Fatality rate of COVID-19 in patients with malignancies: a sytematic review and meta-analysis
Authors: Zeinab Mohseni Afshar, Maliheh Dayani, Mehdi Naderi, Farnia Ghanbarveisi, Samira Shiri, Fatemeh Rajati
Journal: Journal of Infection (2020)

With great interest, we read the recently published letter by Ma et al. (2020)1Jia Ma Jing Yin Yu Qian Yuan Wu Clinical characteristics and prognosis in cancer patients with COVID-19: A single center's retrospective study.J Infect. 2020; Google Scholar who describe the demographics, clinical features, and prognosis of cancer patients with COVID-19 infection. In this study fatality rate of the COVID-19 in patients with malignancies reported as 13.5%. To have a better estimation of fatality rate, in this letter, we aimed to summarize the fatality rate among cancer patients with COVID-19 infection using meta-analysis. It is currently well known that one of the most important risk factors for COVID-19 morbidity and mortality is comorbid conditions, of which, immunosuppression might be the most challenging one. There are limited evidences about the relationship between COVID-19 severity and cancer. However, few available publications indicated more fatality rate and poorer prognosis of this novel virus in cancer patients compared to general population. Also, it has been observed that patients with cancer are more likely to be admitted to the intensive care unit (ICU), to require invasive ventilation, and even more likely to die.2Wenhua Liang Weijie Guan Ruchong Chen Wei Wang Jianfu Li Ke Xu et al.Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China.Lancet Oncol. 2020; 21: 335-337Abstract Full Text Full Text PDF PubMed Scopus (3290) Google Scholar Case fatality rate (CFR) is the likelihood of an infection to result in death. We conducted a systematic search on published studies limited to ones between December 30, 2019 and May 7, 2020 in PubMed, EMBASE, and Scopus. EndNote X8.000 software was used to manage the records and exclude duplicates. We used the search MeSH terms and relevant text-words including (2019 novel coronavirus OR COVID-19 OR SARS-CoV-2 OR nCoV-2019) AND (cancer OR neoplasms OR malignancy OR tumor OR carcinoma) AND (mortality OR fatality OR death). Eligible articles were those that described the case fatality rate (CFR) of COVID-19 in cancer patients. The two investigators (MN, Z MA), independently extracted data from the literature. We extracted the following variables: author, date, age, sex, number of total patients with malignancy, the proportion of death among them in each study. Case fatality was calculated as percentage of patients with cancer and infected by COVID-19 who died within hospitalization period. The meta-analysis was performed using R version 3.2.3. Pooled case fatality rates and their 95% confidence intervals (95% CIs) were used to summarize the weighted effect size for each study grouping variable using the random-effects model. Publication bias was assessed by funnel plot and Egger's test of asymmetry. From all 122 papers, 9 studies reported fatality rate of cancer patients with COVID-19 in hospital. A total of 805 patients from three countries including Iran (n=1),3Mohamad Nikpouraghdam Jalali Farahani Alireza GholamHossein Alishiri Soleyman Heydari Mehdi Ebrahimnia Hossein Samadinia et al.Epidemiological characteristics of coronavirus disease 2019 (COVID-19) patients in IRAN: A single center study.J Clin Virol. 2020; Google Scholar China (n=7),1Jia Ma Jing Yin Yu Qian Yuan Wu Clinical characteristics and prognosis in cancer patients with COVID-19: A single center's retrospective study.J Infect. 2020; Google Scholar,2Wenhua Liang Weijie Guan Ruchong Chen Wei Wang Jianfu Li Ke Xu et al.Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China.Lancet Oncol. 2020; 21: 335-337Abstract Full Text Full Text PDF PubMed Scopus (3290) Google Scholar,4Zhang L Zhu F Xie L Wang C Wang J Chen R et al.Clinical characteristics of COVID-19-infected cancer patients: A retrospective case study in three hospitals within Wuhan, China.Ann Oncol. 2020; Abstract Full Text Full Text PDF Scopus (1114) Google Scholar, 5Novel Coronavirus Pneumonia Emergency Response EpidemiologyThe epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China.Zhonghua Liu Xing Bing Xue Za Zhi= Zhonghua Liuxingbingxue Zazhi. 2020; 41: 145PubMed Google Scholar, 6Hirotaka Miyashita Takahisa Mikami Nitin Chopra Takayuki Yamada Svetlana Chernyavsky Dahlia Rizk et al.Do Patients with Cancer Have a Poorer Prognosis of COVID-19? An Experience in New York City.Ann Oncol. 2020; Google Scholar, 7Heng Mei Xiaorong Dong Yadan Wang Liang Tang Yu Hu Managing patients with cancer during the COVID-19 pandemic: frontline experience from Wuhan.Lancet Oncol. 2020; 21: 634-636Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar, 8Wenjuan He Lei Chen Li Chen Guolin Yuan Yun Fang Wenlan Chen et al.COVID-19 in persons with haematological cancers.Leukemia. 2020; : 1-9PubMed Google Scholar and USA (n=1)9Vikas Mehta Sanjay Goel Rafi Kabarriti Daniel Cole Mendel Goldfinger Ana Acuna-Villaorduna et al.Case Fatality Rate of Cancer Patients with COVID-19 in a New York Hospital System.Cancer Discov. 2020; Google Scholar were studied. The most frequent malignancies was breast cancer (n=95). Two studies didn't report the type of the malignancies. Seven studies reported the mean age of the patients. Among them, the Mean ± SD age of the all patients was 53.9± 15.7 years. Only four studies presented the number of patients according to the sex, with a male percentage ranged from 53% to 60%. From all, 141 cancer patients died and fatality rate ranged from 5.5% to 60%. In the six studies that reported the sever patients, the proportion of severe cases was more than 38%, with a exception of the one study (11%) (Table 1)Table 1Study CharacteristicsNumber of studyautoryearcountryCancer type n (%)Number of cancer COVIDAge (median)Sex male n (%)Number of deathCase fatality rateSevere cases N(%)1He2020ChinaHematologic n= 1313377(53)8629(69%)2Zhang2020ChinaLung cancer: n= 7 (25.0); Oesophagus cancer: n= 4 (14.3); Breast cancer: n= 3 (10.7); Laryngocarcinoma: n= 2 (7.1); Liver cancer: n= 2 (7.1); Prostate cancer: n= 2 (7.1); Cervical cancer: n= 1 (3.6); Gastric cancer: n= 1 (3.6); Colon cancer: n= 1 (3.6); Rectum cancer: n= 1 (3.6); Nasopharynx cancer: n= 1 (3.6); Endometrial cancer: n= 1 (3.6); Ovarian cancer: n= 1 (3.6); Carcinoma of testis: n= 1 (3.6)286517 (60.7%)828.615 (53.6%)3Nikpouraghdama2020IranNP17NPNP15.88%NP4Mehta2020USAGenitourinary: n= 46; Breast: n= 28; Colorectal: n= 21; Gynecologic: .n= 13; Lung: n= 11; Head & Neck: n= 8; Neuro: n= 8; upper GI: n= 8; Hepatobiliary: n= 7; Bone / Soft tissue: n= 5; Neuroendocrine: n= 3; Pancreas: n= 3; Skin: n= 3) hematologic malignancies: n= 5421869 years (range 10-92 years)127 (58%)6125% solid tumors (lung (55%), gastrointestinal {Colorectal (38%), Pancreas (67%), Upper GI (38%)}, Gynecologic (38%). Genitourinary (15%), Breast (14%); Hematologic (37%).84 (38%)5Liang2020ChinaLung: 5(18%)1863.1NP7397 (39%)6Miyashita2020USABreast: n=57; Prostate: n= 56; Lung: n=23; Urothelial: n= 18; and colon: n= 16; other: n=16433427.52NP3711.0737 (11%)7Liu2020ChinaNP107NPNP65.6NP8Mei2020ChinaHematologic: n=13; Solid tumors: n=2033824 % (hemato: 46•2%; Solid: 10•0%)9Ma2020ChinaColorectal cancer 11 (29.7); Lung cancer 8 (21.6); Breast cancer 7 (18.9); Gynecological cancer 5 (13.5); Other cancers 6 (16.2)376220(54.1 %)513.554.1 %NP: Not provided. Open table in a new tab NP: Not provided. The pooled case fatality rate of cancer patients who infected by COVID-19 was 0.21 (95% CI: 0.12-0.30). A significant heterogeneity was detected (I2 = 0.87%, P < 0.001). (Fig. 1) Patients and number of the included studies were relatively small. Therefore, subgroup analysis was not performed to identify the possible source of study heterogeneity. However, the heterogeneity may be related to type of the cancer and cancer progression, different stage of the malignancies, sample size of the study, and sociodemographic characteristics. All the P values of Egger's tests were more than 0.05. The funnel plot's shape is symmetrical. So, there was no significant publication bias. (P = 0.55). The proportion of severe cases in cancer patients infected by COVID-19 is higher than patients without cancer. We collected only available data from published articles. So, unpublished papers are not included. The pooled fatality rate should be interpreted with caution. Not only for limited information in some primary studies, but for some methodological issues in calculation of the fatality rate. So an accurate estimate of fatality rate may not be obtained in primary studies. As studies didn't report any data about the duration of the patient's hospitalization, we couldn't define case fatality rate during a certain time for example over one month. In addition, we didn't know if the cause of all deaths were actually due to COVID-19 or cancer. Some primary studies have suffered from small sample size, comprising a small cohort of hospitalized cancer patients. In addition, cancer patients who died from COVID-19 out of the hospital were possibly missed and some of them with mild symptoms or who were misdiagnosed are removed from the denumrator, resulting in overestimation or underestimation of the fatality rate. Another issue is the variation of the study design. Some of the primary studies had a poor quality to enter in the meta-analysis. However, a meta-analysis recently conducted by Cao et. al. (2020) showed that the pooled case fatality rate of COVID-19 was 6.8%(CI: 0.04-0.09) in general population. However, this is very lower than we obtained. The leading reason for this outcome might be the cytotoxic chemotherapies or radiations that these population underwent for curative or palliative care (4), which resulted in a systemic immunosuppression. The proportion of severe COVID-19 patients, ranged from 11% to 69%, was also significantly higher than that of the general population.10Dawei Wang Bo Hu Chang Hu Fangfang Zhu Xing Liu Jing Zhang et al.Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China.Jama. 2020; 323: 1061-1069Crossref Scopus (16292) Google Scholar In conclusion, the estimated case fatality rate in patients with malignancies is high. It will be needed to calculate the time trends of case fatality rate in age and sex subgroups with the adequate sample size after emerging more data. All the authors declare that there are no conflicts of interest. We acknowlege the Student Research Committee,KUMS, Kermanshah, Iran. We also gratefullyacknowledge Vice Chancellery for Research andTechnology Kermanshah University of Medical Sciencesfor financial support with ethical registration code: IR.KUMS.REC.1399.336.