Abstract
The novel COVID-19 outbreak has affected more than 200 countries and territories as of March 2020. Given that patients with cancer are generally more vulnerable to infections, systematic analysis of diverse cohorts of patients with cancer affected by COVID-19 are needed. We performed a multi-center study including 105 cancer patients and 536 age-matched non-cancer patients confirmed with COVID-19. Our results showed COVID-19 patients with cancer had higher risks in all severe outcomes. Patients with hematological cancer, lung cancer, or with metastatic cancer (stage IV) had the highest frequency of severe events. Non-metastatic cancer patients experienced similar frequencies of severe conditions to those observed in patients without cancer. Patients who received surgery had higher risks of having severe events, while patients with only radiotherapy did not demonstrate significant differences in severe events when compared to patients without cancer. These findings indicate that cancer patients appear more vulnerable to SARS-COV-2 outbreak.
Keywords: cancer, COVID-19, metastatic cancer, lung cancer, immunotherapy
INTRODUCTION
A new (acute respiratory syndrome) coronavirus, named SARS-CoV-2 by the World Health Organization (WHO), has rapidly spread around the world since its first reported case in late December of 2019 from Wuhan, China.1 As of March 2020, this virus has affected more than 200 countries and territories, infecting more than 800,000 individuals and causing over 40,000 deaths.2
With more than 18 million new cases per year globally, cancer affects a significant portion of the population. Individuals affected by cancer are more susceptible to infections due to coexisting chronic diseases, overall poor health status, and systemic immunosuppressive states caused by both cancer and anticancer treatments.3 As a consequence, patients with cancer infected by the SARS-CoV-2 coronavirus may experience more difficult outcomes than other populations. Until now, there is still no systematic evaluation on the effects that the SARS-CoV-2 coronavirus has on patients with cancer in a representative population. A recent study reported a higher risk of severe events in patients with cancer when compared to patients without cancer,4 however, the small sample size of SARS-CoV-2 patients with cancer used in such study limited how representative it was to the whole population and made it difficult to conduct more insightful analyses, such as comparing clinical characteristics of patients with different types of cancer, as well as anticancer treatments.5, 6
Using patient information collected from 14 hospitals in Hubei Province, China, the epicenter of the 2019–2020 COVID-19 outbreak, we describe the clinical characteristics and outcomes (death, ICU admission, development of severe/critical symptoms, and utilization of invasive mechanical ventilation) of patients affected by the SARS-CoV-2 coronavirus for 105 hospitalized patients with cancer and 536 patients without cancer. We document our findings for different cancer types and stages, as well as different types of cancer treatments. We believe the information and insights provided in this study will help improve our understanding of the effects of the SARS-CoV-2 in patients with cancer.
RESULTS
Patients Characteristics
In total, 105 COVID-19 patients with cancer were enrolled in our study for the time period January 1, 2020, to Feb 24, 2020 from 14 hospitals in Wuhan, China. COVID-19 patients without cancer matched by the same hospital, hospitalization time, and age were randomly selected as our control group. Our patient population included 339 females and 302 males. Patients with cancer (median=64.00, IQR= 14.00), when compared to those without cancer (median=63.50, IQR=14.00) had similar age distributions (by design), experienced more in-hospital infections (20 [19.04%] of 105 patients vs 8 [1.49%] of 536 patients, p<0.01), and had more smoking history (36 [34.28%] of 105 patients vs 46 [8.58%] of 536 patients, p<0.01), but had no significant differences in sex, other baseline symptoms, and other comorbidities (Table 1). With respect to signs and symptoms upon admission, COVID-19 patients with and without cancer were similar except for a higher prevalence of chest distress (15 [14.29%] of 105 patients vs 36 [6.16%] of 536 patients, p=0.02).
Table 1.
Characteristics of COVID-19 Patients with and without cancer
| COVID-19 patients with cancer (n=105) | COVID-19 patients without cancer (n=536) | p value | |
|---|---|---|---|
| Age (years) (median/ IQR) | 64.00/14.00 | 63.50/14.00 | 0.25 |
| Sex | |||
| Male | 57/54.72% | 245/45.71% | 0.11 |
| Female | 48/45.28% | 291/54.29% | 0.11 |
| In-hospital Infection | 20/19.04% | 8/1.49% | <0.01 |
| Smoking | 36/34.28% | 46/8.58% | <0.01 |
| Comorbidities | |||
| Hypertension | 30/28.57% | 130/24.25% | 0.40 |
| Cardiovascular disease | 12/11.43% | 39/7.28% | 0.17 |
| Diabetes | 7/6.67% | 29/5.41% | 0.64 |
| Cerebrovascular disease | 5/4.76% | 21/3.92% | 0.60 |
| Chronic kidney disease | 6/5.71% | 22/4.10% | 0.44 |
| Chronic liver disease | 7/6.67% | 35/6.53% | 1.00 |
| Signs and symptoms | |||
| Fever | 68/64.76% | 401/74.81% | 0.04 |
| Dry cough | 57/52.29% | 313/58.40% | 0.45 |
| Sputum production | 16/15.24% | 58/10.82% | 0.24 |
| Fatigue | 30/28.57% | 179/33.40% | 0.36 |
| Myalgia | 6/5.71% | 38/7.09% | 0.83 |
| Nausea or Vomiting | 6/5.71% | 41/7.65% | 0.68 |
| Chest distress | 15/14.29% | 36/6.16% | 0.02 |
| Headache | 7/6.67% | 28/5.22% | 0.49 |
| Sore throat | 11/10.48% | 43/8.02% | 0.44 |
| Treatments | |||
| Antibiotic treatments | 81/77.14% | 361/67.35% | 0.05 |
| Antiviral treatments | 75/71.43% | 372/69.40% | 0.68 |
| Systemic glucocorticoids | 19/18.10% | 78/14.55% | 0.35 |
| Oxygen therapy | 48/45.71% | 221/42.02% | 0.48 |
| Noninvasive mechanical ventilation | 11/10.48% | 47/8.77% | 0.58 |
| Invasive mechanical ventilation | 11/10.48% | 15/2.79% | <0.01 |
| Continuous renal-replacement therapy | 4/3.81% | 3/0.56% | <0.01 |
| Extracorporeal membrane oxygenation | 3/2.86% | 2/0.37% | <0.01 |
| Time since cancer diagnosis to hospitalization | |||
| <3 months | 29/27.61% | NA | NA |
| 3–6 months | 17/16.19% | NA | NA |
| 6 months-1year | 11/10.47% | NA | NA |
| 1–3years | 19/18.09% | NA | NA |
| >3 years | 19/18.09% | NA | NA |
| Missing | 10/9.52% | NA | NA |
| Metastatic cancer | 17/16.19% | NA | NA |
| Cancer treatments within 40 days | |||
| Surgery | 8/7.62% | NA | NA |
| Radiotherapy | 13/12.38% | NA | NA |
| Chemotherapy | 17/16.19% | NA | NA |
| Targeted therapy | 4/3.81% | NA | NA |
| Immunotherapy | 6/5.71% | NA | NA |
Data are presented as median(IRQ) or n (%). p values denoted the comparison between COVID-19 patients with cancer and without cancer. NA=not applicable
Clinical outcomes
Compared with COVID-19 patients without cancer, patients with cancer had higher observed death rates (OR 2.34, 95% CI [1.15, 4.77]; p=0.03), higher rates of ICU admission (OR 2.84, 95% CI [1.59, 5.08]; p<0.01), higher rates of having at least one severe or critical symptom (OR 2.79, 95% CI [1.74, 4.41]; p<0.01) and higher chances of needing invasive mechanical ventilation (Figure 1A). we also conducted survival analysis on occurrence of any severe condition which included death, ICU admission, having severe symptoms and utilization of invasive mechanical ventilation (see cumulative incidence curves in Figure 1B). In general, patients with cancer deteriorated more rapidly than those without cancer. These observations are consistent with logistic regression results (Supplementary Figure 1), after adjusting for age, sex, smoking and comorbidities including diabetes, hypertension, chronic obstructive pulmonary disease (COPD). According to our multivariable logistic regression results, patients with cancer still had an excess odds ratio of 2.17 (p=0.06) for death (Supplementary Figure 1A), 1.99 (p<0.01) for experiencing any severe symptoms (Supplementary Figure 1B), 3.13 (p<0.01) for ICU admission (Supplementary Figure 1C) and 2.71 (p=0.04) for utilization of invasive mechanical ventilation (Supplementary Figure 1D, Supplementary Table 1). The consistency of observed odds ratios between multivariable regression model and unadjusted calculation reassures the association between cancer and severe events even in the presence of other factors such as age differences.
Figure 1.
Severe conditions in patients with and without cancer, and patients with different types, stages, and treatments of cancer. Severe conditions include death, ICU admission, having severe/critical symptoms, and usage of invasive mechanical ventilation. Abbreviations: ICU=intensive care unit, IMV=invasive mechanical ventilation.
(A, B) Incidence and survival analysis of severe conditions among COVID-19 patients with cancer and without cancer, (C, D) among patients with different types of cancer, (E, F) among patients with metastatic and non-metastatic cancers, (G, H) among patients with lung cancer, other cancers than lung with lung metastasis, and other cancers than lung without lung metastasis, (I, J) patients received different types of cancer treatments. For A, C, E, G, I, *p values indicate differences between cancer subgroups vs patients without cancer.*p<0.05, **p<0.01. Odd Ratio, 95% CI and p values between different subgroups are listed in Supplementary Table 2. For B, D, F, H, J, Hazard ratio, 95% CI and p values are listed in Supplementary Table 3.
Cancer types
Information regarding potential risks of severe conditions in SARS-CoV-2 associated with each type of cancer were calculated. We compared different conditions among cancer types in Table 2. Lung cancer was the most frequent cancer type (22 [20.95%] of 105 patients), followed by gastrointestinal cancer (13 [12.38%] of 105 patients), breast cancer (11 [10.48%] of 105 patients), thyroid cancer (11 [10.48%] of 105 patients) and hematological cancer (9 [8.57%] of 105 patients). As shown in Figure 1C, D and Supplementary Table 2, patients with hematological cancer including leukemia, lymphoma and myeloma have relatively high death rate (3 [33.33%] of 9 patients), high ICU admission rate (4 [44.44%] of 9 patients), high risks severe/critical symptoms (6[66.67%] of 9 patients), and high chance of utilization of invasive mechanical ventilation (2 [22.22%] of 9 patients). Patients with lung cancer had the second highest risk levels, with death rate (4 [18.18%] of 22 patients), ICU admission rate (6 [27.27%] of 22 patients), risks of severe/critical symptoms (11[50.00%] of 22 patients), and the chance of utilization of invasive mechanical ventilation (4 [18.18%] of 22 patients) (Table 2).
Table 2.
Severe Events in 105 Cancer Patients for Each Types of Cancer
| Cancer types | Total number | Death n% | Average time to death | ICU admission n% | Average time to ICU | Critical symptom n% | Average time to critical | IMV n% | Average time to IMV |
|---|---|---|---|---|---|---|---|---|---|
| Lung cancer | 22/20.95% | 18.18 | 16.75/8.17 | 27.27 | 10.00/6.82 | 50.00 | 8.55/5.71 | 18.18 | 14.50/6.98 |
| Gastrointestinal cancer | 13/12.38% | 7.69 | 24.0/NA | 23.08 | 9.05/6.16 | 30.77 | 8.50/5.85 | 7.69 | 22.00/NA |
| Breast cancer | 11/10.48% | 0.00 | NA/NA | 0.00 | NA/NA | 18.18 | 12.00/7.00 | 0.00 | NA/NA |
| Thyroid cancer | 11/10.48% | 0.00 | NA/NA | 0.00 | NA/NA | 9.09 | 8.00/NA | 0.00 | NA/NA |
| Blood cancer | 9/8.57% | 33.33 | 19.33/1.89 | 44.44 | 2.82/1.80 | 66.67 | 3.83/3.08 | 22.22 | 9.00/NA |
| Cervix cancer | 6/5.71% | 0.00 | NA/NA | 16.67 | 4.00/NA | 33.33 | 7.00/3.00 | 0.00 | NA/NA |
| Esophagus cancer | 6/5.71% | 16.67 | 28.00/NA | 33.33 | 9.52/0.50 | 50.00 | 7.33/2.05 | 16.67 | 16.00/NA |
| All cancer | 105/100% | 11.43 | 19.92/6.13 | 19.05 | 6.5/4.16 | 34.29 | 7.56/5.2 | 9.52 | 14.56/5.68 |
Only cancer types with more than 5 patients were listed. Numbers are presented as n/%; Average time to events are presented as mean/SD (days), from initial onset of COVID-19 symptoms to death/ ICU admission/ critical symptom/ IMV. Abbreviations: NA=not applicable; ICU=intensive care unit; IMV=invasive mechanical ventilation.
Cancer stage
We found that patients with metastatic cancer (stage IV) had even higher risks of death (OR 5.58, 95% CI [1.71, 18.23]; p=0.01), ICU admission (OR 6.59, 95% CI [2.32, 18.72]; p<0.01), having severe conditions (OR 5.97, 95% CI [2.24, 15.91]; p<0.01), and use of invasive mechanical ventilation (OR 55.42, 95%CI [13.21, 232.47]; p<0.01). In contrast, patients with non-metastatic cancer did not demonstrate statistically significant differences compared with patients without cancer, with all p values > 0.05 (Figure 1E, F, Supplementary Table 2 and Supplementary Table 3). In addition, when compared to patients without cancer, patients with lung cancer or other cancers with lung metastasis also showed higher risks of death, ICU admission rates, higher critical symptoms and use of invasive mechanical ventilation, with all p values below 0.01, but other cancers without lung metastasis had no statistically significant differences (p values all >0.05) (Figure G, H and Supplementary Table 3) when compared to patients without cancer.
Cancer treatments
Among the 105 COVID-19 patients with cancer in our study, 13 (12.26%) had radiotherapy, 17 (14.15%) received chemotherapy, 8 (7.62%) received surgery, 4 (3.81%) had targeted therapy, and 6 (5.71%) had immunotherapy within 40 days before the onset of COVID-19 symptoms. All of the targeted therapeutic drugs were epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) for treatment of lung cancer, and all of the immunotherapy drugs were programmed cell death protein 1 (PD-1) inhibitors for treatment of lung cancer. A patient with cancer may have more than one type of therapy. Our observation suggested that patients who received immunotherapy tend to have high rates of death (two [33.33%] of six patients) and high chances of developing critical symptoms (4 [66.67%] of 6 patients). Patients who received surgery demonstrated higher rates of death (2 [25.00%] of 8 patients), higher chances of ICU admission (3 [37.50%] of 8 patients), higher chances of having severe or critical symptoms (5 [62.50%] of 8 patients), and higher use of invasive ventilation (2 [25.00%] of 8 patients) than other treatments excluding immunotherapy. However, patients with cancer who received radiotherapy did not show statistically significant differences in having any severe events when compared with patients without cancer, with p values all>0.10 (Figure 1 I, J). In addition, clinical details on the cancer diagnoses and cancer treatments are summarized in Supplementary Table 4.
Timeline of severe events
To evaluate the time-dependent evolution of the disease, we conducted the timeline of different events for COVID-19 patients with cancer (Figure 2A) and COVID-19 patients without cancer (Figure 2B) with death and other severe events marked in the figure. COVID-19 Patients with cancer have a mean length of stay of 27.01 days (SD 9.52) and patients without cancers have a mean length of stay of 17.75 days (SD 8.64), the difference is significant (Wilcox test p<0.01). To better clarify the contributing factors that might influence outcomes, we also included logistic regression of COVID-19 patients with cancer adjusted by immunosuppression levels in Supplementary Table 5. However, no significant association between immunosuppression and severe outcomes were observed from the analysis (with all p values >0.05).
Figure 2.
Timeline of events for COVID-19 patients. (A) Timeline of events in COVID-19 patients with cancer, (B) Timeline of events in COVID-19 patients without cancer. For visualization purposes, patients without timeline information are excluded and only 105 COVID-19 patients without cancer are shown.
DISCUSSION
The findings in this study suggest that patients with cancer infected with SARS-COV-2 tend to have more severe outcomes when compared to patients without cancer. Patients with hematological cancer, lung cancer, and cancers in metastatic stages demonstrated higher rates of severe events compared to patients without cancer. In addition, patients who underwent cancer surgery showed higher death rates and higher chances of having critical symptoms.
The SARS-COV-2 virus has spread rapidly globally, thus, many countries have not been ready to handle the large volume of people affected by this outbreak due to a lack of knowledge about how this coronavirus affects the general population. To date, reports on the general population infected with SARS-COV-2 suggest elderly males have a higher incidence and death rate. 7, 8 Limited information is known about the outcome of patients with cancer who contract this highly communicable disease. Cancer is among the top causes of death. Asia, Europe, and Northern American have the highest incidence of cancer in the world,9 and at the moment of the writing of this study the SARS-COV-2 virus is mainly spreading in these three areas (Referred as https://www.cdc.gov/media/releases/2020/ s0226-Covid-19-spread.html;https://www.nytimes.com/2020/02/27/world/coronavirusnews.html). While COVID-19 patients with cancer may share some epidemiological features with the general population with this disease, they may also have additional clinical characteristics. Therefore, we conducted this study on patients with cancer with coexisting COVID-19 disease, to evaluate the potential effect of COVID-19 on patients with cancer.
Based on our analysis, COVID-19 patients with cancer tend to have more severe outcomes when compared to the non-cancer population. Although COVID-19 is reported to have a relatively low death rate of 2–3% in the general population,10 patients with cancer and COVID-19 not only have a nearly three-fold increase in the death rate than that of COVID-19 patients without cancer, but also tend to have much higher severity of their illness. Altogether, these findings suggest that patients with cancer are a much more vulnerable population in the current COVID-19 outbreak. Our findings are consistent with those presented in a previous study based on 18 patients with cancer.4 Due to the limited number of patients with cancer in the previous study, the authors concluded that among patients with cancer, age is the only risk factor for the severity of the illness. Based on our data on 105 patients with cancer, we have discovered additional risk factors, including cancer types, cancer stage and cancer treatments may contribute to the severity of the diseases among patients with cancer.
Our data demonstrate that the severity of SARS-COV-2 infected patients is significantly affected by the types of tumors. From our analysis, patients with hematological cancer have the highest severity and death rates among all patients with cancer, and lung cancer follows second. Patients with hematological cancer in our study include patients with leukemia, myeloma, and lymphoma, which have a more compromised immune system than patients with solid tumors.11 These patients all had a rapidly deteriorated clinical course once infected with COVID-19. Since malignant or dysfunctional plasma cells, lymphocytes, or white blood cells in general in hematological malignancies have decreased immunological function,12–14 this could be the main reason why patients with hematological cancer have very high severity and death rates. All the patients with hematological cancer are prone to the complications of serious infection,12–14 which can exacerbate the condition which could have worsened in COVID-19 patients. In our study, 55.56% of patients with hematological cancer had severe immunosuppression, which may the main reason of deteriorated outcomes. Though the small sample size limits representativity of the observation, we believe our finding can serve as an informative starting points for further investigation when larger cohort from a wide range of healthcare providers become available. Among the solid tumors, lung cancer is the highest risk category disease in patients with SARS-COV-2 infection (Figure 1C). Decreased lung function and severe infection in patients with lung cancer could contribute to the worse outcome in this subpopulation.15,16
In our analysis, we classified the SARS-COV-2 infection related high risk factors based on death, severe or critical illness, ICU admission, and the utilization of invasive mechanical ventilation. Using these parameters, we detected a multi-fold increase in risk in the cancer population, in contrast to the non-cancer population. If there were primary or metastatic tumors in the lungs, patients were more to a deteriorated course in a short time. Intriguing, when patients with cancer only had early stage disease without metastasis, we didn’t observe any difference between the cancer and non-cancer population in terms of COVID-19 related death rate or severity (Figure 1E). The stage of cancer diagnosis seemed to play a significant role in the severity and death rate of COVID-19.
Patients with cancer received a wide range of treatments, and we also found that different types of treatments had different influences on the severity and death when these patients contracted COVID-19. Recently, immunotherapy has assumed a very important role in treating tumors, which aids in treatment of cancer by blocking the immune-escape of cancer cells. But in our study, in contrast to patients with cancer with other treatments, patients with immunotherapy had the highest death rate and the most severity of illness, a very puzzling finding. According to pathological studies on the COVID-19 patients, there were desquamation of pneumocytes and hyaline membrane formation, implying that these patients had ARDS.17 ARDS induced by cytokine storm is reported to be the main reason for death of SARS-COV-2 infected patients.18 It is possible that in this setting, immunotherapy induces the release of a large amount of cytokines, which can be toxic to normal cells, including lung epithelial cells,19–21 and therefore lead to a more severe illness. However, in current study the number of patients with immunotherapy was too small, further study with a large case population needs to be conducted in future research.
In addition, COVID-19 patients with cancer who are under active treatment or not under active treatment do not show difference in their outcomes, and there is a significant difference between COVID-19 patients with cancer but not with active treatment and patients without cancer. (Supplementary Table 2). These results indicate that COVID-19 patients with both active treatment and just cancer history have a higher risk of developing severe events than non-cancer COVID-19 patients. The possible reasons could be due to some known cancer-related complications, for example: anaemia, hypoproteinaemia, or dyspnoea in early phase of COVID-19.22 We considered that cancer had a lifetime effect on patients and that cancer survivors always need routine follow-up after primary resection. Therefore, in clinical COVID-19 patient management, equivalent attentions need to be paid to those with cancer no matter they are under active therapeutics or not during the outbreak of COVID-19.
This study has several limitations. Though the cohort of COVID-19 patients with cancer is one of the largest in Hubei province, China, the epicenter of the initial outbreak, a larger cohort from the whole country or even from multiple countries will be more representative. Large scale national level and international research collaboration will be necessary to achieve this. At the initial stage of the outbreak, data collection and research activities were not a priority of the hospitals. Therefore, it was not possible to record and collect some data that are potentially informative for our analysis in a timely manner. In addition, due to urgency of clinical treatment, medical data used in this study were largely disconnected from the patients’ historical electronic medical records, which are mostly stored with a different healthcare provider than the medical center providing COVID-19 care. This left us with limited information about each patient.
Our study is the mid-size cohort study on this topic and will provide much-needed information on risk factors of this population. We hope that our findings will help countries better protect patients with cancer affected by the ongoing COVID-19 pandemic.
METHODS
Study design and patients
We conducted a multi-center study focusing on the clinical characteristics of confirmed cases of COVID-19 patients with cancer in 14 hospitals in Hubei province, China, all of the 14 hospitals served as government designated hospitals for patients diagnosed with COVID-19 (listed in the Supplementary Appendix). COVID-19 was diagnosed according to the WHO interim guidance.23 Patients with cancer confirmed with COVID-19 that hospitalized from January 1, 2020 to February 24, 2020 were enrolled. SARS-CoV-2 infected patients without cancer matched by the same hospital and hospitalization time were randomly selected as our control group. In addition, as age is one of the major predictors of severity of respiratory diseases like COVID-19,4 we excluded from our analysis 117 younger COVID-19 patients without cancer so that median ages of patients with cancer (median=64.0- IRQ=14.00) and patients without cancers (median=63.5, IQR=14.00) would be comparable. Four clinical outcomes were monitored up to February 24, 2020, the final date of follow-up. This case series was approved by the institutional ethics board of Zhongnan Hospital of Wuhan University (No. 2020029). It is worth pointing out that due to limited resources and information available in early stages of this outbreak, sample sizes of some sub-groups were small and collection of data for patients with better matched clinical characteristics was not possible. This limited the current study design.
Procedures
Medical records of patients were acquired by the data collection team of the above 14 hospitals. A team of physicians who had been taking care of patients with SARS-COV-2 infection reviewed the data. We used a standardized case-report form to collect clinical data. Primary cancer characteristics and detailed treatment information were extracted from past medical records by oncologists in the Hubei Anti-Cancer Association. Data were entered into a computerized database. Cases with insufficient records of previous disease history were excluded. Information collected included demographic data, medical history, comorbidities, symptoms, vital signs, blood routine test, chest computed tomographic (CT) scans. Only cancer treatments within 40 days before the onset of COVID-19 symptoms were considered for this study. Each patient’s medical record was reviewed by at least two oncologists. Our institutional ethics review board approved the study and waived the need for informed consent.
End Points and Assessments
There were four primary outcomes analyzed in this study: death, admission into the intensive care unit (ICU), development of severe or critical symptoms, and utilization of invasive mechanical ventilation.The clinical destination of severe/critical symptoms follow the 5th edition of 2019 Novel Coronavirus Disease (COVID-19) Diagnostic criteria published by the National Health Commission in China, including septic shock, acute respiratory distress syndrome, acute kidney injury, disseminated intravascular coagulation, rhabdomyolysis.
Statistical analysis
The aim of this study was to report clinical outcomes of COVID-19 patients with cancers. For categorical data, percentages of patients in each category were calculated. The Wilcoxon rank sum test was used to compare continuous data and Fisher’s exact test was used to compare categorical data from different categories without multi-test adjustment. Multivariable logistic regression was used to estimate odd ratios and 95% confidence intervals of each factor of interest with outcomes after data was normalized using Z-scores. The odds ratios were adjusted by age, sex, diabetes, hypertension, smoking and COPD at admission. Time from onset of symptoms to severe outcomes was investigated using survival analysis, with follow-up from initial onset of symptoms until February 24, 2020. Multivariable Cox regression was conducted to estimate the hazard ratios and their corresponding 95% confidence interval. Similar to logistic regression, Cox regression were adjusted by age, sex, diabetes, hypertension, smoking and COPD at admission. The Kaplan-Meier product-limit estimator was used to conduct survival analysis. All survival analyses were conducted using Lifelines 0.24.0 in Python environment.
Supplementary Material
SIGNIFICANCE.
Since this is the first large cohort study on this topic, our report will provide the much-needed information that will benefit global cancer patients. As such, we believe it is extremely important that our study be disseminated widely to alert clinicians and patients.
ACKNOWLEDGMENTS
The study is funded by grants [National Natural Science Foundation of China 8197103302/H16 (Hong-Bing Cai); the Singapore Ministry of Health’s National Medical Research Council under its Singapore Translational Research (STaR) Investigator Award MOH-STaR18nov-0002 (Daniel G Tenen); NIH/NHLBI Grant P01HL095489 and Xiu Research Fund (Li Chai)]. Editorial support was provided by the institutional ethics board of Zhongnan Hospital of Wuhan University (No. 2020029).
Footnotes
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Hong-Bing Cai declares funding from the NSCI.
Daniel G. Tenen declares funding from Ministry of Health’s National Medical Research Council under its Singapore Translational Research (STaR) Investigator Award.
Li Chai declares funding from National Institutes of Health and Xiu Research Fund.
All other authors declare no competing interests.
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