Russian Influenza Research Articles

Evaluation of the preventive effectiveness of russian influenza vaccines in the epidemic seasons of 2018-2021

Monitoring the effectiveness of influenza vaccines annually enables the development of measures aimed at decreasing influenza incidence, hospitalization, and mortality rates. The epidemiological effectiveness of several Russian domestic influenza vaccines was evaluated in St. Petersburg in the 2018-2021 epidemic seasons. Male and female participants (N = 6912) aged 18-23 were monitored from 2018 to 2021. Sovigripp, Grippol Plus, Ultrix, and Ultrix Quadri inactivated influenza vaccines were used for immunization. In 2018-2019, when the vaccine strains fully matched the circulating influenza viruses, prophylactic vaccination resulted in a 2.7 to 7.1-fold reduction in influenza cases. The protective effectiveness of the vaccines against influenza and acute respiratory infections (ARIs) totalled 52.4%, reaching 73.0% effectiveness against influenza after laboratory confirmation. In the epidemic season 2019-2020, when the circulating viruses and vaccine strains did not fully match, the incidence of influenza and ARIs reduced twice due to vaccination; the total vaccine effectiveness against influenza and ARIs amounted to 50.0%. The Grippol Plus, Ultrix, and Ultrix Quadri vaccines proved to be the most effective, demonstrating a total effectiveness of 70.6%-75.0% and a 65.5%-83.5% effectiveness against influenza A and B. In the 2020-2021 epidemic season, no data on the preventive effectiveness of the influenza vaccines could be obtained due to the outbreak of COVID-19 and the absence of detectable influenza virus shedding in the study participants. The results obtained are consistent with WHO experts’ estimates which indicate that modern influenza vaccines reduce the incidence of influenza in adults by 70-90% if the vaccine strains match the circulating virus strains.

Origin of the H1N1 (Russian influenza) pandemic of 1977-A risk assessment using the modified Grunow-Finke tool (mGFT).

In 1977, the Soviet Union (Union of Soviet Socialist Republics [USSR]) notified the World Health Organization (WHO) about an outbreak of H1N1 influenza, which later spread to many countries. The H1N1 strain of 1977 reappeared after being absent from the world for over 20 years. This pandemic simultaneously spread to several cities in the USSR and China. Many theories have been postulated to account for the emergence of this pandemic, including natural and unnatural origins. The purpose of this study was to use the modified Grunow-Finke risk assessment tool (modified Grunow-Finke tool [mGFT]) to investigate the origin of the 1977 H1N1 pandemic. Data was collected from WHO archives and published documents. The assessment of the pandemic's origin involved the utilization of a modified version of the original Grunow-Finke risk assessment tool (GFT). Using the mGFT, the final score was 37 out of 60 points (probability: 62%), indicating a high likelihood that the Russian influenza pandemic of 1977 was of unnatural origin. Several variables supported this finding, including the sudden re-emergence of a previously extinct strain, a genetic signature of laboratory modification for vaccine development, and unusual epidemiology. Inter-rater reliability was moderate to high. By applying the mGFT to the 1977 Russian influenza pandemic, we established a high probability that this pandemic was of unnatural origin. Although this is not definitive, it is consistent with the possibility that it originated from an incompletely attenuated live influenza vaccine. The mGFT is a useful risk analysis tool to evaluate the origin of epidemics.

Clinical trial of tolerability, safety, and immunogenicity of the Russian influenza inactivated split vaccine Flu-m in children from 6 months to 9 years of age

Purpose: To study the reactogenicity, safety and immunogenicity of the Russian vaccine Flu-M in comparison with Vaxigrip vaccine for influenza prevention in children aged from 6 months to 9 years (phase III).Materials and Methods. In 2021, a clinical study was conducted in which children aged 6 months to 9 years were immunized with Flu-M vaccine (produced by SPbSRIVS, Russia) and Vaxigrip vaccine (produced by Sanofi Pasteur S.A., France). After randomization one group of children was vaccinated with Flu-M, the other with Vaxigrip, and monitored for 180±3 days after vaccination. Children vaccinated between 3 and 9 years of age were studied in phase I, and between 6 months and 3 years of age in phase II. Tolerability and safety were assessed by the frequency and extent of adverse events, as well as by the assessment of vital signs and physical examination. Immunological efficacy assessment criteria were geometric mean antibody titer, seroconversion level, seroconversion factor, seroprotection level.Results. Both vaccines (Flu-M and Vaxigrip) were shown to be well tolerated by children of both age groups. No serious adverse events or severe adverse events were reported in the study. Immunological efficacy criteria were achieved for both vaccines for all strains of influenza virus in children of both age groups at 28 and 56 days after vaccination. No cases of influenza or acute respiratory infections were seen at 180±3 days postvaccination.Conclusion. The results of the clinical study show that the Flu-M and Vaxigrip vaccines are comparable in both age groups of children.The trial is registered at ClinicalTrials.gov (NCT 05470582).

Reactive systemic vasculitis in the course of a coronavirus OC43 infection: a case report

This case report details a severe systemic failure following a coronavirus OC43 (HCoV-OC43) infection. A 78-year-old man, who had been vaccinated against SARS-CoV-2, was hospitalized for a flu-like infection and abdominal pain, revealing bilateral hemorrhagic adrenal infarctions with secondary adrenal failure. Imagery examinations showed adrenal necrosis and multiple ischemic cerebral strokes. A multiplex retro-transcriptase polymerase chain reaction (RT-PCR) became positive for HCoV-OC43. Cardio-vascular, infectious, and auto-immune exams were negative. A steroid medication finally allowed clinical improvement, and the diagnosis of reactional vasculitis was retained. An unknown pathogenicity of HCoV-OC43 is possible, considering that RT-PCR research is rarely made. The hypothesis of cross-reactions with SARS-CoV-2 antivaccine antibodies is also feasible. At last, the possible former virulence of HCoV-OC43 is being researched, in the event that this virus is connected to the 1889 Russian influenza pandemic. The development of multiplex RT-PCR would enable the study of other HCV-OC43 infections.

Review on the Epizootiological Situation on Highly Pathogenic Avian Influenza around the World and in Russia in 2022

This paper describes the current situation on highly pathogenic avian influenza virus in 2022 and provides forecast of the possible further spread of avian influenza in Russia. In 2022, the circulation of a wide variety of highly pathogenic avian influenza virus subtypes, which have epizootiological and epidemiological significance, was recorded in the world. Outbreaks caused by highly pathogenic avian influenza virus were reported in over 60 countries. In addition, human infections with influenza viruses of the A(H5Nx) and A(H9N2) subtypes were registered. There was a large-scale epizootic which affected more than 10 regions of the European part of Russia and the Russian Far East in 2022. Outbreaks among wild birds and poultry were caused by the highly pathogenic influenza virus A(H5N1) of the clade 2.3.4.4b, at the same time genetic and antigenic diversity was observed among viruses circulating in Russia. Thus, an essential geographical role of the territory of Russia in the global spread of avian influenza virus has been shown once again, which highlights the importance of continuous avian influenza virus surveillance in the country.

SARS, MERS and COVID-19-Associated Renal Pathology

Coronaviruses are a large group of RNA viruses, the most notable representatives of which are SARS-CoV, MERS-CoV and SARS-CoV-2. Human coronavirus infections were first documented in the 1960s, when members causing seasonal common colds were successfully replicated in human embryonal trachea and kidney cell cultures and classified based on electron microscopy. The history of coronaviruses stretched far back to that point, however, with some representatives causing disease in animals identified several decades prior and evolutionary data pointing towards the origin of this viral group more than 55 million years ago. In the short time period of research since they were discovered, coronaviruses have shown significant diversity, genetic peculiarities and varying tropism, resulting in the three identified causative agents of severe disease in humans—SARS, MERS and the most recent one, COVID-19, which has surpassed the previous two due to causing a pandemic resulting in significant healthcare, social and political consequences. Coronaviruses are likely to have caused pandemics long before, such as the so-called Asian or Russian influenza. Despite being epitheliotropic viruses and predominantly affecting the respiratory system, these entities affect multiple systems and organs, including the kidneys. In the kidneys, they actively replicate in glomerular podocytes and epithelial cells of the tubules, resulting in acute kidney injury, seen in a significant percentage of severe and fatal cases. Furthermore, the endothelial affinity of the viruses, resulting in endotheliitis, increases the likelihood of thrombotic microangiopathy, damaging the kidneys in a two-hit mechanism. As such, recently, COVAN has been a suggested nomenclature change indicating renal involvement in coronavirus infections and its long-lasting consequences.

Being Ambulant with Corona Walker

ABSTRACT Corona Walker lived and died in Dartmouth, Nova Scotia at the end of the 19th century. Her headstone records that she died on 11 January 1889, at the age of 18 years, coincidentally less than a year before the Russian Influenza pandemic. There is no memoir, diary, obituary or other first-hand account to be found for her. Walking and writing in the neighbourhoods of her resting place is a method of simultaneously imagining the past and bringing Corona into the present. In this speculative biography, the imagined female protagonist assembles, disassemblesand reassembles as she moves through the city. This work of research creation is situated within spatial, walking-based visual arts practices and is grounded in multisensory experiences of sites, weathers and bodies. The compassionate imagining of Corona Walker affords glimpses of a future to be realised in the aftermath of tragedy.

The enigma of the 1889 Russian flu pandemic: A coronavirus?

The “Russian flu”, which raged from 1889 to 1894, is considered as the first pandemic of the industrial era for which statistics have been collected. This planetary event started in Turkestan and hit the Russian Empire, before reaching all European countries, the United States of America, and the whole world. Contemporaries were surprised by its high contagiousness as evidenced by attack rates averaging 60% in urban populations, its rapid spread in successive waves circling the globe in a few months by rail and sea, and the tendency of the disease to relapse. Despite its low case-fatality rate (0.10%-0.28%), it is estimated to have caused one million deaths worldwide. On serological grounds, it is generally accepted that the causative agent of Russian influenza was Myxovirus influenzae, the virus identified for all influenza pandemics since the “Spanish flu” of 1918. In light of the Covid-19 pandemic, which has underscored the extraordinary epidemic potential of coronaviruses, this assumption has recently been questioned. Coronaviruses come from wild reservoirs (bats, rodents, birds, …). They induce respiratory symptoms mimicking influenza, possibly leading to respiratory distress with pneumonia. In addition to the Covid-19 pandemic, recent deadly and limited epidemics, such as SARS in 2002 and MERS in 2012, have occurred. Russian influenza presented as an influenza-like syndrome with clinical peculiarities (multivisceral and neurological involvement, skin rash, early iterative relapses), evoking some particularities of Covid-19. Four other coronaviruses circulating in the human population for decades (HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1) have been found to be responsible for 15 to 30% of seasonal colds. All of these viruses are of animal origin. Recently, phylogenetic studies have revealed the genetic proximity between a bovine coronavirus BCoV and the human virus HCoV-OC43, indicating that the latter emerged around 1890, at the time of the Russian flu, when an epizootic was raging among cattle throughout Europe. Could the current human virus be the attenuated remnant that appeared after the Russian flu in 1894? Was there a coronavirus pandemic before Covid-19 ?

Development of specific immunity in laboratory animals after co-immunization against seasonal influenza and COVID-19

Introduction. In clinical practice, the differential diagnosis of COVID-19 can be challenging during the flu season, entailing serious consequences such as delays in appropriate control measures against the SARS-CoV-2 pandemic. Another problem is posed by co-infection of SARS-CoV-2 and influenza virus (IV), which significantly contributes to the severity of the COVID-19 disease. This study was aimed to explore the cross-impact of co-administration of Russian influenza and COVID-19 vaccines on development of specific immunity in laboratory animals.Materials and methods. The study was conducted on BALB/c mice. The animals were inoculated intramuscularly with the vaccine for COVID-19 prevention (CoviVac) and the vaccine for influenza prevention (Flu-M). The sera from the immunized animals were examined separately. Three IV strains were used in the hemagglutination inhibition assay. Antibodies (Abs) against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay (ELISA). The neutralization test was performed to detect virus neutralizing antibodies against SARS-CoV-2 and IV.Results. Relatively high titers of specific Abs were found in the groups of animals inoculated with one vaccine and with two vaccines concurrently. In the groups of animals inoculated with CoviVac and with two vaccines concurrently, both in the ELISA test and in the neutralization test, the average titers of specific Abs against SARSCoV- 2 did not demonstrate any statistical difference. The group of animals inoculated concurrently with two vaccines demonstrated statistically higher titers of Abs against IV after the second immunization compared to the group of animals inoculated with Flu-M.Discussion. The study has shown that post-vaccination immunity both to IV and to SARS-CoV-2 develops after co-vaccination with two vaccines. The observed enhanced post-vaccination immune response to IV in the coimmunized laboratory animals needs further research.Conclusion. The performed studies suggest the possibility of co-administration of two vaccines to prevent influenza and COVID-19.

Evaluation of the Preventive Effectiveness of Influenza Vaccines in the Epidemic Season 2019–2020 in St. Petersburg

Background. The vaccine is the best available instrument to prevent influenza and reduce the risks of major disease complications and mortality. The vaccine effectiveness during the influenza season depends on a number of factors: (1) a person vaccinated (their age and health status); (2) the vaccine formulation; (3) types and subtypes of the circulating viruses; (4) vaccination timeline, as the immune response fades over time. An influenza vaccine can yield different effectiveness in people who have been infected or vaccinated previously and in those who have not been yet exposed to the circulating viruses. At present, trivalent and quadrivalent influenza vaccines are registered and produced in Russia. It allows for vaccination of all social groups, including high-risk populations, and for increasing the number of vaccinated individuals yearly. Russian Federation constantly improves the production of influenza vaccines, introducing new variants of vaccine formulations into national clinical usage. It is thus essential to monitor and analyze the changes in the effectiveness of influenza vaccines every season.Aim of the study. To evaluate of the effectiveness of Russian domestic influenza vaccines during the epidemic season 2019–2020 in St. Petersburg compared to the season 2018–2019.Materials and Methods. 3315 female and male adult participants aged 18 years and older were monitored from October 2019 to March 2020. The group included university students and tutors, researchers, and production and office workers of industrial enterprises. Sovigripp, Grippol Plus, Ultrix, and Ultrix Quadri influenza vaccines were used for immunization.Results and Discussion. In the context of incomplete correspondence between the viruses circulating in Russia and the strains used in the vaccines, the vaccination of the St. Petersburg population during the epidemic season 2019-2020 with Sovigripp, Grippol Plus, Ultrix, and Ultrix Quadri influenza vaccines cumulatively reduced influenza and ARI incidences by half; the total vaccine effectiveness against influenza and ARI amounted to 50.0%. The strongest preventive effect was identified for Grippol Plus, Ultrix, and Ultrix Quadri which demonstrated the total vaccine effectiveness from 70.6% to 75.0%, and their effectiveness against influenza A and B viruses reached from 65.5% to 83.5%.Conclusion. In the context of incomplete correspondence between the viral strains used in the vaccines and the strains circulating in Russia and St. Petersburg during the epidemic season 2019- 2020 and considering the active circulation of non-influenza viruses such as rhinoviruses and adenoviruses, we found a moderate preventive effectiveness of the influenza vaccines during the seasonal epidemic increase in ARI cases. Russian domestic influenza vaccines were shown to have good acceptability, be safe, and non-reactogenic.

Overview of the Epizootiological Situation on Highly Pathogenic Avian Influenza in Russia in 2020

This review describes the current situation on highly pathogenic avian influenza virus in 2020 and provides forecast of the possible further spread of avian influenza in Russia. In 2020, the circulation of a wide variety of highly pathogenic avian influenza virus subtypes which have epizootiological and epidemiological significance was recorded in the world. Outbreaks of highly pathogenic avian influenza were reported in over 30 countries. Apart from this, human infections with influenza viruses of the A/H5Nx and A/H9N2 subtypes were reported. There was a large-scale epizootic in Russia in 2020, which affected more than 10 regions. Outbreaks among wild birds and poultry were caused by the highly pathogenic influenza virus A/H5N8 of clade 2.3.4.4b. As a result of those outbreaks, more than 1.5 mil. poultry were killed or perished. It was revealed that strains of the influenza virus isolated in Russia have a high degree of identity with the strains circulating in Europe and Southeast Asia. Thus, it was shown again that the territory of Russia plays an important role in the global spread of avian influenza virus.

"The Most Disastrous and Fatal Epidemic": Mortality Statistics During the 1890 Russian Influenza Epidemic in Connecticut.

During the Russian influenza pandemic, which reached the United States in late 1889, US public health officials attempted to document the number of deaths associated with this disease outbreak. A historical perspective illuminates the complex categories used to classify deaths from influenza-associated diseases; substantial changes in weekly, monthly, and yearly death totals; and thoughtful efforts by health officials to measure the epidemic as it happened. The 1114 influenza deaths reported by the Connecticut State Board of Health in the 3 years after the January 1890 outbreak must be supplemented by the notable increases in the number of deaths from respiratory diseases, which elevates the likely toll to more than 7000 deaths during the epidemic. Whereas historians of public health have primarily examined efforts to control communicable diseases, this case study of mortality statistics reported by town officials and analyzed by the Connecticut State Board of Health demonstrates how officers of the local boards of health also responded to unexpected outbreaks of a familiar disease such as influenza. Understanding how organizations measured influenza-associated mortality illustrates an important stage in the development of American public health and also makes an important contribution to studying pandemics in history.

Phase III, Randomized, Double-Blind, Placebo Controlled Trial of Efficacy, Safety and Tolerability of Antiviral Drug Umifenovir vs Standard Care of Therapy in Non-Severe Covid-19 Patients

SummaryBackground: SARS-Cov2 has caused millions of deaths worldwide and effective antivirals are not yet available. We evaluated the efficacy, tolerability and safety of Umifenovir, a drug used originally against influenza in Russia and China, in non-severe COVID19 adult patients from India. Method : A double-blind placebo controlled Phase III trial spread over 3 hospitals in Lucknow, India viz. King George’s Medical University, ERAs Lucknow Medical College and Ram Manohar Lohia Institute of Medical Sciences was carried out. RT-PCR confirmed COVID19 patients in the age group from 18-75 yrs. were recruited and further stratified into Mild-asymptomatic and Moderate cases. Exclusions included, pregnant or lactating women, severe patients, those suffering from Acute respiratory distress syndrome (ARDS), sepsis shock, requiring invasive ventilator support, ECMO or shock requiring vasopressor support, severe liver disease, severe renal impairment, comorbid conditions like asthma, diabetes with second-third line medicines as defined in the WHO guidance document. Patients were randomized 1:1 on placebo with standard care of therapy or Umifenovir (800 mg BID, maximum 14 days) with standard care of therapy respectively. Computerized randomization was carried out for each group separately through sequentially numbered, opaque, sealed envelopes (SNOSE) in block sizes of six and was administered independently through clinical-site coordinators and to have sufficient number of Mild-asymptomatic and moderate patients. The primary endpoint for Asymptotic-mild patients was time to nasopharyngeal swab negativity by two RT-PCR tests for SARS COV2 antigens taken 24 hrs apart from the date of randomization. For Moderate patients, the average change in the ordinal scale from the baseline scores from randomization on the eight-point ordinal scale as defined by WHO was calculated as the primary endpoint. This trial is registered with the Clinical Trial Registry of India (CTRI) Number: CTRI/2020/09/027535.Findings: A total of 132 patients were recruited in the trial after screening between 3rd October 2020 to 28th April 2021. Of these, 9 patients withdrew consent/ stopped medication on their own. The remaining 123 patients were almost equally distributed into Asymptomatic (35%), Mild (32%) and Moderate (33%) symptoms groups respectively. No Serious adverse events were noted in any of the patients. Only few minor events like headache, stomach ache and nausea were reported and this also was observed almost equally between the Umifenovir and Standard-of-care arms respectively. In the Primary endpoint corresponding to the Mild-asymptomatic patient group (n=82), we found that 73% patients in the Umifenovir arm were RT-PCR negative on the 5th day (P=0.004), while only 40% patients in the placebo arm were negative. In the moderate group, the WHO scores for the Umifenovir arm corresponded to faster clinical improvement as compared to the Placebo arm (P=0.125 on day 3). In the Mild-asymptomatic group, the clinical improvement assessed by the WHO score on day 5 was statistically significant (P=0.019) in the Umifenovir arm compared to the placebo arm and agrees well with the primary endpoint results. Interpretation: Umifenovir is efficacious for Mild-asymptomatic patients and meets the primary and secondary endpoint criteria of the trial. The drug is safe and well tolerated at a dosage of 800 mg BID, maximum 14 days, in adult patients. It exhibits faster time to cure with median 5 days (95%CI, 5-14) in Umifenovir group and median 7 days (95%CI, 5-14) for the placebo group. In moderate patients, administration of Umifenovir co-relates with faster clinical recovery, albeit with less statistical significance. In future studies, the drug should be evaluated as a prophylactic in high-risk adults, and for efficacy in children and pregnant/lactating women.

Taking pandemic sequelae seriously: from the Russian influenza to COVID-19 long-haulers

In January, 1892, the English social reformer and women's rights campaigner Josephine Butler wrote to her son, Stanley, to complain of fatigue and a general declension of the spirits. Butler attributed her symptoms to an attack of “Russian influenza” the previous Christmas, which had left her with painful conjunctivitis and inflamed lungs. “I don't think I ever remember being so weak, not even after the malaria fever at Genoa”, she confessed. 3 months later there was little improvement. “I am so weak that if I read or write for half an hour I become so tired and faint that I have to lie down,” Butler informed a friend.

Overview of the Epizootiological Situation on Highly Pathogenic Avian Influenza Virus in Russia in 2019

This review describes the current situation on highly pathogenic avian influenza virus in 2019 and predicts the possible further spread of avian influenza in Russia. In 2019 outbreaks were reported among wild birds and poultry, as well as human infections with influenza viruses of the subtypes H5Nx, H7N9 and H9N2 in several countries. In 2019, only two outbreaks of highly pathogenic avian influenza H5N8 in Russia occurred. Both outbreaks were recorded in January at poultry farm in the Rostov Region. In addition, in May 2019 avian influenza virus of H14N7 subtype was isolated from a wild bird during the avian influenza virus surveillance in Tomsk Region. In June 2019, a strain of H13N2 subtype was isolated in the territory of Kamchatka Region, then, in August 2019, an influenza virus of H13N6 subtype was isolated in the Saratov Region. It was revealed that some strains of avian influenza virus isolated in Russia have a high degree of identity with strains circulating in South-East Asia. This was shown by the phylogenetic analysis of A/ H5Nx influenza viruses previously isolated in the Saratov Region and the Socialist Republic of Vietnam during the avian influenza virus surveillance. Thus, it was demonstrated again that the territory of Russia plays a key geographical role in the global spread of avian influenza virus.

Study on the research and compatible application of inonotus obliquusin the treatment of influenza in Russia

This article introduces the research and application methods of the Russian medicinal and edible fungus inonotus obliquus in the treatment of influenza, which has shown that Inonotus obliquushas certain inhibiting effect on respiratory viruses and can be used to treat influenza .Besides, it could be combined with herbal plants like Echinacea, Acorus calamus L. root, Anisum, Cerasus vulgaris Mill. gum, Syzygium aromaticum, Geranium flower, Chamomilla recutita, Myristica, Origanum vulgare L., which have effect on treatinginfluenza andrehabilitation. Key words: Medicinal fungi; Inonotus obliquus; Influenza; Antiviral; Compatibility; Russia

Umifenovir treatment is not associated with improved outcomes in patients with coronavirus disease 2019: a retrospective study

ObjectivesCoronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Umifenovir (Arbidol®) is an antiviral drug being used to treat influenza in Russia and China. This study aimed to investigate the effectiveness and safety of umifenovir for COVID-19. MethodsA retrospective study was performed in a non-intensive care unit (ICU) ward in Jinyintan Hospital from 2 February 2020 to 20 March 2020. COVID-19 was confirmed by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay of pharyngeal swab specimens. The confirmed patients were divided into the umifenovir group and the control group according to the use of umifenovir. The main outcomes were the rate of negative pharyngeal swab tests for SARS-CoV-2 within 1 week after admission and the time for the virus to turn negative. The negativity time of SARS-CoV-2 was defined as the first day of a negative test if the nucleic acid of SARS-CoV-2 was negative for two consecutive tests. ResultsA total of 81 COVID-19 patients were included, with 45 in the umifenovir group and 36 in the control group. Baseline clinical and laboratory characteristics were comparable between the two groups. Thirty-three out of 45 (73%) patients in the umifenovir group tested negative for SARS-CoV-2 within 7 days after admission, the number was 28/36 (78%) in the control group (p 0.19). The median time from onset of symptoms to SARS-CoV-2 turning negative was 18 days (interquartile range (IQR) 12–21) in the umifenovir group and 16 days (IQR 11–21) in the control group (p 0.42). Patients in the umifenovir group had a longer hospital stay than patients in the control group (13 days (IQR 9–17) vs 11 days (IQR 9–14), p 0.04). No deaths or severe adverse reactions were found in both groups. DiscussionUmifenovir might not improve the prognosis or accelerate SARS-CoV-2 clearance in non-ICU patients. A randomized control clinical trial is needed to assess the efficacy of umifenovir.

Assessment of the antiviral activity of 2HCl*H-His-Rim compound compared to the anti-influenza drug Arbidol for influenza caused by A/duck/Novosibirsk/56/05 (H5N1) (Influenza A virus, Alphainfluenzavirus, Orthomyxoviridae).

The emergence of influenza virus strains with drug resistance to antiviral drugs requires finding new compounds, potential direct-acting inhibitors. Аdamantane compounds drugs used since the 1960s have lost their activity the resulting due to resistance. Only neuraminidase inhibitors such as zanamivir and oseltamivir have been approved by WHO for influenza treatment. The Russian pharmaceutical drug Arbidol (Umifenovirum) is actively used in Russia. This drug is used to treat influenza in Russia, China and most post-Soviet republics. This work presents a new derivative of aminoadamantane - dichlorohydrate L-histidyl-1-adamantayl ethylamine (2HCl*H-His-Rim), which showed a high level of inhibition of strains of influenza virus A in vitro. Comparison of antiviral properties of the new synthetic low-molecular inhibitor of influenza A virus replication and Arbidol drug pharmacy. The compound 2HCl*H-His-Rim was obtained by classical peptide synthesis methods. It was identified by methods of mass spectrometry, infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR). Its antiviral properties have been studied in vitro for monolayer of cells Vero-E6 infected with a high-virulent strain of A/duck/Novosibirsk/56/06 (H5N1) influenza virus at various injection schemes of the investigated compounds. The antiviral activity of the 2HCl*H-His-Rim compound against the highly pathogenic strain of the influenza A/H5N1 virus was slightly higher than for the known pharmacy drug arbidol. The difference in antiviral activity of these two compounds is explained by different mechanisms of action on the viral particle. The 2HCl*H-His-Rim compound can be recommended as a candidate for preclinical and clinical trials in order to obtain an etiotropic antiviral drug based on it, due to its high efficacy and economic and synthetic availability. The synthetic compound 2HCl*H-His-Rim acts on influenza A virus variants resistant to Rimantadine and Amantadine.

Severe cases of seasonal influenza in Russia in 2017-2018

Aim. Evaluation of herd immunity prior to the 2017-2018 influenza season, and characterization of influenza viruses isolated from severe or fatal influenza cases and from influenza cases in people vaccinated in the fall of 2017. Materials and methods. Evaluation of herd immunity in hemagglutination inhibition assay. Isolation of influenza viruses. Antigenic and genetic analysis. Results. Prior to epidemic season 33-47% of blood sera samples collected on the territory of Russia showed presence of protective antibody titers against vaccine strains of influenza A, 24-30% of samples — against B/Victoria. During 2017-2018 epidemic season 87 influenza A and B viruses were isolated. A(H1N1)pdm09 strains belonged to clade 6B.1, B/Yamagata strains to clade 3, and B/Victoria strains to clade 1A; they were antigenically similar to corresponding vaccine strains. A(H3N2) viruses belonged to clade 3C.2a and were difficult to characterize antigenically. One strain of influenza virus А(H1N1pdm09) was resistant to oseltamivir and had H275Y amino acid substitution in neuraminidase. All other isolates were susceptible to neuraminidase inhibitors. Conclusion. Influenza vaccination with vaccine effective against current circulating strains and treatment with neuraminidase inhibitor drugs at first manifestation of clinical signs of influenza disease are effective means of population protection against influenza.

Severe cases of seasonal influenza in Russia in 2017-2018.

The 2017–2018 influenza epidemic season in Russia was characterized by a relatively low morbidity and mortality. We evaluated herd immunity prior to the 2017–2018 influenza season in hemagglutination inhibition assay, and performed characterization of influenza viruses isolated from severe or fatal influenza cases and from influenza cases in people vaccinated in the fall of 2017. During the 2017–2018 epidemic season, 87 influenza A and B viruses were isolated and viruses of the 75 influenza cases, including selected viral isolates and viruses analyzed directly from the original clinical material, were genetically characterized. The analyzed A(H1N1)pdm09 viruses belonged to clade 6B.1, B/Yamagata-like viruses belonged to clade 3, and B/Victoria-like viruses belonged to clade 1A and they were antigenically similar to the corresponding vaccine strains. A(H3N2) viruses belonged to clade 3C.2a and were difficult to characterize antigenically and the analysis indicated antigenic differences from the corresponding egg-grown vaccine strain. The next generation sequencing revealed the presence of D222/G/N polymorphism in the hemagglutinin gene in 32% of the analyzed A(H1N1)pdm09 lethal cases. This study demonstrated the importance of monitoring D222G/N polymorphism, including detection of minor viral variants with the mutations, in the hemagglutinin gene of A(H1N1)pdm09 for epidemiological surveillance. One strain of influenza virus A(H1N1)pdm09 was resistant to oseltamivir and had the H275Y amino acid substitution in the NA protein. All other isolates were susceptible to NA inhibitors. Prior to the 2017–2018 epidemic season, 67.4 million people were vaccinated, which accounted for 46.6% of the country's population. Just before the epidemic season 33–47% and 24–30% of blood sera samples collected within the territory of Russia showed the presence of protective antibody titers against vaccine strains of influenza A and influenza B/Victoria-like, respectively. Mass vaccination of the population had evidently reduced the severity of the flu epidemic during the 2017–2018 influenza epidemic season in Russia.