Autoantibodies Neutralizing Type I Interferons in 20% of COVID-19 Deaths in a French Hospital

Journal of Clinical Immunology, Journal Year: 2022, Volume and Issue: 42(3), P. 459 - 470

Published: Jan. 27, 2022

Language: Английский

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Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses

Brain, Journal Year: 2022, Volume and Issue: 145(11), P. 4097 - 4107

Published: Sept. 6, 2022

COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms common, seemingly unrelated to severity. The true frequency underlying mechanisms of injury are unknown, but exaggerated host inflammatory responses appear be key driver We investigated the dynamics of, relationship between, serum markers brain [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) total tau] dysregulated response (autoantibody production cytokine profiles) in 175 patients admitted 45 influenza. During hospitalization, sera from demonstrated elevations NfL GFAP severity-dependent manner, evidence ongoing active at follow-up 4 months later. These biomarkers were pro-inflammatory cytokines presence autoantibodies large number different antigens. Autoantibodies commonly seen against lung surfactant proteins also such as myelin glycoprotein. Commensurate findings influenza cohort. A distinct process characterized elevation tau was follow-up, which appeared independent initial disease severity not immune unlike GFAP. results demonstrate that common consequence both influenza, therefore likely feature severe viral infection more broadly. occurs context dysregulation innate adaptive responses, no single pathogenic mechanism clearly responsible.

Language: Английский

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Nasally delivered interferon-λ protects mice against infection by SARS-CoV-2 variants including Omicron

Cell Reports, Journal Year: 2022, Volume and Issue: 39(6), P. 110799 - 110799

Published: April 21, 2022

Although vaccines and monoclonal antibody countermeasures have reduced the morbidity mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, variants constellations of mutations in spike gene jeopardize their efficacy. Accordingly, antiviral interventions that are resistant to further virus evolution needed. The host-derived cytokine interferon lambda (IFN-λ) has been proposed as a possible treatment based on studies human 2019 (COVID-19) patients. Here, we show IFN-λ protects against SARS-CoV-2 B.1.351 (Beta) B.1.1.529 (Omicron) three strains conventional ACE2 transgenic mice. Prophylaxis or therapy nasally delivered IFN-λ2 limits infection historical variant upper lower tracts without causing excessive inflammation. In lung, is produced preferentially epithelial cells acts radio-resistant protect infection. Thus, inhaled may promise for evolving develop resistance antibody-based countermeasures.

Language: Английский

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Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Science Immunology, Journal Year: 2022, Volume and Issue: 8(90)

Published: June 14, 2022

Life-threatening “breakthrough” cases of critical COVID-19 are attributed to poor or waning antibody (Ab) response SARS-CoV-2 vaccines in individuals already at risk. Preexisting auto-Abs neutralizing type I IFNs underlie least 15% pneumonia unvaccinated individuals; their contribution hypoxemic breakthrough vaccinated people is unknown. We studied a cohort 48 (aged 20 86 years) who received two doses messenger RNA (mRNA) vaccine and developed infection with 2 weeks 4 months later. Ab levels the vaccine, neutralization virus, were measured plasma. Forty-two had no known deficiency B cell immunity normal vaccine. Among them, 10 (24%) 43 years). Eight these patients both IFN-α2 IFN-ω, whereas neutralized IFN-ω only. No patient IFN-β. Seven ng/ml three 100 pg/ml D614G Delta efficiently, one slightly less efficiently. Two only Despite mRNA inoculations presence circulating Abs capable SARS-CoV-2, may notable proportion cases, highlighting importance this particularly vulnerable population.

Language: Английский

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Lower disease activity but higher risk of severe COVID-19 and herpes zoster in patients with systemic lupus erythematosus with pre-existing autoantibodies neutralising IFN-α

Annals of the Rheumatic Diseases, Journal Year: 2022, Volume and Issue: 81(12), P. 1695 - 1703

Published: Aug. 16, 2022

Objectives Type-I interferons (IFNs-I) have potent antiviral effects. IFNs-I are also overproduced in patients with systemic lupus erythematosus (SLE). Autoantibodies (AAbs) neutralising IFN-α, IFN-β and/or IFN-ω subtypes strong determinants of hypoxemic COVID-19 pneumonia, but their impact on inflammation remains unknown. Methods We retrospectively analysed a monocentric longitudinal cohort 609 SLE. Serum AAbs against IFN-α were quantified by ELISA and functionally assessed abolishment Madin-Darby bovine kidney cell protection IFN-α2 vesicular stomatitis virus challenge. Serum-neutralising activity IFN-α2, was determined reporter luciferase assay. SARS-CoV-2 antibody responses measured wild-type spike antigen, while serum-neutralising the historical strain variants concerns. Results Neutralising non-neutralising anti-IFN-α antibodies present at frequency 3.3% 8.4%, respectively, individuals unlike AAbs, associated reduced serum levels likelihood to develop active disease. However, they predispose an increased risk herpes zoster severe pneumonia. Severe pneumonia SLE is mostly combined neutralisation different IFNs-I. Finally, do not interfere vaccine humoral immunogenicity. Conclusion The production anti-IFN-I likely be consequence SLE-associated high IFN-I levels, beneficial effect disease activity, yet greater viral risk. This finding reinforces recommendations for vaccination

Language: Английский

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