key: cord-0710976-60ejee29 authors: Wang, J.; Song, Q.; Chen, Y.; Wang, Z.; Chu, Q.; Gong, H.; Cai, S.; Dong, X.; Xu, B.; Hu, W.; Wang, Q.; Li, L.; Yang, J.; Xie, Z.; Luo, Z.; Liu, J.; Luo, X.; Ren, J.; Rao, Z.; Xu, X.; Pan, D.; Hu, Z.; Feng, G.; Hu, C.; Luo, L.; Lu, H.; Ran, R.; Jin, J.; Xu, Y.; Yang, Y.; Zhang, Z.; Kuang, L.; Wang, R.; Dong, Y.; Sun, J.; Yi, T.; Wu, H.; Liu, M.; Xu, J.; Duan, J.; Zhao, Z.; Wang, G.; He, J. title: Systematic investigations of COVID-19 in 283 cancer patients date: 2020-05-03 journal: nan DOI: 10.1101/2020.04.28.20083246 sha: 0d6578570cccb074e98edee339334b26dd7dc2f8 doc_id: 710976 cord_uid: 60ejee29 Background: Cancer patients are considered to be highly susceptible to viral infections, however, the comprehensive features of COVID-19 in these patients remained largely unknown. The present study aimed to assess the clinical characteristics and outcomes of COVID-19 in a large cohort of cancer patients. Design, Setting, and Participants: Data of consecutive cancer patients admitted to 33 designated hospitals for COVID-19 in Hubei province, China from December 17, 2019 to March 18, 2020 were retrospectively collected. The follow-up cutoff date was April 02, 2020. The clinical course and survival status of the cancer patients with COVID-19 were measured, and the potential risk factors of severe events and death were assessed through univariable and multivariable analyses. Results: A total of 283 laboratory confirmed COVID-19 patients (50% male; median age, 63.0 years [IQR, 55.0 to 70.0]) with more than 20 cancer types were included. The overall mortality rate was 18% (50/283), and the median hospitalization stay for the survivors was 26 days. Amongst all, 76 (27%) were former cancer patients with curative resections for over five years without recurrence. The current cancer patients exhibited worse outcomes versus former cancer patients (overall survival, HR=2.45, 95%CI 1.10 to 5.44, log-rank p=0.02; mortality rate, 21% vs 9%). Of the 207 current cancer patients, 95 (46%) have received recent anti-tumor treatment, and the highest mortality rate was observed in the patients receiving recent chemotherapy (33%), followed by surgery (26%), other anti-tumor treatments (19%), and no anti-tumor treatment (15%). In addition, a higher mortality rate was observed in patients with lymphohematopoietic malignancies (LHM) (53%, 9/17), and all seven LHM patients with recent chemotherapy died. Multivariable analysis indicated that LHM (p=0.001) was one of the independent factors associating with critical illness or death. Conclusions: This is the first systematic study comprehensively depicting COVID-19 in a large cancer cohort. Patients with tumors, especially LHM, may have poorer prognosis of COVID-19. Additional cares are warranted and non-emergency anti-tumor treatment should be cautiously used for these patients under the pandemic. Since the publicly reported coronavirus disease 2019 caused by severe acute 111 respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in December, 2019 1 and the 112 subsequent evidences of its human-to-human transmission property released in January 113 2020, 2 there has been an extremely rapid spread of the novel coronavirus around the globe. 114 The World Health Organization (WHO) has declared a global health emergency on January Cancer patients, as a special population who usually have a high demand for 121 intensive care and are frequently systematically immunosuppressed, are considered to be 122 more susceptible to the infection. 6 Accordingly, a considerable amount of cancer patients 123 may have been subjected to COVID-19 during the pandemic, which has attracted 124 increasing attention from the clinicians. [6] [7] [8] [9] Recent studies with small cohorts (n = 12 to 28) 125 of SARS-CoV-2 infected cancer patients have proposed the potentially higher 126 susceptibility and poorer prognosis of COVID-19 in cancer patients compared to the 127 overall population. 6, 8, 10 However, the study population in these reports are too limited to 128 provide conclusive evidences, and the characteristics of COVID-19 in cancer patients 129 remained largely unknown. Herein, we carried out the present large retrospective study for 130 the comprehensive investigation of the clinical characteristics, prognosis, survival status, 131 and potential risk factors of severe events of COVID-19 in a large cohort of Chinese cancer 132 patients. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. and further reviewed and confirmed by two independent physicians from each hospital. The data were analyzed by two independent statisticians (GW and YuXu). All 153 inconsistencies were reviewed and confirmed by the Medical Review Board composed of 154 physicians from departments of oncology, thoracic surgery, and pulmonary and critical care 155 medicine. Patient identity protection was maintained throughout the study. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 3, 2020. CoV-2 until death due to any cause. The clinical pathological variables, symptoms, and chest CT scan results in the patients 176 were statistically described. Continuous variables were described by median (IQR) and 177 categorical variables were described by number (percentages). To assess the differences 178 between different subset of population, Mann-Whitney test was performed for continuous 179 variables and chi-square test was performed for categorical variables. For hospitalization 180 stay, Kaplan-Meier curves were plotted and compared by using a log-rank test with 181 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. A total of 283 cancer patients who were admitted to 33 designated hospitals with laboratory 196 confirmed diagnosis of COVID-19 were included in the study ( Table 1) CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. . https://doi.org/10.1101/2020.04.28.20083246 doi: medRxiv preprint 8 (49%) with locally advanced or advanced diseases. Compared with the former cancer 206 patients, the current cancer patients were more likely to exhibit severe symptoms (29% vs 207 17%) on admission. The most common symptoms on admission were fever (73%), cough (68%), fatigue 209 (49%), sputum (41%), and dyspnea (40%) (supplementary table S1). Baseline chest CT . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. with recent chemotherapy (33%), followed by surgery (26%), other treatments (19%), and 252 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. The rapid spreading of COVID-19 has swept the globe, leading to a worldwide pandemic. The present study has provided the first comprehensive depiction of the clinicopathological CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. the studied cohort (6.0%, 3.2% for leukemia and 3.5% for lymphoma), which almost 293 doubles that of the prevalence of LHM in the overall cancer population in China (3.8%, 294 1.8% for leukemia and 2.1% for lymphoma), 13 indicating that these patients may be more 295 susceptible to SARS-CoV-2 infection. In addition, an even higher rate of death cases was 296 observed in patients with LHM (53%) compared with the patients with solid tumors (18%), 297 and all of the LHM patients who were treated with recent chemotherapy died. Collectively, 298 our results further suggested that the worse outcomes in SARS-CoV-2 infected cancer 299 patients may be attributed to both the intrinsic immunocompromised status from the 300 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. . https://doi.org/10.1101/2020.04.28.20083246 doi: medRxiv preprint 12 malignancies and the immunosuppression caused by active anti-tumor treatments. Accordingly, anti-tumor treatment, especially chemotherapy, should be used with great 302 caution to reduce the potential negative effects on the patients. 303 Previous reports suggested that age and coexisting conditions were potential risk 304 factors associated with disease severity. 14-16 Given the higher median age in our cancer 305 cohort (63 years) than the reported median age of 47-year-old in the general COVID-19 306 patients, the effect of age on the disease severity was weakened, providing a relatively 307 lower level of significance (OR, 1.94, 95%CI 1.12-3.37) in the univariable analysis 308 compared to the other variables (table 2). Our study further showed that LHM, an elevated 309 baseline neutrophil, DBIL, creatinine, troponin, and the severe symptoms at onset illness 310 were independently associated with the development of critical or death cases in cancer 311 patients with COVID-19, which may provide important implications for the patient cares. There are several limitations in this study. Firstly, this study was conducted in a 313 retrospective setting. Nevertheless, the patient population in this study was relatively large, 314 and the patients were consecutively included irrespective of their baseline characteristics 315 including the clinical symptoms, which will reduce the potential bias of the study 316 population. Secondly, this study focused on the investigation of patients with cancer 317 infected with SARS-CoV-2, and no direct comparison was conducted between the infected 318 cancer patients and the non-cancer patients. Despite that, comparisons have been made 319 between the current and the former cancer patients, who were considered to exhibit 320 relatively more likely to cancer-free patients as a reference. Besides, the studied population 321 came from as many as 33 designated hospitals in Hubei province, China, which is 322 considered to be fairly representative for the overall condition of COVID-19 cancer 323 patients in Hubei province, and thus was compared with the data of general COVID-19 324 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. . https://doi.org/10.1101/2020.04.28.20083246 doi: medRxiv preprint 13 patients in Hubei province over the same period. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. . https://doi.org/10. 1101 /2020 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020 . . https://doi.org/10.1101 /2020 Chemotherapy 46 (16) 0 (0) 46 (22) Targeted therapy 12 (4) 0 (0) 12 (6) Others 14 (5) 0 (0) 14 (7) Diabetes . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. . https://doi.org/10. 1101 /2020 Ground glass opacity Yes vs. no 0.72 (0.37-1.40) 0.33 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 3, 2020. Clinical features of patients infected with 2019 novel 360 coronavirus in Wuhan, China. Lancet Early Transmission Dynamics in Wuhan, China The New England journal of medicine World Health Organization. Coronavirus diease (COVID-19) pandemic CRP=C-reactive protein; hsCRP=high sensitivity C-reactive protein; LHM= Lymphohematopoietic cancer. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)The copyright holder for this preprint this version posted May 3, 2020. shown from their onset illness (left), most severe severity level (middle), to last follow-up visit (right). The patients with different severity levels were demonstrated in different colors. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 3, 2020. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)The copyright holder for this preprint this version posted May 3, 2020. . https://doi.org/10. 1101 /2020