Resolution Consensus Statement Neutralizing monoclonal antibodies for treatment of COVID-19 - a role in the treatment of vulnerable categories of patients.

In December 2022, the Council of Experts was held. It purpose was to determine the place of virus-neutralizing monoclonal antibodies (NMA) in the ethiotropic treatment of COVID-19 in vulnerable categories of patients. The main issues were identified and their solutions were proposed. At the first visit of pregnant women due to COVID-19, proactive identification of risk factors and early prescription of NMA are recommended, preferably - with published safety data in this category of patients (casirivimab + imdevimab). In patients with oncological and other chronic (rheumatology, pulmonology, gastroenterology) diseases, prophylactic use of NMA is recommended. regardless of the severity of the disease. For patients with chronic pathology regardless of the severity of the disease an early prescription of ethiotropic therapy must be provided, combating the long-term circulation of the virus. To solve the problem of late treatment prescription, it is necessary to: use rapid tests, prescribe NMA if indicated, even if the patient presents late, introduce digital technologies to transfer information about COVID-19 cases between healthcare institutions (HI), create call centers for primary triage of patients, daily hospitals to reduce the burden on the HI. The issue of NMA using related to changes in their activity against new variants of SARS-CoV-2 remains relevant. Among the proposed solutions are: priority of indications over information about the activity of NMA, the diversification of the choice of NMA in HI, taking into account clinical experience, indications for use and prognosis of NMA activity, the use of combined forms of NMA (for example, casirivimab + imdevimab) or a combination of NMA with other means of ethiotropic therapy.Copyright © 2023, Dynasty Publishing House. All rights reserved.

ALTERED AMINO ACID PROFILES OF THE "MOTHER-FETUS" SYSTEM IN COVID-19

Systemic nature of the human body response to SARS-CoV-2 requires dedicated analysis at the molecular level. COVID-19 during pregnancy affects maternal health and may entail complications in the early neonatal period and possibly long-term consequences for the offspring. The aim of the study was to assess the impact of COVID-19 on amino acid profiles in maternal venous blood, amniotic fluid and umbilical cord blood in order to develop a diagnostic panel accounting for possible consequences. The main group included 29 pregnant patients with a confirmed diagnosis of COVID-19 and the control group included 17 somatically healthy pregnant women. Amino acid profiles of the biological fluids were measured by high-performance liquid chromatography combined to mass spectrometry (HPLC-MS) and assessed in logistic regression models. The analysis revealed altered content of certain amino acids, their biosynthetic precursors and metabolites in the biological fluids collected from patients with COVID-19 possibly reflecting the development of systemic inflammatory reaction and associated changes in gene expression profiles. These findings may guide further research into health outcomes for neonates born from mothers infected with SARS-CoV-2 during pregnancy. The study may help to develop advanced recommendations and differential care protocols for pregnant women and newborns diagnosed with COVID-19.

THE 2019 NOVEL CORONAVIRUS INFECTION AND PREGNANCY: WHAT DO WE KNOW?

The COVID-19 pandemic resulting from the emergence of the SARS- CoV-2 virus remains a serious global health problem. An analysis has been made of the available modern foreign and Russian literature on topical issues of the 2019 novel coronavirus infection during pregnancy. Despite the tsunami of published information, many issues remain disputable and controversial and require further study. To date, little is known about the impact of the 2019 novel coronavirus infection on pregnancy. This review considers the physiological changes during pregnancy, which make pregnant women vulnerable to contamination and severe infection, as well as the possibility of intrauterine transmission, lactation during COVID-19, and specific preventive measures. Conclusion: Understanding that pregnant women are a vulnerable population at high risk for severe COVID-19 infection is essential to improve obstetric care during a pandemic. Medical personnel should conduct educational conversations with pregnant women and/or puerperas about the importance of adhering to non-specific prevention and vaccination measures to reduce adverse obstetric and neonatal outcomes.

Pregnancy outcomes after maternal covid-19 vaccination during pregnancy: Preliminary data

COVID-19 significantly raises risk during pregnancy. Currently, available evidence suggests that pregnant women are more susceptible to COVID-19 than the general population [1]. Pregnant women with COVID-19 are at increased risk of severe illness, death, and adverse pregnancy outcomes [2–4]. The most effective way to prevent the disease is vaccination. Current research evidence suggests that approved COVID-19 vaccines are safe, effective, and unlikely to pose any dangers to pregnant women or fetuses [5]. National and international associations issued guidelines supporting COVID-19 vaccination in pregnant and lactating women [6]. In the Russian Federation, vaccination of pregnant women with the Gam-COVID-Vac (Sputnik V) vaccine has been permitted since June 2021. Results of animal preclinical studies suggest no adverse impact of the Gam-COVID-Vac vaccine on the course of pregnancy and fetal, embryonic, and prenatal development of offspring [7]. Objective: This study aimed to analyze pregnancy complications after maternal COVID-19 vaccination with domestic vaccines during pregnancy. Region, 75 from Trans-Baikal Krai, 76 from Yaroslavl Region, 89 from Yamalo-Nenets Autonomous Okrug, and 92 from Sevastopol. Most of the women were vaccinated with Gam-COVID-Vac (Sputnik V) vaccine (91.6%) and received two vaccine doses (57.9%). Most of the patients were vaccinated in the first trimester of pregnancy, including 683 (88.4%), 51 (6.6%), and 39 (5%) before 12 weeks, from 12 to 22 weeks, and after 22 weeks of pregnancy, respectively.

Morphometric Parameters of Placental Villi in Parturient Women with COVID-19.

We performed a comparative morphological analysis of placental villi in parturient women with mild and moderate COVID-19 infection. The area and perimeter of terminal villi, their capillaries, and syncytiotrophoblast were assessed on immunohistochemical preparations with antibodies to CD31 using an image analysis system; the parameters of fetal vascular component in the placental villi were also assessed. Changes in the studied parameters differed in parturient women with mild and moderate COVID-19 infection. The observed increase in the total perimeter with a simultaneous decrease in the total capillary area and the degree of vascularization of the placental villi in parturient women with COVID-19 indicates impairment of circulation in the fetal compartment and the development of placental hypoxia, which can be the cause of unfavorable neonatal outcomes.

Changes in amino acid profile of cord blood plasma and amniotic fluid of mothers with COVID-19

Neonates born to mothers with COVID-19 are at risk for infection, they may have high risk of complications during the neonatal period, and long-term health consequences. The study was aimed to define the amino acid profile of blood plasma and amniotic fluid in patients with COVID-19 in order to assess the relationship between the COVID-19 infection during the antenatal period, and metabolomic alterations in the “intrauterine” patient. The levels of 31 amino acids in the samples of amniotic fluid and cord blood plasma of pregnant women with COVID-19, obtained during delivery, were assessed by high-performance liquid chromatography-mass spectrometry. The index group included 29 patients with confirmed diagnosis of COVID-19, and the control group included 17 healthy women with uncomplicated pregnancies. There were significant (p < 0.05) differences in the concentrations of eight amino acids between the studied groups. Logistic regression models were developed (sensitivity 0.84;specificity 1) making it possible to define, whether the assessed amniotic fluid was obtained from COVID-19 patients. Significant differences in the concentrations of four amino acids were observed in the umbilical cord blood. The models developed made it possible to define whether the studied cord blood plasma belonged to controls or to COVID-19 patients (sensitivity and specificity 1). Three amino acids were detected, and their levels were significantly different in COVID-19 patients simultaneously in two points (amniotic fluid and cord blood plasma), depicting the fetal metabolome in a holistic manner. The impact of the virus on those infected results in pronounced metabolomic alterations in the amniotic fluid and the fetal cord blood plasma, which may lead to impaired programming of protein production, but never show up at birth.

The Number of Syncytial Knots and VEGF Expression in Placental Villi in Parturient Woman with COVID-19 Depends on the Disease Severity.

A comparative morphological study was carried out to analyze the number of syncytial knots and VEGF expression in placental villi in parturient women with COVID-19 categorized by the disease severity. The number of syncytial knots was assessed on specimens stained with hematoxylin and eosin. VEGF expression was determined by immunohistochemical analysis in syncytiotrophoblast and villous endothelial cells. Morphological study of the placenta tissue of parturient women with COVID-19 showed increased numbers of syncytial knots in the villi, indicating the development of preplacental hypoxia. High VEGF expression in syncytiotrophoblast and vascular endotheliocytes reflects a stereotyped response to hypoxia and can underlie the development of a preeclampsia-like syndrome. The number of syncytial knots and VEGF expression in placental villi in parturient women with COVID-19 depended on the disease severity.

THE IMPACT OF THE NOVEL CORONAVIRUS INFECTION COVID-19 ON THE MOTHER-PLACENTA-FETUS SYSTEM

Impaired placental development during early pregnancy associated with systemic damage to the vascular endothelium in patients with COVID-19 may result in a number of complications. The study was aimed to reveal histological and immunohistochemical (IHC) features of placental tissue in pregnant women with COVID-19 at different stages of gestation, and to examine the contribution of those to pathogenesis of the disease involving mother-placenta-fetus system. The following two groups of pregnant women were studied: index group of 66 patients with COVID-19, and comparison group of 40 women with no symptoms of viral infection. Macroscopic and microscopic examination, and the IHC analysis of placental samples were carried out. Clinical and anamnestic characteristics of patients with COVID-19 were analyzed taking into account disease severity, delivery route and perinatal outcome. ICH staining using primary antibody revealed elevated expression of proinflammatory factors (TNF alpha, IL8) and reduced level of anti-inflammatory factors (IL4) in placental structures of patients with moderate and severe.OVID-19 (rho < 0.05). The villous tree rearrangement and the development of subclinical placental insufficiency, which could in some cases be decompensated during labor, resulting in clinical manifestations of acute fetal hypoxia were detected in the placental samples obtained from the index group patients. The obstetrical tactics for mothers with COVID-19 should be decided individually based on the risk factors;continuous cardiotocography should be used during labor. It may be appropriate to conduct IHC analysis of placenta in puerperant women with COVID-19 in order to fine-tune the tactics of neonatal management and to predict possible neonatal complications.