Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study

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Summary

Background

Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19.

Methods

This multicentre, retrospective, cohort study included adult patients (aged ≥18 years) with diagnosis of a WHO-defined haematological malignancy admitted to 66 Italian hospitals between Feb 25 and May 18, 2020, with laboratory-confirmed and symptomatic COVID-19. Data cutoff for this analysis was June 22, 2020. The primary outcome was mortality and evaluation of potential predictive parameters of mortality. We calculated standardised mortality ratios between observed death in the study cohort and expected death by applying stratum-specific mortality rates of the Italian population with COVID-19 and an Italian cohort of 31 993 patients with haematological malignancies without COVID-19 (data up to March 1, 2019). Multivariable Cox proportional hazards model was used to identify factors associated with overall survival. This study is registered with ClinicalTrials.gov, NCT04352556, and the prospective part of the study is ongoing.

Findings

We enrolled 536 patients with a median follow-up of 20 days (IQR 10–34) at data cutoff, 85 (16%) of whom were managed as outpatients. 440 (98%) of 451 hospitalised patients completed their hospital course (were either discharged alive or died). 198 (37%) of 536 patients died. When compared with the general Italian population with COVID-19, the standardised mortality ratio was 2·04 (95% CI 1·77–2·34) in our whole study cohort and 3·72 (2·86–4·64) in individuals younger than 70 years. When compared with the non-COVID-19 cohort with haematological malignancies, the standardised mortality ratio was 41·3 (38·1–44·9). Older age (hazard ratio 1·03, 95% CI 1·01–1·05); progressive disease status (2·10, 1·41–3·12); diagnosis of acute myeloid leukaemia (3·49, 1·56–7·81), indolent non-Hodgin lymphoma (2·19, 1·07–4·48), aggressive non-Hodgkin lymphoma (2·56, 1·34–4·89), or plasma cell neoplasms (2·48, 1·31–4·69), and severe or critical COVID-19 (4·08, 2·73–6·09) were associated with worse overall survival.

Interpretation

This study adds to the evidence that patients with haematological malignancies have worse outcomes than both the general population with COVID-19 and patients with haematological malignancies without COVID-19. The high mortality among patients with haematological malignancies hospitalised with COVID-19 highlights the need for aggressive infection prevention strategies, at least until effective vaccination or treatment strategies are available.

Funding

Associazione italiana contro le leucemie, linfomi e mieloma–Varese Onlus.

Related collections

Most cited references 26

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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chaolin Huang, Yeming Wang, Xingwang Li … (2020)

Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

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Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Fei Zhou, Ting Yu, Ronghui Du … (2020)

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

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Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

Zunyou Wu, Jennifer M. McGoogan (2020)

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Author and article information

Contributors

Francesco Passamonti

Journal

Journal ID (nlm-ta): Lancet Haematol

Journal ID (iso-abbrev): Lancet Haematol

Title: The Lancet. Haematology

Publisher: Elsevier Ltd.

ISSN (Electronic): 2352-3026

Publication date PMC-release: 13 August 2020

Publication date (Electronic): 13 August 2020

Affiliations

[a ]Department of Medicine and Surgery, University of Insubria and ASST Sette Laghi, Ospedale di Circolo of Varese, Varese, Italy

[b ]Haematology, ASST-Spedali Civili, Brescia, Italy

[c ]Department of Molecular Medicine, University of Pavia, Pavia, Italy

[d ]Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

[e ]Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont and Ospedale Maggiore della Carità, Novara, Italy

[f ]Seràgnoli Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine, Bologna University School of Medicine, Bologna, Italy

[g ]Hematology, Azienda USL-IRCCS Reggio Emilia, Reggio Emilia, Italy

[h ]Hematology, Ospedale Policlinico San Martino, Genoa, Italy

[i ]Department of Medicine, Section of Hematology, University of Verona, Verona, Italy

[j ]Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy

[k ]Humanitas Clinical and Research Hospital—IRCCS and Department of Biomedical Sciences, Humanitas University, Milan, Italy

[l ]Fondazione IRCCS Ca' Granda—Ospedale Maggiore Policlinico, Milan, Italy

[m ]Hematology, Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy

[n ]Department of Hematology, Università degli Studi di Milano-Bicocca, Milan, Italy

[o ]Laboratory of Healthcare Research & Pharmacoepidemiology, Department of Statistics and Quantitative Methods, Università degli Studi di Milano-Bicocca, Milan, Italy

[p ]National Centre for Healthcare Research and Pharmacoepidemiology, Milan, Italy

[q ]Dipartimento di Medicina interna e Specialità mediche, University of Genoa, Genoa, Italy

[r ]Hematology, ASST Cremona, Cremona, Italy

[s ]Stem Cell Transplant Center, AOU Citta' della Salute e della Scienza, Turin, Italy

[t ]Hematology, Azienda Ospedaliero Universitaria Sant'Anna, Ferrara, Italy

[u ]Hematology, Dipartimento di Chirurgia e Specialità Medico Chirurgiche, Università degli Studi di Catania, Catania, Italy

[v ]Dipartimento di Medicina e Chirurgia, University of Parma, Parma, Italy

[w ]Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

[x ]Hematology, ASST Ovest Milanese, Milan, Italy

[y ]Department of Clinical and Biological Sciences, Università di Torino, Turin, Italy

[z ]Department of Medicine, University of Perugia, Perugia, Italy

[aa ]Ospedale di Bolzano, Bolzano, Italy

[ab ]Hematology, Ospedale Ca' Foncello, Treviso, Italy

[ac ]Dipartimento di Onco- Ematologia, Azienda Ospedaliera Ospedali Riuniti Marche Nord, Pesaro, Italy

[ad ]Hematology, Ospedale San Bortolo, Vicenza, Italy

[ae ]Hematology, University Hospital Sant'Andrea, Sapienza, Rome, Italy

[af ]Department of Clinical and Molecular Medicine, Sapienza, University of Rome, Rome, Italy

[ag ]Hematology, Department of Translational and Precision Medicine, Sapienza, University of Rome, Rome, Italy

[ah ]Hematology, Ospedale degli Infermi di Rimini, Rimini, Italy

[ai ]Hematology, Santa Maria delle Croci, Ravenna, Italy

[aj ]Hematology, Santa Croce Hospital, Cuneo, Italy

[ak ]Hematology, Ospedale Valduce, Como, Italy

[al ]Hematology, Ospedale Antonio Cardarelli, Naples, Italy

[am ]Dipartimento Strutturale Aziendale Medicina, University of Padova, Padova, Italy

[an ]Hematology, Ospedale di Piacenza, Piacenza, Italy

[ao ]Hematology, Istituto Europeo di Oncologia, Milan, Italy

[ap ]Hematology, Istituto Tumori Giovanni Paolo II, Bari, Italy

[aq ]Hematology, Ospedale degli Infermi, Biella, Italy

[ar ]Ematologia, USL 6 Livorno, Livorno, Italy

[as ]Hematology, San Giovanni Addolorata Hospital, Rome, Italy

[at ]Dipartimento di Scienze Cliniche e Sperimentali, University of Brescia, Brescia, Italy

[au ]Dipartimento Oncologico, ASST Valle Olona, Busto Arsizio, Italy

[av ]Hematology, Ospedale dell'Angelo di Mestre, Venice, Italy

[aw ]Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto, University of Modena and Reggio Emilia, Azienda Ospedaliera Universitaria, Modena, Italy

[ax ]Hematology, Ospedale San Giovanni di Dio e Ruggi D'Aragona, Salerno, Italy

[ay ]UOC Ematologia con Trapianto, Ospedale Santa Maria Goretti, Latina, Italy

[az ]Hematology, Ospedale Santa Maria Goretti, Latina, Italy

[ba ]Hematology, Ospedali Riuniti Azienda Ospedaliera Universitaria di Foggia, Foggia, Italy

[bb ]Hematology and Transplant Unit, Ospedale Vito Fazzi, Lecce, Italy

[bc ]Hematology, Ospedali Riuniti di Ancona, Ancona, Italy

[bd ]Hematology Unit, University of Siena, Azienda Ospedaliero Universitaria Senese, Siena, Italy

[be ]Hematology, Ospedale SS Annunziata, Taranto, Italy

[bf ]Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy

[bg ]Department of Emergency and Organ Transplantation, “Aldo Moro” University School of Medicine and Unit of Hematology and Stem Cell Transplantation, AOU Consorziale Policlinico, Bari, Italy

[bh ]Hematology and Transfusion Medicine, L Sacco University Hospital, Milan, Italy

[bi ]Dipartimento di Medicina Specialistica, University of Udine, Udine, Italy

[bj ]Hematology, Fondazione Policlinico Tor Vergata, Rome, Italy

[bk ]Hematology, Istituto Nazionale Tumori IRCCS “Fondazione G Pascale”, Naples, Italy

[bl ]Hematology, Mazzoni Hospital, Ascoli Piceno, Italy

[bm ]Hematology, Camillo-Forlanini Hospital, Rome, Italy

[bn ]Unit of Hematology, Stem Cell Transplantation, University Campus Bio-Medico, Rome, Italy

[bo ]Department of Clinical Medicine and Surgery, Federico II Hospital, Naples, Italy

[bp ]Dipartimento di Scienze Radiologiche ed Ematologiche, Fondazione Policlinico Universitario A Gemelli–IRCCS–Università Cattolica del Sacro Cuore, Rome, Italy

[bq ]Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, University of Milano

Author notes

[* ]Correspondence to: Prof Francesco Passamonti, Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy francesco.passamonti@ 123456uninsubria.it

Article

Publisher ID: S2352-3026(20)30251-9

DOI: 10.1016/S2352-3026(20)30251-9

PMC ID: 7426107

PubMed ID: 32798473

SO-VID: ec970eed-b82b-4639-990f-d518897ad492

License:

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