Outcomes in Persistent COVID-19 Pneumonia in Patients Receiving Anti-CD20 Therapy: A Potential Role for IVIG Therapy

Abstract Rationale: Coronavirus disease 2019 (Covid-19) has caused unprecedented challenges in treating immunocompromised patients, particularly those receiving anti-CD20-based B cell depleting therapies (e.g., rituximab, ocrelizumab) for conditions like B cell hematologic malignancies, rheumatoid arthritis, or multiple sclerosis. Patients receiving anti-CD20 therapy are often unable to mount an effective immune response to Covid-19, putting them at risk of severe disease outcomes. We encountered patients with persistent Covid-19 pneumonia and sought to better characterize this population and associations between IVIG use and outcomes. Methods: We identified patients receiving anti-CD20 therapy diagnosed with persistent Covid-19 pneumonia by providers at National Jewish Health or the University of Colorado. Our case definition for persistent Covid-19 pneumonia required persistent Covid positivity on nasopharyngeal or bronchoalveolar lavage (BAL) testing ≥28 days after initial diagnosis and radiographic evidence of pneumonia in a patient who had received anti-CD20 therapy within the past year. A retrospective review was performed to obtain demographic and clinical data, and to assess outcomes. Results: Thirty patients with persistent Covid-19 pneumonia were identified. The median age was 56 years old (IQR 48.5, 74.3) and 72% were female. All patients received rituximab or ocrelizumab. Indications for anti-CD20 therapy included rheumatoid arthritis (n=12, 40%), multiple sclerosis (n=7, 23%), vasculitis (n=5, 17%), and hematologic disorders (n=4, 13%). 23% of patients were receiving additional immunosuppressive therapy prior to the diagnosis of persistent Covid-19 infection. The median duration of persistent Covid-19 infection was 77 days (IQR 46, 129). Ten patients (33%) had cleared their nasopharynx but were diagnosed with persistent Covid-19 infection with PCR testing on BAL specimens. 16 patients required invasive mechanical ventilation or heated high-flow oxygen. 53% of patients received IVIG in addition to standard therapies for severe Covid-19 pneumonia. The use of IVIG was associated with improved outcomes with a reduction in the combined endpoint of mortality or persistent supplemental oxygen requirements at 30 days (13% vs 30%, p = 0.028). Conclusions: We describe a large cohort of patients on anti-CD20 therapy with persistent Covid19 pneumonia. A substantial fraction of this cohort cleared their nasopharynx but had persistent lower respiratory tract infections that required BAL testing to achieve a diagnosis. B cell depletion decreases humoral immune responses to primary antigens and reduces memory B cells leading to a decrease in antibody production to recall antigens. Cross-neutralization activity against Covid-19 is found in currently available IVIG formulations and may account for the observed clinical improvement in this patient population.