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1. A Cohort of Patients with COVID-19 in a Major Teaching Hospital in Europe

Author

Alberto M. Borobia, Antonio J. Carcas, Francisco Arnalich, Rodolfo Álvarez-Sala, Jaime Monserrat-Villatoro, Manuel Quintana, Juan Carlos Figueira, Rosario M. Torres Santos-Olmo, Julio García-Rodríguez, Alberto Martín-Vega, Antonio Buño, Elena Ramírez, Gonzalo Martínez-Alés, Nicolás García-Arenzana, M. Concepción Núñez, Milagros Martí-de-Gracia, Francisco Moreno Ramos, Francisco Reinoso-Barbero, Alejandro Martin-Quiros, Angélica Rivera Núñez, Jesús Mingorance, Carlos J. Carpio Segura, Daniel Prieto Arribas, Esther Rey Cuevas, Concepción Prados Sánchez, Juan J. Rios, Miguel A. Hernán, Jesús Frías, and José R. Arribas

Subjects
COVID19, SARS-CoV-2, Spain, Europe, Medicine
Abstract

Background: Since the confirmation of the first patient infected with SARS-CoV-2 in Spain in January 2020, the epidemic has grown rapidly, with the greatest impact on the region of Madrid. This article describes the first 2226 adult patients with COVID-19, consecutively admitted to La Paz University Hospital in Madrid. Methods: Our cohort included all patients consecutively hospitalized who had a final outcome (death or discharge) in a 1286-bed hospital of Madrid (Spain) from 25 February (first case admitted) to 19 April 2020. The data were manually entered into an electronic case report form, which was monitored prior to the analysis. Results: We consecutively included 2226 adult patients admitted to the hospital who either died (460) or were discharged (1766). The patients’ median age was 61 years, and 51.8% were women. The most common comorbidity was arterial hypertension (41.3%), and the most common symptom on admission was fever (71.2%). The median time from disease onset to hospital admission was 6 days. The overall mortality was 20.7% and was higher in men (26.6% vs. 15.1%). Seventy-five patients with a final outcome were transferred to the intensive care unit (ICU) (3.4%). Most patients admitted to the ICU were men, and the median age was 64 years. Baseline laboratory values on admission were consistent with an impaired immune-inflammatory profile. Conclusions: We provide a description of the first large cohort of hospitalized patients with COVID-19 in Europe. Advanced age, male sex, the presence of comorbidities and abnormal laboratory values were more common among the patients with fatal outcomes.

Published
2020
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2. Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

Author

Barbara Wanjiru Citarella, Christiana Kartsonaki, Elsa D. Ibáñez-Prada, Bronner P. Gonçalves, Joaquin Baruch, Martina Escher, Mark G. Pritchard, Jia Wei, Fred Philippy, Andrew Dagens, Matthew Hall, James Lee, Demetrios James Kutsogiannis, Evert-Jan Wils, Marília Andreia Fernandes, Bharath Kumar Tirupakuzhi Vijayaraghavan, Prasan Kumar Panda, Ignacio Martin-Loeches, Shinichiro Ohshimo, Arie Zainul Fatoni, Peter Horby, Jake Dunning, Jordi Rello, Laura Merson, Amanda Rojek, Michel Vaillant, Piero Olliaro, Luis Felipe Reyes, S.A. Moharam, Sabriya Abdalasalam, Alaa Abdalfattah Abdalhadi, Naana Reyam Abdalla, Walaa Abdalla, Almthani Hamza Abdalrheem, Ashraf Abdalsalam, Saedah Abdeewi, Esraa Hassan Abdelgaum, Mohamed Abdelhalim, Mohammed Abdelkabir, Israa Abdelrahman, Sheryl Ann Abdukahil, Lamees Adil Abdulbaqi, Salaheddin Abdulhamid, Widyan Abdulhamid, Nurul Najmee Abdulkadir, Eman Abdulwahed, Rawad Abdunabi, Ryuzo Abe, Laurent Abel, Ahmed Mohammed Abodina, Amal Abrous, Lara Absil, Kamal Abu Jabal, Nashat Abu Salah, Abdurraouf Abusalama, Tareg Abdallah Abuzaid, Subhash Acharya, Andrew Acker, Elisabeth Adam, Safia Adem, Manuella Ademnou, Francisca Adewhajah, Diana Adrião, Anthony Afum-Adjei Awuah, Melvin Agbogbatey, Saleh Al Ageel, Aya Mustafa Ahmed, Musaab Mohammed Ahmed, Shakeel Ahmed, Zainab Ahmed Alaraji, Abdulrahman Ahmed Elhefnawy Enan, Reham Abdelhamid Ahmed Khalil, Ali Mostafa Ahmed Mohamed Abdelaziz, Kate Ainscough, Eka Airlangga, Tharwat Aisa, Ali Aisha, Bugila Aisha, Ali Ait Hssain, Younes Ait Tamlihat, Takako Akimoto, Ernita Akmal, Chika Akwani, Eman Al Qasim, Ahmed Alajeeli, Ahmed Alali, Razi Alalqam, Aliya Mohammed Alameen, Mohammed Al-Aquily, Zinah A. Alaraji, Khalid Albakry, Safa Albatni, Angela Alberti, Osama Aldabbourosama, Tala Al-dabbous, Amer Aldhalia, Abdulkarim Aldoukali, Senthilkumar Alegesan, Marta Alessi, Beatrice Alex, Kévin Alexandre, Abdulrahman Al-Fares, Asil Alflite, Huda Alfoudri, Qamrah Alhadad, Hoda Salem Alhaddad, Maali Khalid Mohamed Abdalla Alhasan, Ahmad Nabil Alhouri, Hasan Alhouri, Adam Ali, Imran Ali, Maha TagElser Mohammed Ali, Syed Ali Abbas, Yomna Ali Abdelghafar, Naseem Ali Sheikh, Kazali Enagnon Alidjnou, Mahmoud Aljadi, Sarah Aljamal, Mohammed Alkahlout, Akram Alkaseek, Qabas Alkhafajee, Clotilde Allavena, Nathalie Allou, Lana Almasri, Abdulrahman Almjersah, Raja Ahmed Alqandouz, Walaa Alrfaea, Moayad Alrifaee, Rawan Alsaadi, Yousef Al-Saba'a, Entisar Alshareea, Eslam Alshenawy, Aneela Altaf, João Melo Alves, João Alves, Rita Alves, Joana Alves Cabrita, Maria Amaral, Amro Essam Amer, Nur Amira, Amos Amoako Adusei, John Amuasi, Roberto Andini, Claire Andrejak, Andrea Angheben, François Angoulvant, Sophia Ankrah, Séverine Ansart, Sivanesen Anthonidass, Massimo Antonelli, Carlos Alexandre Antunes de Brito, Ardiyan Apriyana, Yaseen Arabi, Irene Aragao, Francisco Arancibia, Carolline Araujo, Antonio Arcadipane, Patrick Archambault, Lukas Arenz, Jean-Benoît Arlet, Christel Arnold-Day, Lovkesh Arora, Rakesh Arora, Elise Artaud-Macari, Diptesh Aryal, Angel Asensio, Elizabeth A. Ashley, Muhammad Ashraf, Muhammad Sheharyar Ashraf, Abir Ben Ashur, Franklin Asiedu-Bekoe, Namra Asif, Mohammad Asim, Grace Assi, Jean Baptiste Assie, Amirul Asyraf, Fouda Atangana, Ahmed Atia, Minahel Atif, Asia Atif Abdelrhman Abdallahrs, Anika Atique, Moad Atlowly, AM Udara Lakshan Attanyake, Johann Auchabie, Hugues Aumaitre, Adrien Auvet, Abdelmalek Awad Ali Mohammed, Eyvind W. Axelsen, Ared Ayad, Ahmed Ayman Hassan Helmi, Laurène Azemar, Mohammed Azizeldin, Cecile Azoulay, Hakeem Babatunde, Benjamin Bach, Delphine Bachelet, Claudine Badr, Roar Bævre-Jensen, Nadia Baig, John Kenneth Baillie, J Kevin Baird, Erica Bak, Agamemnon Bakakos, Nazreen Abu Bakar, Hibah Bileid Bakeer, Ashraf Bakri, Andriy Bal, Mohanaprasanth Balakrishnan, Irene Bandoh, Firouzé Bani-Sadr, Renata Barbalho, Nicholas Yuri Barbosa, Wendy S. Barclay, Saef Umar Barnett, Michaela Barnikel, Helena Barrasa, Cleide Barrigoto, Marie Bartoli, Joaquín Baruch, Romain Basmaci, Muhammad Fadhli Hassin Basri, AbdAlkarim Batool, Denise Battaglini, Jules Bauer, Diego Fernando Bautista Rincon, Denisse Bazan Dow, Abigail Beane, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Aleksandr Beljantsev, David Bellemare, Anna Beltrame, Beatriz Amorim Beltrão, Marine Beluze, Nicolas Benech, Lionel Eric Benjiman, Suzanne Bennett, Luís Bento, Jan-Erik Berdal, Lamis Berdeweel, Delphine Bergeaud, Hazel Bergin, Giulia Bertoli, Lorenzo Bertolino, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Amar Bhatt, Krishna Bhavsar, Isabella Bianchi, Claudia Bianco, Sandra Bichoka, Farah Nadiah Bidin, Felwa Bin Humaid, Mohd Nazlin Bin Kamarudin, Muhannud Binnawara, Zeno Bisoffi, Patrick Biston, Laurent Bitker, Mustapha Bittaye, Jonathan Bitton, Pablo Blanco-Schweizer, Catherine Blier, Frank Bloos, Mathieu Blot, Filomena Boccia, Laetitia Bodenes, Debby Bogaert, Anne-Hélène Boivin, Ariel Bolanga, Isabela Bolaños, Pierre-Adrien Bolze, François Bompart, Aurelius Bonifasius, Joe Bonney, Diogo Borges, Raphaël Borie, Hans Martin Bosse, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, Sabelline Bouchez, Damien Bouhour, Kévin Bouiller, Laurence Bouillet, Camile Bouisse, Latsaniphone Bountthasavong, Anne-Sophie Boureau, John Bourke, Maude Bouscambert, Aurore Bousquet, Marielle Boyer-Besseyre, Maria Boylan, Fernando Augusto Bozza, Axelle Braconnier, Cynthia Braga, Timo Brandenburger, Filipa Brás Monteiro, Luca Brazzi, Dorothy Breen, Patrick Breen, David Brewster, Kathy Brickell, Tessa Broadley, Helen Brotherton, Alex Browne, Nicolas Brozzi, Sonja Hjellegjerde Brunvoll, Marjolein Brusse-Keizer, Petra Bryda, Nina Buchtele, Polina Bugaeva, Marielle Buisson, Danilo Buonsenso, Erlina Burhan, Donald Buri, Aidan Burrell, Ingrid G. Bustos, Denis Butnaru, André Cabie, Susana Cabral, Joana Cabrita, Eder Caceres, Cyril Cadoz, Rui Caetano Garcês, Kate Calligy, Jose Andres Calvache, João Camões, Valentine Campana, Paul Campbell, Josie Campisi, Cecilia Canepa, Mireia Cantero, Janice Caoili, Pauline Caraux-Paz, Sheila Cárcel, Filipa Cardoso, Filipe Cardoso, Nelson Cardoso, Sofia Cardoso, Simone Carelli, Nicolas Carlier, Thierry Carmoi, Gayle Carney, Inês Carqueja, Marie-Christine Carret, François Martin Carrier, Ida Carroll, Gail Carson, Maire-Laure Casanova, Mariana Cascão, Siobhan Casey, José Casimiro, Bailey Cassandra, Silvia Castañeda, Nidyanara Castanheira, Guylaine Castor-Alexandre, Ivo Castro, Ana Catarino, François-Xavier Catherine, Paolo Cattaneo, Roberta Cavalin, Giulio Giovanni Cavalli, Alexandros Cavayas, Adrian Ceccato, Masaneh Ceesay, Shelby Cerkovnik, Minerva Cervantes-Gonzalez, Muge Cevik, Anissa Chair, Catherine Chakveatze, Adrienne Chan, Meera Chand, Jean-Marc Chapplain, Charlotte Charpentier, Julie Chas, Muhammad Mobin Chaudry, Jonathan Samuel Chávez Iñiguez, Anjellica Chen, Yih-Sharng Chen, Léo Chenard, Matthew Pellan Cheng, Antoine Cheret, Thibault Chiarabini, Julian Chica, Suresh Kumar Chidambaram, Leong Chin Tho, Catherine Chirouze, Davide Chiumello, Sung-Min Cho, Bernard Cholley, Danoy Chommanam, Marie-Charlotte Chopin, Yock Ping Chow, Ting Soo Chow, Nathaniel Christy, Hiu Jian Chua, Jonathan Chua, Jose Pedro Cidade, José Miguel Cisneros Herreros, Anna Ciullo, Jennifer Clarke, Rolando Claure-Del Granado, Sara Clohisey, Cassidy Codan, Caitriona Cody, Jennifer Coles, Megan Coles, Gwenhaël Colin, Michael Collins, Pamela Combs, Jennifer Connolly, Marie Connor, Anne Conrad, Elaine Conway, Graham S. Cooke, Hugues Cordel, Amanda Corley, Sabine Cornelis, Alexander Daniel Cornet, Arianne Joy Corpuz, Andrea Cortegiani, Grégory Corvaisier, Camille Couffignal, Sandrine Couffin-Cadiergues, Roxane Courtois, Stéphanie Cousse, Juthaporn Cowan, Rachel Cregan, Gloria Crowl, Jonathan Crump, Claudina Cruz, Marc Csete, Ailbhe Cullen, Matthew Cummings, Gerard Curley, Elodie Curlier, Colleen Curran, Paula Custodio, Ana da Silva Filipe, Charlene Da Silveira, Al-Awwab Dabaliz, John Arne Dahl, Darren Dahly, Umberto D'Alessandro, Peter Daley, Zaina Dalloul, Heidi Dalton, Jo Dalton, Seamus Daly, Juliana Damas, Joycelyn Dame, Cammandji Damien, Nick Daneman, Jorge Dantas, Frédérick D'Aragon, Gillian de Loughry, Diego de Mendoza, Etienne De Montmollin, Rafael Freitas de Oliveira França, Ana Isabel de Pinho Oliveira, Rosanna De Rosa, Cristina De Rose, Thushan de Silva, Peter de Vries, Jillian Deacon, David Dean, Alexa Debard, Bianca DeBenedictis, Marie-Pierre Debray, Nathalie DeCastro, William Dechert, Romain Decours, Eve Defous, Isabelle Delacroix, Alexandre Delamou, Eric Delaveuve, Karen Delavigne, Nathalie M. Delfos, Ionna Deligiannis, Andrea Dell'Amore, Christelle Delmas, Pierre Delobel, Corine Delsing, Elisa Demonchy, Emmanuelle Denis, Dominique Deplanque, Pieter Depuydt, Diane Descamps, Mathilde Desvallées, Santi Dewayanti, Pathik Dhangar, Alpha Diallo, Souleymane Taran Diallo, Sylvain Diamantis, André Dias, Fernanda Dias Da Silva, Rodrigo Diaz, Juan Jose Diaz, Priscila Diaz, Bakary K. Dibba, Kévin Didier, Jean-Luc Diehl, Wim Dieperink, Jérôme Dimet, Vincent Dinot, Fara Diop, Alphonsine Diouf, Yael Dishon, Cedric Djadda, Félix Djossou, Annemarie B. Docherty, Helen Doherty, Arjen M. Dondorp, Christl A. Donnelly, Yoann Donohue, Sean Donohue, Peter Doran, Céline Dorival, Eric D'Ortenzio, Yash Doshi, Phouvieng Douangdala, James Joshua Douglas, Renee Douma, Nathalie Dournon, Joanne Downey, Mark Downing, Thomas Drake, Aoife Driscoll, Ibrahim Kwaku Duah, Claudio Duarte Fonseca, Vincent Dubee, François Dubos, Audrey Dubot-Pérès, Alexandre Ducancelle, Toni Duculan, Susanne Dudman, Abhijit Duggal, Paul Dunand, Mathilde Duplaix, Emanuele Durante-Mangoni, Lucian Durham, III, Bertrand Dussol, Juliette Duthoit, Xavier Duval, Anne Margarita Dyrhol-Riise, Sim Choon Ean, Ada Ebo, Marco Echeverria-Villalobos, Michael Edelstein, Siobhan Egan, Linn Margrete Eggesbø, Khadeja Ehzaz, Carla Eira, Mohammed El Sanharawi, Marwan El Sayed, Mohammed Elabid, Mohamed Bashir Elagili, Subbarao Elapavaluru, Mohammad Elbahnasawy, Sohail Elboshra, Brigitte Elharrar, Jacobien Ellerbroek, Merete Ellingjord-Dale, Hamida ELMagrahi, Mohammad Muatasm Elmubark, Loubna Elotmani, Lauren Eloundou, Philippine Eloy, Basma Elshaikhy, Tarek Elshazly, Wafa Elsokni, Aml Ahmed Eltayeb, Iqbal Elyazar, Zarief Kamel Emad, Hussein Embarek, Isabelle Enderle, Tomoyuki Endo, Gervais Eneli, Chan Chee Eng, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Haneen Esaadi, Mariano Esperatti, Hélène Esperou, Catarina Espírito Santo, Marina Esposito-Farese, Rachel Essaka, Lorinda Essuman, João Estevão, Manuel Etienne, Anna Greti Everding, Mirjam Evers, Isabelle Fabre, Marc Fabre, Ismaila Fadera, Asgad Osman Abdalla Fadlalla, Amna Faheem, Arabella Fahy, Cameron J. Fairfield, Zul Fakar, Komal Fareed, Pedro Faria, Ahmed Farooq, Hanan Fateena, Mohamed Fathi, Salem Fatima, Karine Faure, Raphaël Favory, Mohamed Fayed, Niamh Feely, Jorge Fernandes, Susana Fernandes, François-Xavier Ferrand, Eglantine Ferrand Devouge, Joana Ferrão, Mário Ferraz, Benigno Ferreira, Isabel Ferreira, Bernardo Ferreira, Sílvia Ferreira, Nicolas Ferriere, Céline Ficko, Claudia Figueiredo-Mello, William Finlayson, Thomas Flament, Tom Fletcher, Aline-Marie Florence, Letizia Lucia Florio, Brigid Flynn, Deirdre Flynn, Jean Foley, Victor Fomin, Tatiana Fonseca, Patricia Fontela, Karen Forrest, Simon Forsyth, Denise Foster, Giuseppe Foti, Berline Fotso, Erwan Fourn, Robert A. Fowler, Marianne Fraher, Diego Franch-Llasat, Christophe Fraser, John F. Fraser, Marcela Vieira Freire, Ana Freitas Ribeiro, Craig French, Caren Friedrich, Ricardo Fritz, Stéphanie Fry, Nora Fuentes, Masahiro Fukuda, G. Argin, Valérie Gaborieau, Rostane Gaci, Massimo Gagliardi, Jean-Charles Gagnard, Amandine Gagneux-Brunon, Abdou Gai, Sérgio Gaião, Linda Gail Skeie, Adham Mohamed Galal Mohamed Ramadan, Phil Gallagher, Carrol Gamble, Yasmin Gani, Arthur Garan, Rebekha Garcia, Julia Garcia-Diaz, Esteban Garcia-Gallo, Navya Garimella, Denis Garot, Valérie Garrait, Basanta Gauli, Anatoliy Gavrylov, Alexandre Gaymard, Johannes Gebauer, Eva Geraud, Louis Gerbaud Morlaes, Nuno Germano, Malak Ghemmeid, Praveen Kumar Ghisulal, Jade Ghosn, Marco Giani, Tristan Gigante, Elaine Gilroy, Guillermo Giordano, Michelle Girvan, Valérie Gissot, Gezy Giwangkancana, Daniel Glikman, Petr Glybochko, Eric Gnall, Geraldine Goco, François Goehringer, Siri Goepel, Jean-Christophe Goffard, Jin Yi Goh, Brigitta Golács, Jonathan Golob, Kyle Gomez, Joan Gómez-Junyent, Marie Gominet, Alicia Gonzalez, Patricia Gordon, Isabelle Gorenne, Laure Goubert, Cécile Goujard, Tiphaine Goulenok, Margarite Grable, Jeronimo Graf, Edward Wilson Grandin, Pascal Granier, Giacomo Grasselli, Lorenzo Grazioli, Christopher A. Green, Courtney Greene, William Greenhalf, Segolène Greffe, Domenico Luca Grieco, Matthew Griffee, Fiona Griffiths, Ioana Grigoras, Albert Groenendijk, Fassou Mathias Grovogui, Heidi Gruner, Yusing Gu, Jérémie Guedj, Martin Guego, Anne-Marie Guerguerian, Daniela Guerreiro, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Maisa Guimarães de Castro, Thomas Guimard, Marieke Haalboom, Daniel Haber, Ali Hachemi, Abdurrahman Haddud, Nadir Hadri, Wael Hafez, Fakhir Raza Haidri, Fatima Mhd Rida Hajij, Sheeba Hakak, Adam Hall, Sophie Halpin, Shaher Hamdan, Abdelhafeez Hamdi, Jawad Hameed, Ansley Hamer, Raph L. Hamers, Rebecca Hamidfar, Bato Hammarström, Naomi Hammond, Terese Hammond, Lim Yuen Han, Matly Hanan, Rashan Haniffa, Kok Wei Hao, Hayley Hardwick, Ewen M. Harrison, Janet Harrison, Samuel Bernard Ekow Harrison, Alan Hartman, Sulieman Hasan, Mohammad Ali Nabil Hasan, Mohd Shahnaz Hasan, Junaid Hashmi, Madiha Hashmi, Amoni Hassan, Ebtisam Hassanin, Muhammad Hayat, Ailbhe Hayes, Leanne Hays, Jan Heerman, Lars Heggelund, Ahmed Helmi, Ross Hendry, Martina Hennessy, Aquiles Rodrigo Henriquez-Trujillo, Maxime Hentzien, Diana Hernandez, Andrew Hershey, Liv Hesstvedt, Astarini Hidayah, Eibhlin Higgins, Rupert Higgins, Samuel Hinton, Hiroaki Hiraiwa, Haider Hirkani, Hikombo Hitoto, Antonia Ho, Yi Bin Ho, Alexandre Hoctin, Isabelle Hoffmann, Wei Han Hoh, Oscar Hoiting, Rebecca Holt, Jan Cato Holter, Juan Pablo Horcajada, Ikram Houas, Mabrouka Houderi, Catherine L. Hough, Stuart Houltham, Jimmy Ming-Yang Hsu, Jean-Sébastien Hulot, Abby Hurd, Iqbal Hussain, Aliae Mohamed Hussein, Mahmood Hussein, Fatima Ibrahim, Bashir Ibran, Samreen Ijaz, M. Arfan Ikram, Carlos Cañada Illana, Patrick Imbert, Muhammad Imran Ansari, Rana Imran Sikander, Hugo Inácio, Carmen Infante Dominguez, Yun Sii Ing, Mariachiara Ippolito, Vera Irawany, Sarah Isgett, Tiago Isidoro, Nadiah Ismail, Margaux Isnard, Mette Stausland Istre, Junji Itai, Daniel Ivulich, Danielle Jaafar, Salma Jaafoura, Hamza Jaber, Julien Jabot, Clare Jackson, Abubacarr Jagne, Stéphane Jaureguiberry, Denise Jaworsky, Florence Jego, Anilawati Mat Jelani, Synne Jenum, Ruth Jimbo-Sotomayor, Ong Yiaw Joe, Ruth Noemí Jorge García, Silje Bakken Jørgensen, Cédric Joseph, Mark Joseph, Swosti Joshi, Mercé Jourdain, Philippe Jouvet, Anna Jung, Hanna Jung, Dafsah Juzar, Ouifiya Kafif, Florentia Kaguelidou, Neerusha Kaisbain, Thavamany Kaleesvran, Sabina Kali, Karl Trygve Kalleberg, Smaragdi Kalomoiri, Muhammad Aisar Ayadi Kamaluddin, Armand Saloun Kamano, Zul Amali Che Kamaruddin, Nadiah Kamarudin, Kavita Kamineni, Darshana Hewa Kandamby, Kong Yeow Kang, Darakhshan Kanwal, Dyah Kanyawati, Mohamed Karghul, Pratap Karpayah, Todd Karsies, Daisuke Kasugai, Kevin Katz, Christy Kay, Lamees Kayyali, Seán Keating, Pulak Kedia, Andrea Kelly, Aoife Kelly, Claire Kelly, Niamh Kelly, Sadie Kelly, Yvelynne Kelly, Maeve Kelsey, Kalynn Kennon, Sommay Keomany, Maeve Kernan, Younes Kerroumi, Sharma Keshav, Shams Khail, Sarah Khaled, Imrana Khalid, Antoine Khalil, Irfan Khan, Quratul Ain Khan, Sushil Khanal, Abid Khatak, Krish Kherajani, Michelle E. Kho, Denisa Khoo, Ryan Khoo, Saye Khoo, Muhammad Nasir Khoso, Amin Khuwaja, Khor How Kiat, Yuri Kida, Peter Kiiza, Beathe Kiland Granerud, Anders Benjamin Kildal, Jae Burm Kim, Antoine Kimmoun, Detlef Kindgen-Milles, Nobuya Kitamura, Eyrun Floerecke Kjetland Kjetland, Paul Klenerman, Rob Klont, Gry Kloumann Bekken, Stephen R. Knight, Robin Kobbe, Paa Kobina Forson, Chamira Kodippily, Malte Kohns Vasconcelos, Sabin Koirala, Mamoru Komatsu, Franklina Korkor Abebrese, Volkan Korten, Stephanie Kouba, Mohamed Lamine Kourouma, Karifa Kourouma, Arsène Kpangon, Karolina Krawczyk, Ali Kredan, Vinothini Krishnan, Sudhir Krishnan, Oksana Kruglova, Anneli Krund, Pei Xuan Kuan, Ashok Kumar, Deepali Kumar, Ganesh Kumar, Mukesh Kumar, Dinesh Kuriakose, Ethan Kurtzman, Demetrios Kutsogiannis, Galyna Kutsyna, Ama Kwakyewaa Bedu-Addo, Sylvie Kwedi, Konstantinos Kyriakoulis, Marie Lachatre, Marie Lacoste, John G. Laffey, Nadhem Lafhej, Marie Lagrange, Fabrice Laine, Olivier Lairez, Sanjay Lakhey, Marc Lambert, François Lamontagne, Marie Langelot-Richard, Vincent Langlois, Eka Yudha Lantang, Marina Lanza, Cédric Laouénan, Samira Laribi, Delphine Lariviere, Stéphane Lasry, Sakshi Lath, Naveed Latif, Youssef Latifeh, Odile Launay, Didier Laureillard, Yoan Lavie-Badie, Andy Law, Cassie Lawrence, Teresa Lawrence, Minh Le, Clément Le Bihan, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Soizic Le Mestre, Gwenaël Le Moal, Vincent Le Moing, Hervé Le Nagard, Ema Leal, Marta Leal Santos, Biing Horng Lee, Heng Gee Lee, Su Hwan Lee, Jennifer Lee, Todd C. Lee, Yi Lin Lee, Gary Leeming, Bénédicte Lefebvre, Laurent Lefebvre, Benjamin Lefèvre, Sylvie LeGac, Merili-Helen Lehiste, Jean-Daniel Lelievre, François Lellouche, Adrien Lemaignen, Véronique Lemee, Anthony Lemeur, Gretchen Lemmink, Ha Sha Lene, Jenny Lennon, Rafael León, Marc Leone, Tanel Lepik, Quentin Lepiller, François-Xavier Lescure, Olivier Lesens, Mathieu Lesouhaitier, Amy Lester-Grant, Andrew Letizia, Sophie Letrou, Bruno Levy, Yves Levy, Claire Levy-Marchal, Katarzyna Lewandowska, Erwan L'Her, Gianluigi Li Bassi, Janet Liang, Ali Liaquat, Geoffrey Liegeon, Kah Chuan Lim, Wei Shen Lim, Chantre Lima, Bruno Lina, Lim Lina, Andreas Lind, Maja Katherine Lingad, Guillaume Lingas, Sylvie Lion-Daolio, Keibun Liu, Marine Livrozet, Patricia Lizotte, Antonio Loforte, Navy Lolong, Leong Chee Loon, Diogo Lopes, Dalia Lopez-Colon, Anthony L. Loschner, Paul Loubet, Bouchra Loufti, Guillame Louis, Silvia Lourenco, Lara Lovelace-Macon, Lee Lee Low, Marije Lowik, Jia Shyi Loy, Jean Christophe Lucet, Carlos M. Luna, Olguta Lungu, Miles Lunn, Liem Luong, Nestor Luque, Dominique Luton, Olavi Maasikas, Moïse Machado, Sara Machado, Gabriel Macheda, Mustafa Magzoub, Rafael Mahieu, Sophie Mahy, Ana Raquel Maia, Lars S. Maier, Oumou Maiga Ascofare, Mylène Maillet, Thomas Maitre, Nimisha Abdul Majeed, Maximilian Malfertheiner, Nadia Malik, Paddy Mallon, Fernando Maltez, Denis Malvy, Victoria Manda, Laurent Mandelbrot, Frank Manetta, Julie Mankikian, Edmund Manning, Aldric Manuel, Veronika Maráczi, Ceila Maria Sant′Ana Malaque, Flávio Marino, Samuel Markowicz, Ana Marques, Catherine Marquis, Laura Marsh, Brian Marsh, Megan Marshal, John Marshall, Celina Turchi Martelli, Dori-Ann Martin, Emily Martin, Guillaume Martin-Blondel, Alessandra Martinelli, F. Eduardo Martinez, Martin Martinot, Alejandro Martín-Quiros, Ana Martins, João Martins, Nuno Martins, Caroline Martins Rego, Gennaro Martucci, Olga Martynenko, Eva Miranda Marwali, Marsilla Marzukie, David Maslove, Sabina Mason, Sobia Masood, Fatma Masoud, Moise Massoma, Palmer Masumbe, Mohd Basri Mat Nor, Moshe Matan, Henrique Mateus Fernandes, Meghena Mathew, Christina Mathew, Mathieu Mattei, Laurence Maulin, Juergen May, Javier Maynar, Mayfong Mayxay, Thierry Mazzoni, Lisa Mc Sweeney, Colin McArthur, Naina McCann, Peter McCanny, Aine McCarthy, Anne McCarthy, Colin McCloskey, Rachael McConnochie, Sherry McDermott, Sarah E. McDonald, Aine McElroy, Samuel McElwee, Natalie McEvoy, Allison McGeer, Kenneth A. McLean, Paul McNally, Bairbre McNicholas, Edel Meaney, Cécile Mear-Passard, Maggie Mechlin, Nastia Medombou, Omar Mehkri, Ferruccio Mele, Luis Melo, Kashif Ali Memon, João João Mendes, Ogechukwu Menkiti, Kusum Menon, France Mentré, Alexander J. Mentzer, Emmanuelle Mercier, Noémie Mercier, Antoine Merckx, Mayka Mergeay-Fabre, Blake Mergler, António Mesquita, Roberta Meta, Osama Metwally, Agnès Meybeck, Dan Meyer, Alison M. Meynert, Vanina Meysonnier, Mehdi Mezidi, Céline Michelanglei, Isabelle Michelet, Efstathia Mihelis, Vladislav Mihnovit, Duha Milad Abdullah, Jennene Miller, Hugo Miranda-Maldonado, Nor Arisah Misnan, Nik Nur Eliza Mohamed, Nouralsabah Mohamed, Tahira Jamal Mohamed, Alaa Mohamed Ads, Ahmed Reda Mohamed Elsayed Abdelhalim, Libya Mohammed, Shrouk Fawze Mohammed Mostafa, Manahil Omer Abdelrahman Mohammedahmed, Omer Abdullah Mohammedelhassan, Asma Moin, Walaa Mokhtar, Elena Molinos, Brenda Molloy, Mary Mone, Agostinho Monteiro, Claudia Montes, Giorgia Montrucchio, Sarah Moore, Shona C. Moore, Lina Morales Cely, Marwa Morgom, Lucia Moro, Catherine Motherway, Ana Motos, Hugo Mouquet, Clara Mouton Perrot, Julien Moyet, Suleiman Haitham Mualla, Mohamed Muftah, Aisha Kalsoom Mufti, Ng Yong Muh, Mo'nes Muhaisen, Dzawani Muhamad, Jimmy Mullaert, Fredrik Müller, Karl Erik Müller, Daniel Munblit, Syed Muneeb Ali, Nadeem Munir, Laveena Munshi, Aisling Murphy, Patrick Murray, Marlène Murris, Srinivas Murthy, Himed Musaab, Alamin Mustafa, Mus'ab Mustafa, Dana Mustafa, Himasha Muvindi, Dimitra Melia Myrodia, Farah Nadia Mohd-Hanafiah, Behzad Nadjm, Dave Nagpal, Alex Nagrebetsky, Blanka Nagybányai-Nagy, Herwin Nanda Boudoin, Mangala Narasimhan, Nageswaran Narayanan, Prashant Nasa, Rashid Nasim Khan, Ahmad Nasrallah, Adel Gerges Nassif Metri, Alasdair Nazerali-Maitland, Nadège Neant, Holger Neb, Nikita Nekliudov, Matthew Nelder, Erni Nelwan, Raul Neto, Emily Neumann, Wing Yiu Ng, Pauline Yeung Ng, Anthony Nghi, Duc Nguyen, Orna Ni Choileain, Niamh Ni Leathlobhair, Nerissa Niba, Alistair D. Nichol, Prompak Nitayavardhana, Stephanie Nonas, Nurul Amani Mohd Noordin, Nurul Faten Izzati Norharizam, Anita North, Alessandra Notari, Mahdad Noursadeghi, Adam Nowinski, Saad Nseir, Leonard Numfor, Nurnaningsih Nurnaningsih, Dwi Utomo Nusantara, Elsa Nyamankolly, Anders Benteson Nygaard, Fionnuala O. Brien, Annmarie O. Callaghan, Annmarie O'Callaghan, Giovanna Occhipinti, Derbrenn OConnor, Max O'Donnell, Lawrence Ofori-Boadu, Tawnya Ogston, Takayuki Ogura, Tak-Hyuk Oh, Sophie O'Halloran, Katie O'Hearn, Sally-Ann Ohene, João Oliveira, Larissa Oliveira, Piero L. Olliaro, Cinderella Omar Rageh Elnaggar, Alsarrah Ali Mohammed Omer, Pierre Ondobo, David S.Y. Ong, Jee Yan Ong, Wilna Oosthuyzen, Anne Opavsky, Peter Openshaw, Saijad Orakzai, Claudia Milena Orozco-Chamorro, Jamel Ortoleva, Mohamed Osama Elsayed Soliman, Javier Osatnik, Linda O'Shea, Miriam O'Sullivan, Eman Othman, Siti Zubaidah Othman, Nadia Ouamara, Rachida Ouissa, Micheal Owusu, Ama Akyampomaa Owusu-Asare, Eric Oziol, Maïder Pagadoy, Justine Pages, Amanda Palacios, Massimo Palmarini, Giovanna Panarello, Hem Paneru, Lai Hui Pang, Mauro Panigada, Nathalie Pansu, Aurélie Papadopoulos, Rachael Parke, Melissa Parker, Jérémie Pasquier, Bruno Pastene, Fabian Patauner, Drashti Patel, Mohan Dass Pathmanathan, Luís Patrão, Patricia Patricio, Lisa Patterson, Rajyabardhan Pattnaik, Christelle Paul, Mical Paul, Jorge Paulos, William A. Paxton, Jean-François Payen, Sandra L. Peake, Kalaiarasu Peariasamy, Giles J. Peek, Florent Peelman, Nathan Peiffer-Smadja, Vincent Peigne, Mare Pejkovska, Paolo Pelosi, Ithan D. Peltan, Rui Pereira, Daniel Perez, Thomas Perpoint, Antonio Pesenti, Vincent Pestre, Lenka Petrou, Michele Petrovic, Ventzislava Petrov-Sanchez, Frank Olav Pettersen, Gilles Peytavin, Richard Odame Philips, Ooyanong Phonemixay, Soulichanya Phoutthavong, Michael Piagnerelli, Walter Picard, Olivier Picone, Maria de Piero, Djura Piersma, Carlos Pimentel, Raquel Pinto, Catarina Pires, Lionel Piroth, Ayodhia Pitaloka, Chiara Piubelli, Riinu Pius, Simone Piva, Laurent Plantier, Hon Shen Png, Julien Poissy, Ryadh Pokeerbux, Sergio Poli, Georgios Pollakis, Diane Ponscarme, Diego Bastos Porto, Andra-Maris Post, Douwe F. Postma, Pedro Povoa, Diana Póvoas, Jeff Powis, Sofia Prapa, Viladeth Praphasiri, Sébastien Preau, Christian Prebensen, Jean-Charles Preiser, Anton Prinssen, Gamage Dona Dilanthi Priyadarshani, Lucia Proença, Sravya Pudota, Bambang Pujo Semedi, Mathew Pulicken, Peter Puplampu, Gregory Purcell, Luisa Quesada, Vilmaris Quinones-Cardona, Else Quist-Paulsen, Mohammed Quraishi, Fadi Qutishat, Maia Rabaa, Christian Rabaud, Ebenezer Rabindrarajan, Aldo Rafael, Marie Rafiq, Abdelrahman Ragab, Mutia Rahardjani, Arslan Rahat Ullah, Ahmad Kashfi Haji Ab Rahman, Rozanah Abd Rahman, Fernando Rainieri, Giri Shan Rajahram, Pratheema Ramachandran, Nagarajan Ramakrishnan, José Ramalho, Ahmad Afiq Ramli, Blandine Rammaert, Grazielle Viana Ramos, Asim Rana, Rajavardhan Rangappa, Ritika Ranjan, Christophe Rapp, Aasiyah Rashan, Thalha Rashan, Ghulam Rasheed, Menaldi Rasmin, Indrek Rätsep, Cornelius Rau, Tharmini Ravi, Ali Raza, Andre Real, Stanislas Rebaudet, Sarah Redl, Brenda Reeve, Attaur Rehman, Muhammad Osama Rehman Khalid, Dag Henrik Reikvam, Renato Reis, Jonathan Remppis, Martine Remy, Hongru Ren, Hanna Renk, Anne-Sophie Resseguier, Matthieu Revest, Oleksa Rewa, Maria Ines Ribeiro, Antonia Ricchiuto, David Richardson, Denise Richardson, Laurent Richier, Siti Nurul Atikah Ahmad Ridzuan, Ana L. Rios, Asgar Rishu, Patrick Rispal, Karine Risso, Maria Angelica Rivera Nuñez, Chiara Robba, André Roberto, Stephanie Roberts, Charles Roberts, David L. Robertson, Olivier Robineau, Anna Roca, Ferran Roche-Campo, Paola Rodari, Simão Rodeia, Bernhard Roessler, Claire Roger, Pierre-Marie Roger, Roberto Roncon-Albuquerque, Jr., Mélanie Roriz, Manuel Rosa-Calatrava, Michael Rose, Dorothea Rosenberger, Andrea Rossanese, Matteo Rossetti, Patrick Rossignol, Carine Roy, Benoît Roze, Desy Rusmawatiningtyas, Clark D. Russell, Maeve Ryan, Steffi Ryckaert, Aleksander Rygh Holten, Isabela Saba, Sairah Sadaf, Musharaf Sadat, Valla Sahraei, Abdurraouf Said, Nadia Saidani, Pranya Sakiyalak, Fodé Bangaly Sako, Moamen Salah, Ali Alaa Salah Eldin Mohamed Abbas, Nawal Salahuddin, Leonardo Salazar, Jodat Saleem, Mohammed Saleh Alyasiri, Talat Ahmed Abu Salem, Gabriele Sales, Charlotte Salmon Gandonniere, Hélène Salvator, Dana Samardali, Shaden Samardali, Yehia Samir Shaaban Aly Orabi, Emely Sanchez, Olivier Sanchez, Kizy Sanchez de Oliveira, Angel Sanchez-Miralles, Vanessa Sancho-Shimizu, Gyan Sandhu, Zulfiqar Sandhu, Pierre-François Sandrine, Oana Săndulescu, Marlene Santos, Shirley Sarfo-Mensah, Bruno Sarmento Banheiro, Iam Claire E. Sarmiento, Benjamine Sarton, Ankana Satya, Sree Satyapriya, Rumaisah Satyawati, Egle Saviciute, Yen Tsen Saw, Justin Schaffer, Tjard Schermer, Arnaud Scherpereel, Marion Schneider, János Schnur, Stephan Schroll, Michael Schwameis, Gary Schwartz, Janet T. Scott, James Scott-Brown, Nicholas Sedillot, Tamara Seitz, Jaganathan Selvanayagam, Mageswari Selvarajoo, Malcolm G. Semple, Rasidah Bt Senian, Eric Senneville, Claudia Sepulveda, Filipa Sequeira, Tânia Sequeira, Ary Serpa Neto, Ellen Shadowitz, Syamin Asyraf Shahidan, Hamza Shahla, Laila Shalabi, Haitam Shames, Anuraj Shankar, Shaikh Sharjeel, Pratima Sharma, Catherine A. Shaw, Victoria Shaw, John Robert Sheenan, Dr. Rajesh Mohan Shetty, Rohan Shetty, Mohiuddin Shiekh, Nobuaki Shime, Keiki Shimizu, Sally Shrapnel, Shubha Kalyan Shrestha, Pramesh Sundar Shrestha, Hoi Ping Shum, Nassima Si Mohammed, Ng Yong Siang, Moses Siaw-Frimpong, Jeanne Sibiude, Bountoy Sibounheuang, Nidhal Siddig, Atif Siddiqui, Maqsood Ahmed Siddiqui, Louise Sigfrid, Fatoumata Sillah, Piret Sillaots, Catarina Silva, Maria Joao Silva, Rogério Silva, Benedict Sim Lim Heng, Wai Ching Sin, Dario Sinatti, Mahendra Singh, Punam Singh, Pompini Agustina Sitompul, Karisha Sivam, Vegard Skogen, Sue Smith, Benjamin Smood, Coilin Smyth, Morgane Snacken, Dominic So, Tze Vee Soh, Lene Bergendal Solberg, Joshua Solomon, Tom Solomon, Emily Somers, Agnès Sommet, Myung Jin Song, Rima Song, Tae Song, Jack Song Chia, Arne Søraas, Albert Sotto, Edouard Soum, Ana Chora Sousa, Marta Sousa, Maria Sousa Uva, Vicente Souza-Dantas, Mamadou Saliou Sow, Alexandra Sperry, Elisabetta Spinuzza, B. P. Sanka Ruwan Sri Darshana, Shiranee Sriskandan, Sarah Stabler, Thomas Staudinger, Stephanie-Susanne Stecher, Trude Steinsvik, Ymkje Stienstra, Birgitte Stiksrud, Eva Stolz, Amy Stone, Anca Streinu-Cercel, Adrian Streinu-Cercel, Geoff Strong, Ami Stuart, David Stuart, Richa Su, Decy Subekti, Gabriel Suen, Jacky Y. Suen, Prasanth Sukumar, Asfia Sultana, Charlotte Summers, Dubravka Supic, Deepashankari Suppiah, Magdalena Surovcová, Atie Suwarti, Andrey Svistunov, Sarah Syahrin, Augustina Sylverken, Konstantinos Syrigos, Jaques Sztajnbok, Konstanty Szuldrzynski, Shirin Tabrizi, Fabio S. Taccone, Lysa Tagherset, Shahdattul Mawarni Taib, Sara Taleb, Cheikh Talla, Jelmer Talsma, Renaud Tamisier, Maria Lawrensia Tampubolon, Kim Keat Tan, Yan Chyi Tan, Hiroyuki Tanaka, Taku Tanaka, Hayato Taniguchi, Huda Taqdees, Arshad Taqi, Coralie Tardivon, Yousef Tarek Kamal Mostafa, Ali Tarhabat, Pierre Tattevin, M Azhari Taufik, Hassan Tawfik, Tze Yuan Tee, João Teixeira, Sofia Tejada, Marie-Capucine Tellier, Sze Kye Teoh, Vanessa Teotonio, François Téoulé, Olivier Terrier, Nicolas Terzi, Hubert Tessier-Grenier, Adrian Tey, Alif Adlan Mohd Thabit, Anand Thakur, Zhang Duan Tham, Suvintheran Thangavelu, Elmi Theron, Vincent Thibault, Simon-Djamel Thiberville, Benoît Thill, Jananee Thirumanickam, Niamh Thompson, Shaun Thompson, Emma C. Thomson, David Thomson, Mathew Thorpe, Surain Raaj Thanga Thurai, Ryan S. Thwaites, Paul Tierney, Vadim Tieroshyn, Peter S. Timashev, Jean-François Timsit, Noémie Tissot, Fiona Toal, Jordan Zhien Yang Toh, Maria Toki, Kristian Tonby, Sia Loong Tonnii, Marta Torre, Antoni Torres, Margarida Torres, Rosario Maria Torres Santos-Olmo, Hernando Torres-Zevallos, Aboubacar Tounkara, Michael Towers, Fodé Amara Traoré, Tony Trapani, Cécile Tromeur, Ioannis Trontzas, Tiffany Trouillon, Jeanne Truong, Christelle Tual, Sarah Tubiana, Helen Tuite, Alexis F. Turgeon, Jean-Marie Turmel, Lance C.W. Turtle, Anders Tveita, Pawel Twardowski, Makoto Uchiyama, PG Ishara Udayanga, Andrew Udy, Roman Ullrich, Alberto Uribe, Asad Usman, Effua Usuf, Timothy M. Uyeki, Cristinava Vajdovics, Piero Valentini, Luís Val-Flores, Stijn Van de Velde, Marcel van den Berge, Machteld van der Feltz, Job van der Palen, Paul van der Valk, Nicky Van Der Vekens, Peter Van der Voort, Sylvie Van Der Werf, Laura van Gulik, Jarne Van Hattem, Carolien van Netten, Ilonka van Veen, Noémie Vanel, Henk Vanoverschelde, Michael Varrone, Shoban Raj Vasudayan, Charline Vauchy, Pavan Kumar Vecham, Shaminee Veeran, Aurélie Veislinger, Sebastian Vencken, Sara Ventura, Annelies Verbon, José Ernesto Vidal, César Vieira, Deepak Vijayan, Judit Villar, Pierre-Marc Villeneuve, Andrea Villoldo, Gayatri Vishwanathan, Benoit Visseaux, Hannah Visser, Chiara Vitiello, Manivanh Vongsouvath, Harald Vonkeman, Fanny Vuotto, Suhaila Abdul Wahab, Noor Hidayu Wahab, Nadirah Abdul Wahid, Marina Wainstein, Laura Walsh, Wan Fadzlina Wan Muhd Shukeri, Chih-Hsien Wang, Steve Webb, Katharina Weil, Tan Pei Wen, Hassi Wesam, Sanne Wesselius, T. Eoin West, Murray Wham, Bryan Whelan, Nicole White, Paul Henri Wicky, Aurélie Wiedemann, Surya Otto Wijaya, Keith Wille, Sue Willems, Bailey Williams, Patricia J. Williams, Virginie Williams, Jessica Wittman, Calvin Wong, Xin Ci Wong, Yew Sing Wong, Teck Fung Wong, Natalie Wright, Lim Saio Xian, Ioannis Xynogalas, Siti Rohani Binti Mohd Yakop, Masaki Yamazaki, Elizabeth Yarad, Yazdan Yazdanpanah, Nicholas Yee Liang Hing, Abdelrahman Yehia Mahmoud Abdelaal, Cécile Yelnik, Chian Hui Yeoh, Stephanie Yerkovich, Touxiong Yiaye, Toshiki Yokoyama, Hodane Yonis, Obada Yousif, Saptadi Yuliarto, Akram Zaaqoq, Marion Zabbe, Gustavo E. Zabert, Kai Zacharowski, Masliza Zahid, Maram Zahran, Nor Zaila Binti Zaidan, Maria Zambon, Miguel Zambrano, Alberto Zanella, Nurul Zaynah, Hiba Zayyad, Alexander Zoufaly, and David Zucman

Subjects
COVID-19, Non-respiratory symptoms, Respiratory symptoms, Risk factors, Mortality, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

Published
2024
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3. The prognostic impact of SIGLEC5-induced impairment of CD8+ T cell activation in sepsisResearch in context

Author

Roberto Lozano-Rodríguez, José Avendaño-Ortíz, Karla Montalbán-Hernández, Juan Carlos Ruiz-Rodríguez, Ricardo Ferrer, Alejandro Martín-Quirós, Charbel Maroun-Eid, Juan José González-López, Anna Fàbrega, Verónica Terrón-Arcos, María Gutiérrez-Fernández, Elisa Alonso-López, Carolina Cubillos-Zapata, María Fernández-Velasco, Rebeca Pérez de Diego, Pablo Pelegrin, Carlos García-Palenciano, Francisco J. Cueto, Carlos del Fresno, and Eduardo López-Collazo

Subjects
Sepsis, Immune checkpoint, SIGLEC5, T-cell exhaustion, Biomarker, HIF1α, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: Sepsis is associated with T-cell exhaustion, which significantly reduces patient outcomes. Therefore, targeting of immune checkpoints (ICs) is deemed necessary for effective sepsis management. Here, we evaluated the role of SIGLEC5 as an IC ligand and explored its potential as a biomarker for sepsis. Methods: In vitro and in vivo assays were conducted to both analyse SIGLEC5's role as an IC ligand, as well as assess its impact on survival in sepsis. A multicentre prospective cohort study was conducted to evaluate the plasmatic soluble SIGLEC5 (sSIGLEC5) as a mortality predictor in the first 60 days after admission in sepsis patients. Recruitment included sepsis patients (n = 346), controls with systemic inflammatory response syndrome (n = 80), aneurism (n = 11), stroke (n = 16), and healthy volunteers (HVs, n = 100). Findings: SIGLEC5 expression on monocytes was increased by HIF1α and was higher in septic patients than in healthy volunteers after ex vivo LPS challenge. Furthermore, SIGLEC5-PSGL1 interaction inhibited CD8+ T-cell proliferation. Administration of sSIGLEC5r (0.8 mg/kg) had adverse effects in mouse endotoxemia models. Additionally, plasma sSIGLEC5 levels of septic patients were higher than HVs and ROC analysis revealed it as a mortality marker with an AUC of 0.713 (95% CI, 0.656–0.769; p

Published
2023
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4. Rationale for combined therapies in severe-to-critical COVID-19 patients

Author

Aitor Gonzaga, Etelvina Andreu, Luis M. Hernández-Blasco, Rut Meseguer, Karima Al-Akioui-Sanz, Bárbara Soria-Juan, Jose Carlos Sanjuan-Gimenez, Cristina Ferreras, Juan R. Tejedo, Guillermo Lopez-Lluch, Rosa Goterris, Loreto Maciá, Jose M. Sempere-Ortells, Abdelkrim Hmadcha, Alberto Borobia, Jose L. Vicario, Ana Bonora, Cristobal Aguilar-Gallardo, Jose L. Poveda, Cristina Arbona, Cristina Alenda, Fabian Tarín, Francisco M. Marco, Esperanza Merino, Francisco Jaime, José Ferreres, Juan Carlos Figueira, Carlos Cañada-Illana, Sergio Querol, Manuel Guerreiro, Cristina Eguizabal, Alejandro Martín-Quirós, Ángel Robles-Marhuenda, Antonio Pérez-Martínez, Carlos Solano, and Bernat Soria

Subjects
COVID-19, cytokine storm, immunomodulation, mesenchymal stromal cells, SARS-CoV-2, advanced therapies, Immunologic diseases. Allergy, RC581-607
Abstract

An unprecedented global social and economic impact as well as a significant number of fatalities have been brought on by the coronavirus disease 2019 (COVID-19), produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute SARS-CoV-2 infection can, in certain situations, cause immunological abnormalities, leading to an anomalous innate and adaptive immune response. While most patients only experience mild symptoms and recover without the need for mechanical ventilation, a substantial percentage of those who are affected develop severe respiratory illness, which can be fatal. The absence of effective therapies when disease progresses to a very severe condition coupled with the incomplete understanding of COVID-19’s pathogenesis triggers the need to develop innovative therapeutic approaches for patients at high risk of mortality. As a result, we investigate the potential contribution of promising combinatorial cell therapy to prevent death in critical patients.

Published
2023
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5. Brand-specific estimates of influenza vaccine effectiveness for the 2021–2022 season in Europe: results from the DRIVE multi-stakeholder study platform

Author

Anke L. Stuurman, Antonio Carmona, Jorne Biccler, Alexandre Descamps, Miriam Levi, Ulrike Baum, Ainara Mira-Iglesias, Stefania Bellino, Uy Hoang, Simon de Lusignan, Roberto Bonaiuti, Bruno Lina, Caterina Rizzo, Hanna Nohynek, Javier Díez-Domingo, DRIVE Study Contributors, Anca Cristina Drăgănescu, Oana Săndulescu, Daniela Piţigoi, Victor Daniel Miron, Anca Streinu-Cercel, Anuţa Bilaşco, Adrian Streinu-Cercel, Dragoş Florea, Ovidiu Vlaicu, Simona Paraschiv, Leontina Bănică, Dan Oţelea, Monika Redlberger-Fritz, Eva Geringer, Amparo López-Bernus, Ana Haro Perez, Nieves Gutierrez Zufiaurre, Cristina Carbonell Muñoz, Miguel Marcos Martin, Muñoz Juan Luis Bellido, Isabel Gil Rodríguez, Antonio Muro Alvarez, Moncef Belhassen Garcia, Giancarlo Icardi, Stefano Mosca, Donatella Panatto, Emanuele Montomoli, Silvana Castaldi, Andrea Orsi, Alexander Domnich, Maria Chironna, Daniela Loconsole, Ilaria Manini, Christian Napoli, Alessandra Torsello, Elena Pariani, and Piero Luigi Lai, Susana Otero-Romero, Andrés Antón Pagarolas, Cristina Andrés, Ingrid Carbonés, Oleguer Pares, Mar Fornaguera, Anna Oller, Xavier Salgado, Patricia Tejerina, Cristina Martinez, Alejandro Orrico-Sánchez, F. Xavier López-Labrador, Beatriz Mengual-Chuliá, Judit Sánchez Soler, María Jinglei Casanova Palomino, Juan Mollar-Maseres, Miguel Tortajada-Girbés, Noelia Rodríguez-Blanco, Mario Carballido-Fernández, Raquel Andreu Ivorra, Àngels Sierra Fortuny, Beatriz Segura Segura, Cristina Mingot Ureta, Sagrario Corrales Díaz-Flores, Ángela Sánchez Pla, María Dolores Tirado Balaguer, Juan Alberola, José Miguel Nogueira, Juan J Camarena, Francisco Arjona-Zaragozí, Maruan Shalabi Benavent, José Luis López-Hontangas, María Dolores Gómez, Alejandro Martín-Quirós, Carlos Cañada Illana, Emilio Cendejas, Irma Casas García, Guillermo Mena Pinilla, María Esteve Pardo, Lola Álamo Junquera, Cristina Casañ, Sandra Fernandez Morodo, Agueda Hernández, Pere-Joan Cardona, Marta Segura, Andreu C. Pelegrin, Sara González-Gómez, Verónica Saludes, Elisa Martró, Valtýr Stefánsson Thors, Kristín L. Björnsdóttir, Liem Luong, Zineb Lesieur, Yacine Saidi, Rebecca Bauer, Christine Pereira, Philippe Vanhems, Fabrice Lainé, Florence Galtier, Xavier Duval, Christine Durier, Paolo Bonanni, Alfredo Vannacci, and Claudia Ravaldi

Subjects
vaccine effectiveness, influenza, influenza vaccines, test-negative design, post authorization, real-world evidence, Public aspects of medicine, RA1-1270
Abstract

IntroductionDevelopment of Robust and Innovative Vaccine Effectiveness (DRIVE) was a European public–private partnership (PPP) that aimed to provide annual, brand-specific estimates of influenza vaccine effectiveness (IVE) for regulatory and public health purposes. DRIVE was launched in 2017 under the umbrella of the Innovative Medicines Initiative (IMI) and conducted IVE studies from its pilot season in 2017–2018 to its final season in 2021–2022.MethodsIn 2021–2022, DRIVE conducted four primary care-based test-negative design (TND) studies (Austria, Italy, Iceland, and England; involving >1,000 general practitioners), nine hospital-based TND studies (France, Iceland, Italy, Romania, and Spain, for a total of 21 hospitals), and one population-based cohort study in Finland. In the TND studies, patients with influenza-like illness (primary care) or severe acute respiratory infection (hospital) were enrolled, and laboratory tested for influenza using RT-PCR. Study contributor-specific IVE was calculated using logistic regression, adjusting for age, sex, and calendar time, and pooled by meta-analysis.ResultsIn 2021–2022, pooled confounder-adjusted influenza vaccine effectiveness (IVE) estimates against laboratory-confirmed influenza (LCI) overall and per type and subtype/lineage was produced, albeit with wide confidence intervals (CI). The limited circulation of influenza in Europe did not allow the network to reach the optimal sample size to produce precise IVE estimates for all the brands included. The most significant IVE estimates were 76% (95% CI 23%−93%) for any vaccine and 81% (22%−95%) for Vaxigrip Tetra in adults ≥65 years old and 64% (25%−83%) for Fluenz Tetra in children (TND primary care setting), 85% (12%−97%) for any vaccine in adults 18–64 years (TND hospital setting), and 38% (1%−62%) in children 6 months−6 years (population-based cohort, mixed setting).DiscussionOver five seasons, DRIVE collected data on >35,000 patients, more than 60 variables, and 13 influenza vaccines. DRIVE demonstrated that estimating brand-specific IVE across Europe is possible, but achieving sufficient sample size to obtain precise estimates for all relevant stratifications remains a challenge. Finally, DRIVE's network of study contributors and lessons learned have greatly contributed to the development of the COVID-19 vaccine effectiveness platform COVIDRIVE.

Published
2023
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6. mRNA-1273 boost after BNT162b2 vaccination generates comparable SARS-CoV-2-specific functional responses in naïve and COVID-19-recovered individuals

Author

Roberto Lozano-Rodríguez, José Avendaño-Ortíz, Verónica Terrón, Karla Montalbán-Hernández, José Casalvilla-Dueñas, Marta Bergón-Gutiérrez, Pablo Mata-Martínez, Alejandro Martín-Quirós, Miguel Ángel García-Garrido, Álvaro del Balzo-Castillo, María Peinado, Laura Gómez, Irene Llorente-Fernández, Gema Martín-Miguel, Carmen Herrero-Benito, Lissette López-Morejón, Carmen Vela-Olmo, Carolina Cubillos-Zapata, Eduardo López-Collazo, and Carlos del Fresno

Subjects
mRNA vaccine, COVID-19 booster, SARS-CoV-2-specific, naïve, recovered from COVID-19, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionCOVID-19 vaccines based on mRNA have represented a revolution in the biomedical research field. The initial two-dose vaccination schedule generates potent humoral and cellular responses, with a massive protective effect against severe COVID-19 and death. Months after this vaccination, levels of antibodies against SARS-CoV-2 waned, and this promoted the recommendation of a third vaccination dose.MethodsWe have performed an integral and longitudinal study of the immunological responses triggered by the booster mRNA-1273 vaccination, in a cohort of health workers previously vaccinated with two doses of the BNT162b2 vaccine at University Hospital La Paz located in Madrid, Spain. Circulating humoral responses and SARS-CoV-2-specific cellular reactions, after ex vivo restimulation of both T and B cells (cytokines production, proliferation, class switching), have been analyzed. Importantly, all along these studies, the analyses have been performed comparing naïve and subjects recovered from COVID-19, addressing the influence of a previous infection by SARS-CoV-2. Furthermore, as the injection of the third vaccination dose was contemporary to the rise of the Omicron BA.1 variant of concern, T- and B-cell-mediated cellular responses have been comparatively analyzed in response to this variant.ResultsAll these analyses indicated that differential responses to vaccination due to a previous SARS-CoV-2 infection were balanced following the boost. The increase in circulating humoral responses due to this booster dropped after 6 months, whereas T-cell-mediated responses were more stable along the time. Finally, all the analyzed immunological features were dampened in response to the Omicron variant of concern, particularly late after the booster vaccination.ConclusionThis work represents a follow-up longitudinal study for almost 1.5 years, analyzing in an integral manner the immunological responses triggered by the prime-boost mRNA-based vaccination schedule against COVID-19.

Published
2023
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7. An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients

Author

Bronner P Gonçalves, Matthew Hall, Waasila Jassat, Valeria Balan, Srinivas Murthy, Christiana Kartsonaki, Malcolm G Semple, Amanda Rojek, Joaquín Baruch, Luis Felipe Reyes, Abhishek Dasgupta, Jake Dunning, Barbara Wanjiru Citarella, Mark Pritchard, Alejandro Martín-Quiros, Uluhan Sili, J Kenneth Baillie, Diptesh Aryal, Yaseen Arabi, Aasiyah Rashan, Andrea Angheben, Janice Caoili, François Martin Carrier, Ewen M Harrison, Joan Gómez-Junyent, Claudia Figueiredo-Mello, James Joshua Douglas, Mohd Basri Mat Nor, Yock Ping Chow, Xin Ci Wong, Silvia Bertagnolio, Soe Soe Thwin, Anca Streinu-Cercel, Leonardo Salazar, Asgar Rishu, Rajavardhan Rangappa, David SY Ong, Madiha Hashmi, Gail Carson, Janet Diaz, Rob Fowler, Moritz UG Kraemer, Evert-Jan Wils, Peter Horby, Laura Merson, Piero L Olliaro, and ISARIC Clinical Characterisation Group

Subjects
COVID-19, Omicron, fatality, emergence, epidemiology, symptoms, Medicine, Science, Biology (General), QH301-705.5
Abstract

Background: Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings. Methods: Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. Results: Our analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61–0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population. Conclusions: Although clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome. Funding: Bronner P. Gonçalves, Peter Horby, Gail Carson, Piero L. Olliaro, Valeria Balan, Barbara Wanjiru Citarella, and research costs were supported by the UK Foreign, Commonwealth and Development Office (FCDO) and Wellcome [215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z]; and Janice Caoili and Madiha Hashmi were supported by the UK FCDO and Wellcome [222048/Z/20/Z]. Peter Horby, Gail Carson, Piero L. Olliaro, Kalynn Kennon and Joaquin Baruch were supported by the Bill & Melinda Gates Foundation [OPP1209135]; Laura Merson was supported by University of Oxford’s COVID-19 Research Response Fund - with thanks to its donors for their philanthropic support. Matthew Hall was supported by a Li Ka Shing Foundation award to Christophe Fraser. Moritz U.G. Kraemer was supported by the Branco Weiss Fellowship, Google.org, the Oxford Martin School, the Rockefeller Foundation, and the European Union Horizon 2020 project MOOD (#874850). The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views of the European Commission. Contributions from Srinivas Murthy, Asgar Rishu, Rob Fowler, James Joshua Douglas, François Martin Carrier were supported by CIHR Coronavirus Rapid Research Funding Opportunity OV2170359 and coordinated out of Sunnybrook Research Institute. Contributions from Evert-Jan Wils and David S.Y. Ong were supported by a grant from foundation Bevordering Onderzoek Franciscus; and Andrea Angheben by the Italian Ministry of Health “Fondi Ricerca corrente–L1P6” to IRCCS Ospedale Sacro Cuore–Don Calabria. The data contributions of J.Kenneth Baillie, Malcolm G. Semple, and Ewen M. Harrison were supported by grants from the National Institute for Health Research (NIHR; award CO-CIN-01), the Medical Research Council (MRC; grant MC_PC_19059), and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE) (award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award IS-BRC-1215-20013), and NIHR Clinical Research Network providing infrastructure support. All funders of the ISARIC Clinical Characterisation Group are listed in the appendix.

Published
2022
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8. Prior SARS‐CoV‐2 infection balances immune responses triggered by four EMA‐approved COVID‐19 vaccines: An observational study

Author

Roberto Lozano‐Rodríguez, Verónica Terrón‐Arcos, Karla Montalbán‐Hernández, José Carlos Casalvilla‐Dueñas, Marta Bergón‐Gutierrez, Alejandro Pascual‐Iglesias, Jaime Valentín Quiroga, Luis A. Aguirre, Rebeca Pérez de Diego, Carmen Vela‐Olmo, Lissette López‐Morejón, Alejandro Martín‐Quirós, Álvaro del Balzo‐Castillo, María A. Peinado‐Quesada, Miguel A. García‐Garrido, Laura Gómez‐Lage, Carmen Herrero‐Benito, Irene Llorente‐Fernández, Gema Martín‐Miguel, Margarita Torrejón, Carolina Cubillos‐Zapata, Carlos del Fresno, José Avendaño‐Ortiz, and Eduardo López‐Collazo

Subjects
Medicine (General), R5-920
Published
2022
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9. Potential Role of the Galectin-9/TIM-3 Axis in the Disparate Progression of SARS-CoV-2 in a Married Couple: A Case Report

Author

Alejandro Martín-Quirós, Charbel Maroun-Eid, José Avendaño-Ortiz, Roberto Lozano-Rodríguez, Jaime Valentín Quiroga, Verónica Terrón, Karla Montalbán-Hernández, Miguel A. García-Garrido, Elena Muñoz del Val, Álvaro del Balzo-Castillo, Carolina Rubio, Carolina Cubillos-Zapata, Luis A. Aguirre, and Eduardo López-Collazo

Subjects
covid-19, immune checkpoints, galectin-9, tim-3, sars-cov-2, sepsis, Medicine (General), R5-920
Abstract

We report the disparate clinical progression of a couple infected by SARS-CoV-2 based on their immune checkpoint (IC) levels and immune cell distribution in blood from admission to exitus in patient 1 and from admission to discharge and recovery in patient 2. A detailed clinical follow-up accompanied by a longitudinal analysis of immune phenotypes and IC levels is shown. The continuous increase in the soluble IC ligand galectin-9 (Gal-9) and the increment in T-cell immunoglobulin and mucin domain-containing 3 (TIM-3) protein in T cells in patient 1 suggests an activation of the Gal-9/TIM-3 axis and, subsequently, a potential cell exhaustion in this patient that did not occur in patient 2. Our data indicate that the Gal-9/TIM-3 axis could be a potential target in this clinical setting, along with a patent effector memory T-cell reduction.

Published
2021
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10. The immune checkpoints storm in COVID‐19: Role as severity markers at emergency department admission

Author

José Avendaño‐Ortiz, Roberto Lozano‐Rodríguez, Alejandro Martín‐Quirós, Verónica Terrón, Charbel Maroun‐Eid, Karla Montalbán‐Hernández, Jaime Valentín‐Quiroga, Miguel Ángel García‐Garrido, Elena Muñoz del Val, Álvaro del Balzo‐Castillo, María Peinado, Laura Gómez, Carmen Herrero‐Benito, Carolina Rubio, José Carlos Casalvilla‐Dueñas, Paloma Gómez‐Campelo, Alejandro Pascual‐Iglesias, Carlos del Fresno, Luis A. Aguirre, and Eduardo López‐Collazo

Subjects
Medicine (General), R5-920
Published
2021
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11. Inflammatory cytokines and organ dysfunction associate with the aberrant DNA methylome of monocytes in sepsis

Author

Clara Lorente-Sorolla, Antonio Garcia-Gomez, Francesc Català-Moll, Víctor Toledano, Laura Ciudad, José Avendaño-Ortiz, Charbel Maroun-Eid, Alejandro Martín-Quirós, Mónica Martínez-Gallo, Adolfo Ruiz-Sanmartín, Álvaro García del Campo, Ricard Ferrer-Roca, Juan Carlos Ruiz-Rodriguez, Damiana Álvarez-Errico, Eduardo López-Collazo, and Esteban Ballestar

Subjects
Sepsis, DNA methylation, Cytokines, Endotoxin tolerance, Monocytes, Medicine, Genetics, QH426-470
Abstract

Abstract Background Sepsis, a life-threatening organ dysfunction caused by a dysregulated systemic immune response to infection, associates with reduced responsiveness to subsequent infections. How such tolerance is acquired is not well understood but is known to involve epigenetic and transcriptional dysregulation. Methods Bead arrays were used to compare global DNA methylation changes in patients with sepsis, non-infectious systemic inflammatory response syndrome, and healthy controls. Bioinformatic analyses were performed to dissect functional reprogramming and signaling pathways related to the acquisition of these specific DNA methylation alterations. Finally, in vitro experiments using human monocytes were performed to test the induction of similar DNA methylation reprogramming. Results Here, we focused on DNA methylation changes associated with sepsis, given their potential role in stabilizing altered phenotypes. Tolerized monocytes from patients with sepsis display changes in their DNA methylomes with respect to those from healthy controls, affecting critical monocyte-related genes. DNA methylation profiles correlate with IL-10 and IL-6 levels, significantly increased in monocytes in sepsis, as well as with the Sequential Organ Failure Assessment score; the observed changes associate with TFs and pathways downstream to toll-like receptors and inflammatory cytokines. In fact, in vitro stimulation of toll-like receptors in monocytes results in similar gains and losses of methylation together with the acquisition of tolerance. Conclusion We have identified a DNA methylation signature associated with sepsis that is downstream to the response of monocytes to inflammatory signals associated with the acquisition of a tolerized phenotype and organic dysfunction.

Published
2019
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12. Differential Immune Checkpoint and Ig-like V-Type Receptor Profiles in COVID-19: Associations with Severity and Treatment

Author

Roberto Lozano-Rodríguez, Verónica Terrón-Arcos, Raúl López, Juan Martín-Gutiérrez, Alejandro Martín-Quirós, Charbel Maroun-Eid, Elena Muñoz del Val, Carlos Cañada-Illana, Alejandro Pascual Iglesias, Jaime Valentín Quiroga, Karla Montalbán-Hernández, José Carlos Casalvilla-Dueñas, Miguel A. García-Garrido, Álvaro del Balzo-Castillo, María A. Peinado-Quesada, Laura Gómez-Lage, Carmen Herrero-Benito, Ray G. Butler, José Avendaño-Ortiz, and Eduardo López-Collazo

Subjects
COVID-19, immune phenotype, immune-checkpoints, Ig-like V-type receptors, secondary infections, corticosteroids, Medicine
Abstract

Identifying patients’ immune system status has become critical to managing SARS-CoV-2 infection and avoiding the appearance of secondary infections during a hospital stay. Despite the high volume of research, robust severity and outcome markers are still lacking in COVID-19. We recruited 87 COVID-19 patients and analyzed, by unbiased automated software, 356 parameters at baseline emergency department admission including: high depth immune phenotyping and immune checkpoint expression by spectral flow cytometry, cytokines and other soluble molecules in plasma as well as routine clinical variables. We identified 69 baseline alterations in the expression of immune checkpoints, Ig-like V type receptors and other immune population markers associated with severity (O2 requirement). Thirty-four changes in these markers/populations were associated with secondary infection appearance. In addition, through a longitudinal sample collection, we described the changes which take place in the immune system of COVID-19 patients during secondary infections and in response to corticosteroid treatment. Our study provides information about immune checkpoint molecules and other less-studied receptors with Ig-like V-type domains such as CD108, CD226, HVEM (CD270), B7H3 (CD276), B7H5 (VISTA) and GITR (CD357), defining these as novel interesting molecules in severe and corticosteroids-treated acute infections.

Published
2022
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13. Proteins from SARS-CoV-2 reduce T cell proliferation: A mirror image of sepsis

Author

José Avendaño-Ortiz, Roberto Lozano-Rodríguez, Alejandro Martín-Quirós, Charbel Maroun-Eid, Verónica Terrón, Jaime Valentín, Karla Montalbán-Hernández, Fátima Ruiz de la Bastida, Miguel A. García-Garrido, Carolina Cubillos-Zapata, Álvaro del Balzo-Castillo, Luis A. Aguirre, and Eduardo López-Collazo

Subjects
Inflammation, Infectious disease, Pathology, Virology, Immunology, COVID19, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

Increased cytokine levels, acute phase reactants and immune checkpoint expression changes have been described in patients with Coronavirus Disease 2019 (COVID-19). Here, we have reported a monocyte polarization towards a low HLA-DR and high PD-L1 expression after long exposure to proteins from SARS-CoV-2. Moreover, CD86 expression was also reduced over SARS-CoV-2 proteins exposure. Additionally, T-cells proliferation was significantly reduced after stimulation with these proteins. Eventually, patients with long-term SARS-CoV-2 infection also exhibited a significant blockade of T-cells proliferation.

Published
2020
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14. Oxygen Saturation on Admission Is a Predictive Biomarker for PD-L1 Expression on Circulating Monocytes and Impaired Immune Response in Patients With Sepsis

Author

José Avendaño-Ortiz, Charbel Maroun-Eid, Alejandro Martín-Quirós, Roberto Lozano-Rodríguez, Emilio Llanos-González, Víctor Toledano, Paloma Gómez-Campelo, Karla Montalbán-Hernández, César Carballo-Cardona, Luis A. Aguirre, and Eduardo López-Collazo

Subjects
monocytes, sepsis, PD-L1, oxygen saturation, T cell exhaustion, hypoxemia, Immunologic diseases. Allergy, RC581-607
Abstract

Sepsis is a pathology in which patients suffer from a proinflammatory response and a dysregulated immune response, including T cell exhaustion. A number of therapeutic strategies to treat human sepsis, which are different from antimicrobial and fluid resuscitation treatments, have failed in clinical trials, and solid biomarkers for sepsis are still lacking. Herein, we classified 85 patients with sepsis into two groups according to their blood oxygen saturation (SaO2): group I (SaO2 ≤ 92%, n = 42) and group II (SaO2 > 92%, n = 43). Blood samples were taken before any treatment, and the immune response after ex vivo LPS challenge was analyzed, as well as basal expression of PD-L1 on monocytes and levels of sPD-L1 in sera. The patients were followed up for 1 month. Taking into account reinfection and exitus frequency, a significantly poorer evolution was observed in patients from group I. The analysis of HLA-DR expression on monocytes, T cell proliferation and cytokine profile after ex vivo LPS stimulation confirmed an impaired immune response in group I. In addition, these patients showed both, high levels of PD-L1 on monocytes and sPD-L1 in serum, resulting in a down-regulation of the adaptive response. A blocking assay using an anti-PD-1 antibody reverted the impaired response. Our data indicated that SaO2 levels on admission have emerged as a potential signature for immune status, including PD-L1 expression. An anti-PD-1 therapy could restore the T cell response in hypoxemic sepsis patients with SaO2 ≤ 92% and high PD-L1 levels.

Published
2018
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15. A System Dynamics Model to Predict the Human Monocyte Response to Endotoxins

Author

Enrique Álvarez, Víctor Toledano, Fernando Morilla, Enrique Hernández-Jiménez, Carolina Cubillos-Zapata, Aníbal Varela-Serrano, José Casas-Martín, José Avendaño-Ortiz, Luis A. Aguirre, Francisco Arnalich, Charbel Maroun-Eid, Alejandro Martín-Quirós, Manuel Quintana Díaz, and Eduardo López-Collazo

Subjects
monocytes, endotoxin tolerance, inflammation, bacterial lipopolysaccharide, mathematical model, Immunologic diseases. Allergy, RC581-607
Abstract

System dynamics is a powerful tool that allows modeling of complex and highly networked systems such as those found in the human immune system. We have developed a model that reproduces how the exposure of human monocytes to lipopolysaccharides (LPSs) induces an inflammatory state characterized by high production of tumor necrosis factor alpha (TNFα), which is rapidly modulated to enter into a tolerant state, known as endotoxin tolerance (ET). The model contains two subsystems with a total of six states, seven flows, two auxiliary variables, and 14 parameters that interact through six differential and nine algebraic equations. The parameters were estimated and optimized to obtain a model that fits the experimental data obtained from human monocytes treated with various LPS doses. In contrast to publications on other animal models, stimulation of human monocytes with super-low-dose LPSs did not alter the response to a second LPSs challenge, neither inducing ET, nor enhancing the inflammatory response. Moreover, the model confirms the low production of TNFα and increased levels of C–C motif ligand 2 when monocytes exhibit a tolerant state similar to that of patients with sepsis. At present, the model can help us better understand the ET response and might offer new insights on sepsis diagnostics and prognosis by examining the monocyte response to endotoxins in patients with sepsis.

Published
2017
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