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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. Antibody escape, the risk of serotype formation, and rapid immune waning: Modeling the implications of SARS-CoV-2 immune evasion

   https://doi.org/10.1371/journal.pone.0292099  

   Albright, Catherine; Van_Egeren, Debra; Thakur, Aditya; Chakravarty, Arijit; White, Laura F; Stoddard, Madison (October 2023, PLOS ONE)

   Kolawole, Olatunji Matthew (Ed.)

   As the COVID-19 pandemic progresses, widespread community transmission of SARS-CoV-2 has ushered in a volatile era of viral immune evasion rather than the much-heralded stability of “endemicity” or “herd immunity.” At this point, an array of viral strains has rendered essentially all monoclonal antibody therapeutics obsolete and strongly undermined the impact of vaccinal immunity on SARS-CoV-2 transmission. In this work, we demonstrate that antibody escape resulting in evasion of pre-existing immunity is highly evolutionarily favored and likely to cause waves of short-term transmission. In the long-term, invading strains that induce weak cross-immunity against pre-existing strains may co-circulate with those pre-existing strains. This would result in the formation of serotypes that increase disease burden, complicate SARS-CoV-2 control, and raise the potential for increases in viral virulence. Less durable immunity does not drive positive selection as a trait, but such strains may transmit at high levels if they establish. Overall, our results draw attention to the importance of inter-strain cross-immunity as a driver of transmission trends and the importance of early immune evasion data to predict the trajectory of the pandemic. 

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4. Vaccination, immunity, and the changing impact of COVID-19 on infant health

   https://doi.org/10.1073/pnas.2311573120  

   Torche, Florencia; Nobles, Jenna (December 2023, Proceedings of the National Academy of Sciences)

   In utero exposure to COVID-19 infection may lead to large intergenerational health effects. The impact of infection exposure has likely evolved since the onset of the pandemic as new variants emerge, immunity from prior infection increases, vaccines become available, and vaccine hesitancy persists, such thatwheninfection is experienced is as important aswhetherit is experienced. We examine the changing impact of COVID-19 infection on preterm birth and the moderating role of vaccination. We offer the first plausibly causal estimate of the impact of maternal COVID-19 infection by using population data with no selectivity, universal information on maternal COVID-19 infection, and linked sibling data. We then assess change in this impact from 2020 to 2023 and evaluate the protective role of COVID-19 vaccination on infant health. We find a substantial adverse effect of prenatal COVID-19 infection on the probability of preterm birth. The impact was large during the first 2 y of the pandemic but had fully disappeared by 2022. The harmful impact of COVID-19 infection disappeared almost a year earlier in zip codes with high vaccination rates, suggesting that vaccines might have prevented thousands of preterm births. The findings highlight the need to monitor the changing consequences of emerging infectious diseases over time and the importance of mitigation strategies to reduce the burden of infection on vulnerable populations. 

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5. Understanding the implications of under-reporting, vaccine efficiency and social behavior on the post-pandemic spread using physics informed neural networks: A case study of China

   https://doi.org/10.1371/journal.pone.0290368  

   Ghosh, Samiran; Ogueda-Oliva, Alonso; Ghosh, Aditi; Banerjee, Malay; Seshaiyer, Padmanabhan (November 2023, PLOS ONE)

   Lal, Rajnesh (Ed.)

   In late 2019, the emergence of COVID-19 in Wuhan, China, led to the implementation of stringent measures forming the zero-COVID policy aimed at eliminating transmission. Zero-COVID policy basically aimed at completely eliminating the transmission of COVID-19. However, the relaxation of this policy in late 2022 reportedly resulted in a rapid surge of COVID-19 cases. The aim of this work is to investigate the factors contributing to this outbreak using a new SEIR-type epidemic model with time-dependent level of immunity. Our model incorporates a time-dependent level of immunity considering vaccine doses administered and time-post-vaccination dependent vaccine efficacy. We find that vaccine efficacy plays a significant role in determining the outbreak size and maximum number of daily infected. Additionally, our model considers under-reporting in daily cases and deaths, revealing their combined effects on the outbreak magnitude. We also introduce a novel Physics Informed Neural Networks (PINNs) approach which is extremely useful in estimating critical parameters and helps in evaluating the predictive capability of our model. 

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