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We read with interest the recent report by Geisen et al,1 who describe the immunogenicity and safety profile of two mRNA-based anti-SARS-CoV-2 vaccines in a cohort of 26 patients with chronic arthritides, psoriasis and other inflammatory diseases, compared with 42 healthy controls. The majority of subjects were health professionals, which makes the 14-day post-vaccinal observations provided by the authors particularly informative for high-risk settings, such as hospitals. Extensive data about the impact of anti-SARS-CoV-2 vaccines in patients with immune-mediated disorders are eagerly awaited, since people living with these diseases were excluded from registration trials,2–4 despite constituting a risk group for severe SARS-CoV-2-realated disease (COVID-19)5–7 and, potentially, for adverse immune-mediated post-vaccinal events.8–11
To contribute in filling this knowledge gap, we studied 55 consecutive patients (54 health professionals) with rheumatic diseases and primary immunodeficiencies, for a median (IQR) of 66 (42–75) days from the first and 45 (20–52) days from the second dose of the BNT162b2 vaccine2 (detailed methods: online supplemental material 1). Thirty-eight patients (69%) had one or more comorbidities, including allergy in 22 cases (table 1).
At time of vaccination, 42/55 patients had been in remission for 20 (5–29) months. The median disease duration was 11 (5–18) years. Fifty-one patients (93%) were taking one or more immunosuppressive/immunomodulating drugs beside other treatments (online supplemental tables 1 and 2).
No patient had evidence of SARS-CoV-2 infection during follow-up. Thirty-eight patients (69%) reported at least one symptom after the first (47%), the second (56%) or both doses (35%; online supplemental table 3) with a median timing of 24 hours for onset and 48 hours for resolution. Symptoms after the first dose predicted having symptoms after the second one (OR=3.85, 95% CI 1.23 to 12.01; p=0.020). All events were mild and included more frequently constitutional symptoms (49%) and local pain at injection site (38%). Constitutional symptoms were more frequent after the second than after the first dose (38 vs 18%; p=0.033; online supplemental table 4).
Adverse events were more frequent in women than in men (78% vs 30%; p=0.006) and less frequent in IgG4-related disease (IgG4RD, 29%) than in other patients (75%; p=0.024). The median age was lower in patient with (49 (39–55) years) than in those without adverse events (58 (46–66); p=0.021). No association was found with disease duration, remission, duration of remission or previous COVID-19. All four patients with inflammatory spondyloarthropathies had adverse events after the first (χ2=4.81; p=0.044 compared with other diseases) and second dose, with symptom severity slightly increasing across the two doses (online supplemental table 5). No other factors were associated to adverse events after the first dose. Adverse events after the second dose were more frequent in women (67% vs 10% in men; p=0.001), patients with allergy history (77% vs 42% in patients with no allergy; p=0.014), especially to drugs (82% vs 45% in patients with no history of drug allergy; p=0.017), connective tissue diseases (80% vs 48% in patients with other disorders; p=0.037) and patients without IgG4RD (65% vs 0% in IgG4RD; p=0.002).
Constitutional symptoms were more frequent in patients with arthritis than in other patients (84% vs 31%; p<0.001). Specifically, these patients showed higher frequencies of fever (47% vs 11%; p=0.006), and arthralgia/myalgia (47% vs 17%; p=0.025). Constitutional symptoms were particularly frequent in patients with rheumatoid arthritis (77% vs 40% in other patients; p=0.029), those taking methotrexate (73% vs 38% in patients with other treatments; p=0.033) and/or anti-tumour necrosis factor alpha (anti-TNF) agents (83% vs 40% in patients taking other medication; p=0.010). More generally, constitutional symptoms were more frequent among patients taking biological disease modifying anti-rheumatic drugs (70%) than other drugs (24%; p=0.001). Patients with connective tissue diseases reported local pain with a higher frequency (67%) than patients with other immune-mediated diseases (28%; p=0.012) and had a 40% prevalence of constitutional symptoms. Furthermore, no patient with systemic lupus erythematosus (n=12) or taking hydroxychloroquine (n=18) had post-vaccination fever. By contrast, fever prevalence was 30% in patients without SLE (p=0.050) and 33% in patients not taking hydroxychloroquine (p=0.005). A history of allergy was associated with both constitutional symptoms (68% vs 36% prevalence in patients with vs without allergy, respectively; p=0.029) and injection-site pain (59% vs 24% prevalence in patients with vs without allergy, respectively; p=0.012). Drug allergy history was specifically more frequent among patients with post-vaccinal fever (62% vs 21% in patients with no fever; p=0.013).
In summary, consistent with the work of Geisen et al 1 and others,12 13 we provide novel real-life evidence supporting the safe and possibly effective use of the BNT162b2 vaccine in high-risk patients with primary immunodeficiencies, rheumatic disorders, allergy and multiple comorbidities, at least in the short-term, independent of disease remission and immunosuppression at time of vaccination. Furthermore, our results suggest that post-vaccinal symptoms might develop with distinct patterns according to the underlying pathogenic background and/or to the superimposed effect of treatments.
This study was part of the Panimmuno research protocol (conforming to the Declaration of Helsinki and approved by the IRCCS Ospedale San Raffaele ethics committee with reference code 22/INT/2018).
We are grateful to the B.I.R.D. Foundation Europe, Costozza di Longare (VI), Italy for its support to the School of Allergy and Immunology of the Università Vita-Salute San Raffaele, Milan, Italy.
GAR, ED-T and LM contributed equally.
Collaborators The OSR-COVAX study group: Elena M Baldissera; Enrica P Bozzolo; Nicola Boffini; Giulia Di Colo; Corrado Campochiaro; Adriana Cariddi; Giacomo De Luca; Matteo Bellone; Silvia Sartorelli; Angelo A Manfredi; Giulio Cavalli; Alessandro Tomelleri; Chiara Asperti; Gaia Mancuso; Nicola Farina; Ambra Mascheri; Nicoletta Saporiti.
Contributors GAR, ED-T, LM, M-RY, LD designed the study. GAR, ED-T, LM collected clinical data. GAR analysed the data. All authors contributed to the critical analysis of the results and to revise the manuscript draft. All authors approved the final version of the article and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work will appropriately be investigated and resolved.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; internally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.