TY - JOUR
T1 - Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection
AU - Ryan, Feargal J.
AU - Hope, Christopher M.
AU - Masavuli, Makutiro G.
AU - Lynn, Miriam A.
AU - Mekonnen, Zelalem A.
AU - Yeow, Arthur Eng Lip
AU - Garcia-Valtanen, Pablo
AU - Al-Delfi, Zahraa
AU - Gummow, Jason
AU - Ferguson, Catherine
AU - O’Connor, Stephanie
AU - Reddi, Benjamin A.J.
AU - Hissaria, Pravin
AU - Shaw, David
AU - Kok-Lim, Chuan
AU - Gleadle, Jonathan M.
AU - Beard, Michael R.
AU - Barry, Simon C.
AU - Grubor-Bauk, Branka
AU - Lynn, David J.
PY - 2022/1/14
Y1 - 2022/1/14
N2 - 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.
AB - 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.
KW - Antibody responses
KW - Convalescent patients
KW - COVID-19
KW - Immunity
KW - Immunophenotyping
KW - Infection
KW - Long COVID
KW - Post COVID-19 condition
KW - Post-acute sequelae of COVID-19 (PASC)
KW - RNA-Seq
KW - SARS-CoV-2
KW - T cell
UR - http://www.scopus.com/inward/record.url?scp=85123022663&partnerID=8YFLogxK
U2 - 10.1186/s12916-021-02228-6
DO - 10.1186/s12916-021-02228-6
M3 - Article
AN - SCOPUS:85123022663
SN - 1741-7015
VL - 20
JO - BMC Medicine
JF - BMC Medicine
IS - 1
M1 - 26
ER -