SARS-CoV-2 infection after vaccination in patients with inflammatory rheumatic and musculoskeletal diseases

Lawson‐Tovey, Saskia; Hyrich, Kimme L; Gossec, Laure; Strangfeld, Anja; Carmona, Loreto; Raffeiner, Bernd; Yardimci, G. K.; Tréfond, Ludovic; Roux, Nicolas; Rodrigues, Ana Maria; Papagoras, Charalampos; Mateus, Elsa F; Mariette, Xavier; Machado, Pedro

doi:10.1136/annrheumdis-2021-221217

Cited by 32 publications

(27 citation statements)

References 10 publications

(5 reference statements)

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“…Breakthrough infections were higher (7.4%) in our study as Kerala (a state in Southern India) was facing the second wave due to delta variant during this period when the study was conducted 13. There are two studies, one each from Europe and the United States, which reported lower breakthrough infections (<1%, 4.7%, respectively) in patients with AIRD postvaccination 8 9. They had a similar patient profile with the most common disease subtype being RA.…”

Section: Discussionmentioning

confidence: 99%

“…Data from two large European registries showed a breakthrough rate of less than 1% from all patients with AIRD and a single centre American study found this to be 4.7%. However, breakthrough infection was associated with a much higher risk of death (8%–13%) and post-COVID-19 sequelae (8%) 8 9. Thus, it is of utmost importance to identify and mitigate risk factors for breakthrough infections.…”

Section: Introductionmentioning

confidence: 99%

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Postvaccination antibody titres predict protection against COVID-19 in patients with autoimmune diseases: survival analysis in a prospective cohort

et al. 2022

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IntroductionTo assess the incidence and risk factors for breakthrough COVID-19 infection in a vaccinated cohort of patients with autoimmune rheumatic diseases (AIRDs) and determine whether antibodies to receptor binding domain of spike protein (anti-RBD) serve as a reliable predictor of susceptibility to such infections.MethodsPatients with AIRDs who had completed two doses of SARS-CoV2 vaccines were included and anti-RBD antibodies were determined 4–6 weeks post the second vaccine dose and stratified into good responders (GR) (>212 IU), inadequate responders (IR) (0.8–212 IU) and non-responders (NR) (<0.8 IU). Patients who had completed a minimum of 8 weeks interval after the second dose of vaccine were followed up every 2 months to identify breakthrough infections. All sero converted patients who had contact with COVID-19 were also analysed for neutralising antibodies.ResultsWe studied 630 patients of AIRDs (mean age 55.2 (±11.6) years, male to female ratio of 1:5.2). The majority of patients had received AZD1222 (495, 78.6%) while the remaining received the BBV152 vaccine. The mean antibody titre was 854.1 (±951.9), and 380 (60.3%) were GR, 143 (22.7%) IR and 107 (16.9%) NR.Breakthrough infections occurred in 47 patients (7.4%) at a mean follow-up of 147.3 (±53.7) days and were proportionately highest in the NR group (19; 17.75%), followed by the IR group (13; 9.09%) and least in the GR group (15; 3.95%). On log-rank analysis, antibody response (p<0.00001), vaccine(p=0.003) and mycophenolate mofetil (p=0.007) were significant predictors of breakthrough infections. On multivariate Cox regression, only NR were significantly associated with breakthrough infections (HR: 3.6, 95% CI 1.58 to 8.0, p=0.002). In sero converted patients with contact with COVID-19, neutralisation levels were different between those who developed and did not develop an infection.ConclusionBreakthrough infections occurred in 7.4% of patients and were associated with seronegativity following vaccination. This provides a basis for exploring postvaccination antibody titres as a biomarker in patients with AIRD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Postvaccination antibody titres predict protection against COVID-19 in patients with autoimmune diseases: survival analysis in a prospective cohort

et al. 2022

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“…Strategies to rescue the immunogenicity in these patients by repeating a full vaccine course [32] or giving a third dose [33] might be explored in larger studies. Peripheral lymphocytes subpopulations (especially CD19 + counts > 27 cells/μL) are predictive of vaccine response and there is a short period observed from vaccine to infection [34,35], that may indicate the importance of detecting primary non-responders. These findings preliminary suggest that patients treated with anti-CD20 may deserve attention on B-cell reconstitution and/or antibody testing and strict adherence to personal protective measures.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of antibody response to BNT162b2 mRNA COVID-19 vaccine in patients affected by immune-mediated inflammatory diseases up to 5 months after vaccination

et al. 2021

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SARS-CoV-2 vaccination with mRNA product BNT162b2 elicited high immunogenicity in healthy subjects in trials. This study aims to better understand the factors that influence the humoral immune response to vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs). We enrolled patients and healthy healthcare workers control group (HCW) that underwent mRNA BNT162b2 vaccination and measured the serum IgG anti-S-RBD response at booster dose (T1), one month after booster dose (T2) and up to 5 months (T3). Demographic, disease-specific and vaccination data were recorded. Vaccination response of 551 participants naïve to SARS-CoV-2 infection were included in HCW and 102 in the IMID group, analyzing separately those on anti-CD20. At T2 all naïve HCW developed anti-S-RBD-IgG, while 94% of IMID responded (p < 0.001). IMID patients had a significantly different level of IgG than HCW at both T1 (p = 0.031), T2 (p < 0.001), while there was no significant difference at T3. There were no statistically significant differences according to the IMID type or to ongoing treatment with immunosuppressants, corticosteroids or biological drugs other than anti-CD20. The proportion and magnitude of response was significantly lower in IMID treated with anti-CD20 drugs. There was a correlation with age at T1 and at T2 but not at T3, stronger in patients than in HCW. Immune response close after BNT162b2 vaccination is reduced in patients with IMID, but there is no significant difference at 5 months. The measured reduction is related to age and the disease itself rather than treatments, with the exception of anti-CD20 drugs.

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“…While patients with IMIDs on BCDTs have been recognized to be vulnerable to severe COVID-19 infections, 3,4,6,7 relatively scant data exist regarding their risks for and outcomes of breakthrough infections 2,18 . The current cohort of breakthrough patients consisted of nearly equal numbers of patients with rheumatic and neuro-inflammatory disease and most (91.9%) were either fully vaccinated or boosted, with only 6 (8.1%) with incomplete vaccination.…”

Section: Discussionmentioning

confidence: 99%

Breakthrough SARS-CoV-2 infections in immune mediated disease patients undergoing B cell depleting therapy

Calabrese

Kirchner

Husni

et al. 2022

Preprint

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Objectives: Immunocompromised patients with immune mediated inflammatory diseases (IMIDs), undergoing therapy with B cell depleting agents are among the most vulnerable to experience severe COVID-19 disease as well as respond sub-optimally to SARS CoV-2 vaccines yet little is known about the frequency or severity of breakthrough infection in this population. We have analyzed a large cohort of vaccinated IMIDs patients undergoing B cell depleting therapy for the presence of breakthrough infection and assessed their outcomes. Methods: Utilizing specific ICD codes the pharmacy records and COVID-19 registry at the Cleveland clinic were used to identify all patients with IMIDS treated with B cell depleting monoclonal antibodies who were vaccinated against SARs CoV-2 and experienced breakthrough infections. Each EMR record was hand-reviewed to extract clinical data including vaccine history, demographics, comorbidities, other therapies, details of B cell depleting therapy, and outcomes. Univariate and multivariable logistic/proportional-odds regression models were used to examine the risk factors for severe outcomes. Results: Of 1696 IMIDS patients on B cell depleting therapies 74 developed breakthrough COVID-19. Outcomes were severe with 24 (35%) hospitalized, 11 (15%) patients requiring critical care and 6 (8 %) deaths. Monoclonal antibodies were used on an outpatient basis to treat 21 with only a single patient requiring hospitalization without oxygen support and no deaths. Conclusions: In IMIDS patients on B cell depleting therapies breakthrough infections are frequent and associated with severe outcomes. Outpatient use of monoclonal antibody therapy was associated with enhanced clinical outcomes.

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SARS-CoV-2 infection after vaccination in patients with inflammatory rheumatic and musculoskeletal diseases

Cited by 32 publications

References 10 publications

Postvaccination antibody titres predict protection against COVID-19 in patients with autoimmune diseases: survival analysis in a prospective cohort

Postvaccination antibody titres predict protection against COVID-19 in patients with autoimmune diseases: survival analysis in a prospective cohort

Evaluation of antibody response to BNT162b2 mRNA COVID-19 vaccine in patients affected by immune-mediated inflammatory diseases up to 5 months after vaccination

Breakthrough SARS-CoV-2 infections in immune mediated disease patients undergoing B cell depleting therapy

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