Breakthrough SARS-CoV-2 Infections, Hospitalizations, and Mortality in Vaccinated Patients With Cancer in the US Between December 2020 and November 2021

Abstract

Importance: Limited data have been presented to examine breakthrough SARS-CoV-2 infections, hospitalizations, and mortality in vaccinated patients with cancer in the US.

Objectives: To examine the risk of breakthrough SARS-CoV-2 infection, hospitalizations, and mortality in vaccinated patients with cancer between December 2020 and November 2021.

Design, setting, and participants: Retrospective cohort study of electronic health records (EHRs) of vaccinated patients from a multicenter and nationwide database in the US during the period of December 2020 through November 2021. The study population comprised patients who had documented evidence of vaccination (2 doses of Moderna or Pfizer-BioNTech or single dose of Janssen/Johnson & Johnson vaccines) in their EHRs from December 2020 to November 2021 and had no SARS-CoV-2 infection prior to vaccination.

Exposures: The 12 most common cancers combined and separately; recent vs no recent encounter for cancer; and breakthrough SARS-CoV-2 infection.

Main outcomes and measures: Time trends of incidence proportions of breakthrough SARS-CoV-2 infections from December 2020 to November 2021 in vaccinated patients with all cancer; cumulative risks of breakthrough infections in vaccinated patients for all cancer and 12 common cancer types; hazard ratios (HRs) and 95% CIs of breakthrough infections between propensity score-matched patients with vs without cancer and between propensity score-matched patients with cancer who had a recent medical encounter for cancer vs those who did not; overall risks, HRs, and 95% CIs of hospitalizations and mortality in patients with cancer who had breakthrough infections vs those who did not.

Results: Among 45 253 vaccinated patients with cancer (mean [SD] age, 68.7 [12.4] years), 53.5% were female, 3.8% were Asian individuals, 15.4% were Black individuals, 4.9% were Hispanic individuals, and 74.1% were White individuals. Breakthrough SARS-CoV-2 infections in patients with cancer increased from December 2020 to November 2021 and reached 52.1 new cases per 1000 persons in November 2021. The cumulative risk of breakthrough infections in patients with all cancer was 13.6%, with highest risk for pancreatic (24.7%), liver (22.8%), lung (20.4%), and colorectal (17.5%) cancers, and lowest risk for thyroid (10.3%), endometrial (11.9%), and breast (11.9%) cancers, vs 4.9% in the noncancer population (P < .001). Patients with cancer had significantly increased risk for breakthrough infections vs patients without cancer (HR, 1.24; 95% CI, 1.19-1.29), with greatest risk for liver (HR, 1.78; 95% CI, 1.38-2.29), lung (HR, 1.73; 95% CI, 1.50-1.99), pancreatic (HR, 1.64; 95% CI, 1.24-2.18), and colorectal (HR, 1.53; 95% CI, 1.32-1.77) cancers and lowest risk for thyroid (HR, 1.07; 95% CI, 0.88-1.30) and skin (HR, 1.17; 95% CI, 0.99-1.38) cancers. Patients who had medical encounters for cancer within the past year had higher risk for breakthrough infections than those who did not (HR, 1.24; 95% CI, 1.18-1.31). Among patients with cancer, the overall risk for hospitalizations and mortality was 31.6% and 3.9%, respectively, in patients with breakthrough infections, vs 6.7% and 1.3% in those without breakthrough infections (HR for hospitalization: 13.48; 95% CI, 11.42-15.91; HR for mortality: 6.76; 95% CI, 4.97-9.20).

Conclusions and relevance: This cohort study showed significantly increased risks for breakthrough infection in vaccinated patients with cancer, especially those undergoing active cancer care, with marked heterogeneity among specific cancer types. Breakthrough infections in patients with cancer were associated with significant and substantial risks for hospitalizations and mortality.

Figure 1.. Time Trend of Incidence Proportions (New Cases per 1000 Persons) of Breakthrough SARS-CoV-2 Infections From December 2020 to November 2021 in Vaccinated Patients With All Cancer and Patients Without Cancer

Figure 2.. Hazard Ratios for Breakthrough SARS-CoV-2 Infections in Vaccinated Patients With Cancer (Cancer Cohort) Compared With Propensity Score–Matched Patients Without Cancer (Noncancer Cohort)

Breakthrough SARS-CoV-2 infections were followed in both cohorts starting 14 days after full vaccination up to November 30, 2021. Two cohorts were matched for demographics (age, sex, race and ethnicity), socioeconomic determinants of health, comorbidities, and vaccine types.

Figure 3.. Overall Risks of Hospitalization and Mortality in Patients With Breakthrough Infection vs Patients Without Breakthrough Infections

Kaplan-Meier curves for overall risks for hospitalizations in patients with cancer who had breakthrough infections and in matched patients with cancer who had no breakthrough infection (the numbers at risk at 205, 217, and 232 days were 349, 217, and 91, respectively) (A); overall mortality in patients with cancer who had breakthrough infections and in matched patients with cancer who had no breakthrough infections (the number at risk at 325 days was 2588) (B); overall risks for hospitalizations in patients without cancer who had breakthrough infections and in matched patients with cancer who had no breakthrough infections (C); and overall mortality in patients without cancer who had breakthrough infections and in matched patients without cancer who had no breakthrough infections (D). Shaded areas represent 95% CIs.