Received: 2 February 2022 Revised: 9 July 2022 Accepted: 17 July 2022 DOI: 10.1002/mus.27681 CLINICAL RESEARCH ARTICLE COVID-19 Vaccination in Autoimmune Diseases (COVAD) study: Vaccine safety in idiopathic inflammatory myopathies Albert Gil-Vila MD1 | Naveen Ravichandran MD, DM2 | 1 3 Albert Selva-O'Callaghan MD, PhD | Parikshit Sen | Arvind Nune MD4 | Prithvi Sanjeevkumar Gaur5 | Raquel Arànega Gonzalez MD6 | James B. Lilleker MRCP, PhD7,8 | Mrudula Joshi9 | Vishwesh Agarwal MBBS10 | Sinan Kardes MD11 | Minchul Kim PhD12 | 13,14,15 16 Jessica Day FRACP, PhD | Ashima Makol MBBS, MD | Marcin Milchert MD, PhD17 | Tamer Gheita MD18 | Babur Salim MD19 | 20 21 Tsvetelina Velikova MD, PhD | Abraham Edgar Gracia-Ramos MD | Ioannis Parodis MD, PhD22,23 | Elena Nikiphorou MD, MBBS24,25 | 26,27 Ai Lyn Tan MD, MRCP | Tulika Chatterjee MD, MPH12 | 28,29 Lorenzo Cavagna MD, PhD | Miguel A. Saavedra MD30 | Samuel Katsuyuki Shinjo MD, PhD31 | Nelly Ziade FRCP, PhD32,33 | 34 35 Johannes Knitza MD, MHBA | Masataka Kuwana MD, PhD | Oliver Distler MD36 | Hector Chinoy FRCP, PhD7,37,38 | Vikas Agarwal DM, FRCP2 | Rohit Aggarwal MD, MS39 | 2,7,40,41 Latika Gupta MD, DM | and the COVAD Study Group* Correspondence Latika Gupta, Department of Rheumatology, Abstract Royal Wolverhampton Hospitals NHS Trust, Introduction/Aims: In this study we investigated COVID-19 vaccination–related Wolverhampton WV10 0QP, UK. Email: drlatikagupta@gmail.com adverse events (ADEs) 7 days postvaccination in patients with idiopathic inflamma- tory myopathies (IIMs) and other systemic autoimmune and inflammatory disorders Funding information National Institution for Health Research (SAIDs). Manchester Biomedical Research Methods: Seven-day vaccine ADEs were collected in an international patient self- Centre (to H.C.). reported e-survey. Descriptive statistics were obtained and multivariable regression was performed. Abbreviations: ADE, adverse drug event; ASSD, anti-synthetase syndrome; BLR, binary logistic regression; CI, confidence interval; CNI, calcineurin inhibitor; DM, dermatomyositis; HC, healthy control; HCQ, hydroxychloroquine; IBM, inclusion-body myositis; IIM, idiopathic Inflammatory myopathies; IVIg, intravenous immunoglobulin; JDM, juvenile dermatomyositis; NAM, necrotizing myositis; OM, overlap myositis; NS, not significant; OM, overlap myositis; OR, odds ratio; PM, polymyositis; SAID, systemic autoimmune and inflammatory disorder. Albert Gil-Vila and Parikshit Sen contributed equally to this article. Rohit Aggarwal and Latika Gupta contributed equally to this article. *A complete listing of COVAD Study Group authors and their affiliations is provided in the Supplementary Material. For affiliation refer to page 435 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2022 The Authors. Muscle & Nerve published by Wiley Periodicals LLC. 426 wileyonlinelibrary.com/journal/mus Muscle & Nerve. 2022;66:426–437. GIL-VILA ET AL. 427 Results: Ten thousand nine hundred respondents were analyzed (1227 IIM cases, 4640 SAID cases, and 5033 healthy controls [HCs]; median age, 42 [interquartile range, 30-455] years; 74% female; 45% Caucasian; 69% completely vaccinated). Major ADEs were reported by 76.3% of the IIM patients and 4.6% reported major ADEs. Patients with active IIMs reported more frequent major (odds ratio [OR], 2.7; interquar- tile range [IQR], 1.04-7.3) and minor (OR, 1.5; IQR, 1.1-2.2) ADEs than patients with inactive IIMs. Rashes were more frequent in IIMs (OR, 2.3; IQR, 1.2-4.2) than HCs. ADEs were not impacted by steroid dose, although hydroxychloroquine and intravenous/ subcutaneous immunoglobulins were associated with a higher risk of minor ADEs (OR, 1.9; IQR, 1.1-3.3; and OR, 2.2; IQR, 1.1-4.3, respectively). Overall, ADEs were less fre- quent in inclusion-body myositis (IBM) and BNT162b2 (Pfizer) vaccine recipients. Discussion: Seven-day postvaccination ADEs were comparable in patients with IIMs, SAIDs, and HCs, except for a higher risk of rash in IIMs. Patients with dermatomyosi- tis with active disease may be at higher risk, and IBM patients may be at lower risk of specific ADEs. Overall, the benefit of preventing severe COVID-19 through vaccina- tion likely outweighs the risk of vaccine-related ADEs. Our results may inform future guidelines regarding COVID-19 vaccination in patients with SAIDs, specifically in those with IIMs. Studies to evaluate long-term outcomes and disease flares are needed to shed more light on developing future COVID-19 vaccination guidelines. KEYWORDS COVID-19, dermatomyositis, myositis, rheumatology, vaccination 1 | I N T RO DU CT I O N medications and potentially impacted by comorbid illness may predispose IIM patients to an increased risk of postvaccination ADEs, including aller- The development of vaccines against the novel coronavirus has gic reactions, anaphylaxis, and disease flares.9,10 Concerns have recently improved outcomes after COVID-19 infection in the general population. emerged that adjuvants and immune activators in vaccines induce auto- Several reports have demonstrated the safety and efficacy of COVID-19 immune disease flares and de-novo immune thrombotic and demyelinat- vaccines in the general population, but there are significant gaps in ing events.11,12 Poor characterization of postvaccination ADEs in IIM vaccine safety and efficacy data in vulnerable populations, including patients due to a lack of vaccine safety and efficacy study in this group patients with systemic autoimmune and inflammatory disorders (SAIDs), may have contributed to vaccine hesitancy.13,14 Therefore, there is a 1–3 those on immunosuppressive medications, and in pregnant women. need for evidence-based vaccine safety data with proper characterization The exclusion of patients with SAIDs and those on immunosuppressive of post-vaccination ADEs to potentially improve vaccination rates in medication from the initial vaccine safety trials has inevitably resulted in patients with IIM, a vulnerable patient group. a paucity of safety and efficacy data of COVID-19 vaccination in this In this study, we evaluated the short-term safety of COVID-19 vulnerable patient group. Although recent studies have included rheu- vaccination using a patient self-reported global multicenter electronic matic disorders, significant gaps exist in understanding the safety of survey. COVID-19 vaccination in patients with rare diseases, such as idiopathic inflammatory myopathies (IIMs).4–6 The study on vaccination-related adverse events (ADEs) in dermatomyositis (DM) from the TrinetX 2 | METHODS (Cambridge, MA) database has looked at the overall 1-, 30-, and 60-day ADEs after three vaccines (BNT162b2, mRNA-1273, and Ad26.COV.2.S) 2.1 | Study design 7 used in USA. The study included a total of 6104 vaccinated dermatomy- ositis (DM) patients from the USA. DM patients demonstrated a higher This is an international, online, cross-sectional, multicenter survey, rate of ADEs compared with age-matched healthy controls (HCs). The part of the COVID-19 Vaccination in Autoimmune Diseases (COVAD) studies so far available on vaccine ADEs in SAIDs or IIMs are largely study.15 Informed consent of the participants was obtained via a 8 regional and small. Studies claiming to be global have had an cover letter. Approval was obtained from the local institutional ethics underrepresentation of various ethnic groups (blacks and Asians).4 committee as per local guidelines, and the Checklist for Reporting An interplay between underlying autoimmunity and dysregulated Results of the Internet E-Surveys was adhered to when reporting immune pathways compounded by the effect of immunosuppressive results.16,17 428 GIL-VILA ET AL. 2.2 | Data collection 2.4 | Active and inactive disease A comprehensive patient-self reporting electronic survey was developed, Active and inactive disease 4 weeks before vaccination were assessed consisting of a questionnaire of 36 COVID-19–related and SAID-related by patients' response to questions about their symptoms before vacci- questions, which included demographic details; SAID diagnosis; treat- nation (eg rash, muscle weakness, joint pain, and swelling, etc) and ment details; current symptom status; COVID-19 infection history, need to step-up immunosuppression (Supplementary Methods). including symptoms, duration, and complications (hospitalization and need for oxygen therapy); COVID-19 vaccination details; 7-day short- term postvaccination ADEs (based on criteria from the US Centers for 2.5 | ADEs postvaccination Disease Control and Prevention); and patient-reported outcome mea- sures, as per the Patient Reported Outcomes Measurement Information Seven-day ADEs were categorized as injection-site pain and reaction, System tool.18 After vetting by international experts, pilot testing, revi- minor ADEs, major ADEs, and hospitalizations. Minor ADEs included sions, validation, and translation into 18 languages, the survey was hosted myalgia, body aches, fever, chills, nausea and vomiting, headache, on an online platform (surveymonkey.com) and circulated by the interna- rashes, fatigue, diarrhea, abdominal pain, high pulse rate or palpita- tional COVAD Study Group (over 110 physicians) in health-care centers tions, rise in blood pressure, fainting, difficulty in breathing, dizziness, in at least 94 countries (Supplementary Data), as well as through numer- and chest pain. Major ADEs consisted of serious reactions to vaccina- ous social media platforms and online patient-support groups. Patients tion requiring urgent medical attention, including anaphylaxis, a with multiple overlapping autoimmune diseases were put into all the cor- marked difficulty in breathing, throat closure (choking), and severe responding categories. Convenience sampling was used and all partici- rashes.19 Other ADEs that were not listed were reported as “others” pants over 18 years of age were included. Electronic protocols were used via an open-ended question. to remove duplicate responses from a single respondent. Methods have been detailed at length in the published COVAD study protocol.15 2.6 | Statistical analysis 2.3 | Data extraction Chi-square and Mann-Whitney U tests were used for categorical and con- tinuous variables, respectively. The variables expected to be indepen- Data were retrieved on September 30, 2021. Patients who had not dently significant between IIMs, SAIDs, and HCs, and between different received even a single dose of any COVID-19 vaccine at the time IIM subtypes, after univariable analysis, underwent binary logistic regres- of survey completion, and who had not completed the survey in sion analysis with adjustment for factors considered relevant based on full, were excluded from the analysis (Figure 1). Multiple relevant evidence from current literature and clinical judgment, including the fac- variables were extracted from the survey responses of the included tors of age, gender, ethnicity, immunosuppressant use, and vaccine participants, including COVID-19 infection history and 7-day received, and stratified by country of origin. The results for continuous postvaccination ADEs. variables are expressed as median (interquartile range [IQR]). P < .05 was FIGURE 1 Data extraction. GIL-VILA ET AL. 429 considered significant. The Bonferroni-corrected P value for univariate had received both primary doses of the COVID-19 vaccine. The largest analysis was taken as significant (P < 0.0125 for 2  2 chi-square analysis). number of respondents received the BNT162b2 (Pfizer) vaccine (39.8%), Nonparametric tests were used because the data were not normally dis- followed by theChadOx1 nCOV-19 vaccine (Oxford/AstraZeneca). Of tributed (by Kolmogorov-Smirnov test and Shapiro-Wilk test). Statistical the IIM patients, 34% had dermatomyositis, 17% had polymyositis, and analysis was performed using SPSS version 20 (IBM Corporation, Armonk, 23% had inclusion-body myositis (IBM). Other population characteristics NY) and R software version 3.5.3 (R Core Team, Vienna, Austria). of the study cohort are provided in Tables S1 and S5, and Tables S1,S2, and S6. 3 | RESULTS 3.2 | Post–COVID-19 vaccination–associated 3.1 | Population characteristics ADEs in patients with IIM Of the 16 328 total respondents, 2866 had not received a single dose of Any ADE was seen in 76.5%, with minor ADEs in 76.3% and major any COVID-19 vaccine at the time of survey completion and 2562 did ADEs in 4.6%. All-cause hospitalization was seen in 0.6%. Minor ADEs not complete the survey in full and were thus excluded from further most commonly seen were fatigue, myalgia, and fever. Severe rashes analysis (Figure 1). The 10 900 vaccinated respondents included in the were statistically more frequent in IIM patients when compared with analysis (74% female; median age, 42 [IQR, 30-55] years; 46% Caucasian) HCs (Table 5). were primarily from Turkey, Mexico, India, UK, and the USA, and con- Of the 102 patients with DM who reported a rash in the 4 weeks sisted of 11.2% with IIMs, 42.6% with other SAIDs, and 46.2% HCs. The prevaccination, 47 had a heliotrope rash, 66 had Gottron papules, most common SAIDs reported in the cohort were rheumatoid arthritis, 17 had Holster signs, 51 had a malar rash, 63 had a V sign, 42 had a followed by IIM and hyper/hypothyroidism. Of the respondents, 69% forearm/arm rash, and 60 had “mechanic's hands.” Of the 22 patients TABLE 1 Population characteristics Total (%) IIMs (%) Other SAIDs HCs (%) Variable (n = 10 900) (n = 1227) (%) (n = 4640) (N = 5033) Age (range), in years 42 (30-55) 49 (38-61) 47 (36-57) 33 (25-46) Gender M:F 2432:8558 (1:2.9) 283:782 (1:2.76) 568:3249 (1:5.7) 1491:2798 (1:1.8) Ethnicity Caucasian 4972 (46) 882 (72) 2303 (49) 1787 (35) African American or of African origin 83 (0.7) 34 (3) 22 (0.5) 27 (0.5) Asian 2018 (18) 71 (6) 781 (17) 1166 (23) Hispanic 1193 (11) 49 (4) 399 (8.5) 745 (15) Native American/Indigenous/Pacific Islander 342 (3) 1 (0) 18 (0.4) 323 (6) Do not wish to disclose 449 (4) 13 (1) 191 (4) 245 (5) Other 865 (8) 21 (2) 127 (3) 717 (14) Vaccine received BNT162b2 (Pfizer)-BioNTech 4333 (39) 645 (53) 2042 (44) 1443 (28.7) ChadOx1 nCOV-19 (Oxford/AstraZeneca) 1456 (13) 124 (10) 845 (18) 487 (9.7) JNJ-78436735 (JOHNSON AND JOHNSON) 95 (1) 15 (1.2) 42 (1) 38 (0.8) MRNA-1273 (Moderna) 910 (8) 360 (29) 387 (8) 163 (3.2) NVX-CoV2373 (Novovax) 14 (0.1) 0 (0) 10 (0.2) 4 (0.1) ChAdOx1 nCoV-19 (Covishield Serum Institute India) 1194 (11) 43 (3.5) 430 (9) 721 (14) BBV152 (Covaxin Bharat Biotech) 248 (2) 15 (1.2) 111 (2) 122 (2.4) Gam-COVID-Vac (Sputnik) 204 (2) 4 (0.3) 64 (1) 136 (2.7) BBIBP-CorV (Sinopharm) 1821 (17) 4 (0.3) 374 (8) 1443 (28.7) Not sure 62 (0.5) 0 (0) 27 (0.5) 35 (0.7) Others 563 (5) 17 (1.4) 309 (6) 238 (4.7) Discontinued medicines before vaccination 773 (13) 147 (12) 626 (13) --- Duration of discontinuing medicines (days) 13 (7-21) 14 (7-21) 12 (7-21) --- Abbreviations: HC, healthy control; IIM, idiopathic inflammatory myopathy; SAID, systemic autoimmune and inflammatory disease. 430 GIL-VILA ET AL. who had a rash after vaccination, 31% had inactive disease before more frequent in patients with active IIM compared with inactive disease vaccination, 27% had a DM rash, 27% had muscle weakness, 22% had before vaccination (Table 2). joint pain in the hands, and 4.5% had joint pain in other regions. The increase in postvaccination rashes could have represented a flare of a DM rash as 69% had active disease before vaccination. 3.4 | Post–COVID-19 vaccination–associated ADEs in patients with IIM based on immunosuppression received 3.3 | Post–COVID-19 vaccination–associated ADEs in patients with active and inactive IIM Although the wide variety of treatments used for IIMs results in a low frequency for each, an adjusted analysis shows that IIM patients who Among the IIM patients, 855 had active IIM 4 weeks before vaccina- were on rituximab (n = 40, 3%) more frequently had chills (odds ratio tion and 352 had inactive disease. Any ADE after COVID-19 vaccina- [OR], 2.6; IQR, 1.2-5.8; P = .012) and dizziness (OR, 3.9; IQR, 1.3-11; tion was more frequent in active IIM cases. Any minor ADE, myalgia, P = .010) after vaccination. Among the intravenous/subcutaneous body ache, headache fatigue, dizziness, and overall major ADE were immunoglobulin recipients (n = 117, 9%), any minor ADE (OR, 2.2; TABLE 2 Comparison of vaccination-related ADEs among active and inactive IIM cases Univariate Multivariable Active IIMa Inactive IIMa (n = 855) (n = 352) OR (95% CI) P value OR (95% CI) P value Any ADE 681 (79.6) 242 (68.8) 1.7 (1.3-2.3) <.001 1.6 (1.1-2.2) .006 Injection site pain 557 (65) 216 (61) .213 Minor ADEs Any minor ADE 679 (79.4) 242 (68.8) 1.7 (1.3-2.3) <.001 1.5 (1.1-2.2) .007 Myalgia 117 (13.7) 25 (7) 2 (1.3-3.2) .001 2.2 (1.3-3.8) .002 Body ache 178 (21) 49 (14) 1.6 (1.1-2.2) .005 1.5 (1.07-2.3) .020 Fever 112 (13) 37 (10.5) --- .214 Chills 134 (15.7) 38 (10.8) 1.5 (1.04-2.2) .028 1.3 (0.8-2.1) .162 Nausea and vomiting 60 (7) 12 (3.4) 2.1 (1.1-4) .016 1.7 (0.8-3.6) .107 Headache 212 (25) 55 (15.6) 1.7 (1.2-2.4) <.001 1.5 (1.04-2.1) .028 Rashes 25 (2.9) 9 (2.6) .726 Fatigue 266 (31.1) 73 (20.7) 1.7 (1.2-2.3) <.001 1.5 (1.08-2.1) .015 Diarrhea 22 (2.6) 5 (1.4) .218 Abdominal pain 24 (2.8) 3 (0.9) .051 High pulse rate or palpitations 21 (2.5) 6 (1.7) .422 Rise in blood pressure 5 (0.6) 3 (0.9) .603 Fainting 2 (0.2) 2 (0.6) .358 Difficulty in breathing 9 (1.1) 1 (0.3) .181 Dizziness 51 (6) 7 (2) 3.1 (1.4-6.9) .003 2.5 (1.08-5.9) .031 Chest pain 14 (1.6) 2 (0.6) .140 Major ADEs Any major ADE 49 (5.7) 6 (1.7) 3.5 (1.4-8.2) .002 2.7 (1.04-7.3) .040 Anaphylaxis 5 (0.6) 0 (0) .151 Marked difficulty in breathing 5 (0.6) 3 (0.9) .603 Throat closure 4 (0.5) 0 (0) .199 Severe rashes 7 (0.8) 1 (0.3) .298 Hospitalization 5 (0.6) 2 (0.6) .972 Notes: Chi-square test was used for categorical variables and Mann-Whitney U test used for continuous variables. Factors adjusted in multivariable analysis (binary logistic regression) include age, gender, ethnicity, vaccine received, number of vaccine doses received, and immunosuppressants received. Abbreviations: ADE, adverse drug event; CI, confidence interval; IIM, idiopathic inflammatory myopathy; OR, odds ratio. a Data expressed as number (%). GIL-VILA ET AL. 431 IQR, 1.1-4.3; P = .019) was more frequent and muscle pain (OR, 0.28; subtypes (Table 3 and Table S3). The risk of major ADEs and hospitali- IQR, 0.1-0.7; P =.01) was less frequent. zations remained consistent across different IIM subtypes with a very small absolute risk (0%-2%), but the numbers were too small (n = 0-10) to draw firm conclusions. 3.5 | Post–COVID-19 vaccination–associated ADEs between patients with different IIM subtypes 3.6 | Comparison of post–COVID-19 vaccination There was no significant difference for risk of overall minor ADEs ADE among patients with IIM by vaccine type between the different IIM subtypes. However, a higher risk of head- ache was observed in DM patients compared with other IIM subtypes After adjustment for baseline variables, IIM patients receiving the in the adjusted analysis, although the absolute risk of rash was very ChAdOx1 nCoV-19 vaccine (Covishield Serum Institute India) were at low across IIM subtypes (0%-5%). In contrast to their DM counter- a higher risk of myalgia and fever compared with the other vaccine parts, patients with IBM appeared to be less affected by postvaccina- recipients. There was a significantly higher overall risk of minor ADEs, tion ADEs, with a lower risk of myalgia compared with other IIM as well as a higher individual risk of injection site pain, chills, rashes, TABLE 3 COVID infection and COVID-19 vaccination–associated ADEs in IIM subtypesa DM PM IBM ASSD NAM OM JDM (n = 418) (n = 207) (n = 284) (n = 136) (n = 52) (n = 116) (n = 14) Injection-site pain 298 (71)*** 136 (65) 145 (51)*** 88 (65) 31 (59) 73 (63) 11 (78) Minor ADEs Myalgia 46 (11) 35 (17)* 15 (5)b*** 22 (16) 4 (7) 16 (14) 3 (21) Body ache 90 (21) 42 (20) 27 (9)*** 33 (24) 8 (15) 30 (13) 2 (14) ** Fever 64 (15) 28 (13) 19 (7) 14 (10) 5 (9) 19 (16) 2 (14) Chills 66 (16) 29 (14) 23 (8)** 26 (19) 7 (13) 22 (19) 2 (14) ** Nausea and vomiting 32 (8) 6 (3) 7 (2.5)* 9 (7) 4 (7) 14 (12) 1 (7) Headache 123 (29)b*** 37 (18) 29 (10)*** 32 (23) 10 (19) 36 (31)* 2 (14) b,*** * Rashes 21 (5) 2 (1) 1 (0.4) 3 (2) 1 (2) 6 (5) 0 (0) Fatigue 138 (33)** 63 (30) 47 (16)*** 40 (29) 19 (36) 34 (29) 6 (43) Diarrhea 13 (3) 2 (1) 4 (1.4) 2 (1.5) 1 (2) 7 (6)* 0 (0) Abdominal pain 11 (3) 3 (1) 5 (2) 3 (2) 2 (4) 3 (3) 0 (0) High pulse rate or palpitations 8 (2) 6 (3) 2 (0.7) 4 (3) 1 (2) 5 (4) 1 (7) Rise in blood pressure 3 (0.7) 1 (0.5) 0 (0) 1 (0.7) 0 (0) 3 (3)* 0 (0) ** Fainting 4 (1) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Difficulty in breathing 6 (1) 1 (0.5) 1 (0.4) 1 (0.7) 1 (2) 1 (1) 0 (0) ** * Dizziness 20 (5) 11 (5) 4 (1.4) 7 (5) 5 (10) 11 (9) 2 (14) Chest pain 7 (2) 0 (0) 1 (0.4) 4 (3) 1 (2) 3 (3) 1 (7) Major ADEs Anaphylaxis 5 (0.4) 2 (1) 2 (0.7) 0 (0) 0 (0) 0 (0) 0 (0) Marked difficulty in breathing 9 (0.7) 0 (0) 1 (0.4) 3 (2) 0 (0) 0 (0) 0 (0) Throat closure 4 (0.3) 1 (0.5) 1 (0.4) 1 (0.7) 0 (0) 0 (0) 1 (7) Severe rashes 10 (0.8) 1 (0.5) 0 (0) 0 (0) 1 (2) 1 (1) 0 (0) Hospitalization 7 (0.6) 2 (1) 1 (0.4) 1 (0.7) 0 (0) 1 (1) 0 (0) Notes: Chi-square test used for categorical variables and Mann-Whitney U test used for scale variables. Comparisons are between each IIM subtype vs the rest of IIM subtypes. Bold indicates increased OR vs the others. Bold+underlined indicates decreased OR vs the others. Abbreviations: ADE, adverse drug event; ASSD, anti-synthetase syndrome; CI, confidence interval; DM, dermatomyositis; IBM, inclusion-body myositis; IIM, idiopathic inflammatory myopathies; JDM, juvenile dermatomyositis; NAM, necrotizing myositis; OD, odds ratio; OM, overlap myositis; PM, polymyositis. a Data expressed as number (%). b Significant in BLR (binary logistic regression) adjusted for age, gender, ethnicity, immunosuppressant dose, and stratified by country. * P < .05, **P < .005, ***P < .001. 432 GIL-VILA ET AL. TABLE 4 Vaccine ADEs based on COVID-19 vaccine received among IIM patients (vs rest of vaccines) BNT162b2 ChadOx1 nCOV-19 (Oxford/ MRNA-1273 ChAdOx1 nCoV-19 (Covishield (Pfizer) (n = 634) AstraZeneca) (n = 124) (Moderna) (n = 360) Serum Institute India) (n = 43) Injection-site pain 398 (62) 69 (55)a* 273 (76)a*** 25 (58) Minor ADEs Any minor ADE 456 (71)a*** 96 (77) 303 (85)a*** 35 (81) a*** a* Myalgia 55 (8) 23 (18) 44 (12) 15 (35)a*** Body ache 99 (15)a*** 35 (28)a* 76 (21) 12 (28) a*** Fever 49 (7) 26 (21)a* 54 (15) 18 (42)a*** Chills 72 (11)a*** 29 (23)a* 65 (18)*,a 4 (9) * Nausea and vomiting 22 (3) a*** 15 (12) 31 (8)*,a 5 (11) a*** a** Headache 120 (18) 41 (33) 91 (25) 10 (23) Rashes 10 (1.5)a** 5 (4) 21 (6)a*** 1 (2) Fatigue 178 (27) 37 (29) 120 (33)* 7 (16)* Diarrhea 14 (2) 8 (6)* 8 (2) 1 (2) a*** Abdominal pain 12 (2) 9 (7) 7 (2) 2 (4) High pulse rate or palpitations 12 (2) 8 (6)a** 7 (2) 2 (4) Rise in blood pressure 7 (1) 3 (2) 1 (0.2) 1 (2) Fainting 5 (0.7) 1 (1) 1 (0.2) 1 (2) Difficulty in breathing 7 (1) 1 (1) 4 (1) 2 (4) Dizziness 21 (3)a,* 9 (7) 25 (6)* 3 (7) Chest pain 10 (1.5) 2 (1.6) 4 (1) 2 (4) Major ADEs Any major ADE 22 (3.3)* 11 (8.3)* 17 (4.7) 3 (7) Anaphylaxis 3 (0.4) 3 (2)* 1 (0.2) 1 (2) Marked difficulty in breathing 6 (1) 2 (1.6) 4 (1) 1 (2) Throat closure 1 (0.1)* 2 (1.6) 2 (0.5) 1 (2) Severe rashes 6 (1) 3 (2) 2 (0.5) 1 (2) Hospitalization 2 (0.2) 1 (1) 3 (0.8) 1 (2) Notes: Chi-square test used for categorical variables and Mann-Whitney U test used for scale variables. Bold indicates increased odds ratio vs the remaining vaccines. Bold+underlined indicates decreased odds ratio vs remaining vaccines. Abbreviations: ADE, adverse drug event; AID, autoimmune disease; HC, healthy control; IIM, idiopathic inflammatory myopathy. *P < .05, **P < .005, ***P < .001. a Significant according to binary logistic regression adjusted for age, gender, ethnicity, and immunosuppressant dose, and stratified by country. and nausea and vomiting, observed in IIM patients receiving the MRNA- minor ADEs, patients with IIM were at a higher risk of rashes com- 1273 vaccine (Moderna). Similarly, IIM patients receiving the ChAdOx1 pared with HCs, although the absolute risk of rash in both IIMs and nCOV-19 vaccine had a higher risk of myalgia, fever, chills, headache, HCs was very low (1%-2%) (Table 5 and Table S3). The absolute risk abdominal pain, and tachycardia/palpitations, yet a lower risk of of major ADEs and hospitalizations was low (0%–4%), and was similar injection-site pain compared with other vaccine recipients (Table 4 and between IIM patients and HCs (Table 5). Table S4). Conversely, IIM patients receiving the BNT162b2 vaccine had a lower overall risk (Table 4 and Table S4). The absolute risk in IIMs, SAIDs, and HCs, as well as in different IIM subtypes, was very small (<2% 3.8 | Post–COVID-19 vaccination–associated in most cases) across vaccine types (Table S5). ADEs in patients with IIM compared with other SAIDs The incidence of injection site pain was similar in IIM patients (63%) 3.7 | Post–COVID-19 vaccination–associated and other SAID patients (65%). Although the risk of most minor ADEs ADEs in patients with IIM compared with HCs was lower in IIM patients than in other SAID patients, the differences observed in uncontrolled univariable analysis did not attain signifi- The incidence of injection site pain was similar in IIM patients (63%) cance after multivariable analysis with baseline adjustment. Regard- and HCs (62%), with a very small absolute risk difference. Among less, the absolute risk in both IIM and SAID patients was very low GIL-VILA ET AL. 433 TABLE 5 Effects of COVID-19 vaccination in patients with IIMs vs other SAIDs and HCs IIMsa Other SAIDsa HCsa (n = 1227) (n = 4640) (n = 5033) OR 1 (CI) OR 2 (CI) P1 P2 Injection-site pain 784 (63) 3036 (65) 3138 (62) .316 .365 Minor ADEs Myalgia 144 (12) 777 (17) 778 (15.5) 0.6 (0.5-0.8) 0.7 (0.6-0.8) <.001 <.001 Body ache 233 (19) 1067 (23) 1082 (21) 0.8 (0.7-0.9) .003 .055 Fever 151 (12) 863 (18) 960 (19) 0.6 (0.5-0.7) 0.6 (0.5-0.7) <.001 <.001 Chills 176 (14) 714 (15) 631 (12.5) .365 .104 Nausea and vomiting 74 (6) 311 (7) 222 (4.4) 1.3 (1-1.8) .398 .021 Headache 271 (22) 1290 (28) 1125 (22.4) 0.7 (0.6-0.8) <.001 .884 Rashes 34 (3) 91 (2) 48 (1) 2.9 (1.8-4.5) .081 <.001 Fatigue 348 (28) 1511 (32) 1359 (27) 0.8 (0.7-0.9) <.001 .395 Diarrhea 29 (2.4) 174 (4) 120 (2.4) 0.6 (0.4-0.9) .018 .945 Abdominal pain 27 (2) 126 (3) 72 (1.4) .314 .059 High pulse rate or palpitations 27 (2) 166 (4) 125 (2.5) 0.6 (0.4-0.9) .016 .527 Rise in blood pressure 8 (0.6) 65 (1) 47 (0.9) 0.5 (0.2-0.9) .035 .328 Fainting 4 (0.3) 23 (0.5) 16 (0.3) .435 .980 Difficulty in breathing 10 (0.2) 59 (1) 50 (1) .187 .543 Dizziness 58 (4.8) 291 (6) 229 (4.4) 0.7 (0.5-0.99) .042 .498 Chest pain 17 (1.4) 81 (2) 60 (1.2) .381 .611 Others 77 (6) 431 (9) 270 (5) .567 .247 Major ADEs Anaphylaxis 5 (0.4) 6 (0.1) 5 (0.1) 5 (1.3-19) .060 .070 Marked difficulty in breathing 9 (0.7) 27 (0.6) 27 (0.5) .545 .430 Throat closure 4 (0.3) 23 (0.5) 4 (0.3) .435 .167 Severe rashes 10 (0.8) 31 (0.7) 15 (0.3) 2.7 (1.2-6) .583 .011 Others 40 (3) 149 (3) 56 (1) 2.9 (1.9-4.4) .945 .042 Hospitalization 7 (0.6) 20 (0.4) 11 (0.2) 2.5 (1-6.7) .521 .042 Notes: Bold values are statistically significant (P < .05). Chi-square test used for categorical variables and Mann-Whitney U test used for continuous variables. Abbreviations: ADE, adverse drug event; CI, confidence interval; HC, healthy control; IIM, idiopathic inflammatory myopathy; OR, odds ratio; OR1, OR between IIMs and other SAIDs; OR2 OR between IIMs and HCs; P1 P value between IIMs and other SAIDs, P2 P value between IIMs and HCs; SAID, systemic autoimmune and inflammatory disorder. a Data expressed as number (%). (0.6%-1%) (Table 4 and Table S3). Major ADEs and hospitalizations reported higher minor ADE, major ADE, and any ADE overall. Consid- were rare in IIM and other SAID patients, with a low absolute risk ering the potentially severe consequences of SARS-CoV-2 infection, (0%-4%) and no significant differences between the two groups our study adds to the growing body of evidence indicating that the (Table 5). benefit of preventing severe COVID-19 through vaccination in SAIDs, especially in IIMs, likely outweighs the risk of postvaccination ADEs, and thus supports guidance statements by the American College of 4 | DISCUSSION Rheumatology that encourage COVID-19 vaccination in patients with rheumatic diseases.19 Our results provide insights that may inform Overall, COVID-19 vaccination is safe in patients with IIMs and other future guidelines regarding COVID-19 vaccination in patients with SAIDs, and the majority of minor vaccine ADEs are easily manageable. SAIDs, specifically in IIM. COVID-19 vaccination in DM may lead to a mild increase in some Although large-scale studies regarding COVID-19 vaccination minor ADEs, mainly rash, without increasing either major ADEs or safety in autoimmune diseases are lacking, the safety data gleaned hospitalization rate. This could be due to flares of cutaneous disease from general population and small studies of immunocompromised postvaccination. Those with active disease before vaccination patients are reassuring. In a small, single-center cohort, Geisen et al 434 GIL-VILA ET AL. demonstrated the safety and efficacy of SARS-CoV-2 mRNA vaccines, This study has some limitations. Our data are based on patient showing no considerable side effects.20 Regarding IIM patients, the self-reported information, which could not be verified by medical data thus far is even more limited.21 records. Our population also represented a convenience sample, Among IIM patients, those with active disease reported higher where low-income patients without internet access, those with minor, major, and overall ADEs after vaccination. This is due to the severe disability, and those deceased were not represented. People cycle of autoimmunity triggering reactions and vice versa. Similar of African and African-American ethnicity were underrepresented 7 results have been demonstrated in other autoimmune diseases. in the cohort. Furthermore, we did not obtain information on the Among IIM subgroups, minor ADEs appear to be increased in DM and treatment required for the hospitalized patients after vaccination less frequent in IBM. However, it is important to note that subset ana- ADEs. Patients receiving immunosuppressive and biological drugs lyses by vaccine type were limited by small numbers, preventing firm may have impaired humoral responses, although the role of clinical conclusions. Specifically, few respondents had major postvaccine significance of this altered immune response is not yet clearly ADEs and hospitalizations. The absolute risk in IIMs, SAIDs, and HCs, understood.23 Furthermore, severe ADEs were rarely observed. as well as in different IIM subtypes, was very small (<2% in most Thus, limited events in each subgroup, such as major ADEs and cases) across vaccine types. It is well known that skin rash in DM hospitalization, would make it difficult to find any statistically sig- 22 patients may be exacerbated by environmental insults, and hence nificant correlations. Finally, the survey used in our study focused plausible that COVID-19 vaccination could also induce a flare of pre- on short-term ADEs, and long-term outcomes and disease flares existing rashes in these patients. Although the pathogenesis of IBM were not assessed. remains poorly understood, it has been shown to be an interplay between an autoimmune and degenerative disorder, yet antibody against cN-1A (NT5-c1A) has been identified.23 Autoimmunity is 5 | CONC LU SION thought to be an important part of IBM pathogenesis, but other fac- tors appear to be at play, as manifest by the prominent degenerative In this study we have shown that COVID-19 vaccination has a favor- features and mitochondrial dysfunction on muscle biopsy analysis. able short-term safety profile in IIM patients as in healthy individuals This may provide a possible explanation for the differences in minor and those with other SAIDs. Marginally higher ADRs, such as rashes, ADEs between IBM and DM. The other possibility is that DM and may have been related to disease phenotype and did not lead to an overlap myositis patients are at an increased risk of rashes inherent in increased hospitalization rate. Those with active disease before vacci- the disease phenotype, accounting for reporting bias in this patient- nation reported higher ADEs. Among IIM patients, the DM patients reported e-survey. Patients with active disease normally have rashes, may have been predisposed to specific ADEs, whereas those with and these may be misconstrued as vaccine ADEs. Whether this rash IBM subgroup had fewer reported ADEs. Studies on long-term out- worsened was unfortunately not specifically queried by the survey. comes and disease flares are needed to shed more light on developing Notably, seven patients had inactive disease, and later developed future COVID-19 vaccination guidelines. rashes. Even if it is true that the possibility of a postvaccine flare can- not be substantiated, long-term studies analyzing patients’ physical ROLE OF THE FU NDING SOURCE function and other organ involvement may provide further insight into This research did not receive any specific grant from funding agencies the possibility of disease flares, as data at 7 days are insufficient to in the public, commercial, or not-for-profit sectors. substantiate these speculations. With respect to vaccine type, our data suggest that IIM DECLARATION S patients have lower ADEs with BNT162b2 (Pfizer), ChadOx1 The views expressed in this publication are those of the authors and nCOV-19 (Oxford/AstraZeneca), and MRNA-1273 (Moderna) vac- not necessarily those of the National Health Service, the National cines, when compared with other autoimmune disease patients Institute for Health Research, or the Department of Health. and HCs. Within the IIM cohort, patients receiving the BNT162b2 vaccine were more protected from most minor ADEs when com- ET HICAL APPROVAL STATEMENT pared with MRNA-1273, ChadOx1 nCOV-19, and ChAdOx1 nCoV- We confirm that we have read the Journal's position on issues 19 recipients. To explain these differences, several aspects need to involved in ethical publication and affirm that this report is consistent be considered: different criteria, depending on the country or with those guidelines. region for approval of vaccination; different treatment when vacci- Ethical approval was obtained from the Institutional Ethics Com- nation took place; and different post-manufacturing processes. mittee of Sanjay Gandhi Postgraduate Institute of Medical Sciences, The type of vaccine and adjuvants present, their interaction with Raebareli Road, Lucknow, 226,014. the underlying immune dysfunction, and the interplay with the immunosuppressive medications taken by most of these patients AUTHOR CONTRIBU TIONS may affect the efficacy and safety of these vaccines in patients Conceptualization: A.G.V., N.R., P.S., A.N., A.S.O., L.G., V.A., and R.A.; with IIM and other SAIDs. Further studies are required to ascertain data curation: all authors; formal analysis: A.G.V., N.R., L.G., and R.A.; the safety profile of the various vaccines. investigation: A.G.V., N.R., A.S.O., P.S., L.G., and R.A.; methodology: GIL-VILA ET AL. 435 23 A.G.V., N.R., P.S., L.G., J.B.L., H.C., and R.A.; software: L.G.; validation: Department of Rheumatology, Faculty of Medicine and Health, V.A., R.A., J.B.L., H.C., and L.G.; visualization: R.A., V.A., and L.G.; writ- Örebro University, Örebro, Sweden 24 ing of original draft: A.G.V., N.R., P.S., A.N., A.S.O., L.G., and R.A.; writ- Centre for Rheumatic Diseases, King's College London, London, UK 25 ing, review, and editing: all authors. Rheumatology Department, King's College Hospital, London, UK 26 Disclaimer: No part of this manuscript is copied or published else- NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals where in whole or in part. Trust, Leeds, UK 27 Leeds Institute of Rheumatic and Musculoskeletal Medicine, AFFILIATIONS University of Leeds, Leeds, UK 1 28 Systemic Autoimmune Diseases Unit, Vall d'Hebron General Department of Rheumatology, Fondazione IRCCS Policlinico San  noma de Barcelona, Hospital, Medicine Department, Universitat Auto Matteo, Pavia, Italy 29 Barcelona, Spain Rheumatology Unit, Dipartimento di Medicine Interna e Terapia 2 Department of Clinical Immunology and Rheumatology, Sanjay Medica, Università degli studi di Pavia, Pavia, Lombardy, Italy 30 Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India Departamento de Reumatología Hospital de Especialidades 3 Maulana Azad Medical College, Delhi, India Dr. Antonio Fraga Mouret, Centro Médico Nacional La Raza, IMSS, 4 Southport and Ormskirk Hospital NHS Trust, Southport, UK Mexico City, Mexico 5 31 Smt. Kashibai Navale Medical and General Hospital, Pune, India Division of Rheumatology, Faculdade de Medicina FMUSP, 6 Internal Medicine Department, Hospital Clinic, Barcelona, Spain Universidade de São Paulo, São Paulo, Brazil 7 32 Centre for Musculoskeletal Research, Division of Musculoskeletal Rheumatology Department, Saint-Joseph University, Beirut, Lebanon 33 and Dermatological Sciences, School of Biological Sciences, Faculty of Rheumatology Department, Hotel-Dieu de France Hospital, Beirut, Biology, Medicine and Health, Manchester Academic Health Science Lebanon 34 Centre, University of Manchester, Manchester, UK Medizinische Klinik 3-Rheumatologie und Immunologie, 8 Neurology, Manchester Centre for Clinical Neurosciences, Northern Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Care Alliance NHS Foundation Trust, Salford, UK Erlangen-Nürnberg, Erlangen, Germany 9 35 Byramjee Jeejeebhoy Government Medical College and Sassoon Department of Allergy and Rheumatology, Nippon Medical School General Hospitals, Pune, India Graduate School of Medicine, Tokyo, Japan 10 36 Mahatma Gandhi Mission Medical College, Navi Mumbai, Department of Rheumatology, University Hospital Zurich, Maharashtra, India University of Zurich, Zurich, Switzerland 11 37 Department of Medical Ecology and Hydroclimatology, Istanbul National Institute for Health Research Manchester Biomedical Faculty of Medicine, Istanbul University, Istanbul, Turkey Research Centre, Manchester University NHS Foundation Trust, 12 Center for Outcomes Research, Department of Internal Medicine, University of Manchester, Manchester, UK 38 University of Illinois College of Medicine Peoria, Peoria, Illinois Department of Rheumatology, Salford Royal Hospital Northern 13 Department of Rheumatology, Royal Melbourne Hospital, Parkville, Care Alliance NHS Foundation Trust, Salford, UK 39 Victoria, Australia Division of Rheumatology and Clinical Immunology, University of 14 Walter and Eliza Hall Institute of Medical Research, Parkville, Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 40 Victoria, Australia Department of Rheumatology, Royal Wolverhampton Hospital NHS 15 Department of Medical Biology, University of Melbourne, Parkville, Trust, Wolverhampton, UK 41 Victoria, Australia City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, 16 Division of Rheumatology, Mayo Clinic, Rochester, Minnesota Birmingham, UK 17 Department of Internal Medicine, Rheumatology, Geriatrics and Clinical Immunology, Pomeranian Medical University in Szczecin, ACKNOWLEDG MENTS Szczecin, Poland The authors are grateful to all respondents for completing their question- 18 Rheumatology Department, Kasr Al Ainy School of Medicine, Cairo naires. We also thank the Myositis Association, Myositis India, Myositis University, Cairo, Egypt UK, Myositis Support and Understanding, the Myositis Global Network, 19 Rheumatology Department, Fauji Foundation Hospital, Rawalpindi, Deutsche Gesellschaft für Muskelkranke e.V. (DGM), Dutch and Swedish Pakistan Myositis patient support groups, Cure JM, Cure IBM, Sjögren's India 20 Department of Clinical Immunology, Medical Faculty, University Foundation, Patients Engage, Scleroderma India, Lupus UK, Lupus Swe- Hospital "Lozenetz," Sofia University St. Kliment Ohridski, Sofia, Bulgaria den, the Emirates Arthritis Foundation, EULAR PARE, the ArLAR research 21 Department of Internal Medicine, General Hospital, National group, the AAAA patient group, the APLAR myositis special interest Medical Center “La Raza,” Instituto Mexicano del Seguro Social, group, the Thai Rheumatism Association, PANLAR, NRAS, the Anti-Syn- Mexico City, Mexico thetase Syndrome support group, and various other patient support 22 Division of Rheumatology, Department of Medicine Solna, groups and organizations for their contributions in dissemination of this Karolinska Institutet and Karolinska University Hospital, Stockholm, survey. Finally, we thank all members of the COVAD Study Group for Sweden their invaluable role in data collection. COVAD Study Group: Bhupen 436 GIL-VILA ET AL. Barman, Yogesh Preet Singh, Rajiv Ranjan, Avinash Jain, Sapan C Pandya, DATA AVAILABILITY STAT EMEN T Rakesh Kumar Pilania, Aman Sharma, Manesh Manoj M, Vikas Gupta, All data is available as a manuscript in the supplementary material. Chengappa G Kavadichanda, Pradeepta Sekhar Patro, Sajal Ajmani, Sanat Additional data is available on request. Phatak, Rudra Prosad Goswami, Abhra Chandra Chowdhury, Ashish Jacob Mathew, Padnamabha Shenoy, Ajay Asranna, Keerthi Talari Bom- OR CID makanti, Anuj Shukla, Arunkumar R Pande, Kunal Chandwar, Döndü Albert Gil-Vila https://orcid.org/0000-0003-2786-2009 Üsküdar Cansu, John D Pauling, Chris Wincup, Ashima Makol, Nicoletta Naveen Ravichandran https://orcid.org/0000-0003-2014-3925 Del Papa, Gianluca Sambataro, Atzeni Fabiola, Marcello Govoni, Simone Albert Selva-O'Callaghan https://orcid.org/0000-0003-2823-9761 Parisi, Elena Bartoloni Bocci, Gian Domenico Sebastiani, Enrico Fusaro, Parikshit Sen https://orcid.org/0000-0002-1630-6026 Marco Sebastiani, Luca Quartuccio, Franco Franceschini, Pier Paolo Sai- Arvind Nune https://orcid.org/0000-0002-3849-614X naghi, Giovanni Orsolini, Rossella De Angelis, Maria Giovanna Danielli, Prithvi Sanjeevkumar Gaur https://orcid.org/0000-0002-2341- Vincenzo Venerito, Lisa S Traboco, Suryo Anggoro Kusumo Wibowo, 1932 Jorge Rojas Serrano, Ignacio García-De La Torre, Erick Adrian Zamora James B. Lilleker https://orcid.org/0000-0002-9230-4137 Tehozol, Jesús Loarce-Martos, Sergio Prieto-González, Akira Yoshida, Mrudula Joshi https://orcid.org/0000-0001-7312-351X Ran Nakashima, Shinji Sato, Naoki Kimura, Yuko Kaneko, Stylianos Vishwesh Agarwal https://orcid.org/0000-0002-0986-8354 Tomaras, Margarita Aleksandrovna Gromova, Or Aharonov, Ihsane Hma- Sinan Kardes https://orcid.org/0000-0002-6311-8634 mouchi, Leonardo Santos Hoff, Margherita Giannini, François Maurier, Minchul Kim https://orcid.org/0000-0001-9737-6255 Julien Campagne, Alain Meyer, Melinda Nagy-Vincze, Daman Langguth, Jessica Day https://orcid.org/0000-0001-8528-4361 Vidya Limaye, Merrilee Needham, Nilesh Srivastav, Marie Hudson, Ashima Makol https://orcid.org/0000-0002-8748-898X Océane Landon-Cardinal, Syahrul Sazliyana Shaharir, Wilmer Gerardo Marcin Milchert https://orcid.org/0000-0002-0943-8768  nio Pereira Silva, João Eurico Fonseca, Olena Rojas Zuleta, José Anto Tamer Gheita https://orcid.org/0000-0002-1155-9729 Zimba. Babur Salim https://orcid.org/0000-0001-8430-9299 Tsvetelina Velikova https://orcid.org/0000-0002-0593-1272 CONF LICT S OF INTE R ES T Abraham Edgar Gracia-Ramos https://orcid.org/0000-0003-1842- J.D. has received research funding from CSL, Ltd. A.L.T. has received 2554 honoraria for advisory boards and speaking for AbbVie, Gilead, Jans- Ioannis Parodis https://orcid.org/0000-0002-4875-5395 sen, Lilly, Novartis, BNT162b2 (Pfizer), and UCB. E.N. has received Elena Nikiphorou https://orcid.org/0000-0001-6847-3726 speaker honoraria or participated on advisory boards for Celltrion, Ai Lyn Tan https://orcid.org/0000-0002-9158-7243 BNT162b2 (Pfizer), Sanofi, Gilead, Galapagos, AbbVie, and Lilly, and Tulika Chatterjee https://orcid.org/0000-0001-8844-851X holds research grants from BNT162b2 (Pfizer) and Lilly. H.C. has Lorenzo Cavagna https://orcid.org/0000-0003-3292-1528 received grant support from Eli Lilly and UCB, consulting fees from Miguel A. Saavedra https://orcid.org/0000-0003-0687-9944 Novartis, Eli Lilly, Orphazyme, and AstraZeneca, and speaker fees Samuel Katsuyuki Shinjo https://orcid.org/0000-0002-3682-4517 from UCB and Biogen. I.P. has received research funding and/or hon- Nelly Ziade https://orcid.org/0000-0002-4479-7678 oraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly, Johannes Knitza https://orcid.org/0000-0001-9695-0657 Gilead, GlaxoSmithKline, Janssen, Novartis, and Hoffmann-La Roche. Masataka Kuwana https://orcid.org/0000-0001-8352-6136 N.Z. has received speaker fees, advisory board fees, and research Oliver Distler https://orcid.org/0000-0002-0546-8310 grants from BNT162b2 (Pfizer), Roche, AbbVie, Eli Lilly, NewBridge, Hector Chinoy https://orcid.org/0000-0001-6492-1288 Sanofi-Aventis, Boehringer Ingelheim, Janssen, and Pierre Fabre (none Vikas Agarwal https://orcid.org/0000-0002-4508-1233 related to this work). O.D. has/had consultancy relationship with Rohit Aggarwal https://orcid.org/0000-0001-7531-8038 and/or has received research funding from or has served as a speaker Latika Gupta https://orcid.org/0000-0003-2753-2990 for the following companies in the area of potential treatments for systemic sclerosis and its complications in the past 3 years: AbbVie, RE FE RE NCE S Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, 1. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383:2603- Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, 2615. doi:10.1056/NEJMoa2034577. Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, 2. Tariq J, Gupta L. Safety and efficacy of COVID-19 vaccines in pregnant women with rheumatic diseases: an immunologic perspective. Rheumatol Sanofi, Serodapharm, Topadur, and UCB. O.D. has also issued a patent Int. 2021;41:1545-1547. doi:10.1007/s00296-021-04918-z. “mir-29 for the Treatment of Systemic Sclerosis” (US8247389, 3. Wack S, Patton T, Ferris LK. COVID-19 vaccine safety and efficacy in EP2331143). R.A. has/had a consultancy relationship with and/or has patients with immune-mediated inflammatory disease: review of received research funding from the following companies: Bristol available evidence. J Am Acad Dermatol. 2021;85:1274-1284. doi:10. 1016/j.jaad.2021.07.054. Myers-Squibb, BNT162b2 (Pfizer), Genentech, Octapharma, CSL Beh- 4. Sattui SE, Liew JW, Kennedy K, et al. Early experience of COVID-19 ring, Mallinckrodt, AstraZeneca, Corbus, Kezar, AbbVie, Janssen, Alex- vaccination in adults with systemic rheumatic diseases: results from ion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, and Roivant. the COVID-19 Global Rheumatology Alliance Vaccine Survey. RMD The remaining authors declare no conflicts of interest. 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