Regional outcomes of severe acute respiratory syndrome coronavirus 2 infection in hospitalised patients with haematological malignancy

Abstract Objectives We sought to characterise the outcomes of patients with haematological malignancy and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in hospital in our regional network of 7 hospitals. Methods Consecutive hospitalised patients with haematological malignancy and SARS‐CoV‐2 infection were identified from 01/03/2020 to 06/05/2020. Outcomes were categorised as death, resolved or ongoing. The primary outcome was preliminary case fatality rate (pCFR), defined as the number of cases resulting in death as a proportion of all diagnosed cases. Analysis was primarily descriptive. Results 66 Patients were included, overall pCFR was 51.5%. Patients ≥ 70 years accounted for the majority of hospitalised cases (42, 63%) and fatalities (25, 74%). Mortality was similar between females (52%) and males (51%). Immunosuppressive or cytotoxic treatment within 3 months of the diagnosis of SARS‐CoV‐2 infection was associated with a significantly higher pCFR of 70%, compared with 28% in those not on active treatment (P = .0013, 2 proportions z test). Conclusions Mortality rates in patients with haematological malignancy and SARS‐CoV‐2 infection in hospital are high supporting measures to minimise the risk of infection in this population.


| INTRODUC TI ON
The pandemic spread of COVID-19 (coronavirus disease 2019) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has so far caused over 400 000 confirmed deaths worldwide. Preliminary pre-print data from 16 749 hospitalised patients in the United Kingdom (UK) suggest a mortality of at least 33% in unselected hospitalised patients. 1 Risk factors associated with more severe outcomes include increasing age, pre-existing lung disease, diabetes, hypertension and cancer. 2 The risk of SARS-CoV-2 to patients with cancer, and particularly haematological malignancy, is not yet fully clarified.
Early data suggested that patients with cancer are at increased risk of death if contracting this virus. [3][4][5][6] However, numbers of patients with malignancy were low with marked heterogeneity of diagnoses, and little information was presented on treatment history. With regard to haematological malignancies, a cohort study from Wuhan, China, identified 11 patients with haematological malignancy and COVID-19, of whom 8 (72%) did not survive. 4 A further study of 25 patients, of whom 24 had a malignant haematological diagnosis, reported a one-month mortality rate of COVID-19 infection of 40%. 7 Two recent multicentre retrospective cohort studies of patients with COVID-19 compared patients with cancer with age-matched controls without cancer. Both of these studies have suggested that patients with haematological cancers may be at greatest risk of severe complications of COVID-19 when compared with other malignancies. The first study reported a higher odds ratio of death of 2.3 in 105 patients with cancer compared to age-matched controls. 8 The 9 patients with haematological malignancy had the worst outcomes, with significantly increased risk of intensive care admission, need for ventilation and death. The second cohort study reported on 218 COVID-positive patients with a malignant diagnosis, reporting an increased case fatality rate of 2-3 compared to age-matched controls. 9 The 54 patients with haematological malignancy had a case fatality rate of 37%, worse than that of solid organ cancers.
Patients with haematological cancers are likely to be at high risk of infectious complications of viral respiratory infections from both immune dysregulation as an intrinsic part of the malignancy, as well as of the immunosuppressive and cytotoxic treatment. 10 In time, it will be important to identify from large data sets the diagnoses and treatments which convey the greatest risk to this patient group, and large prospective studies are underway to assemble this information.
We present outcome data for all hospitalised COVID-19 positive patients with a diagnosis of haematological malignancy from our region, which includes seven hospitals serving a population of 2.8 million patients, 11 as a first attempt to understand in more detail the outcome of these patients.

| ME THODS
Consecutive cases were identified prospectively by clinical teams across our regional cancer network from 01/03/2020 to 06/05/2020 and reported to a central database. Patients were required to be hospitalised and positive for SARS-CoV-2 RNA by reverse transcriptase quantitative polymerase chain reaction (qPCR) of nose and throat swab, or with clinical and radiological features consistent with COVID-19, where the clinical team judged COVID-19 was the most likely diagnosis. All patients had a current haematological malignancy under ongoing treatment or in clinical follow-up. COVID-19 was treated according to local practice with many patients entering clinical trials.
Patients who were not admitted to hospital were not included in the analysis because of variation in outpatient testing strategy over time and between hospitals. Patients with asymptomatic non-malignant conditions, for example monoclonal gammopathy of uncertain significance, were excluded. Patient baseline characteristics collected included age, gender, haematological diagnosis, method of diagnosis of SARS-CoV-2, current haematological treatment and prior lines of treatment.
The primary outcome was preliminary case fatality rate (pCFR), defined as the number of cases resulting in death as proportion of all diagnosed cases. 12 Outcomes were categorised as either death; resolved (patients who were no longer symptomatic and judged to have recovered from the infection by their clinical team); or ongoing (patients remained in hospital with symptoms attributed to SARS-CoV-2 infection).
Analysis was primarily descriptive with the two proportions Z test used to compare pCFR in the population of patients who received immunosuppressive or cytotoxic treatment in the 3 months prior to SARS-CoV-2 infection and the population who did not receive such treatment. Mortality is high at 51.5% overall and significantly higher in those who received immunosuppressive or cytotoxic treatment in the last three months (70%) than in those who did not (28%). In total, there were 34 deaths; therefore, the overall pCFR was 51.5%, with patients over the age of 70 accounting for the major-

| D ISCUSS I ON
At present, the true incidence of COVID-19 in patients with haematological malignancy is not known, since only those with symptoms sufficient for hospital admission, or those already admitted who developed symptoms, were tested, in line with national guidance at the time. The true case fatality rate of COVID-19 in this patient group is therefore likely to be significantly lower than that reported in this paper. In line with other studies, advancing age appears to be a key correlate of poor outcome in patients hospitalised with COVID-19 infection, with a pCFR amongst those with haematological cancers of 59.5% in those over 70 years, as compared to 37.5% in those under 70 (Figure 1). F I G U R E 1 Regional outcomes of hospitalised patients with haematological malignancy and severe acute respiratory syndrome coronavirus 2 infection by age and gender. Outcomes shown categorised as death, ongoing symptomatic infection in hospital and resolved. CFR, case fatality rate defined as deaths as a proportion of all cases; F, female; M, male A relevant question is what proportion of the regional population with haematological malignancy these 66 patients represent. Hospital data on the numbers of patients fulfilling the UK government's criteria for shielding were available from 2 hospitals covering a total of population of 1.27 million. In these hospitals, 3334 patients were identified, equivalent to 263 per 100 000 population, which accords with the UK Haematological Malignancy Research Network prevalence data indicating a prevalence of 167/100 000 for haematological malignancy diagnosed in the last 3 years or 388/100 000 diagnosed in the last 10 years. 13 We therefore estimate a regional population of  Our data support attempts to reduce the contact of individuals from this group with the healthcare system to minimise nosocomial infections. 16 This group of patients need to be prioritised in consideration of how best to use a SARS-CoV-2 vaccine, and included in clinical trials of novel therapies to treat COVID-19.
The submission of patient data to national and international databases is strongly encouraged, since numbers are insufficient at present to answer the questions that clinicians and patients alike are posing, regarding the relative risks of different diagnoses and treatments. These more complete data will, in time, be fundamental in enabling us to build an informed consensus about future management of haematological malignancy in the era of COVID-19.