[Pre-exposure prophylaxis of new COVID-19 coronavirus infection with tixagevimab/cilgavimab in adult Moscow patients with primary immunodeficiencies].

BACKGROUND: Primary immunodeficiencies (PIDs), now known as inborn errors of immunity, are a group of inherited diseases caused by defects in the genes that control the immune response. Patients with PIDs have risks of developing a severe course and/or death in COVID-19. Passive immunization with long-acting monoclonal antibodies (MABs) to SARS-CoV-2 should be considered as pre-exposure prophylaxis in patients with PIDs. Tixagevimab/cilgavimab is a combination of MABs that bind to the SARS-CoV-2 spike protein. AIM: To evaluate the efficacy and safety of pre-exposure prophylaxis of new SARS-CoV-2 infection in PIDs with the combination of tixagevimab/cilgavimab. MATERIALS AND METHODS: Forty eight patients diagnosed with PIDs were included in the study. Median follow-up after drug administration was 174 days. The total number of confirmed coronavirus infections in patients with PIDs as well as 6 months before and after administration of MAT were assessed. RESULTS: In the analyzed cohort, the overall incidence of COVID-19 from pandemic onset to MABs administration was 75% (36/48), with 31% (11/36) of over-infected patients having had the infection more than once. The incidence of COVID-19 immediately 6 months before the introduction of tixagevimab/cilgavimab was 40%. All patients who had COVID-19 after pre-exposure prophylaxis had a mild infection. The incidence of COVID-19 6 months after tixagevimab/cilgavimab administration significantly decreased compared to the incidence 6 months before administration (7 and 40%, respectively; p<0.001). CONCLUSION: The use of tixagevimab/cilgavimab in patients with PIDs is effective as pre-exposure prophylaxis and reduces the risk of severe COVID-19.

[Molecular epidemiological analysis of SARS-CoV-2 genovariants in Moscow and Moscow region].

INTRODUCTION: SARS-CoV-2, a severe acute respiratory illness virus that emerged in China in late 2019, continues to spread rapidly around the world, accumulating mutations and thus causing serious concern. Five virus variants of concern are currently known: Alpha (lineage B.1.1.7), Beta (lineage B.1.351), Gamma (lineage P.1), Delta (lineage B.1.617.2), and Omicron (lineage B.1.1.529). In this study, we conducted a molecular epidemiological analysis of the most prevalent genovariants in Moscow and the region. The aim of the study is to estimate the distribution of various variants of SARS-CoV-2 in Moscow city and the Moscow Region. MATERIALS AND METHODS: 227 SARS-CoV-2 sequences were used for analysis. Isolation of the SARS-CoV-2 virus was performed on Vero E6 cell culture. Sequencing was performed by the Sanger method. Bioinformatic analysis was carried out using software packages: MAFFT, IQ-TREE v1.6.12, jModelTest 2.1.7, Nextstrain, Auspice v2.34. RESULTS: As a result of phylogenetic analysis, we have identified the main variants of the virus circulating in Russia that have been of concern throughout the existence of the pandemic, namely: variant B.1.1.7, which accounted for 30% (9/30), AY.122, which accounted for 16.7% (5/30), BA.1.1 with 20% (6/30) and B.1.1 with 33.3% (10/30). When examining Moscow samples for the presence of mutations in SARS-CoV-2 structural proteins of different genovariants, a significant percentage of the most common substitutions was recorded: S protein D614G (86.7%), P681H/R (63.3%), E protein T9I (20.0%); M protein I82T (30.0%), D3G (20.0%), Q19E (20.0%) and finally N protein R203K/M (90.0%), G204R/P (73.3 %). CONCLUSION: The study of the frequency and impact of mutations, as well as the analysis of the predominant variants of the virus are important for the development and improvement of vaccines for the prevention of COVID-19. Therefore, ongoing molecular epidemiological studies are needed, as these data provide important information about changes in the genome of circulating SARS-CoV-2 variants.

[Causes of death in the Moscow region according to medical death certificates]. / Prichiny smerti v Moskovskoi oblasti po dannym meditsinskikh svidetel'stv o smerti.

OBJECTIVE: Determination of the leading causes of death based on data from primary medical death certificates (MDCs) depending on the place of death. MATERIAL AND METHODS: From the electronic database of the Main Department of the Civil Registry Office of the Moscow Region (the USR registry office system) for 2021, all cases were selected in which diseases were indicated as the primary cause of death (PCD); all codes of external causes, injuries and poisonings were excluded. A total of 109.126 cases, 50.6% died in the hospital, 34% died at home, and 16.4% died elsewhere. Bureau of Forensic Medical Examination (BFME) issued 45.2% of MSS. Taking into account the frequency of use of ICD codes, the clinical similarity of individual codes, 20 groups were formed, which accounted for 90.1% of deaths from diseases. RESULTS: The frequency of registration of individual groups of causes of death largely depends on the place of death. 5 leading groups of causes of death were established: 1) in general from COVID-19 23.55%, chronic ischemic heart disease (CIHD-1) without postinfarction cardiosclerosis, aneurysm and ischemic cardiomyopathy (CMP) 14.5%, from encephalopathy indefinite (EI) 11.4%, malignant neoplasms (MN) 11.3%, stroke 6.2%; 2) in a hospital from COVID-19 45%, stroke 10%, MN 8.3%; CIHD-1 7.1%, CIHD with a history of MI/ischemic CMP 2.7%; 3) at home from CIHD-1 21.8%, EI 21.5%, MN 15.5%, from diseases associated with alcohol 3.3% and brain cyst 3.3%; 4) elsewhere from CIHD-1 22.7%, EI 21.6%, MN 12%, from other forms of acute coronary artery disease 5.4%, alcohol-associated diseases 4.8%. Acute MI ranked 6th among deaths in general - 2.7%. PCD is also associated with the place of issue of the MDCs - 90% of the MDC with the indication of EI and «other degenerative diseases of the nervous system¼ as the cause of death were issued by the BFME. Not a single MDC issued by the BFME contained such PCDs as "old age" or "brain cyst". CONCLUSION: The nosological structure of the causes of death and the issuance of individual ICD codes in the MDC as a PCD varies significantly depending on the place of death and the issuance of the MDC. The reasons need to be further clarified. The use of codes that are not permitted for use has been registered.

[HOSPITAL MORBIDITY OF CHILDREN IN THE CITY OF MOSCOW DURING THE COVID-19 PANDEMIC].

The article presents information on trends in hospital morbidity of child population in Moscow, as well as morbidity of children in the first year of life. Authors used population data and information from Form No. 14 of the Federal statistical observational study "Information on the activities of the medical organization departments providing inpatient medical care" between 2014 and 2021.In addition to the general indexes, the article presents categories of diseases that were significantly affected by changes in the lifestyle of children during the COVID-19 pandemic. Significant fluctuations in the incidence of infectious diseases are worth noting as they are certainly related to both fragmentations in groups of children during the pandemic, and proper nutrition, which led to positive changes in hospital morbidity due to gastrointestinal disorders. Changes in education, social isolation, better control over hygiene by the government, society and parents has led to unprecedented positive dynamics in morbidity rates of certain diseases. It is worth noting that the COVID-19 infection during pregnancy didn't lead to expected high increases in morbidity rates associated with diseases in the perinatal period.In addition to hospital morbidity, the article presents data on mortality in 24-hour inpatient facilities, as well as changes in the proportion of emergency admissions of patients under 18 to Moscow state hospitals.

[ORGANIZATION OF GENOMIC SURVEILLANCE FOR SARS-CoV-2 WITHIN THE MOSCOW CITY HEALTH DEPARTMENT].

An important goal of COVID-19 surveillance is to detect outbreaks using modern molecular epidemiology techniques based on methods to decode the full genome of the virus, since rapidly evolving RNA viruses, which include SARS-CoV-2, are constantly accumulating changes in their genomes. In addition to using these changes to identify the different virus lines spreading in the population, the availability of sequence information is very important. It will allow the identification of altered variants that may be more transmissible, cause more severe forms of disease, or be undetectable by existing diagnostic test systems. The global scientific community is particularly interested in changes in the spike protein (S-protein, Spike) because they are responsible for binding and penetration into the host cell, lead to false-negative results in diagnostic tests, and affect transmission rates, health outcomes, therapeutic interventions, and vaccine efficacy.Genomic surveillance uses next-generation sequencing (NGS) applications and makes data on the full genome of the virus available. These methods offer new means to detect variants that differ phenotypically or antigenically. This approach promotes earlier prediction as well as effective strategies to mitigate and contain outbreaks of SARS-CoV-2 and other new viruses long before they spread worldwide.Today, molecular typing of strains is playing an increasingly important role in this process, as it makes it possible to identify samples that share a common molecular «fingerprint¼.

[COVID-19 pandemic and alcohol use patterns in Moscow population: forensic aspects]. / Pandemiya COVID-19 i patterny upotrebleniya alkogolya sredi naseleniya Moskvy: sudebno-meditsinskie aspekty.

The presents an analysis of the trend of the postmortem ethanol tests in biological samples obtained from the deceased in Moscow in April-May 2019 and 2020. In total, 7110 reports of forensic chemistry studies were examined; all cases were classified by the age of the deceased, following the modern generational theory to study patterns of alcohol consumption in these age groups and the impact of the COVID-19 pandemic. Stable patterns of alcoholic behavior were revealed in the groups of the deceased. It was shown that, on average, every 3rd representative of Generations «X¼ and «Y¼ consumes alcohol shortly before death; the highest average blood ethanol levels were found in representatives of Generations «Y¼ and «X¼. The number of positive ethanol test results increased in April-May 2020 among males of the baby boom and Generation «X¼ compared to the same period in 2019. The patterns identified can be used to further study the contribution of alcohol consumption to mortality.

SARS-CoV-2 infection in children in Moscow in 2020: clinical features and impact on circulation of other respiratory viruses: SARS-CoV-2 infection in children in Moscow in 2020.

OBJECTIVES: This study aimed to estimate the impact of the COVID-19 pandemic on the circulation of non-SARS-CoV-2 respiratory viruses and the clinical characteristics of COVID-19 in hospitalized children. METHODS: A total of 226 and 864 children admitted to the Children's City Clinical Hospital with acute respiratory infection in September to November of 2018 and 2020 in Moscow were tested for respiratory viruses using multiplex polymerase chain reaction (PCR) and Mycoplasma pneumoniae/Chlamydia pneumoniae using enzyme-linked immunosorbent assay. RESULTS: The detection rate of non-SARS-CoV-2 viruses in 2020 was lower than in 2018, 16.9% versus 37.6%. An increase in the median age of children with respiratory viruses was observed during the pandemic (3 years vs 1 year). There was no significant difference in the frequency of intensive care unit (ICU) admission in children with SARS-CoV-2 and other respiratory virus infections (2.7% vs 2.9%). SARS-CoV-2 and human rhinoviruses, human metapneumoviruses, and human adenoviruses showed significantly lower than expected co-detection rates during co-circulation. An increase in body mass index (BMI) or bacterial coinfection leads to an increased risk of ICU admission and a longer duration of COVID-19 in children. CONCLUSIONS: The COVID-19 pandemic led to significant changes in the epidemiological characteristics of non-SARS-CoV-2 respiratory viruses during the autumn peak of the 2020 pandemic, compared with the same period in 2018.

[Monitoring the spread of the SARS-CoV-2 (Coronaviridae: Coronavirinae: Betacoronavirus; Sarbecovirus) variants in the Moscow region using targeted high-throughput sequencing].

INTRODUCTION: Since the outbreak of the COVID-19 pandemic caused by SARS-CoV-2 novel coronavirus, the international community has been concerned about the emergence of mutations altering some biological properties of the pathogen like increasing its infectivity or virulence. Particularly, since the end of 2020, several variants of concern have been identified around the world, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2). However, the existing mechanism of detecting important mutations are not always effective enough, since only a relatively small part of all pathogen samples can be examined by whole genome sequencing due to its high cost. MATERIAL AND METHODS: In this study, we have designed special primer panel and used it for targeted highthroughput sequencing of several significant S-gene (spike) regions of SARS-CoV-2. The Illumina platform averaged approximately 50,000 paired-end reads with a length of ≥150 bp per sample. This method was used to examine 579 random samples obtained from COVID-19 patients in Moscow and the Moscow region from February to June 2021. RESULTS: This study demonstrated the dynamics of distribution of several SARS-CoV-2 strains and its some single mutations. It was found that the Delta strain appeared in the region in May 2021, and became prevalent in June, partially displacing other strains. DISCUSSION: The obtained results provide an opportunity to assign the viral samples to one of the strains, including the previously mentioned in time- and cost-effective manner. The approach can be used for standardization of the procedure of searching for mutations in individual regions of the SARS-CoV-2 genome. It allows to get a more detailed data about the epidemiological situation in a region.

[EXPERIENCE OF FORMING OPERATIONAL AREAS OF OPERATION OF THE CHILDREN'S POLYCLINIC DURING THE PANDEMIC COVID-19].

The article presents the experience of the city children's polyclinic No. 133 of the Moscow Department of Health in a difficult epidemiological situation associated with a new infection COVID-19. A description of the stages of the organizational work of a polyclinic in a pandemic is given, including such areas as: a) conducting lectures and webinars for doctors and nurses of a medical organization, introducing recommended methods for diagnosing and treating COVID-19, creating and observing conditions for the personal safety of employees; b) the formation of tools and a database for analytical work; creation of registers of patients and employees of the polyclinic in order to monitor and evaluate the effectiveness of work; characteristics of the structures of age-specific morbidity in children who have undergone a new coronavirus infection and community-acquired pneumonia with substantiated confirmation for them of compulsory dispensary observation and rehabilitation measures; description of the development of routing of healthy and sick children, operational identification and continuous analysis of difficulties in the work of the polyclinic during this period; c) the formation of distance technologies in treatment and prophylactic work with patients, organized group and individual exercise therapy classes, including respiratory rehabilitation gymnastics for children who have undergone a new coronavirus infection; development of an organizational algorithm for the formation of medical and nursing teams for visiting patients with COVID-19 at home and individual teams for visiting patients for patronage. The organization of this treatment and prophylactic work was approved and a confirmation was received from the Ministry of Health of the Russian Federation of the right to replicate the experience gained from the work of the polyclinic in the conditions of COVID-19.

[DENTAL CARE FOR MOSCOW REGION CITIZENS IN THE CONDITIONS OF THE COVID-19 PANDEMIC (APRIL-JUNE 2020)].

It is known that the oral cavity is an epidemiological hazard due to the high level of viral and bacterial contamination. Despite the narrow specialization and distant connection with the problem of viral pneumonia, dentists, nevertheless, are at risk of contracting the new coronavirus infection COVID-19. To reduce the epidemiological activity the provision of routine dental care was suspended in the vast majority of regions of the Russian Federation including the Moscow region, from the end of March 2020 to June 20, 2020. During the entire period of routine medical care suspended, the Moscow region chief dentist's team was daily monitoring information about applied patients. The suspension of routine medical care has reduced the number of cases of COVID-19 infection contact transmission in medical organizations during the period of the most active increase in the morbidity. In addition, the decrease in the number of patients enabled medical organizations to reduce the number of medical personnel, which contributed to a decrease in the percentage of morbidity among doctors.

[The characteristics of population mortality of the Russian Federation, the Central Federal Okrug and City of Moscow in 2020].

To preserve the country's population is among one of the most vital tasks over the period of existence of the new Russia and constitutes the subject of national security. The article presents the results of analysis of population mortality rate of the Russian Federation, the Central Federal Okrug and City of Moscow during the first eight months of 2020 towards to concurrent period of 2019. In January-March 2020, the population total mortality rate, retaining prevalent trends of number of preceding years, decreased in the Russian Federation by 3.8%, in the Central Federal Okrug by 3.0% and in City of Moscow by 3.9%. However, since April-May the situation has changed dramatically and, according to the results of January-August, mortality by this time has increased, and its growth made up to 6.5% in the Russian Federation, 7.8% in the Central Federal Okrug and 15.6% in the City of Moscow. In May 2020, the gain of absolute number of the deceased in the Russian Federation by months (towards to concurrent month of 2019) made up to 11.9%, in June to 18.6%, in July to 19.7% and in August to 9.6%. In Moscow, the peak values of this increase were noted in May - 57.2% and in June - 41.6% In the conditions of new coronavirus infection pandemic, the share of COVID-19, as main cause of death (ICD-10 codes U07.1 and U07.2), in the structure of total mortality in April-August consisted 3.2% and in the structure of excess deaths in May-August - 28.6%. The increase of mortality and continued decrease of birth rate resulted in increasing of natural population loss by 1.5 times and more and reached such values as -3.6 in the Russian Federation, -4.9 in the Central Federal Okrug and -1.6 in the City of Moscow (per 1000 of population). The process of depopulation of the Russian nation not only retained, but significantly has become significantly aggravated.

[Organizing the medical care for the COVID-19 patients in non-infectious Moscow hospital: reassignment experience].

AIM: To present the results of work of National Medical Research Center of Treatment and Rehabilitation, reassigned for COVID-19 patients treatment during pandemic. Run-up methodology, procedures and working process organization are detailed. MATERIALS AND METHODS: 354 COVID-19 patients were treated from 13.04.2020 to 10.06.2020 [age 59 (470) years, 56% women, body mass index 28.5 (24.932.2) kg/m2]. Patients were admitted at 8 (611) day of sickness. In-hospital stay was 16 (1420) days. RESULTS: NEWS scale at the day of admittance was 2 (14); 2 (13) in patients discharged alive and 6 (47) in died patients, p=0.0001. So prognostic accuracy of NEWS scale was confirmed as very well (area under ROC-curve = 0.819). 69 patients (19.5%) were treated at intensive care department for 7 (413) days. 13 patients died, 11 of them had COVID-19 as direct or indirect cause of death. Total in-hospital mortality was 3.67%, in-hospital mortality of COVID-19 patients 3.1%. 17 healthcare workers (HCW), contacted with COVID-19 patients were infected (2.67%). 4 HCW, who had no direct contact with patients were also infected and 7 HCW were infected before the first patient was admitted. No one of them died. CONCLUSION: Complex tasks of healthcare organization during COVID-19 pandemic can be solved quickly with acceptable quality, characterized by low levels of patients; mortality and HCW infection.

[Risk factors for the early development of septic shock in patients with severe COVID-19].

AIM: In a retrospective study, we evaluated factors associated with the early development of septic shock in patients with severe COVID-19. MATERIALS AND METHODS: We collected medical records of the intensive care unit patients submitted by the local COVID-19 hospitals across Russia to the Federal Center for the Critical Care at the Sechenov First Moscow State Medical University (Sechenov University). Septic shock in crticially ill patients requiring mechanical ventilation was defined as a need in vasopressors to maintain blood pressure. RESULTS: We studied 1078 patients with severe COVID-19 who were admitted to the intensive care units for respiratory support. There were 611 males and 467 females. The mean age was 61.013.7 years. Five hundred twenty five medical records (48.7%) were received from the Moscow hospitals, 159 (14.7%) from the Moscow region, and 394 (36.5%) from the hospitals located in 58 regions of the Russian Federation. In 613 (56.9%) patients, diagnosis of SARS-CoV-2 infection was confirmed by PCR, and in the other cases it was established on the basis of the clinical picture and the results of the chest CT scan. Septic shock developed in 214 (19.9%) of 1078 patients. In the logistic regression model, the risk of septic shock in patients older than 50 years was higher than in patients of a younger age (OR 2.34; 95% CI 1.533.67; p0.0001). In patients with more severe SARS-CoV-2 infection, there was an increase in the prevalence of cardiovascular diseases, including coronary heart disease and atrial fibrillation, type 2 diabetes and malignant tumors. The risk of septic shock in patients with three or more concomitant diseases was higher than in patients without any concomitant chronic diseases (OR 1.76; 95% CI 1.762.70). CONCLUSION: The risk of septic shock in patients with acute respiratory distress syndrome induced by SARS-CoV-2 is higher in patients older than 50 years with concomitant diseases, although a severe course of the disease is also possible in younger patients without any concomitant disorders.

[Analysis of human coronaviruses circulation].

INTRODUCTION: The novel SARS-CoV-2 coronavirus, which emerged at the end of 2019 and caused a worldwide pandemic, triggered numerous questions about the epidemiology of the novel COVID-19 disease and  about wellknown coronavirus infections, which used to be given little attention due to their mild symptoms. THE PURPOSE: The routine screening-based multiyear retrospective observational study of prevalence and circulation patterns of epidemic-prone human coronaviruses in Moscow. MATERIAL AND METHODS: The real-time polymerase chain reaction was used to detect RNA of human coronaviruses (HCoVs) in nasal and throat swabs from 16,511 patients with an acute respiratory infection (ARI), aged 1 month to 95 years (children accounted for 58.3%) from January 2016 to March 2020, and swabs from 505 relatively healthy children in 2008, 2010 and 2011. Results. HCoVs were yearly found in 2.6-6.1% of the examined patients; the detection frequency was statistically higher in adults than in children, regardless of sex. At the height of the disease incidence in December 2019, HCoVs were detected in 13.7% of the examined, demonstrating a two-fold increase as compared to the multi-year average for that month. The statistical frequency of HCoV detection in ARI pediatric patients under 6 years was significantly higher than in their healthy peers (3.7 vs 0.7%, p = 0.008). CONCLUSION: HCoVs circulate annually, demonstrating a winter-spring seasonal activity pattern in the Moscow Region and reaching peak levels in December. Over the years of observation, the HCoV epidemic activity reached maximum levels in December 2019-February 2020 and decreased in March to the multi-year average. Amid a growing number of SARS-CoV-2 cases imported to Moscow in March 2020, the HCoV detection frequency dropped sharply, which can be explained by the competition between different coronaviruses and by the specificity of HCoV detection with the diagnostic test kit used in this study.

[Patterns of the SARS-CoV-2 epidemic spread in a megacity].

The purpose of the study is to analyze patterns demonstrated by the COVID-19 epidemic process in a megacity during the increase, stabilization and reduction in the incidence, and to evaluate the effectiveness of the epidemic prevention measures. MATERIALS AND METHODS: The comprehensive study incorporating epidemiological, molecular genetic and  statistical research methods was conducted to analyze the spread of SARS-CoV-2 in Moscow during the COVID- 19 pandemic. RESULTS AND DISCUSSION: It was found that the exponential growth in COVID-19 cases was prevented due to the most stringent control and restrictive measures deployed in Moscow to break the chains of SARS-CoV-2 transmission and due to people who were very disciplined in complying with the self-isolation rules. The  analysis of the dynamics in detection of new COVID-19 cases showed that in a megacity, the impact of social distancing and self-isolation would become apparent only after 3.5 incubation periods, where the maximum length of the period is 14 days. It was discovered that the detection frequency of SARS-CoV-2 RNA in relatively healthy population and its dynamics are important monitoring parameters, especially during the increase and stabilization in the COVID-19 incidence, and are instrumental in predicting the development of the epidemic situation within a range of 1-2 incubation periods (14-28 days). In Moscow, the case fatality rate was 1.73% over the observation period (6/3/2020-23/6/2020). CONCLUSION: The epidemiological analysis of the COVID-19 situation in Moscow showed certain patterns of the SARS-CoV-2 spread and helped evaluate the effectiveness of the epidemic prevention measures aimed at  breaking the routes of transmission of the pathogen.