COVID-19 Hemostasis Changes and Clinical Outcomes in Vaccinated Vs Unvaccinated Cancer Patients

Introduction

Infection with COVID-19 is known to induce a hypercoagulable state. Among patients with severe COVID-19 who require hospitalization, this prothrombotic environment is associated with increased risks of thromboembolic events, elevated coagulopathy markers, and poorer overall outcomes. However, the impact of severe COVID-19 on patients with malignancies-a group already at higher risk for thrombotic events-has been less thoroughly investigated. Additionally, the effects of COVID-19 vaccination on outcomes in this high-risk population remain unclear.

Methods

In this retrospective study, we analyzed 369 patients with malignancies who were admitted to MD Anderson Cancer Center (MDACC) for moderate to severe COVID-19 infection between March 19th, 2020 to December 2, 2021. This was the first admission for acute COVID-19 in all patients. All admissions occurred prior to the first confirmed omicron variant of COVID-19 in the USA. Patients were subdivided based on their COVID-19 vaccination status. The objective was to compare clinical outcomes and coagulopathy markers between cancer patients with acute COVID-19 who had received the vaccination and those who had not. Confirmation of COVID-19 infections was done by PCR within seven days of admission. The primary clinical outcome measured in this study was adverse events, defined as the occurrence of thrombotic events, admission to an Intensive Care Unit (ICU), intubation/mechanical ventilation, or death. Secondary objective included comparing markers of coagulopathy and inflammation between patient subgroups by vaccination status.

Patient demographics including gender, race, cancer type, and medical comorbidities were obtained. The Chi-square test, Fisher's exact test, and Wilcoxon rank-sum test were used to compare the groups where appropriate. Univariate and multivariate Cox proportional hazards (PH) regression analyses were used to investigate the association between clinical factors and overall survival. The median time to death was estimated using the Kaplan-Meier curve and compared between groups using the log-rank test. All statistical analyses were performed using SAS version 9.4. All statistical tests used a significance level of 5%.

Results

The vaccinated cohort consisted of 37 patients (10%) and the unvaccinated cohort included 332 patients (90%). Covariates obtained between groups including type of malignancy, use of immune checkpoint inhibitors, chemotherapy use within 30 days of admission, and cancer status (refractory versus stable/remission) were not significantly different between the two cohorts. In our study, vaccine status was significantly associated with overall survival. Based on the results of our multivariate model, which included covariates such as vaccine status, race, BMI, cancer type, and hypertension, patients who received at least one dose the vaccine were at greater risk of death compared to those who did not (HR: 3.70, p < 0.0001). Additionally, race was also significantly associated with overall survival with Black/African Americans (AA) being at lowest risk of death compared to other patients (HR: 0.39, p = 0.0004). Of the medical comorbidities, hypertension was associated with the greater risk of death compared to those without (HR: 1.64, p = 0.0085). Patients who received vaccination and had hypertension were at a significantly higher risk of death compared to those who were not vaccinated and did not have hypertension (HR: 5.92, p < 0.0001).

Conclusion

Our study found that patients who received the vaccination were associated with worse outcomes and overall survival. A possible explanation for this finding is that cancer patients who required hospitalization for acute COVID-19 despite receiving primary prevention had more serious disease. This could be represented in another covariate that our initial methods did not capture. Additionally, our finding that hypertension is associated with worse survival in acute COVID has been seen in a recent study by the AHA. Our finding that AA patients had better outcomes is contrary to what has previously been published and data from the CDC. An explanation is that our patients may not be representative of the general population given their cancer status. Further investigation with long-term studies is necessary to better characterize outcomes and thrombotic risk in this high-risk patient population.

Rojas Hernandez:Dr. Rojas-Hernandez has received research support from ANTHOS therapeutics.: Research Funding.