B‐Cell Depletion Relative to Tumor Necrosis Factor Inhibition Extends the Duration of Viral Shedding in COVID‐19 among Autoimmune Disease Patients: A Matched Prospective Cohort Study

OBJECTIVE:To investigate SARS-CoV-2 viral shedding duration in autoimmune patients using B cell depleting (BCD) therapy or tumor necrosis factor inhibitors (TNFi) and immunocompetent comparators. METHODS:We conducted a matched cohort analysis among participants in POSITIVES, a prospective study enrolling outpatients with acute COVID-19 within five days of diagnosis. Anterior nasal swabs were self-collected thrice weekly over two weeks and then weekly until two negative polymerase chain reaction (PCR) results. We compared autoimmune cases on BCD or TNFi at baseline with immunocompetent comparators, matched using a propensity score based on age, sex, race and ethnicity, number of COVID-19 vaccinations, calendar time, and antiviral use. Survival methods with Cox proportional hazards modeling was used to compare the time to undetectable PCR. RESULTS:We enrolled 16 BCD users and 30 TNFi users, each matched to 33 and 53 immunocompetent comparators, respectively. The most common autoimmune disease was rheumatoid arthritis (31% among BCD and 53% among TNFi). About 60% used an antiviral, and the mean number of COVID-19 vaccinations was 4.3. At the time of infection, BCD users had significantly longer viral shedding duration than comparators (median 15 vs 7 days; hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.22-0.86; P = 0.017). The median time to undetectable viral load was similar between TNFi users and comparators (10 vs 8 days; HR 0.77, 95% CI 0.48-1.23; P = 0.27). CONCLUSION:BCD users had eight days longer viral shedding duration than immunocompetent comparators; TNFi users and comparators had similar viral shedding duration. These findings inform clinical and public health strategies for autoimmune patients with COVID-19.