SARS-CoV-2 primary and breakthrough infections in patients with cancer: Implications for patient care

Abstract

Initial reports of SARS-CoV-2 caused COVID-19 suggested that patients with malignant diseases were at increased risk for infection and its severe consequences. In order to provide early United States population-based assessments of SARS-CoV-2 primary infections in unvaccinated patients with hematologic malignancies or cancer, and SARS-CoV-2 breakthrough infections in vaccinated patients with hematologic malignancies or cancer, we conducted retrospective studies using two, unique nationwide electronic health records (EHR) databases. Using these massive databases to provide highly statistically significant data, our studies demonstrated that, compared to patients without malignancies, risk for COVID-19 was increased in patients with all cancers and with all hematologic malignancies. Risks varied with specific types of malignancy. Patients with hematologic malignancies or cancer were at greatest risk for COVID-19 during the first year after diagnosis. Risk for infection was increased for patients 65 years and older, compared to younger patients and among Black patients compared to white patients. When patients with hematologic malignancies or cancer were vaccinated against SARS-CoV-2, their risk for breakthrough infections was decreased relative to primary infections but remained elevated relative to vaccinated patients without malignancies. Compared to vaccinated patients without malignancies, vaccinated patients with hematologic malignancy or cancer showed increased risk for infection at earlier post vaccination time points. As with primary infections, risk for breakthrough infections was greatest in patients during their first year of hematologic malignancy or cancer. There were no signs of racial disparities among vaccinated patients with hematologic malignancies or cancer. These results provide the population basis to understand the significance of subsequent immunologic studies showing relative defective and delayed immunoresponsiveness to SARS-CoV-2 vaccines among patients with hematologic malignancies and cancers. These studies further provide the basis for recommendations regarding COVID-19 vaccination, vigilance and maintaining mitigation strategies in patients with hematologic malignancies and cancers.

Keywords: COVID-19; Cancer; Hematologic malignancies; SARS-CoV-2.

Fig. 1

Comparison of risk of primary or breakthrough SARS-CoV-2 infections in patients with all cancer and hematologic malignancy. The outcome “Primary infection” during February–August 2020 was compared between the “All-cancer” cohort that comprised patients who had a diagnosis of cancer but no prior SARS-CoV-2 infections and the “Not cancer” cohort that comprised patients who did not have diagnosis of cancer nor prior SARS-CoV-2 infections. Similar comparision was performed between the “Hematologic malignancy” cohort that comprised patients who had a diagnosis of a hematological malignancy but no prior SARS-CoV-2 infections and the “Not cancer cohort” described above.The outcome “Breaktrhough infection” between December 2020 and November 2021 was compared between the “All-cancer” cohort that comprised fully vaccinated patients who had a diagnosis of cancer but no prior SARS-CoV-2 infections and the “Not cancer” cohort that comprised patients who did not have diagnosis of cancer nor prior SARS-CoV-2 infections. Similar comparision was performed between the “Hematologic malignancy cohort” that comprised fully vaccinated patients who had a diagnosis of a hematological malignancy but no prior SARS-CoV-2 infections and the “Not cancer cohort” described above.

Fig. 2

Comparison risk of hospitalization among patients with primary or breakthrough SARS-CoV-2 infections between All cancer, Not Cancer and Hematologic maligancy cohorts. All cancer – patients who had a preexisting diagnosis of cancer and a SARS-CoV-2 infection between February–August 2020 (“Primary infection”) or fully vaccinated patients who had a preexisting diagnosis of cancer and a breakthrough SARS-CoV-2 infection between December 2020 and November 2021 (“Breakthrough infection”). All cancer – patients who had no preexisting diagnosis of cancer but had a SARS-CoV-2 infection between February–August 2020 (“Primary infection”) or fully vaccinated patients who had no preexisting diagnosis of cancer but a breakthrough SARS-CoV-2 infection between December 2020 and November 2021 (“Breakthroug infection”). Hematologic malignancy – patients who had a preexisting diagnosis of hematologic malignancy and a SARS-CoV-2 infection between February–August 2020 (“Primary infection”) or fully vaccinated patients who had a preexisting diagnosis of hematologic malignancy and a breakthrough SARS-CoV-2 infection between December 2020 and November 2021 (“Breakthrough infection”).

Fig. 3

Comparison overall mortality rate among patients with primary or breakthrough SARS-CoV-2 infections between All cancer, Not Cancer and Hematologic maligancy cohorts. All cancer – patients who had a preexisting diagnosis of cancer and a SARS-CoV-2 infection between February–August 2020 (“Primary infection”) or fully vaccinated patients who had a preexisting diagnosis of cancer and a breakthrough SARS-CoV-2 infection between December 2020 and November 2021 (“Breakthrough infection”). All cancer – patients who had no preexisting diagnosis of cancer but had a SARS-CoV-2 infection between February–August 2020 (“Primary infection”) or fully vaccinated patients who had no preexisting diagnosis of cancer but a breakthrough SARS-CoV-2 infection between December 2020 and November 2021 (“Breakthroug infection”). Hematologic malignancy – patients who had a preexisting diagnosis of hematologic malignancy and a SARS-CoV-2 infection between February–August 2020 (“Primary infection”) or fully vaccinated patients who had a preexisting diagnosis of hematologic malignancy and a breakthrough SARS-CoV-2 infection between December 2020 and November 2021 (“Breakthrough infection”).