Geography Influences Susceptibility to SARS-CoV-2 Serological Response in Patients With Inflammatory Bowel Disease: Multinational Analysis From the ICARUS-IBD Consortium
Authors: Wong Serre-Yu , Wellens Judith , Helmus Drew , Marlow Luke , Brann Stephanie , Martinez Pazos Vicky , Weinberg Alan , Moran Hunter R , McGregor Colleen , Vermeire Séverine , Watanabe Kenji , Kamikozuru Koji , Ahuja Vineet , Vermani Shubi , Lindsay James O , Kingston Ashley , Dutta Usha , Kaur Harmandeep , Silverberg Mark S , Milgrom Raquel , Chien Ng Siew , Mak Joyce Wing Yan , Cadwell Ken , Thompson Craig , Colombel Jean-Frédéric , Satsangi Jack ,   ICARUS-IBD Consortium, Ambrose Tim , Brain Oliver , Walsh Alissa , Klenerman Paul , Travis Simon , Edmans Matthew , Dixon Rebekah , Navalurkar Reema , Gold Stephanie , Lacoste Joshua , Chen Clara , Halfvarson Jonas , Bergemalm Daniel , Rubin David T , Abreu Maria T , Allez Matthieu , Anne Neil Jessica , Sota Stela , Ku Jang Kyung , Ching Krystal , Venzon Mericien , Yao Xiaomin , Bernard Lucie , Cowger Tori L , Accorsi Emma , Wiseman Dean , Riggs Alexa , Stanley Stephanie , Reyes-Mercedes Pamela , Mendiolaza Michelle , Nunez Sara , Phillipe Brianne , Chen Xin , Tankelevich Michael , Jimenez Darwin , Ramos Julio , Kedia Saurabh , Yokoyama Yoko , Kawai Mikio , Sato Toshiyuki , Kojima Kentaro , Nagase Kazuko , Nakamura Shiro , Miyazaki Takako , Kakimoto Kazuki , Kamata Noriko , Hosomi Shuhei , Nishishita Masakazu , Chan Alicia , Sharma Vishal , Singh Kumar Anupam , Samanta Jayanta , Shah Jimil , Sinha S K , Cipriano Bessie , Lee Irish , Ruocco Giuseppe , Garcia Nicole , Choi Natalie , Alejandra Quintero Maria 
Published: June 2023

Abstract

Background
Beyond systematic reviews and meta-analyses, there have been no direct studies of serological response to COVID-19 in patients with inflammatory bowel disease (IBD) across continents. In particular, there has been limited data from Asia, with no data reported from India. The ICARUS-IBD (International study of COVID-19 Antibody Response Under Sustained immunosuppression in IBD) consortium assessed serological response to SARS-CoV-2 in patients with IBD in North America, Europe, and Asia.

Methods
The ICARUS-IBD study is a multicenter observational cohort study spanning sites in 7 countries. We report seroprevalence data from 2303 patients with IBD before COVID-19 vaccination between May 2020 and November 2021. SARS-CoV-2 anti-spike and anti-nucleocapsid antibodies were analyzed.

Results
The highest and lowest SARS-CoV-2 anti-spike seropositivity rates were found in Asia (81.2% in Chandigarh and 57.9% in Delhi, India; and 0% in Hong Kong). By multivariable analysis, country (India: odds ratio [OR], 18.01; 95% confidence interval [CI], 12.03-26.95; P &lt; .0001; United Kingdom: OR, 2.43; 95% CI, 1.58-3.72; P &lt; .0001; United States: OR, 2.21; 95% CI, 1.27-3.85; P = .005), male sex (OR, 1.46; 95% CI, 1.07-1.99; P = .016), and diabetes (OR, 2.37; 95% CI, 1.04-5.46; P = .039) conferred higher seropositivity rates. Biological therapies associated with lower seroprevalence (OR, 0.22; 95% CI, 0.15-0.33; P &lt; .0001). Multiple linear regression showed associations between anti-spike and anti-nucleocapsid titers with medications (P &lt; .0001) but not with country (P = .3841).

Conclusions
While the effects of medications on anti-SARS-CoV-2 antibody titers in patients with IBD were consistent across sites, geographical location conferred the highest risk of susceptibility to serologically detectable SARS-CoV-2 infection. Over half of IBD patients in India were seropositive prior to vaccination. These insights can help to inform shielding advice, therapeutic choices, and vaccine strategies in IBD patients for COVID-19 and future viral challenges.