Cold Agglutinin Disease and COVID-19: A Scoping Review of Treatments and Outcomes

Jackson S. Musuuza, Silpa Kumar, Dheeraj Kumar Posa, Aakash Hans, Sankett Nayyar, Leslie Christensen, Gilbert-Roy Kamoga


Background: Reports suggest that patients with both acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and cold agglutinin disease (CAD) may experience poorer survival when treated with rituximab. We conducted a scoping review to evaluate severe outcomes, including intensive care unit (ICU) admission and mortality, in coronavirus disease 2019 (COVID-19) patients with CAD on various treatments, including rituximab.

Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). Four literature databases were searched on December 19, 2023, for studies reporting lab-confirmed SARS-CoV-2 and CAD, excluding rheumatological conditions.

Results: Of the 741 screened articles, 19 were included. Studies, predominantly case reports (17/19) or case series (2/19), were mainly from the USA (8/19) and India (3/19), with others across Europe and Asia. Among 23 patients (61% female, median age 61 years), 21/23 had a new CAD diagnosis; only two had pre-existing CAD. Overall, 74% recovered, 21% died, and outcomes for one were unreported. Nine (39%) were ICU-admitted. Of rituximab-treated patients (n = 4), 25% were ICU-admitted, none died. Non-rituximab treatments (n = 19) saw 42% ICU admissions and 26% mortality.

Conclusions: This review found no increased risk of severe outcomes in CAD and COVID-19 patients treated with rituximab.

J Clin Med Res. 2024;16(1):8-14


Cold agglutinin disease; COVID-19; Rituximab; Severe outcomes; SARS-CoV-2; Autoimmune cytopenia; Poor survival

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