Study on the clinical outcomes of COVID-19 infection and immune responses following the third booster dose of inactivated COVID-19 vaccine in hematologic disease patients

Background Patients with hematologic diseases may have impaired immunity owing to their underlying diseases and immunosuppressive treatments. Evidence on documented SARS-CoV-2 RT-PCR outcomes and responses to inactivated COVID-19 vaccines remains limited. Methods This retrospective study analyzed three independently identified populations: 20,813 individuals tested by SARS-CoV-2 RT-PCR, 2,438 tested for anti-SARS-CoV-2 IgG, and 1,946 adults tested after two or three vaccine doses. Intervals to documented RT-PCR negativity were analyzed only among positive individuals with subsequent negative results. Vaccination analyses were adjusted for age, sex, testing interval, and disease group. Monthly comparisons were cross-sectional. Serial antibody measurements were analyzed separately. Results Recorded RT-PCR positivity was lower among tested individuals with hematologic diseases (4.77% vs. 10.74%; p < 0.001). Among 64/64 positive individuals with and 381/2,091 without hematologic diseases who had documented subsequent negative results, median intervals to negativity were 5.05 versus 3.99 days (difference, 1.06 days; 95% CI, 0.73–2.21; p < 0.001). Within the hematologic disease group, longer intervals were observed after prior immunosuppressive treatment (5.99 vs. 3.97 days); haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients had the longest descriptive median interval (6.97 days). In the separate IgG-testing population, positivity did not differ significantly (86.00% vs. 90.16%; p = 0.174). Three versus two doses were associated with higher neutralizing antibody (NAb) positivity (94.1% vs. 77.3%; adjusted prevalence ratio [aPR], 1.281; 95% CI, 1.232–1.332) and IgG positivity (97.2% vs. 83.4%; aPR, 1.229; 95% CI, 1.189–1.271). Among 20 paired participants, 19 had higher NAb levels after the third dose. Among three-dose recipients, NAb positivity was 25/32 (78.13%) with hematologic diseases, 36/42 (85.71%) with solid tumors, and 743/780 (95.26%) without documented hematologic disease or solid tumors (overall p < 0.001). Conclusion Among RT-PCR-positive individuals with documented subsequent negativity, intervals were modestly longer with hematologic diseases. Within this group, median intervals were longer after immunosuppressive treatment, and longest among haploidentical allo-HSCT recipients. Differential availability of negative results warrants caution. Three inactivated vaccine doses were associated with higher NAb and IgG positivity overall. Among three-dose recipients, NAb positivity was lower with hematologic diseases than without documented hematologic disease or solid tumors.