Increased Presence of Antibodies against Type I Interferons and Human Endogenous Retrovirus W in Intensive Care Unit COVID-19 Patients

Abstract

In this work, we report the increased presence of IFN autoantibodies in correlation with HERV-W-env autoantibodies in ICU COVID-19 patients. The novelty of the results is in the association of these IFN autoantibodies with autoantibodies against HERV-W-env, a protein recently discovered to be overexpressed in lymphocytes of COVID-19 patients and correlated with severe disease and pneumonia.

Human endogenous retroviruses and the inflammatory response: A vicious circle associated with health and illness

“…As already observed in autoimmune diseases, Simula et al. (2022) described the presence of anti-HERV-W-env and anti-INF I antibodies in ICU COVID-19 patients ( 140 ), suggesting that the inflammatory component of severe COVID-19 may be related to the presence of HERV antigens.…”

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

“…Following on from the 1984 description of autoantibodies (auto-Abs) against type I IFNs in a single patient with disseminated zoster ( Pozzetto et al, 1984 ), we showed that preexisting auto-Abs neutralizing type I IFNs underlie ≥15% of cases of life-threatening COVID-19 pneumonia ( Bastard et al, 2020 ; Bastard et al, 2021a ; Zhang et al, 2022 ; Puel et al, 2022 ) and 30% of severe adverse reactions to the yellow fever vaccine ( Bastard et al, 2021c ). These findings have since been widely replicated ( Abers et al, 2021 ; Acosta-Ampudia et al, 2021 ; Bastard et al, 2021d ; Chang et al, 2021 ; Chauvineau-Grenier et al, 2021 ; Goncalves et al, 2021 ; Koning et al, 2021 ; Lemarquis et al, 2021 ; Meisel et al, 2021 ; Savvateeva et al, 2021 ; Solanich et al, 2021 ; Troya et al, 2021 ; Van Der Wijst et al, 2021 ; Vazquez et al, 2021 ; Wang et al, 2021 ; Ziegler et al, 2021 ; Akbil et al, 2022 ; Busnadiego et al, 2022 ; Carapito et al, 2022 ; Credle et al, 2022 ; Eto et al, 2022 ; Frasca et al, 2022 ; Lamacchia et al, 2022 ; Mathian et al, 2022 ; Raadsen et al, 2022 ; Simula et al, 2022 ; Soltani-Zangbar et al, 2022 ). Individuals with auto-Abs against type I IFNs are, thus, susceptible to at least two life-threatening viral infections.…”

From rare disorders of immunity to common determinants of infection: Following the mechanistic thread

“…In a subsequent study, the neutralization of lower, more physiological concentrations of IFN-a and/or IFN-u (100 pg/mL, again with plasma diluted 1/10), and of IFN-b, was found to underlie 15% of critical cases, and 20% of cases in patients over the age of 80 years (Bastard et al, 2021a). These studies have been replicated in at least 26 other cohorts in the Americas, Europe, and Asia (Abers et al, 2021;Acosta-Ampudia et al, 2021;Akbil et al, 2022;Bastard et al, 2021;Busnadiego et al, 2022;Carapito et al, 2021;Chang et al, 2021;Chauvineau-Grenier et al, 2022;Eto et al, 2022;Frasca et al, 2022;Goncalves et al, 2021;Koning et al, 2021;Lamacchia et al, 2022;Lemarquis et al, 2021;Mathian et al, 2022;Meisel et al, 2021;Raadsen et al, 2022;Savvateeva et al, 2021;Simula et al, 2022;Solanich et al, 2021;Soltani-Zangbar et al, 2022;Troya et al, 2021;van der Wijst et al, 2021;Vazquez et al, 2021;Wang et al, 2021;Ziegler et al, 2021). These auto-Abs had been known for 40 years, in patients treated with recombinant IFN-a or -b (Zhang et al, 2022a), or with autoimmune conditions, such as systemic lupus erythematosus (SLE), myasthenia gravis, thymoma, autoimmune polyendocrinopathy syndrome type 1 (APS-1), immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX), or RAG1/ RAG2 hypomorphic mutations (Bastard et al, 2020(Bastard et al, , 2021d.…”

“…In a subsequent study, the neutralization of lower, more physiological concentrations of IFN-α and/or IFN-ω (100 pg/mL, again with plasma diluted 1/10), and of IFN-β, was found to underlie 15% of critical cases, and 20% of cases in patients over the age of 80 years ( Bastard et al., 2021a ). These studies have been replicated in at least 26 other cohorts in the Americas, Europe, and Asia ( Abers et al., 2021 , Acosta-Ampudia et al., 2021 , Akbil et al., 2022 , Bastard et al, 2021 , Busnadiego et al., 2022 , Carapito et al., 2021 , Chang et al., 2021 , Chauvineau-Grenier et al., 2022 , Eto et al ., 2022 , Frasca et al., 2022 , Goncalves et al., 2021 , Koning et al., 2021 , Lamacchia et al, 2022 , Lemarquis et al, 2021 , Mathian et al, 2022 , Meisel et al, 2021 , Raadsen et al., 2022 , Savvateeva et al., 2021 , Simula et al, 2022 , Solanich et al., 2021 , Soltani-Zangbar et al, 2022 , Troya et al., 2021 , van der Wijst et al., 2021 , Vazquez et al., 2021 , Wang et al., 2021 , Ziegler et al., 2021 .…”