key: cord-0934673-d74d3ai8 authors: Ramani, Vinod K.; Naik, Radheshyam title: A narrative review of the pathophysiology of COVID‐19 infection among cancer patients: Current evidence and research perspectives date: 2021-01-26 journal: Health Sci Rep DOI: 10.1002/hsr2.237 sha: c8a5908916bad4274cd68cbfdc8d556620a5f774 doc_id: 934673 cord_uid: d74d3ai8 INTRODUCTION: The mechanism by which a suppressed immune system of a cancer patient makes them susceptible to COVID‐19 is still unclear. Any delay or discontinuation of cancer care due to the pandemic is expected to have a detrimental impact on the outcome of cancer. A few studies have addressed the incidence of COVID‐19 among cancer patients, but the small sample size of such studies makes it difficult to draw inference to the general population. METHODS: For our review, ‘Pubmed’ database and Google search engines were used for searching the relevant articles. The criterion used for review includes their relevance to the defined review question, which is the pathophysiological mechanism of COVID‐19 among cancer patients and the relevant therapeutic interventions therewith. This review includes 20 studies and other relevant literature which address the determinants of COVID‐19 among Cancer patients. RESULTS: Delay in cancer diagnosis will increase the stage progression of cancer patients and increased mortality in the future. A short delay in administering cancer related treatment to aid the odds of patient surviving the acute SARS‐CoV‐2 infection, should be at the discretion of the treating Physician. Oncologists dilemma in the current situation includes titrating the density of drug doses and intensity of treatment regimen, for the optimal management of metastatic and adjuvant cancer patients. Patients are thus subjected to suboptimal treatment and undetected disease recurrence, To circumvent the immunosuppressive effects of chemotherapy, Providers need to consider staggered regimen or alternate therapies such as biological/immunotherapy, targeted therapy, anti‐angiogenic drugs, hormone therapy and/or antibody‐based therapeutics. CONCLUSION: This review provides insights on the pathogenesis of SARS‐CoV‐2, which could enable Physicians in formulating therapeutic strategies for the management of severe patients, more so in Oncology settings, thus reducing the mortality. The key is to balance the continuation of urgent cancer care, but rationing the elective treatment according to the circumstances. pared with the general population, due to their systemic immunosuppressive state caused by the malignancy and anticancer treatment. This could be the reason for the poor prognosis of such patients infected with COVID-19. However, smoking could increase the gene expression of angiotensin-converting enzyme 2 (ACE 2) and confound this association as a risk factor. 5 Multidisciplinary teams involved with cancer care are expected to customize the regimen as per each patient's health condition, either continuing urgent or rationing other treatment. 6 During the earlier coronavirus epidemics such as severe acute respiratory syndrome (SARS) and middle-east respiratory syndrome (MERS), deaths were due to respiratory failure unlike with COVID-19, which results in multiple organ dysfunction. 5 During 2015, the MERS epidemic resulted in a mortality rate of 84% among tumor affected subjects, which was twice that in non-oncology subjects. 7 The protracted influenza A virus subtype, H1N1 epidemic, during 2009 resulted in a 18.5% higher mortality among cancer subjects. Tumors are connected with an increased expression of immunosuppressive cytokines, augmented functional immunosuppressive leukocyte population, and decreased proinflammatory danger signals, which may dampen the immune system and augment the probability of infectious complications. 7 The SARS-CoV-2 interacts with the ACE2 functional receptor and TMPRSS2, which is a serine protease, widely distributed in multiple organs. The varying risk of infection, stroke, hypertension, or diabetes among different ethnic groups is due to the varied ACE2 gene polymorphisms. Given the correlation between ACE2 receptor density and COVID-19 uptake in human cells, its differential analyses could differentiate the clinical outcomes and severity of the patients' symptoms. The elevated susceptibility to COVID-19 among smokers is due to the increased gene expression of ACE2 induced by tobacco. Antihypertensives, such as ACE inhibitors, tend to promote the greater expression of ACE2 in the heart and lungs, and such patients may have a higher risk of COVID-19 infection when compared to the others. 8 The initial evidence from China regarding the extrapulmonary effects of SARS-CoV-2 among humans shows that 12% of patients without underlying cardiovascular disease experienced heart damage. The laboratory result of such patients shows increased levels of cardiac troponin and D-dimer, or episode of cardiac arrest during hospitalization for COVID-19. The multiorgan failure (including myocarditis, venous thromboembolism, and acute respiratory distress syndrome [ARDS] ) and consequent death could be the result of secondary hemophagocytic lymphohistiocytosis (sHLH). This multiorgan hyperinflammatory condition is due to the hyperactivation of cytotoxic T lymphocytes, macrophages, and natural killer cells. 8 This review 8 Cancer patients are at risk of viral infection and the magnitude of effect depends on the type of cancer, recent sessions of chemotherapy, radiotherapy or surgical interventions, and presence of comorbidities (diabetes, cardiovascular disease, and metabolic syndrome). This review provides insights to the pathogenesis of SARS-CoV-2, which will enable the physician to formulate therapeutic strategies for management of severe patients, more so in oncology settings for reducing the mortality. In Zheng et al's 12 include fatigue, fever, dry cough, dyspnea, along with blood profile changes such as lymphopenia, and high levels of highly sensitive Creactive protein. 3 The authors assess the frequent manifestation of anemia and hypoproteinemia among cancer patients, due to their nutritional deterioration that might adversely affect their immune competence and increase their susceptibility to respiratory pathogens. This study reports that lung cancer patients with COVID-19 are likely to develop severe anoxia and progress more rapidly, possibly due to their worse baseline lung function and endurance. We could thus infer that there is an increased need to treat cancer patients infected with COVID-19, with special emphasis on lung cancer patients. However, the studies by Liang et al, 5 Yu et al, 11 and Zheng et al 12 are affected either by the retrospective nature of evidence, small sample size, and limited duration of follow-up. 19 21 These issues mandate the need for conducting either an age-stratified analysis or an age-gender paired analysis. Xu et al's 12 patients is lymphopenia, which, in turn, has an impact on disease severity and mortality. The computerized tomography (CT) imaging findings of COVID-19 infection are characterized by ground-glass opacity and patchy con- In this context, we need to assess the attenuation role of PAR The reprioritization of healthcare services due to the COVID-19 pandemic has affected the screening and diagnosis of cancer. The inherent fear of contracting this contagious pathogen from a healthcare facility dissuades patients/beneficiaries from accessing cancer care. The combination of perceived risk (for clinicians and patients) and redeployment of staff will result in diagnostic delays, which could affect survival. Delay in diagnosis will increase the stage progression of cancer patients, and increased mortality in the future. Once the pandemic has passed its peak, this inaccessibility might cause a surge in demand for cancer-related services. The need-of-the-hour is provi- Any delay or discontinuation of cancer care due to the pandemic could have a detrimental impact on the outcome of cancer. The key is to balance the continuation of urgent cancer care, but rationing the elective treatment according to the circumstance. We need to be mindful of the equivocal prognosis due to these ad hoc adaptations, while simultaneously prioritizing patients with substantial improvement in the quality of life or overall survival gain. The pandemic preparedness plan should include evidence-based continuity of care for cancer patients, for countering the collateral damage due to reallocation of resources. During the course of this pandemic, it is an exhaustive challenge to secure the supply chain of cancer medicines and devices. The absence of a tailored approach of care to cancer patients seems more detrimental than SARS-CoV-2 infection in a cancer patient. 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