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

Autor: 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
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: BMC Medicine, Vol 20, Iss 1, Pp 1-23 (2022)
Druh dokumentu: article
ISSN: 1741-7015
DOI: 10.1186/s12916-021-02228-6
Popis: 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.
Databáze: Directory of Open Access Journals
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