Comparison of Natural and BNT162b2 Vaccine-induced Immunity, with and without an Enhancer or Booster Dose, on the Risk of COVID-19-Related Hospitalization in Israel

Introduction: With the COVID-19 pandemic ongoing, accurate assessment of population immunity and the effectiveness of booster and enhancer vaccines is critical. Methods We compare COVID-19-related hospitalization incidence rate ratios, adjusted for potential demographic, clinical and health-seeking-behavior confounders, in 2,412,755 individuals (235,552,274 person-days), across four exposures: 2 BNT162b2 doses, 5 or more months prior ("non-recent vaccine immunity"); 3 BNT162b2 doses (“boosted vaccine immunity”); previous COVID-19, with or without a subsequent BNT162b2 dose (“natural immunity” and “enhanced natural immunity” respectively). Results Compared with non-recent vaccine immunity, COVID-19-related hospitalization incidence rate ratios are 11% (9%-13%) for boosted vaccine immunity, 34% (23%-50%) for natural immunity and 25% (17%-39%) for enhanced natural immunity. Conclusion We demonstrate that natural immunity (enhanced or not) provides better protection against COVID-19-related hospitalization than non-recent vaccine immunity, but less protection than that attained from booster vaccination. Additionally, our results suggest that vaccinating individuals with natural immunity further enhances their protection.

Development of the ELISA Test System for Quantitative Determination of IgG to the Varizella zoster virus in Human Serum and Assessment of its Diagnostic Efficiency

Relevance. The introduction of Varicella vaccine prophylaxis explains the need to develop a methodology for monitoring the vaccination effectiveness and the intensity of population immunity. This problem can be solved using quantitative immunoassay methods. Aim. Development of an enzyme-linked immunosorbent assay for the concentration of class G immunoglobulins (AB) to Varicella zoster virus (VZV) determining and assessing its functional characteristics and diagnostic efficiency. Materials and methods. Recombinant antigen GE VZV. WHO International Standard for Antibodies to VZV W1044. Blood serum samples from healthy people and patients with Chickenpox and Herpes zoster, blood serum samples containing IgG antibodies to herpes simplex viruses of the first and second types, cytomegalovirus, Epstein-Barr virus. Anti-VZV ELISA (IgG) reagent kit (Euroimmun, Germany). Indirect enzyme-linked immunosorbent assay. Immunization of animals with recombinant antigen GE, isolation, and purification of specific antibodies. Conjugation of monoclonal antibodies to human IgG with antibodies to antigen GE and with horseradish peroxidase. Results. An enzyme-linked immunosorbent assay in «an indirect» format has been developed to determine the specific antibodies to VZV concentration (IU/ml) in human serum/plasma. An artificial calibrator for determining the concentration of AB-VZV had been synthesized and standardized according to the International WHO-standard W1044. The main functional characteristics of the developed enzyme-linked immunosorbent assay are determined in accordance with GOST 51352-2013. The diagnostic kit was tested on blood serum samples from children with chickenpox (n = 43), adults with Herpes zoster (n = 158), healthy individuals (n = 781). The diagnostic sensitivity of the test system was 85%, the diagnostic specificity was 87% according to the ROC analysis. The absence of cross-reactivity of the test system was shown on samples with serological markers of other herpesvirus infections (n = 94). Comparative trials of the developed test system and its commercial analog, the Anti-VZV ELISA (IgG) reagent kit, did not reveal statistically significant differences between their functional characteristics. Conclusions. The developed test system for determining of the AB-VZV concentration in human serum/plasma in terms of its functional characteristics meets the GOST requirements, is characterized by high diagnostic efficiency, can be used to monitor the effectiveness of vaccine prophylaxis and strength of population immunity, as well as to assess the immune response in chickenpox and Herpes zoster.

Vaccination-infection interval determines cross-neutralization potency to SARS-CoV-2 Omicron after breakthrough infection by other variants

Background The immune profile against SARS-CoV-2 has dramatically diversified due to a complex combination of exposure to vaccines and infection by various lineages/variants, likely generating a heterogeneity in protective immunity in a given population. To further complicate this, the Omicron variant, with numerous spike mutations, has emerged. These circumstances have created the need to assess the potential of immune evasion by the Omicron in individuals with various immune histories. Methods The neutralization susceptibility of the variants including the Omicron and their ancestor was comparably assessed using a panel of plasma/serum derived from individuals with divergent immune histories. Blood samples were collected from either mRNA vaccinees or from those who suffered from breakthrough infections by the Alpha/Delta with multiple time intervals following vaccination. Findings The Omicron was highly resistant to neutralization in fully vaccinated individuals without a history of breakthrough infections. In contrast, robust cross-neutralization against the Omicron were induced in vaccinees that experienced breakthrough infections. The time interval between vaccination and infection, rather than the variant types of infection, was significantly correlated with the magnitude and potency of Omicron-neutralizing antibodies. Conclusions Immune histories with breakthrough infections can overcome the resistance to infection by the Omicron, with the vaccination-infection interval being the key determinant of the magnitude and breadth of neutralization. The diverse exposure history in each individual warrants a tailored and cautious approach to understanding population immunity against the Omicron and future variants. Funding This study was supported by grants from the Japan Agency for Medical Research and Development (AMED).

A Theoretical Linguistic Fuzzy Rule-Based Compartmental Modeling for the COVID-19 Pandemic

Recently COVID-19 pandemic has affected the whole world quite seriously. The number of new infectious cases and death cases are rapidly increasing over time. In this study, a theoretical linguistic fuzzy rule-based Susceptible-Exposed-Infectious-Isolated-Recovered (SEIIsR) compartmental model has been proposed to predict the dynamics of the transmission of COVID-19 over time considering population immunity and infectiousness heterogeneity based on viral load in the model. The model’s equilibrium points have been calculated and stability analysis of the model’s equilibrium points has been conducted. Consequently, the fuzzy basic reproduction number, R0f of the fuzzy model has been formulated. Finally, the temporal dynamics of different compartmental populations with immunity and infectiousness heterogeneity using the fuzzy Mamdani model are delineated and some disease control policies have been suggested to get over the infection in no time.

Characteristic of herd immunity among the population of Stavropol region amid the COVID-19 epidemic

Introduction. The first pandemic in the 21st century, caused by the pathogenic representative of the coronavirus SARS-CoV-2, began in the Chinese city of Wuhan, where the first outbreak of coronavirus pneumonia was recorded in December 2019. The disease spread so quickly around the world that already on February 11, 2020, WHO was forced to declare a pandemic of the “coronavirus disease 2019” COVID-19. The first case of COVID-19 in the Stavropol Territory was registered on March 20, 2020, and three weeks later, starting from the 15th week of the year, a steady increase in the incidence began, which lasted until the 52nd week. During the study period, the incidence increased from 21.1 to 28.3 per hundred thousand of the population. Growth 1.3 times.Purpose: to determine the dynamics of population immunity among the population of the Stavropol Territory in 2020-2021. during the period of an epidemic increase in the incidence of COVID-19. Materials and methods. The SARS-CoV-2 study was carried out according to a unified methodology within the framework of the program for assessing the population immunity of the population of the Russian Federation, developed by Rospotrebnadzor with the participation of the St. Pasteur. In total, 2688 people were examined, divided into 7 age groups. In the examined individuals, the level of specific IgG to the SARS-CoV-2 nucleocapsid was determined by the enzyme immunoassay.Results. The level of seroprevalence among residents of the Stavropol Territory was 9.8%. The largest proportion of seropositive individuals was found in the age groups 1-6 and 7-13 years old (19.2% and 19.7%, respectively). Seroprevalence had no gender differences and ranged from 9.3% to 10.8%. When assessing the distribution of the proportion of seropositive persons in different geographic territories of the region, it was found that the maximum proportion was found in the Kochubeevsky district (23.1%), the minimum in Kislovodsk (7.7%). Among convalescents, the content of specific antibodies to SARS-CoV-2 was noted in 73.3%, which is 7.8 times higher than the average population level. When conducting seromonitoring in the 2nd half of 2020, a 10-fold increase in seroprevalence was recorded, accompanied by a decrease in incidence from the 5th week of 2021. Among asymptomatic volunteers in whom SARS-CoV-2 RNA was detected by the polymerase chain reaction, antibody titers to viruses were found in 78.6%, which corresponds to the seroprevalence of convalescents. The proportion of seropositive persons among those who have come into contact with COVID-19 patients was 16.4%, (1.8 times higher than the average for the population). Out of 262 seroprevalent volunteers, the asymptomatic form of SARS-CoV-2 was detected in 92% of the examined, which indicates a significant role of the number of asymptomatic forms of infection in the epidemic process of COVID-19.Conclusion. The results of assessing the population immunity of the population of the Stavropol Territory indicate that it has not yet reached the threshold level at which a decrease in the intensity of the COVID-19 epidemic process can be expected.

Population immunity to SARS-CoV-2 in US states and counties due to infection and vaccination, January 2020-November 2021

Importance: Prior infection and vaccination both contribute to population-level SARS-CoV-2 immunity. Population-level immunity will influence future transmission and disease burden. Objective: For each US county and state, we estimated the fraction of the population with prior immunological exposure to SARS-CoV-2 (ever infected with SARS-CoV-2 and/or received one or more doses of a COVID-19 vaccine) as well as the fraction with effective protection against infection and severe disease from prevalent SARS-CoV-2 variants, from January 1st, 2020, to October 31st, 2021. Design, settings, participants: We used daily SARS-CoV-2 infection estimates for each US state and county, derived based on reported data on COVID-19 cases and deaths. We collated county-level vaccination coverage data and estimated the fraction of individuals both vaccinated and previously infected using the Census Bureau Household Pulse Survey. We used published evidence on natural and vaccine-induced immunity, and how protection wanes over time. We used a Bayesian model to synthesize evidence and estimate population immunity outcomes. Main Outcomes and Measures: Primary outcomes were the fraction of the population with (i) a history of exposure to SARS-CoV-2 infection or COVID-19 vaccination or both, (ii) effective protection against infection, and (iii) effective protection against severe disease. We estimated outcomes for each US state and county from January 1st, 2020, to October 31st, 2021. Results: The estimated percentage of the US population with a history of SARS-CoV-2 infection or vaccination, as of October 31, 2021, was 86.2% (95%CrI: 82.2%-93.0%), compared to 24.9% (95%CrI: 18.5%-34.1%) on January 1, 2021. State-level estimates for October 31, 2021, ranged between 72.2% (95%CrI: 62.5%-83.3%, West Virginia) and 92.3% (95%CrI: 88.6%-96.1%, Florida). Accounting for waning, the effective protection against infection with prevalent strains as of October 31 was 49.9% (95%CrI: 45.4%-56.6%) nationally and ranged between 37.2% (95%CrI: 33.4%-44.7%, Vermont) and 59.5% (95%CrI: 56.4%-66.0%, Florida). Effective protection against severe disease was 77.4% (95%CrI: 73.7%-83.4%) nationally and ranged between 62.9% (95%CrI: 55.2%-73.3%, West Virginia) and 83.8% (95%CrI: 80.7%-88.0%, Florida). Conclusions and Relevance: The fraction of the population with effective protection against SARS-CoV-2 infection and severe COVID-19 varies across the United States, but a substantial proportion of the population remains susceptible.

Estimating the impact of low influenza activity in 2020 on population immunity and future influenza seasons in the United States

Backgrounds Influenza activity in the 2020-21 season was remarkably low, likely due to implementation of public health preventive measures such as social distancing, mask-wearing, and school closure. With waning immunity, the impact of low influenza activity in the 2020-21 on the following season is unknown. Method We built a multi-strain compartmental model that captures immunity over multiple influenza seasons in the US. Compared to the counterfactual case, where influenza activity remained at the normal level in 2020-21, we estimated the change in the number of hospitalizations when the transmission rate was decreased by 20% in 2020-21. We varied the level of vaccine uptake and effectiveness in 2021-22. We measured the change in population immunity over time by varying the number of seasons with lowered influenza activity. Results With the lowered influenza activity in 2020-21, the model estimated 102,000 [95% CI: 57,000-152,000] additional hospitalizations in 2021-22, without changes in vaccine uptake and effectiveness. The estimated changes in hospitalizations varied depending on the level of vaccine uptake and effectiveness in the following year. Achieving 50% increase in vaccine coverage was necessary to avert the expected increase in hospitalization in the next influenza season. If the low influenza activity were to continue over several seasons, population immunity would remain low during those seasons, with 48% the population susceptible to influenza infection. Conclusion Our study projecteda large compensatory influenza season in 2021-22 due to a light season in 2020-21. However, higher influenza vaccine uptake would reduce this projected increase in influenza.

Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterised by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, whilst the second and third waves were driven by the Beta and Delta variants respectively. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng Province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, predicted to influence antibody neutralization and spike function4. Here, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.

South African Population Immunity and Severe Covid-19 with Omicron Variant

Background We conducted a seroepidemiological survey from October 22 to December 9, 2021, in Gauteng Province, South Africa, to determine SARS-CoV-2 immunoglobulin G (IgG) seroprevalence primarily prior to the fourth wave of coronavirus disease 2019 (Covid-19), in which the B.1.1.529 (Omicron) variant is dominant. We evaluated epidemiological trends in case rates and rates of severe disease through to December 15, 2021, in Gauteng. Methods We contacted households from a previous seroepidemiological survey conducted from November 2020 to January 2021, plus an additional 10% of households using the same sampling framework. Dry blood spot samples were tested for anti-spike and anti-nucleocapsid protein IgG using quantitative assays on the Luminex platform. Daily case and death data, weekly excess deaths, and weekly hospital admissions were plotted over time. Results Samples were obtained from 7010 individuals, of whom 1319 (18.8%) had received a Covid-19 vaccine. Overall seroprevalence ranged from 56.2% (95% confidence interval [CI], 52.6 to 59.7) in children aged <12 years to 79.7% (95% CI, 77.6 to 81.5) in individuals aged >50 years. Seropositivity was 6.22-fold more likely in vaccinated (93.1%) vs unvaccinated (68.4%) individuals. Epidemiological data showed SARS-CoV-2 infection rates increased more rapidly than in previous waves but have now plateaued. Rates of hospitalizations and excess deaths did not increase proportionately, remaining relatively low. Conclusions We demonstrate widespread underlying SARS-CoV-2 seropositivity in Gauteng Province prior to the current Omicron-dominant wave, with epidemiological data showing an uncoupling of hospitalization and death rates from infection rate during Omicron circulation.

SARS-CoV-2 transmission dynamics in South Africa and epidemiological characteristics of the Omicron variant

Within days of first detection, Omicron SARS-CoV-2 variant case numbers grew exponentially and spread globally. To better understand variant epidemiological characteristics, we utilize a model-inference system to reconstruct SARS-CoV-2 transmission dynamics in South Africa and decompose novel variant transmissibility and immune erosion. Accounting for under-detection of infection, infection seasonality, nonpharmaceutical interventions, and vaccination, we estimate that the majority of South Africans had been infected by SARS-CoV-2 before the Omicron wave. Based on findings for Gauteng province, Omicron is estimated 100.3% (95% CI: 74.8 - 140.4%) more transmissible than the ancestral SARS-CoV-2 and 36.5% (95% CI: 20.9 - 60.1%) more transmissible than Delta; in addition, Omicron erodes 63.7% (95% CI: 52.9 - 73.9%) of the population immunity, accumulated from prior infections and vaccination, in Gauteng.