Immune-Mediated Disease Flares or New-Onset Disease in 27 Subjects Following mRNA/DNA SARS-CoV-2 Vaccination

 Immune-Mediated Disease Flares or New-Onset Disease in 27 Subjects Following mRNA/DNA SARS-CoV-2 Vaccination

Academic Editor: Eduardo Gomez-Casado

Vaccines 2021, 9(5), 435; https://doi.org/10.3390/vaccines9050435

Abstract

Background: Infectious diseases and vaccines can occasionally cause new-onset or flare of immune-mediated diseases (IMDs). The adjuvanticity of the available SARS-CoV-2 vaccines is based on either TLR-7/8 or TLR-9 agonism, which is distinct from previous vaccines and is a common pathogenic mechanism in IMDs. Methods: We evaluated IMD flares or new disease onset within 28-days of SARS-CoV-2 vaccination at five large tertiary centres in countries with early vaccination adoption, three in Israel, one in UK, and one in USA. We assessed the pattern of disease expression in terms of autoimmune, autoinflammatory, or mixed disease phenotype and organ system affected. We also evaluated outcomes. Findings: 27 cases included 17 flares and 10 new onset IMDs. 23/27 received the BNT - 162b2 vaccine, 2/27 the mRNA-1273 and 2/27 the ChAdOx1 vaccines. The mean age was 54.4 ± 19.2 years and 55% of cases were female. Among the 27 cases, 21 (78%) had at least one underlying autoimmune/rheumatic disease prior the vaccination. Among those patients with a flare or activation, four episodes occurred after receiving the second-dose and in one patient they occurred both after the first and the second-dose. In those patients with a new onset disease, two occurred after the second-dose and in one patient occurred both after the first (new onset) and second-dose (flare). For either dose, IMDs occurred on average 4 days later. Of the cases, 20/27 (75%) were mild to moderate in severity. Over 80% of cases had excellent resolution of inflammatory features, mostly with the use of corticosteroid therapy. Other immune-mediated conditions included idiopathic pericarditis (n = 2), neurosarcoidosis with small fiber neuropathy (n = 1), demyelination (n = 1), and myasthenia gravis (n = 2). In 22 cases (81.5%), the insurgence of Adverse event following immunization (AEFI)/IMD could not be explained based on the drug received by the patient. In 23 cases (85.2%), AEFI development could not be explained based on the underlying disease/co-morbidities. Only in one case (3.7%), the timing window of the insurgence of the side effect was considered not compatible with the time from vaccine to flare. Interpretation: Despite the high population exposure in the regions served by these centers, IMDs flares or onset temporally-associated with SARS-CoV-2 vaccination appear rare. Most are moderate in severity and responsive to therapy although some severe flares occurred. Funding: none.

3. Results

We identified 27 cases of IMDs (15 females, 55.6%; 12 males, 44.4%; mean age 54.44 ± 19.20 years). 21 had an autoimmune/rheumatic background. This could be further subcategorized as autoimmune (n = 11, 52.4%), autoinflammatory (n = 4, 19.0%) and mixed pattern (n = 6, 28.6%) disorders before COVID-19 vaccination. In six patients (22.2%), there was no autoimmune/rheumatic background and patients presented new-onset rheumatic and musculoskeletal (RMD) and non-RMD disorders 

Other factors such as alternative infectious triggers, active COVID-19 infection around vaccination, joint trauma or major surgery as triggering events were not found, although patients were not systematically tested for SARS-CoV-2 infection unless there were typical symptoms.

Twenty-three (85.2%), two (7.4%), and two (7.4%) received the BNT-162b2, mRNA-1273 and ChAdOx1 vaccines, respectively. Twenty cases (74.1%) were reported in Israel, five (18.5%) in the UK, and two (7.4%) in the USA.

The average time between vaccination and new-onset or flare of symptoms was 4 days (median of 4 days [1–25 days] in those who developed an IMD after the first dose and a median of 4 days [1–7 days] in those after the second dose) with most cases occurring after the first inoculation (77.8%). Twelve cases flared after the first vaccine dose, one case flared after both the first and the second vaccine dose, and four cases flared only after the second vaccine dose. Fifteen cases (55.6%) did not receive the second vaccination.

Although we did not formally collect data on well-known vaccine adverse reactions such as fever, headaches, myalgia, and arm pain following vaccination, these features did not appear to be severe from review of medical records. Most IMDs were mild-to-moderate in terms of severity (n = 20, 74.1%).

In 22 cases (81.5%), the development of AEFI/IMD could not be explained based on the drug received by the patient. In 23 cases (85.2%), AEFI development could not be explained based on the underlying disease/co-morbidities. Only in one case (3.7%), the timing window of the insurgence of the side effect was considered not compatible with the time from vaccine to flare

READ THE FULL TEXT HERE: https://www.mdpi.com/2076-393X/9/5/435/htm