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.

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.

Protecting the herd with vaccination.

How much do COVID-19 vaccines reduce transmission? The answer is a moving target.

Comparing the impact of vaccination strategies on the spread of COVID-19, including a novel household-targeted vaccination strategy.

With limited availability of vaccines, an efficient use of the limited supply of vaccines in order to achieve herd immunity will be an important tool to combat the wide-spread prevalence of COVID-19. Here, we compare a selection of strategies for vaccine distribution, including a novel targeted vaccination approach (EHR) that provides a noticeable increase in vaccine impact on disease spread compared to age-prioritized and random selection vaccination schemes. Using high-fidelity individual-based computer simulations with Oslo, Norway as an example, we find that for a community reproductive number in a setting where the base pre-vaccination reproduction number R = 2.1 without population immunity, the EHR method reaches herd immunity at 48% of the population vaccinated with 90% efficiency, whereas the common age-prioritized approach needs 89%, and a population-wide random selection approach requires 61%. We find that age-based strategies have a substantially weaker impact on epidemic spread and struggle to achieve herd immunity under the majority of conditions. Furthermore, the vaccination of minors is essential to achieving herd immunity, even for ideal vaccines providing 100% protection.

Impact of vaccination on the COVID-19 pandemic in U.S. states.

Governments worldwide are implementing mass vaccination programs in an effort to end the novel coronavirus (COVID-19) pandemic. Here, we evaluated the effectiveness of the COVID-19 vaccination program in its early stage and predicted the path to herd immunity in the U.S. By early March 2021, we estimated that vaccination reduced the total number of new cases by 4.4 million (from 33.0 to 28.6 million), prevented approximately 0.12 million hospitalizations (from 0.89 to 0.78 million), and decreased the population infection rate by 1.34 percentage points (from 10.10 to 8.76%). We built a Susceptible-Infected-Recovered (SIR) model with vaccination to predict herd immunity, following the trends from the early-stage vaccination program. Herd immunity could be achieved earlier with a faster vaccination pace, lower vaccine hesitancy, and higher vaccine effectiveness. The Delta variant has substantially postponed the predicted herd immunity date, through a combination of reduced vaccine effectiveness, lowered recovery rate, and increased infection and death rates. These findings improve our understanding of the COVID-19 vaccination and can inform future public health policies.

Analyses of Confirmed COVID-19 Cases Among Korean Military Personnel After Mass Vaccination.

BACKGROUND: The military was one of the first groups in Korea to complete mass vaccination against the coronavirus disease 2019 (COVID-19) due to their high vulnerability to COVID-19. To confirm the effect of mass vaccination, this study analyzed the patterns of confirmed cases within Korean military units. METHODS: From August 1 to September 15, 2021, all epidemiological data regarding confirmed COVID-19 cases in military units were reviewed. The number of confirmed cases in the units that were believed to have achieved herd immunity (i.e., ≥ 70% vaccination) was compared with the number of cases in the units that were not believed to have reached herd immunity (< 70% vaccination). Additionally, trends in the incidence rates of COVID-19 in the military and the entire Korean population were compared. RESULTS: By August 2021, 85.60% of military personnel were fully vaccinated. During the study period, a total of 174 COVID-19 cases were confirmed in the 39 units. More local transmission (herd immunity group vs. non-herd immunity group [%], 1 [0.91] vs. 39 [60.94]) and hospitalizations (12 [11.01] vs. 13 [27.08]) occurred in the units that were not believed to have achieved herd immunity. The percentage of fully vaccinated individuals among the confirmed COVID-19 cases increased over time, possibly due to the prevalence of the delta variant. Nevertheless, the incidence rate remained lower in military units than in the general Korean population. CONCLUSION: After completing mass vaccination, the incidence rates of COVID-19 infection in the military were lower than those in the national population. New cluster infections did not occur in vaccinated units, thereby suggesting that herd immunity has been achieved in these military units. Further research is needed to determine the extent to which levels of non-pharmacological intervention can be reduced in the future.

COVID-19 herd immunity v. learning to live with the virus.

Mutations of SARS-CoV-2 have been associated with increased transmissibility and occasionally reduced sensitivity to neutralising antibody activity induced by past ancestry virus infection or current COVID-19 vaccines. Nevertheless, COVID-19 vaccines have consistently demonstrated high efficacy and effectiveness against COVID-19 severe disease, hospitalisation and death, including disease caused by designated variants of concern. In contrast, COVID-19 vaccines are more heterogeneous in reducing the risk of infection and mild COVID19, and are modestly effective in interrupting virus transmission. Ongoing mutations of SARS-CoV-2 resulting in increased transmissibility and relative evasion of neutralising antibody activity induced by past virus infection or COVID-19 vaccines are likely. The duration of protection induced by COVID-19 vaccines is modelled to be relatively short in protecting against infection and mild COVID-19, but is likely to be 2 - 3 years against severe disease. Current experience from the UK and Israel demonstrates that even with high levels of COVID19 vaccine coverage (>85% of the adult population), resurgences with new variants of concern remain a strong probability. Nevertheless, such resurgences are not mirrored by high rates of hospitalisation and death compared with what was experienced in relatively COVID-19 vaccine-naive populations. Even though COVID-19 vaccines are unlikely to result in a herd immunity state, their ability to protect against severe COVID-19 and death could allow for a return to normalcy once a large enough proportion of the adult population in a country has been vaccinated.

Contact-adjusted Immunity Levels against SARS-CoV-2 in Korea and Prospects for Achieving Herd Immunity.

The proportion of population vaccinated cannot be directly translated into the herd immunity. We have to account for the age-stratified contact patterns to calculate the population immunity level, since not every individual gathers evenly. Here, we calculated the contact-adjusted population immunity against severe acute respiratory syndrome coronavirus 2 in South Korea using age-specific incidence and vaccine uptake rate. We further explored options to achieve the theoretical herd immunity with age-varying immunity scenarios. As of June 21, 2021, when a quarter of the population received at least one dose of a coronavirus disease 2019 (COVID-19) vaccine, the contact-adjusted immunity level was 12.5% under the social distancing level 1. When 80% of individuals aged 10 years and over gained immunity, we could achieve a 58.2% contact-adjusted immunity level. The pros and cons of vaccinating children should be weighed since the risks of COVID-19 for the young are less than the elderly, and the long-term safety of vaccines is still obscure.

Modelling infectious diseases with herd immunity in a randomly mixed population.

The conventional susceptible-infectious-recovered (SIR) model tends to magnify the transmission dynamics of infectious diseases, and thus the estimated total infections and immunized population may be higher than the threshold required for infection control and eradication. The study developed a new SIR framework that allows the transmission rate of infectious diseases to decline along with the reduced risk of contact infection to overcome the limitations of the conventional SIR model. Two new SIR models were formulated to mimic the declining transmission rate of infectious diseases at different stages of transmission. Model A utilized the declining transmission rate along with the reduced risk of contact infection following infection, while Model B incorporated the declining transmission rate following recovery. Both new models and the conventional SIR model were then used to simulate an infectious disease with a basic reproduction number (r0) of 3.0 and a herd immunity threshold (HIT) of 0.667 with and without vaccination. Outcomes of simulations were assessed at the time when the total immunized population reached the level predicted by the HIT, and at the end of simulations. Further, all three models were used to simulate the transmission dynamics of seasonal influenza in the United States and disease burdens were projected and compared with estimates from the Centers for Disease Control and Prevention. For the simulated infectious disease, in the initial phase of the outbreak, all three models performed expectedly when the sizes of infectious and recovered populations were relatively small. As the infectious population increased, the conventional SIR model appeared to overestimate the infections even when the HIT was achieved in all scenarios with and without vaccination. For the same scenario, Model A appeared to attain the level predicted by the HIT and in comparison, Model B projected the infectious disease to be controlled at the level predicted by the HIT only at high vaccination rates. For infectious diseases with high r0, and at low vaccination rates, the level at which the infectious disease was controlled cannot be accurately predicted by the current theorem. Transmission dynamics of infectious diseases with herd immunity can be accurately modelled by allowing the transmission rate of infectious diseases to decline along with the reduction of contact infection risk after recovery or vaccination. Model B provides a credible framework for modelling infectious diseases with herd immunity in a randomly mixed population.

Vaccination versus infection with SARS-CoV-2: Establishment of a high avidity IgG response versus incomplete avidity maturation.

Avidity is defined as the binding strength of immunoglobulin G (IgG) toward its target epitope. Avidity is directly related to affinity, as both processes are determined by the best fit of IgG to epitopes. We confirm and extend data on incomplete avidity maturation of IgG toward severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein (NP), spike protein-1 (S1), and its receptor-binding domain (RBD) in coronavirus disease 2019 (COVID-19) patients. In SARS-CoV-2-infected individuals, an initial rise in avidity maturation was ending abruptly, leading to IgG of persistently low or intermediate avidity. Incomplete avidity maturation might facilitate secondary SARS-CoV-2 infections and thus prevent the establishment of herd immunity. Incomplete avidity maturation after infection with SARS-CoV-2 (with only 11.8% of cases showing finally IgG of high avidity, that is, an avidity index > 0.6) was contrasted by regular and rapid establishment of high avidity in SARS-CoV-2 naïve individuals after two vaccination steps with the BioNTech messenger RNA (mRNA) Vaccine (78% of cases with high avidity). One vaccination step was not sufficient for induction of complete avidity maturation in vaccinated SARS-CoV-2 naïve individuals, as it induced high avidity only in 2.9% of cases within 3 weeks. However, one vaccination step was sufficient to induce high avidity in individuals with previous SARS-CoV-2 infection.

SARS-CoV-2 outbreak in a synagogue community: longevity and strength of anti-SARS-CoV-2 IgG responses.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic is still ongoing along with the global vaccination efforts against it. Here, we aimed to understand the longevity and strength of anti-SARS-CoV-2 IgG responses in a small community (n = 283) six months following local SARS-COV-2 outbreak in March 2020. Three serological assays were compared and neutralisation capability was also determined. Overall 16.6% (47/283) of the participants were seropositive and 89.4% (42/47) of the IgG positives had neutralising antibodies. Most of the symptomatic individuals confirmed as polymerase chain reaction (PCR) positive during the outbreak were seropositive (30/32, 93.8%) and 33.3% of the individuals who quarantined with a PCR confirmed patient had antibodies. Serological assays comparison revealed that Architect (Abbott) targeting the N protein LIASON® (DiaSorin) targeting the S protein and enzyme-linked immunosorbent assay (ELISA) targeting receptor binding domain detected 9.5% (27/283), 17.3% (49/283) and 17% (48/283), respectively, as IgG positives. The latter two assays highly agreed (kappa = 0.89) between each other. In addition, 95%, (19/20, by ELISA) and 90.9% (20/22, with LIASON) and only 71.4% (15/21, by Architect) of individuals that were seropositive in May 2020 were found positive also in September. The unexpected low rate of overall immunity indicates the absence of un-noticed, asymptomatic infections. Lack of overall high correlation between the assays is attributed mainly to target-mediated antibody responses and suggests that using a single serological assay may be misleading.

COVID-19 vaccines and herd immunity: Perspectives, challenges and prospects.

The coronavirus disease 2019 (COVID-19) is one of the biggest public health threats in the 21st century. Nearly every country in the world has been affected by COVID-19. The magnitude of the problem, with over 179 million confirmed cases and 3.8 million deaths worldwide, has driven researchers to search for vaccines to combat the disease. The discovery and development of a new vaccine, from the initial stage to the vaccine finally reaching the patients, usually take many years. However, given the urgency of the situation, many clinical trials on the COVID-19 vaccines have been conducted at extraordinary speed, whereas several vaccines against SARS-CoV-2 are being administered worldwide. This article gives an overview of the different types of COVID-19 vaccines, with a focus on those with promising results and are commonly used worldwide. It also gives an overview of herd immunity and discusses the challenges in achieving herd immunity through the global vaccination campaigns. Last but not least, some strategies that may be used to address these challenges are discussed.

Will SARS-CoV-2 Become Just Another Seasonal Coronavirus?

The future prevalence and virulence of SARS-CoV-2 is uncertain. Some emerging pathogens become avirulent as populations approach herd immunity. Although not all viruses follow this path, the fact that the seasonal coronaviruses are benign gives some hope. We develop a general mathematical model to predict when the interplay among three factors, correlation of severity in consecutive infections, population heterogeneity in susceptibility due to age, and reduced severity due to partial immunity, will promote avirulence as SARS-CoV-2 becomes endemic. Each of these components has the potential to limit severe, high-shedding cases over time under the right circumstances, but in combination they can rapidly reduce the frequency of more severe and infectious manifestation of disease over a wide range of conditions. As more reinfections are captured in data over the next several years, these models will help to test if COVID-19 severity is beginning to attenuate in the ways our model predicts, and to predict the disease.