ABSTRACT
Introduction. In severe cases of coronavirus disease 2019 (COVID-19) pulmonary infiltration is accompanied by cytokine storm syndrome (CSS) development. Besides COVID-19, CSS can be triggered by the range of pathologies, which include hemophagocytic lymphohistiocytosis (sHLH) and septic shock (SS). The aim of this study was to compare immunological profiles in fatal cases of COVID-19, sHLH and SS. Material and methods. Serum levels of IL-1β, IL-2, IL-6, IL-8, IL-10, IL-17A, IL-18, IFN-γ, TNF-α, procalcitonin, neopterin, ferritin with percent of glycosylated fraction (% GF) were measured in 37 COVID-19 fatal cases, collected during 2020 year prospectively;and in 39 sHLH and 47 SS fatal cases, collected within 2018–2019 years retrospectively. Comparison groups also included 194 non-fatal COVID-19 cases and 20 healthy donors, collected during 2020 year. Cytokine concentrations, procalcitonin and neopterin were measured by enzyme-linked immunosorbent assay;the ferritin level was determined by the turbidimetry method. The percent of glycosylated ferritin fraction (% GF) was calculated by the modified method of M. Worwood et al. Results. Deceased patients with COVID-19 had higher IL-6, IL-8, IL-10, IL-18, procalcitonin median levels compared to the survived. Meanwhile IL-8, IL-18, IFN-γ, TNFα and ferritin concentrations were significantly lower in deceased COVID-19 patients compared to sHLH and SS. The levels of IL-6 and procalcitonin in fatal COVID-19 were comparable to SS, but significantly higher than in sHLH. Leucocytes were higher in COVID-19 compared to both SS and sHLH. Conclusion. Each fatal condition was accompanied by specific features of the cytokine profile: high IL-6 combined with low IFN-γ, TNFα in COVID-19;high IL-8, IL-6 with low IL-17A, IL-2 in SS;high IL-18, ferritin, IFN-γ with low IL-6, procalcitonin, % GF in sHLH.
ABSTRACT
Thrombophilia, as well as multiple organ dysfunction, are typical manifestations of the severe new coronavirus infection that closely resemble the clinical signs of catastrophic antiphospholipid syndrome (CAPS). The objective: to assess whether catastrophic antiphospholipid syndrome is an essential manifestation of severe forms of COVID-19. Subjects and methods. 45 patients diagnosed with the new coronavirus infection (SARS-CoV-2) and a severe course of viral pneumonia (more than 3 points on the NEWS score by the admission, CT 3-4, oxygenation index below 100, the need for at least high-flow oxygen therapy). They were assessed for the development of CAPS due to signs of progressing organ dysfunction despite the ongoing intensive therapy, suspected pulmonary embolism and progressing venous thrombosis of a lower extremity or subclavian vein. It was an essential provision that they should have no signs of bacterial infection (blood procalcitonin should be below 0.5 μg/l). The antiphospholipid syndrome was diagnosed based on the detection of antibodies to β-2-glycoprotein in the blood (A/t β-2-GP1 IgGAM, A/t β-2-GP1 IgM, A/t β-2-GP1 IgG) and to cardiolipin (A/t CL IgM, A/t CL IgG) by ELISA tests. The course of the disease was monitored using other routine clinical (temperature, complete blood and urine counts) tests and blood panel tests reflecting the severity of the systemic inflammatory response (ferritin, CRP, interleukins 6 and 18), and the state of the hemostatic, respiratory, circulatory, liver and kidney systems. Results. Antiphospholipid antibodies (aAPL) moderately exceeding the reference values were detected in 9 out of 45 patients (20%), mainly due to IgA and IgM isotypes to β-2-glycoprotein and IgM isotype to cardiolipin. The assessment of the antibody titer in 5 patients over time (after 7 days) revealed a decrease, but it did not affect the outcome (four of them died). In 36 patients, some traces of aAPL were found that did not reach the lower limit of the norm, despite the uniformity of the clinical signs and similarity of biochemical parameters reflecting the severity of organ disorders. The absence of antibodies did not prevent the development of thrombotic complications (thrombosis of large vessels and pulmonary embolism in 5 patients). There were no other manifestations often associated with CAPS (thrombocytopenia, hemolytic anemia, decreased fibrinogen concentration in the blood). Conclusion. Catastrophic antiphospholipid syndrome is not inevitable in severe COVID-19 cases, however, it can develop as one of the manifestations of thrombophilia that occurs in such patients. © 2021 New Terra Publishing House. All rights reserved.