The association between macrovascular complications and intensive care admission, invasive mechanical ventilation, and mortality in people with diabetes hospitalized for coronavirus disease-2019 (COVID-19)
Authors: Llauradó Gemma , Vlacho Bogdan , Wargny Matthieu , Ruan Yue , Franch-Nadal Josep , Domingo Pere , Gourdy Pierre , Saulnier Pierre-Jean , Hadjadj Samy , Wild Sarah H. , Rea Rustam , Cariou Bertrand , Khunti Kamlesh , Mauricio Dídac ,   for the CORONADO, the ABCD COVID-19 diabetes national audit, HM Hospitales investigators and the Hospital del Mar - Hospital de la Santa Creu i Sant Pau Diabetes Research Group, Arroyo Juan Antonio , Chillarón Juan-José , Corcoy Rosa , Güerri Roberto , Mata-Cases Manel , Ortega Emilio , Pichelin Matthieu , Saignes Maëva , Saunier Jeanne , Andaloussi Selma El , Martin-Gauthier Joëlle , Rebouilleau Emily , Roman Tanguy , Mahot Pascale , Pichelin Matthieu , Fournier-Guilloux Anne-Laure , Mauduit Nicolas , Corbel Edith Bigot- , Boureau Anne-Sophie , De Dekcer Laure , Ernould Audrey , Primot Claire , Seguin Anne , Joliveau Marielle , Pouvreau Sonia , Fournier Chloé , Thureau Jeremy , Fonteneau Edith , Hublain Pamela , Agasse Carole , De Kergaradec Mathilde , Minville Vincent , Vardon-Bounes Fanny , Martin-Blondel Guillaume , Tramunt Blandine , Turnin Marie-Christine , Hanaire Hélène , Mansuy Jean-Michel , Fabre Didier , Arhainx Marie-Blanche , Cazals Laurent , Combes Laure , Lami Emmanuelle , Megarbane Bruno , Leroy Pierre , Gautier Jean-François , Vidal-Trecan Tiphaine , Riveline Jean-Pierre , Laplanche Jean-Louis , Mouly Stéphane , Potier Louis , Roussel Ronan , Taher Malak , Abouleka Yawa , Yaker Fetta , Carlier Aurelie , Boutten Anne , Hallot-Feron Marilyne , Mourah Fadila , Thivolet Charles , Blond Emilie , Rolland Muriel , Mendez Josep Verdecho , Alexandre Marine , Pottecher Julien , Richer Emilie , Meyer Laurent , Luca Florina , Lessinger Jean-Marc , Bahougne Thibault , Guerci Bruno , Benzirar Siham , Malaplate Catherine , Matton Thierry , Poissy Julien , Faure Karine , Fontaine Pierre , Baudoux Florence , Vambergue Anne , Pekar Jean David , Lambert Marc , Yelnik Cécile , Bruandet Amélie , Petit Laurent , Neau Didier , Rigalleau Vincent , Berard Annie , Galioot Amandine , Coudroy Remy , Thille Arnaud , Robert René , Roblot-Cazenave France , Rammaert Blandine , Saulnier Pierre Jean , Piguel Xavier , Benhenda Nesrine , Husson Camille , Olivier Celine , Torremocha Florence , Fraty Mathilde , D’assigny Marie Flamen , Miot Aurelie , Bossard Valentin , Klouche Kada , Makinson Alain , Sultan Ariane , Bonnet Jean-Baptiste , Foulongne Vincent , Galtier Florence , Aubron Cécile , Ansart Séverine , Kerlan Véronique , Quiniou Pascale , Carre Jean- Luc , Quesnot Stéphane , Laviolle Bruno , Schwebel Carole , Epaulard Olivier , Benhamou Pierre-Yves , Betry Cécile , Borel Anne-Laure , Lablanche Sandrine , Guergour Dorra , Duclos Catherine , Cosson Emmanuel , Guyot Erwan , Deniau Aurore , Nguyen Phucthutrang , Reznik Yves , Joubert Michael , Allouche Stéphane , Guittet Lydia , Grange Steven , Etienne Manuel , Prévost Gaëtan , Brunel Valéry , Lagier Jean-Christophe , Raoult Didier , Dutour Anne , Gaborit Bénédicte , Boulllu Sandrine , Darmon Patrice , Lasbleiz Adèle , Cerino Mathieu , Romain Fanny , Houssays Marie , Quenot Jean Pierre , Piroth Lionel , Vergès Bruno , Duvillard Laurence , Bonnotte Bernard , Mercat Alain , Dubee Vincent , Allix Ingrid , Rodien Patrice , Dhersin Robin , Lebeault Maylis , Trzepizur Wojciech , Loison Jocelyne , Brangier Antoine , Asfar Pierre , Reynier Pascal , Larcher Françoise , Joubaud Françoise , Andreu Marie-Rita , Urbanski Geoffrey , Hubert Laurent , Annweiler Cedric , Dellamonica Jean , Courjon Johan , Chevalier Nicolas , Chinetti Giulia , Chafai Magda , Mourvillier Bruno , Bani-Sadr Firouze , Barraud Sarra , Delemer Brigitte , Gillery Philippe , Labedade Pascale , Chabrol Amélie , Penfornis Alfred , Petit Catherine , Amadou Coralie , Adler Maxime , Dubost Clément , Conan Pierre-Louis , Bordier Lyse , Ceppa Franck , Garcia Cyril , Sollier Mathilde , Dupuy Olivier , Laplance Sophie , Billuart Olivier , Aroulanda Marie Joseph , Olivier Frédérique , Ayon Florence , Wilhelm Nathalie , Epelboin Loic , Sabbah Nadia , Charpin Aurelie , Squara Pierre , Belliard Olivier , Dubois Claude , Marre Michel , Auchabie Johann , Courtois Roxane , Duriez Thierry , Mergey Tiphaine , Vallee Laura , Seguin Laetitia , Al-Salameh Abdallah , Lanoix Jean-Philippe , Soriot-Thomas Sandrine , Bourgeois-Descouls Anne-Marie , Desailloud Rachel , Germain Natacha , Galusca Bogdan , Belleton Gwenaelle , Marouani Nesrine , Palaghiu Delia , Hammour Amira , Berdaguer Fernando , Klopfenstein Thimothée , Zayet Hajer , Winiszewski Patrice , Zanusso Marie , Garnier Pauline , Julier Ingrid , Hamzaoui Karim , Marty-Gres Sophie , Sadki Tarik El , Cadot Lucile , Dubost Jean-Louis , Gonfroy Céline , Campinos Catherine , Martres Pascale , Coulhon Marie Pierre , Allou Nicolas , Bachir Marwa , Hoang Stella , Kembellec Candice , Suply Olivia , Kharcha Fatima , Devouge Anne-Claire , Flaus-Furmanuk Anna , Madeline Isabelle , Ehinger Vincent , Bastard Sophie , Raffray Loic , Renou Frederic , Bojarsk Aude , Borsu Karine , Gorlin Angelique , Di Bernardo Servane , Van Ut Carole Truong , Renaud Stephane , Vignoles Antoine , Foch Emilie , Masse Laurie , Grand Hubert , Ferrand Helene , Raffaitin-Cardin Christelle , Zellagui Hadjer , Castang-Brachet Celine , Boury Frederique , Tena Ana Alvarez , Moura Isabelle , Kalfon Pierre , Pasteur Louis , Darasteanu Juliana , Pasteur Louis , Monier Arnaud , Pasteur Louis , Foucault Pascal , Pasteur Louis , Depuille Alexandra , Pasteur Louis , Laugier-Robiolle Stéphanie , Caneiro Patrick , Basso Maud , Larger Etienne , Bouam Samir , Benzenati Wahiba , Bachir Leila Ait , Pillegand Camille Cussac , Vasse Marc , Michard Christophe , Montanier Nathanaëlle , Millot Luc , Crepet Françoise , Ratsimba Danielle , Bouiller Kevin , Borot Sophie , Bruckert Isabelle , Clergeot Annie , Schillo Franck , Vignes Dorothée , Bourgeon-GhittoriLachgar Muriel , De Cursay Claire Lambert , Levante Stéphane , Auregan Jean Charles , Merlet Antoine , Zaragoza Cécile , Arnault Gwénaëlle , Le Loupp Anne-Gaëlle , Lesieur Olivier , Roncato-Saberan Mariam , Gouet Didier , Lemari Romain , Allano Hong-An , Vivier Emmanuel , Pariset Caroline , Luyton Cédric , Marchand Lucien , Doroszewski Fanny , Pecquet Matthieu , Perard Laurent , Vuillermoz-Blas Sylvie , Kacki Nicolas , Charrier Patricia , Ducet-Boiffard Amélie , Du Roure Françoise Desroys , Bourron Olivier , Bonnefont-Rousselot Dominique , Laroche Suzanne , Phan Franck , Hartemann Agnès , Caussy Cyrielle , Disse Emmanuel , Blond Emilie , Guerin Claude , Perpoint Thomas , Moulin Philippe , Cartier Régine , Hariri Geoffroy , Chopin Dorothée , Vatier Camille , Bourcigaux Nathalie , Chaigneau Emmanuelle , Christin-Maitre Sophie , Donadille Bruno , Feve Bruno , Lamothe Sophie , Sarfati Julie , Pernet Pascal , Chambon Anne , Demarsy Delphine , Campagne Hugo , Latil-Plat Françoise , Berne Monica , Grinand Marilyne , Touzet Marion , Zabulon Aydrey , Craspag Jocelyne , Ledoux Catherine , Contaret Cedric , Janand-Delenne Blandine , Giraud Anaïs , Lacrimini Marie Lou , Arrivie Joëlle , Ancelle Deborah , Guillois Carine , Fremy Bénédicte , Chaalal Amina , Barrande Gaëlle , Dorange Anne , Rouanet Eglantine , Seret-Begue Dominique , Saoud Audrey , Guedj Anne-Marie , Bedos Nathalie , Velayoudom Fritz-Line , Dumas Marie , Gonda Benoite , Coffin Christine , Gibiat Stéphanie , Lungo Myriam , Bully Chantal , Serusclat Pierre , Bully Stella , Carre Patricia , Leberre Jean-Philippe , Elkhoury Carlos , Thieux Marine , Paradisi-Prieur Laetitia , Wilmot Emma , Wild Sarah , Field Ben , Narendran Parth , Gandhi Rajiv , Harris Sophie , Nagi Dinesh , Ryder Robert , Davies Jim , Harris Steve , Freeman Oliver , Maylor Ben , Várnai Kinga A. , Roadknight Gail , Cul Melissa , Edwards Amy , Gelding Susan , Gunganah Kirun , Aung Pyei , Banerjee Moulinath , Chakera Ali , Rouse Dominique , Ahmed Syed Haris , Cheung Ho Yee , Roberts Hywel , Seal Susan , Shah Syed Saah , Hayat Amir , Mohandas Cynthia , Aung Htet Htet , Chel Su Khant , Lin Nyan , Narula Kavitia , Quadri Furruq , Yin Su Lei , Yin Yin , Alkundi Alamin , Musa Abdelmajid , Birbeck Emma , Bodmer Charles , Bossman Irene , Kumar Sathis , Dashora Umesh , Toubi Elizabeth , Zafar Mansoor , Patel Vinod , Gopinath Amitha , Allan Belinda , Karim Remat , Appuhamillage Dharshana , Ayoub Khubaib , Harris Sophie , Ilangaratne Charmaine , Iqbal Maliha , Maclean Rory , Mustafa Omar , Baxter Susan , Adamus Malgorzata , Baynes Kevin , Sivappriyan Siva , D’Costa Ryan , Nagi Dinesh , Parfitt Vernon , Islam Mazharul , Nasir Sadia , Roadknight Gail , Várnai Kinga , Vasan Senthil , Devah Vilashini Arul , Kavvoura Foteini , Ficken Lina , Gilham James , Simpson Vincent , Walker Neil , Aziz Umaira , Karra Efthimia , Patel Dipesh , Rosenthal Miranda , Curran Tracy , Paisley Angela , Cull Melissa , De P Parijat , Khine May Thin , Qayyam Pari , Ryder Robert , Sarkar Priscilla , Gandhi Rajiv , Field Ben , Clark James , Hogan Vesna , Jackson Lauren , Williamson Jamie-Leigh , Younes R. , Robin Lucy , Grixti Lydia , Tee Suann , Sathya Abilash , Wilmot Emma , Patel Mayank , Holmes Catherine , Hanif Wasim , Ghosh Sandip , Narendran Parth , Ahmad Ehtasham , Ahmed Ejaz , Davies Melanie , Hartshorn Steven , Khunti Kamlesh , Simons Lee , Webb David , Maylor Ben , Davies Jim , Freeman Oliver , Harris Steve , Brahma Anupam , Pramodh Seshadri , Frew Katy , Mackenzie Alison , Wild Abigail , Casey Helen , Morrison Deborah , McKeag Conor , Sillars Anne , Stirling Angus , Smeeton Fiona , Muhammad Syed , Obuobie Kofi , Yin Win , Agarwal Neera , Atkinson Mike , Ambati Sai , Khan Rahim , Nalla Preethi , Tabasum Arshiya , Zouras Stamatios , Mallipedhi Akhila , Chudleigh Richard , Williams David , Cianferani Mallory , Ludwig Lisa , Paul Caroline , Lachgar Hamoud 
Published: October 2022

Abstract
Background
It is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19.

Methods
We conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020—October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization. Output from individual logistic regression models for each cohort was combined in a meta-analysis.

Results
Complete data were available for 4,106 (60.4%) individuals. Of these, 1,652 (40.2%) had any prior macrovascular disease of whom 28.5% of patients died. Mortality was higher for people with compared to those without previous macrovascular disease (37.7% vs 22.4%). The combined crude odds ratio (OR) for previous macrovascular disease and mortality for all four cohorts was 2.12 (95% CI 1.83–2.45 with an I2 of 60%, reduced after adjustments for age, sex, type of diabetes, hypertension, microvascular disease, ethnicity, and BMI to adjusted OR 1.53 [95% CI 1.29–1.81]) for the three cohorts. Further analysis revealed that ischemic heart disease and cerebrovascular disease were the main contributors of adverse outcomes. However, proportions of people admitted to ICU (adjOR 0.48 [95% CI 0.31–0.75], I2 60%) and the use of IMV during hospitalization (adjOR 0.52 [95% CI 0.40–0.68], I2 37%) were significantly lower for people with previous macrovascular disease.

Conclusions
This large multinational study of people with diabetes mellitus hospitalized for COVID-19 demonstrates that previous macrovascular disease is associated with higher mortality and lower proportions admitted to ICU and treated with IMV during hospitalization suggesting selective admission criteria. Our findings highlight the importance correctly assess the prognosis and intensive monitoring in this high-risk group of patients and emphasize the need to design specific public health programs aimed to prevent SARS-CoV-2 infection in this subgroup.