ABSTRACT
ObjectiveVaccination decreases the risk of severe COVID-19 but its impact on post-acute sequelae of COVID-19 (PASC) is unclear among patients with systemic autoimmune rheumatic diseases (SARDs) who may have blunted vaccine immunogenicity and be vulnerable to PASC. MethodsWe prospectively enrolled SARD patients from a large healthcare system who survived acute infection to complete surveys. The symptom-free duration and the odds of PASC (any symptom lasting [≥] 28 or 90 days) were evaluated using restricted mean survival time and multivariable logistic regression, respectively, among those with and without breakthrough infection ([≥] 14 days after initial vaccine series). ResultsAmong 280 patients, the mean age was 53 years, 80% were female, and 82% were white. The most common SARDs were inflammatory arthritis (59%) and connective tissue disease (24%). Those with breakthrough infection had more upper respiratory symptoms, and those with non-breakthrough infection had more anosmia, dysgeusia, and joint pain. Compared to those with non-breakthrough COVID-19 infection (n=164), those with breakthrough infection (n=116) had significantly more symptom-free days over the follow-up period (+28.9 days, 95% CI: 8.83, 48.89; p=0.005) and lower odds of PASC at 28 and 90 days (aOR 0.49, 95% CI: 0.29, 0.83 and aOR 0.10, 95% CI: 0.04, 0.22, respectively). ConclusionVaccinated patients with SARDs were less likely to experience PASC compared to those not fully vaccinated. These findings support the benefits of vaccination for patients with SARDs and suggest that the immune response to acute infection is important in the pathogenesis of PASC in SARD patients. Key MessagesO_ST_ABSWhat is already known on this topic?C_ST_ABSO_LIPost-acute sequelae of COVID-19 (PASC) affects 20-50% of COVID-19 survivors, though the impact of vaccination on the risk and severity of PASC is unclear, especially among those with systemic autoimmune rheumatic diseases (SARDs) who may have impaired responses to vaccines and be particularly vulnerable to PASC. C_LI What this study adds?O_LIIn this prospective cohort of SARD patients recovering from COVID-19, we found that those with breakthrough vs non-breakthrough infection had more symptom-free days over the follow-up period (adjusted difference +28.9 days, 95% CI: 8.38, 48.89; p=0.005) and a lower odds of PASC at 28 days (aOR 0.49, 95% CI: 0.29, 0.83) and at 90 days (aOR 0.10, 95% CI: 0.04, 0.22). C_LIO_LIPatient-reported pain and fatigue scores were lower, reflecting less severe pain and fatigue, in those with breakthrough infection compared to those with non-breakthrough infection. C_LI How this study might affect research, practice, or policy?O_LIThis study extends our understanding of the benefits of vaccination against COVID-19 in patients living with SARDs and reinforces the importance of vaccinating this vulnerable population. C_LIO_LIOur findings suggest that the initial immune response to acute SARS-CoV-2, as influenced by vaccination, affects PASC risk but this requires further study. C_LI
ABSTRACT
ObjectiveRheumatic disease patients on certain immunomodulators are at increased risk of impaired humoral response to SARS-CoV-2 vaccines. We aimed to identify factors associated with breakthrough infection among patients with rheumatic diseases. MethodsWe identified patients with rheumatic diseases being treated with immunomodulators in a large healthcare system who received at least two doses of either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) vaccines or one dose of the Johnson & Johnson-Janssen (J&J) vaccine. We followed patients until SARS-CoV-2 infection, death, or December 15, 2021, when the Omicron variant became dominant in our region. We estimated the association of baseline characteristics with the risk of breakthrough infection using multivariable Cox regression. ResultsWe analyzed 11,468 patients (75% female, mean age 60 years). Compared to antimalarial monotherapy, multiple immunomodulators were associated with higher risk of infection: anti-CD20 monoclonal antibodies (aHR 5.20, 95% CI: 2.85, 9.48), CTLA-4 Ig (aHR 3.52, 95% CI: 1.90, 6.51), mycophenolate (aHR 2.31, 95% CI: 1.25, 4.27), IL-6 inhibitors (aHR 2.15, 95% CI: 1.09, 4.24), JAK inhibitors (aHR 2.02, 95% CI: 1.01, 4.06), and TNF inhibitors (aHR 1.70, 95% CI: 1.09, 2.66). mRNA-1273 recipients had a lower risk of breakthrough infection compared to BNT162b2 recipients (aHR 0.66, 95% CI: 0.50, 0.86). There was no association of sex, body mass index, smoking status, race, or ethnicity with risk of breakthrough infection. ConclusionAmong patients with rheumatic diseases, multiple immunomodulators were associated with increased risk of breakthrough infection. These results highlight the need for additional mitigation strategies in this vulnerable population.
