Sex differences in COVID-19 mortality risk in patients on kidney function replacement therapy
Authors: Vart Priya , Duivenvoorden Raphaël , Adema Aaltje , Covic Adrian , Finne Patrik , Braak Nicole Heijtink-ter , Laine Kaisa , Noordzij Marlies , Schouten Marcel , Jager Kitty J. , Gansevoort Ron T. ,   ERACODA Collaborators, van der Net Jeroen B. , Essig Marie , du Buf-Vereijken Peggy W. G. , van Ginneken Betty , Maas Nanda , van Jaarsveld Brigit C. , Bemelman Frederike J. , Klingenberg-Salahova Farah , Heenan-Vos Frederiek , Vervloet Marc G. , Nurmohamed Azam , Vogt Liffert , Abramowicz Daniel , Verhofstede Sabine , Maoujoud Omar , Malfait Thomas , Fialova Jana , Melilli Edoardo , Favà Alexandre , Cruzado Josep M. , Perez Nuria Montero , Lips Joy , Krepel Harmen , Adilovic Harun , Radulescu Daniela , Hengst Maaike , Konings Constantijn , Rydzewski Andrzej , Braconnier Philippe , Weis Daniel , Gellert Ryszard , Oliveira João , Alferes Daniela G. , Zakharova Elena V. , Ambühl Patrice Max , Guidotti Rebecca , Walker Andrea , Lepeytre Fanny , Rabaté Clémentine , Rostoker Guy , Marques Sofia , Azasevac Tijana , Majstorovic Gordana Strazmester , Katicic Dajana , ten Dam Marc , Krüger Thilo , Brzosko Szymon , Liakopoulos Vassilios , Zanen Adriaan L. , Logtenberg Susan J. J. , Fricke Lutz , Kuryata Olexandr , Slebe Jeroen J. P. , ElHafeez Samar Abd , Kemlin Delphine , van de Wetering Jacqueline , Reinders Marlies E. J. , Hesselink Dennis A. , Kal-van Gestel J. , Eiselt Jaromir , Kielberger Lukas , El-Wakil Hala S. , Verhoeven Martine , Logan Ian , Canal Cristina , Facundo Carme , Ramos Ana M. , Debska-Slizien Alicja , Veldhuizen Nicoline M. H. , Tigka Eirini , Konsta Maria Anna Polyzou , Panagoutsos Stylianos , Mallamaci Francesca , Postorino Adele , Cambareri Francesco , Matceac Irina , Nistor Ionut , Groeneveld J. H. M. , Jousma Jolanda , van Buren Marjolijn , Diekmann Fritz , Oppenheimer Federico , Blasco Miquel , Pereira Tiago Assis , Santos Augusto Cesar S. , Arias-Cabrales Carlos , Crespo Marta , Llinàs-Mallol Laura , Buxeda Anna , Tàrrega Carla Burballa , Redondo-Pachon Dolores , Jimenez Maria Dolores Arenas , Mendoza-Valderrey Alberto , Martins Ana Cristina , Mateus Catarina , Alvila Goncalo , Laranjinha Ivo , Hofstra Julia M. , Siezenga Machiel A. , Franco Antonio , Arroyo David , Castellano Sandra , Rodríguez-Ferrero Maria Luisa , Manzanos Sagrario Balda , Barrios R. Haridian Sosa , Lemahieu Wim , Bartelet Karlijn , Dirim Ahmet Burak , Demir Erol , Sever Mehmet Sukru , Turkmen Aydin , Şafak Seda , Hollander Daan A. M. J. , Büttner Stefan , de Vries Aiko P. J. , Meziyerh Soufian , van der Helm Danny , Mallat Marko , Bouwsma Hanneke , Sridharan Sivakumar , Petruliene Kristina , Maloney Sharon-Rose , Verberk Iris , van der Sande Frank M. , Christiaans Maarten H. L. , Hemmelder Marc H. , MohanKumar N. , Di Luca Marina , Tuğlular Serhan Z. , Kramer Andrea B. , Beerenhout Charles , Luik Peter T. , Kerschbaum Julia , Tiefenthaler Martin , Watschinger Bruno , Stepanov Vadim A. , Zulkarnaev Alexey B. , Turkmen Kultigin , Gandolfini Ilaria , Maggiore Umberto , Fliedner Anselm , Åsberg Anders , Mjoen Geir , Miyasato Hitoshi , de Fijter Carola W. H. , Mongera Nicola , Pini Stefano , de Biase Consuelo , Kerckhoffs Angele , van de Logt Anne Els , Maas Rutger , Hilbrands Luuk B. , Lebedeva Olga , Lopez Veronica , Reichert Louis J. M. , Verhave Jacobien , Titov Denis , Parshina Ekaterina V. , Zanoli Luca , Marcantoni Carmelita , van Kempen Gijs , van Gils-Verrij Liesbeth E. A. , Harty John C. , Meurs Marleen , Myslak Marek , Battaglia Yuri , Lentini Paolo , den Deurwaarder Edwin , Stendahl Maria , Rahimzadeh Hormat , Rychlik Ivan , Cabezas-Reina Carlos J. , Roca Ana Maria , Nauta Ferdau , Sahin İdris , Goffin Eric , Kanaan Nada , Labriola Laura , Devresse Arnaud , Diaz-Mareque Anabel , Coca Armando , de Arriba Gabriel , Meijers Björn K. I. , Naesens Maarten , Kuypers Dirk , Desschans Bruno , Tonnerlier Annelies , Wissing Karl M. , Dedinska Ivana , Pessolano Giuseppina , Malik Shafi , Dounousi Evangelia , Papachristou Evangelos , Berger Stefan P. , Sanders Jan Stephan F. , Franssen Casper F. M. , Özyilmaz Akin , Ponikvar Jadranka Buturović , Pernat Andreja Marn , Kovac Damjan , Arnol Miha , Ekart Robert , Abrahams Alferso C. , Molenaar Femke M. , van Zuilen Arjan D. , Meijvis Sabine C. A. , Dolmans Helma , Tantisattamo Ekamol , Esposito Pasquale , Krzesinski Jean-Marie , Barahira Jean Damacène , Gallieni Maurizio , Martin-Moreno Paloma Leticia , Guglielmetti Gabriele , Guzzo Gabriella , Toapanta Nestor , Soler Maria Jose , Luik Antinus J. , van Kuijk Willi H. M. , Stikkelbroeck Lonneke W. H. , Hermans Marc M. H. , Rimsevicius Laurynas , Righetti Marco , Islam Mahmud 
Published: October 2022

In the general population with COVID-19, the male sex is an established risk factor for mortality, in part due to a more robust immune response to COVID-19 in women. Because patients on kidney function replacement therapy (KFRT) have an impaired immune response, especially kidney transplant recipients due to their use of immunosuppressants, we examined whether the male sex is still a risk factor for mortality among patients on KFRT with COVID-19. From the European Renal Association COVID-19 Database (ERACODA), we examined patients on KFRT with COVID-19 who presented between February 1st, 2020, and April 30th, 2021. 1204 kidney transplant recipients (male 62.0%, mean age 56.4 years) and 3206 dialysis patients (male 61.8%, mean age 67.7 years) were examined. Three-month mortality in kidney transplant recipients was 16.9% in males and 18.6% in females (p = 0.31) and in dialysis patients 27.1% in males and 21.9% in females (p = 0.001). The adjusted HR for the risk of 3-month mortality in males (vs females) was 0.89 (95% CI 65, 1.23, p = 0.49) in kidney transplant recipients and 1.33 (95% CI 1.13, 1.56, p = 0.001) in dialysis patients (pinteraction = 0.02). In a fully adjusted model, the aHR for the risk of 3-month mortality in kidney transplant recipients (vs. dialysis patients) was 1.39 (95% CI 1.02, 1.89, p = 0.04) in males and 2.04 (95% CI 1.40, 2.97, p < 0.001) in females (pinteraction = 0.02). In patients on KFRT with COVID-19, the male sex is not a risk factor for mortality among kidney transplant recipients but remains a risk factor among dialysis patients. The use of immunosuppressants in kidney transplant recipients, among other factors, may have narrowed the difference in the immune response to COVID-19 between men and women, and therefore reduced the sex difference in COVID-19 mortality risk.