[Etiology of severe community - acquired pneumonia in adults: results of the first Russian multicenter study].

AIM: to study the etiology of severe community - acquired pneumonia (SCAP) in adults in Russian Federation. SCAP is distinguished by high mortality and socio - economic burden. Both etiology and antimicrobial resistance are essential for appropriate antibiotic choice. MATERIALS AND METHODS: A prospective cohort study recruited adults with confirmed diagnosis of SCAP admitted to multi - word hospitals of six Russian cities in 2014-2018. Etiology was confirmed by routine culture of blood, respiratory (sputum, endotracheal aspirate or bronchoalveolar lavage) and when appropriate, autopsy samples, urinary antigen tests (L. pneumophila serogroup 1, S. pneumoniae); real - time PCR for identification of "atypical" bacterial pathogens (M. pneumoniae, C. pneumoniae, L. pneumophila) and respiratory viruses (influenza viruses A and B, parainfluenza, human metapneumovirus, etc.) was applied. RESULTS: Altogether 109 patients (60.6% male; mean age 50.8±18.0 years old) with SCAP were enrolled. Etiological agent was identified in 65.1% of patients, S. pneumoniae, rhinovirus, S. aureus and K. pneumoniae were the most commonly isolated pathogens (found in 43.7, 15.5, 14.1 and 11.3% of patients with positive results of microbiological investigations, respectively). Bacteriemia was seen in 14.6% of patients and most commonly associated with S. pneumoniae. Co - infection with 2 or more causative agents was revealed in 36.6% of cases. Combination of bacterial pathogens (mainly S. pneumoniae with S. aureus or/and Enterobacterales) prevailed - 57.7% of cases; associations of bacteria and viruses were identified in 38.5% of patients, different viruses - in one case. CONCLUSION: S. pneumoniae was the most common pathogen in adults with SCAP. A high rate of respiratory viruses (mainly rhinovirus and influenza viruses) identification both as mixt infection with bacteria and mono - infection should be taken into account.

[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.

[Underestimated infection - on the question of the human adenovirus pathogenicity factors.]

Human adenoviruses cause different organ infections of varying severity, from asymptomatic to severe cases with lethal outcome, that are registered everywhere. Detailed and focused study of factors predisposing to a severe course of infection is required. The literature contains information indicating the association of severe adenoviral respiratory diseases with certain types of adenovirus, primarily type 7. This review highlights the possible causes of increased pathogenicity of some types of adenovirus and their association with severe forms of infection. Pathogenicity factors include the ability of adenovirus to bind the specific cellular receptors, the formation of subviral particles, the interaction with blood proteins, in particular the coagulation factor X, as well as the features of the early genes E1A, E1B, E3, E4. In addition, the severity of the disease may be affected by the presence or absence of pre-existing antibodies specific to certain types of adenoviruses. Chronic diseases or immunosuppression also increase the risk of severe adenovirus infection. The information presented in this review may elucidate the pathogenesis of adenovirus infection, and help to develop new features for prevention and treatment.

Virus susceptibility and clinical effectiveness of anti-influenza drugs during the 2010-2011 influenza season in Russia.

BACKGROUND: Antiviral drugs are critical adjuncts to influenza vaccination. This study determined the in vitro susceptibilities of influenza A and B viruses isolated in the 2010-2011 season in Russia to the neuraminidase inhibitor oseltamivir and the hemagglutinin fusion inhibitor umifenovir and clinical efficacy of this antiviral drugs in this season. METHODS: The antiviral potency of these drugs against A(H1N1)pdm09 virus in mice was assessed. Importantly, the clinical effectiveness of oseltamivir and umifenovir was evaluated in a retrospective study conducted in 26 regions of Russia. RESULTS: All tested viruses (n=36) were susceptible to oseltamivir and umifenovir in vitro. Oseltamivir (10mg/kg/day) and umifenovir (60 mg/kg/day) significantly increased the survival of mice challenged with A/California/04/2009 (H1N1)pdm09 virus (p<0.05). Influenza infection was laboratory-confirmed in 442 patients among 1462 patients hospitalized with acute respiratory infections. The treatment of influenza-infected patients within 48h of symptom onset with oseltamivir and umifenovir was associated with a significant decrease in the duration of illness (2-3 days) and symptoms (p<0.001). Pneumonia was observed in none of the patients treated with oseltamivir and in 0.3% of the patients treated with umifenovir, compared to 23.7% of patients who did not receive antiviral therapy (p<0.001). CONCLUSIONS: This study provided experimental and clinical evidence of the efficacy of oseltamivir and umifenovir against influenza viruses, representatives of which have continued to circulate in post-pandemic seasons.

[GENETIC CHARACTERISTICS OF INFLUENZA A/H3N2 AND B VIRUSES THAT HAD CIRCULATED IN RUSSIA IN 2013 - 2015].

AIM: Establish genetic characteristics, carry out phylogenetic analysis and determination of molecular markers of resistance to etiotropic preparations against influenza A/H3N2 and B viruses that had circulated in Russia in 2013 - 2015. MATERIALS AND METHODS: 80 biological samples containing influenza A/H3N2 virus RNA and 31 samples containing influenza B virus RNA were studied. Sequencing of PCR fragments was carried out inABI-3 100 PRIZMTM GeneticAnalyzer (AppliedBiosystems, USA) and using MiSeq (Illumina, USA). Data treatment and analysis was carried out using CLC v.3.6.5., DNASTAR and BioNumerics v.6.5. programs. RESULTS: In 2013 -2014 A/Texas/50/2012-like-clade 3C.3 influenza A/H3N2 viruses dominated, 10% belonged to subclade 3C.2a and 10% - to 3C.3b. Most of the viruses (8 1%) of 2014 - 2015 were of 3C.2a clade, the portion of viruses belonging to 3C.3b and 3C.3a was 9 and 10%. Yamagata-like viruses predominated among the studied influenza B viruses, only 1 virus of 2014 - 2015 belonged to Victoria lineage, 1 reassortant of Yamagata and Victoria lineages was detected. Rimantadine- resistance mutationS3 lN(M2 protein) was detected in all the influenza A/H3N2 viruses. Mutations determining resistance to oseltamivir (NA gene) were not detected in influenza A/H3N2 and B viruses. CONCLUSION: Increase of influenza morbidity in 2014 - 2015 was determined by the emergence of influenza A/H3N2 and B viruses, antigenically distinct from those that had circulated previously and those included into the vaccine, thus resulting in the WHO decision to change A/ H3N2 and B components of the 2015 - 2016 vaccine: Simultaneous circulation of 2 lineages of influenza B virus and emergence of their reassortants gives evidence on the necessity of use of quadrivalent vaccines, containing both lineages.

[A case of adenovirus infection complicated by gram-negative polymicrobial sepsis: A clinical and morphological observation].

Among respiratory infections, adenovirus infection (ADVI), in the presence of which there may be severe pneumonia that frequently results in a fatal outcome, occupies particular attention. ADVI in patients without immunodeficiency is usually mild and shows a limited extent of injury. At the same time the disease in immunocompromised individuals may be severe, presenting with viremia, evolving sepsis, and high death rates. The paper gives a characteristic example of severe ADVI and its fatal outcome.

[ADENOVIRUSES IN THE ETIOLOGICAL STRUCTURE OF ACUTE RESPIRATORY VIRAL INFECTION IN MOSCOW IN 2004 - 2014].

AIM: Study prevalence of adenovirus species and serotypes that had caused acute respiratory viral infection (ARVI) in Moscow in 2004 - 2014. MATERIALS AND METHODS: Material from respiratory tract of 4731 patients with ARVI and 663 conditionally healthy children and adults was used. ARVI causative agents were detected by PCR with real-time detection using AmpliSens reagent kits (CRIE, Moscow). Membership of adenoviruses to a certain serotype was determined by sequencing of hexon gene segment. Adenoviruses that had caused ARD in servicemen in 2010 - 2014 were also studied. RESULTS: ARVI causative agents were detected in 64.6% ill children and 58% of adults. Respiratory-syncytial and rhinoviruses prevailed in children, influenza A virus--in adults. Adenoviruses were detected in 6.9% of ill children and 2.9% of adults during the whole year, with a rise in October-December. B and C species occurred at an equal frequency, E species was found less often. Serotypes 3 and 2 prevailed in 34% and 21% of cases of adenovirus mono-infection, respectively, serotypes 7, 6 and 4 occurred less often. 4 out of 5 outbreaks of adenovirus infection in servicemen were caused by serotype 7. Adenoviruses were absent in the group of healthy adults, in conditionally healthy children were detected in 0.4% of cases and were attributed to serotypes 1 and 2. CONCLUSION: Etiological structure of ARVI was studied for the last decade. Adenovirus infection ranked 5th in children and 7th in adults. 9 serotypes of 3 species of respiratory adenoviruses were identified. Varying prevalence of species and serotypes depending in season, clinical diagnosis and patient age was demonstrated.

[Adenovirus pneumonia with a fatal outcome in adults].

AIM: To retrospectively analyze the medical records of patients who have died from complications of community-acquired pneumonia (CAP) caused by adenovirus serotype 7. SUBJECTS AND METHODS: CAP was diagnosed in patients (6 men aged 19-24 years and 1 woman aged 49 years) on the basis of clinical, laboratory, and radiological findings. Adenoviral pneumonia was established by real-time polymerase chain reaction (PCR). Adenovirus DNA was detected in the patients' autopsy samples (lungs, brain, spleen, liver, blood). The adenoviruses were referred to as B1 serotype 7 on the basis of hexone gene sequencing results. Other potential causative agents of pneumonia were excluded by a battery of molecular genetic tests for a wide range of viral and bacterial pathogens of acute respiratory tract infections. RESULTS: In all cases, the disease began acutely with fever (37.8 to 39 °C), weakness, headache, a sore throat, a dry, unproductive cough or runny nose. Clinical deterioration during symptomatic therapy led to hospital admission for CAP on disease days 2-11. The patients continued to feel worse during massive antibiotic therapy, by switching a drug one to six times and by simultaneously using 2-4 antibiotics and intensive therapy. Death occurred on disease days 10-24. Postmortem examination of all the patients revealed acute respiratory distress syndrome and multiple organ failure. CONCLUSION: Adenovirus pneumonia causes diagnostic and therapeutic problems for clinicians. The clinical introduction of PCR methods for the diagnosis of viral infections allow the clinicians to elaborate and timely use effective management tactics in patients with adenoviral pneumonia and to prevent their death. It is necessary to design etiotropic therapy agents and to introduce the specific prevention of adenovirus infection in risk groups.