IMPAIRED HUMORAL RESPONSE IN LYMPHOMA PATIENTS SURVIVING THE ACUTE PHASE OF COVID‐19

Abstract

Introduction: The ability to generate an adequate and durable immune response to SARS-CoV-2 in B-cell lymphoma patients (pts) treated with immunochemotherapy is still unclear. We monitored antibody levels during convalescence in COVID-19 survivors with lymphoma, compared to other hematologic diseases (HemD) and healthy controls (Ctrls). Methods: Seventeen pts with non-Hodgkin lymphoma (NHL) [follicular (FL): 9; diffuse large B-cell (DLBCL): 8] surviving the acute phase of virologic-proven COVID-19 were evaluated at 3 timepoints (TP) after nasal swab negativity: +1 (TP1), +3 (TP3), and +6 (TP6) months; 28 pts affected by HemD (10 multiple myeloma, 8 chronic lymphoproliferative disorders, 10 myelodysplastic/chronic myeloproliferative syndromes) and 17 Ctrls were also evaluated at the same TP. Antibody (Ab) levels to nucleocapsid (N-Ab) and spike (S-Ab) virus proteins were measured using a highly sensitive luciferase-immunoprecipitation system (LIPS) assay. Positive levels were 125000 LU for N-Ab and 45000 LU for S-Ab. Results: Mean N- and S-Ab levels were lower in FL and DLBCL than in other HemD pts, both at TP1 (N-Ab 1217517 vs 2205610 LU, p = 0.03; S-Ab 580444 vs 1184453 LU, p = 0.049) and at TP3 (N-Ab 850510 vs 2094487 LU p = 0.012, S-Ab 605284 vs 1230946 LU, p = 0.074). At TP6 N-Ab levels declined in all subgroups, while S-Ab levels remained stable. At TP1, compared to HemD, significantly less FL and DLCBL pts reached positive levels of N-Ab (93% vs 59% p = 0.017) and of S-Ab (86% vs 47%; P: 0.008). Positive levels of N-Ab and S-Ab were also more frequent in Ctrls (100% and 87%; p = 0.007 and 0.028) than in NHL pts. Rates of seroprotection remained lower in NHL pts also at TP3 and TP6. Rituximab (RTX) had been given to 14/17 NHL pts, either ≥6 months in 5 (prior RTX) or <6 months in 9 pts (ongoing RTX) before Covid-19 diagnosis. Ongoing RTX had a markedly negative effect on S-Ab levels since none of 9 patients seroconverted at TP1 compared to 5/5 prior RTX pts (P = 0.0005). No changes occurred in the rate of seroprotected pts also at TP3 and TP6 except for 1 ongoing RTX pt who reached protective levels at TP6 (see figure). Overall seroprotective Ab at any TP were present in 2 of 18 determinations in ongoing RTX pts, despite RTX treatment discontinuation, and in 15 of 15 determination in prior RTX pts (p = 0.0001). Keywords: Aggressive B-cell non-Hodgkin lymphoma, Indolent non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.