Association of COVID-19 Vaccination With SARS-CoV-2 Infection in Patients With Cancer: A US Nationwide Veterans Affairs Study

Abstract

Importance: Patients with cancer are at increased risk for severe COVID-19, but it is unknown whether SARS-CoV-2 vaccination is effective for them.

Objective: To determine the association between SARS-CoV-2 vaccination and SARS-CoV-2 infections among a population of Veterans Affairs (VA) patients with cancer.

Design, setting, and participants: Retrospective, multicenter, nationwide cohort study of SARS-CoV-2 vaccination and infection among patients in the VA health care system from December 15, 2020, to May 4, 2021. All adults with solid tumors or hematologic cancer who received systemic cancer-directed therapy from August 15, 2010, to May 4, 2021, and were alive and without a documented SARS-CoV-2 positive result as of December 15, 2020, were eligible for inclusion. Each day between December 15, 2020, and May 4, 2021, newly vaccinated patients were matched 1:1 with unvaccinated or not yet vaccinated controls based on age, race and ethnicity, VA facility, rurality of home address, cancer type, and treatment type/timing.

Exposures: Receipt of a SARS-CoV-2 vaccine.

Main outcomes and measures: The primary outcome was documented SARS-CoV-2 infection. A proxy for vaccine effectiveness was defined as 1 minus the risk ratio of SARS-CoV-2 infection for vaccinated individuals compared with unvaccinated controls.

Results: A total of 184 485 patients met eligibility criteria, and 113 796 were vaccinated. Of these, 29 152 vaccinated patients (median [IQR] age, 74.1 [70.2-79.3] years; 95% were men; 71% were non-Hispanic White individuals) were matched 1:1 to unvaccinated or not yet vaccinated controls. As of a median 47 days of follow-up, 436 SARS-CoV-2 infections were detected in the matched cohort (161 infections in vaccinated patients vs 275 in unvaccinated patients). There were 17 COVID-19-related deaths in the vaccinated group vs 27 COVID-19-related deaths in the unvaccinated group. Overall vaccine effectiveness in the matched cohort was 58% (95% CI, 39% to 72%) starting 14 days after the second dose. Patients who received chemotherapy within 3 months prior to the first vaccination dose were estimated to have a vaccine effectiveness of 57% (95% CI, -23% to 90%) starting 14 days after the second dose vs 76% (95% CI, 50% to 91%) for those receiving endocrine therapy and 85% (95% CI, 29% to 100%) for those who had not received systemic therapy for at least 6 months prior.

Conclusions and relevance: In this cohort study, COVID-19 vaccination was associated with lower SARS-CoV-2 infection rates in patients with cancer. Some immunosuppressed subgroups may remain at early risk for COVID-19 despite vaccination, and consideration should be given to additional risk reduction strategies, such as serologic testing for vaccine response and a third vaccine dose to optimize outcomes.

Figure 1.. Cumulative Incidence of SARS-CoV-2 Infection After First Vaccine Dose in the Overall Matched Cohort

Cumulative incidence curves of SARS-CoV-2 infection in the overall matched cohort using time zero as the date of the first dose of vaccination. The difference in cumulative incidence is illustrated in the gray bottom graph. Shaded areas indicate 95% CIs calculated by bootstrapping.

Figure 2.. Cumulative Incidence of SARS-CoV-2 Infection After First Vaccine Dose in Patients Receiving Current Treatment With Chemotherapy-Containing Regimens and Endocrine Therapy

Cumulative incidence curves of SARS-CoV-2 infection among patients receiving current treatment with (A) a chemotherapy-containing regimen and (B) an endocrine therapy regimen at the time of vaccination. Time zero is the date of the first dose of vaccination or entry as an unvaccinated control. The difference in cumulative incidence is illustrated in the gray bottom graphs. Shaded areas indicate 95% CIs calculated by bootstrapping. Current treatment is defined as systemic therapy received within the 3 months prior to vaccination (if in the vaccinated group) or prior to entry date (if in the unvaccinated group).