INFLAMMATORY CYTOKINES AND COVID-19 ASSOCIATED COAGULOPATHY IN PREGNANCY: A PROSPECTIVE, CASE-CONTROL STUDY
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Background. Coronavirus disease 2019 (COVID-19) is associated with enhanced inflammatory response and disturbed hemostasis balance. Little is known about the association between the COVID-19-induced inflammatory response and hemostasis alterations in pregnancy, and their associations with the clinical course. Aims. To test a comprehensive set of inflammatory cytokines in pregnant women with/without COVID-19 and correlate results with a global test of hemostasis (thrombin generation assay, TGA), as well as with maternal and perinatal outcomes. Methods. In this single-center observational case-control study, 100 women with acute COVID-19 at 24-40 gestational weeks (COVID-19+ group) and 100 healthy age- and gestational week-matched pregnant women (COVID-19- group) were enrolled. All women were outpatients with mild/no symptoms at admission. Acute infection was confirmed/ruled out using SARS-CoV-2 RT-PCR and/or antigen test. Blood was taken on admission and the levels of 13 inflammatory cytokines/chemokines (IL-6, IL-1ß, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-10, IL-8, IL-12p70, IL-17A, IL-18, IL-23, IL-33) were analyzed using the LEGENDPlex bead-based immunoassay by flow cytometry. TGA was performed from all samples, and lag time, endogenous thrombin potential, peak thrombin were calculated. Detailed clinical parameters of pregnancy, labour and postpartum period were registered. All women were followed for 6 weeks postpartum. Results. In the COVID-19+ group, IL-6, IFN-α2, IFN-γ, MCP-1, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33 were significantly increased as compared to the non-infected group. TG was significantly decreased in the COVID-19+ vs. COVID-19- group (peak thrombin: 531±139 vs. 594±104 nM, p=0.017). Admission IL1, and IL-33 were significantly lower, while IL-18 was significantly higher in cases when COVID-19 became more severe (stage 2 disease requiring O2 therapy, n=9 patients). In the COVID 19+ group, postpartum hemorrhage (PPH) developed in 4 cases, associated with significantly increased IL-8, IL-17A and IL-23 levels vs. those without PPH. IL-6, IFN-α2, MCP-1, IL-10, IL-17A and IL-18 showed a significant negative correlation with TG parameters. Thrombotic events did not occur in either group. Conclusions. Third trimester COVID-19+ pregnancies were associated with increased inflammatory cytokine levels and decreased TG. Increased IL-8, IL-17A and IL-23 levels were suggestive of future PPH events, warranting further investigations in larger cohorts.