key: cord-1026310-2wkrp3ql
authors: Boekel, Laura; Kummer, Laura Y; van Dam, Koos P J; Hooijberg, Femke; van Kempen, Zoé; Vogelzang, Erik H; Wieske, Luuk; Eftimov, Filip; van Vollenhoven, Ronald; Kuijpers, Taco W; van Ham, S Marieke; Tas, Sander W; Killestein, Joep; Boers, Maarten; Nurmohamed, Mike T; Rispens, Theo; Wolbink, Gertjan
title: Adverse events after first COVID-19 vaccination in patients with autoimmune diseases
date: 2021-06-18
journal: Lancet Rheumatol
DOI: 10.1016/s2665-9913(21)00181-8
sha: 58cae6c04290d5acb9785c52dcb7aeac70b77fad
doc_id: 1026310
cord_uid: 2wkrp3ql

nan

study were asked (but not obliged) to recruit their own healthy control participant who was of the same sex and of comparable age (age difference <5 years). Data were collected via online questionnaries distributed via email. Information on demographic data and medication use were collected at baseline, and data on adverse events of COVID-19 vaccinations were collected between April 14 and April 30, 2021.

Participants were asked whether they had received a COVID-19 vaccination. Vaccinated participants were asked to report whether they experienced any local or systemic adverse events in the first 7 days following vaccination, and if so, to report on the severity and duration of the adverse events. Mild adverse events were defined as unpleasant reactions that did not limit daily activities, moderate adverse events as those that limited daily activities, and severe adverse events as those that required medical attention. Serious adverse events were defined as reactions that resulted in hospital admission. Systemic adverse events included fever, chills and shiver, general malaise, nausea, diarrhoea, myalgia, arthralgia, headache, and fatigue. Patients with rheumatic diseases and healthy controls were asked whether they experienced an increased number of joint complaints in the first 2 months after vaccination. All patients with autoimmune diseases were asked whether they experienced a change in their autoimmune disease up to 2 months after vaccination. Additional questions were included to assess whether vaccination would lead to an improved sense of security or quality of life among patients and controls.

All participants who completed the questionnaire at least 4 days after their first COVID-19 vaccination were included in the analyses. We used multivariable logistic regression analyses to compare the occurrence of any adverse event, systemic adverse events, and moderateto-severe adverse events between patients and controls. Effect modification was investigated for age (stratified to participants aged ≤55 years vs >55 years), sex, and vaccine type. A threshold of p<0·05 was used for interaction terms to identify effect modifiers. Additionally, we did exploratory analyses to compare adverse events between vaccine types, male and female participants, and participants older and younger than 55 years without correction for multiple testing. The research protocols were approved by the medical ethical committee of the VU University medical center (registration number 2020.169 and 2020.370). All participants provided informed consent.

The questionnaire was sent to 2515 patients with autoimmune diseases and 903 healthy controls, of whom 1780 patients and 660 controls completed the questionnaire. 505 patients (including 204 patients with rheumatoid arthritis and 81 patients with multiple sclerosis) and 203 healthy controls completed the questionnaire at least 4 days after receiving their first COVID-19 vaccination and were included in the analyses (appendix p 1). The median number of days between the first vaccination and completing the questionnaire was 15 days (IQR 10-25) for patients and 15 days (10-34) for controls . The mean age of both patients and controls was 64 years (SD 11), and 329 (65%) of 505 patients and 133 (66%) of 203 controls were women (appendix p 2). patients with rheumatoid arthritis or multiple sclerosis were compared with healthy controls (appendix p 5).

Age was a significant effect modifier in the association between autoimmune status and the risk of moderate or severe adverse events, but additional age-stratified multivariable regression analyses did not reach statistical significance in both strata (data not shown). Vaccination with ChAdOx1 nCoV-19, female sex, and younger age (≤55 years) were independently associated with an increased likelihood of reporting any adverse event, systemic adverse events, and moderate or severe adverse events after a COVID-19 vaccination (appendix p 5). All results remained similar when participants who completed the questionnaire within 7 days after the first COVID-19 vaccination were excluded from the analyses.

Most participants (217 [75%] of 289 patients and 91 [76%] of 120 controls) indicated that they felt safer from 2 weeks after their first COVID-19 vaccination (appendix p 5). Additionally, 58 (20%) of 288 patients and 17 (14%) of 120 controls also reported to perceive an overall improvement in their quality of life.

Analysis of the results of our questionnaire demonstrate that adverse events of COVID-19 vaccinations in patients with autoimmune diseases are comparable with controls, independent of the type of vaccine. The observed adverse events consisted of expected transient local or systemic reactions that were mostly self-limiting. The frequency of participants who reported adverse events was lower than that reported in clinical trials, 6 but similar to a nationwide observational study on adverse events of COVID-19 vaccinations in the general population done in the UK. 7 Our data are consistent with previous studies that reported higher frequencies of adverse events in women and younger people. 6, 7 We did not observe any serious adverse events, but the number of participants included in our study was too low to draw conclusions about rare serious events. Additionally, our data suggest that COVID-19 vaccinations do not seem to trigger autoimmune disease flares, which is in accordance with data from previous small studies that assessed consequences of mRNA vaccines in patients with autoimmune diseases. 8, 9 However, a limitation of our study is that data on disease activity were based on self-report rather than validated disease activity measures, and we did not assess the duration and severity of disease flares. Known pathophysiological effects of mRNA on the innate immune system could be both immunostimulatory and immunosuppressive, 10, 11 thus as COVID-19 vaccines are the first mRNA vaccines to be widely applied, prospective controlled studies with adequate follow-up are required to draw robust conclusions about long-term effects of COVID-19 vaccines on autoimmune disease activity. Another limitation of our study was that control participants were not a random sample of the general population, nor were they an exact match for patients with autoimmune diseases with regard to age and sex distribution. However, we adjusted for these variables as possible confounders in our analysis. We found that vaccination had favourable effects on psychological wellbeing; the majority of participants indicated that they felt safer after receiving a COVID-19 vaccination, and 20% of patients with autoimmune diseases reported a perceived overall increase of their quality of life. Overall, our data indicated that COVID-19 vaccines are well tolerated by patients with autoimmune diseases. Such findings might reassure patients who remain hesitant about COVID-19 vaccinations, and help physicians in guiding their patients towards accepting such vaccines.

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