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      The impact of the COVID-19 pandemic on cancer care

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          Abstract

          The COVID-19 pandemic has disrupted the spectrum of cancer care, including delaying diagnoses and treatment and halting clinical trials. In response, healthcare systems are rapidly reorganizing cancer services to ensure that patients continue to receive essential care while minimizing exposure to SARS-CoV-2 infection.

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          Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

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            Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

            China and the rest of the world are experiencing an outbreak of a novel betacoronavirus known as severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). 1 By Feb 12, 2020, the rapid spread of the virus had caused 42 747 cases and 1017 deaths in China and cases have been reported in 25 countries, including the USA, Japan, and Spain. WHO has declared 2019 novel coronavirus disease (COVID-19), caused by SARS-CoV-2, a public health emergency of international concern. In contrast to severe acute respiratory system coronavirus and Middle East respiratory syndrome coronavirus, more deaths from COVID-19 have been caused by multiple organ dysfunction syndrome rather than respiratory failure, 2 which might be attributable to the widespread distribution of angiotensin converting enzyme 2—the functional receptor for SARS-CoV-2—in multiple organs.3, 4 Patients with cancer are more susceptible to infection than individuals without cancer because of their systemic immunosuppressive state caused by the malignancy and anticancer treatments, such as chemotherapy or surgery.5, 6, 7, 8 Therefore, these patients might be at increased risk of COVID-19 and have a poorer prognosis. On behalf of the National Clinical Research Center for Respiratory Disease, we worked together with the National Health Commission of the People's Republic of China to establish a prospective cohort to monitor COVID-19 cases throughout China. As of the data cutoff on Jan 31, 2020, we have collected and analysed 2007 cases from 575 hospitals (appendix pp 4–9 for a full list) in 31 provincial administrative regions. All cases were diagnosed with laboratory-confirmed COVID-19 acute respiratory disease and were admitted to hospital. We excluded 417 cases because of insufficient records of previous disease history. 18 (1%; 95% CI 0·61–1·65) of 1590 COVID-19 cases had a history of cancer, which seems to be higher than the incidence of cancer in the overall Chinese population (285·83 [0·29%] per 100 000 people, according to 2015 cancer epidemiology statistics 9 ). Detailed information about the 18 patients with cancer with COVID-19 is summarised in the appendix (p 1). Lung cancer was the most frequent type (five [28%] of 18 patients). Four (25%) of 16 patients (two of the 18 patients had unknown treatment status) with cancer with COVID-19 had received chemotherapy or surgery within the past month, and the other 12 (25%) patients were cancer survivors in routine follow-up after primary resection. Compared with patients without cancer, patients with cancer were older (mean age 63·1 years [SD 12·1] vs 48·7 years [16·2]), more likely to have a history of smoking (four [22%] of 18 patients vs 107 [7%] of 1572 patients), had more polypnea (eight [47%] of 17 patients vs 323 [23%] of 1377 patients; some data were missing on polypnea), and more severe baseline CT manifestation (17 [94%] of 18 patients vs 1113 [71%] of 1572 patients), but had no significant differences in sex, other baseline symptoms, other comorbidities, or baseline severity of x-ray (appendix p 2). Most importantly, patients with cancer were observed to have a higher risk of severe events (a composite endpoint defined as the percentage of patients being admitted to the intensive care unit requiring invasive ventilation, or death) compared with patients without cancer (seven [39%] of 18 patients vs 124 [8%] of 1572 patients; Fisher's exact p=0·0003). We observed similar results when the severe events were defined both by the above objective events and physician evaluation (nine [50%] of 18 patients vs 245 [16%] of 1572 patients; Fisher's exact p=0·0008). Moreover, patients who underwent chemotherapy or surgery in the past month had a numerically higher risk (three [75%] of four patients) of clinically severe events than did those not receiving chemotherapy or surgery (six [43%] of 14 patients; figure ). These odds were further confirmed by logistic regression (odds ratio [OR] 5·34, 95% CI 1·80–16·18; p=0·0026) after adjusting for other risk factors, including age, smoking history, and other comorbidities. Cancer history represented the highest risk for severe events (appendix p 3). Among patients with cancer, older age was the only risk factor for severe events (OR 1·43, 95% CI 0·97–2·12; p=0·072). Patients with lung cancer did not have a higher probability of severe events compared with patients with other cancer types (one [20%] of five patients with lung cancer vs eight [62%] of 13 patients with other types of cancer; p=0·294). Additionally, we used a Cox regression model to evaluate the time-dependent hazards of developing severe events, and found that patients with cancer deteriorated more rapidly than those without cancer (median time to severe events 13 days [IQR 6–15] vs 43 days [20–not reached]; p<0·0001; hazard ratio 3·56, 95% CI 1·65–7·69, after adjusting for age; figure). Figure Severe events in patients without cancer, cancer survivors, and patients with cancer (A) and risks of developing severe events for patients with cancer and patients without cancer (B) ICU=intensive care unit. In this study, we analysed the risk for severe COVID-19 in patients with cancer for the first time, to our knowledge; only by nationwide analysis can we follow up patients with rare but important comorbidities, such as cancer. We found that patients with cancer might have a higher risk of COVID-19 than individuals without cancer. Additionally, we showed that patients with cancer had poorer outcomes from COVID-19, providing a timely reminder to physicians that more intensive attention should be paid to patients with cancer, in case of rapid deterioration. Therefore, we propose three major strategies for patients with cancer in this COVID-19 crisis, and in future attacks of severe infectious diseases. First, an intentional postponing of adjuvant chemotherapy or elective surgery for stable cancer should be considered in endemic areas. Second, stronger personal protection provisions should be made for patients with cancer or cancer survivors. Third, more intensive surveillance or treatment should be considered when patients with cancer are infected with SARS-CoV-2, especially in older patients or those with other comorbidities.
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              Prolonged presence of SARS-CoV-2 viral RNA in faecal samples

              We present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time RT-PCR results of all respiratory and faecal samples from patients with coronavirus disease 2019 (COVID-19) at the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China, throughout the course of their illness and obligated quarantine period. Real-time RT-PCR was used to detect COVID-19 following the recommended protocol (appendix p 1). Patients with suspected SARS-CoV-2 were confirmed after two sequential positive respiratory tract sample results. Respiratory and faecal samples were collected every 1–2 days (depending on the availability of faecal samples) until two sequential negative results were obtained. We reviewed patients' demographic information, underlying diseases, clinical indices, and treatments from their official medical records. The study was approved by the Medical Ethical Committee of The Fifth Affiliated Hospital of Sun Yat-sen University (approval number K162-1) and informed consent was obtained from participants. Notably, patients who met discharge criteria were allowed to stay in hospital for extended observation and health care. Between Jan 16 and March 15, 2020, we enrolled 98 patients. Both respiratory and faecal samples were collected from 74 (76%) patients. Faecal samples from 33 (45%) of 74 patients were negative for SARS CoV-2 RNA, while their respiratory swabs remained positive for a mean of 15·4 days (SD 6·7) from first symptom onset. Of the 41 (55%) of 74 patients with faecal samples that were positive for SARS-CoV-2 RNA, respiratory samples remained positive for SARS-CoV-2 RNA for a mean of 16·7 days (SD 6·7) and faecal samples remained positive for a mean of 27·9 days (10·7) after first symptom onset (ie, for a mean of 11·2 days [9·2] longer than for respiratory samples). The full disease course of the 41 patients with faecal samples that were positive for SARS-CoV-2 RNA is shown in the figure . Notably, patient 1 had positive faecal samples for 33 days continuously after the respiratory samples became negative, and patient 4 tested positive for SARS-CoV-2 RNA in their faecal sample for 47 days after first symptom onset (appendix pp 4–5). Figure Timeline of results from throat swabs and faecal samples through the course of disease for 41 patients with SARS-CoV-2 RNA positive faecal samples, January to March, 2020 A summary of clinical symptoms and medical treatments is shown in the appendix (pp 2–3, 6–8). The presence of gastrointestinal symptoms was not associated with faecal sample viral RNA positivity (p=0·45); disease severity was not associated with extended duration of faecal sample viral RNA positivity (p=0·60); however, antiviral treatment was positively associated with the presence of viral RNA in faecal samples (p=0·025; appendix pp 2–3). These associations should be interpreted with caution because of the possibility of confounding. Additionally, the Ct values of all three targeted genes (RdRp, N, E) in the first faecal sample that was positive for viral RNA were negatively associated with the duration of faecal viral RNA positivity (RdRp gene r= –0·34; N gene r= –0·02; and E gene r= –0·16), whereas the correlation of the Ct values with duration of faecal sample positivity was only significant for RdRp (p=0·033; N gene p=0·91; E gene p=0·33). Our data suggest the possibility of extended duration of viral shedding in faeces, for nearly 5 weeks after the patients' respiratory samples tested negative for SARS-CoV-2 RNA. Although knowledge about the viability of SARS-CoV-2 is limited, 1 the virus could remain viable in the environment for days, which could lead to faecal–oral transmission, as seen with severe acute respiratory virus CoV and Middle East respiratory syndrome CoV. 2 Therefore, routine stool sample testing with real-time RT-PCR is highly recommended after the clearance of viral RNA in a patient's respiratory samples. Strict precautions to prevent transmission should be taken for patients who are in hospital or self-quarantined if their faecal samples test positive. As with any new infectious disease, case definition evolves rapidly as knowledge of the disease accrues. Our data suggest that faecal sample positivity for SARS-CoV-2 RNA normally lags behind that of respiratory tract samples; therefore, we do not suggest the addition of testing of faecal samples to the existing diagnostic procedures for COVID-19. However, the decision on when to discontinue precautions to prevent transmission in patients who have recovered from COVID-19 is crucial for management of medical resources. We would suggest the addition of faecal testing for SARS-CoV-2. 3 Presently, the decision to discharge a patient is made if they show no relevant symptoms and at least two sequential negative results by real-time RT-PCR of sputum or respiratory tract samples collected more than 24 h apart. Here, we observed that for over half of patients, their faecal samples remained positive for SARS-CoV-2 RNA for a mean of 11·2 days after respiratory tract samples became negative for SARS-CoV-2 RNA, implying that the virus is actively replicating in the patient's gastrointestinal tract and that faecal–oral transmission could occur after viral clearance in the respiratory tract. Determining whether a virus is viable using nucleic acid detection is difficult; further research using fresh stool samples at later timepoints in patients with extended duration of faecal sample positivity is required to define transmission potential. Additionally, we found patients normally had no or very mild symptoms after respiratory tract sample results became negative (data not shown); however, asymptomatic transmission has been reported. 4 No cases of transmission via the faecal–oral route have yet been reported for SARS-CoV-2, which might suggest that infection via this route is unlikely in quarantine facilities, in hospital, or while under self-isolation. However, potential faecal–oral transmission might pose an increased risk in contained living premises such as hostels, dormitories, trains, buses, and cruise ships. Respiratory transmission is still the primary route for SARS-CoV-2 and evidence is not yet sufficient to develop practical measures for the group of patients with negative respiratory tract sample results but positive faecal samples. Further research into the viability and infectivity of SARS-CoV-2 in faeces is required.
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                Author and article information

                Contributors
                e.a.mossialos@lse.ac.uk
                Journal
                Nat Cancer
                Nat Cancer
                Nature Cancer
                Nature Publishing Group US (New York )
                2662-1347
                20 May 2020
                : 1-3
                Affiliations
                [1 ]ISNI 0000 0004 1756 7003, GRID grid.453604.0, The Health Foundation, ; London, UK
                [2 ]ISNI 0000 0001 0789 5319, GRID grid.13063.37, Department of Health Policy, , London School of Economics and Political Science, ; London, UK
                [3 ]ISNI 0000000121885934, GRID grid.5335.0, Department of Public Health and Primary Care, , University of Cambridge, ; Cambridge, UK
                [4 ]ISNI 000000041936754X, GRID grid.38142.3c, Brigham and Women’s Hospital Dana-Farber Cancer Institute, , Harvard Medical School, ; Boston, USA
                [5 ]ISNI 0000 0001 0789 5319, GRID grid.13063.37, Department of Health Policy, , London School of Economics and Political Science, ; London, UK
                [6 ]ISNI 0000 0001 2113 8111, GRID grid.7445.2, Institute of Global Health Innovation, , Imperial College London, ; London, UK
                Author information
                http://orcid.org/0000-0002-8454-4640
                http://orcid.org/0000-0003-0197-5451
                Article
                74
                10.1038/s43018-020-0074-y
                7238956
                35121972
                d8d95afa-9744-4f50-979e-2746ee6967df
                © Springer Nature America, Inc. 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

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                oncology,health services,health policy
                oncology, health services, health policy

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