Elevated IFNA1 and suppressed IL12p40 associated with persistent hyperinflammation in COVID-19 pneumonia

Front Immunol. 2023 Jan 27:14:1101808. doi: 10.3389/fimmu.2023.1101808. eCollection 2023.

Abstract

Introduction: Despite of massive endeavors to characterize inflammation in COVID-19 patients, the core network of inflammatory mediators responsible for severe pneumonia stillremain remains elusive.

Methods: Here, we performed quantitative and kinetic analysis of 191 inflammatory factors in 955 plasma samples from 80 normal controls (sample n = 80) and 347 confirmed COVID-19 pneumonia patients (sample n = 875), including 8 deceased patients.

Results: Differential expression analysis showed that 76% of plasmaproteins (145 factors) were upregulated in severe COVID-19 patients comparedwith moderate patients, confirming overt inflammatory responses in severe COVID-19 pneumonia patients. Global correlation analysis of the plasma factorsrevealed two core inflammatory modules, core I and II, comprising mainly myeloid cell and lymphoid cell compartments, respectively, with enhanced impact in a severity-dependent manner. We observed elevated IFNA1 and suppressed IL12p40, presenting a robust inverse correlation in severe patients, which was strongly associated with persistent hyperinflammation in 8.3% of moderate pneumonia patients and 59.4% of severe patients.

Discussion: Aberrant persistence of pulmonary and systemic inflammation might be associated with long COVID-19 sequelae. Our comprehensive analysis of inflammatory mediators in plasmarevealed the complexity of pneumonic inflammation in COVID-19 patients anddefined critical modules responsible for severe pneumonic progression.

Keywords: COVID-19; IFNa; IL-12p40; SARS-CoV-2; inflammation; pneumonia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19*
  • Humans
  • Inflammation
  • Inflammation Mediators
  • Interferon-alpha
  • Kinetics
  • Post-Acute COVID-19 Syndrome
  • SARS-CoV-2

Substances

  • Inflammation Mediators
  • IFNA1 protein, human
  • Interferon-alpha

Grants and funding

This work was supported by grants from the Korea National Institute of Health Infrastructural Research Program (4800–4861–312–210–13), operation of data center for national biomedical data resources (2021-NI-017-00), the National Research Foundation (NRF) funded by the Ministry of Science and ICT (2021M3A9I2080490), 2022 Joint Research Project of Institutes of Science and Technology (to NHC), and the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (2022R1A6A3A1307317). KJ and UP received a scholarship from the BK21-plus education program provided by the National Research Foundation of Korea.