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      Clinical Portrait of the SARS-CoV-2 Epidemic in European Patients with Cancer

      research-article
      1 , * , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 6 , 9 , 22 , 6 , 8 , 19 , 9 , 6 , 2 , 3 , 15 , 18 , 21 , 2 , 11 , 5 , 12 , 1 , 3 , 10 , 6 , 9 , 6 , 5 , 22 , 3 , 11 , 6 , 5 , 6 , 23 , 24 , 25 , 25 , 4 , 22 , 8 , 26 , 2 , 27 , 27 , 2 , 8 , 26 , 11 , 28 , 3 , 12
      (Collab), (Collab), (Collab), (Collab), (Collab), (Collab), (Collab), (Collab)
      Cancer Discovery
      American Association for Cancer Research

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Higher risk of death from COVID-19 among patients with cancer was correlated with male sex, greater age, presence of multiple comorbidities, advanced-stage disease, and active disease; there was no association between risk and anticancer treatment.

          Abstract

          The SARS-CoV-2 pandemic significantly affected oncology practice across the globe. There is uncertainty as to the contribution of patients' demographics and oncologic features to severity and mortality from COVID-19 and little guidance as to the role of anticancer and anti–COVID-19 therapy in this population. In a multicenter study of 890 patients with cancer with confirmed COVID-19, we demonstrated a worsening gradient of mortality from breast cancer to hematologic malignancies and showed that male gender, older age, and number of comorbidities identify a subset of patients with significantly worse mortality rates from COVID-19. Provision of chemotherapy, targeted therapy, or immunotherapy did not worsen mortality. Exposure to antimalarials was associated with improved mortality rates independent of baseline prognostic factors. This study highlights the clinical utility of demographic factors for individualized risk stratification of patients and supports further research into emerging anti–COVID-19 therapeutics in SARS-CoV-2–infected patients with cancer.

          Significance:

          In this observational study of 890 patients with cancer diagnosed with SARS-CoV-2, mortality was 33.6% and predicted by male gender, age ≥65, and comorbidity burden. Delivery of cancer therapy was not detrimental to severity or mortality from COVID-19. These patients should be the focus of shielding efforts during the SARS-CoV-2 pandemic.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

            In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
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              Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

              Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
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                Author and article information

                Journal
                Cancer Discov
                Cancer Discov
                candisc
                Cancer Discovery
                American Association for Cancer Research
                2159-8274
                2159-8290
                October 2020
                31 July 2020
                31 July 2020
                : 10
                : 10
                : 1465-1474
                Affiliations
                [1 ]Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom.
                [2 ]Oncology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.
                [3 ]Medical Oncology, Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Barcelona, Spain.
                [4 ]Infectious Diseases, Vall d'Hebron University Hospital, Barcelona, Spain.
                [5 ]Department of Oncology and National Centre for HIV Malignancy, Chelsea and Westminster Hospital, London, United Kingdom.
                [6 ]Cancer Division, University College London Hospitals, London, United Kingdom.
                [7 ]Departament of Medical Oncology, ICO L'Hospitalet, Oncobell Program (IDIBELL), CIBERONC, Hospitalet de Llobregat, Barcelona, Spain.
                [8 ]Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center - IRCCS, Rozzano, Milan, Italy.
                [9 ]Department of Medical Oncology, Catalan Institute of Oncology, University Hospital Josep Trueta, Girona, Spain.
                [10 ]Department of Medical Oncology, Catalan Institute of Oncology, Badalona, Spain.
                [11 ]Department of Medical Oncology, Hospital Clinic, Barcelona, Spain.
                [12 ]Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale and Maggiore della Carita' Hospital, Novara, Italy.
                [13 ]Multidisciplinary Breast Pathology and Translational Research Unit, ASST Cremona, Cremona, Italy.
                [14 ]Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
                [15 ]Medical Oncology Unit, Spedali Civili, Brescia, Italy.
                [16 ]Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
                [17 ]Medical Oncology Unit, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy.
                [18 ]Infrastruttura Ricerca Formazione Innovazione, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.
                [19 ]Department of Gynecology and Obstetrics, Breast Center and Gynecological Cancer Center and CCC Munich, University Hospital Munich, Munich, Germany.
                [20 ]Policlinico Universitario Campus Bio-Medico, Rome, Italy.
                [21 ]Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
                [22 ]Division of Haematology, Department of Translational Medicine, University of Piemonte Orientale and Maggiore della Carita' Hospital, Novara, Italy.
                [23 ]Department of Translational Medicine, Unit of Medical Statistics, University of Piemonte Orientale and Cancer Epidemiology, CPO Piemonte, Novara, Italy.
                [24 ]Department of Internal Medicine, Hospital Clinic, Barcelona, Spain.
                [25 ]Haematology Department, ICO Hospitalet, Hospitalet de Llobregat, IDIBELL, Universitat de Barcelona, Barcelona, Spain.
                [26 ]Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
                [27 ]Department of Haematology, Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Barcelona, Spain.
                [28 ]Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, Barcelona, Spain.
                Author notes
                [* ] Corresponding Author: David J. Pinato, Imperial College London, Hammersmith Campus, Du Cane Road, W12 0NN London, United Kingdom. Phone: 44-0207-594-2799; E-mail: david.pinato@ 123456imperial.ac.uk
                Article
                CD-20-0773
                10.1158/2159-8290.CD-20-0773
                7668225
                32737082
                0a0cd14a-3dc3-41b5-b24c-c7ef119a0ac9
                ©2020 American Association for Cancer Research.

                This article is made available via the PMC Open Access Subset for unrestricted re-use, except commercial resale, and analyses in any form or by any means with acknowledgment of the original source. These permissions are granted for the duration of the Covid-19 pandemic or until revoked in writing. Upon expiration of these permissions, PMC is granted a license to make this article available via PMC and Europe PMC, subject to existing copyright protections.

                History
                : 29 May 2020
                : 22 June 2020
                : 28 July 2020
                Page count
                Figures: 1, Tables: 3, Equations: 0, References: 26, Pages: 10
                Funding
                Funded by: Wellcome Trust, http://dx.doi.org/10.13039/100004440;
                Award ID: PS3416
                Award Recipient :
                Funded by: AIRC, http://dx.doi.org/10.13039/501100005010;
                Award ID: 21198
                Award Recipient :
                Funded by: AIRC, http://dx.doi.org/10.13039/501100005010;
                Award ID: 14230
                Award Recipient :
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