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      Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study

      research-article
      , MD a , , , MD b , , , PhD c , , , PhD d , , , MD d , , PharmD e , , PhD f , , PhD d , , MD g , , MD h , , MD i , j , , PhD k , , MD l , , MD m , , MD b , , MD n , , MD o , , MD p , , MD q , , MD r , , MD r , , MD s , , MD t , , MD u , , MD n , , MD u , , MD v , , MD t , , MD w , , MD x , , MD s , , MD y , , MD z , , MD aa , , MD ab , , MD g , ac , , MD ad , , MD i , j , , MD y , , MSN p , , MS v , , MS z , , MD ae , , MD c , , MD af , , MD af , , MD ag , , MD ah , , MD y , , MD ai , , MD ah , , MD ai , , APRN c , , MD b , , MD w , , MD ae , , MS b , , MD aj , , MD ak , , MD q , , MD af , , MD al , , MD w , , MD ad , , MD aa , , MD i , j , , MD ac , , MD aj , , MD ai , , PhD d , , MD i , j , , , MD d , , , MD d , , * , COVID-19 and Cancer Consortium
      Lancet (London, England)
      Elsevier Ltd.

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          Summary

          Background

          Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness.

          Methods

          In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing.

          Findings

          Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57–76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53–2·21), male sex (1·63, 1·07–2·48), smoking status (former smoker vs never smoked: 1·60, 1·03–2·47), number of comorbidities (two vs none: 4·50, 1·33–15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11–7·18), active cancer (progressing vs remission: 5·20, 2·77–9·77), and receipt of azithromycin plus hydroxychloroquine ( vs treatment with neither: 2·93, 1·79–4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07–0·84) or the US-Midwest (0·50, 0·28–0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality.

          Interpretation

          Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments.

          Funding

          American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.

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          Most cited references29

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          Clinical Characteristics of Coronavirus Disease 2019 in China

          Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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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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              SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

              Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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                Author and article information

                Contributors
                Journal
                Lancet
                Lancet
                Lancet (London, England)
                Elsevier Ltd.
                0140-6736
                1474-547X
                28 May 2020
                28 May 2020
                Affiliations
                [a ]Advanced Cancer Research Group, Kirkland, WA, USA
                [b ]Dana-Farber Cancer Institute, Boston, MA, USA
                [c ]Mays Cancer Center, UT Health San Antonio MD Anderson Cancer Center, San Antonio, TX, USA
                [d ]Vanderbilt-Ingram Cancer Center at Vanderbilt University Medical Center, Nashville, TN, USA
                [e ]Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA
                [f ]MD Anderson Cancer Center, Houston, TX, USA
                [g ]University of Connecticut, Farmington, CT, USA
                [h ]Sylvester Comprehensive Cancer Center at the University of Miami, Miami, FL, USA
                [i ]Fred Hutchinson Cancer Research Center, Seattle, WA, USA
                [j ]University of Washington, Seattle, WA, USA
                [k ]Count Me In, Cambridge, MA, USA
                [l ]Lausanne University, Lausanne, Switzerland
                [m ]Advocate Aurora Health, Milwaukee, WI, USA
                [n ]Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, QC, Canada
                [o ]Mayo Clinic Cancer Center, Phoenix, AZ, USA
                [p ]Winship Cancer Institute of Emory University, Atlanta, GA, USA
                [q ]McGill University Health Centre, Montreal, QC, Canada
                [r ]Hospital Universitario 12 de Octubre, Madrid, Spain
                [s ]Stamford Hospital, Stamford, CT, USA
                [t ]Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
                [u ]The Warren Alpert Medical School of Brown University, Providence, RI, USA
                [v ]St. Elizabeth Healthcare, Edgewood, KY, USA
                [w ]Stanford University, Stanford, CA, USA
                [x ]Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
                [y ]Cleveland Clinic, Cleveland, OH, USA
                [z ]Smilow Cancer Hospital at Yale New Haven, New Haven, CT, USA
                [aa ]Mayo Clinic Cancer Center, Rochester, MN, USA
                [ab ]Herbert Irving Comprehensive Cancer Center at Columbia University, New York, NY, USA
                [ac ]Hartford Health Care, Hartford, CT, USA
                [ad ]University of Kansas Medical Center, Kansas City, KS, USA
                [ae ]Moores Cancer Center, University of California San Diego, La Jolla, CA, USA
                [af ]The Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA
                [ag ]School of Public Health, Brown University, Providence, RI, USA
                [ah ]Willis-Knighton Cancer Center, Shreveport, LA, USA
                [ai ]Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
                [aj ]Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, USA
                [ak ]Stanley S Scott Cancer Center, LSU Health, New Orleans, LA, USA
                [al ]Mount Auburn Hospital, Cambridge, MA, USA
                Author notes
                [* ]Correspondence to: Dr Jeremy L Warner, Vanderbilt-Ingram Cancer Center at Vanderbilt University Medical Center, Nashville, TN 37232, USA jeremy.warner@ 123456vumc.org
                [†]

                Contributed equally

                Article
                S0140-6736(20)31187-9
                10.1016/S0140-6736(20)31187-9
                7255743
                32473681
                f9cce1a5-878e-49c2-987b-7efd22cd90f4
                © 2020 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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