PB2270: CLEARANCE OF PERSISTENT SARS-COV2 INFECTION WITH ANTIBODY CONTAINING PLASMA IN LEUKEMIA AND LYMPHOMA PATIENTS

Abstract

Background: Patients with hematological malignancies or other reasons for inadequate immune response are at high risk for poor outcome of COVID-19 disease. In addition, a significant fraction of patients unable to mount an antibody response fail to clear SARS-Cov2 virus putting them at risk for clinical deterioration. Also, persistent COVID-19 infection impedes further treatment of the underlying disease. So far, no treatment has been established for persistent COVID-19 infection in immunocompromised patients. Aims: Here, we treated eight immunocompromised patients with active SARS-COV2 infection with plasma from convalescent or/and vaccinated donors in a case series of individual treatments. Methods: Patients were eligible for treatment if active SARS-Cov2 infection was confirmed at least 14 days after initial detection. In two out of eight patients sequencing results confirmed the omicron variant. Therapies before plasma treatment included antivirals and monoclonal antibodies. Underlying diseases were B-ALL (n=3; including one patient after allogeneic stem cell transplantation), multiple myeloma (n=2), lymphoma (n=2) and immunosuppression after kidney transplantation (n=1). Median age was 48 years (range 7 – 78). Antibody containing plasma was obtained from healthy donors either after confirmed SARS-COV2 infection or after mRNA vaccination. Overall, 22 treatment cycles were administered in 8 patients (median 2, range 1 to 7). For each patient the available plasma with the highest titers of neutralizing antibodies and matching blood type was administered. Results: Neutralizing antibody titers in plasma were median 1:320 (range 1:40 to 1:2560). Titers of neutralizing antibodies in convalescent plasma (n=10 treatments; median titer: 1:80) were lower than in vaccinated donor plasma (median 1:320; p=0.058, Mann-Whitney U test) (n=12 treatments). Median Ct-values of viral load before treatment were 20.5 (range 14.9 to 37.3). After treatment (median 5 days), the Ct-values changed to median 26.9 (range 19.5 to non-detectable). The median fold decrease in viral load was estimated to be 127-fold with a range from 0.8 to >2x104 (p<10-4, paired t-test). Similar reductions in viral load were achieved after administration of either plasma from convalescent (median 109) or vaccinated donors. SARS-COV2 virus was cleared in 7 of 8 (87.5%) patients with ongoing treatment in one patient. No specific adverse events were observed. Figure 1: Fold reduction in viral load after a single treatment with anti-SARS-COV2 containing plasma. Image:Summary/Conclusion: Plasma with high titers of neutralizing SARS-COV2 antibodies can clear persistent infection in patients with hematological malignancies and immunocompromised patients. Plasma obtained either from convalescent patients or vaccinated donors might constitute an effective and inexpensive treatment in this situation.