Cancer Increases Risk of Breakthrough COVID-19

Cancer increased risk of COVID-19 among the vaccinated, with subsequent "significant and substantial" hospitalizations and mortality.


Patients with cancer were found at increased risk of breakthrough COVID-19 and subsequent "significant and substantial" risk for hospitalizations and mortality, in a large cohort study of vaccinated persons with and without cancer.

"Our studies show that even vaccinated cancer patients are at increased risk for significant and substantially severe outcomes from COVID-19 breakthrough infections," Nathan Berger, MD, Center for Science, Health and Society, Case Western Reserve University, Cleveland, OH, told Contagion.

"While there are variations in risk depending on type and timing of cancer, we advise all cancer patients to be fully vaccinated, including boosters, and to exercise vigilance in maintaining COVID-19 mitigation strategies," Berger said.

The investigators accessed medical records in the TriNetX Analytics network, a database comprising approximately 90 million patients of 66 health care organizations across the US. They identified 45,253 patients with a diagnosis of at least 1 of 12 common types of cancer who had not contracted SARS-CoV-2 infection before being vaccinated (with 2 doses of Moderna or Pfizer-BioNTech or single dose of Janssen/Johnson&Johnson vaccine); and a matched cohort of 590,014 vaccinated patients without cancer. The incidence and course of COVID-19 after vaccination was determined for the study period of December 2020 through November 2021.

Berger and colleagues reported that 13.6% of patients across all cancers developed COVID-19 after vaccination compared to 4.9% in the non-cancer population; corresponding to a significantly greater risk with cancer (HR 1.24; 95% CI 1.19-1.29). The highest incidence of, and commensurate risk for breakthrough infection was associated with cancer of the pancreas (24.7%), liver (22.8%), lung (20.4%) and colorectal (17.5%). Lower incidences, albeit with still higher risk than patients without cancer, were associated with cancers of thyroid (10.3%), endometrial (11.9%) and breast 11.9%).

"We hypothesize that the heterogeneity of risk for breakthrough infections in cancer patients not undergoing therapy is associated with cancer itself and related degrees of both humoral- and cell-mediated immunosuppression," Berger commented.

The investigators pointed out that although risk of developing COVID-19 despite vaccination varied by type of cancer, that the hematological cancers which can impair antibody response were associated with lower risk than some solid tumors.

"The differential rate of breakthrough infection with different cancers does not comport with demonstrated deficiency in antibody response to mRNA vaccines, suggesting the additional importance of cell-mediated immunity and other host actors in resisting infection and determining disease susceptibility and severity," Berger explained.

Risk of breakthrough infection was particularly elevated among those receiving medical care for the cancer within the previous year relative to those without medical encounters for their cancer (HR 1.24; 1.18-1.31). This finding was consistent across such variables as cancer types, comorbidities and cancer treatments.

Berger and colleagues suggest that the patients with medical encounters for cancer in the prior year could have had active cancer while others had less active conditions or were cancer free."Nonetheless, these results further indicate that active cancer in itself and/or active cancer treatments may have played important roles," they indicated.

The investigators also found that breakthrough COVID-19 in patients with cancer was associated with higher risk of more severe outcomes, including mortality, than in patients without cancer.Overall hospitalization risk was 31.6% in patients with cancer and breakthrough infection, compared to 25.9% in those without cancer. Overall mortality risk was 6.7% in patients with cancer and breakthrough infections, compared to 2.7% in those with breakthrough infections, but without cancer.

"With the emergence of SARS-CoV-2 virus variants and the waning immunity of vaccines, the findings raise the consideration for the development and implementation of enhanced mitigation strategies in vaccinated patients with specific cancers, especially those undergoing active cancer care," Berger and colleagues wrote.

Berger suggested that additional studies could inform development and refinement of mitigation strategies.

"To better understand the protection or risk of COVID-19 breakthrough infection in vaccinated patients with cancer, more studies are required on both extent and duration of humoral- and cell-mediated immune mechanisms, as well as improved strategies for enhancing cell-mediated immunity," he said. "Studies are also needed to demonstrate efficacy of passive immunization strategies for patients with cancer."

In an on-line comment accompanying the study, Binh Ngo, MD, Keck USC School of Medicine, Los Angeles, CA, related the study findings to the need "to go beyond vaccination in caring for our vulnerable patients;" and called for early antiviral treatment and increased use of immune modifying agents.

"There is a clear need for study of additional measures beyond vaccination for those patients at risk," Ngo commented.