Flares in autoimmune rheumatic diseases in the post-COVID-19 vaccination period—a cross-sequential study based on COVAD surveys
Authors: Jagtap Kshitij , Naveen R , Day Jessica , Sen Parikshit , Vaidya Binit , Nune Arvind , Nikiphorou Elena , Tan Ai Lyn , Agarwal Vishwesh , Saha Sreoshy , Shinjo Samuel Katsuyuki , Ziade Nelly , Joshi Mrudula , Velikova Tsvetelina , Milchert Marcin , Parodis Ioannis , Edgar Gracia-Ramos Abraham , Cavagna Lorenzo , Kuwana Masataka , Knitza Johannes , Makol Ashima , Patel Aarat , Pauling John D , Wincup Chris , Barman Bhupen , Zamora Tehozol Erick Adrian , Rojas Serrano Jorge , García-De La Torre Ignacio , Colunga-Pedraza Iris J , Merayo-Chalico Javier , Chibuzo Okwara Celestine , Katchamart Wanruchada , Goo Phonpen Akawatcharangura , Shumnalieva Russka , Chen Yi-Ming , Hoff Leonardo Santos , El Kibbi Lina , Halabi Hussein , Sazliyana Shaharir Syahrul , Hasan A T M Tanveer , Dey Dzifa , Gutiérrez Carlos Enrique Toro , Caballero-Uribe Carlo Vinicio , Lilleker James B , Salim Babur , Gheita Tamer , Chatterjee Tulika , Saavedra Miguel A , Distler Oliver ,   COVAD Study Group, Griger Zoltán , Kardes Sinan , Andreoli Laura , Lini Daniele , Schreiber Karen , Vince Melinda Nagy , Singh Yogesh Preet , Ranjan Rajiv , Jain Avinash , Pandya Sapan C , Pilania Rakesh Kumar , Sharma Aman , Manesh Manoj M , Gupta Vikas , Kavadichanda Chengappa G , Patro Pradeepta Sekhar , Ajmani Sajal , Phatak Sanat , Goswami Rudra Prosad , Chowdhury Abhra Chandra , Mathew Ashish Jacob , Shenoy Padnamabha , Asranna Ajay , Bommakanti Keerthi Talari , Shukla Anuj , Pande Arunkumar R , Chandwar Kunal , Ghodke Akanksha , Boro Hiya , Fazal Zoha Zahid , Cansu Döndü Üsküdar , Yıldırım Reşit , Gasparyan Armen Yuri , Del Papa Nicoletta , Sambataro Gianluca , Fabiola Atzeni , Govoni Marcello , Parisi Simone , Bocci Elena Bartoloni , Sebastiani Gian Domenico , Fusaro Enrico , Sebastiani Marco , Quartuccio Luca , Franceschini Franco , Sainaghi Pier Paolo , Orsolini Giovanni , De Angelis Rossella , Danielli Maria Giovanna , Venerito Vincenzo , Grignaschi Silvia , Giollo Alessandro , Alluno Alessia , Ioannone Florenzo , Fornaro Marco , Traboco Lisa S , Wibowo Suryo Anggoro Kusumo , Loarce-Martos Jesús , Prieto-González Sergio , Gonzalez Raquel Aranega , Yoshida Akira , Nakashima Ran , Sato Shinji , Kimura Naoki , Kaneko Yuko , Gono Takahisa , Tomaras Stylianos , Proft Fabian Nikolai , Holzer Marie-Therese , Gromova Margarita Aleksandrovna , Aharonov Or , Griger Zoltán , Hmamouchi Ihsane , El Bouchti Imane , Baba Zineb , Giannini Margherita , Maurier François , Campagne Julien , Meyer Alain , Langguth Daman , Limaye Vidya , Needham Merrilee , Srivastav Nilesh , Hudson Marie , Landon-Cardinal Océane , Zuleta Wilmer Gerardo Rojas , Arbeláez Álvaro , Cajas Javier , Silva José António Pereira , Fonseca João Eurico , Zimba Olena , Bohdana Doskaliuk , Ima-Edomwonyi Uyi , Dedeke Ibukunoluwa , Airenakho Emorinken , Madu Nwankwo Henry , Yerima Abubakar , Olaosebikan Hakeem , Becky A , Koussougbo Oruma Devi , Palalane Elisa , So Ho , Ugarte-Gil Manuel Francisco , Chinchay Lyn , Bernaola José Proaño , Pimentel Victorio , Fathi Hanan Mohammed , Mohammed Reem Hamdy A , Harifi Ghita , Fuentes-Silva Yurilís , Cabriza Karoll , Losanto Jonathan , Colaman Nelly , Cachafeiro-Vilar Antonio , Bautista Generoso Guerra , Ho Enrique Julio Giraldo , Nunez Lilith Stange , Cristian Vergara M , Báez Jossiell Then , Alonzo Hugo , Pastelin Carlos Benito Santiago , Salinas Rodrigo García , Obiols Alejandro Quiñónez , Chávez Nilmo , Ordóñez Andrea Bran , Argueta Sandra , Llerena Gil Alberto Reyes , Sierra-Zorita Radames , Arrieta Dina , Hidalgo Eduardo Romero , Saenz Ricardo , Idania Escalante M , Calapaqui Wendy , Quezada Ivonne , Arredondo Gabriela , Chinoy Hector , Agarwal Vikas , Aggarwal Rohit , Gupta Latika 
Published: March 2023

Abstract

Objective
Flares of autoimmune rheumatic diseases (AIRDs) following COVID-19 vaccination are a particular concern in vaccine-hesitant individuals. Therefore, we investigated the incidence, predictors and patterns of flares following vaccination in individuals living with AIRDs, using global COVID-19 Vaccination in Autoimmune Diseases (COVAD) surveys.

Methods
The COVAD surveys were used to extract data on flare demographics, comorbidities, COVID-19 history, and vaccination details for patients with AIRDs. Flares following vaccination were identified as patient-reported (a), increased immunosuppression (b), clinical exacerbations (c) and worsening of PROMIS scores (d). We studied flare characteristics and used regression models to differentiate flares among various AIRDs.

Results
Of 15 165 total responses, the incidence of flares in 3453 patients with AIRDs was 11.3%, 14.8%, 9.5% and 26.7% by definitions a–d, respectively. There was moderate agreement between patient-reported and immunosuppression-defined flares (K = 0.403, P = 0.022). Arthritis (61.6%) and fatigue (58.8%) were the most commonly reported symptoms. Self-reported flares were associated with higher comorbidities (P = 0.013), mental health disorders (MHDs) (P &lt; 0.001) and autoimmune disease multimorbidity (AIDm) (P &lt; 0.001).
In regression analysis, the presence of AIDm [odds ratio (OR) = 1.4; 95% CI: 1.1, 1.7; P = 0.003), or a MHD (OR = 1.7; 95% CI: 1.1, 2.6; P = 0.007), or being a Moderna vaccine recipient (OR = 1.5; 95% CI: 1.09, 2.2; P = 0.014) were predictors of flares. Use of MMF (OR = 0.5; 95% CI: 0.3, 0.8; P = 0.009) and glucocorticoids (OR = 0.6; 95% CI: 0.5, 0.8; P = 0.003) were protective.
A higher frequency of patients with AIRDs reported overall active disease post-vaccination compared with before vaccination (OR = 1.3; 95% CI: 1.1, 1.5; P &lt; 0.001).

Conclusion
Flares occur in nearly 1 in 10 individuals with AIRDs after COVID vaccination; people with comorbidities (especially AIDm), MHDs and those receiving the Moderna vaccine are particularly vulnerable. Future avenues include exploring flare profiles and optimizing vaccine strategies for this group.