DMARD disruption, disease flare, and prolonged symptom duration after acute COVID-19 among participants with rheumatic disease: A prospective study (preprint)

Objective: To describe disease-modifying antirheumatic drug (DMARD) disruption, rheumatic disease flare/activity, and prolonged COVID-19 symptom duration among COVID-19 survivors with systemic autoimmune rheumatic diseases (SARDs). Methods: We surveyed patients with SARDs after confirmed COVID-19 at Mass General Brigham to investigate post-acute sequelae of COVID-19. We obtained data on demographics, clinical characteristics, COVID-19 symptoms/course, and patient-reported measures. We examined baseline predictors of prolonged COVID-19 symptom duration (defined as lasting [≥]28 days) using logistic regression. Results: We analyzed surveys from 174 COVID-19 survivors (mean age 52 years, 81% female, 80% White, 50% rheumatoid arthritis) between March 2021 and January 2022. Fifty-one percent of 127 respondents on any DMARD reported a disruption to their regimen after COVID-19 onset. For individual DMARDs, 56-77% had any change, except for hydroxychloroquine (23%) and rituximab (46%). SARD flare after COVID-19 was reported by 41%. Global patient-reported disease activity was worse at the time of survey than before COVID-19 (mean 6.6, SD 2.9 vs. 7.6, SD 2.3, p<0.001). Median time to COVID-19 symptom resolution was 14 days (IQR 9,29). Prolonged symptom duration of [≥]28 days occurred in 45%. Hospitalization for COVID-19 (OR 3.54, 95%CI 1.27-9.87) and initial COVID-19 symptom count (OR 1.38 per symptom, 95%CI 1.17-1.63) were associated with prolonged symptom duration. Respondents experiencing prolonged symptom duration had higher RAPID3 scores (p=0.007) and more pain (p<0.001) and fatigue (p=0.03) compared to those without prolonged symptoms. Conclusion: DMARD disruption, SARD flare, and prolonged symptom duration were common in this prospective study of COVID-19 survivors, suggesting substantial impact on SARDs after acute COVID-19.

COVID-19 Outcomes Among Users of CD20 Inhibitors for Immune-Mediated Diseases: A Comparative Cohort Study (preprint)

ObjectivePatients with immune-mediated diseases treated with CD20 inhibitors may have worse COVID-19 outcomes due to impaired humoral immunity, but differences versus the general population are unknown. MethodsWe identified patients with immune-mediated diseases who received CD20 inhibitors within one year prior to the index date of PCR-confirmed COVID-19 between January 31, 2020, and January 31, 2021. Comparators with COVID-19 were matched up to 5:1 by age, sex, and PCR date. Hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization, mechanical ventilation, and death in CD20 inhibitor users versus comparators were estimated using Cox regression. ResultsWe identified 114 cases with COVID-19 who had received CD20 inhibitors for immune-mediated diseases (mean age 55 years, 70% female) and 559 matched comparators with COVID-19 (mean age 54 years, 70% female). CD20 inhibitor-treated cases had higher mortality (aHR 2.16; 95% CI: 1.03 to 4.54) than matched comparators. Risks of hospitalization (aHR 0.88; 95% CI: 0.62 to 1.26) and mechanical ventilation (aHR 0.82; 95% CI: 0.36 to 1.87) were similar. Similar trends were seen in analyses according to type of indication (e.g., rheumatic or neurologic disease) and duration of CD20 inhibitor use (<1 or [≥]1 year), and after excluding patients with interstitial lung disease, cancer, and those on glucocorticoids prior to COVID-19 diagnosis. ConclusionsPatients who received CD20 inhibitors for immune-mediated diseases prior to COVID-19 had higher mortality following COVID-19 than matched comparators, highlighting the urgent need to mitigate excess risks in CD20 inhibitor users during the ongoing pandemic. Key MessagesO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIPatients with immune-mediated diseases treated with CD20 inhibitors may have worse COVID-19 outcomes than those treated with other immunomodulatory medications, but differences compared to the general population are unknown. C_LI What does this study add?O_LICD20 inhibitor-treated cases had over two-fold higher risk of mortality than matched general population comparators, although risks of hospitalization and mechanical ventilation were similar. C_LI How might this impact on clinical practice or future developments?O_LIThere is an urgent need for risk mitigation strategies, such as SARS-CoV-2 monoclonal antibodies or booster vaccinations, for patients with immune-mediated diseases treated with CD20 inhibitors during the ongoing COVID-19 pandemic. C_LI

Clinical characteristics and outcomes of COVID-19 breakthrough infections among vaccinated patients with systemic autoimmune rheumatic diseases (preprint)

ObjectiveTo describe the characteristics of COVID-19 vaccine breakthrough infections among systemic autoimmune rheumatic disease (SARD) patients. MethodsWe identified SARDs patients in a large healthcare system with COVID-19 vaccination [≥]14 days prior to a positive SARS-CoV-2 molecular test. Details of the patients SARD, vaccination status, and COVID-19 infection were extracted. ResultsOf 340 confirmed COVID-19 infections among SARDs patients between December 11th, 2020 (date of first COVID-19 vaccine approval in the US) and July 30th, 2021, we identified 16 breakthrough infections. Seven (44%) received the Pfizer-BioNtech vaccine, five (31%) received the Moderna vaccine, and four (25%) received the Janssen/Johnson & Johnson vaccine. The most common SARDs included rheumatoid arthritis (6, 38%), inflammatory myopathy (3, 19%), and systemic lupus erythematosus (3, 19%). Rituximab (5, 31%), glucocorticoids (4, 25%), and mycophenolate mofetil (4, 25%) were the most frequent treatments. Among the breakthrough infections, 15 (93%) were symptomatic, six (38%) were hospitalized, one (6%) required mechanical ventilation, and two (13%) died. ConclusionsSymptomatic, including severe, breakthrough infections were observed in SARDs patients; many were on treatments associated with attenuated antibody responses to vaccination. Further studies are needed to determine the rate of breakthrough infection associated with SARD treatments and other features. Key messagesO_ST_ABSWhat is already known about this subject?C_ST_ABSBreakthrough infections following COVID-19 vaccination are expected but some patients with systemic autoimmune rheumatic diseases (SARDs) may be at higher risk because of blunted antibody responses to vaccination associated with rheumatic disease treatments and other factors that remain poorly understood. What does this study add?We identify and describe 16 COVID-19 vaccine breakthrough infections within the Mass General Brigham system between December 11th, 2020 and June 26th, 2021. The vast majority of cases were symptomatic and two were fatal. How might this impact on clinical practice or future developments?This study complements observations regarding the attenuated antibody response to COVID-19 vaccination in patients with SARDs by identifying serious clinical outcomes from breakthrough infections in patients receiving DMARDs that have been reported to have blunted vaccine responses. Our study identifies characteristics of COVID-19 breakthrough infections that may guide the prioritization of booster vaccines and other risk-mitigating strategies in patients with SARDs.