SARS-CoV-2 Humoral Immunity Persists Following Rituximab Therapy

Abstract

Long-term humoral immunity is mediated by short-lived plasma cells (replenished by memory B cells) and long-lived plasma cells. Their relative contributions are uncertain for immunity to SARS-CoV-2, especially given the widespread use of novel mRNA vaccines. Yet, this has far-reaching implications in terms of the need for regular booster doses in the general population and perhaps even revaccination in patients receiving B cell-depleting therapy. We aimed to characterise anti-SARS-CoV-2 antibody titres in patients receiving Rituximab following previous SARS-CoV-2 vaccination. We recruited 10 fully vaccinated patients (age: 16.9 ± 2.52 years) with childhood-onset nephrotic syndrome, not in relapse, receiving Rituximab for their steroid/calcineurin-inhibitor sparing effect. Antibodies to SARS-CoV-2 spike (S) and nucleocapsid (N) proteins were measured immediately prior to Rituximab and again ~6 months later, using the Roche Elecys® Anti-SARS-CoV-2 (S) assay. All ten patients were positive for anti-S antibodies prior to Rituximab, with six patients (60%) having titres above the upper limit of detection (>12,500 U/mL). Following Rituximab therapy, there was a reduction in anti-S titres (p = 0.043), but all patients remained positive for anti-S antibodies, with five patients (50%) continuing to have titres >12,500 U/mL. Six patients (60%) were positive for anti-N antibodies prior to Rituximab. Following Rituximab therapy, only three of these six patients remained positive for anti-N antibodies (p = 0.036 compared to anti-S seroreversion). Humoral immunity to SARS-CoV-2 is likely to be mediated in part by long-lived plasma cells.

Long-Term Observation of SARS-CoV-2 Vaccination Response upon High Efficacy Treatment in Multiple Sclerosis—A Real-World Scenario

“…In any case, our data outline that immunisation prior to the initiation of anti-CD20 results in the long-term perseverance of a sufficient immune response. This is in line with previous reports on sustained antibody levels under anti-CD20 therapy [ 45 , 46 ]. Those pwMS who were initially immunised prior to the initiation of treatment with s-S1P displayed similar levels of antibodies to those that were immunised under treatment, once more confirming that treatment with s-S1P does not impact antibody development [ 10 ].…”

Back to the Future: Immune Protection or Enhancement of Future Coronaviruses

“…Finally, in a group of patients with childhood-onset nephrotic syndrome who received rituximab for its steroid/calcineurin-inhibitor sparing effect, SARS-CoV-2 antibodies largely persisted. This indicates that long-lived plasma cells play a major role in maintaining antibody levels [ 32 ].…”

“…Finally, in a group of patients with childhood-onset nephrotic syndrome who received rituximab for its steroid/calcineurin-inhibitor sparing effect, SARS-CoV-2 antibodies largely persisted. This indicates that long-lived plasma cells play a major role in maintaining antibody levels [32]. Soresina et al described the cases of two X-linked agammaglobulinemia (XLA) patients who developed pneumonia as a clinical manifestation of SARS-CoV-2 infection but did recover without requiring oxygen ventilation or intensive care treatment [25].…”