Clinical outcomes in cancer patients with COVID‐19

Abstract Background Early 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. Aim To 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 results Of 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. Conclusion Active 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.

2 (SARS-CoV-2). The resultant coronavirus disease 2019  has led to over 2 700 000 deaths. 1 Cancer patients are vulnerable to infection with community acquired respiratory viruses due to a variety of factors including immunocompromised status secondary to malignancy itself, predisposition for malnutrition, and immunosuppressive treatments. 2,3 These same factors confer an increased risk for developing complications of respiratory viral infections, such as lower respiratory tract illness and hypoxemic respiratory failure, and raised concern that cancer patients would be particularly susceptible to severe COVID-19. 4,5 Earlier reports from China suggested that both patients with active cancer or a history of malignancy are at heightened risk for contracting SARS-CoV-2 and suffering worse disease outcomes. [6][7][8][9][10] These findings were subsequently corroborated by studies from around the world. [11][12][13][14][15] However, more recent data revealed similar morbidity and mortality of hospitalized COVID-19 patients with active malignancy compared to individuals without cancer matched by age and number of comorbidities. 16  A report on all COVID-19 patients at NYU Langone Health between March 1 and April 8, 2020 documented that age and comorbidities were associated with worse outcomes and found that 24.3% of hospitalized patients died. 18 In this study, we aimed to evaluate whether and to what degree cancer status is associated with known variables of worse COVID-19 outcomes in a cohort of hospitalized patients.

| Study population
We included adult patients who were hospitalized between March 16, 2020 and July 31, 2020 at NYU Langone Hospital -Tisch/Kimmel, NYU Langone Orthopedic Hospital, NYU Langone Hospital -Brooklyn, and NYU Langone Hospital -Long Island. To be included in this study, patients needed to have a current or past diagnosis of cancer, and a laboratory confirmed diagnosis of SARS-CoV-2 infection as determined by reverse transcription polymerase chain reaction (RT-PCR) of a nasopharyngeal swab specimen. Cancer status was categorized as active cancer versus a history of cancer based on the available data, which was sometimes limited because many individuals received their oncology care at other institutions. Patients were classified as having active malignancy if (1) they received treatment within 6 months of their COVID-19 diagnosis but did not achieve cure, (2) they had measurable disease, or (3) the outpatient or inpatient notes documented that disease was present at the time of their hospitalization. Patients were classified as having a history of cancer if (1) there was no evidence of measurable disease, (2) there were no treatments administered within 6 months of their COVID-19 diagnosis, and (3) the outpatient or inpatient notes documented that disease was in remission at the time of hospitalization.
Patients with non-invasive tumors and those with non-metastatic, nonmelanoma skin cancers were excluded from this study.

| Statistical analyses
We present categorical variables as frequencies with proportions and continuous variables as median values with standard deviations. We used the Chi-square test (or the Fisher exact test when appropriate) to compare categorical data, and Student's t test for continuous data.
We used multivariable Cox proportional hazards models to analyze the association between cancer status and all-cause mortality, ICU admission, and use of IMV. The multivariable models were adjusted for baseline clinical and demographic characteristics and pre-existing medical comorbidities. The full list of covariates is provided in Appendix S1. Patients who had a code status of DNR/DNI were excluded from the multivariable models evaluating ICU admission and use of IMV. Every patient was included in the multivariable model examining all-cause mortality regardless of code status. Missing laboratory values were excluded. Statistical tests were two-sided and p < .05 was considered significant. All analyses were performed using R version 4.0.2.

patients with PCR-proven COVID-19 were hospitalized at NYU
Langone Health during the study period. 221 (3.3%) had active malignancy and 359 (5.3%) had a history of cancer ( Figure 1 and Table 1 18 Our findings support the growing body of evidence that malignancy portends worse COVID-19 prognosis, and demonstrate that the risk may even apply to those without active disease.
Survival in our cohort was worse than that of other hospitalized cancer patients from the same time period. Most studies reported an in-hospital mortality ranging between 20% and 30%. 6,9,11,12,16 Several factors might have contributed to this discrepancy. First, the median age of our patients was higher than it was in multiple other studies. 6,9,11 Second, the majority of our patients had multiple preexisting conditions. 27  our cohort, this was not a consequence of resource availability as our institution faced challenges during the surge in NYC, but not to the point of suffering significant supply shortages or needing to ration care. 18 There are several limitations in our study. Many patients in our cohort received their oncology care outside of NYU, which limited available information. We limited our dataset to patients with a positive RT-PCR test, which has a well-described false negative rate. 14 In addition, many of our patients were hospitalized before glucocorticoids became the standard of care for treating hypoxic respiratory failure from SARS-CoV-2. 28 The available evidence suggests that systemic steroids confer a survival benefit in critically ill COVID-19 patients. 29 More data are also needed to understand the short-and long-term implications for cancer patients who receive corticosteroids but are also undergoing anti-cancer treatments potentially compromised by steroid use. 30 In conclusion, this is, to our knowledge, the first study to directly compare the clinical characteristics and illness phenotype of COVID-19 in patients with active malignancy versus a history of cancer. Our data suggest that the morbidity does not differ based on cancer status, but mortality is worse in individuals with active cancer. This speaks to the importance of continuing cancer care during the pandemic with as few interruptions as possible. Since both groups appear to be at higher risk for poor COVID-19 outcomes relative to the general population, the need to proceed with routine management and

CONFLICT OF INTEREST
The authors have stated explicitly that there are no conflicts of interest in connection with this article.

AUTHOR CONTRIBUTIONS
All authors had full access to the data in the study and take responsi-

ETHICAL STATEMENT
The NYU Langone Health institutional review board approved this study (IRB #10362). Informed written consent was obtained from all patients.

DATA AVAILABILITY STATEMENT
The data from this study can be made available upon reasonable request to the corresponding author. The data are not publicly available due to privacy or ethical restrictions.