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      COVID-19 Infection in Cancer Patients: How Can Oncologists Deal With These Patients?

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          Abstract

          The world is facing a new pandemic caused by a novel beta coronavirus (COVID 19), which causes severe respiratory coronavirus syndrome (SARS-CoV-2). Unfortunately, there are currently no US Food and Drug Administration (FDA) approved medications for the treatment of COVID-19 patients. High mortality rates in frail patients is a notable feature of the virus registered since the onset of COVID-19 pandemic. Above all, elderly patients or those with underlying chronic illnesses and compromised immune system are most at risk (1). Thus, the consideration is that the possible coexistence, in the same individual, of a cancer diagnosis and a COVID-19 infection could generate a synergistic negative prognostic effect. About the prevalence, the only available data are reported in a retrospective study on 1,590 COVID-19 patients from 575 Chinese hospitals, wherein 1% of them had a history of malignancy (2). Among cancer patients, 25% of them had recently received chemotherapy or surgical treatment, while the others were in follow-up. Multivariate analysis showed that a history of cancer was associated with a higher risk of serious/negative events (OR = 5.399, P = 0.003), with a median time in their development of 13 vs. 43 days in non-cancer patients (P < 0.0001; hazard ratio = 3.56, 95% confidence interval = 1.65–7.69). Therefore, the diagnosis of cancer was shown to be an important comorbidity associated with a higher rate of intensive care admissions. Several questions still remain unanswered in this scenario: (1) Do routine screening programs need to continue as usual? (2) What should be the correct management for a positive COVID-19 patient before or after a cycle of chemotherapy, immunotherapy, and/or targeted therapy? (3) What policies are being adopted in every single country to manage oncology departments? (4) How should fragile patients with the advanced disease be treated when they are in areas heavily affected by the virus? (5) What are the ethical and practical implications? In other words, how can oncologists deal with these patients? Can we find these answers by analyzing the data available in the literature? Unfortunately, it is not possible. At present, the follow-up period from the moment of the COVID-19 pandemic onset is too short to reach definitive conclusions. According to recent American Cancer Society guidelines for cancer patients during the COVID-19 pandemic, screening programs should be delayed (3). It should appear to be a reasonable choice during this COVID-19 crisis period to carry out a risk/benefit balance in every patient evaluation, especially when the potential benefit of an oncological intervention in terms of cancer recurrence/overall survival is so small that it doesn't counterbalance the potential risk of death from COVID-19. Certainly, triage by telephone with the possible identification of symptomatic patients and at the entrance of hospital structures with the monitoring of body temperature and saturation could reduce the probability for health personnel and for the patients themselves to be exposed to the risk of contagion. Cancer thoracic/abdominal surgery sometimes requires recovery in intensive care units. How should these needs be managed need in emergency situations? On the other hand, the risk is that a localized disease may become metastatic over time. Patients in treatment for neoadjuvant/adjuvant treatments should continue their treatments, and, if it is possible should also receive longer intervals between a cycle, longer treatments, and the avoiding of weekly infusions, considering every specific drug schedule. For advanced cancer patients, it should be decided on a case-by-case basis, taking into consideration the relationship between health risks and benefits, whether to delay or suspend ongoing treatments for a period, miming the already known “drug holiday.” So, the considerable risk is that patients will survive COVID-19, but then endanger their lives due to the absence of sufficient cancer care. Last but not least, the alterations in the mood of these patients cannot be underestimated, just like this aspect cannot be underestimated among clinicians and paramedics working in oncology departments. The follow up of patients without evidence of recurrence should be postponed or carried out through “remote visits,” through telephone, email, or other telemedicine tools, reserving the possibility to access the cancer center only in selected cases. It should not be suggested that accompanying persons/family members/caregivers of cancer patients should stay in waiting rooms, or should access rooms where anti-cancer therapy and outpatient clinics are administered. It is advisable to avoid visits to patients during their hospitalization, only suggesting the presence of a single family member/companion, after specific authorization, only for a limited time. As mentioned above, particular attention should be reserved for older cancer patients, due to their comorbidities. And what is to be decided regarding oncological research? Cancer Research UK proposes to stop recruiting patients in several clinical trials with two aims: to reduce patient overflow and to dedicate time and financial resources to patients affected by COVID-19 looking for clinical research treatment (4). More recently, based on a consensus of experts, ASCO (5) recommended several suggestions including the use of proper hand washing, hygiene, and minimizing exposure to sick contacts with the use of masks for patients, indicating a comprehensive evaluation in those with fever or respiratory symptoms. Moreover, ASCO did not make a recommendation with respect to COVID-19 testing in patients with cancer. Regarding cancer patients affected by COVID-19, treatment should not be reinitiated until symptoms of COVID-19 have resolved. Regarding all cancer patients, maintenance chemotherapy may be stopped, if possible intravenous chemotherapy should be orally administrated less frequently at clinics, and decisions on chemotherapy treatments should consider the aim of care evaluating the risk/benefit assessment. Regarding adjuvant treatments, delays or modifying main treatments may compromise disease control and long-term survival. In an international position paper, several experts have published some suggestions on the treatment of cancer patients in the COVID-19 era (6). In particular, as ASCO experts, these authors recommended a clear communication and education about hand hygiene, infection control measures, high-risk exposure, and the signs and symptoms of COVID-19. They recommended a strong consideration of the new risk/benefit balance for active intervention, postponing elective surgery, or chemotherapy with low risk of progression analyzing each patient's case. Another topic of interest should be the future after the Covid-19 crisis ends. Even if the grip of the pandemic loosens, the SARS-CoV-2 could infect other people, especially more brittle patients, such as cancer ones. The return to a normal style of life must be gradual. But for these patients, can it ever be? We will probably have to wait for a vaccine against this virus, as for the flu, with the aim to better protect the health of these patients. It's a challenging and stressful time for cancer patients under the situation of the worldwide COVID-19 pandemic. In a period of social distancing, cancer patients excluded from outpatient and hospital flows should be brought closer to oncologists through the multimedia means of communication and it should deepen the new chapter of telemedicine. A focus should be placed on the delivery of health-related services and information via media/electronic information. It should allow for oncologists to contact all patients that cannot go to the hospital for monitoring on their health status and suggest care when possible. So far, telemedicine would be considered as a strong ligand between patients and oncologists which could guarantee the continuum of care and follow them without losing clinical and human contact. Can we maintain the survival standard by limiting access and therapies? Could we affect the overall quality of life? Or on the contrary, by continuing to administer the same treatment, could we facilitate the spread of the epidemic among these patients by limiting their survival? We believe it is an ethical and moral duty not to abandon these patients in their physical and psychological weakness at this particular historical moment. It remains the task of all investigators to collect data that can be observed, in particular in regards to the possible correlation between immunosuppression and the course of the disease, considering the recent initial evidence of immunosuppressive treatment activities in COVID-19 patients affected by lung complications. Last but not least, individual protection measures for all healthcare professionals are clearly essential in order to protect their health as well as that of their patients and family members. Probably, this international crisis will lead us to reconsider the Ars Medica, which aims to identify the right patient balance between cancer under-treatment and its increase in cancer-related mortality and active cancer treatments potentially linked to a greater risk of death from COVID-19 complications. Author Contributions OB and NS concepted the study. AD, BB, AG, and AR developed the study. Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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          Most cited references3

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          A Novel Coronavirus from Patients with Pneumonia in China, 2019

          Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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            A Practical Approach to the Management of Cancer Patients During the Novel Coronavirus Disease 2019 ( COVID ‐19) Pandemic: An International Collaborative Group

            Abstract The outbreak of coronavirus disease 2019 (COVID‐19) has rapidly spread globally since being identified as a public health emergency of major international concern and has now been declared a pandemic by the World Health Organization (WHO). In December 2019, an outbreak of atypical pneumonia, known as COVID‐19, was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), is characterized by rapid human‐to‐human transmission. Many cancer patients frequently visit the hospital for treatment and disease surveillance. They may be immunocompromised due to the underlying malignancy or anticancer therapy and are at higher risk of developing infections. Several factors increase the risk of infection, and cancer patients commonly have multiple risk factors. Cancer patients appear to have an estimated twofold increased risk of contracting SARS‐CoV‐2 than the general population. With the WHO declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such a pandemic on cancer patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the management of cancer patients in any infectious pandemic. In this review, the potential challenges associated with managing cancer patients during the COVID‐19 infection pandemic will be addressed, with suggestions of some practical approaches. Implications for Practice The main management strategies for treating cancer patients during the COVID‐19 epidemic include clear communication and education about hand hygiene, infection control measures, high‐risk exposure, and the signs and symptoms of COVID‐19. Consideration of risk and benefit for active intervention in the cancer population must be individualized. Postponing elective surgery or adjuvant chemotherapy for cancer patients with low risk of progression should be considered on a case‐by‐case basis. Minimizing outpatient visits can help to mitigate exposure and possible further transmission. Telemedicine may be used to support patients to minimize number of visits and risk of exposure. More research is needed to better understand SARS‐CoV‐2 virology and epidemiology.
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              SARS-CoV-2 is an appropriate name for the new coronavirus

              We have read with great interest the Correspondence by Shibo Jiang and colleagues, 1 in which they propose a name change for the newly emerged coronavirus, 2 which was recently designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses. 3 The authors argued that the use of SARS in the virus name could confuse the public about the disease that it causes; in addition, they noted that the name SARS-CoV-2 is not consistent with the disease name chosen by WHO, coronavirus disease 2019. The authors also indicated that scientifically, SARS-CoV-2 is naturally occurring and different from other SARS-like or SARS-related coronaviruses that are mainly characterised by their genome sequences. Furthermore, given the probability of future attenuation of this virus to a low-pathogenic form, the authors predict that the use of the name SARS-CoV-2 might have adverse effects, both socially and economically. On these grounds, the authors suggest that the name of the new virus is changed to human coronavirus 2019 (HCoV-19). Although these concerns and suggestions are appreciated, we feel that the adoption of SARS-CoV-2 by the Coronavirus Study Group was appropriate. To facilitate good practice and scientific exchange, the International Committee on Taxonomy of Viruses has established standardised formats for classifying viruses. Under these rules, a newly emerged virus is normally assigned to a species based on phylogeny and taxonomy. 4 Through DivErsity pArtitioning by hieRarchical Clustering-based analyses, 5 the newly emerged coronavirus was deemed not sufficiently novel but is a sister virus to SARS-CoV, the primary viral isolate defining the species. The SARS-CoV species includes viruses such as SARS-CoV, SARS-CoV_PC4-227, and SARSr-CoV-btKY72. SARS-CoV-2 is the newest member of this viral species. The use of SARS in naming SARS-CoV-2 does not derive from the name of the SARS disease but is a natural extension of the taxonomic practice for viruses in the SARS species. The use of SARS for viruses in this species mainly refers to their taxonomic relationship to the founding virus of this species, SARS-CoV. In other words, viruses in this species can be named SARS regardless of whether or not they cause SARS-like diseases. The relationship between the name of a viral pathogen and its associated diseases is complex. Although the International Committee on Taxonomy of Viruses is responsible for naming viral species, WHO is responsible for naming the diseases caused by newly emerging viruses. For various reasons, the name of a disease and its causative viral pathogen can be different, as exemplified by acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV). We also believe that the use of the name SARS-CoV-2 will not affect social stability and economic development in the affected countries, as the authors envision. Given that the cross-species transmission of SARS-CoV-2 is currently not well understood, and no effective approach to stop such zoonotic transmission has been established, SARS-related coronaviruses, such as SARS-CoV-2 (or even SARS-CoV-3 in the future), might continue to emerge and re-emerge. This has been exemplified in the transmission of Middle East respiratory syndrome-related coronavirus, in which multiple spillover events occurred from camels to humans, resulting in human infections. 6 Thus, keeping SARS in the names of viruses of that species would be beneficial to keep the general public vigilant and prepared to respond quickly in the event of a new viral emergence. Should SARS-CoV-2 be significantly attenuated to the point of becoming a new low-pathogenic or non-pathogenic virus, such attenuated viral isolates could be named as low-pathogenic human coronaviruses, such as LPH-CoV. We believe that the naming of SARS-CoV-2 by the Coronavirus Study Group is aligned with the goals of the International Committee on Taxonomy of Viruses to facilitate good practice and scientific exchange. Given that SARS-CoV-2 is already being used in the scientific literature, a name change at this stage would cause confusion in the scientific community. With all the uncertainties about this newly emerged pathogenic virus, we suggest keeping SARS-CoV-2 as its name.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                23 April 2020
                2020
                : 10
                : 734
                Affiliations
                [1] 1Medical Oncology Unit IRCCS Istituto Tumori “Giovanni Paolo II” of Bari, University of Bari “Aldo Moro” , Bari, Italy
                [2] 2Immunology Research Center, Tabriz University of Medical Sciences , Tabriz, Iran
                [3] 3Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo , Palermo, Italy
                [4] 4Department of Biomedical Sciences and Medical Oncology, University of Bari , Bari, Italy
                Author notes

                Edited by: Hussain Gadelkarim Ahmed, University of Hail, Saudi Arabia

                Reviewed by: Ibrahim Abdelmageed Ginawi, Ministry of Health, Saudi Arabia; Hao Liu, Southern Medical University, China; Ahmed Abdalla Agab Eldour, Kordofan University, South Sudan

                *Correspondence: Nicola Silvestris nicola.silvestris@ 123456uniba.it

                This article was submitted to Cancer Epidemiology and Prevention, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2020.00734
                7190805
                32391283
                d599c890-0b71-4a23-8137-b9fe7bab8fa4
                Copyright © 2020 Brunetti, Derakhshani, Baradaran, Galvano, Russo and Silvestris.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 23 March 2020
                : 17 April 2020
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 6, Pages: 3, Words: 1907
                Categories
                Oncology
                Opinion

                Oncology & Radiotherapy
                covid-19,cancer,therapy,screening,prognosis
                Oncology & Radiotherapy
                covid-19, cancer, therapy, screening, prognosis

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