Efficacy of booster doses in augmenting waning immune responses to COVID-19 vaccine in patients with cancer.

Anti-COVID-19 immunity dynamics were assessed in patients with cancer in a prospective clinical trial. Waning of immunity was detected 4-6 months post-vaccination with significant increases in anti-spike IgG titers after booster dosing, and 56% of seronegative patients seroconverted post-booster vaccination. Prior anti-CD20/BTK inhibitor therapy was associated with reduced vaccine efficacy.

Seroconversion rates following COVID-19 vaccination among patients with cancer.

As COVID-19 adversely affects patients with cancer, prophylactic strategies are critically needed. Using a validated antibody assay against SARS-CoV-2 spike protein, we determined a high seroconversion rate (94%) in 200 patients with cancer in New York City that had received full dosing with one of the FDA-approved COVID-19 vaccines. On comparison with solid tumors (98%), a significantly lower rate of seroconversion was observed in patients with hematologic malignancies (85%), particularly recipients following highly immunosuppressive therapies such as anti-CD20 therapies (70%) and stem cell transplantation (73%). Patients receiving immune checkpoint inhibitor therapy (97%) or hormonal therapies (100%) demonstrated high seroconversion post vaccination. Patients with prior COVID-19 infection demonstrated higher anti-spike IgG titers post vaccination. Relatively lower IgG titers were observed following vaccination with the adenoviral than with mRNA-based vaccines. These data demonstrate generally high immunogenicity of COVID-19 vaccination in oncology patients and identify immunosuppressed cohorts that need novel vaccination or passive immunization strategies.

Correlation of Coagulation Parameters With Clinical Outcomes During the Coronavirus-19 Surge in New York: Observational Cohort.

IMPORTANCE: COVID-19 has caused a worldwide illness and New York became the epicenter of COVID-19 in the United States from Mid-March to May 2020. OBJECTIVE: To investigate the coagulopathic presentation of COVID and its natural course during the early stages of the COVID-19 surge in New York. To investigate whether hematologic and coagulation parameters can be used to assess illness severity and death. DESIGN: Retrospective case study of positive COVID inpatients between March 20, 2020-March 31, 2020. SETTING: Montefiore Health System main hospital, Moses, a large tertiary care center in the Bronx. PARTICIPANTS: Adult inpatients with positive COVID tests hospitalized at MHS. EXPOSURE FOR OBSERVATIONAL STUDIES: Datasets of participants were queried for demographic (age, sex, socioeconomic status, and self-reported race and/or ethnicity), clinical and laboratory data. MAIN OUTCOME AND MEASURES: Relationship and predictive value of measured parameters to mortality and illness severity. RESULTS: Of the 225 in this case review, 75 died during hospitalization while 150 were discharged home. Only the admission PT, absolute neutrophil count (ANC) and first D-Dimer could significantly differentiate those who were discharged alive and those who died. Logistic regression analysis shows increased odds ratio for mortality by first D-Dimer within 48 hrs. of admission. The optimal cut-point for the initial D-Dimer to predict mortality was found to be 2.1 µg/mL. 15% of discharged patients required readmission and more than a third of readmitted patients died (5% of all initially discharged). CONCLUSION: We describe here a comprehensive assessment of hematologic and coagulation parameters in COVID-19 and examine the relationship of these to mortality. We demonstrate that both initial and maximum D-Dimer values are biomarkers that can be used for survival assessments. Furthermore, D-Dimer may be useful to follow up discharged patients.

Low ADAMTS13 Activity Correlates with Increased Mortality in COVID-19 Patients.

The causes of coagulopathy associated with coronavirus disease 2019 (COVID-19) are poorly understood. We aimed to investigate the relationship between von Willebrand factor (VWF) biomarkers, intravascular hemolysis, coagulation, and organ damage in COVID-19 patients and study their association with disease severity and mortality. We conducted a retrospective study of 181 hospitalized COVID-19 patients randomly selected with balanced distribution of survivors and nonsurvivors. Patients who died had significantly lower ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity, significantly elevated lactate dehydrogenase levels, significantly increased shistocyte/RBC fragment counts, and significantly elevated VWF antigen and activity levels compared with patients discharged alive. These biomarkers correlate with markedly elevated D-dimers. Additionally, only 30% of patients who had an ADAMTS13 activity level of less than 43% on admission survived, yet 60% of patients survived who had an ADAMTS13 activity level of greater than 43% on admission. In conclusion, COVID-19 may present with low ADAMTS13 activity in a subset of hospitalized patients. Presence of schistocytes/RBC fragment and elevated D-dimer on admission may warrant a work-up for ADAMTS13 activity and VWF antigen and activity levels. These findings indicate the need for future investigation to study the relationship between endothelial and coagulation activation and the efficacy of treatments aimed at prevention and/or amelioration of microangiopathy in COVID-19.

Anticoagulation in COVID-19: Effect of Enoxaparin, Heparin, and Apixaban on Mortality.

BACKGROUND: Mortality in coronavirus disease of 2019 (COVID-19) is associated with increases in prothrombotic parameters, particularly D-dimer levels. Anticoagulation has been proposed as therapy to decrease mortality, often adjusted for illness severity. OBJECTIVE: We wanted to investigate whether anticoagulation improves survival in COVID-19 and if this improvement in survival is associated with disease severity. METHODS: This is a cohort study simulating an intention-to-treat clinical trial, by analyzing the effect on mortality of anticoagulation therapy chosen in the first 48 hours of hospitalization. We analyzed 3,625 COVID-19+ inpatients, controlling for age, gender, glomerular filtration rate, oxygen saturation, ventilation requirement, intensive care unit admission, and time period, all determined during the first 48 hours. RESULTS: Adjusted logistic regression analyses demonstrated a significant decrease in mortality with prophylactic use of apixaban (odds ratio [OR] 0.46, p = 0.001) and enoxaparin (OR = 0.49, p = 0.001). Therapeutic apixaban was also associated with decreased mortality (OR 0.57, p = 0.006) but was not more beneficial than prophylactic use when analyzed over the entire cohort or within D-dimer stratified categories. Higher D-dimer levels were associated with increased mortality (p < 0.0001). When adjusted for these same comorbidities within D-dimer strata, patients with D-dimer levels < 1 µg/mL did not appear to benefit from anticoagulation while patients with D-dimer levels > 10 µg/mL derived the most benefit. There was no increase in transfusion requirement with any of the anticoagulants used. CONCLUSION: We conclude that COVID-19+ patients with moderate or severe illness benefit from anticoagulation and that apixaban has similar efficacy to enoxaparin in decreasing mortality in this disease.

Evidence for secondary thrombotic microangiopathy in COVID-19.

The causes of coagulopathy associated with COVID-19 disease are poorly understood. We aimed to investigate the relationship between markers of endothelial activation, intravascular hemolysis, coagulation, and organ damage in COVID-19 patients and study their association with disease severity and mortality. We conducted a retrospective study of 181 hospitalized COVID-19 patients randomly selected with equal distribution of survivors and non-survivors. Patients who died had significantly lower ADAMTS13 activity, significantly higher LDH, schistocytes and von Willebrand Factor levels compared to patients discharged alive. Only 30% of patients with an initial ADAMTS13 activity <43% survived vs. 60% with ADAMTS13 ≥43% who survived. In conclusion, COVID-19 may manifest as a TMA-like illness in a subset of hospitalized patients. Presence of schistocytes on admission may warrant a work-up for TMA. These findings indicate the need for future investigation to study the relationship between endothelial and coagulation activation and the efficacy of TMA treatments in COVID-19.