key: cord-1006114-xk8w757n authors: Joharatnam-Hogan, Nalinie; Hochhauser, Daniel; Shiu, Kai-Keen; Rush, Hannah; Crolley, Valerie; Wilson, William; Sharma, Anand; Muhammad, Aun; Anwar, Muhammad; Vasdev, Nikhil; Goldstein, Robert; Kantser, Ganna; Saha, Aramita; Raja, Fharat; Bridgewater, John; Khan, Khurum title: Outcomes of the 2019 novel coronavirus in patients with or without a history of cancer: a multi-centre North London experience date: 2020-09-14 journal: Ther Adv Med Oncol DOI: 10.1177/1758835920956803 sha: 90d49d4aae643d075aa5c9e2759ba18d20c14447 doc_id: 1006114 cord_uid: xk8w757n BACKGROUND: This study aims to compare the outcomes of COVID-19-positive disease in patients with a history of cancer to those without. METHODS: We retrospectively collected clinical data and outcomes of COVID-19 positive cancer patients treated consecutively in five North London hospitals (cohort A). Outcomes recorded included time interval between most recent anti-cancer treatment and admission, severe outcome [a composite endpoint of intensive care unit (ITU) admission, ventilation and/or death] and mortality. Outcomes were compared with consecutively admitted COVID-19 positive patients, without a history of cancer (cohort B), treated at the primary centre during the same time period (1 March–30 April 2020). Patients were matched for age, gender and comorbidity. RESULTS: The median age in both cohorts was 74 years, with 67% male, and comprised of 30 patients with cancer, and 90 without (1:3 ratio). For cohort B, 579 patients without a history of cancer and consecutively admitted were screened from the primary London hospital, 105 were COVID-19 positive and 90 were matched and included. Excluding cancer, both cohorts had a median of two comorbidities. The odds ratio (OR) for mortality, comparing patients with cancer to those without, was 1.05 [95% confidence interval (CI) 0.4–2.5], and severe outcome (OR 0.89, 95% CI 0.4–2.0) suggesting no increased risk of death or a severe outcome in patients with cancer. Cancer patients who received systemic treatment within 28 days had an OR for mortality of 4.05 (95% CI 0.68–23.95), p = 0.12. On presentation anaemia, hypokalaemia, hypoalbuminaemia and hypoproteinaemia were identified predominantly in cohort A. Median duration of admission was 8 days for cancer patients and 7 days for non-cancer. CONCLUSION: A diagnosis of cancer does not appear to increase the risk of death or a severe outcome in COVID-19 patients with cancer compared with those without cancer. If a second spike of virus strikes, rational decision making is required to ensure optimal cancer care. The 2019 novel coronavirus disease (COVID- 19) was first detected as a case of pneumonia of unknown cause in late 2019 in Wuhan, China. 1 On 11 March 2020, the World Health Organisation (WHO) declared COVID-19 a pandemic due to the global spread of this new disease and the significant risk of further transmission. 2 As of 29 May 2020, there were 269,127 confirmed cases in the United Kingdom (UK), with 37,837 deaths. 3 The pathogen causing COVID-19, the severe acute respiratory syndrome coronavirus (SARS-CoV-2), is an enveloped RNA virus belonging to Outcomes of the 2019 novel coronavirus in patients with or without a history of cancer: a multi-centre North London experience the family of Coronaviridae and is one of seven species of coronavirus known to infect humans. Four strains typically cause common cold symptoms and two, Severe Acute Respiratory Syndrome coronovirus (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-CoV), can cause fatal respiratory diseases. 4 The clinical spectrum of COVID-19 ranges from asymptomatic infection to severe respiratory failure and death. 5 A retrospective study of 191 adult inpatients in Wuhan found an increased odds of death with older age [odds ratio (OR) 1.10, 95% confidence interval (CI) 1.03- 1.17] , and in those with coronary heart disease and diabetes. 5 Individuals with serious chronic medical conditions, including cardiovascular disease, diabetes, and lung disease, are deemed vulnerable and considered to be at higher risk of critical illness, 6 particularly acute respiratory distress syndrome (ARDS). 7 In a prospective nationwide analysis of 1590 patients with COVID-19 in China, 18 (1%) had a history of cancer, which is higher than the prevalence of cancer in the general Chinese population. These patients were more likely to have a severe event [39% versus 8% in patients without cancer, hazard ratio (HR) 5.34, 95% CI 1.8-16.18, p = 0.0003], defined as the requirement of invasive ventilation or death. 8, 9 Of the cancer patients with previous history available, the majority were undergoing routine follow up after primary resection (12 out of 16), with the rest having received chemotherapy or surgery within the past month (4 out of 16). 8 However, this study had a small sample size of cancer patients, with significant heterogeneity between diseases. 10 The majority of patients were cancer survivors; thus, it is unclear whether these outcomes can be generalised to the oncology population, and outcome is likely to be confounded by a higher median age than those without cancer. 11 A similar retrospective study of 28 patients with a history of cancer from three Wuhan hospitals found that lung cancer was the most prevalent tumour amongst COVID-positive patients (25%). Patients who had received their last systemic anticancer treatment (SACT) within 14 days had an increased risk of developing severe events (HR = 4.079, 95% CI 1.086-15.322, p = 0.037), 12 highlighting the importance of carefully reviewing the necessity and priority of SACT in these potentially high-risk patients during the pandemic. A larger multi-centre study of 105 cancer patients compared with age matched non-cancer patients in Wuhan, China also demonstrated an increased risk of death, intensive care unit (ITU) admission and requirement for ventilation; however, cohorts were not fully matched. 13 One of the bigger challenges with COVID-19 is its long incubation period ( Figure 1 ) and potential spread through asymptomatic patients. In cancer patients, there is likely to be considerable difficulty in assessing patients suitability for chemotherapy, as oncologists often rely only on symptoms and haematological/biochemical parameters, as well Another significant challenge for these patients is the consideration of re-starting chemotherapy, or commencing any other oncological intervention such as immunotherapy or oral targetted therapy in COVID-19 positive patients. It has been suggested in a case report that recurrence in patients with previously positive COVID-19 may occur, or that patients may remain persistently positive despite resolution of symptoms. 14 15 Although studies in individuals with cancer suggest worse outcomes in these patients, to our knowledge comparisons with matched cohorts have yet to be carried out outside of China. Here, we present a study of 30 patients with cancer matched to 90 patients without a history of cancer (at a ratio of 1:3), admitted with COVID-19 in five North London Hospitals (Figure 2 ), to expand on the data in this setting and to determine if a diagnosis of cancer significantly worsens COVID-19 related outcomes. The study data includes patients admitted and diagnosed with COVID-19 between 1 March and 30 April 2020 at five London hospitals. We defined a confirmed diagnosis of COVID-19 based on reverse-transcription polymerase chain reaction (RT-PCR) from respiratory tract swabs. Cohort A comprised 30 patients with a history of cancer (both solid organ and haematological). Clinically relevant outcomes were then compared with 90 SARS-CoV-2 RT-PCR positive patients without a history of cancer, matched by age, gender and number of comorbidities, consecutively admitted at the primary centre during the same time period (cohort B). 16, 17 ; however, as the control group are matched to cancer patients on age and comorbidities, it is expected that their mortality rate will be notably worse. Under the assumption that the true rate of mortality in the non-cancer patients is 10%, with 30 patients in cohort A and 90 in cohort B, we would have 80% power to detect an OR of 5.1 or higher at the 5% significance level. Logistic regression was used to determine the OR for mortality and severe outcomes in those with a diagnosis of cancer versus those without. Baseline factors were compared between cancer and noncancer patients using chi-squared tests and their prognostic value was assessed using logistic regression; p values < 0.05 were considered significant. To our knowledge, this is the first report comparing the outcomes of COVID-19 positive patients with a history of cancer with their non-cancer counterparts in the UK. This study demonstrates that COVID-19 infection carries a significant risk of morbidity and mortality for all patients regardless of their history of malignancy. The results of the oncology-specific patients are comparable with literature from a similar series of patients with cancer and COVID-19 in Wuhan, China. 12, 13 In this study of 30 cancer patients, no significant increased risk of mortality or severe outcome (including ventilation or ITU admission) was demonstrated compared with an age/ gender and comorbidity matched cohort of noncancer patients. Clinical features of both cohorts were consistent with previous studies. Typical laboratory features in both groups included anaemia, lymphopenia and an elevated CRP; however, patients with cancer significantly more frequently had features of anaemia, hypokalaemia and hypoproteinaemia on presentation (although the former two may be a consequence of anti-cancer therapy and the latter a reflection of malnutrition associated with malignancy, advanced disease and frailty). These were features also reported in the cancer patients in Wuhan. 12 The combined mortality of both cohorts (36%) is significantly higher than the current estimation of mortality in hospitalised patients (>5%) 16, 17 ; however, both groups of patients had significant co-morbidities, of the same median number (two excluding malignancy). A history of malignancy did not appear to increase the mortality rate compared with those without cancer, acknowledging that this cohort study has a small sample size. Of the 11 cancer patients who died, all had received anti-cancer therapy, and the majority in the palliative setting of advanced disease. Patients were more likely to die if treatment had been administered within 28 days of admission, corroborating Zhang et al.'s dataset, although our data has not shown a significant result. 12 During the course of the publication process of the current paper, we acknowledge another retrospective cohort study published with somewhat conflicting data 13 ; however, this may be explained by the differences in the patient population of individuals in Wuhan compared with those in the UK and the retrospective nature of both studies. Our data show that outcomes between cancer and non-cancer patients were comparable. Whilst patients with cancer tend to have underlying immunosuppression from SACT, and therefore perhaps more inclined to contract infection, cytokine storm syndrome might be the primary reason for mortality in COVID-19 positive patients more generally. 18 Contrary to the general hypothesis that patients on immunosuppressive regimes such as chemotherapy are at particular risk of adverse outcomes after contracting COVID-19, immunosuppression may paradoxically work in their favour, by dampening this cytokine storm response. A recent study suggested use of immunosuppressive therapies such as steroids, intravenous immunoglobulin, selective cytokine blockade (e.g. anakinra/tocilizumab) or Janus kinase (JAK) inhibition might act as potential therapeutic options. 18 Based on the data presented here, there was no excess in mortality in the cancer cohort despite many patients being actively treated with anti-cancer therapy. However, the majority of patients in the cancer cohort who died had received systemic anti-cancer therapy within the last 28 days. Thus, cautious consideration should be made of the risk/benefit profile of palliative SACT in the setting of the COVID-19 pandemic to minimise the potential risks of mortality in already vulnerable patients. We acknowledge the limitations to this study, including the retrospective sample and small sample size. To address this, we increased the sample size of the non-cancer patients to a ratio of 1:3. Amongst the patients with cancer, there was significant heterogeneity between tumour types, including variability in stage and other clinicopathological factors. The prevalence of different tumour types admitted in this study is described in Table 3 , with prostate cancer the most frequent, and colorectal and lung cancers the next most prevalent. Given the small sample size, we are unable to define a relation of severity of COVID-19 disease with different cancer types, and this cohort likely reflects the prevalence of cancers treated at these North London hospitals. Patient data was obtained from five different London hospitals, in which treatment may vary, and this therefore may have an impact on prognostic factors. Patients were age-, gender-, comorbidity-and date-matched to reduce selection bias. Our data suggested that systemic anticancer treatment within 28 days may increase the risk of mortality from COVID-19 (although results were not significant). However, this result may be confounded by the fact that most of these patients were receiving treatment in the palliative setting and therefore perhaps may be suggestive of worse disease leading to death, rather than a treatment effect. We acknowledge the above limitations. Given the urgent timeline of an evolving and rapidly progressing pandemic, we elected not to wait for a larger sample size, as we prioritise the early release of data to assist global physicians and oncologists to make real-time decisions. In the UK, at the time of writing, the government had closed all non-essential places of work, limited travel to key-workers only and was encouraging social distancing. 19 Due to the significant burden on the National Health Service (NHS) over the coming months, and potential risks to cancer patients, the prioritisation of chemotherapy was recommended in March 2020 to meet capacity and mitigate the risks of COVID-19 on balance with optimally treating cancer, with a number of guidelines published. 20 Cancer remains a significant global cause of death, and consideration should be given to re-escalating cancer services to normal at the earliest opportunity. Further studies are required to evaluate the impact of the COVID-19 infection and the consequences of the slowdown of services on cancer outcomes. 21 COVID-19 is a significant cause for healthcare, societal and economic concern globally. Previous work has demonstrated older patients and those with significant comorbidity are at greatest risk of morbidity and mortality from the virus. Patients with cancer are at higher risk of immunosuppression on cancer therapy, with possible increased incidence of infection based on data from China. Whilst acknowledging the limitations of the study, compared with patients without cancer, our study found no evidence that patients with cancer are more likely to have a severe outcome or mortality from COVID-19. Whilst extra caution is warranted in administration of SACT pertaining to risk of immunosuppression, this data does not demonstrate a higher risk to cancer patients compared with their non-cancer counterparts. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China World Health Organisation. Rolling Updates on Coronavirus Disease (COVID-19) Department of Health and Social Care and Public Health England. Number of coronavirus (COVID-19) cases and risk in the UK A novel coronavirus from patients with pneumonia in China Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Comorbidities and multi-organ injuries in the treatment of COVID-19 Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China COVID-19 and cancer: lessons from a pooled meta-analysis Risk of COVID-19 for patients with cancer Risk of COVID-19 for patients with cancer Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China Patients with cancer appear more vulnerable to SARS-COV-2: a multi-center study during the COVID-19 outbreak Recurrence of positive SARS-CoV-2 RNA in COVID-19: a case report COVID-19 rapid guideline: delivery of systemic anticancer treatments Understanding pathways to death in patients with COVID-19 Denominator matters in estimating COVID-19 mortality rates COVID-19: consider cytokine storm syndromes and immunosuppression Department of Health and Social Care and Public Health England. Next stage of expanded coronavirus (COVID-19) public information campaign launches Cancer guidelines during the COVID-19 pandemic Cancer management in India during Covid-19 Visit SAGE journals online journals.sagepub.com/ home/tam All authors approved the manuscript Datasets generated or analysed during the current study are available on request The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. No patient identifiable information was used in this study Research and development approval was sought from North Middlesex University Hospital where the study was primarily conducted (primary centre) The authors received no financial support for the research, authorship, and/or publication of this article. Valerie Crolley https://orcid.org/0000-0001-7263-4051 Supplemental material for this article is available online.