key: cord-0795046-4m0v3mhl authors: Yigenoglu, Tugce Nur; Ata, Naim; Altuntas, Fevzi; Bascı, Semih; Sinan Dal, Mehmet; Korkmaz, Serdal; Namdaroglu, Sinem; Basturk, Abdulkadir; Hacıbekiroglu, Tuba; Dogu, Mehmet Hilmi; Berber, İlhami; Dal, Kursat; Erkurt, Mehmet Ali; Turgut, Burhan; Ilgu, Mahir; Celik, Osman; Imrat, Ersan; Birinci, Suayip title: The Outcome of COVID‐19 in Patients with Hematological Malignancy date: 2020-08-10 journal: J Med Virol DOI: 10.1002/jmv.26404 sha: 3633e2d97cc4621dabe7de60d4ce9cf51590a1ec doc_id: 795046 cord_uid: 4m0v3mhl INTRODUCTION: In this study, we aim to report the outcome of COVID‐19 in patients with hematological malignancy in Turkey. METHOD: The data of laboratory‐confirmed 188,897 COVID‐19 patients diagnosed between March 11, 2020 and June 22, 2020 included in the Republic of Turkey, Ministry of Health database were analyzed retrospectively. All of the COVID‐19 patients with hematological malignancy (n=740) were included in the study and an age, gender and comorbidity matched COVID‐19 patients without cancer (n=740) at 1:1 ratio was used for comparison. RESULTS: Non Hodgkin lymphoma (30.1%), myelodysplastic syndrome (19.7%), myeloproliferative neoplasm (15.7%), were the most common hematological malignancies. The rates of severe and critical disease were significantly higher in patients with hematological malignancy compared to the patients without cancer (p=0.001). The rates of hospital and intensive care unit (ICU) admission were higher in patients with hematological malignancy compared to the patients without cancer (p=0.023, p=0.001, respectively). The length of hospital stay and ICU stay were similar between groups (p=0.7, p=0.3; retrospectively). The rate of mechanical ventilation (MV) support was higher in patients with hematological malignancy compared to the control group (p=0.001). The case fatality rate (CFR) was 13.8% in patients with hematological malignancy, and it was 6.8% in the control group (p=0.001). CONCLUSION: This study reveals that there is an increased risk of COVID‐19 related serious events (ICU admission, MV support or death) in patients with hematological malignancy compared to COVID‐19 patients without cancer and supports high vulnerability of patients with hematological malignancy in the current pandemic. This article is protected by copyright. All rights reserved. Most of Coronaviruses (CoVs) are pathogenic to humans, but they rarely cause severe infections. However, in the last two decades, two CoVs caused severe infections in humans: The Severe Acute Respiratory Syndrome (SARS) Cov (SARS-CoV) and the Middle East Respiratory Syndrome (MERS) CoV (MERS-CoV). [1] [2] [3] At the end of 2019, a cluster of pneumonia patients with an unidentified cause was observed in Wuhan, China. After the genetic analysis of the virus, it was understood that these pneumonia cases were caused by the 2019 Novel CoV (2019-nCoV), which was later named as SARS-CoV-2. 4, 5 The new disease presented with similar clinical findings to SARS-CoV and MERS-CoV, such as fever, dyspnea, and multilobed lesions in the computed tomography of the thorax. The disease caused by SARS-CoV-2 was named as COVID-19, by the World Health Organisation (WHO). It was declared a pandemic, on March 11, 2020. 6, 7 Older age and comorbidities such as diabetes, hypertension, or cardiac disease are risk factors for a more aggressive clinical course in patients with COVID-19. 8 In addition, in a previous report, it was reported that in 39% of COVID-19 patients with cancer had severe events such as intensive care unit (ICU) admission, need of mechanical ventilation (MV) and death during the COVID-19 course, whereas only 8% of COVID-19 patients without cancer had those severe events. The more aggressive clinical course of cancer patients with COVID-19 may be attributed to immunosuppression due to the chemotherapies, radiotherapy, or immunosuppressive drugs they are receiving or increased co-existing medical conditions or lung invasion by the primary tumor itself or metastasis. Patients with hematological malignancies may be more vulnerable than patients with solid tumors because of the immune system dysfunction they have. 9,10 However, there is only a limited number of studies about COVID-19 in patients with hematological malignancy, and most of these data are based on case series. Therefore, in this study, we aim to report the outcome of COVID-19 in patients with hematological malignancies treated in Turkey. Ethics committee approval was obtained from the Republic of Turkey Ministery of Health. The data of laboratory-confirmed 188,897 COVID-19 patients diagnosed between March 11, 2020 and June 22, 2020 included in the Republic of Turkey, Ministry of Health database were analyzed retrospectively. All of the COVID-19 patients with hematological malignancy (n=740) were included in the study and an This article is protected by copyright. All rights reserved. age, gender, and comorbidity matched COVID-19 patients without cancer (n=740) at 1:1 ratio was used for comparison. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 RNA were performed using nasopharyngeal swabs. Total nucleic acid extraction of nasopharyngeal swabs of viral isolates was performed using a biospeedy Severe COVID-19 was defined as the existence of dyspnea, blood oxygen saturation ≤ 93%, PaO2 / FiO2 < 300 and > 50% progression in lung infiltrates within 24 to 48 hours. Critical COVID-19 was defined as the existence of respiratory failure, septic shock and/or multiple organ dysfunctions. 10 Data analysis was performed using IBM SPSS v26 software. Variables assessed for normal distribution with the Kolmogorov Smirnov test. Categorical data were presented as number-percentages, and numerical data were presented as median, minimum, and maximum. Differences between categorical variables were analyzed with the Chi-Square test, and numeric variables were compared with the Mann-Whitney U test. In total, there were 1480 laboratory-confirmed COVID-19 patients; 740 of them had hematological malignancy and the other 740 were consisting the age, sex, and comorbidity matched cohort. Demographic and clinical characteristics of all patients in the study are given in Table 1 . Hypertension was the most common comorbid disease in COVID-19 patients with hematological malignancy and was observed in 51.2% of the patients. The rate of lopinavir/ritonavir use was higher in patients with hematological malignancy compared to control group (p = 0.013) ( Table 1) . Severe course of COVID-19 was observed in 15.5% of patients with hematological malignancy wheras it was observed in 13% of patients without cancer. In addition, the rate of critically ill COVID-19 patients was 13.2% among patients with hematological malignancy wheras it was 6.6% among patients without cancer. The rates of severe and critical diseases were significantly higher in patients with hematological malignancy compared to the patients without cancer (p=0.001). The rates of hospital and ICU admission were higher in patients with hematological malignancy compared to the patients without cancer (p=0.023, p=0.001, respectively). The length of hospital stay and ICU stay were similar between groups (p=0.7, p=0.3; retrospectively). The rate of MV support was higher in patients with hematological malignancy compared to the control group (p=0.001). The case fatality rate (CFR) was 13.8% in patients with hematological malignancy, and it was 6.8% in the control Accepted Article group (p=0.001) ( Table 2 ). The highest CFR among COVID-19 patients with hematological malignancy was observed in HCL (44%) followed by AML (20%) and MM (19.5%). When hematological malignancies were classified into 2 groups according to their origins as lymphoid malignancies (NHL, HL, ALL, CLL, HCL, MM) and myeloid malignancies (AML, MDS, MPN, CML); no significant difference was observed regarding CFR (p=0.6). The distribution of the deceased patients according to their hematological malignancies is given in Table 3 . No significant difference was observed between deceased patients with hematological malignancy and deceased patients without cancer regarding gender, age, number of comorbidity, and COVID-19 treatment they received (Table 4 ). The prevalence of cancer in patients with COVID-19 is uncertain. Previous studies from China reported that 1 to 2% of COVID-19 patients had cancer, and a study from the United States of America reported that 6% of hospitalized patients with COVID-19 had cancer. In Lombardy, Italy, they observed that 8% of the patients admitted to the ICU for COVID-19 had cancer. In a meta-analysis, the prevalence of cancer was 2% among COVID-19 patients. [11] [12] [13] [14] Although there are reports about the prevalence of cancer among COVID-19 patients, the data about the prevalence of hematological malignancies among COVID-19 patients is very limited. In our study, we found that 0.39% of the laboratory confirmed COVID-19 patients had hematological malignancy. The most common hematological malignancies in COVID-19 patients were NHL (30.1%) followed by MDS (19.7%). There is also less knowledge existing in the literature about the disease course in COVID-19 patients with hematological malignancies. In a previous study, researchers analyzed the data of 105 patients with cancer hospitalized for COVID-19 and compared their results to patients without cancer. Among 105 COVID-19 patients with cancer, 9 had hematological malignancy. When compared to patients without cancer, they found that patients with cancer had higher death rates, higher rates of ICU admission, and more severe COVID-19 course and had a higher rate of MV support. In addition, they observed that patients with hematologic malignancies, lung cancer, and metastatic cancer had the highest frequency of severe events. 15 In the study conducted by Mehta et al., ICU admission rate and MV support rate were higher This article is protected by copyright. All rights reserved. in patients with hematological malignancy (26%) compared to patients with solid tumors (19%); however, this did not achieve statistical significance. 16 In our study, severe course of COVID-19 was observed in 15.5% of patients with hematological malignancy wheras it was observed in 13% of patients without cancer. In addition, the rate of critically ill COVID-19 patients was 13.2% among patients with hematological malignancy wheras it was 6.6% among patients without cancer. We found that the rates of severe and critical diseases were significantly higher in patients with hematological malignancy compared to the patients without cancer. The rates of ICU and hospital admission, MV support were higher in COVID-19 patients with hematological malignancy compared to the control group. This finding supports the hypothesis of the high probability of immunopathogenic damage due to a cytokine storm because of the increased risk of an immunological hyperactivation induced by SARS-CoV-2 in hematological malignancies involving T lymphocytes, natural killer cells, histiocytes and antigen presenting cells. 17 In a previous study, the mortality rate in myeloid malignancies In conclusion, it is important to consider that patients with hematological malignancy are immunocompromised and our study reveals that there is an increased Genetic Recombination, and Pathogenesis of Coronaviruses Advances in clinical diagnosis and treatment of severe acute respiratory syndrome Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia A Novel Coronavirus from Patients with Pneumonia in China A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster The World Health Organization (WHO) Has Officially Named the Disease Caused by the Novel Coronavirus as COVID-19 Clinical Characteristics of Coronavirus Disease 2019 in China Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China FDA. 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