OBTAINING AND USING ERYTHROCYTE ANTIGENIC MELIIDOSIS DIAGNOSTIC AGENT IN THE ANALYSIS OF SERUM SAMPLES FROM MELIIDOSIS-ENDEMIC PROVINCES HA GIANG, LANG SON AND QUANG NINH OF THE SOCIALIST REPUBLIC OF VIETNAM.

Melioidosis is a particularly dangerous infection with endemic distribution caused by the Gram-negative microorganism from the pathogenicity group II Burkholderia pseudomallei. In endemic countries, melioidosis holds one of the leading places in mortality rate after HIV, tuberculosis and, in recent years, COVID-19. The natural ecological pathogen niches are located in tropical and subtropical climate zones, primarily in Southeast Asia and Australia, where its existence as a species is maintained in moist soil and water in a certain temperature environmental range. However, at present, more and more often cases of melioidosis are registered outside endemic territories, which emphasizes the relevance of improving the means and methods of laboratory diagnostics of this disease both for countries located in the zone of natural foci as well as for local healthcare of the countries after importation of this poorly known infection into their territory. In such countries, including the Russian Federation, the population has no natural immunity to the pathogen, and therefore this infection acquires even greater clinical and epidemiological significance. In the Volgograd Plague Control Research Institute, an erythrocyte antigenic melioidosis diagnostic agent for IHA was designed allowing to detect the presence of serum melioidosis antibodies. The diagnostic agent was obtained on the basis of a biological carrier - ram erythrocytes sensitized with isolated protein antigenic complexes of B. pseudomallei. The high analytical characteristics of the diagnostic agent were confirmed on sera models of immunized and recovering experimental animals. Using the obtained set of reagents, the level of serum antibodies against the causative agent of melioidosis was studied in residents from the 3 provinces of Vietnam (Ha Giang, Lang Son and Quang Ninh), as well as in control group composed of residents of the Volgograd region. In samples obtained from a non-endemic region, not more than 25% of cases contained IHA titers at lower than 1:10 dilution, which is apparently due to cross-reactivity of serum immunoglobulins. Positive serum samples from clinically healthy residents of Ha Giang, Lang Son and Quang Ninh provinces were at a titer of 1:10 detected in 71.5%, in dilutions of 1:20-1:80 - in 28.5% of cases. Thus, we believe that serum antibody titer of 1:80 established in the IHA results, has a diagnostic significance, reflecting the intensity of the anti-melioidosis populational immunity.Copyright © 2022 Saint Petersburg Pasteur Institute. All rights reserved.

SARS-CoV-2 and microbiome: pathology, implications and therapeutic options

A multidisciplinary approach in the treatment of COVID-19 warrants close attention to the role of the intestinal microbiome in terms of disease pathology, disruption of local and systemic homeostasis, and possible treatment strategies. Dysbiotic disorders affect the immune system on the level of postvaccination immunity, influencing the likelihood and severity of SARS-CoV-2 infection, indicating the importance of intestinal microbiota in the prevention of complications and risk reduction. The fundamental factor in the stability of the intestinal microflora is a diet that includes regular consumption of probiotic foods, which support healthy microbiota. Restoration of damaged intestinal microbiota in cases of dysbiosis requires specific supplements and foods, which vary significantly for each symbiont. In clinical practice, the most appropriate approach is a differentiated one, taking into account the severity of the dysbiotic condition, comorbidities, and the age of the patients. A bacteria consortium of the human microbiome is the basis for a bioprobiotics complex with targeted action. The translational benefits of such therapy in most common COVID-19 syndromes are in detail presented in this chapter. We discuss the role of SARS-CoV-2 infection on the microbiota, as well as pathogenetic mechanisms of microbiota disruption, local and systemic influencing factors, and treatment strategies. © 2023 Elsevier Inc. All rights reserved.

OBTAINING AND USING ERYTHROCYTE ANTIGENIC MELIIDOSIS DIAGNOSTIC AGENT IN THE ANALYSIS OF SERUM SAMPLES FROM MELIIDOSIS-ENDEMIC PROVINCES HA GIANG, LANG SON AND QUANG NINH OF THE SOCIALIST REPUBLIC OF VIETNAM.

Melioidosis is a particularly dangerous infection with endemic distribution caused by the Gram-negative microorganism from the pathogenicity group II Burkholderia pseudomallei. In endemic countries, melioidosis holds one of the leading places in mortality rate after HIV, tuberculosis and, in recent years, COVID-19. The natural ecological pathogen niches are located in tropical and subtropical climate zones, primarily in Southeast Asia and Australia, where its existence as a species is maintained in moist soil and water in a certain temperature environmental range. However, at present, more and more often cases of melioidosis are registered outside endemic territories, which emphasizes the relevance of improving the means and methods of laboratory diagnostics of this disease both for countries located in the zone of natural foci as well as for local healthcare of the countries after importation of this poorly known infection into their territory. In such countries, including the Russian Federation, the population has no natural immunity to the pathogen, and therefore this infection acquires even greater clinical and epidemiological significance. In the Volgograd Plague Control Research Institute, an erythrocyte antigenic melioidosis diagnostic agent for IHA was designed allowing to detect the presence of serum melioidosis antibodies. The diagnostic agent was obtained on the basis of a biological carrier - ram erythrocytes sensitized with isolated protein antigenic complexes of B. pseudomallei. The high analytical characteristics of the diagnostic agent were confirmed on sera models of immunized and recovering experimental animals. Using the obtained set of reagents, the level of serum antibodies against the causative agent of melioidosis was studied in residents from the 3 provinces of Vietnam (Ha Giang, Lang Son and Quang Ninh), as well as in control group composed of residents of the Volgograd region. In samples obtained from a non-endemic region, not more than 25% of cases contained IHA titers at lower than 1:10 dilution, which is apparently due to cross-reactivity of serum immunoglobulins. Positive serum samples from clinically healthy residents of Ha Giang, Lang Son and Quang Ninh provinces were at a titer of 1:10 detected in 71.5%, in dilutions of 1:20-1:80 - in 28.5% of cases. Thus, we believe that serum antibody titer of 1:80 established in the IHA results, has a diagnostic significance, reflecting the intensity of the anti-melioidosis populational immunity. Copyright © 2022 Saint Petersburg Pasteur Institute. All rights reserved.

OBTAINING AND USING ERYTHROCYTE ANTIGENIC MELIIDOSIS DIAGNOSTIC AGENT IN THE ANALYSIS OF SERUM SAMPLES FROM MELIIDOSIS-ENDEMIC PROVINCES HA GIANG, LANG SON AND QUANG NINH OF THE SOCIALIST REPUBLIC OF VIETNAM

Melioidosis is a particularly dangerous infection with endemic distribution caused by the Gram-negative microorganism from the pathogenicity group II Burkholderia pseudomallei. In endemic countries, melioidosis holds one of the leading places in mortality rate after HIV, tuberculosis and, in recent years, COVID-19. The natural ecological pathogen niches are located in tropical and subtropical climate zones, primarily in Southeast Asia and Australia, where its existence as a species is maintained in moist soil and water in a certain temperature environmental range. However, at present, more and more often cases of melioidosis are registered outside endemic territories, which emphasizes the relevance of improving the means and methods of laboratory diagnostics of this disease both for countries located in the zone of natural foci as well as for local healthcare of the countries after importation of this poorly known infection into their territory. In such countries, including the Russian Federation, the population has no natural immunity to the pathogen, and therefore this infection acquires even greater clinical and epidemiological significance. In the Volgograd Plague Control Research Institute, an erythrocyte antigenic melioidosis diagnostic agent for IHA was designed allowing to detect the presence of serum melioidosis antibodies. The diagnostic agent was obtained on the basis of a biological carrier - ram erythrocytes sensitized with isolated protein antigenic complexes of B. pseudomallei. The high analytical characteristics of the diagnostic agent were confirmed on sera models of immunized and recovering experimental animals. Using the obtained set of reagents, the level of serum antibodies against the causative agent of melioidosis was studied in residents from the 3 provinces of Vietnam (Ha Giang, Lang Son and Quang Ninh), as well as in control group composed of residents of the Volgograd region. In samples obtained from a non-endemic region, not more than 25% of cases contained IHA titers at lower than 1:10 dilution, which is apparently due to cross-reactivity of serum immunoglobulins. Positive serum samples from clinically healthy residents of Ha Giang, Lang Son and Quang Ninh provinces were at a titer of 1:10 detected in 71.5%, in dilutions of 1:20-1:80 - in 28.5% of cases. Thus, we believe that serum antibody titer of 1:80 established in the IHA results, has a diagnostic significance, reflecting the intensity of the anti-melioidosis populational immunity. Copyright © 2022 Saint Petersburg Pasteur Institute. All rights reserved.

Influenza A(H7N9) Pandemic Preparedness: Assessment of the Breadth of Heterologous Antibody Responses to Emerging Viruses from Multiple Pre-Pandemic Vaccines and Population Immunity.

Influenza A(H7N9) viruses remain as a high pandemic threat. The continued evolution of the A(H7N9) viruses poses major challenges in pandemic preparedness strategies through vaccination. We assessed the breadth of the heterologous neutralizing antibody responses against the 3rd and 5th wave A(H7N9) viruses using the 1st wave vaccine sera from 4 vaccine groups: 1. inactivated vaccine with 2.8 µg hemagglutinin (HA)/dose + AS03A; 2. inactivated vaccine with 5.75 µg HA/dose + AS03A; 3. inactivated vaccine with 11.5 µg HA/dose + MF59; and 4. recombinant virus like particle (VLP) vaccine with 15 µg HA/dose + ISCOMATRIX™. Vaccine group 1 had the highest antibody responses to the vaccine virus and the 3rd/5th wave drifted viruses. Notably, the relative levels of cross-reactivity to the drifted viruses as measured by the antibody GMT ratios to the 5th wave viruses were similar across all 4 vaccine groups. The 1st wave vaccines induced robust responses to the 3rd and Pearl River Delta lineage 5th wave viruses but lower cross-reactivity to the highly pathogenic 5th wave A(H7N9) virus. The population in the United States was largely immunologically naive to the A(H7N9) HA. Seasonal vaccination induced cross-reactive neuraminidase inhibition and binding antibodies to N9, but minimal cross-reactive antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies to A(H7N9).

Can high COVID-19 vaccination rates in adults help protect unvaccinated children? Evidence from a unique mass vaccination campaign, Schwaz/Austria, March 2021.

BackgroundAfter an outbreak of the SARS-CoV-2 Beta variant in the district of Schwaz/Austria, vaccination with Comirnaty vaccine (BNT162b2 mRNA, BioNTech-Pfizer) had been offered to all adult inhabitants (≥ 16 years) in March 2021. This made Schwaz one of the most vaccinated regions in Europe at that time (70% of the adult population took up the offer). In contrast, all other Austrian districts remained with low vaccine coverage.AimWe studied whether this rapid mass vaccination campaign provided indirect protection to unvaccinated individuals such as children (< 16 years) living in the same district.MethodsTo study the effect of the campaign we used two complementary approaches. We compared infection rates among the population of children (< 16 years) in Schwaz with (i) the child population from similar districts (using the synthetic control method), and (ii) with the child population from municipalities along the border of Schwaz not included in the campaign (using an event study approach).ResultsBefore the campaign, we observed very similar infection spread across the cohort of children in Schwaz and the control regions. After the campaign, we found a significant reduction of new cases among children of -64.5% (95%-CI: -82.0 to -30.2%) relative to adjacent border municipalities (using the event study model). Employing the synthetic control method, we observed a significant reduction of -42.8% in the same cohort.ConclusionOur results constitute novel evidence of an indirect protection effect from a group of vaccinated individuals to an unvaccinated group.

The end of the COVID-19 pandemic.

There are no widely accepted, quantitative definitions for the end of a pandemic such as COVID-19. The end of the pandemic due to a new virus and the transition to endemicity may be defined based on a high proportion of the global population having some immunity from natural infection or vaccination. Other considerations include diminished death toll, diminished pressure on health systems, reduced actual and perceived personal risk, removal of restrictive measures and diminished public attention. A threshold of 70% of the global population having being vaccinated or infected was probably already reached in the second half of 2021. Endemicity may still show major spikes of infections and seasonality, but typically less clinical burden, although some locations are still hit more than others. Death toll and ICU occupancy figures are also consistent with a transition to endemicity by end 2021/early 2022. Personal risk of the vast majority of the global population was already very small by end 2021, but perceived risk may still be grossly overestimated. Restrictive measures of high stringency have persisted in many countries by early 2022. The gargantuan attention in news media, social media and even scientific circles should be tempered. Public health officials need to declare the end of the pandemic. Mid- and long-term consequences of epidemic waves and of adopted measures on health, society, economy, civilization and democracy may perpetuate a pandemic legacy long after the pandemic itself has ended.

Estimates of Presumed Population Immunity to SARS-CoV-2 by State in the United States, August 2021.

BACKGROUND: Information is needed to monitor progress toward a level of population immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sufficient to disrupt viral transmission. We estimated the percentage of the US population with presumed immunity to SARS-CoV-2 due to vaccination, natural infection, or both as of August 26, 2021. METHODS: Publicly available data as of August 26, 2021, from the Centers for Disease Control and Prevention were used to calculate presumed population immunity by state. Seroprevalence data were used to estimate the percentage of the population previously infected with SARS-CoV-2, with adjustments for underreporting. Vaccination coverage data for both fully and partially vaccinated persons were used to calculate presumed immunity from vaccination. Finally, we estimated the percentage of the total population in each state with presumed immunity to SARS-CoV-2, with a sensitivity analysis to account for waning immunity, and compared these estimates with a range of population immunity thresholds. RESULTS: In our main analysis, which was the most optimistic scenario, presumed population immunity varied among states (43.1% to 70.6%), with 19 states with ≤60% of their population having been infected or vaccinated. Four states had presumed immunity greater than thresholds estimated to be sufficient to disrupt transmission of less infectious variants (67%), and none were greater than the threshold estimated for more infectious variants (≥78%). CONCLUSIONS: The United States remains a distance below the threshold sufficient to disrupt viral transmission, with some states remarkably low. As more infectious variants emerge, it is critical that vaccination efforts intensify across all states and ages for which the vaccines are approved.

Study of the level and structure of population immunity to sars-cov2 in the population of the republic of tatarstan during the second peak of the spread of covid-19

Background. The COVID-19 pandemic has become a serious challenge for all of humanity due to the rapid global spread, high frequency of severe forms, increased mortality and required the development of new approaches to managing epidemiological processes. Serological studies are the most important tool for monitoring the infectious process, identifying risk groups, assessing the effect of vaccines used and epidemiological projections. Purpose. Conducting serological monitoring in relation to the modern transferred new coronavirus infection determining the level and structure of population immunity to SARS-CoV-2 in the population of the Republic of Tatarstan;maintaining the period of spread of COVID-19 from August to December 2020. Materials and methods. The study involved 41 444 residents of the Republic of Tatarstan, who filled out questionnaires that included clinical, anamnestic data and an epidemiological history in relation to COVID-19, who were tested for the presence of common antibodies (IgG, IgA and IgM) to the SARS coronavirus. CoV-2 by the method of enhanced chemiluminescence on the VITROS 3600 analyzer using the VITROS Anti-SARS-CoV-2 Total Reagent Pack test systems. Statistical processing was carried out by methods of variation statistics and correlation analysis according to the Pearson method using MS Excel and WinPepi. Results. Seropositivity to SARS-CoV-2 in the population of the Republic of Tatarstan averaged 35.8 ± 0.235%. An increase in the level of seropositive persons was noted from 29.95 ± 0.674% in August to 68 ± 9.33% in December. The highest proportion of seropositive individuals was found in was found in the group of the able-bodied population aged 18–59 years. The average geometric titer of antibodies was 4.2 (4.09–4.31), among seropositive – 89.29 (88.13–90.46). In the social and professional structure of the population, the largest proportion of seropositive individuals was found in was found among production workers 40.35 ± 2.177, creative professions – 40 ± 9.798;health care 35.24 ± 0.389;34.26 ± 1.218 unemployed and 33.06 ± 2.479 civil servants. Among the residents of the Republic of Tatarstan, seropositive to the SARS-CoV-2 virus, the proportion of asymptomatic forms of infection was 82.59 ± 0.446%. Сonclusions. There is a positive dynamics of seropositivity among the population of the Republic of Tatarstan. The results of sero-epidemiological monitoring can be used to predict the epidemiological situation, plan measures for specific and non-specific prophylaxis of COVID19. ©Sadykov MN et al.

[The social demographic aspects of vaccination of population of Russia in the context of COVID-19 pandemic].

The pandemic of the new corona-virus infection COVID-19 will be over only when population immunity will be developed. This condition can be achieved by both vaccination and surviving disease in natural way. The WHO recommends the first mode for achieving population immunity, since immune response to vaccine is similar to that one developed while surviving natural infection, but with minimal risks to health and life. The article presents the results of sociological survey organized with purpose of studying the attitude of Russians to vaccination against COVID-19 infection. The results of the survey demonstrated that at present, 22% of respondents are ready to be vaccinated i.e. they responded positively to the corresponding question. The following main factors determining population attitude to vaccination were identified. First, there is statistically significant correlation between vaccination readiness and education level: respondents with higher level of education are more likely to be vaccinated against COVID-19. Secondly, in general, the population is quite positive about the response of the National health care to the corona-virus pandemic. However, the percentage of population that is positive about vaccination can be higher if it would be possible to apply foreign-made vaccines in Russia. Thirdly, still there is large percentage of population believing that vaccination with medications that have not passed long-term clinical trials can result in health negative consequences. Fourthly, the majority of respondents experienced various manifestations of the pandemic on themselves: either they have been ill themselves, or their relatives and friends were ill or died and almost all of them somehow limited their common mobility.The survey results did not established statistically significant differences in distribution of responses among males and females. We assume that in order to develop positive attitude of population to vaccination, and specifically to Russian-made vaccines, more extensive information campaign is needed to be implemented. Also, significant increase of percentage of vaccinated population can be achieved if clearly defined requirements for availability of COVID-19 vaccination would be adopted on the international level. Actually, this is key condition for restoring international mobility and removing restrictions in national economies.

Predictors of COVID-19 Vaccine Intention among the Saudi Arabian Population: A Cross-Sectional Survey.

The long-term solution to managing the current COVID-19 pandemic is through mass immunization of the population. However, uncertainty or unwillingness to receive the vaccine could be a barrier in attaining sufficient vaccine coverage. Therefore, understanding the psychology of the population towards the vaccines against COVID-19 is of paramount importance. Our study was aimed at determining the predictors of COVID-19 vaccine intention in the Saudi Arabian population. A structured questionnaire guided by the 'Report of the SAGE working group on vaccine hesitancy' was administered during a span of two months among the general population from all administrative regions of Saudi Arabia, proceeding the launch of the vaccination campaign. In total, 879 out of 1600 subjects responded and completed the survey (response rate 54.9%). About 56 percent of the participants intended to be vaccinated. The predictors of a higher intention to vaccinate included those 50 years of age or older, male subjects, people suffering from systemic disease/s, subjects who were not previously infected with COVID-19, those who follow the updates about COVID-19 vaccines, and adults with a higher level of anxiety about contracting coronavirus (p < 0.05). Results from our study and other similar studies can aid policy makers and stakeholders in planning effective strategies based on the changing behavior of the population.

Immunity to SARS-CoV-2 induced by infection or vaccination.

Adaptive immune responses play critical roles in viral clearance and protection against re-infection, and SARS-CoV-2 is no exception. What is exceptional is the rapid characterization of the immune response to the virus performed by researchers during the first 20 months of the pandemic. This has given us a more detailed understanding of SARS-CoV-2 compared to many viruses that have been with us for a long time. Furthermore, effective COVID-19 vaccines were developed in record time, and their rollout worldwide is already making a significant difference, although major challenges remain in terms of equal access. The pandemic has engaged scientists and the public alike, and terms such as seroprevalence, neutralizing antibodies, antibody escape and vaccine certificates have become familiar to a broad community. Here, we review key findings concerning B cell and antibody (Ab) responses to SARS-CoV-2, focusing on non-severe cases and anti-spike (S) Ab responses in particular, the latter being central to protective immunity induced by infection or vaccination. The emergence of viral variants that have acquired mutations in S acutely highlights the need for continued characterization of both emerging variants and Ab responses against these during the evolving pathogen-immune system arms race.

Seropositivity in blood donors and pregnant women during the first year of SARS-CoV-2 transmission in Stockholm, Sweden.

BACKGROUND: In Sweden, social restrictions to contain SARS-CoV-2 have primarily relied upon voluntary adherence to a set of recommendations. Strict lockdowns have not been enforced, potentially affecting viral dissemination. To understand the levels of past SARS-CoV-2 infection in the Stockholm population before the start of mass vaccinations, healthy blood donors and pregnant women (n = 5,100) were sampled at random between 14 March 2020 and 28 February 2021. METHODS: In this cross-sectional prospective study, otherwise-healthy blood donors (n = 2,600) and pregnant women (n = 2,500) were sampled for consecutive weeks (at four intervals) throughout the study period. Sera from all participants and a cohort of historical (negative) controls (n = 595) were screened for IgG responses against stabilized trimers of the SARS-CoV-2 spike (S) glycoprotein and the smaller receptor-binding domain (RBD). As a complement to standard analytical approaches, a probabilistic (cut-off independent) Bayesian framework that assigns likelihood of past infection was used to analyse data over time. SETTING: Healthy participant samples were randomly selected from their respective pools through Karolinska University Hospital. The study was carried out in accordance with Swedish Ethical Review Authority: registration number 2020-01807. PARTICIPANTS: No participants were symptomatic at sampling, and blood donors were all over the age of 18. No additional metadata were available from the participants. RESULTS: Blood donors and pregnant women showed a similar seroprevalence. After a steep rise at the start of the pandemic, the seroprevalence trajectory increased steadily in approach to the winter second wave of infections, approaching 15% of all individuals surveyed by 13 December 2020. By the end of February 2021, 19% of the population tested seropositive. Notably, 96% of seropositive healthy donors screened (n = 56) developed neutralizing antibody responses at titres comparable to or higher than those observed in clinical trials of SARS-CoV-2 spike mRNA vaccination, supporting that mild infection engenders a competent B-cell response. CONCLUSIONS: These data indicate that in the first year since the start of community transmission, seropositivity levels in metropolitan in Stockholm had reached approximately one in five persons, providing important baseline seroprevalence information prior to the start of vaccination.

COVID-19 Dynamics: A Heterogeneous Model.

The mathematical model reported here describes the dynamics of the ongoing coronavirus disease 2019 (COVID-19) epidemic, which is different in many aspects from the previous severe acute respiratory syndrome (SARS) epidemic. We developed this model when the COVID-19 epidemic was at its early phase. We reasoned that, with our model, the effects of different measures could be assessed for infection control. Unlike the homogeneous models, our model accounts for human population heterogeneity, where subpopulations (e.g., age groups) have different infection risks. The heterogeneous model estimates several characteristics of the epidemic more accurately compared to the homogeneous models. According to our analysis, the total number of infections and their peak number are lower compared to the assessment with the homogeneous models. Furthermore, the early-stage infection increase is little changed when population heterogeneity is considered, whereas the late-stage infection decrease slows. The model predicts that the anti-epidemic measures, like the ones undertaken in China and the rest of the world, decrease the basic reproductive number but do not result in the development of a sufficient collective immunity, which poses a risk of a second wave. More recent developments confirmed our conclusion that the epidemic has a high likelihood to restart after the quarantine measures are lifted.

COVID-19 zugzwang: Potential public health moves towards population (herd) immunity.

COVID-19 is pandemic, and likely to become endemic, possibly returning with greater virulence. Outlining potential public health actions, including hygiene measures, social distancing and face masks, and realistic future advances, this paper focuses on the consequences of taking no public health action; the role of natural changes such as weather; the adverse public health consequences of lockdowns; testing for surveillance and research purposes; testing to identify cases and contacts, including the role of antibody tests; the public health value of treatments; mobilising people who have recovered; population (a synonym for herd) immunity through vaccination and through natural infection; involving the entire population; and the need for public debate. Until there is a vaccine, population immunity is going to occur only from infection. Allowing infection in those at very low risk while making it safer for them and wider society needs consideration but is currently taboo. About 40-50% population immunity is sufficient to suppress an infection with a reproduction number of about 1 or slightly more. Importantly, in children and young people COVID-19 is currently rarely fatal, roughly comparable with influenza. The balance between the damage caused by COVID-19 and that caused by lockdowns needs quantifying. Public debate, including on population immunity, informed by epidemiological data, is now urgent.