Human genetic and immunological determinants of critical COVID-19 pneumonia

Zhang, Qian; Bastard, Paul; Karbuz, Adem; Gervais, Adrian; Tayoun, Ahmad Abou; Aiuti, Alessandro; Belot, Alexandre; Bolze, Alexandre; Gaudet, Alexandre; Бондаренко, Анастасія; Li, Yong; Spaan, András N.; Guennoun, Andrea; Arias, Andrés A.; Planas, Anna M.; Šedivá, Anna; Shcherbina, Anna; Neehus, Anna-Lena; Puel, Anne; Froidure, Antoine; Novelli, Antonio; Parlakay, Aslınur Özkaya; Pujol, Aurora; Yahşi, Aysun; Gülhan, Belgi̇n; Bigio, Benedetta; Boisson, Bertrand; Drolet, Beth A.; Franco, Carlos Andres Arango; Flores, Carlos; Rodríguez‐Gallego, Carlos; Prando, Carolina; Biggs, Catherine M.; Luyt, Charles‐Édouard; Dalgard, Clifton L.; O’Farrelly, Cliona; Matuozzo, Daniela; Dalmau, David; Perlin, David S.; Mansouri, Davood; Beek, Diederik van de; Vinh, Donald C.; Domínguez‐Garrido, Elena; Hsieh, Elena W.Y.; Erdeniz, Emine Hafize; Jouanguy, Emmanuelle; Şevketoğlu, Esra; Talouarn, Estelle; Quirós-Roldán, Eugenia; Andreakos, Evangelos; Husebye, Eystein S.; Alsohime, Fahad; Haerynck, Filomeen; Casari, Giorgio; Novelli, Giuseppe; Aytekin, Gökhan; Morelle, Guillaume; Alkan, Gülsüm; Bayhan, Gülsüm İclal; Feldman, Hagit Baris; Su, Helen C.; Bernuth, Horst von; Resnick, Igor B.; Bustos, Ingrid G.; Meyts, Isabelle; Migeotte, Isabelle; Tancevski, Ivan; Bustamante, Jacinta; Fellay, Jacques; Baghdadi, Jamila El; Martínez-Picado, Javier; Rosain, Jérémie; Manry, Jérémy; Chen, Jie; Christodoulou, John; Bohlen, Jonathan; Franco, José Luis; Li, Juan; Anaya, Juan Manuel; Rojas, Julián; Junqiang, YE; Uddin, K. M. Furkan; Yaşar, Kadriye Kart; Kisand, Kai; Okamoto, Ken‐ichi; Chaïbi, Khalil; Mironska, Kristina; Maródi, László; Abel, Laurent; Rénia, Laurent; Lorenzo, Lazaro; Hammarström, Lennart; Ng, Lisa F. P.; Quintana-Murci, Lluı́s; Erazo, Lucía Victoria; Notarangelo, Luigi D.; Reyes, Luis Felipe; Allende, Luís M.; Imberti, Luisa; Renkilaraj, Majistor Raj Luxman Maglorius; Moncada-Vélez, Marcela; Materna, Marie; Anderson, Mark S.; Gut, Marta; Chbihi, Marwa; Ogishi, Masato; Emiroğlu, Melike; Seppänen, Mikko R. J.; Uddin, M.J.; Shahrooei, Mohammed; Alexander, N. Larcombe; Hatipoğlu, Nevin; Marr, Nico; Akçay, Nihal; Boyarchuk, Oksana; Slabý, Ondřej; Akcan, Özge Metin; Zhang, Peng; Soler‐Palacín, Pere; Gregersen, Peter K.; Brodin, Petter; Garçon, Pierre; Morange, Pierre‐Emmanuel; Pan‐Hammarström, Qiang; Zhou, Qinhua; Philippot, Quentin; Halwani, Rabih; Diego, Rebeca Pérez de; Lévy, Romain; Yang, Rui; Öz, Şadiye Kübra Tüter; Muhsen, Saleh Al; Kanık-Yüksek, Saliha; Espinosa-Padilla, Sara; Ramaswamy, Sathishkumar; Okada, Satoshi; Bozdemir, Şefika Elmas; Aytekin, Selma Erol; Jouanguy, Emmanuelle; Keleş, Sevgi; Şenoğlu, Sevtap; Zhang, Shen-Ying; Duvlis, Sotirija; Constantinescu, Stefan N.; Boisson–Dupuis, Stéphanie; Turvey, Stuart E.; Tangye, Stuart G.; Asano, Takaki; Özçelık, Tayfun; Voyer, Tom Le; Maniatis, Tom; Morio, Tomohiro; Mogensen, Trine H.; Sancho‐Shimizu, Vanessa; Béziat, Vivien; Solanich, Xavier; Bryceson, Yenan T.; Lau, Yu‐Lung; Itan, Yuval; Cobat, Aurélie; Lau, Yu Lung

doi:10.1038/s41586-022-04447-0

Cited by 239 publications

(191 citation statements)

References 209 publications

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“…In contrast, the risk of COVID-19 aggravation among individuals with naAbs to type I IFNs was estimated to be higher (100 pg/mL of IFN-α2 and IFN-ω OR = 5.5, IFN-α2 or IFN-ω OR = 4.7, among patients over 50 years) than those with these modest risk factors. As shown in this study and a previous study (3,5,18), the prevalence of naAbs to type I IFNs is increased with older age and increases throughout life, which might be one of the reasons why age is the most striking epidemiological risk factor. On the other hand, naAbs to type I IFNs were also identi ed in 1% or less of patients with mild to moderate COVID-19.…”

Section: Discussionsupporting

confidence: 77%

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Neutralizing Type I Interferon Autoantibodies in Japanese Patients With Severe COVID-19

Eto

Nukui

Tsumura

et al. 2022

Preprint

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PurposeAutoantibodies (aAbs) to type I interferons (IFNs) have been found in <1% of individuals under the age of 60 in the general population, with the prevalence increasing among those over 65. Neutralizing autoantibodies (naAbs) to type I IFNs have been found in at least 15% of patients with life-threatening COVID-19 pneumonia in several cohorts of primarily European descent. We aimed to define the prevalence of aAbs to IFN-α2 in 3,456 Japanese controls aged 20–91 and of aAbs and naAbs to IFN-α2 and IFN-ω in 627 Japanese COVID-19 patients aged 0–104, among whom were 170 critical, 235 severe, 112 moderate, 105 mild, and 5 asymptomatic infections.MethodsELISA and ISRE reporter assays were used to detect aAbs and naAbs using E. coli-produced IFNs.ResultsIn an uninfected general Japanese population aged 20–91, we found aAbs in 0.087% of individuals. naAbs to type I IFNs (IFN-α2 and/or IFN-ω, 100 pg/mL) were detected in 10.6% of patients with critical infections, 2.6% of patients with severe infections, and ≤1% of patients with asymptomatic to mild infections. They were higher in COVID-19 patients over 50 (5.8%) than in younger patients (0%) and higher in men (5.5%) than in women (1.1%). A significant but not strong correlation between aAbs and naAbs to IFN-α2 existed (r=-0.307, p-value<0.0001), stressing the importance of measuring naAbs.ConclusionIn the largest study focusing on a single ethnic and geographic group, we show that Japanese individuals with pre-existing naAbs have a much higher risk of life-threatening COVID-19 pneumonia.

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Section: Discussionsupporting

confidence: 77%

“…To date, the strong epidemiological risk factor for life-threatening COVID-19 is age (especially >65 years) (2)(3)(4)(5). In contrast, other factors, such as male sex, cardiovascular disease, etc., are modestly associated with COVID-19 aggravation (6-8).…”

Section: Introductionmentioning

confidence: 99%

Neutralizing Type I Interferon Autoantibodies in Japanese Patients With Severe COVID-19

Eto

Nukui

Tsumura

et al. 2022

Preprint

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“…These auto-Abs were mostly found in men (95%), and half the patients carrying them were over the age of 65 yr ( Bastard et al, 2020b ). These findings were subsequently widely replicated in independent cohorts ( Abers et al, 2021 ; Acosta-Ampudia et al, 2021 ; Carapito et al, 2022 ; Chang et al, 2021 ; Chauvineau-Grenier et al, 2022 ; Goncalves et al, 2021 ; Koning et al, 2021 ; Raadsen et al, 2022 ; Solanich et al, 2021 ; Troya et al, 2021 ; van der Wijst et al, 2021 ; Vazquez et al, 2021 ; Wang et al, 2021 ; Zhang et al, 2022 ; Ziegler et al, 2021 ). Consistently, patients with APS-1 and preexisting anti–type I IFN auto-Abs were found to be at very high risk of severe disease upon SARS-CoV-2 infection ( Bastard et al, 2020b ; Beccuti et al, 2020 ; Carpino et al, 2021 ).…”

Section: Neutralizing Auto-abs Against Type I Ifns Underlie Severe Or...mentioning

confidence: 72%

“…Indeed, otherwise healthy patients vulnerable to weakly virulent mycobacteria (Mendelian susceptibility to mycobacterial disease [MSMD]) and/or to the more virulent Mycobaterium tuberculosis , carry inborn errors of IFN-γ, type II IFN immunity ( Bustamante, 2020 ; Yang et al, 2020 ). Patients with inborn errors of type I IFN immunity each suffer from one or a few viral diseases, including herpes simplex virus 1 encephalitis ( Bastard et al, 2020a ; Zhang, 2020b ), influenza A virus pneumonia ( Casanova and Abel, 2021b ; Lim et al, 2019 ; Zhang, 2020a ), severe rhinovirus pulmonary diseases ( Asgari et al, 2017 ; Lamborn et al, 2017 ; Lamborn and Su, 2020 ), hypoxemic COVID-19 pneumonia ( Asano et al, 2021a ; Casanova and Abel, 2021b ; Zhang et al, 2022 ; Zhang et al, 2020 ), or adverse reactions to live-attenuated measles ( Hambleton et al, 2013 ; Hernandez et al, 2019 ) or yellow fever virus vaccines ( Bastard et al, 2021b ; Hernandez et al, 2019 ). Patients with chronic mucocutaneous candidiasis (CMC), which is occasionally associated with staphylococcal disease, carry inborn errors of IL-17A/IL-17F (IL-17A/F; Puel, 2020 ; Puel et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Human autoantibodies underlying infectious diseases

Puel

Bastard

Bustamante

et al. 2022

Journal of Experimental Medicine

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The vast interindividual clinical variability observed in any microbial infection—ranging from silent infection to lethal disease—is increasingly being explained by human genetic and immunological determinants. Autoantibodies neutralizing specific cytokines underlie the same infectious diseases as inborn errors of the corresponding cytokine or response pathway. Autoantibodies against type I IFNs underlie COVID-19 pneumonia and adverse reactions to the live attenuated yellow fever virus vaccine. Autoantibodies against type II IFN underlie severe disease caused by environmental or tuberculous mycobacteria, and other intra-macrophagic microbes. Autoantibodies against IL-17A/F and IL-6 are less common and underlie mucocutaneous candidiasis and staphylococcal diseases, respectively. Inborn errors of and autoantibodies against GM-CSF underlie pulmonary alveolar proteinosis; associated infections are less well characterized. In individual patients, autoantibodies against cytokines preexist infection with the pathogen concerned and underlie the infectious disease. Human antibody-driven autoimmunity can interfere with cytokines that are essential for protective immunity to specific infectious agents but that are otherwise redundant, thereby underlying specific infectious diseases.

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“…This loss of GC was associated with increased frequencies of T-bet + CD11c + extra-follicular B-cells, which have been associated with a strong production of auto-antibodies and poor disease outcome in individuals infected with SARS-CoV-2 [ 181 ]. Indeed, auto-antibodies directed against interferons are one of the key triggering events to critical COVID-19 pneumonia and death in patients who develop this disease [ 182 ]. Unsurprisingly, BAFF was found to be elevated and to persist in individuals with severe disease [ 183 ].…”

Section: Mzps and Similar Populations In Other Diseasesmentioning

confidence: 99%

Marginal Zone B-Cell Populations and Their Regulatory Potential in the Context of HIV and Other Chronic Inflammatory Conditions

Doyon-Laliberté

Aranguren

Poudrier

et al. 2022

IJMS

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Inflammation in the context of Human Immunodeficiency Virus (HIV) establishes early and persists beyond antiretroviral therapy (ART). As such, we have shown excess B-cell activating factor (BAFF) in the blood of HIV-infected progressors, as soon as in the acute phase, and despite successful ART. Excess BAFF was associated with deregulation of the B-cell compartment; notably, with increased frequencies of a population sharing features of both transitional immature (TI) and marginal zone (MZ) B-cells, we termed Marginal Zone precursor-like (MZp). We have reported similar observations with HIV-transgenic mice, Simian Immunodeficiency Virus (SIV)-infected macaques, and more recently, with HIV-infected Beninese commercial sex workers, which suggests that excess BAFF and increased frequencies of MZp B-cells are reliable markers of inflammation in the context of HIV. Importantly, we have recently shown that in healthy individuals, MZps present an important regulatory B-cell (Breg) profile and function. Herein, we wish to review our current knowledge on MZ B-cell populations, especially their Breg status, and that of other B-cell populations sharing similar features. BAFF and its analog A Proliferation-Inducing Ligand (APRIL) are important in shaping the MZ B-cell pool; moreover, the impact that excess BAFF—encountered in the context of HIV and several chronic inflammatory conditions—may exert on MZ B-cell populations, Breg and antibody producing capacities is a threat to the self-integrity of their antibody responses and immune surveillance functions. As such, deregulations of MZ B-cell populations contribute to autoimmune manifestations and the development of MZ lymphomas (MZLs) in the context of HIV and other inflammatory diseases. Therefore, further comprehending the mechanisms regulating MZ B-cell populations and their functions could be beneficial to innovative therapeutic avenues that could be deployed to restore MZ B-cell immune competence in the context of chronic inflammation involving excess BAFF.

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Human genetic and immunological determinants of critical COVID-19 pneumonia

Cited by 239 publications

References 209 publications

Neutralizing Type I Interferon Autoantibodies in Japanese Patients With Severe COVID-19

Neutralizing Type I Interferon Autoantibodies in Japanese Patients With Severe COVID-19

Human autoantibodies underlying infectious diseases

Marginal Zone B-Cell Populations and Their Regulatory Potential in the Context of HIV and Other Chronic Inflammatory Conditions

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