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1. Impact of waning immunity against SARS-CoV-2 severity exacerbated by vaccine hesitancy

   https://doi.org/10.1371/journal.pcbi.1012211  

   Saad-Roy, Chadi M; Morris, Sinead E; Boots, Mike; Baker, Rachel E; Lewis, Bryan L; Farrar, Jeremy; Marathe, Madhav V; Graham, Andrea L; Levin, Simon A; Wagner, Caroline E; et al (August 2024, PLOS Computational Biology)

   Wallqvist, Anders (Ed.)

   The SARS-CoV-2 pandemic has generated a considerable number of infections and associated morbidity and mortality across the world. Recovery from these infections, combined with the onset of large-scale vaccination, have led to rapidly-changing population-level immunological landscapes. In turn, these complexities have highlighted a number of important unknowns related to the breadth and strength of immunity following recovery or vaccination. Using simple mathematical models, we investigate the medium-term impacts of waning immunity against severe disease on immuno-epidemiological dynamics. We find that uncertainties in the duration of severity-blocking immunity (imparted by either infection or vaccination) can lead to a large range of medium-term population-level outcomes (i.e. infection characteristics and immune landscapes). Furthermore, we show that epidemiological dynamics are sensitive to the strength and duration of underlying host immune responses; this implies that determining infection levels from hospitalizations requires accurate estimates of these immune parameters. More durable vaccines both reduce these uncertainties and alleviate the burden of SARS-CoV-2 in pessimistic outcomes. However, heterogeneity in vaccine uptake drastically changes immune landscapes toward larger fractions of individuals with waned severity-blocking immunity. In particular, if hesitancy is substantial, more robust vaccines have almost no effects on population-level immuno-epidemiology, even if vaccination rates are compensatorily high among vaccine-adopters. This pessimistic scenario for vaccination heterogeneity arises because those few individuals that are vaccine-adopters are so readily re-vaccinated that the duration of vaccinal immunity has no appreciable consequences on their immune status. Furthermore, we find that this effect is heightened if vaccine-hesitants have increased transmissibility (e.g. due to riskier behavior). Overall, our results illustrate the necessity to characterize both transmission-blocking and severity-blocking immune time scales. Our findings also underline the importance of developing robust next-generation vaccines with equitable mass vaccine deployment. 

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2. Analysis of the potential efficacy and timing of COVID-19 vaccine on morbidity and mortality

   Haghpanah, F; Lin, G; Levin, SA; Klein, E. (January 2021, EClinicalMedicine)

   null (Ed.)

   Background: COVID-19 vaccines have been approved and made available. While questions of vaccine allocation strategies have received significant attention, important questions remain regarding the potential impact of the vaccine given uncertainties regarding efficacy against transmission, availability, timing, and durability. Methods: We adapted a susceptible-exposed-infectious-recovered (SEIR) model to examine the potential impact on hospitalization and mortality assuming increasing rates of vaccine efficacy, coverage, and administration. We also evaluated the uncertainty of the vaccine to prevent infectiousness as well as the impact on outcomes based on the timing of distribution and the potential effects of waning immunity. Findings: Increased vaccine efficacy against disease reduces hospitalizations and deaths from COVID-19; however, the relative benefit of transmission blocking varied depending on the timing of vaccine distribution. Early in an outbreak, a vaccine that reduces transmission will be relatively more effective than one introduced later in the outbreak. In addition, earlier and accelerated implementation of a less effective vaccine is more impactful than later implementation of a more effective vaccine. These findings are magnified when considering the durability of the vaccine. Vaccination in the spring will be less impactful when immunity is less durable. Interpretation: Policy choices regarding non-pharmaceutical interventions, such as social distancing and face mask use, will need to remain in place longer if the vaccine is less effective at reducing transmission or distributed slower. In addition, the stage of the local outbreak greatly impacts the overall effectiveness of the vaccine in a region and should be considered when allocating vaccines. 

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3. The durability of natural infection and vaccine-induced immunity against future infection by SARS-CoV-2

   Jeffrey P Townsend; Hayley B Hassler; Pratha Sah; Alison P Galvani; Alex Dornburg (July 2022, Proceedings of the National Academy of Sciences of the United States of America)

   The durability of vaccine-mediated immunity to SARS-CoV-2, the durations to breakthrough infection, and the optimal timings of booster vaccination are crucial knowledge for pandemic response. Here, we applied comparative evolutionary analyses to estimate the durability of immunity and the likelihood of breakthrough infections over time following vaccination by BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), ChAdOx1 (Oxford-AstraZeneca), and Ad26.COV2.S (Johnson & Johnson/Janssen). We evaluated anti-Spike (S) immunoglobulin G (IgG) antibody levels elicited by each vaccine relative to natural infection. We estimated typical trajectories of waning and corresponding infection probabilities, providing the distribution of times to breakthrough infection for each vaccine under endemic conditions. Peak antibody levels elicited by messenger RNA (mRNA) vaccines mRNA-1273 and BNT1262b2 exceeded that of natural infection and are expected to typically yield more durable protection against breakthrough infections (median 29.6 mo; 5 to 95% quantiles 10.9 mo to 7.9 y) than natural infection (median 21.5 mo; 5 to 95% quantiles 3.5 mo to 7.1 y). Relative to mRNA-1273 and BNT1262b2, viral vector vaccines ChAdOx1 and Ad26.COV2.S exhibit similar peak anti-S IgG antibody responses to that from natural infection and are projected to yield lower, shorter-term protection against breakthrough infection (median 22.4 mo and 5 to 95% quantiles 4.3 mo to 7.2 y; and median 20.5 mo and 5 to 95% quantiles 2.6 mo to 7.0 y; respectively). These results leverage the tools from evolutionary biology to provide a quantitative basis for otherwise unknown parameters that are fundamental to public health policy decision-making. 

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4. Optimal SARS-CoV-2 vaccine allocation using real-time attack-rate estimates in Rhode Island and Massachusetts

   https://doi.org/10.1186/s12916-021-02038-w  

   Tran, Thu Nguyen-Anh; Wikle, Nathan B.; Albert, Emmy; Inam, Haider; Strong, Emily; Brinda, Karel; Leighow, Scott M.; Yang, Fuhan; Hossain, Sajid; Pritchard, Justin R.; et al (December 2021, BMC Medicine)

   null (Ed.)

   Abstract Background When three SARS-CoV-2 vaccines came to market in Europe and North America in the winter of 2020–2021, distribution networks were in a race against a major epidemiological wave of SARS-CoV-2 that began in autumn 2020. Rapid and optimized vaccine allocation was critical during this time. With 95% efficacy reported for two of the vaccines, near-term public health needs likely require that distribution is prioritized to the elderly, health care workers, teachers, essential workers, and individuals with comorbidities putting them at risk of severe clinical progression. Methods We evaluate various age-based vaccine distributions using a validated mathematical model based on current epidemic trends in Rhode Island and Massachusetts. We allow for varying waning efficacy of vaccine-induced immunity, as this has not yet been measured. We account for the fact that known COVID-positive cases may not have been included in the first round of vaccination. And, we account for age-specific immune patterns in both states at the time of the start of the vaccination program. Our analysis assumes that health systems during winter 2020–2021 had equal staffing and capacity to previous phases of the SARS-CoV-2 epidemic; we do not consider the effects of understaffed hospitals or unvaccinated medical staff. Results We find that allocating a substantial proportion (>75 % ) of vaccine supply to individuals over the age of 70 is optimal in terms of reducing total cumulative deaths through mid-2021. This result is robust to different profiles of waning vaccine efficacy and several different assumptions on age mixing during and after lockdown periods. As we do not explicitly model other high-mortality groups, our results on vaccine allocation apply to all groups at high risk of mortality if infected. A median of 327 to 340 deaths can be avoided in Rhode Island (3444 to 3647 in Massachusetts) by optimizing vaccine allocation and vaccinating the elderly first. The vaccination campaigns are expected to save a median of 639 to 664 lives in Rhode Island and 6278 to 6618 lives in Massachusetts in the first half of 2021 when compared to a scenario with no vaccine. A policy of vaccinating only seronegative individuals avoids redundancy in vaccine use on individuals that may already be immune, and would result in 0.5% to 1% reductions in cumulative hospitalizations and deaths by mid-2021. Conclusions Assuming high vaccination coverage (>28 % ) and no major changes in distancing, masking, gathering size, hygiene guidelines, and virus transmissibility between 1 January 2021 and 1 July 2021 a combination of vaccination and population immunity may lead to low or near-zero transmission levels by the second quarter of 2021. 

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5. Dynamic prioritization of COVID-19 vaccines when social distancing is limited for essential workers

   https://doi.org/10.1073/pnas.2025786118  

   Buckner, Jack H.; Chowell, Gerardo; Springborn, Michael R. (April 2021, Proceedings of the National Academy of Sciences)

   null (Ed.)

   COVID-19 vaccines have been authorized in multiple countries, and more are under rapid development. Careful design of a vaccine prioritization strategy across sociodemographic groups is a crucial public policy challenge given that 1) vaccine supply will be constrained for the first several months of the vaccination campaign, 2) there are stark differences in transmission and severity of impacts from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across groups, and 3) SARS-CoV-2 differs markedly from previous pandemic viruses. We assess the optimal allocation of a limited vaccine supply in the United States across groups differentiated by age and essential worker status, which constrains opportunities for social distancing. We model transmission dynamics using a compartmental model parameterized to capture current understanding of the epidemiological characteristics of COVID-19, including key sources of group heterogeneity (susceptibility, severity, and contact rates). We investigate three alternative policy objectives (minimizing infections, years of life lost, or deaths) and model a dynamic strategy that evolves with the population epidemiological status. We find that this temporal flexibility contributes substantially to public health goals. Older essential workers are typically targeted first. However, depending on the objective, younger essential workers are prioritized to control spread or seniors to directly control mortality. When the objective is minimizing deaths, relative to an untargeted approach, prioritization averts deaths on a range between 20,000 (when nonpharmaceutical interventions are strong) and 300,000 (when these interventions are weak). We illustrate how optimal prioritization is sensitive to several factors, most notably, vaccine effectiveness and supply, rate of transmission, and the magnitude of initial infections. 

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