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

Research output: Contribution to journalArticlepeer-review

145 Citations (Scopus)
64 Downloads (Pure)


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
Issue number1
Publication statusPublished - 14 Jan 2022


  • 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


Dive into the research topics of 'Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection'. Together they form a unique fingerprint.

Cite this