The longitudinal characterization of immune responses in COVID-19 patients reveals novel prognostic signatures for disease severity, patients' survival and long COVID

Front Immunol. 2024 Jul 29:15:1381091. doi: 10.3389/fimmu.2024.1381091. eCollection 2024.

Abstract

Introduction: SARS-CoV-2 pandemic still poses a significant burden on global health and economy, especially for symptoms persisting beyond the acute disease. COVID-19 manifests with various degrees of severity and the identification of early biomarkers capable of stratifying patient based on risk of progression could allow tailored treatments.

Methods: We longitudinally analyzed 67 patients, classified according to a WHO ordinal scale as having Mild, Moderate, or Severe COVID-19. Peripheral blood samples were prospectively collected at hospital admission and during a 6-month follow-up after discharge. Several subsets and markers of the innate and adaptive immunity were monitored as putative factors associated with COVID-19 symptoms.

Results: More than 50 immunological parameters were associated with disease severity. A decision tree including the main clinical, laboratory, and biological variables at admission identified low NK-cell precursors and CD14+CD91+ monocytes, and high CD8+ Effector Memory T cell frequencies as the most robust immunological correlates of COVID-19 severity and reduced survival. Moreover, low regulatory B-cell frequency at one month was associated with the susceptibility to develop long COVID at six months, likely due to their immunomodulatory ability.

Discussion: These results highlight the profound perturbation of the immune response during COVID-19. The evaluation of specific innate and adaptive immune-cell subsets allows to distinguish between different acute and persistent COVID-19 symptoms.

Keywords: COVID-19 patients’ survival; COVID-19 severity; SARS-CoV-2 adaptive immunity; SARS-CoV-2 innate immunity; long COVID.

MeSH terms

  • Adaptive Immunity
  • Adult
  • Aged
  • Biomarkers / blood
  • CD8-Positive T-Lymphocytes / immunology
  • COVID-19* / immunology
  • COVID-19* / mortality
  • Female
  • Humans
  • Immunity, Innate
  • Killer Cells, Natural / immunology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Prognosis
  • SARS-CoV-2* / immunology
  • Severity of Illness Index*

Substances

  • Biomarkers

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: University and Research (PRIN 2017WC8499), EHA, Cellnex (ACT4Covid) to CB; the Italian Ministry of Health (RF-COVID-19) to CB and FCi.