Clinical and genetic determinants of severe course of COVID-19 in pregnant women

Abstract

Objectives: to determine the clinical and genetic determinants of the severe course of COVID-19 in pregnant women in order to identify a risk group and search for therapeutic targets. Materials and methods. 21 patients (group 1) with a severe course of COVID-19 who required intensive care in the Anesthesiology and Intensive Care Unit (AICU) and 126 pregnant women with moderate severity treated in the Infectious-Obstetrics Unit (IOCU) were examined (group 2). Genomic DNA for molecular genetic analysis of gene variants ACE (I/D, rs 4340), PGR (Alu insertion), ESR1 (A351G, rs 9340799), PON1 (C108T, rs 705379) was isolated from the peripheral blood of patients using a commercial Quick-DNA Miniprep Plus Kit (Zymo Research, USA). Variants of ACE and PGR genes were determined using allele-specific polymerase chain reaction; polymerase chain reaction followed by restriction analysis was used to determine ESR1 and PON1 gene variants. Results. Severe course of COVID-19 is observed in 18.2% of pregnant women, critical condition in 7.5%. A third of AICU patients are over 35 years old. Somatic anamnesis was complicated in 23.8% of patients; thyroid gland pathology (14.3%) and varicose disease (19.0%) prevailed. A significant factor in the severe course of COVID-19 is obesity of the III–IV degree in 28.5% cases. The severe course of the disease was associated with complications of pregnancy (oligohydramnios – 52.4%, ahydramnios – 14.3%, fetal growth retardation syndrome – 33.3%, circulatory disorders – 57.1%, fetal distress – 47.6%, preeclampsia – 14.3%), labor (caesarean section – 57.1%, premature birth – 28.6%), disorders of newborns state (asphyxia – 35.6%). These patients are characterized by anemia (58.7%), thrombocytopenia (23.8%), leukocytosis (33.3%), lymphopenia (90.5%), a shift of the leukocyte formula to the left (an increase of rod-nuclear leukocytes by 85.7%). There were significantly increased levels of transaminases: alanine aminotransferase in 47.6%, aspartate aminotransferase in 76.2%. Prothrombotic changes are indicated by a decrease in prothrombin time and activated partial thromboplastin time in 66.7%, which is confirmed by an increase in D-dimer in 85.7% of patients up to the maximum 15,000 ng/ml in 9.5% of women. An increase in inflammation markers (C-reactive protein and interleukin-6 in all AICU patients, procalcitonin in 66.7%) is a reflection of the destructive effect of inflammatory processes. The genetic determinants of the severe course of COVID-19 in pregnant women can be the ID genotype of the ACE I/D rs4340 polymorphism (81.0%), the T2/T2 PROGINS genotype (19.0%), the ESR1 A351G rs9340799 GG genotype (28.5%). Conclusions. The use of separate clinical, laboratory and genetic indicators in pregnant women with COVID-19 will contribute to the selection of the risk group of a coronavirus severe course and the determination of targets of therapeutic impact.

Keywords

• covid-19
• pregnancy
• hemostasis system
• inflammatory markers
• genetic markers