Antibody response and intra‐host viral evolution after plasma therapy in COVID‐19 patients pre‐exposed or not to B‐cell‐depleting agents

Administration of plasma therapy may contribute to viral control and survival of COVID‐19 patients receiving B‐cell‐depleting agents that impair humoral immunity. However, little is known on the impact of anti‐CD20 pre‐exposition on the kinetics of SARS‐CoV‐2‐specific antibodies. Here, we evaluated the relationship between anti‐spike immunoglobulin G (IgG) kinetics and the clinical status or intra‐host viral evolution after plasma therapy in 36 eligible hospitalized COVID‐19 patients, pre‐exposed or not to B‐cell‐depleting treatments. The majority of anti‐CD20 pre‐exposed patients (14/17) showed progressive declines of anti‐spike IgG titres following plasma therapy, contrasting with the 4/19 patients who had not received B‐cell‐depleting agents (p = 0.0006). Patients with antibody decay also depicted prolonged clinical symptoms according to the World Health Organization (WHO) severity classification (p = 0.0267) and SARS‐CoV‐2 viral loads (p = 0.0032) before complete virus clearance. Moreover, they had higher mutation rates than patients able to mount an endogenous humoral response (p = 0.015), including three patients with one to four spike mutations, potentially associated with immune escape. No relevant differences were observed between patients treated with plasma from convalescent and/or mRNA‐vaccinated donors. Our study emphasizes the need for an individualized clinical care and follow‐up in the management of COVID‐19 patients with B‐cell lymphopenia.