?

Goran Rondovic et al. Biomedicines. .

Abstract

Complex immune response to infection has been highlighted, more than ever, during the COVID-19 pandemic. This review explores the immunomodulatory treatment of moderate-to-severe forms of this viral sepsis in the context of specific immunopathogenesis. Our objective is to analyze in detail the existing strategies for the use of immunomodulators in COVID-19. Immunomodulating therapy is very challenging; there are still underpowered or, in other ways, insufficient studies with inconclusive or conflicting results regarding a rationale for adding a second immunomodulatory drug to dexamethasone. Bearing in mind that a "cytokine storm" is not present in the majority of COVID-19 patients, it is to be expected that the path to the adequate choice of a second immunomodulatory drug is paved with uncertainty. Anakinra, a recombinant human IL-1 receptor antagonist, is a good choice in this setting. Yet, the latest update of the COVID-19 Treatment Guidelines Panel (31 May 2022) claims that there is insufficient evidence to recommend either for or against the use of anakinra for the treatment of COVID-19. EMA's human medicines committee recommended extending the indication of anakinra to include treatment of COVID-19 in adult patients only recently (17 December 2021). It is obvious that this is still a work in progress, with few ongoing clinical trials. With over 6 million deaths from COVID-19, this is the right time to speed up this process. Our conclusion is that, during the course of COVID-19, the immune response is changing from the early phase to the late phase in individual patients, so immunomodulating therapy should be guided by individual responses at different time points.

Keywords: COVID-19; anakinra; critical illness; cytokines; immunologic; immunosuppression; immunotherapy; moderate-to-severe pneumonia.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Key elements of host response in COVID-19.
Figure 2
Figure 2
Key elements of the immunomodulatory treatment of COVID-19.
See this image and copyright information in PMC

References

    1. Li H., Liu L., Zhang D., Xu J., Dai H., Tang N., Su X., Cao B. SARS-CoV-2 and viral sepsis: Observations and hypotheses. Lancet. 2020;395:1517–1520. doi: 10.1016/S0140-6736(20)30920-X. - DOI - PMC - PubMed
    1. Vincent J.L. COVID-19: It’s all about sepsis. Future Microbiol. 2021;16:131–133. doi: 10.2217/fmb-2020-0312. - DOI - PMC - PubMed
    1. Schinkel M., Virk H.S., Nanayakkara P.W.B., van der Poll T., Wiersinga W.J. What Sepsis Researchers Can Learn from COVID-19. Am. J. Respir. Crit Care Med. 2021;203:125–127. doi: 10.1164/rccm.202010-4023LE. - DOI - PMC - PubMed
    1. Wiersinga W.J., Rhodes A., Cheng A.C., Peacock S.J., Prescott H.C. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020;324:782–793. doi: 10.1001/jama.2020.12839. - DOI - PubMed
    1. Kox M., Frenzel T., Schouten J., van de Veerdonk F.L., Koenen H.J.P.M., Pickkers P. on behalf of the RCI-COVID-19 study group. COVID-19 patients exhibit less pronounced immune suppression compared with bacterial septic shock patients. Crit. Care. 2020;24:263. doi: 10.1186/s13054-020-02896-5. - DOI - PMC - PubMed