DYNAMICS OF PATHOGENETIC PARAMETERS BY GESTATIONAL TRIMESTERS IN PREGNANT WOMEN WITH COVID-19: CLINICAL-LABORATORY STRATIFICATION AND PHENOTYPIC TRANSFORMATION

Introduction. COVID-19 in pregnant women is characterised by significant phenotypic variability, ranging from asymptomatic disease to severe complications with multi-organ dysfunction. While most studies describe the static laboratory profile of infection, the dynamics of pathogenetic parameters by gestational trimester across distinct phenotypes remain insufficiently explored. Aim. To characterise the dynamics of pathogenetic parameters (cytokine profile, inflammation and dysfunc­tion markers, coagulation parameters, oxygenation and foetal functional status) across gestational trimesters in three COVID-19 pathogenetic phenotypes — inflammatory-cytokine, endothelial-coagulopathic, and hypoxic-adaptive — in pregnant women residing at high and low altitude. Materials and methods. This prospective cohort study enrolled 600 pregnant women with confirmed COVID-19, divided into high-altitude (≥2500 m, n=252) and low-altitude (n=348) groups. Three pathogenetic phenotypes were identified: inflammatory-cytokine (n=250), endothelial-coagulopathic (n=180) and hypoxic-adaptive (n=170). Cytokine profile (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, TNF-α, IFN-γ), specific inflammatory and dysfunction markers (CRP, ferritin, procalcitonin, troponin I, NT-proBNP, sFlt-1/PlGF), haemostasis parameters (D-dimer, fibrinogen, PT, INR, aPTT, antithrombin III, protein C, protein S, vWF, F1+2 fragments, SFMC, FDP), oxygenation (SpO₂ at rest and on exertion) and foetal functional parameters (CTG, biophysical profile, foetal movements, cervical length) were analysed. Statistical analysis: SPSS 26.0, ANOVA, Tukey and Kruskal-Wallis tests; p<0.05 was considered statistically significant. Results. In the inflammatory-cytokine phenotype at high altitude, all cytokine levels and specific markers showed no statistically significant trimester-related dynamics (p>0.05 for all pairs). In the endothelial-coagulopathic phenotype at low altitude, a second-trimester peak of D-dimer was identified (4.22±0.285 μg/mL vs 3.59±0.15 in the third trimester, p=0.049), along with elevated antithrombin III in the second trimester (94.28±1.374% vs 88.08±2.24% in the first, p=0.038; vs 89.05±1.203% in the third, p=0.026) and a nadir of protein C in the second trimester (68.50±2.870% vs 75.80±2.062% in the first, p=0.040). In the hypoxic-adaptive phenotype at low altitude, a moderate decline in resting SpO₂ was observed from the first to third trimester (97.88±0.178% vs 97.37±0.097%, p=0.019), with no significant changes in hormonal indices or foetal functional parameters (p>0.05). Conclusion. Pathogenetic parameters of COVID-19 in pregnant women demonstrate pronounced pheno­type-specific resistance to trimester-related changes, with the sole exception of a second-trimester coagulation peak in the endothelial-coagulopathic phenotype. The observed second-trimester surge in D-dimer warrants intensified anticoagulation monitoring during this period.