Herd immunity to endemic diseases: Historical concepts and implications for public health policy.

BACKGROUND: "Herd immunity" became a contested term during the COVID-19 pandemic. Although the term "herd immunity" is often used to refer to thresholds at which some diseases can be eliminated (e.g., due to mass vaccination), the term has multiple referents. Different concepts of herd immunity have been relevant throughout the history of immunology and infectious disease epidemiology. For some diseases, herd immunity plays a role in the development of an endemic equilibrium, rather than elimination via threshold effects. METHODS: We reviewed academic literature from 1920 to 2022, using historical and philosophical analysis to identify and develop relevant concepts of herd immunity. RESULTS: This paper analyses the ambiguity surrounding the concept of herd immunity during the pandemic. We argue for the need to recapture a long-standing interpretation of this concept as one of the factors that leads to a dynamic endemic equilibrium between a host population and a mutating respiratory pathogen. CONCLUSIONS: Informed by the history of infectious disease epidemiology, we argue that understanding the concept in this way will help us manage both SARS-CoV-2 and hundreds of other seasonal respiratory pathogens with which we live but which have been disrupted due to sustained public health measures/non-pharmaceutical interventions targeting SARS-CoV-2.

SIRS epidemics with individual heterogeneity of immunity waning.

In the current paper we analyse an extended SIRS epidemic model in which immunity at the individual level wanes gradually at exponential rate, but where the waning rate may differ between individuals, for instance as an effect of differences in immune systems. The model also includes vaccination schemes aimed to reach and maintain herd immunity. We consider both the informed situation where the individual waning parameters are known, thus allowing selection of vaccinees being based on both time since last vaccination as well as on the individual waning rate, and the more likely uninformed situation where individual waning parameters are unobserved, thus only allowing vaccination schemes to depend on time since last vaccination. The optimal vaccination policies for both the informed and uniformed heterogeneous situation are derived and compared with the homogeneous waning model (meaning all individuals have the same immunity waning rate), as well as to the classic SIRS model where immunity at the individual level drops from complete immunity to complete susceptibility in one leap. It is shown that the classic SIRS model requires least vaccines, followed by the SIRS with homogeneous gradual waning, followed by the informed situation for the model with heterogeneous gradual waning. The situation requiring most vaccines for herd immunity is the most likely scenario, that immunity wanes gradually with unobserved individual heterogeneity. For parameter values chosen to mimic COVID-19 and assuming perfect initial immunity and cumulative immunity of 12 months, the classic homogeneous SIRS epidemic suggests that vaccinating individuals every 15 months is sufficient to reach and maintain herd immunity, whereas the uninformed case for exponential waning with rate heterogeneity corresponding to a coefficient of variation being 0.5, requires that individuals instead need to be vaccinated every 4.4 months.

Heterogeneous risk attitudes and waves of infection.

Many countries have experienced multiple waves of infection during the COVID-19 pandemic. We propose a novel but parsimonious extension of the SIR model, a CSIR model, that can endogenously generate waves. In the model, cautious individuals take appropriate prevention measures against the virus and are not exposed to infection risk. Incautious individuals do not take any measures and are susceptible to the risk of infection. Depending on the size of incautious and susceptible population, some cautious people lower their guard and become incautious-thus susceptible to the virus. When the virus spreads sufficiently, the population reaches "temporary" herd immunity and infection subsides thereafter. Yet, the inflow from the cautious to the susceptible eventually expands the susceptible population and leads to the next wave. We also show that the CSIR model is isomorphic to the SIR model with time-varying parameters.

Simple economics of vaccination: public policies and incentives.

This paper focuses on the economics of vaccination and, more specifically, analyzes the vaccination decision of individuals using a game-theoretic model combined with an epidemiological SIR model that reproduces the infection dynamics of a generic disease. We characterize the equilibrium individual vaccination rate, and we show that it is below the rate compatible with herd immunity due to the existence of externalities that individuals do not internalize when they decide on vaccination. In addition, we analyze three public policies consisting of informational campaigns to reduce the disutility of vaccination, monetary payments to vaccinated individuals and measures to increase the disutility of non-vaccination. If the public authority uses only one type of policy, herd immunity is not necessarily achieved unless monetary incentives are used. When the public authority is not limited to use only one policy, we find that the optimal public policy should consist only of informational campaigns if they are sufficiently effective, or a combination of informational campaigns and monetary incentives otherwise. Surprisingly, the requirement of vaccine passports or other restrictions on the non-vaccinated are not desirable.

Use of immunology in news and YouTube videos in the context of COVID-19: politicisation and information bubbles.

Background: The COVID-19 pandemic propelled immunology into global news and social media, resulting in the potential for misinterpreting and misusing complex scientific concepts. Objective: To study the extent to which immunology is discussed in news articles and YouTube videos in English and Italian, and if related scientific concepts are used to support specific political or ideological narratives in the context of COVID-19. Methods: In English and Italian we searched the period 11/09/2019 to 11/09/2022 on YouTube, using the software Mozdeh, for videos mentioning COVID-19 and one of nine immunological concepts: antibody-dependent enhancement, anergy, cytokine storm, herd immunity, hygiene hypothesis, immunity debt, original antigenic sin, oxidative stress and viral interference. We repeated this using MediaCloud for news articles.Four samples of 200 articles/videos were obtained from the randomised data gathered and analysed for mentions of concepts, stance on vaccines, masks, lockdown, social distancing, and political signifiers. Results: Vaccine-negative information was higher in videos than news (8-fold in English, 6-fold in Italian) and higher in Italian than English (4-fold in news, 3-fold in videos). We also observed the existence of information bubbles, where a negative stance towards one intervention was associated with a negative stance to other linked ideas. Some immunological concepts (immunity debt, viral interference, anergy and original antigenic sin) were associated with anti-vaccine or anti-NPI (non-pharmacological intervention) views. Videos in English mentioned politics more frequently than those in Italian and, in all media and languages, politics was more frequently mentioned in anti-guidelines and anti-vaccine media by a factor of 3 in video and of 3-5 in news. Conclusion: There is evidence that some immunological concepts are used to provide credibility to specific narratives and ideological views. The existence of information bubbles supports the concept of the "rabbit hole" effect, where interest in unconventional views/media leads to ever more extreme algorithmic recommendations.

Projecting Omicron scenarios in the US while tracking population-level immunity.

Throughout the COVID-19 pandemic, changes in policy, shifts in behavior, and the emergence of new SARS-CoV-2 variants spurred multiple waves of transmission. Accurate assessments of the changing risks were vital for ensuring adequate healthcare capacity, designing mitigation strategies, and communicating effectively with the public. Here, we introduce a model of COVID-19 transmission and vaccination that provided rapid and reliable projections as the BA.1, BA.4 and BA.5 variants emerged and spread across the US. For example, our three-week ahead national projection of the early 2021 peak in COVID-19 hospitalizations was only one day later and 11.6-13.3% higher than the actual peak, while our projected peak in mortality was two days earlier and 0.22-4.7% higher than reported. We track population-level immunity from prior infections and vaccination in terms of the percent reduction in overall susceptibility relative to a completely naive population. As of October 1, 2022, we estimate that the US population had a 36.52% reduction in overall susceptibility to the BA.4/BA.5 variants, with 61.8%, 15.06%, and 23.54% of immunity attributable to infections, primary series vaccination, and booster vaccination, respectively. We retrospectively projected the potential impact of expanding booster coverage starting on July 15, 2022, and found that a five-fold increase in weekly boosting rates would have resulted in 70% of people over 65 vaccinated by Oct 10, 2022 and averted 25,000 (95% CI: 14,400-35,700) deaths during the BA.4/BA.5 surge. Our model provides coherent variables for tracking population-level immunity in the increasingly complex landscape of variants and vaccines and enables robust simulations of plausible scenarios for the emergence and mitigation of novel COVID variants.

Herd immunity versus self-interest motives and norms effects on influenza vaccination intention.

OBJECTIVE: Promoting vaccine uptake is challenging. This research aimed to experimentally test the effect of communication strategies on influenza vaccine uptake intention. We hypothesized that the effect of descriptive norm level (10%-50%-90% of others vaccinated) on intention would vary according to whether the benefits are focused on the individual (self-interest motives) or others (herd-immunity motives). In particular, we predicted that low and high levels of norms would be detrimental in the herd-immunity condition (inverted-U pattern). In contrast, intention should increase linearly with the norm in the self-interest condition. METHOD: A representative sample of the Swiss population answered a survey containing vignettes manipulating norms (within-subjects variable) and motives (between-subjects variable, randomized). Their intention to receive a flu shot was measured for each situation. RESULTS: As expected, a significant simple quadratic effect of norm was obtained in the herd-immunity condition. No linear effect was found in the self-interest condition. A main effect of motives was found: The intention was higher in the herd-immunity condition than in the self-interest condition. Sensitivity analysis showed that our results are robust, except for the simple quadratic effect in the herd-immunity condition. CONCLUSIONS: Herd-immunity motive is more motivating to induce intention to vaccinate against influenza. The effect of norms appears to depend on the motive, and average levels of norms seem to be more motivating than very low and very high levels. The way vaccination is presented can influence adoption rates, and this should be considered when vaccination rates are communicated in the media. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The duty of care and the right to be cared for: is there a duty to treat the unvaccinated?

Vaccine hesitancy or refusal has been one of the major obstacles to herd immunity against Covid-19 in high-income countries and one of the causes for the emergence of variants. The refusal of people who are eligible for vaccination to receive vaccination creates an ethical dilemma between the duty of healthcare professionals (HCPs) to care for patients and their right to be taken care of. This paper argues for an extended social contract between patients and society wherein vaccination against Covid-19 is conceived as essential for the protection of the right of healthcare providers to be taken care of. Thus, a duty of care is only valid when those who can receive vaccination actually receive it. Whenever that is not the case, the continuing functioning of HCPs can only be perceived as supererogatory and not obligatory.

COVID-19 vaccine refusal as unfair free-riding.

Contributions to COVID-19 vaccination programmes promise valuable collective goods. They can support public and individual health by creating herd immunity and taking the pressure off overwhelmed public health services; support freedom of movement by enabling governments to remove restrictive lockdown policies; and improve economic and social well-being by allowing businesses, schools, and other essential public services to re-open. The vaccinated can contribute to the production of these goods. The unvaccinated, who benefit from, but who do not contribute to these goods can be morally criticised as free-riders. In this paper defends the claim that in the case of COVID-19, the unvaccinated are unfair free-riders. I defend the claim against two objections. First, that they are not unfair free-riders because they lack the subjective attitudes and intentions of free-riders; second, that although the unvaccinated may be free-riders, their free-riding is not unfair.

Prevention of respiratory virus transmission by resident memory CD8+ T cells.

An ideal vaccine both attenuates virus growth and disease in infected individuals and reduces the spread of infections in the population, thereby generating herd immunity. Although this strategy has proved successful by generating humoral immunity to measles, yellow fever and polio, many respiratory viruses evolve to evade pre-existing antibodies1. One approach for improving the breadth of antiviral immunity against escape variants is through the generation of memory T cells in the respiratory tract, which are positioned to respond rapidly to respiratory virus infections2-6. However, it is unknown whether memory T cells alone can effectively surveil the respiratory tract to the extent that they eliminate or greatly reduce viral transmission following exposure of an individual to infection. Here we use a mouse model of natural parainfluenza virus transmission to quantify the extent to which memory CD8+ T cells resident in the respiratory tract can provide herd immunity by reducing both the susceptibility of acquiring infection and the extent of transmission, even in the absence of virus-specific antibodies. We demonstrate that protection by resident memory CD8+ T cells requires the antiviral cytokine interferon-γ (IFNγ) and leads to altered transcriptional programming of epithelial cells within the respiratory tract. These results suggest that tissue-resident CD8+ T cells in the respiratory tract can have important roles in protecting the host against viral disease and limiting viral spread throughout the population.

Review: The Landscape of Antiviral Therapy for COVID-19 in the Era of Widespread Population Immunity and Omicron-Lineage Viruses.

The goals of coronavirus disease 2019 (COVID-19) antiviral therapy early in the pandemic were to prevent severe disease, hospitalization, and death. As these outcomes have become infrequent in the age of widespread population immunity, the objectives have shifted. For the general population, COVID-19-directed antiviral therapy should decrease symptom severity and duration and minimize infectiousness, and for immunocompromised individuals, antiviral therapy should reduce severe outcomes and persistent infection. The increased recognition of virologic rebound following ritonavir-boosted nirmatrelvir (NMV/r) and the lack of randomized controlled trial data showing benefit of antiviral therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for standard-risk, vaccinated individuals remain major knowledge gaps. Here, we review data for selected antiviral agents and immunomodulators currently available or in late-stage clinical trials for use in outpatients. We do not review antibody products, convalescent plasma, systemic corticosteroids, IL-6 inhibitors, Janus kinase inhibitors, or agents that lack Food and Drug Administration approval or emergency use authorization or are not appropriate for outpatients.

Clinical Epidemiology and Risk Factors for Critical Outcomes Among Vaccinated and Unvaccinated Adults Hospitalized With COVID-19-VISION Network, 10 States, June 2021-March 2023.

BACKGROUND: The epidemiology of coronavirus disease 2019 (COVID-19) continues to develop with emerging variants, expanding population-level immunity, and advances in clinical care. We describe changes in the clinical epidemiology of COVID-19 hospitalizations and risk factors for critical outcomes over time. METHODS: We included adults aged ≥18 years from 10 states hospitalized with COVID-19 June 2021-March 2023. We evaluated changes in demographics, clinical characteristics, and critical outcomes (intensive care unit admission and/or death) and evaluated critical outcomes risk factors (risk ratios [RRs]), stratified by COVID-19 vaccination status. RESULTS: A total of 60 488 COVID-19-associated hospitalizations were included in the analysis. Among those hospitalized, median age increased from 60 to 75 years, proportion vaccinated increased from 18.2% to 70.1%, and critical outcomes declined from 24.8% to 19.4% (all P < .001) between the Delta (June-December, 2021) and post-BA.4/BA.5 (September 2022-March 2023) periods. Hospitalization events with critical outcomes had a higher proportion of ≥4 categories of medical condition categories assessed (32.8%) compared to all hospitalizations (23.0%). Critical outcome risk factors were similar for unvaccinated and vaccinated populations; presence of ≥4 medical condition categories was most strongly associated with risk of critical outcomes regardless of vaccine status (unvaccinated: adjusted RR, 2.27 [95% confidence interval {CI}, 2.14-2.41]; vaccinated: adjusted RR, 1.73 [95% CI, 1.56-1.92]) across periods. CONCLUSIONS: The proportion of adults hospitalized with COVID-19 who experienced critical outcomes decreased with time, and median patient age increased with time. Multimorbidity was most strongly associated with critical outcomes.

Determining Herd Immunity Thresholds for Hepatitis A Virus Transmission to Inform Vaccination Strategies Among People Who Inject Drugs in 16†US States.

BACKGROUND: Widespread outbreaks of person-to-person transmitted hepatitis A virus (HAV), particularly among people who inject drugs (PWID), continue across the United States and globally. However, the herd immunity threshold and vaccination coverage required to prevent outbreaks are unknown. We used surveillance data and dynamic modeling to estimate herd immunity thresholds among PWID in 16 US states. METHODS: We used a previously published dynamic model of HAV transmission calibrated to surveillance data from outbreaks involving PWID in 16 states. Using state-level calibrated models, we estimated the basic reproduction number (R0) and herd immunity threshold for PWID in each state. We performed a meta-analysis of herd immunity thresholds to determine the critical vaccination coverage required to prevent most HAV outbreaks among PWID. RESULTS: Estimates of R0 for HAV infection ranged from 2.2 (95% confidence interval [CI], 1.9-2.5) for North Carolina to 5.0 (95% CI, 4.5-5.6) for West Virginia. Corresponding herd immunity thresholds ranged from 55% (95% CI, 47%-61%) for North Carolina to 80% (95% CI, 78%-82%) for West Virginia. Based on the meta-analysis, we estimated a pooled herd immunity threshold of 64% (95% CI, 61%-68%; 90% prediction interval, 52%-76%) among PWID. Using the prediction interval upper bound (76%) and assuming 95% vaccine efficacy, we estimated that vaccination coverage of 80% could prevent most HAV outbreaks. CONCLUSIONS: Hepatitis A vaccination programs in the United States may need to achieve vaccination coverage of at least 80% among PWID in order to prevent most HAV outbreaks among this population.

Clinical course and management of COVID-19 in the era of widespread population immunity.

The clinical implications of COVID-19 have changed since SARS-CoV-2 first emerged in humans. The current high levels of population immunity, due to prior infection and/or vaccination, have been associated with a vastly decreased overall risk of severe disease. Some people, particularly those with immunocompromising conditions, remain at risk for severe outcomes. Through the course of the pandemic, variants with somewhat different symptom profiles from the original SARS-CoV-2 virus have emerged. The management of COVID-19 has also changed since 2020, with the increasing availability of evidence-based treatments in two main classes: antivirals and immunomodulators. Selecting the appropriate treatment(s) for patients with COVID-19 requires a deep understanding of the evidence and an awareness of the limitations of applying data that have been largely based on immune-naive populations to patients today who most likely have vaccine-derived and/or infection-derived immunity. In this Review, we provide a summary of the clinical manifestations and approaches to caring for adult patients with COVID-19 in the era of vaccine availability and the dominance of the Omicron subvariants, with a focus on the management of COVID-19 in different patient groups, including immunocompromised, pregnant, vaccinated and unvaccinated patients.

The impact of household structure on disease-induced herd immunity.

The disease-induced herd immunity level [Formula: see text] is the fraction of the population that must be infected by an epidemic to ensure that a new epidemic among the remaining susceptible population is not supercritical. For a homogeneously mixing population [Formula: see text] equals the classical herd immunity level [Formula: see text], which is the fraction of the population that must be vaccinated in advance of an epidemic so that the epidemic is not supercritical. For most forms of heterogeneous mixing [Formula: see text], sometimes dramatically so. For an SEIR (susceptible [Formula: see text] exposed [Formula: see text] infective [Formula: see text] recovered) model of an epidemic among a population that is partitioned into households, in which individuals mix uniformly within households and, in addition, uniformly at a much lower rate in the population at large, we show that [Formula: see text] unless variability in the household size distribution is sufficiently large. Thus, introducing household structure into a model typically has the opposite effect on disease-induced herd immunity than most other forms of population heterogeneity. We reach this conclusion by considering an approximation [Formula: see text] of [Formula: see text], supported by numerical studies using real-world household size distributions. For [Formula: see text], we prove that [Formula: see text] when all households have size n, and conjecture that this inequality holds for any common household size n. We prove results comparing [Formula: see text] and [Formula: see text] for epidemics which are highly infectious within households, and also for epidemics which are weakly infectious within households.

Extending susceptible-infectious-recovered-susceptible epidemics to allow for gradual waning of immunity.

Susceptible-infectious-recovered-susceptible (SIRS) epidemic models assume that individual immunity wanes in one leap, from complete immunity to complete susceptibility. For many diseases immunity on the contrary wanes gradually, something that has become even more evident during COVID-19 pandemic where also recently infected have a reinfection risk, and booster vaccines are given to increase immunity. Here, a novel mathematical model is presented allowing for the gradual decay of immunity following linear or exponential waning functions. The two new models and the SIRS model are compared assuming all three models have the same cumulative immunity. When no intervention is put in place, we find that the long-term prevalence is higher for the models with gradual waning. If aiming for herd immunity by continuous vaccination, it is shown that larger vaccine quantities are required when immunity wanes gradually compared with results obtained from the SIRS model, and this difference is the biggest for the most realistic assumption of exponentially waning of immunity. For parameter choices fitting to COVID-19, the critical amount of vaccine supply is about 50% higher if immunity wanes linearly, and more than 150% higher when immunity wanes exponentially, when compared with the classic SIRS epidemic model.

Personal risk or societal benefit? Investigating adults' support for COVID-19 childhood vaccination.

Parental hesitancy poses a serious threat to the success of the COVID-19 childhood vaccination campaign. We investigate whether adults' opinions on childhood vaccination can be influenced via two survey experiments in Italy (n = 3,633 participants) and the UK (n = 3,314 participants). Respondents were randomly assigned to: a "risk treatment" that highlighted the potential risks of COVID-19 to a child, a "herd immunity treatment" that emphasized the community benefits of pediatric vaccination, or a control message. Participants' probability of supporting COVID-19 childhood vaccination was then assessed on a 0-100 scale. We find that the "risk treatment" reduced the proportion of Italian parents strongly against vaccination by up to 29.6 %, while increasing the proportion of neutral parents by up to 45.0 %. The "herd immunity treatment", instead, was only effective among non-parents, resulting in a lower proportion of individuals against pediatric vaccination and a higher proportion of individuals in favor (both shifted by around 20 %).

Comparison of Achievements in the Implementation of COVID-19 Vaccination in Five Provinces to Establish Herd Immunity in Indonesia in the Perspective of the New Public Service.

This study aims to analyze the achievements of coronavirus disease-2019 (COVID-19) vaccination in five provinces in Indonesia, North Maluku, West Sulawesi, Maluku, West Papua, and Papua. Furthermore, to establish herd immunity in the new normal perspective. Vaccination is important because it is an effective way to build immunity. This method uses qualitative research with a Qualitative Data Analysis Software (QDAS) approach. The source of data was obtained from the official website of the government, the ministry of health, in the category of areas with low vaccination achievement, and data were also obtained by capturing news in credible official media to find the cause of the low vaccination rate in the community. The data analyst uses NVivo12 software to code and visualizes data in graphs, images, and word clouds. The findings of this study indicate that in five provinces in Indonesia, North Maluku (68%), West Sulawesi (76%), Maluku (66%), West Papua (62%), and Papua (41%), the achievement of vaccination implementation is still relatively low. Due to doubts in the community about the status of the vaccine, information and communication education from the government have not been optimal; the environment and geography vary, so it becomes an obstacle in carrying out vaccination.

Influence of herd immunity on norovirus: a long-term field study of repeated viral gastroenteritis outbreaks at the same facilities.

BACKGROUND: Viral acute gastroenteritis (AG) is detected worldwide annually. Outbreaks caused by viruses associated with gastroenteritis have been reported repeatedly at the same facilities in Yokohama, Japan over several years. We investigated the statuses of these repeated outbreaks to consider herd immunity at the facility level. METHODS: Between September 2007 and August 2017, 1459 AG outbreaks were reported at 1099 facilities. Stool samples were collected for virological testing, and the norovirus gene was amplified and sequenced to determine the genotype using the N-terminal region of the capsid. RESULTS: The outbreaks were caused by norovirus, sapovirus, rotavirus A, and rotavirus C. Norovirus was consistently predominant over the 10-year period. Of 1099 facilities, 227 reported multiple outbreaks, of which norovirus-only combinations accounted for 76.2%. More outbreaks were due to different genotype combinations than the same genotype combinations. For facilities that experienced two norovirus outbreaks, the average interval between outbreaks was longer for groups with the same combinations than for groups with different genogroup or genotype combinations, although no statistically significant differences were observed. At 44 facilities, outbreaks occurred repeatedly during the same AG season, and most exhibited combinations of different norovirus genotypes or viruses. Among 49 combinations with the same norovirus genotype at the same facilities over 10 years, the most prevalent genotypes were combinations of genogroup II genotype 4 (GII.4), followed by GII.2, GII.6, GII.3, GII.14, and GI.3. The mean interval between outbreaks was 31.2 ± 26.8 months for all combinations, and the mean intervals were longer for non-GII.4 genotype cases than for GII.4 cases, and statistically significant differences were observed (t-test, P < 0.05). Additionally, these average intervals were longer for kindergarten/nursery schools and primary schools than for nursing homes for older adults (t-test, P < 0.05). CONCLUSIONS: Repeated AG outbreaks at the same facilities in Yokohama during the 10-year study period included mainly norovirus combinations. Herd immunity at the facility level was maintained for at least the same AG season. Norovirus genotype-specific herd immunity was maintained for an average of 31.2 months during the study period, and these intervals differed depending on genotype.