Association of toll-like receptor 7 variants with life-threatening COVID-19 disease in males: Findings from a nested case-control study

Chiara Fallerini; Sergio Daga; Stefania Mantovani; Susanna Mantovani; Elisa Benetti; Nicola Picchiotti; Daniela Francisci; Francesco Paciosi; Elisabetta Schiaroli; Margherita Baldassarri; Francesca Fava; Maria Palmieri; Marco Palmieri; Serena Ludovisi; Francesco Castelli; Eugenia Quiros-Roldan; Massimo Vaghi; Stefano Rusconi; Matteo Siano; Maria Bandini; Ottavia Spiga; Katia Capitani; Simone Furini; Francesca Mari; Alessandra Renieri; Mario U. Mondelli; Elisa Frullanti; Floriana Valentino; Francesca Valentino; Gabriella Doddato; Annarita Giliberti; Rossella Tita; Sara Amitrano; Mirella Bruttini; Susanna Croci; Ilaria Meloni; Maria Antonietta Mencarelli; Marta Mencarelli; Caterina Lo Rizzo; Anna Maria Pinto; Laura Di Sarno; Giada Beligni; Andrea Tommasi; Nicola Iuso; Francesca Montagnani; Massimiliano Fabbiani; Barbara Rossetti; Giacomo Zanelli; Elena Bargagli; Laura Bergantini; Miriana D’Alessandro; Michele D'Alessandro; Paolo Cameli; David Bennett; Federico Anedda; Simona Marcantonio; Sabino Scolletta; Federico Franchi; Francesca Franchi; Maria Antonietta Mazzei; Susanna Guerrini; Edoardo Conticini; Luca Cantarini; Bruno Frediani; Danilo Tacconi; Chiara Spertilli; Marco Feri; Alice Donati; Andrea Donati; Raffaele Scala; Luca Guidelli; Genni Spargi; Marta Corridi; Cesira Nencioni; Leonardo Croci; Gian Piero Caldarelli; Maurizio Spagnesi; Davide Romani; Paolo Piacentini; Elena Desanctis; Silvia Cappelli; Anna Canaccini; Agnese Verzuri; Valentina Anemoli; Agostino Ognibene; Antonella D’Arminio Monforte; Federica Gaia Miraglia; Massimo Girardis; Sophie Venturelli; Stefano Busani; Andrea Cossarizza; Armando Antinori; Alessandra Vergori; Arianna Emiliozzi; Arianna Gabrieli; Agostino Riva; Pier Giorgio Scotton; Francesca Andretta; Sandro Panese; Renzo Scaggiante; Francesca Gatti; Saverio Giuseppe Parisi; Stefano Baratti; Melania Degli Antoni; Matteo Della Monica; Carmelo Piscopo; Mario Capasso; Monica Capasso; Roberta Russo; Immacolata Andolfo; Achille Iolascon; Giuseppe Fiorentino; Massimo Carella; Marco Castori; Giuseppe Merla; Gabriella Maria Squeo; Filippo Aucella; Pamela Raggi; Carmen Marciano; Rita Perna; Raffaella Perna; Matteo Bassetti; Antonio Di Biagio; Maurizio Sanguinetti; Luca Masucci; Serafina Valente; Marco Mandalà; Alessia Giorli; Lorenzo Salerni; Patrizia Zucchi; Pierpaolo Parravicini; Elisabetta Menatti; Tullio Trotta; Ferdinando Giannattasio; Gabriella Coiro; Fabio Lena; Francesco Lena; Domenico A. Coviello; Cristina Mussini; Giancarlo Bosio; Giacomo Bosio; Enrico Martinelli; Sandro Mancarella; Luisa Tavecchia; Marco Gori; Mario Gori; Lia Crotti; Gianfranco Parati; Chiara Gabbi; Isabella Zanella; Marco Rizzi; Franco Maggiolo; Diego Ripamonti; Tiziana Bachetti; Maria Teresa La Rovere; Simona Sarzi-Braga; Maurizio Bussotti; Mario Chiariello; Mary Ann Belli; Simona Dei

doi:10.7554/eLife.67569

Association of toll-like receptor 7 variants with life-threatening COVID-19 disease in males: Findings from a nested case-control study

Chiara Fallerini, Sergio Daga, Stefania Mantovani, Susanna Mantovani, Elisa Benetti, Nicola Picchiotti, Daniela Francisci, Francesco Paciosi, Elisabetta Schiaroli, Margherita Baldassarri, Francesca Fava, Maria Palmieri, Marco Palmieri, Serena Ludovisi, Francesco Castelli, Eugenia Quiros-Roldan, Massimo Vaghi, Stefano Rusconi, Matteo Siano, Maria BandiniOttavia Spiga, Katia Capitani, Simone Furini, Francesca Mari, Alessandra Renieri, Mario U. Mondelli, Elisa Frullanti, Floriana Valentino, Francesca Valentino, Gabriella Doddato, Annarita Giliberti, Rossella Tita, Sara Amitrano, Mirella Bruttini, Susanna Croci, Ilaria Meloni, Maria Antonietta Mencarelli, Marta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Laura Di Sarno, Giada Beligni, Andrea Tommasi, Nicola Iuso, Francesca Montagnani, Massimiliano Fabbiani, Barbara Rossetti, Giacomo Zanelli, Elena Bargagli, Laura Bergantini, Miriana D’Alessandro, Michele D'Alessandro, Paolo Cameli, David Bennett, Federico Anedda, Simona Marcantonio, Sabino Scolletta, Federico Franchi, Francesca Franchi, Maria Antonietta Mazzei, Susanna Guerrini, Edoardo Conticini, Luca Cantarini, Bruno Frediani, Danilo Tacconi, Chiara Spertilli, Marco Feri, Alice Donati, Andrea Donati, Raffaele Scala, Luca Guidelli, Genni Spargi, Marta Corridi, Cesira Nencioni, Leonardo Croci, Gian Piero Caldarelli, Maurizio Spagnesi, Davide Romani, Paolo Piacentini, Elena Desanctis, Silvia Cappelli, Anna Canaccini, Agnese Verzuri, Valentina Anemoli, Agostino Ognibene, Antonella D’Arminio Monforte, Federica Gaia Miraglia, Massimo Girardis, Sophie Venturelli, Stefano Busani, Andrea Cossarizza, Armando Antinori, Alessandra Vergori, Arianna Emiliozzi, Arianna Gabrieli, Agostino Riva, Pier Giorgio Scotton, Francesca Andretta, Sandro Panese, Renzo Scaggiante, Francesca Gatti, Saverio Giuseppe Parisi, Stefano Baratti, Melania Degli Antoni, Matteo Della Monica, Carmelo Piscopo, Mario Capasso, Monica Capasso, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Giuseppe Fiorentino, Massimo Carella, Marco Castori, Giuseppe Merla, Gabriella Maria Squeo, Filippo Aucella, Pamela Raggi, Carmen Marciano, Rita Perna, Raffaella Perna, Matteo Bassetti, Antonio Di Biagio, Maurizio Sanguinetti, Luca Masucci, Serafina Valente, Marco Mandalà, Alessia Giorli, Lorenzo Salerni, Patrizia Zucchi, Pierpaolo Parravicini, Elisabetta Menatti, Tullio Trotta, Ferdinando Giannattasio, Gabriella Coiro, Fabio Lena, Francesco Lena, Domenico A. Coviello, Cristina Mussini, Giancarlo Bosio, Giacomo Bosio, Enrico Martinelli, Sandro Mancarella, Luisa Tavecchia, Marco Gori, Mario Gori, Lia Crotti, Gianfranco Parati, Chiara Gabbi, Isabella Zanella, Marco Rizzi, Franco Maggiolo, Diego Ripamonti, Tiziana Bachetti, Maria Teresa La Rovere, Simona Sarzi-Braga, Maurizio Bussotti, Mario Chiariello, Mary Ann Belli, Simona Dei

Research output: Contribution to journal › Article

Abstract

Background: Recently, loss-of-function variants in TLR7 were identified in two families in which COVID-19 segregates like an X-linked recessive disorder environmentally conditioned by SARS-CoV-2. We investigated whether the two families represent the tip of the iceberg of a subset of COVID-19 male patients. Methods: This is a nested case-control study in which we compared male participants with extreme phenotype selected from the Italian GEN-COVID cohort of SARS-CoV-2-infected participants (<60 y, 79 severe cases versus 77 control cases). We applied the LASSO Logistic Regression analysis, considering only rare variants on young male subsets with extreme phenotype, picking up TLR7 as the most important susceptibility gene.

Original language	English
Pages (from-to)	N/A-N/A
Journal	eLife
Volume	10
DOIs	https://doi.org/10.7554/eLife.67569
Publication status	Published - 2021

Keywords

COVID

Access to Document

10.7554/eLife.67569

Cite this

Fallerini, C., Daga, S., Mantovani, S., Mantovani, S., Benetti, E., Picchiotti, N., Francisci, D., Paciosi, F., Schiaroli, E., Baldassarri, M., Fava, F., Palmieri, M., Palmieri, M., Ludovisi, S., Castelli, F., Quiros-Roldan, E., Vaghi, M., Rusconi, S., Siano, M., ... Dei, S. (2021). Association of toll-like receptor 7 variants with life-threatening COVID-19 disease in males: Findings from a nested case-control study. eLife, 10, N/A-N/A. https://doi.org/10.7554/eLife.67569

@article{2cfaa3c1fe8849d09010677203acae21,

title = "Association of toll-like receptor 7 variants with life-threatening COVID-19 disease in males: Findings from a nested case-control study",

abstract = "Background: Recently, loss-of-function variants in TLR7 were identified in two families in which COVID-19 segregates like an X-linked recessive disorder environmentally conditioned by SARS-CoV-2. We investigated whether the two families represent the tip of the iceberg of a subset of COVID-19 male patients. Methods: This is a nested case-control study in which we compared male participants with extreme phenotype selected from the Italian GEN-COVID cohort of SARS-CoV-2-infected participants (<60 y, 79 severe cases versus 77 control cases). We applied the LASSO Logistic Regression analysis, considering only rare variants on young male subsets with extreme phenotype, picking up TLR7 as the most important susceptibility gene.",

keywords = "COVID, COVID",

author = "Chiara Fallerini and Sergio Daga and Stefania Mantovani and Susanna Mantovani and Elisa Benetti and Nicola Picchiotti and Daniela Francisci and Francesco Paciosi and Elisabetta Schiaroli and Margherita Baldassarri and Francesca Fava and Maria Palmieri and Marco Palmieri and Serena Ludovisi and Francesco Castelli and Eugenia Quiros-Roldan and Massimo Vaghi and Stefano Rusconi and Matteo Siano and Maria Bandini and Ottavia Spiga and Katia Capitani and Simone Furini and Francesca Mari and Alessandra Renieri and Mondelli, {Mario U.} and Elisa Frullanti and Floriana Valentino and Francesca Valentino and Gabriella Doddato and Annarita Giliberti and Rossella Tita and Sara Amitrano and Mirella Bruttini and Susanna Croci and Ilaria Meloni and Mencarelli, {Maria Antonietta} and Marta Mencarelli and Rizzo, {Caterina Lo} and Pinto, {Anna Maria} and Sarno, {Laura Di} and Giada Beligni and Andrea Tommasi and Nicola Iuso and Francesca Montagnani and Massimiliano Fabbiani and Barbara Rossetti and Giacomo Zanelli and Elena Bargagli and Laura Bergantini and Miriana D{\textquoteright}Alessandro and Michele D'Alessandro and Paolo Cameli and David Bennett and Federico Anedda and Simona Marcantonio and Sabino Scolletta and Federico Franchi and Francesca Franchi and Mazzei, {Maria Antonietta} and Susanna Guerrini and Edoardo Conticini and Luca Cantarini and Bruno Frediani and Danilo Tacconi and Chiara Spertilli and Marco Feri and Alice Donati and Andrea Donati and Raffaele Scala and Luca Guidelli and Genni Spargi and Marta Corridi and Cesira Nencioni and Leonardo Croci and Caldarelli, {Gian Piero} and Maurizio Spagnesi and Davide Romani and Paolo Piacentini and Elena Desanctis and Silvia Cappelli and Anna Canaccini and Agnese Verzuri and Valentina Anemoli and Agostino Ognibene and {D{\textquoteright}Arminio Monforte}, Antonella and Miraglia, {Federica Gaia} and Massimo Girardis and Sophie Venturelli and Stefano Busani and Andrea Cossarizza and Armando Antinori and Alessandra Vergori and Arianna Emiliozzi and Arianna Gabrieli and Agostino Riva and Scotton, {Pier Giorgio} and Francesca Andretta and Sandro Panese and Renzo Scaggiante and Francesca Gatti and Parisi, {Saverio Giuseppe} and Stefano Baratti and Antoni, {Melania Degli} and Monica, {Matteo Della} and Carmelo Piscopo and Mario Capasso and Monica Capasso and Roberta Russo and Immacolata Andolfo and Achille Iolascon and Giuseppe Fiorentino and Massimo Carella and Marco Castori and Giuseppe Merla and Squeo, {Gabriella Maria} and Filippo Aucella and Pamela Raggi and Carmen Marciano and Rita Perna and Raffaella Perna and Matteo Bassetti and Biagio, {Antonio Di} and Maurizio Sanguinetti and Luca Masucci and Serafina Valente and Marco Mandal{\`a} and Alessia Giorli and Lorenzo Salerni and Patrizia Zucchi and Pierpaolo Parravicini and Elisabetta Menatti and Tullio Trotta and Ferdinando Giannattasio and Gabriella Coiro and Fabio Lena and Francesco Lena and Coviello, {Domenico A.} and Cristina Mussini and Giancarlo Bosio and Giacomo Bosio and Enrico Martinelli and Sandro Mancarella and Luisa Tavecchia and Marco Gori and Mario Gori and Lia Crotti and Gianfranco Parati and Chiara Gabbi and Isabella Zanella and Marco Rizzi and Franco Maggiolo and Diego Ripamonti and Tiziana Bachetti and Rovere, {Maria Teresa La} and Simona Sarzi-Braga and Maurizio Bussotti and Mario Chiariello and Belli, {Mary Ann} and Simona Dei",

year = "2021",

doi = "10.7554/eLife.67569",

language = "English",

volume = "10",

pages = "N/A--N/A",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications Ltd",

}

Fallerini, C, Daga, S, Mantovani, S, Mantovani, S, Benetti, E, Picchiotti, N, Francisci, D, Paciosi, F, Schiaroli, E, Baldassarri, M, Fava, F, Palmieri, M, Palmieri, M, Ludovisi, S, Castelli, F, Quiros-Roldan, E, Vaghi, M, Rusconi, S, Siano, M, Bandini, M, Spiga, O, Capitani, K, Furini, S, Mari, F, Renieri, A, Mondelli, MU, Frullanti, E, Valentino, F, Valentino, F, Doddato, G, Giliberti, A, Tita, R, Amitrano, S, Bruttini, M, Croci, S, Meloni, I, Mencarelli, MA, Mencarelli, M, Rizzo, CL, Pinto, AM, Sarno, LD, Beligni, G, Tommasi, A, Iuso, N, Montagnani, F, Fabbiani, M, Rossetti, B, Zanelli, G, Bargagli, E, Bergantini, L, D’Alessandro, M, D'Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Franchi, F, Franchi, F, Mazzei, MA, Guerrini, S, Conticini, E, Cantarini, L, Frediani, B, Tacconi, D, Spertilli, C, Feri, M, Donati, A, Donati, A, Scala, R, Guidelli, L, Spargi, G, Corridi, M, Nencioni, C, Croci, L, Caldarelli, GP, Spagnesi, M, Romani, D, Piacentini, P, Desanctis, E, Cappelli, S, Canaccini, A, Verzuri, A, Anemoli, V, Ognibene, A, D’Arminio Monforte, A, Miraglia, FG, Girardis, M, Venturelli, S, Busani, S, Cossarizza, A, Antinori, A, Vergori, A, Emiliozzi, A, Gabrieli, A, Riva, A, Scotton, PG, Andretta, F, Panese, S, Scaggiante, R, Gatti, F, Parisi, SG, Baratti, S, Antoni, MD, Monica, MD, Piscopo, C, Capasso, M, Capasso, M, Russo, R, Andolfo, I, Iolascon, A, Fiorentino, G, Carella, M, Castori, M, Merla, G, Squeo, GM, Aucella, F, Raggi, P, Marciano, C, Perna, R, Perna, R, Bassetti, M, Biagio, AD, Sanguinetti, M , Masucci, L, Valente, S, Mandalà, M, Giorli, A, Salerni, L, Zucchi, P, Parravicini, P, Menatti, E, Trotta, T, Giannattasio, F, Coiro, G, Lena, F, Lena, F, Coviello, DA, Mussini, C, Bosio, G, Bosio, G, Martinelli, E, Mancarella, S, Tavecchia, L, Gori, M, Gori, M, Crotti, L, Parati, G, Gabbi, C, Zanella, I, Rizzi, M, Maggiolo, F, Ripamonti, D, Bachetti, T, Rovere, MTL, Sarzi-Braga, S, Bussotti, M, Chiariello, M, Belli, MA & Dei, S 2021, 'Association of toll-like receptor 7 variants with life-threatening COVID-19 disease in males: Findings from a nested case-control study', eLife, vol. 10, pp. N/A-N/A. https://doi.org/10.7554/eLife.67569

TY - JOUR

T1 - Association of toll-like receptor 7 variants with life-threatening COVID-19 disease in males: Findings from a nested case-control study

AU - Fallerini, Chiara

AU - Daga, Sergio

AU - Mantovani, Stefania

AU - Mantovani, Susanna

AU - Benetti, Elisa

AU - Picchiotti, Nicola

AU - Francisci, Daniela

AU - Paciosi, Francesco

AU - Schiaroli, Elisabetta

AU - Baldassarri, Margherita

AU - Fava, Francesca

AU - Palmieri, Maria

AU - Palmieri, Marco

AU - Ludovisi, Serena

AU - Castelli, Francesco

AU - Quiros-Roldan, Eugenia

AU - Vaghi, Massimo

AU - Rusconi, Stefano

AU - Siano, Matteo

AU - Bandini, Maria

AU - Spiga, Ottavia

AU - Capitani, Katia

AU - Furini, Simone

AU - Mari, Francesca

AU - Renieri, Alessandra

AU - Mondelli, Mario U.

AU - Frullanti, Elisa

AU - Valentino, Floriana

AU - Valentino, Francesca

AU - Doddato, Gabriella

AU - Giliberti, Annarita

AU - Tita, Rossella

AU - Amitrano, Sara

AU - Bruttini, Mirella

AU - Croci, Susanna

AU - Meloni, Ilaria

AU - Mencarelli, Maria Antonietta

AU - Mencarelli, Marta

AU - Rizzo, Caterina Lo

AU - Pinto, Anna Maria

AU - Sarno, Laura Di

AU - Beligni, Giada

AU - Tommasi, Andrea

AU - Iuso, Nicola

AU - Montagnani, Francesca

AU - Fabbiani, Massimiliano

AU - Rossetti, Barbara

AU - Zanelli, Giacomo

AU - Bargagli, Elena

AU - Bergantini, Laura

AU - D’Alessandro, Miriana

AU - D'Alessandro, Michele

AU - Cameli, Paolo

AU - Bennett, David

AU - Anedda, Federico

AU - Marcantonio, Simona

AU - Scolletta, Sabino

AU - Franchi, Federico

AU - Franchi, Francesca

AU - Mazzei, Maria Antonietta

AU - Guerrini, Susanna

AU - Conticini, Edoardo

AU - Cantarini, Luca

AU - Frediani, Bruno

AU - Tacconi, Danilo

AU - Spertilli, Chiara

AU - Feri, Marco

AU - Donati, Alice

AU - Donati, Andrea

AU - Scala, Raffaele

AU - Guidelli, Luca

AU - Spargi, Genni

AU - Corridi, Marta

AU - Nencioni, Cesira

AU - Croci, Leonardo

AU - Caldarelli, Gian Piero

AU - Spagnesi, Maurizio

AU - Romani, Davide

AU - Piacentini, Paolo

AU - Desanctis, Elena

AU - Cappelli, Silvia

AU - Canaccini, Anna

AU - Verzuri, Agnese

AU - Anemoli, Valentina

AU - Ognibene, Agostino

AU - D’Arminio Monforte, Antonella

AU - Miraglia, Federica Gaia

AU - Girardis, Massimo

AU - Venturelli, Sophie

AU - Busani, Stefano

AU - Cossarizza, Andrea

AU - Antinori, Armando

AU - Vergori, Alessandra

AU - Emiliozzi, Arianna

AU - Gabrieli, Arianna

AU - Riva, Agostino

AU - Scotton, Pier Giorgio

AU - Andretta, Francesca

AU - Panese, Sandro

AU - Scaggiante, Renzo

AU - Gatti, Francesca

AU - Parisi, Saverio Giuseppe

AU - Baratti, Stefano

AU - Antoni, Melania Degli

AU - Monica, Matteo Della

AU - Piscopo, Carmelo

AU - Capasso, Mario

AU - Capasso, Monica

AU - Russo, Roberta

AU - Andolfo, Immacolata

AU - Iolascon, Achille

AU - Fiorentino, Giuseppe

AU - Carella, Massimo

AU - Castori, Marco

AU - Merla, Giuseppe

AU - Squeo, Gabriella Maria

AU - Aucella, Filippo

AU - Raggi, Pamela

AU - Marciano, Carmen

AU - Perna, Rita

AU - Perna, Raffaella

AU - Bassetti, Matteo

AU - Biagio, Antonio Di

AU - Sanguinetti, Maurizio

AU - Masucci, Luca

AU - Valente, Serafina

AU - Mandalà, Marco

AU - Giorli, Alessia

AU - Salerni, Lorenzo

AU - Zucchi, Patrizia

AU - Parravicini, Pierpaolo

AU - Menatti, Elisabetta

AU - Trotta, Tullio

AU - Giannattasio, Ferdinando

AU - Coiro, Gabriella

AU - Lena, Fabio

AU - Lena, Francesco

AU - Coviello, Domenico A.

AU - Mussini, Cristina

AU - Bosio, Giancarlo

AU - Bosio, Giacomo

AU - Martinelli, Enrico

AU - Mancarella, Sandro

AU - Tavecchia, Luisa

AU - Gori, Marco

AU - Gori, Mario

AU - Crotti, Lia

AU - Parati, Gianfranco

AU - Gabbi, Chiara

AU - Zanella, Isabella

AU - Rizzi, Marco

AU - Maggiolo, Franco

AU - Ripamonti, Diego

AU - Bachetti, Tiziana

AU - Rovere, Maria Teresa La

AU - Sarzi-Braga, Simona

AU - Bussotti, Maurizio

AU - Chiariello, Mario

AU - Belli, Mary Ann

AU - Dei, Simona

PY - 2021

Y1 - 2021

N2 - Background: Recently, loss-of-function variants in TLR7 were identified in two families in which COVID-19 segregates like an X-linked recessive disorder environmentally conditioned by SARS-CoV-2. We investigated whether the two families represent the tip of the iceberg of a subset of COVID-19 male patients. Methods: This is a nested case-control study in which we compared male participants with extreme phenotype selected from the Italian GEN-COVID cohort of SARS-CoV-2-infected participants (<60 y, 79 severe cases versus 77 control cases). We applied the LASSO Logistic Regression analysis, considering only rare variants on young male subsets with extreme phenotype, picking up TLR7 as the most important susceptibility gene.

AB - Background: Recently, loss-of-function variants in TLR7 were identified in two families in which COVID-19 segregates like an X-linked recessive disorder environmentally conditioned by SARS-CoV-2. We investigated whether the two families represent the tip of the iceberg of a subset of COVID-19 male patients. Methods: This is a nested case-control study in which we compared male participants with extreme phenotype selected from the Italian GEN-COVID cohort of SARS-CoV-2-infected participants (<60 y, 79 severe cases versus 77 control cases). We applied the LASSO Logistic Regression analysis, considering only rare variants on young male subsets with extreme phenotype, picking up TLR7 as the most important susceptibility gene.

KW - COVID

UR - http://hdl.handle.net/10807/231810

U2 - 10.7554/eLife.67569

DO - 10.7554/eLife.67569

M3 - Article

SN - 2050-084X

VL - 10

SP - N/A-N/A

JO - eLife

JF - eLife

ER -

Association of toll-like receptor 7 variants with life-threatening COVID-19 disease in males: Findings from a nested case-control study

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this