Covid-19 among patients with hematological malignancies: A national Israeli retrospective analysis

ABSTRACT

Background: The first COVID-19 patient was diagnosed in Israel in February 2020. It is of importance to evaluate outcomes across patients with hematological malignancies which are generally immunosuppressed and more susceptible to infectious complications. Aims: We aimed to characterize the clinical course of COVID-19 infection among patients with various lymphoid or myeloid malignancies and determine which of these patients were most at risk of severe infection or mortality. Methods: This was a national Israeli multicenter retrospective study. Patients with hematological malignancies who were diagnosed with COVID-19 from February 20, 2020 until January 31, 2021 were centrally reported and included in the retrospective analysis with no need for informed consent signing. Clinical and laboratory data regarding baseline characteristics, hematological management, and course and treatment of the COVID-19 disease were collected. Multivariate regression analyses were used to determine the variables associated with severe disease, hospitalization and mortality. Results: In total, 272 patients from 14 medical centers were included in the analysis. Among them, 140 (51.5%) were men, and the median age was 70yrs. The most frequent malignancies included lymphoma (44.5%), multiple myeloma (22.8%), and chronic lymphocytic leukemia (12.1%). 90 (33.1%) patients developed a severe or critical respiratory infection, and 58 (21.3%) died. According to multivariate regression analyses, both age > 70yrs (OR=2.26;95% CI 1.04;4.95;p=0.041) and current steroid treatment (OR=3.23;95% CI 1.06, 9.90;p=0.040) at time of COVID- 19 diagnosis were associated with severe to critical disease, while current treatment with monoclonal antibodies was associated with mild to moderate disease (OR=2.86;95% CI 1.17, 6.99;p=0.022). Among the 159 hospitalized patients, the hospitalization was longer in patients with severe to critical respiratory infection (IRR=1.53;95% CI 1.36, 1.72;p<0.001), or treated with dexamethasone (IRR=1.22;95% CI 1.08, 1.38;p=0.002), with enoxaparin (IRR=1.18;95% CI 1.06, 1.33;p=0.004) or convalescent plasma (IRR=1.17;95% CI 1.04, 1.32, p=0.012);while the hospitalization was shorter in patients treated with remdesivir (IRR=0.78;95% CI 0.69, 0.89;p<0.001). The mortality rate was higher in patients > 70yrs (OR=3.41;95% CI 1.13, 10.34;p=0.030), with severe to critical infection (OR=27.27;95% CI 7.40, 100.48, p<0.001), or in those treated with dexamethasone (OR=5.89;95% CI 1.47, 23.63;p=0.012) for COVID-19 respiratory condition, and lower in patients treated with remdesivir (OR=0.19, 95% CI 0.04, 0.82, p=0.026). Summary/Conclusion: Respiratory infection with COVID-19 seems to be particularly severe in patients with hematological malignancies. While steroids seem to increase both baseline severity of the infection and mortality, it seems that treatment with remdesivir was associated with reduced mortality and duration of hospitalization. These particularities of haemato-oncological patients may be explained by a remarkably severe COVID-19 viremia that might cause the high mortality rate, while the cytokine release syndrome which generally responds to steroid treatment may be milder in these patients. The management of hematological malignancies during acute COVID-19 infection should be individualized and further investigated.