Clinical and Immunological Characteristics of Prolonged SARS-CoV-2 Omicron Infection in Hematologic Disease

Prolonged viral shedding (PVS) occurs when severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is not adequately cleared and has been associated with poor outcomes. However, it remains unclear whether the immunological and clinical characteristics of Omicron PVS in hematologic disease (HD) are identical to those of earlier variants. We retrospectively analyzed 160 patients with HD with Omicron breakthrough infections. Although the hospitalization rate was high (21.3 %), deaths attributable to COVID-19 occurred in only 2.5% of the cases. PVS developed in 36.9% of the evaluable patients. Factors such as B- and CD4+ T-cell depletion, recent use of anti-CD20 antibodies and bendamustine were found to be significant predictors of PVS. Analysis of T cell phenotypes showed an increase in exhausted CD4+ T cells in PVS, but not in CD8+ cells. Neutralizing activities against recombinant spike proteins for three Omicron subvariants were significantly reduced. Notably, despite the high frequency of PVS, many patients previously treated with anti-CD20 antibodies and bendamustine ultimately recovered. Late-onset interstitial pneumonia is a fatal complication that can occur regardless of viral clearance. Despite the use of high-dose corticosteroids and potent antivirals, the optimal treatment for PVS remains unclear and should be individualized until a more effective strategy is established.