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

Jérémy Manry; Paul Bastard; Adrian Gervais; Tom Le Voyer; Jérémie Rosain; Quentin Philippot; Eleftherios Michailidis; Hans Heinrich Hoffmann; Shohei Eto; Marina Garcia-Prat; Lucy Bizien; Alba Parra-Martínez; Rui Yang; Liis Haljasmägi; Mélanie Migaud; Karita Särekannu; Julia Maslovskaja; Nicolas de Prost; Yacine Tandjaoui-Lambiotte; Charles Edouard Luyt; Blanca Amador-Borrero; Alexandre Gaudet; Julien Poissy; Pascal Morel; Pascale Richard; Fabrice Cognasse; Jesús Troya; Sophie Trouillet-Assant; Alexandre Belot; Kahina Saker; Pierre Garçpn; Jacques G. Rivière; Jean Christophe Lagier; Stéphanie Gentile; Lindsey B. Rosen; Elana Shaw; Tomohiro Morio; Junko Tanaka; David Dalmau; Pierre Louis Tharaux; Damien Sene; Alain Stepanian; Bruno Mégarbane; Vasiliki Triantafyllia; Arnaud Fekkar; James R. Heath; José Luis Franco; Juan Manuel Anaya; Jordi Solé-Violán; Carolina Ramirez-Santana

doi:10.1073/pnas.2200413119

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

Jérémy Manry, Paul Bastard, Adrian Gervais, Tom Le Voyer, Jérémie Rosain, Quentin Philippot, Eleftherios Michailidis, Hans Heinrich Hoffmann, Shohei Eto, Marina Garcia-Prat, Lucy Bizien, Alba Parra-Martínez, Rui Yang, Liis Haljasmägi, Mélanie Migaud, Karita Särekannu, Julia Maslovskaja, Nicolas de Prost, Yacine Tandjaoui-Lambiotte, Charles Edouard LuytBlanca Amador-Borrero, Alexandre Gaudet, Julien Poissy, Pascal Morel, Pascale Richard, Fabrice Cognasse, Jesús Troya, Sophie Trouillet-Assant, Alexandre Belot, Kahina Saker, Pierre Garçpn, Jacques G. Rivière, Jean Christophe Lagier, Stéphanie Gentile, Lindsey B. Rosen, Elana Shaw, Tomohiro Morio, Junko Tanaka, David Dalmau, Pierre Louis Tharaux, Damien Sene, Alain Stepanian, Bruno Mégarbane, Vasiliki Triantafyllia, Arnaud Fekkar, James R. Heath, José Luis Franco, Juan Manuel Anaya, Jordi Solé-Violán, Carolina Ramirez-Santana

Research output: Contribution to journal › Research Article › peer-review

113 Scopus citations

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.

Translated title of the contribution	El riesgo de muerte por COVID-19 es mucho mayor y depende de la edad con autoanticuerpos IFN de tipo I
Original language	English (US)
Article number	e2200413119
Pages (from-to)	1-10
Number of pages	10
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	119
Issue number	21
DOIs	https://doi.org/10.1073/pnas.2200413119
State	Published - May 16 2022

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UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1073/pnas.2200413119

Cite this

Manry, J., Bastard, P., Gervais, A., Le Voyer, T., Rosain, J., Philippot, Q., Michailidis, E., Hoffmann, H. H., Eto, S., Garcia-Prat, M., Bizien, L., Parra-Martínez, A., Yang, R., Haljasmägi, L., Migaud, M., Särekannu, K., Maslovskaja, J., de Prost, N., Tandjaoui-Lambiotte, Y., ... Ramirez-Santana, C. (2022). The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies. Proceedings of the National Academy of Sciences of the United States of America, 119(21), 1-10. Article e2200413119. https://doi.org/10.1073/pnas.2200413119

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title = "The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies",

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.",

author = "J{\'e}r{\'e}my Manry and Paul Bastard and Adrian Gervais and {Le Voyer}, Tom and J{\'e}r{\'e}mie Rosain and Quentin Philippot and Eleftherios Michailidis and Hoffmann, {Hans Heinrich} and Shohei Eto and Marina Garcia-Prat and Lucy Bizien and Alba Parra-Mart{\'i}nez and Rui Yang and Liis Haljasm{\"a}gi and M{\'e}lanie Migaud and Karita S{\"a}rekannu and Julia Maslovskaja and {de Prost}, Nicolas and Yacine Tandjaoui-Lambiotte and Luyt, {Charles Edouard} and Blanca Amador-Borrero and Alexandre Gaudet and Julien Poissy and Pascal Morel and Pascale Richard and Fabrice Cognasse and Jes{\'u}s Troya and Sophie Trouillet-Assant and Alexandre Belot and Kahina Saker and Pierre Gar{\c c}pn and Rivi{\`e}re, {Jacques G.} and Lagier, {Jean Christophe} and St{\'e}phanie Gentile and Rosen, {Lindsey B.} and Elana Shaw and Tomohiro Morio and Junko Tanaka and David Dalmau and Tharaux, {Pierre Louis} and Damien Sene and Alain Stepanian and Bruno M{\'e}garbane and Vasiliki Triantafyllia and Arnaud Fekkar and Heath, {James R.} and Franco, {Jos{\'e} Luis} and Anaya, {Juan Manuel} and Jordi Sol{\'e}-Viol{\'a}n and Carolina Ramirez-Santana",

note = "Publisher Copyright: Copyright {\textcopyright} 2022 the Author(s).",

year = "2022",

month = may,

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doi = "10.1073/pnas.2200413119",

language = "English (US)",

volume = "119",

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journal = "Proceedings of the National Academy of Sciences of the United States of America",

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Manry, J, Bastard, P, Gervais, A, Le Voyer, T, Rosain, J, Philippot, Q, Michailidis, E, Hoffmann, HH, Eto, S, Garcia-Prat, M, Bizien, L, Parra-Martínez, A, Yang, R, Haljasmägi, L, Migaud, M, Särekannu, K, Maslovskaja, J, de Prost, N, Tandjaoui-Lambiotte, Y, Luyt, CE, Amador-Borrero, B, Gaudet, A, Poissy, J, Morel, P, Richard, P, Cognasse, F, Troya, J, Trouillet-Assant, S, Belot, A, Saker, K, Garçpn, P, Rivière, JG, Lagier, JC, Gentile, S, Rosen, LB, Shaw, E, Morio, T, Tanaka, J, Dalmau, D, Tharaux, PL, Sene, D, Stepanian, A, Mégarbane, B, Triantafyllia, V, Fekkar, A, Heath, JR, Franco, JL, Anaya, JM, Solé-Violán, J & Ramirez-Santana, C 2022, 'The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies', Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 21, e2200413119, pp. 1-10. https://doi.org/10.1073/pnas.2200413119

TY - JOUR

T1 - The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

AU - Manry, Jérémy

AU - Bastard, Paul

AU - Gervais, Adrian

AU - Le Voyer, Tom

AU - Rosain, Jérémie

AU - Philippot, Quentin

AU - Michailidis, Eleftherios

AU - Hoffmann, Hans Heinrich

AU - Eto, Shohei

AU - Garcia-Prat, Marina

AU - Bizien, Lucy

AU - Parra-Martínez, Alba

AU - Yang, Rui

AU - Haljasmägi, Liis

AU - Migaud, Mélanie

AU - Särekannu, Karita

AU - Maslovskaja, Julia

AU - de Prost, Nicolas

AU - Tandjaoui-Lambiotte, Yacine

AU - Luyt, Charles Edouard

AU - Amador-Borrero, Blanca

AU - Gaudet, Alexandre

AU - Poissy, Julien

AU - Morel, Pascal

AU - Richard, Pascale

AU - Cognasse, Fabrice

AU - Troya, Jesús

AU - Trouillet-Assant, Sophie

AU - Belot, Alexandre

AU - Saker, Kahina

AU - Garçpn, Pierre

AU - Rivière, Jacques G.

AU - Lagier, Jean Christophe

AU - Gentile, Stéphanie

AU - Rosen, Lindsey B.

AU - Shaw, Elana

AU - Morio, Tomohiro

AU - Tanaka, Junko

AU - Dalmau, David

AU - Tharaux, Pierre Louis

AU - Sene, Damien

AU - Stepanian, Alain

AU - Mégarbane, Bruno

AU - Triantafyllia, Vasiliki

AU - Fekkar, Arnaud

AU - Heath, James R.

AU - Franco, José Luis

AU - Anaya, Juan Manuel

AU - Solé-Violán, Jordi

AU - Ramirez-Santana, Carolina

PY - 2022/5/16

Y1 - 2022/5/16

N2 - 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.

AB - 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.

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U2 - 10.1073/pnas.2200413119

DO - 10.1073/pnas.2200413119

M3 - Research Article

C2 - 35576468

AN - SCOPUS:85131944795

SN - 0027-8424

VL - 119

SP - 1

EP - 10

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

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

IS - 21

M1 - e2200413119

ER -

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

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