Protective role of a tmprss2 variant on severe covid-19 outcome in young males and elderly women

Maria Monticelli; Bruno Hay Mele; Elisa Benetti; Chiara Fallerini; Margherita Baldassarri; Simone Furini; Elisa Frullanti; Francesca Mari; Giuseppina Andreotti; Maria Vittoria Cubellis; Alessandra Renieri; Sergio Daga; Francesca Fava; Floriana Valentino; Gabriella Doddato; Annarita Giliberti; Rossella Tita; Sara Amitrano; Mirella Bruttini; Susanna Croci; Ilaria Meloni; Anna Maria Pinto; Maria Antonietta Mencarelli; Caterina Lo Rizzo; Francesca Montagnani; Laura Di Sarno; Andrea Tommasi; Maria Palmieri; Miriam Lucia Carriero; Diana Alaverdian; Giada Beligni; Nicola Iuso; Gabriele Inchingolo; Massimiliano Fabbiani; Barbara Rossetti; Giacomo Zanelli; Elena Bargagli; Laura Bergantini; Miriana D’Alessandro; Paolo Cameli; David Bennet; Federico Anedda; Simona Marcantonio; Sabino Scolletta; Federico Franchi; Maria Antonietta Mazzei; Susanna Guerrini; Edoardo Conticini; Luca Cantarini; Bruno Frediani; Danilo Tacconi; Chiara Spertilli; Marco Feri; Alice Donati; Raffaele Scala; Luca Guidelli; Genni Spargi; Marta Corridi; Cesira Nencioni; Leonardo Croci; Gian Piero Caldarelli; Maurizio Spagnesi; Paolo Piacentini; Maria Bandini; Elena Desanctis; Silvia Cappelli; Anna Canaccini; Agnese Verzuri; Valentina Anemoli; Agostino Ognibene; Alessandro Pancrazi; Maria Lorusso; Massimo Vaghi; Antonella D’Arminio Monforte; Esther Merlini; Federica Gaia Miraglia; Mario U. Mondelli; Raffaele Bruno; Vecchia Marco; Stefania Mantovani; Serena Ludovisi; Massimo Girardi; Sophie Venturelli; Marco Sita; Andrea Cossarizza; Andrea Antinori; Alessandra Vergori; Arianna Emiliozzi; Stefano Rusconi; Matteo Siano; Arianna Gabrieli; Agostino Riva; Daniela Francisci; Elisabetta Schiarol; Francesco Paciosi; Pier Giorgio Scotton; Francesca Andretta; Sandro Panese; Renzo Scaggiante; Francesca Gatti; Saverio Giuseppe Parisi; Francesco Castelli; Eugenia Quiros-Roldan; Melania Degli Antoni; Isabella Zanella; Matteo Della Monica; Carmelo Piscopo; Mario 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; Matteo Bassetti; Antonio Di Biagio; Maurizio Sanguinetti; Luca Masucci; Serafina Valente; Marco Mandalà; Alessia Giorli; Lorenzo Salerni; Patrizia Zucchi; Pierpaolo Parravicini; Elisabetta Menatti; Stefano Baratti; Tullio Trotta; Ferdinando Giannattasio; Gabriella Coiro; Fabio Lena; Domenico A. Coviello; Cristina Mussini; Giancarlo Bosio; Enrico Martinelli; Sandro Mancarella; Luisa Tavecchia; Lia Crotti; Gian-Franco Parati; Nicola Picchiotti; Marco Gori; Chiara Gabbi; Maurizio Sanarico; Stefano Ceri; Pietro Pinoli; Francesco Raimondi; Filippo Bis-Carini; Alessandra Stella; Marco Rizzi; Franco Maggiolo; Diego Ripamonti; Claudia Suardi; Tiziana Bachetti; Maria Teresa La Rovere; Simona Sarzi-Braga; Maurizio Bussotti; Mattia Bergomi; Katia Capitani; Kristina Zguro; Simona Dei

doi:10.3390/genes12040596

Protective role of a tmprss2 variant on severe covid-19 outcome in young males and elderly women

Maria Monticelli, Bruno Hay Mele, Elisa Benetti, Chiara Fallerini, Margherita Baldassarri, Simone Furini, Elisa Frullanti, Francesca Mari, Giuseppina Andreotti, Maria Vittoria Cubellis, Alessandra Renieri, Sergio Daga, Francesca Fava, Floriana Valentino, Gabriella Doddato, Annarita Giliberti, Rossella Tita, Sara Amitrano, Mirella Bruttini, Susanna CrociIlaria Meloni, Anna Maria Pinto, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Francesca Montagnani, Laura Di Sarno, Andrea Tommasi, Maria Palmieri, Miriam Lucia Carriero, Diana Alaverdian, Giada Beligni, Nicola Iuso, Gabriele Inchingolo, Massimiliano Fabbiani, Barbara Rossetti, Giacomo Zanelli, Elena Bargagli, Laura Bergantini, Miriana D’Alessandro, Paolo Cameli, David Bennet, Federico Anedda, Simona Marcantonio, Sabino Scolletta, Federico Franchi, Maria Antonietta Mazzei, Susanna Guerrini, Edoardo Conticini, Luca Cantarini, Bruno Frediani, Danilo Tacconi, Chiara Spertilli, Marco Feri, Alice Donati, Raffaele Scala, Luca Guidelli, Genni Spargi, Marta Corridi, Cesira Nencioni, Leonardo Croci, Gian Piero Caldarelli, Maurizio Spagnesi, Paolo Piacentini, Maria Bandini, Elena Desanctis, Silvia Cappelli, Anna Canaccini, Agnese Verzuri, Valentina Anemoli, Agostino Ognibene, Alessandro Pancrazi, Maria Lorusso, Massimo Vaghi, Antonella D’Arminio Monforte, Esther Merlini, Federica Gaia Miraglia, Mario U. Mondelli, Raffaele Bruno, Vecchia Marco, Stefania Mantovani, Serena Ludovisi, Massimo Girardi, Sophie Venturelli, Marco Sita, Andrea Cossarizza, Andrea Antinori, Alessandra Vergori, Arianna Emiliozzi, Stefano Rusconi, Matteo Siano, Arianna Gabrieli, Agostino Riva, Daniela Francisci, Elisabetta Schiarol, Francesco Paciosi, Pier Giorgio Scotton, Francesca Andretta, Sandro Panese, Renzo Scaggiante, Francesca Gatti, Saverio Giuseppe Parisi, Francesco Castelli, Eugenia Quiros-Roldan, Melania Degli Antoni, Isabella Zanella, Matteo Della Monica, Carmelo Piscopo, Mario 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, Matteo Bassetti, Antonio Di Biagio, Maurizio Sanguinetti, Luca Masucci, Serafina Valente, Marco Mandalà, Alessia Giorli, Lorenzo Salerni, Patrizia Zucchi, Pierpaolo Parravicini, Elisabetta Menatti, Stefano Baratti, Tullio Trotta, Ferdinando Giannattasio, Gabriella Coiro, Fabio Lena, Domenico A. Coviello, Cristina Mussini, Giancarlo Bosio, Enrico Martinelli, Sandro Mancarella, Luisa Tavecchia, Lia Crotti, Gian-Franco Parati, Nicola Picchiotti, Marco Gori, Chiara Gabbi, Maurizio Sanarico, Stefano Ceri, Pietro Pinoli, Francesco Raimondi, Filippo Bis-Carini, Alessandra Stella, Marco Rizzi, Franco Maggiolo, Diego Ripamonti, Claudia Suardi, Tiziana Bachetti, Maria Teresa La Rovere, Simona Sarzi-Braga, Maurizio Bussotti, Mattia Bergomi, Katia Capitani, Kristina Zguro, Simona Dei

Research output: Contribution to journal › Article

Abstract

The protease encoded by the TMPRSS2 gene facilitates viral infections and has been implicated in the pathogenesis of SARS-CoV-2. We analyzed the TMPRSS2 sequence and correlated the protein variants with the clinical features of a cohort of 1177 patients affected by COVID-19 in Italy. Nine relatively common variants (allele frequency > 0.01) and six missense variants which may affect the protease activity according to PolyPhen-2 in HumVar-trained mode were identified. Among them, p.V197M (p.Val197Met) (rs12329760) emerges as a common variant that has a deleterious effect on the protease and a protective effect on the patients. Its role appears particularly relevant in two subgroups of patients—young males and elderly women—and among those affected by co-morbidities, where the variant frequency is higher among individuals who were mildly affected by the disease and did not need hospitalization or oxygen therapy than among those more severely affected, who required oxygen therapy, ventilation or intubation. This study provides useful information for the identification of patients at risk of developing a severe form of COVID-19, and encourages the usage of drugs affecting the expression of TMPRSS2 or inhibiting protein activity.

Original language	English
Pages (from-to)	596-610
Number of pages	15
Journal	Genes
Volume	12
DOIs	https://doi.org/10.3390/genes12040596
Publication status	Published - 2021

Keywords

COVID-19
Missense mutation
Whole-Exome Sequencing (WES)
V197M
TMPRSS2

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10.3390/genes12040596

Cite this

Monticelli, M., Mele, B. H., Benetti, E., Fallerini, C., Baldassarri, M., Furini, S., Frullanti, E., Mari, F., Andreotti, G., Cubellis, M. V., Renieri, A., Daga, S., Fava, F., Valentino, F., Doddato, G., Giliberti, A., Tita, R., Amitrano, S., Bruttini, M., ... Dei, S. (2021). Protective role of a tmprss2 variant on severe covid-19 outcome in young males and elderly women. Genes, 12, 596-610. https://doi.org/10.3390/genes12040596

@article{105f9bc2ed8f4006ad402ca5c615b6c4,

title = "Protective role of a tmprss2 variant on severe covid-19 outcome in young males and elderly women",

abstract = "The protease encoded by the TMPRSS2 gene facilitates viral infections and has been implicated in the pathogenesis of SARS-CoV-2. We analyzed the TMPRSS2 sequence and correlated the protein variants with the clinical features of a cohort of 1177 patients affected by COVID-19 in Italy. Nine relatively common variants (allele frequency > 0.01) and six missense variants which may affect the protease activity according to PolyPhen-2 in HumVar-trained mode were identified. Among them, p.V197M (p.Val197Met) (rs12329760) emerges as a common variant that has a deleterious effect on the protease and a protective effect on the patients. Its role appears particularly relevant in two subgroups of patients—young males and elderly women—and among those affected by co-morbidities, where the variant frequency is higher among individuals who were mildly affected by the disease and did not need hospitalization or oxygen therapy than among those more severely affected, who required oxygen therapy, ventilation or intubation. This study provides useful information for the identification of patients at risk of developing a severe form of COVID-19, and encourages the usage of drugs affecting the expression of TMPRSS2 or inhibiting protein activity.",

keywords = "COVID-19, Missense mutation, Whole-Exome Sequencing (WES), V197M, TMPRSS2, COVID-19, Missense mutation, Whole-Exome Sequencing (WES), V197M, TMPRSS2",

author = "Maria Monticelli and Mele, {Bruno Hay} and Elisa Benetti and Chiara Fallerini and Margherita Baldassarri and Simone Furini and Elisa Frullanti and Francesca Mari and Giuseppina Andreotti and Cubellis, {Maria Vittoria} and Alessandra Renieri and Sergio Daga and Francesca Fava and Floriana Valentino and Gabriella Doddato and Annarita Giliberti and Rossella Tita and Sara Amitrano and Mirella Bruttini and Susanna Croci and Ilaria Meloni and Pinto, {Anna Maria} and Mencarelli, {Maria Antonietta} and Rizzo, {Caterina Lo} and Francesca Montagnani and Sarno, {Laura Di} and Andrea Tommasi and Maria Palmieri and Carriero, {Miriam Lucia} and Diana Alaverdian and Giada Beligni and Nicola Iuso and Gabriele Inchingolo and Massimiliano Fabbiani and Barbara Rossetti and Giacomo Zanelli and Elena Bargagli and Laura Bergantini and Miriana D{\textquoteright}Alessandro and Paolo Cameli and David Bennet and Federico Anedda and Simona Marcantonio and Sabino Scolletta and Federico 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 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 Paolo Piacentini and Maria Bandini and Elena Desanctis and Silvia Cappelli and Anna Canaccini and Agnese Verzuri and Valentina Anemoli and Agostino Ognibene and Alessandro Pancrazi and Maria Lorusso and Massimo Vaghi and {D{\textquoteright}Arminio Monforte}, Antonella and Esther Merlini and Miraglia, {Federica Gaia} and Mondelli, {Mario U.} and Raffaele Bruno and Vecchia Marco and Stefania Mantovani and Serena Ludovisi and Massimo Girardi and Sophie Venturelli and Marco Sita and Andrea Cossarizza and Andrea Antinori and Alessandra Vergori and Arianna Emiliozzi and Stefano Rusconi and Matteo Siano and Arianna Gabrieli and Agostino Riva and Daniela Francisci and Elisabetta Schiarol and Francesco Paciosi and Scotton, {Pier Giorgio} and Francesca Andretta and Sandro Panese and Renzo Scaggiante and Francesca Gatti and Parisi, {Saverio Giuseppe} and Francesco Castelli and Eugenia Quiros-Roldan and Antoni, {Melania Degli} and Isabella Zanella and Monica, {Matteo Della} and Carmelo Piscopo and Mario 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 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 Stefano Baratti and Tullio Trotta and Ferdinando Giannattasio and Gabriella Coiro and Fabio Lena and Coviello, {Domenico A.} and Cristina Mussini and Giancarlo Bosio and Enrico Martinelli and Sandro Mancarella and Luisa Tavecchia and Lia Crotti and Gian-Franco Parati and Nicola Picchiotti and Marco Gori and Chiara Gabbi and Maurizio Sanarico and Stefano Ceri and Pietro Pinoli and Francesco Raimondi and Filippo Bis-Carini and Alessandra Stella and Marco Rizzi and Franco Maggiolo and Diego Ripamonti and Claudia Suardi and Tiziana Bachetti and Rovere, {Maria Teresa La} and Simona Sarzi-Braga and Maurizio Bussotti and Mattia Bergomi and Katia Capitani and Kristina Zguro and Simona Dei",

year = "2021",

doi = "10.3390/genes12040596",

language = "English",

volume = "12",

pages = "596--610",

journal = "Genes",

issn = "2073-4425",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

}

Monticelli, M, Mele, BH, Benetti, E, Fallerini, C, Baldassarri, M, Furini, S, Frullanti, E, Mari, F, Andreotti, G, Cubellis, MV, Renieri, A, Daga, S, Fava, F, Valentino, F, Doddato, G, Giliberti, A, Tita, R, Amitrano, S, Bruttini, M, Croci, S, Meloni, I, Pinto, AM, Mencarelli, MA, Rizzo, CL, Montagnani, F, Sarno, LD, Tommasi, A, Palmieri, M, Carriero, ML, Alaverdian, D, Beligni, G, Iuso, N, Inchingolo, G, Fabbiani, M, Rossetti, B, Zanelli, G, Bargagli, E, Bergantini, L, D’Alessandro, M, Cameli, P, Bennet, D, Anedda, F, Marcantonio, S, Scolletta, S, Franchi, F, Mazzei, MA, Guerrini, S, Conticini, E, Cantarini, L, Frediani, B, Tacconi, D, Spertilli, C, Feri, M, Donati, A, Scala, R, Guidelli, L, Spargi, G, Corridi, M, Nencioni, C, Croci, L, Caldarelli, GP, Spagnesi, M, Piacentini, P, Bandini, M, Desanctis, E, Cappelli, S, Canaccini, A, Verzuri, A, Anemoli, V, Ognibene, A, Pancrazi, A, Lorusso, M, Vaghi, M, D’Arminio Monforte, A, Merlini, E, Miraglia, FG, Mondelli, MU, Bruno, R, Marco, V, Mantovani, S, Ludovisi, S, Girardi, M, Venturelli, S, Sita, M, Cossarizza, A, Antinori, A, Vergori, A, Emiliozzi, A, Rusconi, S, Siano, M, Gabrieli, A, Riva, A, Francisci, D, Schiarol, E, Paciosi, F, Scotton, PG, Andretta, F, Panese, S, Scaggiante, R, Gatti, F, Parisi, SG, Castelli, F, Quiros-Roldan, E, Antoni, MD, Zanella, I, Monica, MD, Piscopo, C, 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, Bassetti, M, Biagio, AD, Sanguinetti, M , Masucci, L, Valente, S, Mandalà, M, Giorli, A, Salerni, L, Zucchi, P, Parravicini, P, Menatti, E, Baratti, S, Trotta, T, Giannattasio, F, Coiro, G, Lena, F, Coviello, DA, Mussini, C, Bosio, G, Martinelli, E, Mancarella, S, Tavecchia, L, Crotti, L, Parati, G-F, Picchiotti, N, Gori, M, Gabbi, C, Sanarico, M, Ceri, S, Pinoli, P, Raimondi, F, Bis-Carini, F, Stella, A, Rizzi, M, Maggiolo, F, Ripamonti, D, Suardi, C, Bachetti, T, Rovere, MTL, Sarzi-Braga, S, Bussotti, M, Bergomi, M, Capitani, K, Zguro, K & Dei, S 2021, 'Protective role of a tmprss2 variant on severe covid-19 outcome in young males and elderly women', Genes, vol. 12, pp. 596-610. https://doi.org/10.3390/genes12040596

TY - JOUR

T1 - Protective role of a tmprss2 variant on severe covid-19 outcome in young males and elderly women

AU - Monticelli, Maria

AU - Mele, Bruno Hay

AU - Benetti, Elisa

AU - Fallerini, Chiara

AU - Baldassarri, Margherita

AU - Furini, Simone

AU - Frullanti, Elisa

AU - Mari, Francesca

AU - Andreotti, Giuseppina

AU - Cubellis, Maria Vittoria

AU - Renieri, Alessandra

AU - Daga, Sergio

AU - Fava, Francesca

AU - Valentino, Floriana

AU - Doddato, Gabriella

AU - Giliberti, Annarita

AU - Tita, Rossella

AU - Amitrano, Sara

AU - Bruttini, Mirella

AU - Croci, Susanna

AU - Meloni, Ilaria

AU - Pinto, Anna Maria

AU - Mencarelli, Maria Antonietta

AU - Rizzo, Caterina Lo

AU - Montagnani, Francesca

AU - Sarno, Laura Di

AU - Tommasi, Andrea

AU - Palmieri, Maria

AU - Carriero, Miriam Lucia

AU - Alaverdian, Diana

AU - Beligni, Giada

AU - Iuso, Nicola

AU - Inchingolo, Gabriele

AU - Fabbiani, Massimiliano

AU - Rossetti, Barbara

AU - Zanelli, Giacomo

AU - Bargagli, Elena

AU - Bergantini, Laura

AU - D’Alessandro, Miriana

AU - Cameli, Paolo

AU - Bennet, David

AU - Anedda, Federico

AU - Marcantonio, Simona

AU - Scolletta, Sabino

AU - Franchi, Federico

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 - 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 - Piacentini, Paolo

AU - Bandini, Maria

AU - Desanctis, Elena

AU - Cappelli, Silvia

AU - Canaccini, Anna

AU - Verzuri, Agnese

AU - Anemoli, Valentina

AU - Ognibene, Agostino

AU - Pancrazi, Alessandro

AU - Lorusso, Maria

AU - Vaghi, Massimo

AU - D’Arminio Monforte, Antonella

AU - Merlini, Esther

AU - Miraglia, Federica Gaia

AU - Mondelli, Mario U.

AU - Bruno, Raffaele

AU - Marco, Vecchia

AU - Mantovani, Stefania

AU - Ludovisi, Serena

AU - Girardi, Massimo

AU - Venturelli, Sophie

AU - Sita, Marco

AU - Cossarizza, Andrea

AU - Antinori, Andrea

AU - Vergori, Alessandra

AU - Emiliozzi, Arianna

AU - Rusconi, Stefano

AU - Siano, Matteo

AU - Gabrieli, Arianna

AU - Riva, Agostino

AU - Francisci, Daniela

AU - Schiarol, Elisabetta

AU - Paciosi, Francesco

AU - Scotton, Pier Giorgio

AU - Andretta, Francesca

AU - Panese, Sandro

AU - Scaggiante, Renzo

AU - Gatti, Francesca

AU - Parisi, Saverio Giuseppe

AU - Castelli, Francesco

AU - Quiros-Roldan, Eugenia

AU - Antoni, Melania Degli

AU - Zanella, Isabella

AU - Monica, Matteo Della

AU - Piscopo, Carmelo

AU - Capasso, Mario

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 - 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 - Baratti, Stefano

AU - Trotta, Tullio

AU - Giannattasio, Ferdinando

AU - Coiro, Gabriella

AU - Lena, Fabio

AU - Coviello, Domenico A.

AU - Mussini, Cristina

AU - Bosio, Giancarlo

AU - Martinelli, Enrico

AU - Mancarella, Sandro

AU - Tavecchia, Luisa

AU - Crotti, Lia

AU - Parati, Gian-Franco

AU - Picchiotti, Nicola

AU - Gori, Marco

AU - Gabbi, Chiara

AU - Sanarico, Maurizio

AU - Ceri, Stefano

AU - Pinoli, Pietro

AU - Raimondi, Francesco

AU - Bis-Carini, Filippo

AU - Stella, Alessandra

AU - Rizzi, Marco

AU - Maggiolo, Franco

AU - Ripamonti, Diego

AU - Suardi, Claudia

AU - Bachetti, Tiziana

AU - Rovere, Maria Teresa La

AU - Sarzi-Braga, Simona

AU - Bussotti, Maurizio

AU - Bergomi, Mattia

AU - Capitani, Katia

AU - Zguro, Kristina

AU - Dei, Simona

PY - 2021

Y1 - 2021

N2 - The protease encoded by the TMPRSS2 gene facilitates viral infections and has been implicated in the pathogenesis of SARS-CoV-2. We analyzed the TMPRSS2 sequence and correlated the protein variants with the clinical features of a cohort of 1177 patients affected by COVID-19 in Italy. Nine relatively common variants (allele frequency > 0.01) and six missense variants which may affect the protease activity according to PolyPhen-2 in HumVar-trained mode were identified. Among them, p.V197M (p.Val197Met) (rs12329760) emerges as a common variant that has a deleterious effect on the protease and a protective effect on the patients. Its role appears particularly relevant in two subgroups of patients—young males and elderly women—and among those affected by co-morbidities, where the variant frequency is higher among individuals who were mildly affected by the disease and did not need hospitalization or oxygen therapy than among those more severely affected, who required oxygen therapy, ventilation or intubation. This study provides useful information for the identification of patients at risk of developing a severe form of COVID-19, and encourages the usage of drugs affecting the expression of TMPRSS2 or inhibiting protein activity.

AB - The protease encoded by the TMPRSS2 gene facilitates viral infections and has been implicated in the pathogenesis of SARS-CoV-2. We analyzed the TMPRSS2 sequence and correlated the protein variants with the clinical features of a cohort of 1177 patients affected by COVID-19 in Italy. Nine relatively common variants (allele frequency > 0.01) and six missense variants which may affect the protease activity according to PolyPhen-2 in HumVar-trained mode were identified. Among them, p.V197M (p.Val197Met) (rs12329760) emerges as a common variant that has a deleterious effect on the protease and a protective effect on the patients. Its role appears particularly relevant in two subgroups of patients—young males and elderly women—and among those affected by co-morbidities, where the variant frequency is higher among individuals who were mildly affected by the disease and did not need hospitalization or oxygen therapy than among those more severely affected, who required oxygen therapy, ventilation or intubation. This study provides useful information for the identification of patients at risk of developing a severe form of COVID-19, and encourages the usage of drugs affecting the expression of TMPRSS2 or inhibiting protein activity.

KW - COVID-19

KW - Missense mutation

KW - Whole-Exome Sequencing (WES)

KW - V197M

KW - TMPRSS2

KW - COVID-19

KW - Missense mutation

KW - Whole-Exome Sequencing (WES)

KW - V197M

KW - TMPRSS2

UR - http://hdl.handle.net/10807/294316

U2 - 10.3390/genes12040596

DO - 10.3390/genes12040596

M3 - Article

SN - 2073-4425

VL - 12

SP - 596

EP - 610

JO - Genes

JF - Genes

ER -

Protective role of a tmprss2 variant on severe covid-19 outcome in young males and elderly women

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