Patients with cancer at increased risk for breakthrough COVID-19 infection – Healio

June 20, 2022

3 min read

Disclosures: Xu reports no relevant financial disclosures. Berger reports grants from the National Institutes of Health during the conduct of the study. Please see the study for all other authors’ relevant financial disclosures.

Vaccinated patients with cancer had significantly higher risks for breakthrough COVID-19 infection, especially those undergoing active cancer care, compared with individuals without cancer, according to a study published in JAMA Oncology.

Researchers reported marked heterogeneity among cancer types — patients with colorectal pancreatic, lung and liver cancers demonstrated the highest risks. In addition, patients with cancer who developed breakthrough infections had significant and substantial risks for hospitalizations and mortality.

Risk for breakthrough COVID-19 infection.
Data derived from Wang W, et al. JAMA Oncol. 2022;doi:10.1001/jamaoncol.2022.1096.

“Prior studies have shown that patients with cancer had significantly lower antibody response to COVID-19 vaccination. However, it remains unknown if the low antibody response to COVID-19 vaccines translate into significant breakthrough infections, as well as severe outcomes such as hospitalization and death, in real-world populations,” Rong Xu, PhD, professor of biomedical informatics and director of the Center for Artificial Intelligence in Drug Discovery in the School of Medicine, and Nathan A. Berger, MD, Hanna-Payne professor of experimental medicine and director of the Center for Science, Health and Society, both at Case Western Reserve University, told Healio in a joint statement.


The analysis included 45,253 vaccinated patients with cancer (mean age, 68.7 years; standard deviation, 12.4; 53.5% women; 74.1% white), identified through electronic records from a multicenter and nationwide database in the U.S. from December 2020 through November 2021, who had documented evidence of vaccination (two doses of Moderna or Pfizer-BioNTech or a single dose of Janssen/Johnson & Johnson vaccines) and no COVID-19 infection prior to vaccination.

Rong Xu, PhD

Rong Xu

Xu, Berger and colleagues investigated cumulative risks of breakthrough infections in vaccinated patients with any and each of the 12 most common cancer types and calculated HRs of breakthrough infections between propensity score-matched patients with vs. without cancer, as well as between propensity score-matched patients with cancer who had a recent cancer-related medical encounter and those who did not. They also reported overall risks and HRs for hospitalizations and mortality in patients with cancer who had breakthrough infections vs. those who did not.

Key findings

Results showed breakthrough COVID-19 infections in patients with cancer increased during the period analyzed, reaching 52.1 new cases per 1,000 individuals in November 2021.

Nathan A. Berger, MD

Nathan A. Berger

Researchers reported a cumulative risk for breakthrough infection in patients with all types of cancer of 13.6% vs. 4.9% in the noncancer population, with the highest risk among patients with pancreatic (24.7%), liver (22.8%), lung (20.4%) and colorectal (17.5%) cancers. Patients with thyroid (10.3%), endometrial (11.9%) and breast (11.9%) cancers demonstrated the lowest cumulative risk.

Patients with cancer had significantly higher risk for breakthrough infection than patients without cancer (HR = 1.24; 95%CI, 1.19-1.29). Results showed the greatest risk among patients with liver (HR = 1.78; 95% CI, 1.38-2.29), lung (HR = 1.73; 95% CI, 1.5-1.99), pancreatic (HR = 1.64; 95% CI, 1.24-2.18) and colorectal (HR = 1.53; 95% CI, 1.32-1.77) cancers. Those with the lowest risk included patients with thyroid (HR = 1.07; 95% CI, 0.88-1.3) and skin (HR = 1.17; 95% CI, 0.99-1.38) cancers.

Additionally, patients who had cancer-related medical encounters within the past year demonstrated a higher risk for breakthrough infections than those who did not (HR = 1.24; 95% CI, 1.18-1.31).

Researchers also reported that among patients with cancer, those with breakthrough infections had higher risks for hospitalization (31.6% vs. 6.7%; HR = 13.48; 95% CI, 11.42-15.91) and mortality (3.9% vs. 1.3%; HR = 6.76; 95% CI, 4.97-9.2) than those without breakthrough infections.


The results emphasize the need for patients with cancer to maintain mitigation practices, especially with the emerging variants and waning immunity of vaccines, Xu, Berger and colleagues wrote. They called for future research to evaluate breakthrough infections and associated severe outcomes in vaccinated patients with cancer and “to understand the biological mechanisms underlying the marked heterogeneity in breakthrough infections among different cancer types.”

“Future studies are needed to figure out how COVID-19 infection impacts patients with cancer long term, which patients are most vulnerable for long COVID, how to treat long COVID in patients with cancer, and whether long COVID in patients with cancer differs from those without cancer,” Xu and Berger told Healio.

For more information:

Rong Xu, PhD, can be reached at Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106; email:

Nathan A. Berger, MD, can be reached at Center for Science, Health and Society, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106; email: