Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection

Feargal J. Ryan, Christopher M. Hope, Makutiro G. Masavuli, Miriam A. Lynn, Zelalem A. Mekonnen, Arthur Eng Lip Yeow, Pablo Garcia-Valtanen, Zahraa Al-Delfi, Jason Gummow, Catherine Ferguson, Stephanie O’Connor, Benjamin A.J. Reddi, Pravin Hissaria, David Shaw, Chuan Kok-Lim, Jonathan M. Gleadle, Michael R. Beard, Simon C. Barry, Branka Grubor-Bauk, David J. Lynn

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Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious respiratory virus which is responsible for the coronavirus disease 2019 (COVID-19) pandemic. It is increasingly clear that recovered individuals, even those who had mild COVID-19, can suffer from persistent symptoms for many months after infection, a condition referred to as “long COVID”, post-acute sequelae of COVID-19 (PASC), post-acute COVID-19 syndrome, or post COVID-19 condition. However, despite the plethora of research on COVID-19, relatively little is known about the molecular underpinnings of these long-term effects. Methods: We have undertaken an integrated analysis of immune responses in blood at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 patients recovering from mild, moderate, severe, or critical COVID-19 in comparison to healthy uninfected controls. Twenty-one of these patients were referred to a long COVID clinic and > 50% reported ongoing symptoms more than 6 months post-infection. Results: Anti-Spike and anti-RBD IgG responses were largely stable up to 24 wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune populations (T helper, T follicular helper, and regulatory T cells) in convalescent individuals compared to healthy controls, which were most strongly evident at 12 and 16 wpi. RNA sequencing revealed significant perturbations to gene expression in COVID-19 convalescents until at least 6 months post-infection. We also uncovered significant differences in the transcriptome at 24 wpi of convalescents who were referred to a long COVID clinic compared to those who were not. Conclusions: Variation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some individuals.

Original languageEnglish
Article number26
Number of pages23
JournalBMC Medicine
Volume20
Issue number1
DOIs
Publication statusPublished - 14 Jan 2022

Keywords

  • Antibody responses
  • Convalescent patients
  • COVID-19
  • Immunity
  • Immunophenotyping
  • Infection
  • Long COVID
  • Post COVID-19 condition
  • Post-acute sequelae of COVID-19 (PASC)
  • RNA-Seq
  • SARS-CoV-2
  • T cell

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