Factors Associated with COVID-19 Breakthrough Infection in the Pre-Omicron Era Among Vaccinated Patients with Rheumatic Diseases: A Cohort Study
MD Naomi J Patel, MS Xiaosong Wang, MS Xiaoqing Fu, MD Yumeko Kawano, MPH Claire Cook, BA Kathleen M M Vanni, BA&Sc Grace Qian, BA Emily Banasiak, BS Emily Kowalski, ScD Yuqing Zhang, MD, MMSc Jeffrey A Sparks, MD, MSc Zachary S Wallace
doi:10.1101/2022.07.13.22277606
Objective: Rheumatic 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.
Methods: We 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.
Results: We 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.
Conclusion: Among 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. .
week before the Moderna vaccine so Pfizer-BioNTech recipients may have experienced vaccine waning sooner, contributing to the observed higher risk. However, similar observations were made in a study by Hernan et al which rigorously accounted for these differences. 35 Additional studies in the SARD population are needed to determine the potential benefits associated with one vaccine type over another to guide future vaccine strategies in this vulnerable population. The most important way to prevent breakthrough infection is to get vaccinated with an effective vaccine. There were too few subjects who received Johnson & Johnson-Janssen to generate robust results and this vaccine is no longer recommended in the US. Our study has multiple strengths. First, we systematically identified patients with SARDs prescribed immunomodulatory medications prior to vaccination using a rigorous algorithm (90% PPV) applied in a large healthcare system's data warehouse. Second, we identified testconfirmed COVID-19 breakthrough infection using data from both PCR tests as well as antigen tests administered both in the healthcare setting and at home. Third, details regarding comorbidities and medications prescribed were available. Fourth, in contrast to previous studies, over 90% of patients in our cohort received an mRNA-based vaccine, with a similar proportion receiving Pfizer-BioNTech and Moderna. Despite these strengths, our study has certain limitations. First, our outcome of COVID-19..
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