Controlling long-term SARS-CoV-2 infections is important for slowing viral evolution

The rapid emergence and expansion of novel SARS-CoV-2 variants is an unpleasant surprise that threatens our ability to achieve herd immunity for COVID-19. These fitter SARS-CoV-2 variants often harbor multiple point mutations, conferring one or more traits that provide an evolutionary advantage, such as increased transmissibility, immune evasion and longer infection duration. In a number of cases, variant emergence has been linked to long-term infections in individuals who were either immunocompromised or treated with convalescent plasma. In this paper, we explore the mechanism by which fitter variants of SARS-CoV-2 arise during long-term infections using a mathematical model of viral evolution and identify means by which this evolution can be slowed. While viral load and infection duration play a strong role in favoring the emergence of such variants, the overall probability of emergence and subsequent transmission from any given infection is low, suggesting that viral variant emergence and establishment is a product of random chance. To the extent that luck plays a role in favoring the emergence of novel viral variants with an evolutionary advantage, targeting these low-probability random events might allow us to tip the balance of fortune away from these advantageous variants and prevent them from being established in the population.https://www.nature.com/articles/s41598-021-02148-8First author draf

Controlling long-term SARS-CoV-2 infections can slow viral evolution and reduce the risk of treatment failure.

The rapid emergence and expansion of novel SARS-CoV-2 variants threatens our ability to achieve herd immunity for COVID-19. These novel SARS-CoV-2 variants often harbor multiple point mutations, conferring one or more evolutionarily advantageous traits, such as increased transmissibility, immune evasion and longer infection duration. In a number of cases, variant emergence has been linked to long-term infections in individuals who were either immunocompromised or treated with convalescent plasma. In this paper, we used a stochastic evolutionary modeling framework to explore the emergence of fitter variants of SARS-CoV-2 during long-term infections. We found that increased viral load and infection duration favor emergence of such variants. While the overall probability of emergence and subsequent transmission from any given infection is low, on a population level these events occur fairly frequently. Targeting these low-probability stochastic events that lead to the establishment of novel advantageous viral variants might allow us to slow the rate at which they emerge in the patient population, and prevent them from spreading deterministically due to natural selection. Our work thus suggests practical ways to achieve control of long-term SARS-CoV-2 infections, which will be critical for slowing the rate of viral evolution.DGE-1762114 - National Science FoundationPublished versio

Individually Optimal Choices Can Be Collectively Disastrous in COVID-19 Disease Control

Background: The word \u27pandemic\u27 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

Computational identification of antibody-binding epitopes from mimotope datasets

Introduction: A fundamental challenge in computational vaccinology is that most B-cell epitopes are conformational and therefore hard to predict from sequence alone. Another significant challenge is that a great deal of the amino acid sequence of a viral surface protein might not in fact be antigenic. Thus, identifying the regions of a protein that are most promising for vaccine design based on the degree of surface exposure may not lead to a clinically relevant immune response.Methods: Linear peptides selected by phage display experiments that have high affinity to the monoclonal antibody of interest (“mimotopes”) usually have similar physicochemical properties to the antigen epitope corresponding to that antibody. The sequences of these linear peptides can be used to find possible epitopes on the surface of the antigen structure or a homology model of the antigen in the absence of an antigen-antibody complex structure.Results and Discussion: Herein we describe two novel methods for mapping mimotopes to epitopes. The first is a novel algorithm named MimoTree that allows for gaps in the mimotopes and epitopes on the antigen. More specifically, a mimotope may have a gap that does not match to the epitope to allow it to adopt a conformation relevant for binding to an antibody, and residues may similarly be discontinuous in conformational epitopes. MimoTree is a fully automated epitope detection algorithm suitable for the identification of conformational as well as linear epitopes. The second is an ensemble approach, which combines the prediction results from MimoTree and two existing methods

Rapid relaxation of pandemic restrictions after vaccine rollout favors growth of SARS-CoV-2 variants: a model-based analysis

The development and deployment of several SARS-CoV-2 vaccines in a little over a year is an unprecedented achievement of modern medicine. The high levels of efficacy against transmission for some of these vaccines makes it feasible to use them to suppress SARS-CoV-2 altogether in regions with high vaccine acceptance. However, viral variants with reduced susceptibility to vaccinal and natural immunity threaten the utility of vaccines, particularly in scenarios where a return to pre-pandemic conditions occurs before the suppression of SARS-CoV-2 transmission. In this work we model the situation in the United States in May-June 2021, to demonstrate how pre-existing variants of SARS-CoV-2 may cause a rebound wave of COVID-19 in a matter of months under a certain set of conditions. A high burden of morbidity (and likely mortality) remains possible, even if the vaccines are partially effective against new variants and widely accepted. Our modeling suggests that variants that are already present within the population may be capable of quickly defeating the vaccines as a public health intervention, a serious potential limitation for strategies that emphasize rapid reopening before achieving control of SARS-CoV-2.Published versio

Endemicity is not a victory: the unmitigated downside risks of widespread SARS-CoV-2 transmission

The strategy of relying solely on current SARS-CoV-2 vaccines to halt SARS-CoV-2 transmission has proven infeasible. In response, many public-health authorities have advocated for using vaccines to limit mortality while permitting unchecked SARS-CoV-2 spread (“learning to live with the disease”). The feasibility of this strategy critically depends on the infection fatality rate (IFR) of SARS-CoV-2. An expectation exists that the IFR will decrease due to selection against virulence. In this work, we perform a viral fitness estimation to examine the basis for this expectation. Our findings suggest large increases in virulence for SARS-CoV-2 would result in minimal loss of transmissibility, implying that the IFR may vary freely under neutral evolutionary drift. We use an SEIRS model framework to examine the effect of hypothetical changes in the IFR on steady-state death tolls under COVID-19 endemicity. Our modeling suggests that endemic SARS-CoV-2 implies vast transmission resulting in yearly US COVID-19 death tolls numbering in the hundreds of thousands under many plausible scenarios, with even modest increases in the IFR leading to unsustainable mortality burdens. Our findings highlight the importance of enacting a concerted strategy and continued development of biomedical interventions to suppress SARS-CoV-2 transmission and slow its evolution.https://www.mdpi.com/2673-8112/2/12/121Published versio

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.National Science Foundationhttps://www.frontiersin.org/articles/10.3389/fpubh.2022.941773/fullPublished versio

SCIPP: An Expanded Community of Practice - Community Publishing

SCIPP redefines and expands the existing notions about what makes for a vibrant and robust community of practice by partnering CSUSB students and professors with K-12 students, parents, and educators, along with committed community partners. SCIPP encourages curiosity in ways that leads to critical thinking, exploration, risk taking , confidence building, open-mindedness, and other personal traits that equip them with the softskills to be active, critical, and creative contributors to our communities. SCIPP pedagogy embraces our students\u27 collective wisdom and focuses on relational building where multi-directional communication is promoted and students are viewed as equal stakeholders in their own educations. SCIPP puts collaboration into action which in turn fosters community-based lifelong learning. SCIPP provides the open intellectual space for future university students (our K-12 students) to engage with existing university students in meaningful ways so as to sustain interconnected partnerships facilitating community engagement. It supports parents as experts in the education of their children and acknowledges parents as the first conduits to spark their children’s imagination while they actively participate in education enriching activities and programs. Everyone involved is committed to creating a secure and open atmosphere for dreaming, sharing, and learning. Together we explore the aspects of community publishing through collaborative learning in formal and informal settings relating to digital and printed medias