• 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, ReddiBenjamin A JBAJIntensive Care Unit, Royal Adelaide Hospital, Central Adelaide Local Health Network and Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia., Pravin Hissaria, David Shaw, Chuan Kok-Lim, Jonathan M Gleadle, Michael R Beard, Simon C Barry, Branka Grubor-Bauk, and David J Lynn.
• Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, 5001, Australia.
• Bmc Med. 2022 Jan 14; 20 (1): 2626.

BackgroundSevere 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.MethodsWe 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.ResultsAnti-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.ConclusionsVariation 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.© 2022. The Author(s).

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