Abstract

Background: An impaired humoral and cellular immunogenicity to the mRNA SARS-CoV-2 vaccines has been reported in patients diagnosed with hematologic malignancies. Data regarding the effectiveness of SARS-CoV-2 vaccination on COVID-19 evolution an immunocompromised population are still scarce. Aims: To compare disease severity and mortality in a real-life cohort according to the vaccination status of patients diagnosed with hematologic malignancies developing COVID-19 disease. Methods: We retrospectively collected clinical data from the patients with a current or prior history of hematologic malignancy in the last 5 years at Vall d´Hebron Hospital whom suffered a SARS-CoV-2 infection. Patients were unvaccinated between March 2020 and May 2021, and partially or completely vaccinated between May 2021 and January 2022. The primary endpoint was COVID-related mortality according to vaccination status. Secondary endpoints included rate and length of hospitalization, ICU admission, need for supplemental oxygen including high flow oxygen therapy and mechanical ventilation, and severity of COVID-19 disease. Results: Overall, 113 vaccinated and 81 unvaccinated patients developed COVID-19. Both groups were similar in age (median 69 and 72 years, respectively), gender predominance, diagnosis (mainly lymphoproliferative diseases [58% and 53%]), and administered active treatment (mostly anti-CD20 monoclonal antibodies [38% and 37%]). In contrast, more patients received active treatment (78% vs. 48%; p=<0.001) in the vaccinated cohort. Vaccinated patients developed infection by the delta variant in 27% (17/62) and by the omicron variant in 73% of the sequenced cases (45/62). Genotype analysis of the variant in unvaccinated cases is ongoing. Despite the fact that 96% of patients received 2 vaccine doses and 73% also a third boost dose, in only 67% (59/88) of patients basal IgG anti-spike antibodies were detected after vaccination. In comparison with the unvaccinated cohort of patients, vaccinated patients had less severe (17% vs. 42%; p=0.01) and critical (13% vs 28%; p=0.03) COVID-19 infection, lower rates of hospitalization (42% vs. 90%; p=<0.001) with shorter length of stay (median 13 days (IQR 7-34) vs. 11 days (IQR 6-16), and fewer patients needed supplemental oxygen (34% vs. 73%; p=0). Admission rates to ICU were similar between both cohorts. Finally, mortality rate was lower in the vaccinated patients in comparison with the unvaccinated cohort (HR: 0.19 (95%CI 0.09, 0.38); p=<0.001). Of note, in hospitalized patients only, the mortality of the vaccinated cohort was also lower (HR: 0.38 (95%CI 0.19, 0.76); p=0.007). Among vaccinated patients who suffered a severe/critical infection, 52% did not have vaccine seroconversion. Of the vaccinated patients who died (11/113), 6/8 had negative anti-S IgG, 5/9 were infected by the delta variant and 4/9 by omicron, and 10/11 were on active treatment (5/11 with monoclonal antibodies). Image:Summary/Conclusion: In our series, despite the heterogeneity of infection by different viral variants and treatment availability for COVID-19 during the evolution of the pandemic, vaccination has been widely effective at reducing need of hospitalization, severity and mortality of the SARS-CoV-2 infection in hematological patients. Nevertheless, a subgroup of vaccinated patients remains with an adverse outcome and requires further identification and management improvement.

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