Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection
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(Published version)
Date
2022
Authors
Ryan, F.J.
Hope, C.M.
Masavuli, M.G.
Lynn, M.A.
Mekonnen, Z.A.
Yeow, A.E.L.
Garcia-Valtanen, P.
Al-Delfi, Z.
Gummow, J.
Ferguson, C.
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Journal article
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BMC Medicine, 2022; 20(1):26-1-26-23
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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, and 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. 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.
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© The Author(s). 2022 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.