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

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

SUBMITTER: Bastard P

PROVIDER: S-EPMC9210448 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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

Bastard Paul P Vazquez Sara E SE Liu Jamin J Laurie Matthew T MT Wang Chung Yu CY Gervais Adrian A Le Voyer Tom T Le Voyer Tom T Bizien Lucy L Zamecnik Colin C Philippot Quentin Q Rosain Jérémie J Catherinot Emilie E Willmore Andrew A Mitchell Anthea M AM Bair Rebecca R Garçon Pierre P Kenney Heather H Fekkar Arnaud A Salagianni Maria M Poulakou Garyphallia G Siouti Eleni E Sahanic Sabina S Tancevski Ivan I Weiss Günter G Nagl Laurenz L Manry Jérémy J Duvlis Sotirija S Arroyo-Sánchez Daniel D Paz Artal Estela E Rubio Luis L Perani Cristiano C Bezzi Michela M Sottini Alessandra A Quaresima Virginia V Roussel Lucie L Vinh Donald C DC Reyes Luis Felipe LF Garzaro Margaux M Hatipoglu Nevin N Boutboul David D Tandjaoui-Lambiotte Yacine Y Borghesi Alessandro A Aliberti Anna A Cassaniti Irene I Venet Fabienne F Monneret Guillaume G Halwani Rabih R Sharif-Askari Narjes Saheb NS Danielson Jeffrey J Burrel Sonia S Morbieu Caroline C Stepanovskyy Yurii Y Bondarenko Anastasia A Volokha Alla A Boyarchuk Oksana O Gagro Alenka A Neuville Mathilde M Neven Bénédicte B Keles Sevgi S Hernu Romain R Bal Antonin A Novelli Antonio A Novelli Giuseppe G Saker Kahina K Ailioaie Oana O Antolí Arnau A Jeziorski Eric E Rocamora-Blanch Gemma G Teixeira Carla C Delaunay Clarisse C Lhuillier Marine M Le Turnier Paul P Zhang Yu Y Mahevas Matthieu M Pan-Hammarström Qiang Q Abolhassani Hassan H Bompoil Thierry T Dorgham Karim K Gorochov Guy G Laouenan Cédric C Rodríguez-Gallego Carlos C Ng Lisa F P LFP Renia Laurent L Pujol Aurora A Belot Alexandre A Raffi François F Allende Luis M LM Martinez-Picado Javier J Ozcelik Tayfun T Imberti Luisa L Notarangelo Luigi D LD Troya Jesus J Solanich Xavier X Zhang Shen-Ying SY Puel Anne A Wilson Michael R MR Trouillet-Assant Sophie S Trouillet-Assant Sophie S Abel Laurent L Jouanguy Emmanuelle E Ye Chun Jimmie CJ Cobat Aurélie A Thompson Leslie M LM Andreakos Evangelos E Zhang Qian Q Anderson Mark S MS Casanova Jean-Laurent JL DeRisi Joseph L JL

Science immunology 20231222 90

Life-threatening "breakthrough" cases of critical COVID-19 are attributed to poor or waning antibody (Ab) response to SARS-CoV-2 vaccines in individuals already at risk. Preexisting auto-Abs neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; their contribution to hypoxemic breakthrough cases in vaccinated people is unknown. We studied a cohort of 48 individuals (aged 20 to 86 years) who received two doses of a messenger RNA (mRNA) vac ...[more]

PMID: 35857576

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Project description:BackgroundCOVID-19 convalescent plasma (CCP) contains neutralising anti-SARS-CoV-2 antibodies that may be useful as COVID-19 passive immunotherapy in patients at risk of developing severe disease. Such plasma from convalescent patients may also have additional immune-modulatory properties when transfused to COVID-19 patients.MethodsCCP (n = 766) was compared to non-convalescent control plasma (n = 166) for soluble inflammatory markers, ex-vivo inflammatory bioactivity on endothelial cells, neutralising auto-Abs to type I IFNs and reported adverse events in the recipients.FindingsCCP exhibited a statistically significant increase in IL-6 and TNF-alpha levels (0.531 ± 0.04 vs 0.271 ± 0.04; (95% confidence interval [CI], 0.07371-0.4446; p = 0.0061) and 0.900 ± 0.07 vs 0.283 ± 0.07 pg/mL; (95% [CI], 0.3097-0.9202; p = 0.0000829) and lower IL-10 (0.731 ± 0.07 vs 1.22 ± 0.19 pg/mL; (95% [CI], -0.8180 to -0.1633; p = 0.0034) levels than control plasma. Neutralising auto-Abs against type I IFNs were detected in 14/766 (1.8%) CCPs and were not associated with reported adverse events when transfused. Inflammatory markers and bioactivity in CCP with or without auto-Abs, or in CCP whether or not linked to adverse events in transfused patients, did not differ to a statistically significant extent.InterpretationOverall, CCP exhibited moderately increased inflammatory markers compared to the control plasma with no discernible differences in ex-vivo bioactivity. Auto-Abs to type I IFNs detected in a small fraction of CCP were not associated with reported adverse events or differences in inflammatory markers. Additional studies, including careful clinical evaluation of patients treated with CCP, are required in order to further define the clinical relevance of these findings.FundingFrench National Blood Service-EFS, the Association "Les Amis de Rémi" Savigneux, France, the "Fondation pour la Recherche Médicale (Medical Research Foundation)-REACTing 2020".

Project description:BackgroundIn a recent study, autoantibodies neutralizing type I interferons (IFNs) were present in at least 10% of cases of critical COVID-19 pneumonia. These autoantibodies neutralized most type I IFNs but rarely IFN-beta.ObjectivesWe aimed to define the prevalence of autoantibodies neutralizing type I IFN in a cohort of patients with severe COVID-19 pneumonia treated with IFN-beta-1b during hospitalization and to analyze their impact on various clinical variables and outcomes.MethodsWe analyzed stored serum/plasma samples and clinical data of COVID-19 patients treated subcutaneously with IFN-beta-1b from March to May 2020, at the Infanta Leonor University Hospital in Madrid, Spain.ResultsThe cohort comprised 47 COVID-19 patients with severe pneumonia, 16 of whom (34%) had a critical progression requiring ICU admission. The median age was 71 years, with 28 men (58.6%). Type I IFN-alpha- and omega-neutralizing autoantibodies were found in 5 of 47 patients with severe pneumonia or critical disease (10.6%), while they were not found in any of the 118 asymptomatic controls (p = 0.0016). The autoantibodies did not neutralize IFN-beta. No demographic, comorbidity, or clinical differences were seen between individuals with or without autoantibodies. We found a significant correlation between the presence of neutralizing autoantibodies and higher C-reactive protein levels (p = 5.10e-03) and lower lymphocyte counts (p = 1.80e-02). No significant association with response to IFN-beta-1b therapy (p = 0.34) was found. Survival analysis suggested that neutralizing autoantibodies may increase the risk of death (4/5, 80% vs 12/42, 28.5%).ConclusionAutoantibodies neutralizing type I IFN underlie severe/critical COVID-19 stages in at least 10% of cases, correlate with increased C-RP and lower lymphocyte counts, and confer a trend towards increased risk of death. Subcutaneous IFN-beta treatment of hospitalized patients did not seem to improve clinical outcome. Studies of earlier, ambulatory IFN-beta treatment are warranted.

Dataset Information

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

Publications

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

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