key: cord-297425-vcqqssm8
authors: Aries, James A.; Davies, Jeffrey K.; Auer, Rebecca L.; Hallam, Simon L.; Montoto, Silvia; Smith, Matthew; Sevillano, Belen; Foggo, Vanessa; Wrench, Bela; Zegocki, Krzysztof; Agrawal, Samir; Le Dieu, Rifca; Truelove, Edward; Erblich, Thomas; Araf, Shamzah; Okosun, Jessica; Oakervee, Heather; Cavenagh, Jamie D.; Gribben, John G.; Riches, John C.
title: Clinical Outcome of Coronavirus Disease 2019 in Haemato‐oncology Patients
date: 2020-05-18
journal: Br J Haematol
DOI: 10.1111/bjh.16852
sha: 
doc_id: 297425
cord_uid: vcqqssm8

Since being identified in China in December 2019, coronavirus disease 2019 (Covid‐19) has rapidly evolved into a global pandemic with over 4 million cases and more than 270,000 deaths.(1) Following the first reported cases in the United Kingdom (UK) in late January 2020, numbers have continued to rise with 223,060 cases and 32,065 deaths reported as of 11(th) May 2020.(2) Initial reports from China have indicated that Covid‐19 has an overall mortality rate of 1.4%. However, the prognosis varies widely between groups, with age over 60 years and underlying conditions including hypertension, diabetes, cardiovascular disease and cancer identified as risk factors for severe disease and death.(3) The initial reports from China show that patients with cancer are over‐represented among individuals who develop severe Covid‐19 after contracting the virus.(4) Patients with haematological malignancies are expected to be at increased risk of adverse outcomes from this viral infection, due being immunosuppressed as a consequence of the underlying cancer, and from the effects of therapy.

Since being identified in China in December 2019, coronavirus disease 2019 (Covid-19) has rapidly evolved into a global pandemic with over 4 million cases and more than 270,000 deaths.(1) Following the first reported cases in the United Kingdom (UK) in late January 2020, numbers have continued to rise with 223,060 cases and 32,065 deaths reported as of 11 th May 2020.(2) Initial reports from China have indicated that Covid-19 has an overall mortality rate of 1.4%. However, the prognosis varies widely between groups, with age over 60 years and underlying conditions including hypertension, diabetes, cardiovascular disease and cancer identified as risk factors for severe disease and death. (3) The initial reports from China show that patients with cancer are over-represented among individuals who develop severe Covid-19 after contracting the virus.(4) Patients with haematological malignancies are expected to be at increased risk of adverse outcomes from this viral infection, due being immunosuppressed as a consequence of the underlying cancer, and from the effects of therapy. This has led to a variety of recommendations to reduce the risk from Covid-19, including "shielding" by self-isolating at home for prolonged periods, and alterations to therapy such as delaying or even omitting chemotherapy, radiotherapy or transplantation. (5) (6) (7) (8) However, at the time of writing there is virtually no published data on the impact of Covid-19 in patients with haematological malignancies.

We identified 35 adult patients with a known diagnosis of a haematological malignancy under the care of Barts Cancer Centre who developed a laboratoryconfirmed Covid-19 infection between 11 th March and 11 th May, 2020. A confirmed case of Covid-19 was defined by a positive result on a reverse-transcriptasepolymerase-chain-reaction (RT-PCR) assay of a specimen collected on a nasopharyngeal swab. Only laboratory-confirmed cases were included and each

This article is protected by copyright. All rights reserved patient had at least 14 days of follow-up. The demographic and clinical characteristics of the patients are shown in Table 1 . The median age of the patients was 69 years; 66% were men. 12 patients had multiple myeloma, 5 patients had chronic lymphocytic leukaemia, 4 patients respectively had diffuse large B cell lymphoma and acute lymphoblastic leukaemia, 3 patients had follicular lymphoma, 2 patients had acute myeloid leukaemia, along with 1 patient with each of aplastic leukaemia, myelofibrosis, monoclonal gammopathy of undetermined significance, mantle cell lymphoma and myelodysplastic syndrome. 54% of patients were known to have pre-existing hypogammaglobulinaemia at baseline. 24 (69%) patients were on active treatment at the time of Covid-19 diagnosis; the treatment history for each case is given in the data supplement. Many patients had co-existing chronic medical conditions, most frequently hypertension (29%), chronic kidney disease (14%) and diabetes mellitus (15%). The most common symptoms were fever (77%), cough (60%) and shortness of breath (54%). Table 2 shows correlation of clinical and laboratory findings with outcome. As of 11 th May, 14 (40%) patients had died and 21 (60%) patients had recovered. Age was most significantly associated with outcome in our series with all but one of the patients who died being 70 years or older at the time of Covid-19 diagnosis. The number of co-existing comorbidities such as hypertension, chronic kidney disease or diabetes was also predictive of outcome with patients who died having significantly more concurrent diagnoses than patients who recovered. This reflects the observations seen in initial studies where the elderly and those with underlying conditions were at a significantly higher risk for severe disease and death.(3) Importantly we did not see a correlation between active treatment and outcome in our series. Furthermore, we document 15 patients who have recovered from Covid-19 despite being on treatment at the time of diagnosis of their infection, including patients on highly immunosuppressive regimens such as R-CHOP for lymphoma, induction regimens for acute leukaemia and triplet combinations for myeloma. In terms of laboratory parameters hypoxia on admission and a highly elevated Creactive protein level were predictive of a poor outcome. In contrast, there was no association between admission haemoglobin concentration, platelet count or neutrophil:lymphocyte ratio and outcome. Perhaps unexpectedly, patients who recovered had a lower neutrophil and lymphocyte count on admission than the patients who died. This probably reflects inclusion of younger fitter patients receiving more myelosuppressive and lymphodepleting therapy, who nevertheless went on to recover from their infection. However, this highlights that the impact of Covid-19 on haematological parameters such as a lymphopenia, or the prognostic utility of neutrophil:lymphocyte ratio may be confounded by other factors in haematooncology patients. (9, 10) Given the focus on hospital-based testing for suspected Covid-19 in the UK, a crude case fatality rate in a comparable group of hospital-assessed patients of 14.4% can be calculated from current UK government statistics.(2) In contrast we observed a

This article is protected by copyright. All rights reserved case fatality rate of 40% in haemato-oncology patients, which is comparable to the proportion of patients with cancer who reached a composite endpoint of requiring admission to intensive care, invasive ventilation or death in a previous report.(4) Therefore our patients who developed Covid-19 have an approximately 3-fold increased risk of death compared to the general population. Due to the current lack of widespread community testing for Covid-19 in the UK, the case fatality rate reported here is likely to be an overestimate within this patient group. While only patients with laboratory-confirmed Covid-19 were included in our series, we were aware of other haemato-oncology patients who had mild symptoms and were advised to self-isolate at home rather than attend hospital for assessment, and were therefore not tested for SARS-CoV-2. Furthermore, it is likely other patients with no/mild symptoms have not presented to our network.

Our study does have several limitations, including the relatively small sample size and lack of data on patients who developed Covid-19 in the community and were not tested. Ultimately, some of these questions will be addressed by larger multinational and registry studies. However, given the rapidly evolving nature of the global Covid-19 pandemic there is a place for case series in guiding haematological practice during these challenging times. Our data demonstrate that while patients with haematological cancers have worse outcomes after Covid-19 than the background population, the majority still survive. 

Clinical Characteristics of Coronavirus Disease 2019 in China

Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

Acute leukemia in the time of COVID-19

Provision of cancer care during the COVID-19 pandemic

Care of haematology patients in a COVID-19 epidemic

ILROG Emergency Guidelines for Radiation Therapy of Hematological Malignancies During the COVID-19 Pandemic

Hematological findings and complications of COVID-19

Neutrophil-to-lymphocyte ratio and lymphocyte-to-Creactive protein ratio in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis

This article is protected by copyright. All rights reserved

This article is protected by copyright. All rights reserved 0.0006 *A patient with a lymphocytosis due to CLL was excluded for these calculations.