High interleukin-6 levels induced by COVID-19 pneumonia correlate with increased circulating follicular helper T cell frequency and strong neutralization antibody response in the acute phase of Omicron breakthrough infection

Front Immunol. 2024 Apr 17:15:1377014. doi: 10.3389/fimmu.2024.1377014. eCollection 2024.

Abstract

Background: Acute immune responses to coronavirus disease 2019 (COVID-19) are influenced by variants, vaccination, and clinical severity. Thus, the outcome of these responses may differ between vaccinated and unvaccinated patients and those with and without COVID-19-related pneumonia. In this study, these differences during infection with the Omicron variant were investigated.

Methods: A total of 67 patients (including 47 vaccinated and 20 unvaccinated patients) who were hospitalized within 5 days after COVID-19 symptom onset were enrolled in this prospective observational study. Serum neutralizing activity was evaluated using a pseudotyped virus assay and serum cytokines and chemokines were measured. Circulating follicular helper T cell (cTfh) frequencies were evaluated using flow cytometry.

Results: Twenty-five patients developed COVID-19 pneumonia on hospitalization. Although the neutralizing activities against wild-type and Delta variants were higher in the vaccinated group, those against the Omicron variant as well as the frequency of developing pneumonia were comparable between the vaccinated and unvaccinated groups. IL-6 and CXCL10 levels were higher in patients with pneumonia than in those without it, regardless of their vaccination status. Neutralizing activity against the Omicron variant were higher in vaccinated patients with pneumonia than in those without it. Moreover, a distinctive correlation between neutralizing activity against Omicron, IL-6 levels, and cTfh proportions was observed only in vaccinated patients.

Conclusions: The present study demonstrates the existence of a characteristic relationship between neutralizing activity against Omicron, IL-6 levels, and cTfh proportions in Omicron breakthrough infection.

Keywords: Omicron; circulating follicular helper T cell; interleukin-6; neutralizing antibody; pneumonia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Antibodies, Neutralizing* / blood
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • Breakthrough Infections
  • COVID-19 Vaccines* / immunology
  • COVID-19* / blood
  • COVID-19* / immunology
  • Female
  • Humans
  • Interleukin-6* / blood
  • Interleukin-6* / immunology
  • Male
  • Middle Aged
  • Prospective Studies
  • SARS-CoV-2* / immunology
  • T Follicular Helper Cells* / immunology

Substances

  • Antibodies, Neutralizing
  • Interleukin-6
  • Antibodies, Viral
  • COVID-19 Vaccines
  • IL6 protein, human

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Research Program on Emerging and Re-emerging Infectious Diseases from the AMED (grant number JP20he0622035 to YoM, HT, and YYa, and grant number JP21fk0108588 to YoM and HT), a research funding grant from the president of the University of Toyama (to YoM, NH, and YYa), Toyama Pharmaceutical Valley Development Consortium (to YoM, NH, and YYa), Japan Antibiotics Research Association (to HK), and Japan Society for the Promotion of Science KAKENHI program (grant numbers JP22K20768 and JP23K15364 to HK). The funding bodies played no role in the study design, collection, analysis, or interpretation of data, nor in writing the manuscript.