Heterogeneity in Vaccinal Immunity to SARS-CoV-2 Can Be Addressed by a Personalized Booster Strategy.

SARS-CoV-2 vaccinations were initially shown to substantially reduce risk of severe disease and death. However, pharmacokinetic (PK) waning and rapid viral evolution degrade neutralizing antibody (nAb) binding titers, causing loss of vaccinal protection. Additionally, there is inter-individual heterogeneity in the strength and durability of the vaccinal nAb response. Here, we propose a personalized booster strategy as a potential solution to this problem. Our model-based approach incorporates inter-individual heterogeneity in nAb response to primary SARS-CoV-2 vaccination into a pharmacokinetic/pharmacodynamic (PK/PD) model to project population-level heterogeneity in vaccinal protection. We further examine the impact of evolutionary immune evasion on vaccinal protection over time based on variant fold reduction in nAb potency. Our findings suggest viral evolution will decrease the effectiveness of vaccinal protection against severe disease, especially for individuals with a less durable immune response. More frequent boosting may restore vaccinal protection for individuals with a weaker immune response. Our analysis shows that the ECLIA RBD binding assay strongly predicts neutralization of sequence-matched pseudoviruses. This may be a useful tool for rapidly assessing individual immune protection. Our work suggests vaccinal protection against severe disease is not assured and identifies a potential path forward for reducing risk to immunologically vulnerable individuals.

No magic bullet: Limiting in-school transmission in the face of variable SARS-CoV-2 viral loads.

In the face of a long-running pandemic, understanding the drivers of ongoing SARS-CoV-2 transmission is crucial for the rational management of COVID-19 disease burden. Keeping schools open has emerged as a vital societal imperative during the pandemic, but in-school transmission of SARS-CoV-2 can contribute to further prolonging the pandemic. In this context, the role of schools in driving SARS-CoV-2 transmission acquires critical importance. Here we model in-school transmission from first principles to investigate the effectiveness of layered mitigation strategies on limiting in-school spread. We examined the effect of masks and air quality (ventilation, filtration and ionizers) on steady-state viral load in classrooms, as well as on the number of particles inhaled by an uninfected person. The effectiveness of these measures in limiting viral transmission was assessed for variants with different levels of mean viral load (ancestral, Delta, Omicron). Our results suggest that a layered mitigation strategy can be used effectively to limit in-school transmission, with certain limitations. First, poorly designed strategies (insufficient ventilation, no masks, staying open under high levels of community transmission) will permit in-school spread even if some level of mitigation is present. Second, for viral variants that are sufficiently contagious, it may be difficult to construct any set of interventions capable of blocking transmission once an infected individual is present, underscoring the importance of other measures. Our findings provide practical recommendations; in particular, the use of a layered mitigation strategy that is designed to limit transmission, with other measures such as frequent surveillance testing and smaller class sizes (such as by offering remote schooling options to those who prefer it) as needed.

Beyond the new normal: Assessing the feasibility of vaccine-based suppression of SARS-CoV-2.

As the COVID-19 pandemic drags into its second year, there is hope on the horizon, in the form of SARS-CoV-2 vaccines which promise disease suppression and a return to pre-pandemic normalcy. In this study we critically examine the basis for that hope, using an epidemiological modeling framework to establish the link between vaccine characteristics and effectiveness in bringing an end to this unprecedented public health crisis. Our findings suggest that a return to pre-pandemic social and economic conditions without fully suppressing SARS-CoV-2 will lead to extensive viral spread, resulting in a high disease burden even in the presence of vaccines that reduce risk of infection and mortality. Our modeling points to the feasibility of complete SARS-CoV-2 suppression with high population-level compliance and vaccines that are highly effective at reducing SARS-CoV-2 infection. Notably, vaccine-mediated reduction of transmission is critical for viral suppression, and in order for partially-effective vaccines to play a positive role in SARS-CoV-2 suppression, complementary biomedical interventions and public health measures must be deployed simultaneously.

Individually optimal choices can be collectively disastrous in COVID-19 disease control.

BACKGROUND: The word 'pandemic' conjures dystopian images of bodies stacked in the streets and societies on the brink of collapse. Despite this frightening picture, denialism and noncompliance with public health measures are common in the historical record, for example during the 1918 Influenza pandemic or the 2015 Ebola epidemic. The unique characteristics of SARS-CoV-2-its high basic reproduction number (R0), time-limited natural immunity and considerable potential for asymptomatic spread-exacerbate the public health repercussions of noncompliance with interventions (such as vaccines and masks) to limit disease transmission. Our work explores the rationality and impact of noncompliance with measures aimed at limiting the spread of SARS-CoV-2. METHODS: In this work, we used game theory to explore when noncompliance confers a perceived benefit to individuals. We then used epidemiological modeling to predict the impact of noncompliance on control of SARS-CoV-2, demonstrating that the presence of a noncompliant subpopulation prevents suppression of disease spread. RESULTS: Our modeling demonstrates that noncompliance is a Nash equilibrium under a broad set of conditions and that the existence of a noncompliant population can result in extensive endemic disease in the long-term after a return to pre-pandemic social and economic activity. Endemic disease poses a threat for both compliant and noncompliant individuals; all community members are protected if complete suppression is achieved, which is only possible with a high degree of compliance. For interventions that are highly effective at preventing disease spread, however, the consequences of noncompliance are borne disproportionately by noncompliant individuals. CONCLUSIONS: In sum, our work demonstrates the limits of free-market approaches to compliance with disease control measures during a pandemic. The act of noncompliance with disease intervention measures creates a negative externality, rendering suppression of SARS-CoV-2 spread ineffective. Our work underscores the importance of developing effective strategies for prophylaxis through public health measures aimed at complete suppression and the need to focus on compliance at a population level.

In the long shadow of our best intentions: Model-based assessment of the consequences of school reopening during the COVID-19 pandemic.

As the world grapples with the ongoing COVID-19 pandemic, a particularly thorny set of questions surrounds the reopening of primary and secondary (K-12) schools. The benefits of in-person learning are numerous, in terms of education quality, mental health, emotional well-being, equity and access to food and shelter. Early reports suggested that children might have reduced susceptibility to COVID-19, and children have been shown to experience fewer complications than older adults. Over the past few months, our understanding of COVID-19 has been further shaped by emerging data, and it is now understood that children are as susceptible to infection as adults and have a similar viral load during infection, even if asymptomatic. Based on this updated understanding of the disease, we have used epidemiological modeling to explore the feasibility and consequences of school reopening in the face of differing rates of COVID-19 prevalence and transmission. We focused our analysis on the United States, but the results are applicable to other countries as well. We demonstrate the potential for a large discrepancy between detected cases and true infections in schools due to the combination of high asymptomatic rates in children coupled with delays in seeking testing and receiving results from diagnostic tests. Our findings indicate that, regardless of the initial prevalence of the disease, and in the absence of robust surveillance testing and contact-tracing, most schools in the United States can expect to remain open for 20-60 days without the emergence of sizeable disease clusters. At this point, even if schools choose to close after outbreaks occur, COVID-19 cases will be seeded from these school clusters and amplified into the community. Thus, our findings suggest that the debate between the risks to student safety and benefits of in-person learning frames a false dual choice. Reopening schools without surveillance testing and contact tracing measures in place will lead to spread within the schools and within the communities that eventually forces a return to remote learning and leaves a trail of infection in its wake.