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 Table of Contents  
REVIEW ARTICLE
Year : 2022  |  Volume : 3  |  Issue : 1  |  Page : 49-54

Presentation and severity of COVID-19 among cancer patients: A narrative review of existing evidence


1 Epidemiology section, New Delhi Tuberculosis Centre, New Delhi, India
2 School of Medicine, Keele University, Staffordshire, UK
3 Department of Community Medicine, PDU Medical College, Churu, Rajasthan, India

Date of Submission29-Jun-2021
Date of Decision30-Oct-2021
Date of Acceptance11-Dec-2021
Date of Web Publication28-Apr-2022

Correspondence Address:
Dr. Rajesh Kumar Singh
Department of Community Medicine, PDU Medical College, Churu, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JME.JME_63_21

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  Abstract 


Coronavirus disease 2019 (COVID-19) continues to have a serious impact on people, including cancer patients and it was declared a public health emergency of international concern by the World Health Organisation. The present article attempts to review the prevalence, presentation and severity of COVID-19 among confirmed cancer patients from various studies. Cancer patients are vulnerable to COVID-19 and the data suggest that patients with cancer are at an increased risk of death compared to patients without cancer. Majority of patients from various studies presented with fever, cough or shortness of breath. Other symptoms included diarrhoea, nausea and vomiting, ageusia and anosmia. Those who died displayed higher rates of comorbidities compared with those who did not, including cardiovascular disease and hypertension. The risk of death was significantly associated with advancing patient age. Mortality from COVID-19 in cancer patients appears to be principally driven by age, gender and comorbidities.

Keywords: Cancer, co-morbidity, Coronavirus Disease 2019, mortality, neoplasm, prevalence, SARS-COV-2


How to cite this article:
Matta S, Bajpai R, Shekhawat R, Singh RK. Presentation and severity of COVID-19 among cancer patients: A narrative review of existing evidence. J Med Evid 2022;3:49-54

How to cite this URL:
Matta S, Bajpai R, Shekhawat R, Singh RK. Presentation and severity of COVID-19 among cancer patients: A narrative review of existing evidence. J Med Evid [serial online] 2022 [cited 2022 Aug 15];3:49-54. Available from: http://www.journaljme.org/text.asp?2022/3/1/49/344294




  Introduction Top


Coronavirus disease 2019 (COVID-19) continues to have a serious impact on people, including cancer patients.[1] As of 25 June 2021 globally, there were 179,686,071 confirmed cases of COVID-19, including 3,899,172 deaths.[2] Cancer patients are vulnerable to COVID-19 associated illness with strong evidence for higher risk of adverse outcomes compared to the general population. As per the (ASCO) patients with cancer are at increased risk of death compared to patients without cancer. Patient visits to the cancer clinic increase the potential risk of infection, and some cancer treatments may predispose patients to moderate or severe harmful effects of COVID-19.[1],[3],[4] According to a survey of Cancer patients conducted by the American Cancer Society Cancer Action Network, 87% of respondents said the pandemic had affected their health care in some manner (up from 51% in an April 2020 survey), 79% of cancer patients reported delays to their health care (up from 27%) and 17% of patients reported delays to their cancer therapy like chemotherapy, radiation or hormone therapy. Other issues were changes in in-person cancer provider appointments (57%); and delays in access to imaging services (25% up from 20%) and surgical procedures (15% up from 8%). About 46% of respondents said the COVID-19 pandemic had impacted their financial situation and ability to pay for care in some way (up from 38%)[1] Another study indicates that patients with cancer or cancer survivors are at an elevated risk for infection with the SARS-CoV-2 and are associated with severe cases/risk of death. The study also linked severe cases of COVID-19 with cancer.[5] The cancer patients with COVID-19 have poor survival with some studies reporting up to 30% mortality at 1 month.[6] The evidence regarding more likelihood of COVID-19 infection in cancer patients is increasing; hence, we attempt to review the prevalence, presentation and severity of COVID-19 infection in cancer patients based on extensive study of available literature.


  Materials and Methods Top


We have searched the keywords 'COVID-19', 'SARS-CoV-2', 'Cancer', 'Malignancy', 'Neoplasm', 'Tumour' and 'Prevalence' in PubMed, and Google scholar for grey literature. We limited the search to articles published from 1 January 2020 to 5 January 2021. Then, the articles were sorted by relevance to the subject. The most relevant papers were chosen to be reviewed.


  Results Top


Prevalence/incidence of coronavirus disease 2019 in cancer patients

The cancer patients might have more risk of getting COVID-19 infection as compared to non-cancer patients as reported by Liang et al.[7] Piper-Vallillo et al. reported a COVID-19 prevalence of 1%–3% in patients with active or previous malignancy.[8] Marschner et al. with a sample size of 139 patients reported an SARS-CoV-2 prevalence of 0.72%.[9] In another study[10] the infection rate of SARS-CoV-2 in cancer patients in China was 0.79%. [Table 1] shows the prevalence of COVID-19 among cancer patients from various studies.[9],[11],[12],[13],[14],[15],[16],[17]
Table 1: Prevalence of coronavirus disease 2019 among cancer patients

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Presentation

As per BioMed Central (BMC) study,[9] majority of patients presented with fever, cough (47%), shortness of breath (39%), diarrhoea (6%), nausea and vomiting (5%), ageusia (2%) and anosmia (1%). Piper-Vallillo et al. study[8] concluded that the most common symptoms were cough (75%), fatigue (51%), dyspnoea (45%) and fever (45%). It also reported that close to 40% of patients presented with respiratory symptoms and/or CT scan images of COVID-19. Another prominent finding was patients who were positive for COVID-19 were predominantly current or former smokers (87%), white (84%) and older. In Russell et al.'s study[3] 46% of cancer patients diagnosed with COVID-19 presented with cough and 52% had a fever. Piper-Vallillo et al. study also suggested that thoracic oncologists should maintain a broad differential diagnosis for patients presenting with acute symptoms, as nearly 50% of the patients referred for COVID-19 testing were found to have an alternative cause. Alternative diagnosis included treatment-related complications, progressive disease, atypical pneumonia, pulmonary embolism, congestive heart failure and chronic obstructive pulmonary disease flare. Following are some studies showing the presentation of the disease[3],[8],[11],[12],[18] as shown in [Table 2].
Table 2: Presentation of the disease from various studies

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Coronavirus disease 2019 and cancer sites

Assaad et al.[11] reported that cancer patients with COVID-19 had more frequent haematological malignancy as compared to solid tumours. Fillmore et al.[19] also observed a higher prevalence of COVID-19 in patients with haematological malignancy compared with those with solid tumours (10.9% vs. 7.8%, P <.001). The patients with the oesophagus, hepatocellular carcinoma, lung, lymphoma, head and neck, bone cancer, melanoma and other cancers had a lower risk of COVID. Rogado et al.[12] reported among 45 cancer patients with COVID-19 the frequent sites of cancer were lung (37.8%), breast (13.3%), colorectal (13.3%) and prostate (11.1%). Berghoff et al.[13] observed two patients with head-and-neck cancer, one with stomach cancer and one with sarcoma among four COVID-19-positive cancer patients. As per Bersanelli et al.[14] out of nine cancer patients with COVID-19, seven had lung and the rest two had renal and endometrial cancer. Fong et al.[15] reported, out of four COVID-19-positive cancer patients two had Lymphoma and the rest two had pancreatic and biliary tract carcinoma. According to Ramachandran et al.[18] among 53 COVID-19-positive cancer patients, 18.9% had prostate cancer, 15.1% had breast cancer, 15.1% had GIT cancer, 11.3% had haematological malignancy, 9.4% had lung cancer and the rest had, renal, skin, ovarian, brain and head-and-neck cancer.

Severity of coronavirus disease 2019 and mortality among cancer patients

As per Song et al. study,[20] clinical outcomes of COVID-19 are determined by parameters such as age, underlying diseases, the severity of pneumonia and admission to an ICU. A mild COVID-19 severity category was recorded in 412 (52%) patients, with 96 (12%) patients not requiring hospital admission.[21] Three hundred and fifteen (39%) patients required oxygen, and 53 (7%) patients received intensive therapy unit level care.[3] In Lee et al. study, 82% of patients presented with mild/moderate COVID-19 and 18% with severe COVID-19, and 226 (28%) patients died, with reports stating that the death was principally attributable to COVID-19 in most patients.[21] Patients who died were also more likely to present with symptoms of shortness of breath. As per Oh WK study,[22] the probability of dying in infected cancer patients, with a mortality rate (28.6%) is more than ten times higher than that reported in all COVID-19 patients in China. The study also highlighted those anticancer therapies within 14 days of infection (including chemotherapy, immunotherapy and radiation) were an independent predictor of death or other severe events with a hazard ratio >4. There are several studies[3],[8],[11],[12],[14],[23] as shown in [Table 3] which showed similar results.
Table 3: Severity of the disease

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Age groups affected

As per Russell et al. study,[3] 58% of patients were male and aged >60 years while 14% of the cancer population was aged <50 years. More male cancer patients presented with severe disease (68%). In Park et al.'s study, males were associated with a higher risk of severe illness and death due to COVID-19.[24]

Co-morbidities in cancer patients with coronavirus disease 2019

Patients with co-morbid conditions are more susceptible to manifest complications of the viral infection. Elderly patients in long-term care facilities, chronic kidney disease patients and cancer patients may contract/die from the disease. As per Russell et al. study,[3] hypertension was the most reported comorbidity (47%), followed by diabetes mellitus (22%), renal impairment (19%) and cardiovascular disease (19%). Benign lung conditions were commonly seen with severe COVID-19. Similar results were found in Lee et al. study whereby those who died also displayed higher rates of comorbidities compared with those who did not, including cardiovascular disease and hypertension.[21] Similar observations were noted in various other studies as shown in [Table 4].
Table 4: Co-morbidities in cancer patients with coronavirus disease 2019

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Mortality experience and associated factors among cancer patients with coronavirus disease 2019

As per Assaad et al.'s study,[11] the population of cancer patients has been reported to be particularly at risk of early death during COVID-19, with 30-day death rates up to 39% in the initial report versus 2.3% in the general population. Russell et al. quoted that people with cancer are much more likely to die from COVID-19 than those without cancer. Using a median follow-up of 37 days, 34 cancer patients had died of COVID-19 (22%). Several cancer patient characteristics were found to be positively associated with risk of COVID-19 death like being of Asian ethnicity receiving palliative treatment, time since cancer diagnosis >24 months, presenting with dyspnoea, having high C-reactive protein levels. An inverse association with death from COVID-19 was observed with normal albumin levels. A study from Albert Einstein College of Medicine New York reported a 28% fatality rate as compared to the overall mortality rate of 5.8% for COVID-19 in the United States.[25] As per a Lancet study, Mortality from COVID-19 in cancer patients appears to be principally driven by age, gender and co-morbidities.[21] As per Moujaess et al. study, patients with cancer had a higher risk of developing severe events (intensive care unit admission, invasive ventilation or death) compared with patients without cancer.[4] Lee et al. and Oh WK concluded that withholding effective cancer treatments from many cancer patients during the pandemic runs the very real risk of increasing cancer morbidity and mortality, perhaps much more so than COVID-19 itself.[21],[22] Cancer patients on chemotherapy, smokers and transplant recipients are at high risk of COVID-19 infection.[26]

Guidelines and recommendations related to cancer care during the coronavirus disease 2019 pandemic

ASCO[27] recently released a guide to cancer care delivery during the COVID19 pandemic and addressed the recommendations on screening of cancer patients, in-patients and outpatients visits, collection of laboratory samples, home drug infusion options, and engaging in telehealth. Various registries of COVID-19 among cancer patients have been launched. A new registry of such is TERAVOLT (COVID-19 in patients with thoracic malignancies) which collects lung cancer risk-assessment data from various international centres. A few studies[10],[28] have suggested prescreening, telemedicine, switch therapy during the present pandemic. In addition, care providers are advised to limit the use of aerosol-generating procedures like intubations in cancer patients. The Centre for Disease Control recommends high-risk individuals like cancer patients stay home and should avoid air travel.[27],[29],[30],[31]


  Discussion Top


Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020.[32] Cancer is a multi-stage process that generally progresses from a precancerous lesion to a malignant tumour. These changes are the result of the interaction between a person's genetic factors and three categories of external agents, including physical, chemical and biological (certain viruses, bacteria or parasites). The cancer patients need continuous care and undergo diagnostic tests or therapeutic interventions, so their potential for COVID-19 exposure could be very risky, or even fatal.

The review of different studies showed that the prevalence of COVID-19 among cancer patients was <5% in most studies except Assaad et al.'s study,[11] which reported prevalence to be 18.2%. The reasons for the high prevalence in Assaad et al.'s study may be due to the study conducted during the peak time of the first wave of COVID-19, small sample size, and inclusion of suspected patients of COVID-19. The variation in the prevalence of COVID-19 among cancer patients in different geographical regions could be explained by the different rates of the burden of cancer, the incidence of COVID-19, and the adoption of preventive and control measures for COVID-19.[5] The seroprevalence of COVID-19 in cancer patients was reported as 31% in the current review whereas in some studies from Spain and Italy the sero-prevalence of COVID-19 among the general population was found to be 4.6% and 5.6%, respectively.[33],[34] This higher sero-prevalence might be due to their higher risk of exposure as these patients visit the hospital frequently for routine care and lacks adequate immune response due to their specific treatment and the disease.[12]

Based on data available so far, the most common presenting symptoms in patients likely to present with COVID-19 were fever and cough. The mechanism of infection involves the virus binding with the cell membrane-bound angiotensin-converting enzyme-2 (ACE-2) receptor followed by internalisation of the complex.[35] The ACE-2 receptor is widely distributed in the lungs, heart, kidneys, brain and gut, providing a rationale for the wide variety of symptomatology like dyspnoea, fever, cough, fatigue, myalgia and gastrointestinal symptoms (nausea, vomiting, diarrhoea) which were also noted in this review. According to Bersanelli et al.,[14] all patients of COVID-19 with advanced stage of cancer presented with fever and dyspnoea.

The hospitalisation rate due to COVID-19 in the general population was reported <1%, while in this review Piper-Vallillo et al.[8] and Bersanelli et al.[14] showed hospitalisation rates of more than 50% and 100%, respectively, in cancer patients with COVID 19. It might be due to intensive care and supervision required in these cases as they are mostly elderly and with associated co-morbidities.

The study found that most cancer patients with COVID-19 were elderly, this could be due to an increase in the incidence of cancer with age, resulting from the build-up of risks for specific cancers. The overall risk accumulation is combined with the tendency for cellular repair mechanisms to be less effective as a person grows older. The study showed males were associated with a higher risk of severe illness and death due to COVID-19 in cancer patients; it suggests a potential link between certain male-specific cancers and COVID-19 pathogenesis. The reasons for the higher risk of severe COVID-19 illness in males may be accelerated immune ageing, more tendency to smoke, to leave the house and enter the crowded area and regional gender difference in health-seeking behaviour and access to care.[36]

The cancer patients with other co-morbidities such as hypertension and diabetes had a severe illness with poor outcomes than patients without co-morbidities. Analysis of comorbidities showed that hypertension was the most reported co-morbidity in cancer patients with COVID-19. As per Guan et al., the correlation between hypertension and ACE-2 receptor expression could be the probable explanation for patients with hypertension developing the more severe disease.[37]

The mortality rate of COVID-19 in the general population ranged from 0% to 14.6%.[38] In cancer patients with COVID-19 mortality rate was observed in a very high range i.e., 14.6% to 77.8%. Patients who died were often older than 70 and the presence of comorbidities such as hypertension, diabetes and chronic obstructive pulmonary disease.


  Conclusions and Recommendations Top


The present review shows that the prevalence of COVID-19 among cancer patients was quite high with variable clinical presentation. Cancer patients are at higher risk of getting COVID-19 infection as well as adverse outcomes including mortality. More focus needs to be given to the prevention of COVID-19 in cancer patients. Awareness among cancer patients needs to be given priority. Hence, all cancer patients must practice social distancing or isolation and be candidates for early and rapid evaluation for symptoms suspicious for COVID-19, including testing for virus and chest radiography. Considering the seriousness of the situation and recommendations from various above-mentioned studies, routine SARS-CoV-2 testing of patients with cancer seems advisable to detect asymptomatic virus carriers and avoid uncontrolled viral spread.

It is recommended that more focus needs to be given to the prevention of COVID-19 in cancer patients. All cancer patients must be screened for symptoms suspicious for COVID-19, including testing for the virus. It would be appropriate for routine SARS-CoV-2 testing of patients with cancer requiring hospitalised care to detect asymptomatic virus carriers and avoid uncontrolled viral spread. Behaviour Change Communication focussing on social distancing, masks, and sanitisation needs to be given priority among cancer patients. Cancer care should be prioritised in consultation with treating physicians and tele-health services can be utilised. Cancer patients should follow a healthy lifestyle to improve general health and immunity such as a balanced diet rich in fruits and vegetables, regular exercise, adequate sleep and avoiding the use of tobacco and alcohol. Cancer patients should be prioritised for vaccination against COVID-19 if there are no contraindications and according to country-specific recommendations.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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