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

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. Atypical rheumatic manifestations 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.

Remitting seronegative symmetrical synovitis with pitting oedema following BNT162b2 mRNA COVID-19 vaccination

“…A previous case series study described an 83-year-old patient with history of polymyalgia rheumatica who developed RS3PE, 7 days after the first dose of the BNT162b2 mRNA vaccine. 9 The patient had a prompt response to treatment and resolution of his symptoms.…”

Acute autoimmune-like hepatitis with atypical anti-mitochondrial antibody after mRNA COVID-19 vaccination: A novel clinical entity?

“…This does not exclude a triggering role for the mRNA vaccine, which elicits a strong stimulus to innate immunity, due to the intrinsic immunostimulatory properties of mRNA via its recognition by intracellular innate sensors, including toll-like receptors 3 and 7 and components of the inflammasome, resulting in cellular activation leading to interferon I and other pro-inflammatory cytokine and chemokine production [ 1 ]. Of note, new onset of autoimmune diseases with a latency as short as four days after the first mRNA vaccine dose has been reported [ 6 ]. However, we cannot exclude that our patient had had asymptomatic SARS-CoV-2 infection as suggested by positive anti-phospholipid IgA antibodies, in absence of IgG and IgM, a combination that has been reported in COVID-19 patients [ 12 ].…”

“…These vaccines trigger the interferon pathway as part of their mechanism of action, raising concerns about potential safety issues in patients predisposed to autoimmune conditions associated with interferon activation, including autoimmune hepatitis (AIH) [ 1 , 2 ]. A diverse range of autoimmune diseases following COVID-19 and anti-SARS-CoV-2 vaccination are increasingly being reported [ [3] , [4] , [5] , [6] ]. Recently, autoimmune-like hepatitis following mRNA Covid-19 has been reported in four women, only one of whom having pre-existing extrahepatic autoimmune conditions [ [7] , [8] , [9] , [10] ].…”

Administration of COVID-19 vaccines in immunocompromised patients

“…Moreover, 62 subjects (0.3%) out of all subjects in Pfizer-BioNTech clinical trials had rheumatic diseases and received BNT162b2. These subjects showed no relapse or flare-up of the underlying rheumatic condition, although data is still limited [71] .Though, there is a slight probability for disease flares after vaccination [163] .Subjects with rheumatic diseases were excluded from Moderna vaccine clinical trials [70] , and probably none has been included in the clinical trials of the Janssen vaccine [164] . Vaccination against COVID-19 in subjects with an underlying rheumatic disease as a part of vulnerable subject groups has been highly recommended by the United States Center for Disease Control and Prevention (US CDC) [6] , the British Society of Rheumatology (BSR) [165] , and the American College of Rheumatology (ACR) [166] in spite of probable adverse effects following vaccination.In this context, vaccination in rheumatic disease subjects during the quiescent state of the disease is highly recommended as is the case for other vaccines in such patients [167] , [168] .While in subjects with active rheumatic diseases, data is still limited regarding vaccine immunogenicity despite studies showing no evident correlation between the immunogenicity of vaccines and the state of the underlying rheumatic disease such as juvenile systemic lupus erythematosus (SLE) [169] .…”