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  1. Article ; Online: Autoantibodies Neutralizing Type I INFs May Be Associated with Efficacy of Tocilizumab in COVID-19 Pneumonia.

    Chauvineau-Grenier, Angélique / Bastard, Paul / Casanova, Jean-Laurent / Rossi, Benjamin

    Journal of clinical immunology

    2022  Volume 42, Issue 6, Page(s) 1107–1110

    MeSH term(s) Antibodies, Monoclonal, Humanized/therapeutic use ; Autoantibodies ; Humans ; COVID-19 Drug Treatment
    Chemical Substances Antibodies, Monoclonal, Humanized ; Autoantibodies ; tocilizumab (I031V2H011)
    Language English
    Publishing date 2022-06-08
    Publishing country Netherlands
    Document type Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 779361-3
    ISSN 1573-2592 ; 0271-9142
    ISSN (online) 1573-2592
    ISSN 0271-9142
    DOI 10.1007/s10875-022-01295-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Autoantibodies Neutralizing Type I Interferons in 20% of COVID-19 Deaths in a French Hospital.

    Chauvineau-Grenier, Angélique / Bastard, Paul / Servajean, Antoine / Gervais, Adrian / Rosain, Jérémie / Jouanguy, Emmanuelle / Cobat, Aurélie / Casanova, Jean-Laurent / Rossi, Benjamin

    Journal of clinical immunology

    2022  Volume 42, Issue 3, Page(s) 459–470

    Abstract: Recent studies reported the presence of pre-existing autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) in at least 15% of patients with critical COVID-19 pneumonia. In one study, these auto-Abs were found in almost 20% of deceased patients ...

    Abstract Recent studies reported the presence of pre-existing autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) in at least 15% of patients with critical COVID-19 pneumonia. In one study, these auto-Abs were found in almost 20% of deceased patients across all ages. We aimed to assess the prevalence and clinical impact of the auto-Abs to type I IFNs in the Seine-Saint-Denis district, which was one of the most affected areas by COVID-19 in France during the first wave. We tested for the presence of auto-Abs neutralizing type I IFNs in a cohort of patients admitted for critical COVID-19 pneumonia during the first wave in the spring of 2020 in the medicine departments at Robert Ballanger Hospital, Aulnay sous Bois. We found circulating auto-Abs that neutralized 100 pg/mL IFN-α2 and/or IFN-ω in the plasma (diluted 1/10) of 7.9% (11 of 139) of the patients hospitalized for critical COVID-19. The presence of neutralizing auto-Abs was associated with an increased risk of mortality, as these auto-Abs were detected in 21% of patients who died from COVID-19 pneumonia. Deceased patients with and without auto-Abs did not present overt clinical differences. These results confirm both the importance of type I IFN immunity in host defense against SARS-CoV-2 infection and the usefulness of detection of auto-Abs neutralizing type I IFNs in the management of patients.
    MeSH term(s) Autoantibodies ; COVID-19/epidemiology ; Hospitals ; Humans ; Interferon Type I ; SARS-CoV-2
    Chemical Substances Autoantibodies ; Interferon Type I
    Language English
    Publishing date 2022-01-27
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 779361-3
    ISSN 1573-2592 ; 0271-9142
    ISSN (online) 1573-2592
    ISSN 0271-9142
    DOI 10.1007/s10875-021-01203-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Basal serum tryptase: A critical reconsideration of reference values.

    Francois, Fabien / Mauff, Brigitte Le / Waeckel, Louis / de Chaisemartin, Luc / Tabary, Thierry / Dumontet, Erwan / Lecron, Jean Claude / Delamare, Benoit / Boumediene, Ahmed / Chauvineau-Grenier, Angélique / Pescarmona, Remi / Garnier, Lorna / Lambert, Claude

    Allergy

    2023  Volume 78, Issue 11, Page(s) 3003–3006

    MeSH term(s) Humans ; Tryptases ; Reference Values ; Mast Cells ; Mastocytosis ; Anaphylaxis
    Chemical Substances Tryptases (EC 3.4.21.59)
    Language English
    Publishing date 2023-06-26
    Publishing country Denmark
    Document type Letter
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.15790
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Autoantibodies neutralizing type I interferons in 20% of COVID-19 deaths in a French hospital.

    Chauvineau-Grenier, Angélique / Bastard, Paul / Servajean, Antoine / Gervais, Adrian / Rosain, Jérémie / Jouanguy, Emmanuelle / Cobat, Aurélie / Casanova, Jean-Laurent / Rossi, Benjamin

    Research square

    2021  

    Abstract: Recent studies reported the presence of pre-existing autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) in at least 15% of patients with critical or severe COVID-19 pneumonia. In one study, these auto-Abs were found in almost 20% of ... ...

    Abstract Recent studies reported the presence of pre-existing autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) in at least 15% of patients with critical or severe COVID-19 pneumonia. In one study, these auto-Abs were found in almost 20% of deceased patients across all ages. We aimed to assess the prevalence and clinical impact of the auto-Abs to type I IFNs in Seine-Saint-Denis district, which was one of the most affected areas by COVID-19 in France during the first wave. We tested for the presence of auto-Abs neutralizing type I IFNs in a cohort of patients admitted for critical COVID-19 pneumonia during the first wave in the spring of 2020 in medicine departments at Robert Ballanger Hospital, Aulnay sous Bois. We found circulating auto-Abs that neutralized 100 pg/mL IFN-α2 and/or IFN-ω in plasma 1/10 in 7.9% (11 of 139) of patients hospitalized for critical COVID-19. The presence of neutralizing auto-Abs was associated with an increased risk of mortality as these auto-Abs were detected in 21% of patients who died from COVID-19 pneumonia. Deceased patients with and without auto-Abs did not present overt clinical differences. These results confirm both the importance of IFN-I immunity in host defense against SARS-CoV-2 infection and the usefulness of detection of auto-Abs neutralizing type I IFNs in the management of patients.
    Language English
    Publishing date 2021-10-01
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-915062/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies.

    Manry, Jeremy / Bastard, Paul / Gervais, Adrian / Le Voyer, Tom / Rosain, Jérémie / Philippot, Quentin / Michailidis, Eleftherios / Hoffmann, Hans-Heinrich / Eto, Shohei / Garcia-Prat, Marina / Bizien, Lucy / Parra-Martínez, Alba / Yang, Rui / Haljasmägi, Liis / Migaud, Mélanie / Särekannu, Karita / Maslovskaja, Julia / de Prost, Nicolas / Tandjaoui-Lambiotte, Yacine /
    Luyt, Charles-Edouard / Amador-Borrero, Blanca / Gaudet, Alexandre / Poissy, Julien / Morel, Pascal / Richard, Pascale / Cognasse, Fabrice / Troya, Jesus / Trouillet-Assant, Sophie / Belot, Alexandre / Saker, Kahina / Garçon, Pierre / Rivière, Jacques G / Lagier, Jean-Christophe / Gentile, Stéphanie / Rosen, Lindsey / Shaw, Elana / Morio, Tomohiro / Tanaka, Junko / Dalmau, David / Tharaux, Pierre-Louis / Sene, Damien / Stepanian, Alain / Mégarbane, Bruno / Triantafyllia, Vasiliki / Fekkar, Arnaud / Heath, James / Franco, Jose / Anaya, Juan-Manuel / Solé-Violán, Jordi / Imberti, Luisa / Biondi, Andrea / Bonfanti, Paolo / Castagnoli, Riccardo / Delmonte, Ottavia / Zhang, Yu / Snow, Andrew / Holland, Steve / Biggs, Catherine / Moncada-Vélez, Marcela / Arias, Andrés / Lorenzo, Lazaro / Boucherit, Soraya / Anglicheau, Dany / Planas, Anna / Haerynck, Filomeen / Duvlis, Sotirija / Nussbaum, Robert / Ozcelik, Tayfun / Keles, Sevgi / Bousfiha, Aziz / El Bakkouri, Jalila / Ramirez-Santana, Carolina / Paul, Stéphane / Pan-Hammarstrom, Qiang / Hammarstrom, Lennart / Dupont, Annabelle / Kurolap, Alina / Metz, Christine / Aiuti, Alessandro / Casari, Giorgio / Lampasona, Vito / Ciceri, Fabio / Barreiros, Lucila / Dominguez-Garrido, Elena / Vidigal, Mateus / Zatz, Mayana / van de Beek, Diederik / Sahanic, Sabina / Tancevski, Ivan / Stepanovskyy, Yurii / Boyarchuk, Oksana / Nukui, Yoko / Tsumura, Miyuki / Vidaur, Loreto / Tangye, Stuart / Burrel, Sonia / Duffy, Darragh / Quintana-Murci, Lluis / Klocperk, Adam / Kann, Nelli / Shcherbina, Anna / Lau, Yu-Lung / Leung, Daniel / Coulongeat, Matthieu / Marlet, Julien / Koning, Rutger / Reyes, Luis / Chauvineau-Grenier, Angélique / Venet, Fabienne / Monneret, Guillaume / Nussenzweig, Michel / Arrestier, Romain / Boudhabhay, Idris / Baris-Feldman, Hagit / Hagin, David / Wauters, Joost / Meyts, Isabelle / Dyer, Adam / Kennelly, Sean / Bourke, Nollaig / Halwani, Rabih / Sharif-Askari, Fatemeh / Dorgham, Karim / Sallette, Jérôme / Mehlal-Sedkaoui, Souad / AlKhater, Suzan / Rigo-Bonnin, Raúl / Morandeira, Francisco / Roussel, Lucie / Vinh, Donald / Erikstrup, Christian / Condino-Neto, Antonio / Prando, Carolina / Bondarenko, Anastasiia / Spaan, András / Gilardin, Laurent / Fellay, Jacques / Lyonnet, Stanislas / Bilguvar, Kaya / Lifton, Richard / Mane, Shrikant / Anderson, Mark / Boisson, Bertrand / Béziat, Vivien / Zhang, Shen-Ying / Andreakos, Evangelos / Hermine, Olivier / Pujol, Aurora / Peterson, Pärt / Mogensen, Trine Hyrup / Rowen, Lee / Mond, James / Debette, Stéphanie / deLamballerie, Xavier / Burdet, Charles / Bouadma, Lila / Zins, Marie / Soler-Palacin, Pere / Colobran, Roger / Gorochov, Guy / Solanich, Xavier / Susen, Sophie / Martinez-Picado, Javier / Raoult, Didier / Vasse, Marc / Gregersen, Peter / Rodríguez-Gallego, Carlos / Piemonti, Lorenzo / Notarangelo, Luigi / Su, Helen / Kisand, Kai / Okada, Satoshi / Puel, Anne / Jouanguy, Emmanuelle / Rice, Charles / Tiberghien, Pierre / Zhang, Qian / Casanova, Jean-Laurent / Abel, Laurent / Cobat, Aurélie

    Research square

    2022  

    Abstract: SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, ... ...

    Abstract SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.
    Language English
    Publishing date 2022-01-14
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-1225906/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.

    Manry, Jérémy / Bastard, Paul / Gervais, Adrian / Le Voyer, Tom / Rosain, Jérémie / Philippot, Quentin / Michailidis, Eleftherios / Hoffmann, Hans-Heinrich / Eto, Shohei / Garcia-Prat, Marina / Bizien, Lucy / Parra-Martínez, Alba / Yang, Rui / Haljasmägi, Liis / Migaud, Mélanie / Särekannu, Karita / Maslovskaja, Julia / de Prost, Nicolas / Tandjaoui-Lambiotte, Yacine /
    Luyt, Charles-Edouard / Amador-Borrero, Blanca / Gaudet, Alexandre / Poissy, Julien / Morel, Pascal / Richard, Pascale / Cognasse, Fabrice / Troya, Jesús / Trouillet-Assant, Sophie / Belot, Alexandre / Saker, Kahina / Garçon, Pierre / Rivière, Jacques G / Lagier, Jean-Christophe / Gentile, Stéphanie / Rosen, Lindsey B / Shaw, Elana / Morio, Tomohiro / Tanaka, Junko / Dalmau, David / Tharaux, Pierre-Louis / Sene, Damien / Stepanian, Alain / Mégarbane, Bruno / Triantafyllia, Vasiliki / Fekkar, Arnaud / Heath, James R / Franco, José Luis / Anaya, Juan-Manuel / Solé-Violán, Jordi / Imberti, Luisa / Biondi, Andrea / Bonfanti, Paolo / Castagnoli, Riccardo / Delmonte, Ottavia M / Zhang, Yu / Snow, Andrew L / Holland, Steven M / Biggs, Catherine M / Moncada-Vélez, Marcela / Arias, Andrés Augusto / Lorenzo, Lazaro / Boucherit, Soraya / Anglicheau, Dany / Planas, Anna M / Haerynck, Filomeen / Duvlis, Sotirija / Ozcelik, Tayfun / Keles, Sevgi / Bousfiha, Ahmed A / El Bakkouri, Jalila / Ramirez-Santana, Carolina / Paul, Stéphane / Pan-Hammarström, Qiang / Hammarström, Lennart / Dupont, Annabelle / Kurolap, Alina / Metz, Christine N / Aiuti, Alessandro / Casari, Giorgio / Lampasona, Vito / Ciceri, Fabio / Barreiros, Lucila A / Dominguez-Garrido, Elena / Vidigal, Mateus / Zatz, Mayana / van de Beek, Diederik / Sahanic, Sabina / Tancevski, Ivan / Stepanovskyy, Yurii / Boyarchuk, Oksana / Nukui, Yoko / Tsumura, Miyuki / Vidaur, Loreto / Tangye, Stuart G / Burrel, Sonia / Duffy, Darragh / Quintana-Murci, Lluis / Klocperk, Adam / Kann, Nelli Y / Shcherbina, Anna / Lau, Yu-Lung / Leung, Daniel / Coulongeat, Matthieu / Marlet, Julien / Koning, Rutger / Reyes, Luis Felipe / Chauvineau-Grenier, Angélique / Venet, Fabienne / Monneret, Guillaume / Nussenzweig, Michel C / Arrestier, Romain / Boudhabhay, Idris / Baris-Feldman, Hagit / Hagin, David / Wauters, Joost / Meyts, Isabelle / Dyer, Adam H / Kennelly, Sean P / Bourke, Nollaig M / Halwani, Rabih / Sharif-Askari, Fatemeh Saheb / Dorgham, Karim / Sallette, Jérôme / Sedkaoui, Souad Mehlal / AlKhater, Suzan / Rigo-Bonnin, Raúl / Morandeira, Francisco / Roussel, Lucie / Vinh, Donald C / Erikstrup, Christian / Condino-Neto, Antonio / Prando, Carolina / Bondarenko, Anastasiia / Spaan, András N / Gilardin, Laurent / Fellay, Jacques / Lyonnet, Stanislas / Bilguvar, Kaya / Lifton, Richard P / Mane, Shrikant / Anderson, Mark S / Boisson, Bertrand / Béziat, Vivien / Zhang, Shen-Ying / Andreakos, Evangelos / Hermine, Olivier / Pujol, Aurora / Peterson, Pärt / Mogensen, Trine H / Rowen, Lee / Mond, James / Debette, Stéphanie / de Lamballerie, Xavier / Burdet, Charles / Bouadma, Lila / Zins, Marie / Soler-Palacin, Pere / Colobran, Roger / Gorochov, Guy / Solanich, Xavier / Susen, Sophie / Martinez-Picado, Javier / Raoult, Didier / Vasse, Marc / Gregersen, Peter K / Piemonti, Lorenzo / Rodríguez-Gallego, Carlos / Notarangelo, Luigi D / Su, Helen C / Kisand, Kai / Okada, Satoshi / Puel, Anne / Jouanguy, Emmanuelle / Rice, Charles M / Tiberghien, Pierre / Zhang, Qian / Casanova, Jean-Laurent / Abel, Laurent / Cobat, Aurélie

    Proceedings of the National Academy of Sciences of the United States of America

    2022  Volume 119, Issue 21, Page(s) e2200413119

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
    MeSH term(s) Adult ; Age Factors ; Aged ; Aged, 80 and over ; Antibodies, Neutralizing/blood ; Autoantibodies/blood ; Autoimmunity ; COVID-19/immunology ; COVID-19/mortality ; Female ; Humans ; Interferon Type I/immunology ; Male ; Middle Aged ; Risk ; SARS-CoV-2
    Chemical Substances Antibodies, Neutralizing ; Autoantibodies ; Interferon Type I
    Language English
    Publishing date 2022-05-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2200413119
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Autoantibodies neutralizing type I IFNs are present in

    Bastard, Paul / Gervais, Adrian / Le Voyer, Tom / Rosain, Jérémie / Philippot, Quentin / Manry, Jérémy / Michailidis, Eleftherios / Hoffmann, Hans-Heinrich / Eto, Shohei / Garcia-Prat, Marina / Bizien, Lucy / Parra-Martínez, Alba / Yang, Rui / Haljasmägi, Liis / Migaud, Mélanie / Särekannu, Karita / Maslovskaja, Julia / de Prost, Nicolas / Tandjaoui-Lambiotte, Yacine /
    Luyt, Charles-Edouard / Amador-Borrero, Blanca / Gaudet, Alexandre / Poissy, Julien / Morel, Pascal / Richard, Pascale / Cognasse, Fabrice / Troya, Jesus / Trouillet-Assant, Sophie / Belot, Alexandre / Saker, Kahina / Garçon, Pierre / Rivière, Jacques G / Lagier, Jean-Christophe / Gentile, Stéphanie / Rosen, Lindsey B / Shaw, Elana / Morio, Tomohiro / Tanaka, Junko / Dalmau, David / Tharaux, Pierre-Louis / Sene, Damien / Stepanian, Alain / Megarbane, Bruno / Triantafyllia, Vasiliki / Fekkar, Arnaud / Heath, James R / Franco, José Luis / Anaya, Juan-Manuel / Solé-Violán, Jordi / Imberti, Luisa / Biondi, Andrea / Bonfanti, Paolo / Castagnoli, Riccardo / Delmonte, Ottavia M / Zhang, Yu / Snow, Andrew L / Holland, Steven M / Biggs, Catherine / Moncada-Vélez, Marcela / Arias, Andrés Augusto / Lorenzo, Lazaro / Boucherit, Soraya / Coulibaly, Boubacar / Anglicheau, Dany / Planas, Anna M / Haerynck, Filomeen / Duvlis, Sotirija / Nussbaum, Robert L / Ozcelik, Tayfun / Keles, Sevgi / Bousfiha, Ahmed A / El Bakkouri, Jalila / Ramirez-Santana, Carolina / Paul, Stéphane / Pan-Hammarström, Qiang / Hammarström, Lennart / Dupont, Annabelle / Kurolap, Alina / Metz, Christine N / Aiuti, Alessandro / Casari, Giorgio / Lampasona, Vito / Ciceri, Fabio / Barreiros, Lucila A / Dominguez-Garrido, Elena / Vidigal, Mateus / Zatz, Mayana / van de Beek, Diederik / Sahanic, Sabina / Tancevski, Ivan / Stepanovskyy, Yurii / Boyarchuk, Oksana / Nukui, Yoko / Tsumura, Miyuki / Vidaur, Loreto / Tangye, Stuart G / Burrel, Sonia / Duffy, Darragh / Quintana-Murci, Lluis / Klocperk, Adam / Kann, Nelli Y / Shcherbina, Anna / Lau, Yu-Lung / Leung, Daniel / Coulongeat, Matthieu / Marlet, Julien / Koning, Rutger / Reyes, Luis Felipe / Chauvineau-Grenier, Angélique / Venet, Fabienne / Monneret, Guillaume / Nussenzweig, Michel C / Arrestier, Romain / Boudhabhay, Idris / Baris-Feldman, Hagit / Hagin, David / Wauters, Joost / Meyts, Isabelle / Dyer, Adam H / Kennelly, Sean P / Bourke, Nollaig M / Halwani, Rabih / Sharif-Askari, Narjes Saheb / Dorgham, Karim / Sallette, Jérome / Sedkaoui, Souad Mehlal / AlKhater, Suzan / Rigo-Bonnin, Raúl / Morandeira, Francisco / Roussel, Lucie / Vinh, Donald C / Ostrowski, Sisse Rye / Condino-Neto, Antonio / Prando, Carolina / Bonradenko, Anastasiia / Spaan, András N / Gilardin, Laurent / Fellay, Jacques / Lyonnet, Stanislas / Bilguvar, Kaya / Lifton, Richard P / Mane, Shrikant / Anderson, Mark S / Boisson, Bertrand / Béziat, Vivien / Zhang, Shen-Ying / Vandreakos, Evangelos / Hermine, Olivier / Pujol, Aurora / Peterson, Pärt / Mogensen, Trine H / Rowen, Lee / Mond, James / Debette, Stéphanie / de Lamballerie, Xavier / Duval, Xavier / Mentré, France / Zins, Marie / Soler-Palacin, Pere / Colobran, Roger / Gorochov, Guy / Solanich, Xavier / Susen, Sophie / Martinez-Picado, Javier / Raoult, Didier / Vasse, Marc / Gregersen, Peter K / Piemonti, Lorenzo / Rodríguez-Gallego, Carlos / Notarangelo, Luigi D / Su, Helen C / Kisand, Kai / Okada, Satoshi / Puel, Anne / Jouanguy, Emmanuelle / Rice, Charles M / Tiberghien, Pierre / Zhang, Qian / Cobat, Aurélie / Abel, Laurent / Casanova, Jean-Laurent

    Science immunology

    2019  Volume 6, Issue 62

    Abstract: Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We ... ...

    Abstract Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.
    MeSH term(s) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Neutralizing/blood ; Antibodies, Neutralizing/immunology ; Autoantibodies/blood ; Autoantibodies/immunology ; COVID-19/immunology ; COVID-19/mortality ; Case-Control Studies ; Child ; Child, Preschool ; Critical Illness ; Humans ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Infant ; Infant, Newborn ; Interferon Type I/immunology ; Interferon-alpha/immunology ; Middle Aged ; Young Adult
    Chemical Substances Antibodies, Neutralizing ; Autoantibodies ; Immunoglobulin G ; Interferon Type I ; Interferon-alpha ; interferon omega 1
    Language English
    Publishing date 2019-12-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.abl4340
    Database MEDical Literature Analysis and Retrieval System OnLINE

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