Project description:Single-cell RNA-sequencing reveals a shift from focused IFN alpha-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 – a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention.
Project description:BackgroundEarly reports on cancer patients with coronavirus disease 2019 (COVID-19) corroborated speculation that cancer patients are at increased risk for becoming infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and developing severe COVID-19. However, cancer patients are a heterogeneous population and their corresponding risk may be different.AimTo compare COVID-19 presentation in patients with active malignancy to those with a history of cancer to determine the impact of cancer status on COVID-19 outcomes in the two groups.Methods and resultsOf the 6724 patients who were hospitalized at NYU Langone Health (3/16/20-7/31/20) and tested positive for SARS-CoV-2, 580 had either active cancer (n = 221) or a history of cancer (n = 359). We compared the baseline clinicodemographic characteristics and hospital courses of the two groups. We studied the relationship between cancer status and the rate of admission to the intensive care unit (ICU), use of invasive mechanical ventilation (IMV), and all-cause mortality. The two groups had similar laboratory results associated with COVID-19 infection, incidence of venous thromboembolism, and incidence of severe COVID-19. Active cancer status was not associated with the rate of ICU admission (p = .307) or use of IMV (p = .236), but was significantly associated with worse all-cause mortality in both univariate and multivariate analysis with odds ratios of 1.48 (95% confidence interval [CI]: 1.04-2.09; p = .028) and 1.71 (95% CI: 1.12-2.63; p = .014), respectively.ConclusionActive cancer patients had worse survival outcomes compared to patients with a history of cancer despite similar COVID-19 disease characteristics in the two groups. Our data suggest that cancer care should continue with minimal interruptions during the pandemic to bring about response and remission as soon as possible.
Project description:We perform shotgun transcriptome sequencing of human RNA obtained from nasopharyngeal swabs of patients with COVID-19, and identify a molecular signature associated with disease severity
Project description:Cancer patients present a distinct vulnerability to COVID-19. It is unclear if chemotherapy could accentuate the overall risk in these patients. We performed a retrospective analysis linking COVID-19 data and oncological information systems to compare lethality in patients undergoing cytotoxic chemotherapy before COVID-19. We considered patients who received chemotherapy in the last 30 days as in "active treatment", and patients who did not receive drugs in this period as "non-active treatment" for propensity-score pair matching. We also tested the influence of baseline variables in our results in a multivariate model. 66.1% (162/246) of patients in matched active chemotherapy died vs. 70.2% (172/246) in the matched non-active chemotherapy group. The risk of death was positively associated with palliative intent of treatment and hematologic neoplasms. Being in active chemotherapy was not associated with increased mortality compared to non-active treatment. We also noted in exploratory propensity-score matchings that the use of alkylating agents (odds ratio [OR] 0.38, 95% confidence interval [CI], 0.21-0.70) and topoisomerase II inhibitors (OR 0.28, 95% CI 0.14-0.56) were protective factors. This study does not demonstrate an increase in mortality for cancer patients under active cytotoxic chemotherapy with COVID-19.
Project description:The vast majority of SARS-CoV-2 infections are uncomplicated and do not require hospitalization, but these infections contribute to ongoing transmission. There remains a critical need to identify host immune biomarkers predictive of virologic and clinical outcomes in planning future treatment studies of COVID-19. We recently completed a randomized clinical trial of Pegylated PegIinterferon Lambda for treatment of SARS-CoV-2 infected patients conducted in the Stanford COVID-19 CTRU. Leveraging longitudinal samples and data from this trial, we define early immunebaseline and infection-induced signatures that predict the duration of viral shedding, resolution of symptoms, and immunologic memory.
Project description:BackgroundNew 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.MethodsPatients 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.ResultsRecords 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.ConclusionsThe 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 summaryThe 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.
Project description:BackgroundEarly reports suggested increased mortality from COVID-19 in patients with cancer but lacked rigorous comparisons to patients without cancer. We investigated whether a current cancer diagnosis or cancer history is an independent risk factor for death in hospitalized patients with COVID-19.Patients and methodsWe identified patients with a history of cancer admitted to two large hospitals between March 13, 2020, and May 10, 2020, with laboratory-confirmed COVID-19 and matched them 1:2 to patients without a history of cancer.ResultsMen made up 56.2% of the population, with a median age of 69 years (range, 30-96). The median time since cancer diagnosis was 35.6 months (range, 0.39-435); 80% had a solid tumor, and 20% had a hematologic malignancy. Among patients with cancer, 27.8% died or entered hospice versus 25.6% among patients without cancer. In multivariable analyses, the odds of death/hospice were similar (odds ratio [OR], 1.09; 95% confidence interval [CI], 0.65-1.82). The odds of intubation (OR, 0.46; 95% CI, 0.28-0.78), shock (OR, 0.54; 95% CI, 0.32-0.91), and intensive care unit admission (OR, 0.51; 95% CI, 0.32-0.81) were lower for patients with a history of cancer versus controls. Patients with active cancer or who had received cancer-directed therapy in the past 6 months had similar odds of death/hospice compared with cancer survivors (univariable OR, 1.31; 95% CI, 0.66-2.60; multivariable OR, 1.47; 95% CI, 0.69-3.16).ConclusionPatients with a history of cancer hospitalized for COVID-19 had similar mortality to matched hospitalized patients with COVID-19 without cancer, and a lower risk of complications. In this population, patients with active cancer or recent cancer treatment had a similar risk for adverse outcomes compared with survivors of cancer.Implications for practiceThis study investigated whether a current cancer diagnosis or cancer history is an independent risk factor for death or hospice admission in hospitalized patients with COVID-19. Active cancer, systemic cancer therapy, and a cancer history are not independent risk factors for death from COVID-19 among hospitalized patients, and hospitalized patients without cancer are more likely to have severe COVID-19. These findings provide reassurance to survivors of cancer and patients with cancer as to their relative risk of severe COVID-19, may encourage oncologists to provide standard anticancer therapy in patients at risk of COVID-19, and guide triage in future waves of infection.