tetano
Editor, Senior Moderator
BMC Med
. 2022 Jan 14;20(1):26.
doi: 10.1186/s12916-021-02228-6.
Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection
Feargal J Ryan[SUP] #[/SUP][SUP] 1 [/SUP], Christopher M Hope[SUP] #[/SUP][SUP] 2 3 [/SUP], Makutiro G Masavuli[SUP] #[/SUP][SUP] 4 [/SUP], Miriam A Lynn[SUP] #[/SUP][SUP] 1 [/SUP], Zelalem A Mekonnen[SUP] 4 [/SUP], Arthur Eng Lip Yeow[SUP] 4 [/SUP], Pablo Garcia-Valtanen[SUP] 4 [/SUP], Zahraa Al-Delfi[SUP] 4 [/SUP], Jason Gummow[SUP] 5 [/SUP], Catherine Ferguson[SUP] 6 [/SUP], Stephanie O'Connor[SUP] 7 [/SUP], Benjamin A J Reddi[SUP] 7 [/SUP], Pravin Hissaria[SUP] 6 [/SUP], David Shaw[SUP] 6 [/SUP], Chuan Kok-Lim[SUP] 6 8 [/SUP], Jonathan M Gleadle[SUP] 9 10 [/SUP], Michael R Beard[SUP] 11 [/SUP], Simon C Barry[SUP] #[/SUP][SUP] 12 13 [/SUP], Branka Grubor-Bauk[SUP] #[/SUP][SUP] 14 [/SUP], David J Lynn[SUP] #[/SUP][SUP] 15 16 [/SUP]
Affiliations
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.
Keywords: Antibody responses; COVID-19; Convalescent patients; Immunity; Immunophenotyping; Infection; Long COVID; Post COVID-19 condition; Post-acute sequelae of COVID-19 (PASC); RNA-Seq; SARS-CoV-2; T cell.
. 2022 Jan 14;20(1):26.
doi: 10.1186/s12916-021-02228-6.
Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection
Feargal J Ryan[SUP] #[/SUP][SUP] 1 [/SUP], Christopher M Hope[SUP] #[/SUP][SUP] 2 3 [/SUP], Makutiro G Masavuli[SUP] #[/SUP][SUP] 4 [/SUP], Miriam A Lynn[SUP] #[/SUP][SUP] 1 [/SUP], Zelalem A Mekonnen[SUP] 4 [/SUP], Arthur Eng Lip Yeow[SUP] 4 [/SUP], Pablo Garcia-Valtanen[SUP] 4 [/SUP], Zahraa Al-Delfi[SUP] 4 [/SUP], Jason Gummow[SUP] 5 [/SUP], Catherine Ferguson[SUP] 6 [/SUP], Stephanie O'Connor[SUP] 7 [/SUP], Benjamin A J Reddi[SUP] 7 [/SUP], Pravin Hissaria[SUP] 6 [/SUP], David Shaw[SUP] 6 [/SUP], Chuan Kok-Lim[SUP] 6 8 [/SUP], Jonathan M Gleadle[SUP] 9 10 [/SUP], Michael R Beard[SUP] 11 [/SUP], Simon C Barry[SUP] #[/SUP][SUP] 12 13 [/SUP], Branka Grubor-Bauk[SUP] #[/SUP][SUP] 14 [/SUP], David J Lynn[SUP] #[/SUP][SUP] 15 16 [/SUP]
Affiliations
- PMID: 35027067
- DOI: 10.1186/s12916-021-02228-6
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.
Keywords: Antibody responses; COVID-19; Convalescent patients; Immunity; Immunophenotyping; Infection; Long COVID; Post COVID-19 condition; Post-acute sequelae of COVID-19 (PASC); RNA-Seq; SARS-CoV-2; T cell.