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Management of Cancer Patients during COVID-19 Pandemic

ISSN UDC: M ANAGEM ENT OFCANCER PATIENTS DURING COVID-19PANDEM IC XXXX XXXX1,XXX XXXX1,2 1DepartmentofNutritionandHealth,CollegeofMedicineandHealthSciences,UnitedArabEmirates,AlAin, UnitedArabEmirates 2InstituteforHealthandSport,VictoriaUniversity,Melbourne,VIC3030,Australia ABSTRACT The world is fighting a new virus responsible for many deaths globally called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS has various stages ranging from asymptomatic supercarrier status to life-threatening respiratory failure. This virus causes coronavirus disease 2019 (COVID-19), which causes symptoms of cough, fever, and shortness of breath. In more complicated cases, it can progress to respiratory distress syndrome with the risk of septic shock. During the present COVID-19 outbreak, one of the high concerns is the effect of COVID-19 on cancer patients, which necessitates a new effective framework of cancer care. Patients with active cancer require frequent visits to hospitals or clinics to get therapeutic and diagnostic procedures, especially with more significant symptoms. So, it is essential to have COVID-19 screening and adjustment of care for this group of patients at high risk of COVID-19 infection. This review article examined the recent papers which have discussed the cancer patients in the COVID-19 pandemic regarding the risk of mortality, susceptibility to infection, cardiovascular health in cancer patients with COVID-19, and how to manage cancer patients diagnosed with COVID-19. Several papers were analyzed in this review article, along with their results. Keywords :COVID-19, SARS-CoV-2, vaccine, cancer INTRODUCTION Researchers have long hypothesized the relationship between viral infection and cancer development since the 1980s; for example, human infection with the Human Papilloma Virus (HPV) could lead to the development of genital cancer. This discovery was later proven, and its researchers won a Nobel Prize later in 2008. Chronic hepatitis B virus has been reported to cause hepatocellular carcinoma Viruses that could cause tumorigenesis are termed oncoviruses and are accountable for around 15 –20% of cancerous diseases. [4, 9, 30]. The present COVID-19 pandemic first appeared in Wuhan, China, in December 2019 and rapidly spread worldwide. SARS-CoV-2 is an enveloped single-stranded RNA virus that belongs to the subfamily of beta coronaviruses. In December 2019, it was indicated that the virus originated from bats and was transmitted to humans.[32] In contrast to previously identified SARS-related coronaviruses, such as SARS-CoV- 1 and MERS-CoV, SARS-CoV-2 is more contagious, with around 80% of infected individuals having no or only mild symptoms. In contrast, about 20% have severe symptoms that require hospital admission and intensive care unit (ICU) support [9]. It is hypothesized that those with severe symptoms usually have hyper-immune responses, although age and comorbidities, such as MANAGEMENTOFCANCERPATIENTSDURINGCOVID-19PANDEMIC diabetes, cardiovascular disease, and cancer, are associated with poorer outcomes [9,31]. One of the most susceptible groups of the pandemic is cancer patients, as they are severely immunocompromised due to their cancer and the associated treatments (radiation, chemotherapy, steroids, and surgery). Cancer patients rely heavily on the availability of medical resources, making them vulnerable to the impact of the pandemic. Additionally, they have an increased risk of COVID-19 because of their need to have regularly scheduled visits to the hospital, which further increases their risk of contact with infected individuals. Cancer survivors and cancer patients with active anticancer treatment have ahigh risk of admission to ICU, intubation, and death. Hence, cancer patients must deal with the double sword of cancer and COVID-19, increasing their anxiety and confusion. Still, there are many unsolved questions regarding the appropriate care for this group of patients, and oncologists are facing a significant challenge on how to protect their patients with cancer from infection while maintaining routine patient care [1, 15, 21, 27]. METHODOLOGY This research is based on a secondary research strategy. Secondary research is done to collect qualitative data to analyze already published literature. This methodology has benefits as it is cost-effective, saves time, and helps manage the enormous scope of data that would otherwise be complex for the researcher to collect by doing primary research. Additionally, the data collected is trustworthy. A site has been taken from reliable and professional researchers. The review was conducted according to PRISMA guidelines. The most convenient method of gathering secondary data is by using the internet and searching required and relevant data from acknowledged databases. The current research was conducted using the databases of PUBMED; EMBASE, CINAHL, SCOPUS, web of science, and Google Scholar. The search on these databases was refined by using keywords. The keywords used for the current research are COVID-19, SARS-CoV-2, vaccine, and cancer. Only recent articles were chosen, especially those that were published in the English language. The search was completed on April 2, 2021. Studies from all years were included, and the search terms used were XYZ. DEVELOPMENT OF CANCER AND RISK OF MORTALITY IN CANCER PATIENTS WITH COVID-19 The world is dealing with anew severe acute respiratory syndrome, coronavirus 2(SARS- CoV-2), that has caused multiple deaths globally. SARS has alarge diversity of stages ranging from being an asymptomatic supercarrier to life- threatening respiratory failure. This virus has caused coronavirus disease 2019 (COVID-19), with reported symptoms of cough, fever, and shortness of breath. In much more complicated cases, itcan even lead to respiratory distress syndrome with the risk of septic shock. During the current outbreak of COVID-19, one of the highest concerns is the impact of COVID-19 on cancer patients as ithas made the situation severe for them, and their death toll has increased. Geisslinger et al. (2020) discussed how inflammation could cause cancer. Inflammation is anatural physiological process in the human body that protects the body from external pathogens by activation of innate and adaptive immunity. Cancer is believed to be caused by chronic inflammation within the same tissue before the formation of a tumor. This unresolved inflammation can lead to excessive reactive oxygen species (ROS) to kill the infected cells, but ROS also affects the healthy host cells, which results in DNA mutations [9]. Inflammation is followed mainly by tissue remodeling resulting in fibrosis accompanied by tumourigenesis developing lung cancer and hepatocellular carcinoma [15]. Patients infected with COVID-19 have elevated levels of cytokines involved in the growth and the spread of cancer. Thus SARS-CoV-2 infection might have the potential to develop carcinogenic inflammations. It is unclear whether inflammation-induced due to COVID-19 will be long-lasting, leading to chronic inflammation. A pilot study of amale patient aged 72 years old who died from complications of COVID-19 found that his postmortem biopsy via transthoracic needle showed diffuse alveolar damage with loose fibrous plugs. Similar to this case study, an additional analysis of seven patients who died from SARS- CoV-1 infection showed diffuse alveolar damage with mild to moderate fibrosis present in the lung. So, these findings indicated that excessive and MANAGEMENTOFCANCERPATIENTSDURINGCOVID-19PANDEMIC persisting inflammation from viral infections could favor fibrotic lesions, increasing the risk of developing tumors with time. [9, 16] Cavanna et al. (2020) confirmed the mortality risk in cancer patients with COVID-19. The research was based on the medical data of 51 patients with different types of cancers infected with COVID-19 in the hospital from April 4 to May 4, 2020, to report their clinical characteristics and outcome. A registered 25 patients died from treatment for COVID-19. These deceased patients had comorbidities along with cancer, which may play arole in the prognosis of cancer patients with COVID, such as hypertension, diabetes, and chronic obstructive pulmonary disease. Of the admitted 51 patients, 40 had asevere illness, and 31 had comorbidities. Further, it was noted that anticancer treatments within 14 days of COVID-19 infection, such as immunotherapy, chemotherapy, and radiation, were a predictor of death. Laboratory findings showed that C-reactive protein (CRP) and serum lactate dehydrogenase values were significantly higher in patients who died (these biochemical markers are linked to active cancers and are diagnostic of complicated infections) [2, 25, 19] Cavanna et al. (2020) enrolled fifty-one cancer patients from the 973 COVID-19 cases who were admitted to different hospitals between April 4, 2020, and May 4, 2020. Forty-five patients received treatment for COVID-19; 29 received darunavir plus cobicistat and hydroxychloroquine; 10 received lopinavir plus ritonavir and hydroxychloroquine, 6 received hydroxychloroquine alone, and six did not receive anti-COVID-19 therapy. No medication was administered to some because 5of them worsened quickly after hospital admission and died within three days of access. One patient with mild/moderate symptoms of COVID-19 received only supportive therapy. It is postulated that the hazard of death was higher in patients who started treatment more than five days after the onset of symptoms and lower in patients with mild/moderate type of COVID-19 compared with patients with severe/critical type [2]. INDIVIDUALS WITH CANCER ARE MORE SUSCEPTIBLE TO INFECTION Barba et al. (2020) highlighted the recent evidence regarding managing cancer patients during the COVID-19 pandemic and the applicable framework for cancer patient care [1]. Liang hypothesized ahigher risk of COVID-19 in cancer patients than those without cancer as they did a case series of 2,007 COVID-19 cases from 575 hospitals throughout China up to January 31, 2020 [15]. The ratio between the number of COVID-19 patients with cancer and the total number of COVID-19 patients, i.e., 18/1,590, as compared to the incidence of cancer in the China population according to the 2015 report, i.e., 283.83/100,0000 persons/year. Of those 18 cancer patients with COVID-19, detailed data was available only for 14 cancer patients. Extreme caution should be taken concerning the postponement of adjuvant chemotherapy or elective surgery for stable cancer in COVID-19 pandemic areas, which can worsen the patient outcomes [1]. In addition, cancer patients with more severe clinical symptoms were exposed to more chances to visit health facilities and get testing, which increased their risk of SARS-CoV-2 infection, mainly if they exhibited comorbidities. [1] DeRosier (2020) emphasized that the Black race was independently correlated with higher probabilities of hospitalization for COVID-19 compared to white race patients with cancer after the results of a single-center study. He evaluated the effect of race on hospitalization among cancer patients. They recorded 557 patients with cancer from electronic health records who caught COVID-19 between March 1 to June 10. They retrieved patient data, including cancer type and treatment, demographics, and noncancer comorbidities. Among these 557 patients, 325 were female, 79 were Black, and 225 had two or more comorbidities. Before COVID-19 testing, 47 of these 325 patients had obtained any systemic cancer treatment in the last 30 days. Among those 96 patients who required in-patient hospital visits, 18 were black, and among 56 patients who visited the ED, 15 of them were black. It was concluded that there is an association between the Black race with ahigher rate of hospitalization among cancer patients [4] Sinha et al., 2021 noted that cancer patients who are still receiving oncologic therapies, for instance, any targeted therapy or chemotherapy in the last 14 days, developed more severe events. This resulted in a mortality rate of 28.6%. In a viable strategy aimed at reducing the risks of infections, immunization has been adopted for high-risk patients. It is estimated that 20%-30% of MANAGEMENTOFCANCERPATIENTSDURINGCOVID-19PANDEMIC SARS and 50% to 89% of cancer patients with MERS require ICU hospitalization. [39,40] THE EFFECTS OF COVID-19 IN THE CARDIOVASCULAR HEALTH OF CANCER PATIENTS Lenihan et al. (2020) published the cardio- oncology care in the era of the COVID-19 pandemic to review the appropriate utilization of cardio-oncology (C-O) care during COVID-19 as he created afigure that demonstrated an overview of a cancer patient setting regarding changes in medical practice during COVID-19 pandemic. This cardio-oncology care includes proper preparation, modified workflow execution, and excellent care maintenance. Elderly individuals with comorbidities such as cardiovascular (CV) risk factors, established CV disease (CVD), and cancer are at the highest risk for morbidity and mortality if they get SARS –CoV-2. But patients with cancer and CVD will be at the highest risk from SARS –CoV-2 [14]. International Cardio- Oncology Society (2019) recommended general guidance on cardiac safety among cancer patients that is useful for cardiologists, hematologists, and oncologists during and after the COVID-19 pandemic. SARS – CoV-2 may be considered not only arespiratory virus but also aCV virus, which can lead to severe acute lung and CV injury. A study paper published by Guo et al. (2019) confirmed that 27.8% of patients with SARS – CoV-2 had a myocardial injury identified by elevated troponin levels, 20% had arrhythmias, and 16% needed hemodynamic support. High levels of cardiac troponin are an indication of worse outcomes. Also, elevated troponin levels are correlated with increased C-reactive protein levels and exaggerated inflammatory response. [33] It is postulated that exaggerated inflammatory response is one of the critical mechanisms in cardiac dysfunction. Besides exaggerated inflammatory response, there are other potential mechanisms for cardiac dysfunction with COVID-19 that include thrombosis, myocarditis, acute coronary syndrome, and microvascular dysfunction. Angiotensin- converting enzyme-2 receptor (ACE2) is acellular receptor that gives way to viral entry into the human body. This receptor is expressed on lung epithelial cells, vascular endothelial cells, pericytes, cardiomyocytes, and macrophages. SARS –CoV-2 has an outstanding thrombotic feature that causes arterial and venous thrombosis, including pulmonary thrombosis, infarction, and acute lung injury. The mechanism behind this is suggested to be a relation between inflammation markers (interleukin-6), troponin (myocardial injury), and D-dimer (thrombosis/fibrinolysis) to identify patients who suffer from CV consequences. [14, 24] Palaskas (2020) discussed COVID-19 and cardiovascular health among patients with cancer. He summarized in his review the existing evidence of the exposure of patients with cancer and cardiovascular on the effects of the COVID-19 pandemic. Recent studies showed that patients with risk factors of cancer and CV disease are more expected to develop COVID-19 and can have amore severe form of COVID-19. An initial study published in China that included 138 hospitalized patients with COVID-19 reported that 31.1% had a baseline diagnosis of hypertension, whereas 14.1% had abaseline diagnosis of cardiovascular disease. In addition, ICU care was more likely needed in patients with baseline hypertension, diabetes, cardiovascular or cerebrovascular disease. Similar to these results, another meta-analysis of 6studies by Li et al. included 1527 patients. The most common comorbidity in patients infected with COVID-19 is hypertension, found in 17.1% of patients, followed by cardio-cerebrovascular disease at 16.4%, and diabetes in 9.7%. These findings were supported by a cohort study that emphasized an association of increased mortality from COVID-19 infected patients with those with a history of hypertension and cardiovascular disease in alarge multicenter study from the USA, Canada, and Spain, which comprised 928 cancer patients with COVID-19, it is stated that independent factors linked with death from COVID-19 included age, male gender, smoking status, and several comorbidities. [17, 11] Gupta et al., 2021, noted that patients more susceptible to COVID-19 had increased severity of the disease, especially those with cancer and cardiovascular condition. Cardiovascular complications of COVID 19 overlap those encountered during cancer treatment. The study noted that the incidence of cardiovascular complications among patients with COVID 19 increased. This implies monitoring the administration of chemotherapy, diagnosis, and treatment of the disease during the COVID-19.[36, 37] MANAGEMENTOFCANCERPATIENTSDURINGCOVID-19PANDEMIC Some of the main recommendations for cancer patients in this group are to be protected as much as possible from infection risks, especially those from SARS –CoV-19, by applying proper hygiene standards in the health care system, for instance, appropriate hand washing, cleaning of clinical examination instruments and cleaning of examination rooms. In addition, wearing amask is recommended during the risk of high virus spread and exposure to a viral pandemic, along with maximizing personal protection equipment (PPE) for health care professionals, including N95 masks, gowns, gloves, and eye protection. Also, proper physical distancing is always recommended by limiting close contact for those needing clinical testing, physical examination, and echocardiography. [14, 22] CANCER PATIENTS DURING THE COVID-19 PANDEMIC Sahu et al. (2020) provided a basic guideline for managing cancer patients during this COVID-19 pandemic. Prostate, breast, lung, and colorectal tumors are most common among cancer patients in contrast to other malignancies. Cancer patients are exposed to a higher risk of adverse events, for example, the requirement for mechanical ventilation and intensive care unit that can end in death. So, one of the strategies in managing cancer patients during COVID-19 is through telemedicine, where these patient groups can stay indoors and get counseling about any medical concerns. In case the patient is entirely asymptomatic, any laboratory testing and imaging should be postponed, but in symptomatic patients or have disease recurrence, in this case, physicians can use their clinical judgment with consideration to comorbidities, tumor biology, and patient preferences. Although telemedicine can produce additional anxiety for those newly diagnosed with cancer, as they are still uncertain of the type of cancer, prognosis, stage, treatment options, etc., they should balance with the high risk of exposure to COVID-19 [21]. One of the questions is whether to delay chemotherapeutic treatment or continue it, especially in patients with non-metastatic cancers. According to a study done by Liang et al., he suggested that high-risk cancer patients are those who had undergone cancer surgery or chemotherapy before one month in contrast to those who did not have. For those who have stable cancer, Liang suggested that adjuvant chemotherapy or surgery should be a postponement in endemic areas. However, another study published by Zhang et al. not recommend the delay of adjuvant cancer chemotherapy to minimize infection risk in the ongoing pandemic, as they observed that some patients caught COVID-19 infection while receiving chemotherapy at infusion centers. So, Zhang et al. concluded the continuation of chemotherapy for early stages of cancer as the patients are immunocompromised with extreme measures to prevent transmission of COVID-19 infection. In case patients are suspected of any signs of active disease, chemotherapy should be postponed, and proper quarantine should be maintained. In addition, they should be kept in an isolation ward or at-home isolation for at least seven days. [21, 26] In addition, Peng et al. (2020) discussed continuing or stopping anticancer therapy in patients who have confirmed COVID-19 infection. The concern is that infected cancer patients with COVID-19 are at high risk of progressing to severe forms of COVID-19 that require hospital admission, especially if the condition occurs during chemotherapy-induced neutropenia. Also, monitoring oxygen saturations should be offered. It is suggested that cancer treatment should not stop, considering patients with cancer who have HIV1 or hepatitis B; the virus does not re-activate during chemotherapy. [18] Sahu et al. (2020) reviewed the primary guideline for managing cancer patients during this COVID-19 pandemic. He mentioned immune checkpoint inhibitors (ICIs) used in advanced cancer treatment. I aim to enhance the immune system to fight against cancer cells. So, it is said that as it enhances the immune system, this immune modulation will also benefit fighting against COVID-19 disease. However, there is still no current clinical data available on this matter. Additionally, non-urgent surgery for cancer patients should be postponed, like bone marrow transplants (BMT) for multiple myeloma patients; because travel restrictions and donor infection accompany this COID-19 pandemic, bone marrow donors are limited. [21, 20] COVID-19 VACCINE IN CANCER PATIENTS COVID-19 in cancer patients has made the situation worse for them, necessitating anew MANAGEMENTOFCANCERPATIENTSDURINGCOVID-19PANDEMIC practical framework of cancer care. Patients with active cancer require frequent visits to hospitals or clinics to get therapeutic and diagnostic procedures, especially with more significant symptoms. So, it is essential to have COVID-19 screening and adjustment of care for this group of patients at high risk of COVID-19 infection. The reports regarding the efficacy of COVID-19 vaccines have resulted in their emergency approval and utilization. Multiple trials of COVID-19 vaccines did not include patients who have active malignancies. Thus, data regarding the vaccines' tolerability, efficacy, and safety in cancer patients is currently limited. Due to the risks posed by this COVID-19 pandemic, decisions about the use of covid-19 vaccines in patients who participate in trial therapies for investigational anticancer must be addressed immediately. Cancer patients must not be confused regarding enrolling in oncology trials and receiving aCOVID-19 vaccine. Investigators, sponsors of clinical trials, and treating physicians require operational guidance on vaccination for COVID-19 to cancer patients who have been or are seeking to get enrolled in clinical trials. Considering the mortality and high morbidity rate from COVID-19 in cancer patients, the benefits of COVID-19 vaccines are expected to compensate for the risks of adverse events that happen due to its vaccination. Desai et al. (2021) reported that continued quality for oncological care needs that cancer patients, including those who participate in trials, must be given priority for COVID-19 vaccination, and this must not have any influence on their eligibility for trials [6]. CONCLUSION AND FUTURE PROSPECTS The COVID-19 outbreak is amajor global public health pandemic and can have disastrous consequences for cancer patients. Oncologists and care providers for cancer patients must also protect patients and their caregivers from excessive exposure, considering that mortality from COVID- 19 is more significant in cancer patients than in patients without cancer. Generally, additional research is significantly required to understand SARS-CoV-2 pathogenesis and develop vaccines and therapies. Furthermore, the current available SARS-CoV-2 studies are insufficient and should be interpreted cautiously, and more extensive cohort studies are needed. 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