Case Report: Successful treatment of recurrent COVID-19 with intravenous immunoglobulin in a patient with rituximab-induced B-cell depletion and restoration of Fc-mediated effector functions.

We report the case of a 47-year-old woman with neuromyelitis optica spectrum disorder who developed prolonged coronavirus disease 2019 (COVID-19) pneumonia 3 months after receiving rituximab. Rituximab-induced B-cell depletion left her highly susceptible to persistent viral infection, resulting in three serial hospital admissions due to recurrent clinical deterioration despite standard antiviral therapy. During her third admission, her clinical status and radiographic findings continued to decline even after remdesivir and dexamethasone were reinitiated. As salvage therapy, she received a 3-day course of intravenous immunoglobulin (IVIG), resulting in rapid improvement and complete resolution of oxygen requirement. To investigate the therapeutic mechanism, we conducted longitudinal serologic analyses. Before IVIG administration, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific IgG was undetectable, and antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activities were minimal. Following IVIG infusion, IgG titers against both wild-type and Omicron variants increased substantially. Notably, Fc-mediated effector functions, including ADCC and ADCP, were restored and peaked 1 week after treatment, aligning with the patient's clinical recovery. These findings support the mechanistic hypothesis that IVIG benefits individuals with B-cell depletion not only through passive antibody transfer but also by contributing to the restoration of critical immune effector functions. This case suggests that IVIG could be considered as a potential therapeutic adjunct for managing persistent COVID-19 in patients following B-cell-depleting therapy.