The ChoCO-W prospective observational global study: Does COVID-19 increase gangrenous cholecystitis?
Authors: De Simone Belinda , Abu-Zidan Fikri M. , Chouillard Elie , Di Saverio Salomone , Sartelli Massimo , Podda Mauro , Gomes Carlos Augusto , Moore Ernest E. , Moug Susan J. , Ansaloni Luca , Kluger Yoram , Coccolini Federico , Landaluce-Olavarria Aitor , Estraviz-Mateos Begoña , Uriguen-Etxeberria Ana , Giordano Alessio , Luna Alfonso Palmieri , Amín Luz Adriana Hernández , Hernández Adriana María Palmieri , Shabana Amanda , Dzulkarnaen Zakaria Andee , Othman Muhammad Asyraf , Sani Mohamad Ikhwan , Balla Andrea , Scaramuzzo Rosa , Lepiane Pasquale , Bottari Andrea , Staderini Fabio , Cianchi Fabio , Cavallaro Andrea , Zanghì Antonio , Cappellani Alessandro , Campagnacci Roberto , Maurizi Angela , Martinotti Mario , Ruggieri Annamaria , Jusoh Asri Che , Rahman Karim Abdul , Zulkifli Anis Suraya M. , Petronio Barbara , Matías-García Belén , Quiroga-Valcárcel Ana , Mendoza-Moreno Fernando , Atanasov Boyko , Campanile Fabio Cesare , Vecchioni Ilaria , Cardinali Luca , Travaglini Grazia , Sebastiani Elisa , Chooklin Serge , Chuklin Serhii , Cianci Pasquale , Restini Enrico , Capuzzolo Sabino , Currò Giuseppe , Filippo Rosalinda , Rispoli Michele , Aparicio-Sánchez Daniel , Muñóz-Cruzado Virginia Durán , Barbeito Sandra Dios , Delibegovic Samir , Kesetovic Amar , Sasia Diego , Borghi Felice , Giraudo Giorgio , Visconti Diego , Doria Emanuele , Santarelli Mauro , Luppi Davide , Bonilauri Stefano , Grossi Ugo , Zanus Giacomo , Sartori Alberto , Piatto Giacomo , De Luca Maurizio , Vita Domenico , Conti Luigi , Capelli Patrizio , Cattaneo Gaetano Maria , Marinis Athanasios , Vederaki Styliani-Aikaterini , Bayrak Mehmet , Altıntas Yasemin , Uzunoglu Mustafa Yener , Demirbas Iskender Eren , Altinel Yuksel , Meric Serhat , Aktimur Yunus Emre , Uymaz Derya Salim , Omarov Nail , Azamat Ibrahim , Lostoridis Eftychios , Nagorni Eleni-Aikaterini , Pujante Antonio , Anania Gabriele , Bombardini Cristina , Bagolini Francesco , Gonullu Emre , Mantoglu Baris , Capoglu Recayi , Cappato Stefano , Muzio Elena , Colak Elif , Polat Suleyman , Koylu Zehra Alan , Altintoprak Fatih , Bayhan Zülfü , Akin Emrah , Andolfi Enrico , Rezart Sulce , Kim Jae Il , Jung Sung Won , Shin Yong Chan , Enciu Octavian , Toma Elena Adelina , Medas Fabio , Canu Gian Luigi , Cappellacci Federico , D’Acapito Fabrizio , Ercolani Giorgio , Solaini Leonardo , Roscio Francesco , Clerici Federico , Gelmini Roberta , Serra Francesco , Rossi Elena Giulia , Fleres Francesco , Clarizia Guglielmo , Spolini Alessandro , Ferrara Francesco , Nita Gabriela , Sarnari Jlenia , Gachabayov Mahir , Abdullaev Abakar , Poillucci Gaetano , Palini Gian Marco , Veneroni Simone , Garulli Gianluca , Piccoli Micaela , Pattacini Gianmaria Casoni , Pecchini Francesca , Argenio Giulio , Armellino Mariano Fortunato , Brisinda Giuseppe , Tedesco Silvia , Fransvea Pietro , Ietto Giuseppe , Franchi Caterina , Carcano Giulio , Martines Gennaro , Trigiante Giuseppe , Negro Giulia , Vega Gustavo Machain , González Agustín Rodríguez , Ojeda Leonardo , Piccolo Gaetano , Bondurri Andrea , Maffioli Anna , Guerci Claudio , Sin Boo Han , Zuhdi Zamri , Azman Azlanudin , Mousa Hussam , al Bahri Shadi , Augustin Goran , Romic Ivan , Moric Trpimir , Nikolopoulos Ioannis , Andreuccetti Jacopo , Pignata Giusto , D’Alessio Rossella , Kenig Jakub , Skorus Urszula , Fraga Gustavo Pereira , Hirano Elcio Shiyoiti , de Lima Bertuol Jackson Vinícius , Isik Arda , Kurnaz Eray , Asghar Mohammad Sohail , Afzal Ameer , Akbar Ali , Nikolouzakis Taxiarchis Konstantinos , Lasithiotakis Konstantinos , Chrysos Emmanuel , Das Koray , Özer Nazmi , Seker Ahmet , Ibrahim Mohamed , Hamid Hytham K. S. , Babiker Ahmed , Bouliaris Konstantinos , Koukoulis George , Kolla Chrysoula-Christina , Lucchi Andrea , Agostinelli Laura , Taddei Antonio , Fortuna Laura , Agostini Carlotta , Licari Leo , Viola Simona , Callari Cosimo , Laface Letizia , Abate Emmanuele , Casati Massimiliano , Anastasi Alessandro , Canonico Giuseppe , Gabellini Linda , Tosi Lorenzo , Guariniello Anna , Zanzi Federico , Bains Lovenish , Sydorchuk Larysa , Iftoda Oksana , Sydorchuk Andrii , Malerba Michele , Costanzo Federico , Galleano Raffaele , Monteleone Michela , Costanzi Andrea , Riva Carlo , Walędziak Maciej , Kwiatkowski Andrzej , Czyżykowski Łukasz , Major Piotr , Strzałka Marcin , Matyja Maciej , Natkaniec Michal , Valenti Maria Rosaria , Di Vita Maria Domenica Pia , Sotiropoulou Maria , Kapiris Stylianos , Massalou Damien , Veroux Massimiliano , Volpicelli Alessio , Gioco Rossella , Uccelli Matteo , Bonaldi Marta , Olmi Stefano , Nardi Matteo , Livadoti Giada , Mesina Cristian , Dumitrescu Theodor Viorel , Ciorbagiu Mihai Calin , Ammendola Michele , Ammerata Giorgio , Romano Roberto , Slavchev Mihail , Misiakos Evangelos P. , Pikoulis Emmanouil , Papaconstantinou Dimitrios , Elbahnasawy Mohamed , Abdel-elsalam Sherief , Felsenreich Daniel M. , Jedamzik Julia , Michalopoulos Nikolaos V. , Sidiropoulos Theodoros A. , Papadoliopoulou Maria , Cillara Nicola , Deserra Antonello , Cannavera Alessandro , Negoi Ionuţ , Schizas Dimitrios , Syllaios Athanasios , Vagios Ilias , Gourgiotis Stavros , Dai Nick , Gurung Rekha , Norrey Marcus , Pesce Antonio , Feo Carlo Vittorio , Fabbri Nicolo’ , Machairas Nikolaos , Dorovinis Panagiotis , Keramida Myrto D. , Mulita Francesk , Verras Georgios Ioannis , Vailas Michail , Yalkin Omer , Iflazoglu Nidal , Yigit Direnc , Baraket Oussama , Ayed Karim , Ghalloussi Mohamed hedi , Patias Parmenion , Ntokos Georgios , Rahim Razrim , Bala Miklosh , Kedar Asaf , Sawyer Robert G. , Trinh Anna , Miller Kelsey , Sydorchuk Ruslan , Knut Ruslan , Plehutsa Oleksandr , Liman Rumeysa Kevser , Ozkan Zeynep , Kader Saleh Abdel , Gupta Sanjay , Gureh Monika , Saeidi Sara , Aliakbarian Mohsen , Dalili Amin , Shoko Tomohisa , Kojima Mitsuaki , Nakamoto Raira , Atici Semra Demirli , Tuncer Gizem Kilinc , Kaya Tayfun , Delis Spiros G. , Rossi Stefano , Picardi Biagio , del Monte Simone Rossi , Triantafyllou Tania , Theodorou Dimitrios , Pintar Tadeja , Salobir Jure , Manatakis Dimitrios K. , Tasis Nikolaos , Acheimastos Vasileios , Ioannidis Orestis , Loutzidou Lydia , Symeonidis Savvas , de Sá Tiago Correia , Rocha Mónica , Guagni Tommaso , Pantalone Desiré , Maltinti Gherardo , Khokha Vladimir , Abdel-elsalam Wafaa , Ghoneim Basma , López-Ruiz José Antonio , Kara Yasin , Zainudin Syaza , Hayati Firdaus , Azizan Nornazirah , Khei Victoria Tan Phooi , Yi Rebecca Choy Xin , Sellappan Harivinthan , Demetrashvili Zaza , Lekiashvili Nika , Tvaladze Ana , Froiio Caterina , Bernardi Daniele , Bonavina Luigi , Gil-Olarte Angeles , Grassia Sebastiano , Romero-Vargas Estela , Bianco Francesco , Gumbs Andrew A. , Dogjani Agron , Agresta Ferdinando , Litvin Andrey , Balogh Zsolt J. , Gendrikson George , Martino Costanza , Damaskos Dimitrios , Pararas Nikolaos , Kirkpatrick Andrew , Kurtenkov Mikhail , Gomes Felipe Couto , Pisanu Adolfo , Nardello Oreste , Gambarini Fabrizio , Aref Hager , Angelis Nicola de’ , Agnoletti Vanni , Biondi Antonio , Vacante Marco , Griggio Giulia , Tutino Roberta , Massani Marco , Bisetto Giovanni , Occhionorelli Savino , Andreotti Dario , Lacavalla Domenico , Biffl Walter L. , Catena Fausto 
Published: December 2022

Abstract
Background
The incidence of the highly morbid and potentially lethal gangrenous cholecystitis was reportedly increased during the COVID-19 pandemic. The aim of the ChoCO-W study was to compare the clinical findings and outcomes of acute cholecystitis in patients who had COVID-19 disease with those who did not.

Methods
Data were prospectively collected over 6 months (October 1, 2020, to April 30, 2021) with 1-month follow-up. In October 2020, Delta variant of SARS CoV-2 was isolated for the first time. Demographic and clinical data were analyzed and reported according to the STROBE guidelines. Baseline characteristics and clinical outcomes of patients who had COVID-19 were compared with those who did not.

Results
A total of 2893 patients, from 42 countries, 218 centers, involved, with a median age of 61.3 (SD: 17.39) years were prospectively enrolled in this study; 1481 (51%) patients were males. One hundred and eighty (6.9%) patients were COVID-19 positive, while 2412 (93.1%) were negative. Concomitant preexisting diseases including cardiovascular diseases (p < 0.0001), diabetes (p < 0.0001), and severe chronic obstructive airway disease (p = 0.005) were significantly more frequent in the COVID-19 group. Markers of sepsis severity including ARDS (p < 0.0001), PIPAS score (p < 0.0001), WSES sepsis score (p < 0.0001), qSOFA (p < 0.0001), and Tokyo classification of severity of acute cholecystitis (p < 0.0001) were significantly higher in the COVID-19 group. The COVID-19 group had significantly higher postoperative complications (32.2% compared with 11.7%, p < 0.0001), longer mean hospital stay (13.21 compared with 6.51 days, p < 0.0001), and mortality rate (13.4% compared with 1.7%, p < 0.0001). The incidence of gangrenous cholecystitis was doubled in the COVID-19 group (40.7% compared with 22.3%). The mean wall thickness of the gallbladder was significantly higher in the COVID-19 group [6.32 (SD: 2.44) mm compared with 5.4 (SD: 3.45) mm; p < 0.0001].

Conclusions
The incidence of gangrenous cholecystitis is higher in COVID patients compared with non-COVID patients admitted to the emergency department with acute cholecystitis. Gangrenous cholecystitis in COVID patients is associated with high-grade Clavien-Dindo postoperative complications, longer hospital stay and higher mortality rate. The open cholecystectomy rate is higher in COVID compared with non -COVID patients. It is recommended to delay the surgical treatment in COVID patients, when it is possible, to decrease morbidity and mortality rates. COVID-19 infection and gangrenous cholecystistis are not absolute contraindications to perform laparoscopic cholecystectomy, in a case by case evaluation, in expert hands.

Graphical abstract