Three doses of BNT162b2 COVID-19 mRNA vaccine establish long-lasting CD8+ T cell immunity in CLL and MDS patients.

Patients with hematological malignancies are prioritized for COVID-19 vaccine due to their high risk for severe SARS-CoV-2 infection-related disease and mortality. To understand T cell immunity, its long-term persistence, and its correlation with antibody response, we evaluated the BNT162b2 COVID-19 mRNA vaccine-specific immune response in chronic lymphocytic leukemia (CLL) and myeloid dysplastic syndrome (MDS) patients. Longitudinal analysis of CD8+ T cells using DNA-barcoded peptide-MHC multimers covering the full SARS-CoV-2 Spike-protein (415 peptides) showed vaccine-specific T cell activation and persistence of memory T cells up to six months post-vaccination. Surprisingly, a higher frequency of vaccine-induced antigen-specific CD8+ T cells was observed in the patient group compared to a healthy donor group. Furthermore, and importantly, immunization with the second booster dose significantly increased the frequency of antigen-specific CD8+ T cells as well as the total number of T cell specificities. Altogether 59 BNT162b2 mRNA vaccine-derived immunogenic responses were identified, of which 23 established long-term CD8+ T cell memory response with a strong immunodominance for NYNYLYRLF (HLA-A24:02) and YLQPRTFLL (HLA-A02:01) epitopes. In summary, we mapped the vaccine-induced antigen-specific CD8+ T cells and showed a booster-specific activation and enrichment of memory T cells that could be important for long-term disease protection in this patient group.

The COVID-19 infection control response at a large stand-alone comprehensive cancer center in Los Angeles County.

BACKGROUND: The City of Hope National Medical Center (COH) is the only stand-alone comprehensive cancer center in Los Angeles, a county that was deemed a COVID-19 pandemic epicenter at the height of the 2020 winter surge. The immunocompromised patient population frequently experienced delays in infection control guidelines from local and government bodies due to minimal data available in comparison to the general population. This required COH to make swift, informed decisions for the best interest of the patient population. AIM: Here, we review the comprehensive COVID-19 infection control response conducted at COH within the context of a high-risk patient population, predominately comprised of patients with hematologic malignancies. METHODS AND RESULTS: This infection control response focused on prevention of COVID-19 transmission on campus, COVID-19 testing, and isolation management. These efforts consisted of COVID-19 screening, limitation of personnel on campus, source control, contact tracing, COVID-19 vaccination, establishment of in-house testing and implementation and management of COVID-19 testing. Between January 2020 and September 2021, COH implemented a robust in-house testing program, completed well over 1000 contact traces, ensured COVID-19 vaccinations were distributed to all eligible staff and patients, and established an algorithm for COVID-19 infection resolution, all without compromising the number of hematopoietic stem cell transplants (HCTs) performed, surgical volume, or healthcare-associated standardized infection ratios (SIR). CONCLUSION: Institutional collaboration and attention to infection control was pivotal to minimizing the burden of the COVID-19 pandemic.

Reduced Antibodies and Innate Cytokine Changes in SARS-CoV-2 BNT162b2 mRNA Vaccinated Transplant Patients With Hematological Malignancies.

Immunocompromised individuals including patients with hematological malignancies constitute a population at high risk of developing severe disease upon SARS-CoV-2 infection. Protection afforded by vaccination is frequently low and the biology leading to altered vaccine efficacy is not fully understood. A patient cohort who had received bone marrow transplantation or CAR-T cells was studied following a 2-dose BNT162b2 mRNA vaccination and compared to healthy vaccine recipients. Anti-Spike antibody and systemic innate responses were compared in the two vaccine cohorts. The patients had significantly lower SARS-CoV-2 Spike antibodies to the Wuhan strain, with proportional lower cross-recognition of Beta, Delta, and Omicron Spike-RBD proteins. Both cohorts neutralized the wildtype WA1 and Delta but not Omicron. Vaccination elicited an innate cytokine signature featuring IFN-γ, IL-15 and IP-10/CXCL10, but most patients showed a diminished systemic cytokine response. In patients who failed to develop antibodies, the innate systemic response was dominated by IL-8 and MIP-1α with significant attenuation in the IFN-γ, IL-15 and IP-10/CXCL10 signature response. Changes in IFN-γ and IP-10/CXCL10 at priming vaccination and IFN-γ, IL-15, IL-7 and IL-10 upon booster vaccination correlated with the Spike antibody magnitude and were predictive of successful antibody development. Overall, the patients showed heterogeneous adaptive and innate responses with lower humoral and reduced innate cytokine responses to vaccination compared to naïve vaccine recipients. The pattern of responses described offer novel prognostic approaches for potentiating the effectiveness of COVID-19 vaccination in transplant patients with hematological malignancies.

Characterization of coagulopathy and outcomes in cancer patients with severe COVID -19 illness: Longitudinal changes in hospitalized cancer patients.

There is a lack of data focused on the specific coagulopathic derangements in COVID-19 versus non-COVID-19 acutely ill cancer patients. Our objective was to characterize features of coagulopathy in cancer patients with active COVID-19 illness who required hospitalization at MD Anderson in the Texas Medical Center and to correlate those features with thrombotic complications, critical illness, and mortality within the first 30 days after hospital admission for COVID-19 illness. COVID-19 and non-COVID-19 hospitalized cancer patients, with at least five consecutive measures of PT, PTT, d-dimer, and CBC during the same period, were matched 1:1 to perform a retrospective analysis. We reviewed complete blood cell counts with differential, PT, PTT, fibrinogen, D-Dimer, serum ferritin, IL-6, CRP, and peripheral blood smears. Clinical outcomes were thrombosis, mechanical ventilation, critical illness, and death. Compared with matched hospitalized cancer patients without COVID-19, we found elevated neutrophil and lower lymphocyte counts in those with critical illness ( p =  0.00) or death ( p =  0.00); only neutrophils correlated with thrombosis. COVID-19 cancer patients with a platelet count decline during the hospital stay had more frequent critical illness ( p =  0.00) and fatal outcomes ( p =  0.00). Of the inflammatory markers, interleukin-6 showed consistently higher levels in the COVID-19 patients with poor outcomes. The findings of unique platelet changes and coagulopathy during severe COVID-19 illness in the cancer population are of interest to explore disease mechanisms and future risk stratification strategies to help with the management of cancer patients with COVID-19.

Telehealth access among hematology patients during the COVID-19 pandemic in Australia: a cross-sectional survey.

Hematology patients are more vulnerable to the effects of COVID-19 than patients with other cancers. We surveyed hematology patients to better understand their experiences of cancer care during the pandemic. A large reduction was observed in the number of healthcare services accessed by respondents. Telehealth assisted with access but requires improvement.

Proportion of hematological cancer patients with SARS-CoV-2 infection during the COVID-19 pandemic: A systematic review and meta-analysis.

Introduction: The coronavirus disease-2019 (COVID-19) has emerged as a novel infection which has spread rapidly across the globe and currently presents a grave threat to the health of the cancer patient. Objective: The aim of this meta-analysis was to evaluate the proportion of hematological cancer patients with the SARS-CoV-2 infection during the COVID-19 pandemic. Method: A comprehensive literature review was performed on PubMed, Web of Science, Scopus, EKB SciELO, SID, CNKI and Wanfang databases to retrieve all relevant publications up to January 31, 2021. Observational studies, consecutive case-series and case-control studies were included. The proportion for hematological cancer patients with COVID-19 was estimated using the odds ratios (ORs) and 95% confidence interval (95% CIs). Results: Fourteen studies with a total of 3,770 infected cancer patients and 685 hematological cancer cases with COVID-19 were selected. Combined data revealed that the overall proportion of hematological cancer patients with COVID-19 was 16.5% (95% CI 0.130 - 0.208, p ≤ 0.001). The stratified analysis by ethnicity showed that the proportion was 18.8% and 12.4% in Caucasian and Asian hematological cancer patients with COVID-19, respectively. Moreover, subgroup analysis by country of origin showed that its proportion was the highest in the United Kingdom (22.5%), followed by France (17.1%) and China (8.2%). Conclusion: This meta-analysis result indicated that the proportion of hematological cancer patients with SARS-CoV-2 infection during the COVID-19 pandemic was 16.5%. Further larger sample sizes and multicenter studies among different ethnic groups are necessary to get a better assessment of the proportion.

Endothelial Activation and Stress Index (EASIX) as an Early Predictor for Mortality and Overall Survival in Hematological and Non-Hematological Patients with COVID-19: Multicenter Cohort Study.

COVID-19, as a disease involving the endothelium of multiple organs, is characterized by high mortality rates among hospitalized patients. Patients with hematological malignancies are particularly at risk of an unfavorable course of COVID-19. The endothelial activation and stress index (EASIX) score has been used as a simple predictor of overall survival (OS) in specific groups of hematological cancer patients. EASIX, as a biomarker of endothelial dysfunction, might play a prognostic role in patients with COVID-19. Here, we performed a comprehensive retrospective analysis of the EASIX score in 523 hospitalized COVID-19 patients with or without coexisting hematological cancer. Hematological cancer COVID-19 patients had higher EASIX scores compared to the overall population with COVID-19. In hematological patients, EASIX was a strong predictor of the occurrence of sepsis during COVID-19. Our findings demonstrated EASIX as a strong predictor of intensive care unit admission, in-hospital mortality, the occurrence of acute renal failure and the need for hemodialysis, both in hematological and non-hematological COVID-19 patients. Patients with a high EASIX score on COVID-19 diagnosis had significantly inferior OS compared to patients with low EASIX. We showed for the first time that EASIX might serve as a simple, universal prognostic tool of OS in both hematological and non-hematological COVID-19 patients.