ABSTRACT
Background: Patients with lymphopproliferative diseases (LPD) and covid-19 have poor outcome as consequence of inadequate humoral and cellular immunity due to the hematological disease itself but also due to the administered chemotherapy which further increases the risk of complications and mortality. Aims: The aim of this study is to analyze demographic and clinical characteristics, laboratory parameters, the presence of comorbidities, laboratory parameters, disease status, as well as outcome of the patients with COVID-19 and lymphoproliferative disease and compare them with characteristics of covid-19 infection in patients from general population (GP). Methods: This is a prospective multicenter observational study conducted in the following 3 University centers in period from 15 March 2020 to 31 October 2021. The study included hospitalized patients diagnosed with COVID-19 infection: 161 patients with LPD and 162 patients from the GP. Statistical analysis included demographic statistics, the χ2 test, the Mann-Whitney test, Kaplan-Meier method for analysis of survival and multivariate logistic regression model for analysis of risk factors for mortality. Results: In the LPD group, there were 54 patients (33.54%) with chronic lymphocytic leukemia (CLL), 72 patients (44.72%) with Non-Hodgkin lymphoma/Hodgkin lymphoma (NHL/HL) and 35 patients (21.74%) with multiple myeloma (MM). Ninety-six (59,63%) patients were on active treatment and 14(8.7%) patients were newly diagnosed. The LPD and GP group differed significantly in relation to age (66 vs. 54 years), gender (male: 60.2% vs. 75.3%), presence of comorbidities (109, 67.7% vs. 81, 50%) patients, covid score (mild 22.5% vs. 1.9%, moderate 80, 50.3% vs. 121, 74.7%), and severe/critical 44(27.1%) vs. 38(23.4%) patients. Group of patients with LPD had also significantly lower level of hemoglobin, lowest value of lymphocytes, platelets, higher level of CRP, ferritin, Ddimer (on admission and maximal values) and LDH with respect to group of patients from GP. Mortality rate was higher in LPD group of patients than in GP group (45, 28% vs. 26, 16%) patients. Among the LPD group, the highest mortality rate was observed in patients with MM (16, 45.71%) patients, followed by CLL (15, 27.9%) patients and NHL/HL group (14, 19.4%) patients. Independent factors related to survival are high value of D dimer, anemia (hemoglobin <100g/l) and moderate/critical COVID score in LPD group, while maximal value of CRP, anemia, leucocytosis and age (>60 years) in GP group. Summary/Conclusion: Our study showed significant difference in the characteristics and outcome in covid-19 between patients with LPD and patients from GP. Patients with LPD are older, they have significantly higher inflammatory parameters and more frequent presence of comorbidities compared to patients from GP. Independent factors related to survival in the LPD group are high values of D dimer, moderate/critical COVID score and anemia, while maximal values of CRP, anemia and older age are identified in the GP group.
ABSTRACT
Background: Vulnerability of patients (pts) with chronic lymphocytic leukemia (CLL) and their susceptibility to Covid-19 infection is documented in several studies with reported case fatality rates (CFRs) up to 40%, but there is still paucity of data on identifying risk factors of their adverse outcome. Aims: To evaluate demographic, patient-related, CLL-related and Covid-19 related risk factors in hospitalized pts with concurrent CLL and Covid-19. Methods: Total of 81 CLL pts were identified in medical records of three University centers in Belgrade: Clinical Hospital Center (CHC) Zemun, CHC Bezanijska kosa and CHC Zvezdara dedicated to treatment of Covid-19 pts during pandemic (from 15 March 2020 to 31 December 2021). Results: For all 81 pts CFR was 32.1%. Age (median age 68 yrs;range 45-90 yrs) and sex (apparent male prevalence: 61 male and 20 female;M:F=3.05) had no influence on outcome. Pts with Charlson comorbidity index >4 (29/81;35.8%) had significantly higher CFR (38% vs 9.5%, p=0,025). Concerning CLL-directed treatment: 26/81(32.1%) pts were on active treatment (5 pts were on Bruton tyrosine kinase inhibitor, 21pts receiving imunochemotherapy), 11/81(13.6%) pts were in remission on previous lines of therapy, while 44/81(54.3%) pts were treatment naive. CLL treatment history had no impact on CFR, as well as anemia (Hb<100g/l) that was present in 29/81(35.8%)pts, hipogammaglobulinemia (21/81;26%pts) and hiperferritinemia>450ng/mL (50/81;61.7%pts). Of evaluated laboratory parameters, high levels of lactate-dehydrogenase (LDH>2xUNL:6/81;7.4%pts), D-dimer (>1000ng/mL:36/81;44.4%pts), and C-reactive protein (CRP>100mg/L: 31/81;38.3%pts) proved to be associated with adverse outcome;p-values 0.002, 0.039 and <0.001, respectively. According to Covid-19 clinical course, the severe Covid-19 score had 35(43,2%)pts, and critical 19(23.5%)pts. Covid-19 infection was treated according to current National guidelines. Corticosteroids were administrated to 81.5% of pts, antiviral agents to 38.3%, IL-6 receptor inhibitor to 11.1%, antiviral monoclonal antibodies to 7.4% and intravenous immunoglobulin to 19.8% of pts. None of listed therapeutic approaches had impact on CFRs. Antibiotics were administrated to 43/81 (53.1%) of pts with documented or highly suspected concomitant bacterial infection (procaltitonin level>0.5ng/mL and/or chest X-Ray image corresponding to bacterial pneumonia), and the bacterial coinfection had adverse impact on CFR (51.2% vs.10.2%;p<0.001). Significantly higher mortality was documented in pts who needed supplemental oxygen (58/81;71%) (CFR 43.1 vs.4.3%;p<0.001), and intensive care unit (ICU) admission (25/81-30.9%;19/25 needed mechanical ventilation) (CFR 88% vs.7.1%;p<0.001). In multivariate analysis, bacterial coinfection and ICU admission proved to be the most significant adverse parameters influencing outcome (p=0.012). Summary/Conclusion: Our study proved the dismal outcome of CLL pts with concurrent Covid-19. That could be mainly attributed to the high proportion of bacterial coinfections reflecting their frailty and sucessibility to both viral and bacterial infections.