Dynamics of cytokine and antibody responses in community versus hospital SARS-CoV-2 infections

Front Immunol. 2024 Nov 22:15:1468871. doi: 10.3389/fimmu.2024.1468871. eCollection 2024.

Abstract

Introduction: Dysregulated host cytokine responses to SARS-CoV-2 infection are a primary cause of progression to severe disease, whereas early neutralizing antibody responses are considered protective. However, there are gaps in understanding the early temporal dynamics of these immune responses, and the profile of productive immune responses generated by non-hospitalized people with mild infections in the community.

Methods: Here we conducted a prospective cohort study of people with suspected infections/exposures in the US state of North Carolina, before vaccine availability. We recruited participants not only in hospitals/clinics, but also in their homes. With serial sampling, we compared virologic and immunologic factors in 258 community cases versus 114 hospital cases of COVID-19 to define factors associated with severity.

Results: We found that high early neutralizing antibodies were associated with lower nasal viral load, but not protection from hospitalization. Cytokine responses were evaluated in 125 cases, with subsets at first versus second week of illness to assess for time-dependent trajectories. The hospital group demonstrated a higher magnitude of serum IL-6, IL-1R antagonist, IP-10, and MIG; prolonged upregulation of IL-17; and lesser downregulation of GROα, IL-1R antagonist, and MCP1, in comparison to the community group suggesting that these factors may contribute to immunopathology. In the second week of illness, 2-fold increases in IL-6, IL-1R antagonist, and IP-10 were associated with 2.2, 1.8, and 10-fold higher odds of hospitalization respectively, whereas a 2-fold increase in IL-10 was associated with 63% reduction in odds of hospitalization (p<0.05). Moreover, antibody responses at 3-6 months post mild SARS-CoV-2 infections in the community revealed long-lasting antiviral IgM and IgA antibodies as well as a stable set point of neutralizing antibodies that were not waning.

Discussion: Our data provide valuable temporal cytokine benchmarks to track the progression of immunopathology in COVID-19 patients and guide improvements in immunotherapies.

Keywords: SARS-CoV-2; antibodies; community; cytokines; dynamics.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Neutralizing* / blood
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • COVID-19* / immunology
  • Cytokines* / blood
  • Cytokines* / immunology
  • Female
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • North Carolina / epidemiology
  • Prospective Studies
  • SARS-CoV-2* / immunology
  • Viral Load

Substances

  • Cytokines
  • Antibodies, Viral
  • Antibodies, Neutralizing

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. TS was supported by the Duke Global Health Institute Scholars program and the Hanna H. Gray Fellowship from the Howard Hughes Medical Institute. Select laboratory studies were performed in the Regional Biocontainment Laboratory (RBL) at Duke University, which received partial support for construction and renovation from the National Institutes of Health (UC6-AI058607 and G20-AI167200) and facility support from the National Institutes of Health (UC7-AI180254). The MESSI cohort was supported by the U.S. Defense Advanced Projects Agency (DARPA, N66001-09-C-2082 and HR0011-17-2-0069 to CW) and ECHO COVID supplement (DARPA W911NF192011-P00002 to CW and Dr. Xiling Shen), National Institute of Health (NIH) Antibacterial Resistance Leadership Group (ARLG) COVID supplement (3UM1AI104681-08S1 and 3UM1AI066569 to CW), and 2020 COVID-19 Recovery Act from the State of North Carolina Health and Human Services (NC H.H.S. to Dr. Barton Haynes). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.