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
. 2024 Jan 5:10:1280951.
doi: 10.3389/fmed.2023.1280951. eCollection 2023.

Exploring post-SEPSIS and post-COVID-19 syndromes: crossovers from pathophysiology to therapeutic approach

Darcy Holmes  1 , Marta Colaneri  2 , Emanuele Palomba  2 , Andrea Gori  2   3
Affiliations
Review

Exploring post-SEPSIS and post-COVID-19 syndromes: crossovers from pathophysiology to therapeutic approach

Darcy Holmes et al. Front Med (Lausanne). .

Abstract

Sepsis, driven by several infections, including COVID-19, can lead to post-sepsis syndrome (PSS) and post-acute sequelae of COVID-19 (PASC). Both these conditions share clinical and pathophysiological similarities, as survivors face persistent multi-organ dysfunctions, including respiratory, cardiovascular, renal, and neurological issues. Moreover, dysregulated immune responses, immunosuppression, and hyperinflammation contribute to these conditions. The lack of clear definitions and diagnostic criteria hampers comprehensive treatment strategies, and a unified therapeutic approach is significantly needed. One potential target might be the renin-angiotensin system (RAS), which plays a significant role in immune modulation. In fact, RAS imbalance can exacerbate these responses. Potential interventions involving RAS include ACE inhibitors, ACE receptor blockers, and recombinant human ACE2 (rhACE2). To address the complexities of PSS and PASC, a multifaceted approach is required, considering shared immunological mechanisms and the role of RAS. Standardization, research funding, and clinical trials are essential for advancing treatment strategies for these conditions.

Keywords: angiotensin-converting enzyme 2 (ACE2); immune dysfunction; post-acute sequelae of COVID-19 (PASC); post-sepsis syndrome (PSS); renin-angiotensin system (RAS).

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 a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
PSS: post sepsis syndrome; PASC: post-acute sequelae of COVID-19. Depiction of the pathophysiological mechanisms and cytokines cascades involved in PSS and PASC, and their interaction with ACE2.
See this image and copyright information in PMC

References

    1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. . The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. (2016) 315:801–10. doi: 10.1001/jama.2016.0287, PMID: - DOI - PMC - PubMed
    1. Lin GL, McGinley JP, Drysdale SB, Pollard AJ. Epidemiology and immune pathogenesis of viral sepsis. Front Immunol. (2018) 9:2147. doi: 10.3389/fimmu.2018.02147 - DOI - PMC - PubMed
    1. Nakanishi N, Liu K, Kawakami D, Kawai Y, Morisawa T, Nishida T, et al. . Post-intensive care syndrome and its new challenges in coronavirus disease 2019 (COVID-19) pandemic: a review of recent advances and perspectives. J Clin Med. (2021) 10:3870. doi: 10.3390/jcm10173870, PMID: - DOI - PMC - PubMed
    1. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. . Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. (2020) 395:507–13. doi: 10.1016/S0140-6736(20)30211-7, PMID: - DOI - PMC - PubMed
    1. Verano-Braga T, Martins ALV, Motta-Santos D, Campagnole-Santos MJ, Santos RAS. ACE2 in the renin-angiotensin system. Clin Sci. (2020) 134:3063–78. doi: 10.1042/CS20200478 - DOI - PubMed