PURPOSE Coronavirus-2019 (COVID-19) mortality is higher in patients with cancer than in the general population, yet the cancer-associated risk factors for COVID-19 adverse outcomes are not fully characterized. PATIENTS AND METHODS We reviewed clinical characteristics and outcomes from patients with cancer and concurrent COVID-19 at Memorial Sloan Kettering Cancer Center until March 31, 2020 (n = 309), and observed clinical end points until April 13, 2020. We hypothesized that cytotoxic chemotherapy administered within 35 days of a COVID-19 diagnosis is associated with an increased hazard ratio (HR) of severe or critical COVID-19. In secondary analyses, we estimated associations between specific clinical and laboratory variables and the incidence of a severe or critical COVID-19 event. RESULTS Cytotoxic chemotherapy administration was not significantly associated with a severe or critical COVID-19 event (HR, 1.10; 95% CI, 0.73 to 1.60). Hematologic malignancy was associated with increased COVID-19 severity (HR, 1.90; 95% CI, 1.30 to 2.80). Patients with lung cancer also demonstrated higher rates of severe or critical COVID-19 events (HR, 2.0; 95% CI, 1.20 to 3.30). Lymphopenia at COVID-19 diagnosis was associated with higher rates of severe or critical illness (HR, 2.10; 95% CI, 1.50 to 3.10). Patients with baseline neutropenia 14-90 days before COVID-19 diagnosis had worse outcomes (HR, 4.20; 95% CI, 1.70 to 11.00). Findings from these analyses remained consistent in a multivariable model and in multiple sensitivity analyses. The rate of adverse events was lower in a time-matched population of patients with cancer without COVID-19. CONCLUSION Recent cytotoxic chemotherapy treatment was not associated with adverse COVID-19 outcomes. Patients with active hematologic or lung malignancies, peri–COVID-19 lymphopenia, or baseline neutropenia had worse COVID-19 outcomes. Interactions among antineoplastic therapy, cancer type, and COVID-19 are complex and warrant further investigation.
Background New York City (NYC) is the epicenter of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID‐19]) in the United States. Clinical characteristics and outcomes of vulnerable populations, such as those with gynecologic cancer who develop COVID‐19 infections, is limited. Methods Patients from 6 NYC‐area hospital systems with known gynecologic cancer and a COVID‐19 diagnosis were identified. Demographic and clinical outcome data were abstracted through a review of electronic medical records. Results Records for 121 patients with gynecologic cancer and COVID‐19 were abstracted; the median age at the COVID‐19 diagnosis was 64.0 years (interquartile range, 51.0‐73.0 years). Sixty‐six of the 121 patients (54.5%) required hospitalization; among the hospitalized patients, 45 (68.2%) required respiratory intervention, 20 (30.3%) were admitted to the intensive care unit, and 9 (13.6%) underwent invasive mechanical ventilation. Seventeen patients (14.0%) died of COVID‐19 complications. No patient requiring mechanical ventilation survived. On multivariable analysis, hospitalization was associated with an age ≥64 years (risk ratio [RR], 1.73; 95% confidence interval [CI], 1.18‐2.51), African American race (RR, 1.56; 95% CI, 1.13‐2.15), and 3 or more comorbidities (RR, 1.43; 95% CI, 1.03‐1.98). Only recent immunotherapy use (RR, 3.49; 95% CI, 1.08‐11.27) was associated with death due to COVID‐19 on multivariable analysis; chemotherapy treatment and recent major surgery were not predictive of COVID‐19 severity or mortality. Conclusions The case fatality rate among gynecologic oncology patients with a COVID‐19 infection is 14.0%. Recent immunotherapy use is associated with an increased risk of mortality related to COVID‐19 infection. Lay Summary The case fatality rate among gynecologic oncology patients with a coronavirus disease 2019 (COVID‐19) infection is 14.0%; there is no association between cytotoxic chemotherapy and cancer‐directed surgery and COVID‐19 severity or death. As such, patients can be counseled regarding the safety of continued anticancer treatments during the pandemic. This is important because the ability to continue cancer therapies for cancer control and cure is critical.
Acquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival. These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19. Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 525 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we show that CH is associated with severe Covid-19 outcomes (OR = 1.85, 95%=1.15–2.99, p = 0.01), in particular CH characterized by non-cancer driver mutations (OR = 2.01, 95% CI = 1.15–3.50, p = 0.01). We further explore the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH is significantly associated with risk of Clostridium Difficile (HR = 2.01, 95% CI: 1.22–3.30, p = 6×10−3) and Streptococcus/Enterococcus infections (HR = 1.56, 95% CI = 1.15–2.13, p = 5×10−3). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation.
Background Neutropenia is commonly encountered in cancer patients. Recombinant human granulocyte colony-stimulating factor (G-CSF, filgrastim), a cytokine that initiates proliferation and differentiation of mature granulocytes, is widely given to oncology patients to counteract neutropenia, reducing susceptibility to infection. However, the clinical impact of neutropenia and G-CSF use in cancer patients with COVID-19 remains unknown. Methods An observational cohort of 379 actively treated cancer patients with COVID-19 was assembled to investigate links between concurrent neutropenia and G-CSF administration on COVID-19-associated respiratory failure and death. These factors were encoded as time-dependent predictors in an extended Cox model, controlling for age and underlying cancer diagnosis. To determine whether the degree of granulocyte response to G-CSF affected outcomes, the degree of response to G-CSF, based on rise in absolute neutrophil count (ANC) 24 hours after growth factor administration, was also incorporated into a similar Cox model. Results In the setting of active COVID-19 infection, outpatient receipt of G-CSF led to an increased number of hospitalizations (HR: 3.54, 95% CI: 1.25-10.0, P value: 0.017). Furthermore, among inpatients, G-CSF administration was associated with increased need for high levels of oxygen supplementation and death (HR: 3.56, 95% CI: 1.19-10.2, P value: 0.024). This effect was predominantly seen in patients that exhibited a high response to G-CSF based on their ANC increase post-G-CSF administration (HR: 7.78, 95% CI: 2.05-27.9, P value: 0.004). Conclusion The potential risks versus benefits of G-CSF administration should be considered in neutropenic cancer patients with COVID-19, since G-CSF administration may lead to worsening clinical and respiratory status.
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