tetano
Editor, Senior Moderator
Sci Transl Med
. 2023 Sep 6;15(712):eadf6598.
doi: 10.1126/scitranslmed.adf6598. Epub 2023 Sep 6. Humoral immunity to an endemic coronavirus is associated with postacute sequelae of COVID-19 in individuals with rheumatic diseases
Jonathan D Herman[SUP] 1 2 [/SUP], Caroline Atyeo[SUP] 1 [/SUP], Yonatan Zur[SUP] 1 [/SUP], Claire E Cook[SUP] 3 [/SUP], Naomi J Patel[SUP] 3 [/SUP], Kathleen M Vanni[SUP] 4 [/SUP], Emily N Kowalski[SUP] 4 [/SUP], Grace Qian[SUP] 4 [/SUP], Shruthi Srivatsan[SUP] 3 [/SUP], Nancy A Shadick[SUP] 4 [/SUP], Deepak A Rao[SUP] 4 [/SUP], Benjamin Kellman[SUP] 1 [/SUP], Colin J Mann[SUP] 1 [/SUP], Douglas Lauffenburger[SUP] 5 [/SUP], Zachary S Wallace[SUP] 3 [/SUP], Jeffrey A Sparks[SUP] 4 [/SUP], Galit Alter[SUP] 1 5 [/SUP]
Affiliations
Beyond the acute illness caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) infection, about one-fifth of infections result in long-term persistence of symptoms despite the apparent clearance of infection. Insights into the mechanisms that underlie postacute sequelae of COVID-19 (PASC) will be critical for the prevention and clinical management of long-term complications of COVID-19. Several hypotheses have been proposed that may account for the development of PASC, including persistence of virus and dysregulation of immune responses. Among the immunological changes noted in PASC, alterations in humoral immunity have been observed in some patient subsets. To begin to determine whether SARS-CoV-2- or other pathogen-specific humoral immune responses evolve uniquely in PASC, we performed comprehensive antibody profiling against SARS-CoV-2, a panel of endemic pathogens, and a panel of routine vaccine antigens using systems serology in two cohorts of patients with preexisting systemic autoimmune rheumatic disease (SARD) who either developed or did not develop PASC. A distinct qualitative shift observed in Fcγ receptor (FcγR) binding was observed in individuals with PASC. Specifically, individuals with PASC harbored weaker FcγR-binding anti-SARS-CoV-2 antibodies and stronger FcγR-binding antibody responses against the endemic coronavirus OC43. Individuals with PASC developed an OC43 S2-specific antibody response with stronger FcγR binding, linked to cross-reactivity across SARS-CoV-2 and common coronaviruses. These findings identify previous coronavirus imprinting as a potential marker for the development of PASC in individuals with SARDs.
. 2023 Sep 6;15(712):eadf6598.
doi: 10.1126/scitranslmed.adf6598. Epub 2023 Sep 6. Humoral immunity to an endemic coronavirus is associated with postacute sequelae of COVID-19 in individuals with rheumatic diseases
Jonathan D Herman[SUP] 1 2 [/SUP], Caroline Atyeo[SUP] 1 [/SUP], Yonatan Zur[SUP] 1 [/SUP], Claire E Cook[SUP] 3 [/SUP], Naomi J Patel[SUP] 3 [/SUP], Kathleen M Vanni[SUP] 4 [/SUP], Emily N Kowalski[SUP] 4 [/SUP], Grace Qian[SUP] 4 [/SUP], Shruthi Srivatsan[SUP] 3 [/SUP], Nancy A Shadick[SUP] 4 [/SUP], Deepak A Rao[SUP] 4 [/SUP], Benjamin Kellman[SUP] 1 [/SUP], Colin J Mann[SUP] 1 [/SUP], Douglas Lauffenburger[SUP] 5 [/SUP], Zachary S Wallace[SUP] 3 [/SUP], Jeffrey A Sparks[SUP] 4 [/SUP], Galit Alter[SUP] 1 5 [/SUP]
Affiliations
- PMID: 37672567
- DOI: 10.1126/scitranslmed.adf6598
Beyond the acute illness caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) infection, about one-fifth of infections result in long-term persistence of symptoms despite the apparent clearance of infection. Insights into the mechanisms that underlie postacute sequelae of COVID-19 (PASC) will be critical for the prevention and clinical management of long-term complications of COVID-19. Several hypotheses have been proposed that may account for the development of PASC, including persistence of virus and dysregulation of immune responses. Among the immunological changes noted in PASC, alterations in humoral immunity have been observed in some patient subsets. To begin to determine whether SARS-CoV-2- or other pathogen-specific humoral immune responses evolve uniquely in PASC, we performed comprehensive antibody profiling against SARS-CoV-2, a panel of endemic pathogens, and a panel of routine vaccine antigens using systems serology in two cohorts of patients with preexisting systemic autoimmune rheumatic disease (SARD) who either developed or did not develop PASC. A distinct qualitative shift observed in Fcγ receptor (FcγR) binding was observed in individuals with PASC. Specifically, individuals with PASC harbored weaker FcγR-binding anti-SARS-CoV-2 antibodies and stronger FcγR-binding antibody responses against the endemic coronavirus OC43. Individuals with PASC developed an OC43 S2-specific antibody response with stronger FcγR binding, linked to cross-reactivity across SARS-CoV-2 and common coronaviruses. These findings identify previous coronavirus imprinting as a potential marker for the development of PASC in individuals with SARDs.