1. Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection
- Author
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Ryan, Feargal J, Hope, Christopher M, Masavuli, Makutiro G, Lynn, Miriam A, Mekonnen, Zelalem A, Yeow, Arthur Eng Lip, Garcia-Valtanen, Pablo, Al-Delfi, Zahraa, Gummow, Jason, Ferguson, Catherine, O’Connor, Stephanie, Reddi, Benjamin AJ, Hissaria, Pravin, Shaw, David, Kok-Lim, Chuan, Gleadle, Jonathan M, Beard, Michael R, Barry, Simon C, Grubor-Bauk, Branka, and Lynn, David J
- Subjects
Emerging Infectious Diseases ,Vaccine Related ,Pneumonia & Influenza ,Lung ,Pneumonia ,Prevention ,Infectious Diseases ,Genetics ,Biodefense ,2.1 Biological and endogenous factors ,Aetiology ,Infection ,Good Health and Well Being ,Antibodies ,Viral ,COVID-19 ,Humans ,Immune System ,SARS-CoV-2 ,Post-Acute COVID-19 Syndrome ,Immunity ,RNA-Seq ,T cell ,Antibody responses ,Convalescent patients ,Immunophenotyping ,Long COVID ,Post-acute sequelae of COVID-19 ,Post COVID-19 condition ,Medical and Health Sciences ,General & Internal Medicine - Abstract
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.
- Published
- 2022