Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Viral Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1535938
This article is part of the Research Topic The Influence of SARS-CoV-2 Infection and Long-COVID on The Incidence of Viral Coinfection. View all articles

Programmed cell death markers in COVID-19 survivors with and without sepsis

Provisionally accepted
Chandra Shekar Mallarpu Chandra Shekar Mallarpu 1Srinivasa Ikswaja Chelluri Srinivasa Ikswaja Chelluri 2Tapaswi Krishna Katragadda Tapaswi Krishna Katragadda 3Maneendra Singarapu Maneendra Singarapu 3Lakshmi Kiran Chelluri Lakshmi Kiran Chelluri 4*Charitha Madiraju Charitha Madiraju 5*
  • 1 Global Medical Education and Research Foundation, Lakdi-ka-Pul, Hyderabad,, India
  • 2 Bharati Vidyapeeth Medical College, Deemed to be University,, Pune, Maharashtra, India
  • 3 Gleneagles Hospitals,, Lakdi-ka-Pul, Hyderabad,, India
  • 4 Global Medical Education and Research Foundation, Lakdi-ka-Pul, Hyderabad,, United States
  • 5 Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, NJ, United States

The final, formatted version of the article will be published soon.

    Introduction: Sepsis remains a leading cause of mortality, especially in COVID-19 patients, due to delayed diagnosis and limited therapeutic options. While the mechanisms of programmed cell death (PCD) in COVID-19 and sepsis are complex, understanding the molecular markers involved in these processes may aid in assessing disease severity. This study aimed to investigate the roles of PCD markers, inflammatory cytokines, and MHC molecules in distinguishing disease severity in COVID-19 patients with and without sepsis.The study involved adult patients (≥18 years) who survived COVID-19, grouped into four cohorts: COVID-19 with sepsis (C19wSepsis), COVID-19 without sepsis (C19NoSepsis), sepsis alone, and healthy controls. Serum and peripheral blood mononuclear cells (PBMCs) from each cohort were analyzed using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. PCD markers (caspase-3, caspase-1, MLKL, LC3B, p62/SQSTM1), inflammatory cytokines (IL-1-beta, IFN-gamma), and MHC molecules (MHC I-A, MHC II-DRB1) were assessed. Statistical analyses were performed to evaluate differences in marker levels between and within cohorts.The analysis identified two distinct molecular signatures associated with disease severity. The first signature, characterized by elevated levels of secreted markers of PCD, IL-1-beta, IFNgamma, MHC I-A and MHC II-DRB1, was common to the C19wSepsis and C19NoSepsis cohorts. The second signature, which was more prominent in the cellular markers of PCD (caspase-1, caspase-3, MLKL, p62/SQSTM1), was uniquely associated with the C19wSepsis cohort.These findings provide insight into the molecular signatures distinguishing immune responses in COVID-19-related sepsis and may serve as valuable biomarkers for assessing disease severity, while guiding therapeutic interventions in critical care settings.

    Keywords: Sepsis, COVID-19, programmed cell death, caspase-3, caspase-1, MLKL, p62/SQSTM1, Cytokines

    Received: 28 Nov 2024; Accepted: 15 Jan 2025.

    Copyright: © 2025 Mallarpu, Chelluri, Katragadda, Singarapu, Chelluri and Madiraju. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Lakshmi Kiran Chelluri, Global Medical Education and Research Foundation, Lakdi-ka-Pul, Hyderabad,, United States
    Charitha Madiraju, Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, NJ, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.