All-Cause Mortality in COVID-19–Positive and COVID-19–Negative Patients With Cancer

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In a large cohort study reported by Sharafeldin et al in the Journal of Clinical Oncology, researchers from the National COVID Cohort Collaborative (N3C) found that COVID-19–positive vs –negative status was associated with an increased risk of all-cause mortality at 1 year among patients with cancer.

As stated by the investigators, “Variation in risk of adverse clinical outcomes in patients with cancer and COVID-19 has been reported from relatively small cohorts. The National Center for Advancing Translational Sciences N3C is a centralized data resource representing the largest multicenter cohort of COVID-19 cases and controls nationwide.”

Study Details

The study included 398,579 adult outpatients and inpatients with cancer from 50 U.S. centers identified from the N3C cohort with a COVID-19–positive or COVID-19–negative diagnosis between January 1, 2020, and March 25, 2021. Patients were followed from time of an index clinical encounter. At each site, all patients with COVID-19 with any encounter after January 1, 2020, were included in the cohort. All patients without COVID-19 were initially included from contributing sites, and from December 2020, were randomly selected from the corresponding site in a 2:1 ratio to match the overall prevalence of age, sex, and race/ethnicity of patient with COVID-19. The COVID-19–positive analytic cohort was limited to patients with COVID-19 who had their earliest COVID-19 diagnosis within 21 days before and up to 5 days after the start of the index encounter.

Among all patients, the most common cancer types were skin (13.8%), breast (13.7%), prostate (10.6%), hematologic (10.5%), and gastrointestinal (10%).

Among all 398,579 patients, 63,413 (15.9%) were COVID-19–positive and 335,166 were negative. A total of 38,614 COVID-19–positive patients were included in the analytic cohort.

Among the 373,780 patients in the analytic cohort, the index encounter was a hospitalization visit for 204,503 (55%), including 19,515 COVID-19–positive and 184,988 COVID-19–negative patients.


  • Among COVID-19–positive patients, factors significantly associated with increased risk of 1-year all-cause mortality were age > 65 years, male sex, living in Southern and Western U.S. regions, increased number of comorbidities, hematologic malignancies and multisite tumors, and recent cytotoxic therapy.
  • Factors significantly associated with decreased risk were non-Hispanic Black race, recent hormonal therapy, and treatment of COVID-19 with dexamethasone.

Key Findings

For COVID-19–positive vs –negative patients, survival probabilities were 84% vs 82% at 10 days, 55% vs 64% at 30 days, and 35% vs 50% at 90 days (overall P = .07). At 90 days, among COVID-19–positive patients, those with breast cancer had better survival (51%) vs other cancer types, with patients with multisite cancers having the lowest survival (26%).

In analysis adjusting for age, group, sex, race/ethnicity, smoking status, geographic location of patient residence, adjusted Charlson Comorbidity Index, primary cancer type, and cancer treatment at 30 days, COVID-19 positivity was significantly associated with increased risk of 1-year all-cause mortality (hazard ratio [HR] = 1.20, 95% confidence interval [CI] =1.15–1.24, P < .001).

Among COVID-19–positive patients, factors significantly associated with increased risk of 1-year all-cause mortality were age > 65 years (HR = 1.9, 95% CI = 1.3–3.1), male sex (HR = 1.11, 95% CI = 1.02–1.20), living in Southern and Western U.S. regions (HR = 1.3, 95% CI = 1.1–1.6; HR = 1.7, 95% CI = 1.3–2.2), increased number of comorbidities (HR = 2.0, 95% CI = 1.8–2.3), hematologic malignancies (HR = 1.2, 95% CI = 1.0–1.3) and multisite tumors (HR = 1.3, 95% CI = 1.1–1.4), and recent cytotoxic therapy (HR = 1.5, 95% CI = 1.1–2.1). Recent treatment with immunotherapy or targeted therapy was not associated with increased risk.

Factors significantly associated with decreased risk were non-Hispanic Black race (HR = 0.8, 95% CI = 0.7–0.9), recent hormonal therapy (HR = 0.5, 95% CI = 0.3–0.9), and treatment of COVID-19 with dexamethasone (HR = 0.8, 95% CI = 0.7–0.9).

The investigators concluded, “Using N3C, we assembled the largest nationally representative cohort of patients with cancer and COVID-19 to date. We identified demographic and clinical factors associated with increased all-cause mortality in patients with cancer. Full characterization of the cohort will provide further insights into the effects of COVID-19 on cancer outcomes and the ability to continue specific cancer treatments.”

Noha Sharafeldin, MD, PhD, MSc, of the Institute for Cancer Outcomes and Survivorship, O’Neal Comprehensive Cancer Center, The University of Alabama at Birmingham, is the corresponding author for the Journal of Clinical Oncology.

Disclosure: The study was supported by grants from the National Institutes of Health. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.