Rare Predicted Loss-Of-Function Variants of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19

Rare Predicted Loss-Of-Function Variants of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19 Publisher

Matuozzo D^{1, 2} ; Talouarn E^{1, 2} ; Marchal A^{1, 2} ; Zhang P³ ; Manry J^{1, 2} ; Seeleuthner Y^{1, 2} ; Zhang Y⁴ ; Bolze A⁵ ; Chaldebas M³ ; Milisavljevic B³ ; Gervais A^{1, 2} ; Bastard P^{1, 2, 3, 6} ; Asano T³ ; Bizien L^{1, 2} Show All Authors

Matuozzo D^{1, 2}
Talouarn E^{1, 2}
Marchal A^{1, 2}
Zhang P³
Manry J^{1, 2}
Seeleuthner Y^{1, 2}
Zhang Y⁴
Bolze A⁵
Chaldebas M³
Milisavljevic B³
Gervais A^{1, 2}
Bastard P^{1, 2, 3, 6}
Asano T³
Bizien L^{1, 2}
Barzaghi F⁷
Abolhassani H^{8, 9}
Abou Tayoun A^{10, 11}
Aiuti A^{12, 13}
Alavi Darazam I^{14, 15}
Allende LM¹⁶
Alonsoarias R¹⁷
Arias AA^{3, 19, 20}
Aytekin G²¹
Bergman P^{22, 23}
Bondesan S²⁴
Bryceson YT²⁵
Bustos IG²⁶
Cabreramarante O²⁷
Carcel S²⁸
Carrera P²⁴
Casari G^{29, 30}
Chaibi K^{31, 32}
Colobran R^{33, 34, 35}
Condinoneto A³⁶
Covill LE²⁵
Delmonte OM⁴
El Zein L³⁷
Flores C^{38, 39, 40, 41}
Gregersen PK⁴²
Gut M⁴³
Haerynck F⁴⁴
Halwani R⁴⁵
Hancerli S⁴⁶
Hammarstrom L⁸
Hatipoglu N⁴⁷
Karbuz A⁴⁸
Keles S⁴⁹
Kyheng C⁵⁰
Leonlopez R²⁸
Franco JL⁵¹
Mansouri D^{52, 53, 54}
Martinezpicado J^{55, 57, 58, 59}
Metin Akcan O⁴⁹
Migeotte I⁶⁰
Morange PE^{61, 62}
Morelle G⁵⁰
Martinnalda A^{33, 63, 64}
Novelli G^{65, 66}
Novelli A⁶⁷
Palabiyik F⁴⁷
Panhammarstrom Q⁸
De Diego RP⁶⁹
Planasserra L^{70, 71}
Pleguezuelo DE¹⁶
Prando C⁷²
Pujol A^{58, 70, 71}
Reyes LF²⁶
Riviere JG^{33, 63, 64}
Rodriguezgallego C^{73, 74}
Rojas J⁵¹
Roverequerini P^{13, 75}
Schluter A^{70, 71}
Shahrooei M^{76, 77}
Sobh A⁷⁸
Solerpalacin P^{33, 63, 64}
Tandjaouilambiotte Y⁷⁹
Tipu I⁸⁰
Tresoldi C⁸¹
Troya J⁸²
Van De Beek D⁸³
Zatz M⁸⁴
Zawadzki P^{85, 86}
Almuhsen SZ⁸⁷
Alosaimi MF⁸⁷
Alsohime FM⁸⁷
Barisfeldman H^{88, 89}
Butte MJ⁹⁰
Constantinescu SN^{91, 92, 93, 94}
Cooper MA⁹⁵
Dalgard CL^{96, 97}
Fellay J^{98, 99, 100}
Heath JR¹⁰¹
Lau YL¹⁰²
Lifton RP^{103, 104, 105}
Maniatis T^{106, 107}
Mogensen TH^{108, 109}
Von Bernuth H¹¹⁰
Lermine A¹¹¹
Vidaud M¹¹¹
Boland A¹¹²
Deleuze JF¹¹²
Nussbaum R¹¹³
Kahnkirby A¹¹³
Mentre F¹¹⁴
Tubiana S¹¹⁵
Gorochov G¹¹⁶
Tubach F¹¹⁷
Hausfater P^{118, 119}
Casanova JL^{1, 2, 3, 122}
Ozcelik T⁶⁸
Meyts I¹²⁰
Zhang SY^{1, 2, 3}
Puel A^{1, 2, 3}
Notarangelo LD¹²¹
Boissondupuis S^{1, 2, 3}
Su HC⁴
Boisson B^{1, 2, 3}
Jouanguy E^{1, 2, 3}
Zhang Q^{1, 2, 3}
Abel L^{1, 2, 3}
Cobat A^{1, 2, 3}

Source: Genome Medicine Published:2023

Abstract

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old. © 2023, The Author(s).

Related Docs

View other Related Docs

1. Recessive Inborn Errors of Type I Ifn Immunity in Children With Covid-19 Pneumonia, Journal of Experimental Medicine (2022)

2. Human Genetic and Immunological Determinants of Critical Covid-19 Pneumonia, Nature (2022)

3. Covid-19 Infection in Inborn Errors of Immunity and Their Phenocopies: A Systematic Review and Meta-Analysis, Infectious Diseases (2025)

Experts (# of related papers)

View all Related Experts

Nima Rezaei (6)

Nima Parvaneh (4)

Style	Citing Format
MLA	Matuozzo D, et al.. "Rare Predicted Loss-Of-Function Variants of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19." Genome Medicine, vol. 15, no. 1, 2023, pp. -.
APA	Matuozzo D, Talouarn E, Marchal A, Zhang P, Manry J, Seeleuthner Y, Zhang Y, Bolze A, Chaldebas M, Milisavljevic B, Gervais A, Bastard P, Asano T, Bizien L, Barzaghi F, Abolhassani H, Abou Tayoun A, Aiuti A, Alavi Darazam I, ... Cobat A (2023). Rare Predicted Loss-Of-Function Variants of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19. Genome Medicine, 15(1), -.
Chicago	Matuozzo D, Talouarn E, Marchal A, Zhang P, Manry J, Seeleuthner Y, Zhang Y, et al.. "Rare Predicted Loss-Of-Function Variants of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19." Genome Medicine 15, no. 1 (2023): -.
Harvard	Matuozzo D et al. (2023) 'Rare Predicted Loss-Of-Function Variants of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19', Genome Medicine, 15(1), pp. -.
Vancouver	Matuozzo D, Talouarn E, Marchal A, Zhang P, Manry J, Seeleuthner Y, et al.. Rare Predicted Loss-Of-Function Variants of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19. Genome Medicine. 2023;15(1):-.
BibTex	@article{ author = {Matuozzo D and Talouarn E and Marchal A and Zhang P and Manry J and Seeleuthner Y and Zhang Y and Bolze A and Chaldebas M and Milisavljevic B and Gervais A and Bastard P and Asano T and Bizien L and Barzaghi F and Abolhassani H and Abou Tayoun A and Aiuti A and Alavi Darazam I and Allende LM and Alonsoarias R and Arias AA and Aytekin G and Bergman P and Bondesan S and Bryceson YT and Bustos IG and Cabreramarante O and Carcel S and Carrera P and Casari G and Chaibi K and Colobran R and Condinoneto A and Covill LE and Delmonte OM and El Zein L and Flores C and Gregersen PK and Gut M and Haerynck F and Halwani R and Hancerli S and Hammarstrom L and Hatipoglu N and Karbuz A and Keles S and Kyheng C and Leonlopez R and Franco JL and Mansouri D and Martinezpicado J and Metin Akcan O and Migeotte I and Morange PE and Morelle G and Martinnalda A and Novelli G and Novelli A and Palabiyik F and Panhammarstrom Q and De Diego RP and Planasserra L and Pleguezuelo DE and Prando C and Pujol A and Reyes LF and Riviere JG and Rodriguezgallego C and Rojas J and Roverequerini P and Schluter A and Shahrooei M and Sobh A and Solerpalacin P and Tandjaouilambiotte Y and Tipu I and Tresoldi C and Troya J and Van De Beek D and Zatz M and Zawadzki P and Almuhsen SZ and Alosaimi MF and Alsohime FM and Barisfeldman H and Butte MJ and Constantinescu SN and Cooper MA and Dalgard CL and Fellay J and Heath JR and Lau YL and Lifton RP and Maniatis T and Mogensen TH and Von Bernuth H and Lermine A and Vidaud M and Boland A and Deleuze JF and Nussbaum R and Kahnkirby A and Mentre F and Tubiana S and Gorochov G and Tubach F and Hausfater P and Casanova JL and Ozcelik T and Meyts I and Zhang SY and Puel A and Notarangelo LD and Boissondupuis S and Su HC and Boisson B and Jouanguy E and Zhang Q and Abel L and Cobat A}, title = {Rare Predicted Loss-Of-Function Variants of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19}, journal = {Genome Medicine}, volume = {15}, number = {1}, pages = {-}, year = {2023} }
RIS	TY - JOUR AU - Matuozzo D AU - Talouarn E AU - Marchal A AU - Zhang P AU - Manry J AU - Seeleuthner Y AU - Zhang Y AU - Bolze A AU - Chaldebas M AU - Milisavljevic B AU - Gervais A AU - Bastard P AU - Asano T AU - Bizien L AU - Barzaghi F AU - Abolhassani H AU - Abou Tayoun A AU - Aiuti A AU - Alavi Darazam I AU - Allende LM AU - Alonsoarias R AU - Arias AA AU - Aytekin G AU - Bergman P AU - Bondesan S AU - Bryceson YT AU - Bustos IG AU - Cabreramarante O AU - Carcel S AU - Carrera P AU - Casari G AU - Chaibi K AU - Colobran R AU - Condinoneto A AU - Covill LE AU - Delmonte OM AU - El Zein L AU - Flores C AU - Gregersen PK AU - Gut M AU - Haerynck F AU - Halwani R AU - Hancerli S AU - Hammarstrom L AU - Hatipoglu N AU - Karbuz A AU - Keles S AU - Kyheng C AU - Leonlopez R AU - Franco JL AU - Mansouri D AU - Martinezpicado J AU - Metin Akcan O AU - Migeotte I AU - Morange PE AU - Morelle G AU - Martinnalda A AU - Novelli G AU - Novelli A AU - Palabiyik F AU - Panhammarstrom Q AU - De Diego RP AU - Planasserra L AU - Pleguezuelo DE AU - Prando C AU - Pujol A AU - Reyes LF AU - Riviere JG AU - Rodriguezgallego C AU - Rojas J AU - Roverequerini P AU - Schluter A AU - Shahrooei M AU - Sobh A AU - Solerpalacin P AU - Tandjaouilambiotte Y AU - Tipu I AU - Tresoldi C AU - Troya J AU - Van De Beek D AU - Zatz M AU - Zawadzki P AU - Almuhsen SZ AU - Alosaimi MF AU - Alsohime FM AU - Barisfeldman H AU - Butte MJ AU - Constantinescu SN AU - Cooper MA AU - Dalgard CL AU - Fellay J AU - Heath JR AU - Lau YL AU - Lifton RP AU - Maniatis T AU - Mogensen TH AU - Von Bernuth H AU - Lermine A AU - Vidaud M AU - Boland A AU - Deleuze JF AU - Nussbaum R AU - Kahnkirby A AU - Mentre F AU - Tubiana S AU - Gorochov G AU - Tubach F AU - Hausfater P AU - Casanova JL AU - Ozcelik T AU - Meyts I AU - Zhang SY AU - Puel A AU - Notarangelo LD AU - Boissondupuis S AU - Su HC AU - Boisson B AU - Jouanguy E AU - Zhang Q AU - Abel L AU - Cobat A TI - Rare Predicted Loss-Of-Function Variants of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19 JO - Genome Medicine VL - 15 IS - 1 SP - EP - PY - 2023 ER -

Style

Citing Format

MLA

Matuozzo D, et al.. "Rare Predicted Loss-Of-Function Variants of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19." Genome Medicine, vol. 15, no. 1, 2023, pp. -.

APA

Matuozzo D, Talouarn E, Marchal A, Zhang P, Manry J, Seeleuthner Y, Zhang Y, Bolze A, Chaldebas M, Milisavljevic B, Gervais A, Bastard P, Asano T, Bizien L, Barzaghi F, Abolhassani H, Abou Tayoun A, Aiuti A, Alavi Darazam I, ... Cobat A (2023). Rare Predicted Loss-Of-Function Variants of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19. Genome Medicine, 15(1), -.

Chicago

Matuozzo D, Talouarn E, Marchal A, Zhang P, Manry J, Seeleuthner Y, Zhang Y, et al.. "Rare Predicted Loss-Of-Function Variants of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19." Genome Medicine 15, no. 1 (2023): -.

Harvard

Matuozzo D et al. (2023) 'Rare Predicted Loss-Of-Function Variants of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19', Genome Medicine, 15(1), pp. -.

Vancouver

Matuozzo D, Talouarn E, Marchal A, Zhang P, Manry J, Seeleuthner Y, et al.. Rare Predicted Loss-Of-Function Variants of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19. Genome Medicine. 2023;15(1):-.

BibTex

@article{ author = {Matuozzo D and Talouarn E and Marchal A and Zhang P and Manry J and Seeleuthner Y and Zhang Y and Bolze A and Chaldebas M and Milisavljevic B and Gervais A and Bastard P and Asano T and Bizien L and Barzaghi F and Abolhassani H and Abou Tayoun A and Aiuti A and Alavi Darazam I and Allende LM and Alonsoarias R and Arias AA and Aytekin G and Bergman P and Bondesan S and Bryceson YT and Bustos IG and Cabreramarante O and Carcel S and Carrera P and Casari G and Chaibi K and Colobran R and Condinoneto A and Covill LE and Delmonte OM and El Zein L and Flores C and Gregersen PK and Gut M and Haerynck F and Halwani R and Hancerli S and Hammarstrom L and Hatipoglu N and Karbuz A and Keles S and Kyheng C and Leonlopez R and Franco JL and Mansouri D and Martinezpicado J and Metin Akcan O and Migeotte I and Morange PE and Morelle G and Martinnalda A and Novelli G and Novelli A and Palabiyik F and Panhammarstrom Q and De Diego RP and Planasserra L and Pleguezuelo DE and Prando C and Pujol A and Reyes LF and Riviere JG and Rodriguezgallego C and Rojas J and Roverequerini P and Schluter A and Shahrooei M and Sobh A and Solerpalacin P and Tandjaouilambiotte Y and Tipu I and Tresoldi C and Troya J and Van De Beek D and Zatz M and Zawadzki P and Almuhsen SZ and Alosaimi MF and Alsohime FM and Barisfeldman H and Butte MJ and Constantinescu SN and Cooper MA and Dalgard CL and Fellay J and Heath JR and Lau YL and Lifton RP and Maniatis T and Mogensen TH and Von Bernuth H and Lermine A and Vidaud M and Boland A and Deleuze JF and Nussbaum R and Kahnkirby A and Mentre F and Tubiana S and Gorochov G and Tubach F and Hausfater P and Casanova JL and Ozcelik T and Meyts I and Zhang SY and Puel A and Notarangelo LD and Boissondupuis S and Su HC and Boisson B and Jouanguy E and Zhang Q and Abel L and Cobat A}, title = {Rare Predicted Loss-Of-Function Variants of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19}, journal = {Genome Medicine}, volume = {15}, number = {1}, pages = {-}, year = {2023} }

RIS

TY - JOUR
AU - Matuozzo D
AU - Talouarn E
AU - Marchal A
AU - Zhang P
AU - Manry J
AU - Seeleuthner Y
AU - Zhang Y
AU - Bolze A
AU - Chaldebas M
AU - Milisavljevic B
AU - Gervais A
AU - Bastard P
AU - Asano T
AU - Bizien L
AU - Barzaghi F
AU - Abolhassani H
AU - Abou Tayoun A
AU - Aiuti A
AU - Alavi Darazam I
AU - Allende LM
AU - Alonsoarias R
AU - Arias AA
AU - Aytekin G
AU - Bergman P
AU - Bondesan S
AU - Bryceson YT
AU - Bustos IG
AU - Cabreramarante O
AU - Carcel S
AU - Carrera P
AU - Casari G
AU - Chaibi K
AU - Colobran R
AU - Condinoneto A
AU - Covill LE
AU - Delmonte OM
AU - El Zein L
AU - Flores C
AU - Gregersen PK
AU - Gut M
AU - Haerynck F
AU - Halwani R
AU - Hancerli S
AU - Hammarstrom L
AU - Hatipoglu N
AU - Karbuz A
AU - Keles S
AU - Kyheng C
AU - Leonlopez R
AU - Franco JL
AU - Mansouri D
AU - Martinezpicado J
AU - Metin Akcan O
AU - Migeotte I
AU - Morange PE
AU - Morelle G
AU - Martinnalda A
AU - Novelli G
AU - Novelli A
AU - Palabiyik F
AU - Panhammarstrom Q
AU - De Diego RP
AU - Planasserra L
AU - Pleguezuelo DE
AU - Prando C
AU - Pujol A
AU - Reyes LF
AU - Riviere JG
AU - Rodriguezgallego C
AU - Rojas J
AU - Roverequerini P
AU - Schluter A
AU - Shahrooei M
AU - Sobh A
AU - Solerpalacin P
AU - Tandjaouilambiotte Y
AU - Tipu I
AU - Tresoldi C
AU - Troya J
AU - Van De Beek D
AU - Zatz M
AU - Zawadzki P
AU - Almuhsen SZ
AU - Alosaimi MF
AU - Alsohime FM
AU - Barisfeldman H
AU - Butte MJ
AU - Constantinescu SN
AU - Cooper MA
AU - Dalgard CL
AU - Fellay J
AU - Heath JR
AU - Lau YL
AU - Lifton RP
AU - Maniatis T
AU - Mogensen TH
AU - Von Bernuth H
AU - Lermine A
AU - Vidaud M
AU - Boland A
AU - Deleuze JF
AU - Nussbaum R
AU - Kahnkirby A
AU - Mentre F
AU - Tubiana S
AU - Gorochov G
AU - Tubach F
AU - Hausfater P
AU - Casanova JL
AU - Ozcelik T
AU - Meyts I
AU - Zhang SY
AU - Puel A
AU - Notarangelo LD
AU - Boissondupuis S
AU - Su HC
AU - Boisson B
AU - Jouanguy E
AU - Zhang Q
AU - Abel L
AU - Cobat A
TI - Rare Predicted Loss-Of-Function Variants of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19
JO - Genome Medicine
VL - 15
IS - 1
SP -
EP -
PY - 2023
ER -

Science Communicator Platform

Authors

Abstract