Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Paul Bastard; Sara Vazquez; Jamin Liu; Matthew T Laurie; Chung Yu Wang; Adrian Gervais; Tom Le Voyer; Lucy Bizien; Colin Zamecnik; Quentin Philippot; Jérémie Rosain; Emilie Catherinot; Andrew Willmore; Anthea M Mitchell; Rebecca Bair; Pierre Garçon; Heather Kenney; Arnaud Fekkar; Maria Salagianni; Garyphallia Poulakou; Eleni Siouti; Sabina Sahanic; Ivan Tancevski; Günter Weiss; Laurenz Nagl; Jérémy Manry; Sotirija Duvlis; Daniel Arroyo-Sánchez; Estela Paz Artal; Luis Rubio; Cristiano Perani; Michela Bezzi; Alessandra Sottini; Virginia Quaresima; Lucie Roussel; Donald C Vinh; Luis Felipe Reyes; Margaux Garzaro; Nevin Hatipoglu; David Boutboul; Yacine Tandjaoui-Lambiotte; Alessandro Borghesi; Anna Aliberti; Irene Cassaniti; Fabienne Venet; Guillaume Monneret; Rabih Halwani; Narjes Saheb Sharif-Askari; Jeffrey Danielson; Sonia Burrel; Caroline Morbieu; Yurii Stepanovskyy; Anastasia Bondarenko; Alla Volokha; Oksana Boyarchuk; Alenka Gagro; Mathilde Neuville; Bénédicte Neven; Sevgi Keles; Romain Hernu; Antonin Bal; Antonio Novelli; Giuseppe Novelli; Kahina Saker; Oana Ailioaie; Arnau Antolí; Eric Jeziorski; Gemma Rocamora-Blanch; Carla Teixeira; Clarisse Delaunay; Marine Lhuillier; Paul Le Turnier; Yu Zhang; Matthieu Mahevas; Qiang Pan-Hammarström; Hassan Abolhassani; Thierry Bompoil; Karim Dorgham; Guy Gorochov; Cédric Laouenan; Carlos Rodríguez-Gallego; Lisa F P Ng; Laurent Renia; Aurora Pujol; Alexandre Belot; François Raffi; Luis M Allende; Javier Martinez-Picado; Tayfun Ozcelik; Luisa Imberti; Luigi D Notarangelo; Jesus Troya; Xavier Solanich; Shen-Ying Zhang; Anne Puel; Michael R Wilson; Sophie Trouillet-Assant; Laurent Abel; Emmanuelle Jouanguy; Chun Jimmie Ye; Aurélie Cobat; Leslie M Thompson; Evangelos Andreakos; Qian Zhang; Mark S Anderson; Jean-Laurent Casanova; Joseph L Derisi; Cristian Achille; Alessandro Aiuti; Saleh Al-Muhsen; Fahd Al-Mulla; Micol Angelini; Andrés A Arias; Gokhan Aytekin; Fausto Baldanti; Hagit Baris Feldman; Federica Bergami; Catherine M Biggs; Dusan Bogunovic; Alexandre Bolze; Anastasiia Bondarenko; Ahmed A Bousfiha; Petter Brodin; Yenan Bryceson; Carlos D Bustamante; Manish J Butte; Giorgio Casari; John Christodoulou; Antonio Condino-Neto; Stefan N Constantinescu; Francesca Conti; Megan A Cooper; Clifton L Dalgard; Murkesh Desai; Beth A Drolet; Jamila El Baghdadi; Recai Ergun; Dilek Ergun; Sara Espinosa-Padilla; Jacques Fellay; Carlos Flores; José Luis Franco; Antoine Froidure; Stefano Ghirardello; Peter K Gregersen; Bodo Grimbacher; Filomeen Haerynck; David Hagin; Lennart Hammarström; James R Heath; Sarah E Henrickson; Elena W Y Hsieh; Eystein Husebye; Kohsuke Imai; Yuval Itan; Erich D Jarvis; Fikret Kanat; Timokratis Karamitros; Kai Kisand; Vasyl Kopcha; Mykhaylo Korda; Cheng-Lung Ku; Yu-Lung Lau; Yun Ling; Carrie L Lucas; Tom Maniatis; Davood Mansouri; László Maródi; Isabelle Meyts; Joshua D Milner; Kristina Mironska; Trine H Mogensen; Francesco Mojoli; Francisco Morandeira; Tomohiro Morio; Cliona O'Farrelly; Satoshi Okada; Keisuke Okamoto; Michele Pagani; Jean W Pape; Rebeca Perez de Diego; David S Perlin; Graziano Pesole; Andrea Pession; Antonio Piralla; Anna M Planas; Carolina Prando; Lluis Quintana-Murci; Sathishkumar Ramaswamy; Igor Resnick; Raúl Rigo-Bonnin; Vanessa Sancho-Shimizu; Anna Sediva; Mikko R J Seppänen; Mohammed Shahrooei; Anna Shcherbina; Ondrej Slaby; Andrew L Snow; Pere Soler-Palacín; András N Spaan; Stuart G Tangye; Ahmad Abou Tayoun; Baykal Tulek; Stuart E Turvey; K M Furkan Uddin; Mohammed Uddin; Bénédicte Clément; Yumiko Abe-Jones; Saurabh Asthana; Sharvari Bhide; Carolyn S Calfee; Sidney A Carrillo; Suzanna Chak; Zachary Collins; David J Erle; Gabriela K Fragiadakis; Rajani Ghale; Carolyn M Hendrickson; Alejandra Jauregui; Kirsten N Kangelaris; Matthew F Krummel; Charles R Langelier; Tasha Lea; Deanna Lee; Aleksandra Leligdowicz; Carolyn Leroux; Raphael Lota; Michael Matthay; Viet Nguyen; Ravi Patel; Logan Pierce; Priya Prasad; Arjun Arkal Rao; Ahmad Rashid; Nicklaus Rodriguez; Bushra Samad; Cole Shaw; Austin Sigman; Kevin Tang; Luz Torres Altamirano; Alyssa Ward; Prescott G Woodruff; Clotilde Allavena; Claire Andrejak; François Angoulvant; Cecile Azoulay; Delphine Bachelet; Marie Bartoli; Romain Basmaci; Sylvie Behilill; Marine Beluze; Nicolas Benech; Dehbia Benkerrou; Krishna Bhavsar; Laurent Bitker; Lila Bouadma; Maude Bouscambert; Pauline Caraux Paz; Minerva Cervantes-Gonzalez; Anissa Chair; Catherine Chirouze; Alexandra Coelho; Hugues Cordel; Camille Couffignal; Sandrine Couffin-Cadiergues; Eric D’ortenzio; Etienne de Montmollin; Alexa Debard; Marie-Pierre Debray; Dominique Deplanque; Diane Descamps; Mathilde Desvallée; Alpha Diallo; Jean-Luc Diehl; Alphonsine Diouf; Céline Dorival; François Dubos; Xavier Duval; Philippine Eloy; Vincent Enouf; Olivier Epaulard; Hélène Esperou; Marina Esposito-Farese; Manuel Etienne; Denis Garot; Nathalie Gault; Alexandre Gaymard; Jade Ghosn; Tristan Gigante; Morgane Gilg; François Goehringer; Jérémie Guedj; Alexandre Hoctin; Isabelle Hoffmann; Ikram Houas; Jean-Sébastien Hulot; Salma Jaafoura; Ouifiya Kafif; Florentia Kaguelidou; Sabrina Kali; Younes Kerroumi; Antoine Khalil; Coralie Khan; Antoine Kimmoun; Fabrice Laine; Cédric Laouénan; Samira Laribi; Minh Le; Cyril Le Bris; Sylvie Le Gac; Quentin Le Hingrat; Soizic Le Mestre; Hervé Le Nagard; Adrien Lemaignen; Véronique Lemee; François-Xavier Lescure; Sophie Letrou; Yves Levy; Bruno Lina; Guillaume Lingas; Jean Christophe Lucet; Moïse Machado; Denis Malvy; Marina Mambert; Aldric Manuel; France Mentré; Amina Meziane; Hugo Mouquet; Jimmy Mullaert; Nadège Neant; Duc Nguyen; Marion Noret; Aurélie Papadopoulos; Christelle Paul; Nathan Peiffer-Smadja; Vincent Peigne; Ventzislava Petrov-Sanchez; Gilles Peytavin; Huong Pham; Olivier Picone; Valentine Piquard; Julien Poissy; Oriane Puéchal; Manuel Rosa-Calatrava; Bénédicte Rossignol; Patrick Rossignol; Carine Roy; Marion Schneider; Richa Su; Coralie Tardivon; Marie-Capucine Tellier; François Téoulé; Olivier Terrier; Jean-François Timsit; Christelle Tual; Sarah Tubiana; Sylvie van der Werf; Noémie Vanel; Aurélie Veislinger; Benoit Visseaux; Aurélie Wiedemann; Yazdan Yazdanpanah

doi:10.1126/sciimmunol.abp8966

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Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Journal article

Open access

Peer reviewed

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Paul Bastard, Sara Vazquez, Jamin Liu, Matthew T Laurie, Chung Yu Wang, Adrian Gervais, Tom Le Voyer, Lucy Bizien, Colin Zamecnik, Quentin Philippot, …

Science Immunology, Vol.8(90)

14/06/2022

DOI: https://doi.org/10.1126/sciimmunol.abp8966

PMCID: PMC9210448

PMID: 35857576

Abstract

COVID-19 Vaccines

COVID-19

hUMANS

Interferon Type 1

RNA, Messenger

SARS-CoV-2

Vaccination

Vaccines

Life-threatening ‘breakthrough’ cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS-CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals (age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, while two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.

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Title: Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs
Creators - without role: Paul Bastard - Inserm
Sara Vazquez - University of California, San Francisco
Jamin Liu - University of California, San Francisco
Matthew T Laurie - University of California, San Francisco
Chung Yu Wang
Adrian Gervais - Université Paris Cité
Tom Le Voyer - Inserm
Lucy Bizien - Inserm
Colin Zamecnik - University of California, San Francisco
Quentin Philippot - Inserm
Jérémie Rosain - Inserm
Emilie Catherinot - Hôpital Foch
Andrew Willmore - Chan Zuckerberg Initiative
Anthea M Mitchell - Chan Zuckerberg Initiative
Rebecca Bair - University of California, San Francisco
Pierre Garçon - Grand Hôpital de l'Est Francilien
Heather Kenney - Office of Extramural Research
Arnaud Fekkar - Assistance Publique – Hôpitaux de Paris
Maria Salagianni - Academy of Athens
Garyphallia Poulakou - National and Kapodistrian University of Athens
Eleni Siouti - Academy of Athens
Sabina Sahanic - Universität Innsbruck
Ivan Tancevski - Innsbruck Medical University
Günter Weiss - Innsbruck Medical University
Laurenz Nagl - Innsbruck Medical University
Jérémy Manry - Université Paris Cité
Sotirija Duvlis - Goce Delchev University
Daniel Arroyo-Sánchez - Centro de Investigación Biomédica en Red
Estela Paz Artal
Luis Rubio - University of California, San Francisco
Cristiano Perani - Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Michela Bezzi - Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Alessandra Sottini - Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Virginia Quaresima - Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Lucie Roussel - McGill University Health Centre
Donald C Vinh - McGill University Health Centre
Luis Felipe Reyes - Universidad de La Sabana
Margaux Garzaro - Assistance Publique – Hôpitaux de Paris
Nevin Hatipoglu - Sağlık Bilimleri Üniversitesi
David Boutboul - Hôpital Saint-Louis
Yacine Tandjaoui-Lambiotte - Inserm
Alessandro Borghesi - Policlinico San Matteo Fondazione
Anna Aliberti - Policlinico San Matteo Fondazione
Irene Cassaniti - Policlinico San Matteo Fondazione
Fabienne Venet - Hospices Civils de Lyon
Guillaume Monneret - Hôpital Edouard Herriot
Rabih Halwani - University of Sharjah
Narjes Saheb Sharif-Askari - University of Sharjah
Jeffrey Danielson - Office of Extramural Research
Sonia Burrel - Inserm
Caroline Morbieu - Hôpital Louis-Mourier
Yurii Stepanovskyy
Anastasia Bondarenko
Alla Volokha
Oksana Boyarchuk - I.Horbachevsky Ternopil National Medical University
Alenka Gagro - University of Osijek
Mathilde Neuville - Hôpital Foch
Bénédicte Neven - Assistance Publique – Hôpitaux de Paris
Sevgi Keles - Necmettin Erbakan University
Romain Hernu - Hospices Civils de Lyon
Antonin Bal - Hospices Civils de Lyon
Antonio Novelli - Bambino Gesù Children's Hospital
Giuseppe Novelli - University of Rome Tor Vergata
Kahina Saker - Inserm
Oana Ailioaie - Hôpital Raymond-Poincaré
Arnau Antolí - Bellvitge University Hospital
Eric Jeziorski - Université de Montpellier, Pathogenesis and Control of Chronic and Emerging Infections - PCCEI
Gemma Rocamora-Blanch - Bellvitge University Hospital
Carla Teixeira - Centro Hospitalar do Porto
Clarisse Delaunay - Inserm
Marine Lhuillier
Paul Le Turnier - Inserm
Yu Zhang - Office of Extramural Research
Matthieu Mahevas - Institut Mondor de Recherche Biomédicale
Qiang Pan-Hammarström - Karolinska Institutet
Hassan Abolhassani - Karolinska Institutet
Thierry Bompoil
Karim Dorgham - Inserm
Guy Gorochov - Inserm
Cédric Laouenan - Inserm
Carlos Rodríguez-Gallego - Hospital Universitario de Gran Canaria Doctor Negrín
Lisa F P Ng - Agency for Science, Technology and Research
Laurent Renia - Agency for Science, Technology and Research
Aurora Pujol - Centre for Biomedical Network Research on Rare Diseases
Alexandre Belot - École Normale Supérieure de Lyon
François Raffi - Inserm
Luis M Allende - Centro de Investigación Biomédica en Red
Javier Martinez-Picado - Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol
Tayfun Ozcelik
Sevgi Keles - Necmettin Erbakan University
Luisa Imberti - Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Luigi D Notarangelo - National Institute of Allergy and Infectious Diseases
Jesus Troya - Hospital Universitario Infanta Leonor
Xavier Solanich - Institut d'Investigació Biomédica de Bellvitge
Shen-Ying Zhang
Anne Puel - Rockefeller University
Michael R Wilson - University of California, San Francisco
Sophie Trouillet-Assant - Inserm
Laurent Abel - Inserm
Emmanuelle Jouanguy - Inserm
Chun Jimmie Ye - University of California, San Francisco
Aurélie Cobat - Rockefeller University
Leslie M Thompson - University of California, Irvine
Evangelos Andreakos - Academy of Athens
Qian Zhang - Inserm
Mark S Anderson - University of California, San Francisco
Jean-Laurent Casanova - Génétique Evolutive Humaine - Human Evolutionary Genetics
Joseph L Derisi - Chan Zuckerberg Initiative
Laurent Abel - Inserm
Cristian Achille
Alessandro Aiuti
Saleh Al-Muhsen
Fahd Al-Mulla
Mark S Anderson - University of California, San Francisco
Evangelos Andreakos - Academy of Athens
Micol Angelini
Andrés A Arias
Gokhan Aytekin
Fausto Baldanti
Hagit Baris Feldman
Alexandre Belot - Université Claude Bernard Lyon 1
Federica Bergami
Catherine M Biggs
Dusan Bogunovic
Alexandre Bolze
Anastasiia Bondarenko
Ahmed A Bousfiha
Petter Brodin
Yenan Bryceson
Carlos D Bustamante
Manish J Butte
Giorgio Casari
John Christodoulou
Antonio Condino-Neto
Stefan N Constantinescu
Francesca Conti
Megan A Cooper
Clifton L Dalgard
Murkesh Desai
Beth A Drolet
Jamila El Baghdadi
Recai Ergun
Dilek Ergun
Sara Espinosa-Padilla
Jacques Fellay
Carlos Flores
José Luis Franco
Antoine Froidure
Stefano Ghirardello
Peter K Gregersen
Bodo Grimbacher
Filomeen Haerynck
David Hagin
Rabih Halwani - University of Sharjah
Lennart Hammarström
James R Heath
Sarah E Henrickson
Elena W Y Hsieh
Eystein Husebye
Kohsuke Imai
Yuval Itan
Erich D Jarvis
Fikret Kanat
Timokratis Karamitros
Kai Kisand
Vasyl Kopcha
Mykhaylo Korda
Cheng-Lung Ku
Yu-Lung Lau
Yun Ling
Carrie L Lucas
Tom Maniatis
Davood Mansouri
László Maródi
Isabelle Meyts
Joshua D Milner
Kristina Mironska
Trine H Mogensen
Francesco Mojoli
Francisco Morandeira
Tomohiro Morio
Lisa F P Ng - Agency for Science, Technology and Research
Luigi D Notarangelo - National Institute of Allergy and Infectious Diseases
Antonio Novelli - Bambino Gesù Children's Hospital
Giuseppe Novelli - University of Rome Tor Vergata
Cliona O'Farrelly
Satoshi Okada
Keisuke Okamoto
Tayfun Ozcelik
Michele Pagani
Qiang Pan-Hammarström - Karolinska Institutet
Jean W Pape
Rebeca Perez de Diego
David S Perlin
Graziano Pesole
Andrea Pession
Antonio Piralla
Anna M Planas
Carolina Prando
Aurora Pujol - Centre for Biomedical Network Research on Rare Diseases
Lluis Quintana-Murci - Génétique Evolutive Humaine - Human Evolutionary Genetics
Sathishkumar Ramaswamy
Laurent Renia - Agency for Science, Technology and Research
Igor Resnick
Raúl Rigo-Bonnin
Carlos Rodríguez-Gallego - Hospital Universitario de Gran Canaria Doctor Negrín
Vanessa Sancho-Shimizu
Anna Sediva
Mikko R J Seppänen
Mohammed Shahrooei
Anna Shcherbina
Ondrej Slaby
Andrew L Snow
Pere Soler-Palacín
András N Spaan
Ivan Tancevski - Innsbruck Medical University
Stuart G Tangye
Ahmad Abou Tayoun
Baykal Tulek
Stuart E Turvey
K M Furkan Uddin
Mohammed Uddin
Bénédicte Clément
Yumiko Abe-Jones
Saurabh Asthana
Sharvari Bhide
Carolyn S Calfee
Sidney A Carrillo
Suzanna Chak
Zachary Collins
David J Erle
Gabriela K Fragiadakis
Rajani Ghale
Carolyn M Hendrickson
Alejandra Jauregui
Kirsten N Kangelaris
Matthew F Krummel
Charles R Langelier
Tasha Lea
Deanna Lee
Aleksandra Leligdowicz
Carolyn Leroux
Raphael Lota
Michael Matthay
Viet Nguyen
Ravi Patel
Logan Pierce
Priya Prasad
Arjun Arkal Rao
Ahmad Rashid
Nicklaus Rodriguez
Bushra Samad
Cole Shaw
Austin Sigman
Kevin Tang
Luz Torres Altamirano
Alyssa Ward
Andrew Willmore - Chan Zuckerberg Initiative
Michael R Wilson - University of California, San Francisco
Prescott G Woodruff
Laurent Abel - Inserm
Clotilde Allavena
Claire Andrejak
François Angoulvant
Cecile Azoulay
Delphine Bachelet
Marie Bartoli
Romain Basmaci
Sylvie Behilill
Marine Beluze
Nicolas Benech
Dehbia Benkerrou
Krishna Bhavsar
Laurent Bitker
Lila Bouadma
Maude Bouscambert
Pauline Caraux Paz
Minerva Cervantes-Gonzalez
Anissa Chair
Catherine Chirouze
Alexandra Coelho
Hugues Cordel
Camille Couffignal
Sandrine Couffin-Cadiergues
Eric D’ortenzio
Etienne de Montmollin
Alexa Debard
Marie-Pierre Debray
Dominique Deplanque
Diane Descamps
Mathilde Desvallée
Alpha Diallo
Jean-Luc Diehl
Alphonsine Diouf
Céline Dorival
François Dubos
Xavier Duval
Philippine Eloy
Vincent Enouf
Olivier Epaulard
Hélène Esperou
Marina Esposito-Farese
Manuel Etienne
Denis Garot
Nathalie Gault
Alexandre Gaymard
Jade Ghosn
Tristan Gigante
Morgane Gilg
François Goehringer
Jérémie Guedj
Alexandre Hoctin
Isabelle Hoffmann
Ikram Houas
Jean-Sébastien Hulot
Salma Jaafoura
Ouifiya Kafif
Florentia Kaguelidou
Sabrina Kali
Younes Kerroumi
Antoine Khalil
Coralie Khan
Antoine Kimmoun
Fabrice Laine
Cédric Laouénan - Inserm
Samira Laribi
Minh Le
Cyril Le Bris
Sylvie Le Gac
Quentin Le Hingrat
Soizic Le Mestre
Hervé Le Nagard
Adrien Lemaignen
Véronique Lemee
François-Xavier Lescure
Sophie Letrou
Yves Levy
Bruno Lina
Guillaume Lingas
Jean Christophe Lucet
Moïse Machado
Denis Malvy
Marina Mambert
Aldric Manuel
France Mentré
Amina Meziane
Hugo Mouquet
Jimmy Mullaert
Nadège Neant
Duc Nguyen
Marion Noret
Aurélie Papadopoulos
Christelle Paul
Nathan Peiffer-Smadja
Vincent Peigne
Ventzislava Petrov-Sanchez
Gilles Peytavin
Huong Pham
Olivier Picone
Valentine Piquard
Julien Poissy
Oriane Puéchal
Manuel Rosa-Calatrava
Bénédicte Rossignol
Patrick Rossignol
Carine Roy
Marion Schneider
Richa Su
Coralie Tardivon
Marie-Capucine Tellier
François Téoulé
Olivier Terrier
Jean-François Timsit
Christelle Tual
Sarah Tubiana
Sylvie van der Werf
Noémie Vanel
Aurélie Veislinger
Benoit Visseaux
Aurélie Wiedemann
Yazdan Yazdanpanah
Publication Details: Science Immunology, Vol.8(90)
Identifiers: 9934643509311
Academic Unit: Pathogenesis and Control of Chronic and Emerging Infections - PCCEI
Language: English
Resource Type: Journal article
Local Fields: hal-03948899