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Article ; Online: Computational identification of antibody-binding epitopes from mimotope datasets.

Li, Rang / Wilderotter, Sabrina / Stoddard, Madison / Van Egeren, Debra / Chakravarty, Arijit / Joseph-McCarthy, Diane

Frontiers in bioinformatics

2024 Volume 4, Page(s) 1295972

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2024-02-23
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-7647
ISSN (online)	2673-7647
DOI	10.3389/fbinf.2024.1295972
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Looking under the lamp-post: quantifying the performance of contact tracing in the United States during the SARS-CoV-2 pandemic.

Bayly, Henry / Stoddard, Madison / Van Egeren, Debra / Murray, Eleanor J / Raifman, Julia / Chakravarty, Arijit / White, Laura F

BMC public health

2024 Volume 24, Issue 1, Page(s) 595

Abstract: Contact tracing forms a crucial part of the public-health toolbox in mitigating and understanding emergent pathogens and nascent disease outbreaks. Contact tracing in the United States was conducted during the pre-Omicron phase of the ongoing COVID-19 ... ...

Abstract	Contact tracing forms a crucial part of the public-health toolbox in mitigating and understanding emergent pathogens and nascent disease outbreaks. Contact tracing in the United States was conducted during the pre-Omicron phase of the ongoing COVID-19 pandemic. This tracing relied on voluntary reporting and responses, often using rapid antigen tests due to lack of accessibility to PCR tests. These limitations, combined with SARS-CoV-2's propensity for asymptomatic transmission, raise the question "how reliable was contact tracing for COVID-19 in the United States"? We answered this question using a Markov model to examine the efficiency with which transmission could be detected based on the design and response rates of contact tracing studies in the United States. Our results suggest that contact tracing protocols in the U.S. are unlikely to have identified more than 1.65% (95% uncertainty interval: 1.62-1.68%) of transmission events with PCR testing and 1.00% (95% uncertainty interval 0.98-1.02%) with rapid antigen testing. When considering a more robust contact tracing scenario, based on compliance rates in East Asia with PCR testing, this increases to 62.7% (95% uncertainty interval: 62.6-62.8%). We did not assume presence of asymptomatic transmission or superspreading, making our estimates upper bounds on the actual percentages traced. These findings highlight the limitations in interpretability for studies of SARS-CoV-2 disease spread based on U.S. contact tracing and underscore the vulnerability of the population to future disease outbreaks, for SARS-CoV-2 and other pathogens.
MeSH term(s)	Humans ; United States/epidemiology ; SARS-CoV-2 ; COVID-19/diagnosis ; COVID-19/epidemiology ; Contact Tracing/methods ; Pandemics ; Disease Outbreaks
Language	English
Publishing date	2024-02-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2041338-5
ISSN	1471-2458 ; 1471-2458
ISSN (online)	1471-2458
ISSN	1471-2458
DOI	10.1186/s12889-024-18012-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

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

Albright, Catherine / Van Egeren, Debra / Thakur, Aditya / Chakravarty, Arijit / White, Laura F / Stoddard, Madison

PloS one

2023 Volume 18, Issue 10, Page(s) e0292099

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19 ; Immune Evasion ; Pandemics/prevention & control ; Serogroup ; Antibodies, Viral
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2023-10-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0292099
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Looking under the lamp-post: quantifying the performance of contact tracing in the United States during the SARS-CoV-2 pandemic.

Bayly, Henry / Stoddard, Madison / Egeren, Debra Van / Murray, Eleanor J / Raifman, Julia / Chakravarty, Arijit / White, Laura F

Research square

2023

Abstract	Contact tracing forms a crucial part of the public-health toolbox in mitigating and understanding emergent pathogens and nascent disease outbreaks. Contact tracing in the United States was conducted during the pre-Omicron phase of the ongoing COVID-19 pandemic. This tracing relied on voluntary reporting and responses, often using rapid antigen tests (with a high false negative rate) due to lack of accessibility to PCR tests. These limitations, combined with SARS-CoV-2's propensity for asymptomatic transmission, raise the question "how reliable was contact tracing for COVID-19 in the United States"? We answered this question using a Markov model to examine the efficiency with which transmission could be detected based on the design and response rates of contact tracing studies in the United States. Our results suggest that contact tracing protocols in the U.S. are unlikely to have identified more than 1.65% (95% uncertainty interval: 1.62%-1.68%) of transmission events with PCR testing and 0.88% (95% uncertainty interval 0.86%-0.89%) with rapid antigen testing. When considering an optimal scenario, based on compliance rates in East Asia with PCR testing, this increases to 62.7% (95% uncertainty interval: 62.6%-62.8%). These findings highlight the limitations in interpretability for studies of SARS-CoV-2 disease spread based on U.S. contact tracing and underscore the vulnerability of the population to future disease outbreaks, for SARS-CoV-2 and other pathogens.
Language	English
Publishing date	2023-06-06
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-2953875/v1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The gray swan: model-based assessment of the risk of sudden failure of hybrid immunity to SARS-CoV-2

Stoddard, Madison / Yuan, Lin / Sarkar, Sharanya / Van Egeren, Debra / White, Laura / Chakravarty, Arijit

medRxiv

Abstract: In the fourth year of the COVID-19 pandemic, public health authorities worldwide have adopted a strategy of learning to live with SARS-CoV-2. This has involved the removal of measures for limiting viral spread, resulting in a large burden of recurrent ... ...

Abstract	In the fourth year of the COVID-19 pandemic, public health authorities worldwide have adopted a strategy of learning to live with SARS-CoV-2. This has involved the removal of measures for limiting viral spread, resulting in a large burden of recurrent SARS-CoV-2 infections. Crucial for managing this burden is the concept of the so-called wall of hybrid immunity, through repeated reinfections and vaccine boosters, to reduce the risk of severe disease and death. Protection against both infection and severe disease is provided by the induction of neutralizing antibodies (nAbs) against SARS-CoV-2. However, pharmacokinetic (PK) waning and rapid viral evolution both degrade nAb binding titers. The recent emergence of variants with strongly immune evasive potential against both the vaccinal and natural immune responses raises the question of whether the wall of population-level immunity can be maintained in the face of large jumps in nAb binding potency. Here we use an agent-based simulation to address this question. Our findings suggest large jumps in viral evolution may cause failure of population immunity resulting in sudden increases in mortality. As a rise in mortality will only become apparent in the weeks following a wave of disease, reactive public health strategies will not be able to provide meaningful risk mitigation. Learning to live with the virus could thus lead to large death tolls with very little warning. Our work points to the importance of proactive management strategies for the ongoing pandemic, and to the need for multifactorial approaches to COVID-19 disease control.
Keywords	covid19
Language	English
Publishing date	2023-03-01
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.02.26.23286471
Database	COVID19

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Article ; Online: Antibody escape, the risk of serotype formation, and rapid immune waning: modeling the implications of SARS-CoV-2 immune evasion

Albright, Catherine / Van Egeren, Debra / Thakur, Aditya / Chakravarty, Arijit / White, Laura / Stoddard, Madison

medRxiv

Abstract	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 variants 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 antigenic drift 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 variants 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.
Keywords	covid19
Language	English
Publishing date	2023-01-26
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.01.25.23285031
Database	COVID19

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Article ; Online: Fitness variation in isogenic populations leads to a novel evolutionary mechanism for crossing fitness valleys.

Van Egeren, Debra / Madsen, Thomas / Michor, Franziska

Communications biology

2018 Volume 1, Page(s) 151

Abstract: Individuals in a population often have different fitnesses even when they have identical genotypes, but the effect of this variation on the evolution of a population through complicated fitness landscapes is unknown. Here, we investigate how populations ... ...

Abstract	Individuals in a population often have different fitnesses even when they have identical genotypes, but the effect of this variation on the evolution of a population through complicated fitness landscapes is unknown. Here, we investigate how populations with non-genetic fitness variation cross fitness valleys, common barriers to adaptation in rugged fitness landscapes in which a population must pass through a deleterious intermediate to arrive at a final advantageous stage. We develop a stochastic computational model describing the dynamics of an asexually reproducing population crossing a fitness valley, in which individuals of the same evolutionary stage can have variable fitnesses. We find that fitness variation that persists over multiple generations increases the rate of valley crossing through a novel evolutionary mechanism different from previously characterized mechanisms such as stochastic tunneling. By reducing the strength of selection against deleterious intermediates, persistent fitness variation allows for faster adaptation through rugged fitness landscapes.
Language	English
Publishing date	2018-09-26
Publishing country	England
Document type	Journal Article
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-018-0160-1
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Article: Vaccines Alone Cannot Slow the Evolution of SARS-CoV-2.

Van Egeren, Debra / Stoddard, Madison / White, Laura F / Hochberg, Natasha S / Rogers, Michael S / Zetter, Bruce / Joseph-McCarthy, Diane / Chakravarty, Arijit

Vaccines

2023 Volume 11, Issue 4

Abstract: The rapid emergence of immune-evading viral variants of SARS-CoV-2 calls into question the practicality of a vaccine-only public-health strategy for managing the ongoing COVID-19 pandemic. It has been suggested that widespread vaccination is necessary to ...

Abstract	The rapid emergence of immune-evading viral variants of SARS-CoV-2 calls into question the practicality of a vaccine-only public-health strategy for managing the ongoing COVID-19 pandemic. It has been suggested that widespread vaccination is necessary to prevent the emergence of future immune-evading mutants. Here, we examined that proposition using stochastic computational models of viral transmission and mutation. Specifically, we looked at the likelihood of emergence of immune escape variants requiring multiple mutations and the impact of vaccination on this process. Our results suggest that the transmission rate of intermediate SARS-CoV-2 mutants will impact the rate at which novel immune-evading variants appear. While vaccination can lower the rate at which new variants appear, other interventions that reduce transmission can also have the same effect. Crucially, relying solely on widespread and repeated vaccination (vaccinating the entire population multiple times a year) is not sufficient to prevent the emergence of novel immune-evading strains, if transmission rates remain high within the population. Thus, vaccines alone are incapable of slowing the pace of evolution of immune evasion, and vaccinal protection against severe and fatal outcomes for COVID-19 patients is therefore not assured.
Language	English
Publishing date	2023-04-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines11040853
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Article ; Online: Fitness variation in isogenic populations leads to a novel evolutionary mechanism for crossing fitness valleys

Debra Van Egeren / Thomas Madsen / Franziska Michor

Communications Biology, Vol 1, Iss 1, Pp 1-

2018 Volume 9

Abstract: Debra Van Egeren et al. present a stochastic computational model of the dynamics ...

Abstract	Debra Van Egeren et al. present a stochastic computational model of the dynamics of an asexually reproducing population, such as somatic or cancer cells, crossing a fitness valley. They find that fitness variation persisting across generations promotes weaker selection against deleterious intermediates, thereby increasing the rate of valley crossing.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2018-09-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Looking under the lamp-post: quantifying the performance of contact tracing in the United States during the SARS-CoV-2 pandemic

Bayly, Henry / Stoddard, Madison / Van Egeren, Debra / Murray, Eleanor J / Raifman, Julia / Chakravarty, Arijit / White, Laura

medRxiv

Abstract	Contact tracing forms a crucial part of the public-health toolbox in mitigating and understanding emergent pathogens and nascent disease outbreaks. Contact tracing in the United States was conducted during the pre-Omicron phase of the ongoing COVID-19 pandemic. This tracing relied on voluntary reporting and responses, often using rapid antigen tests (with a high false negative rate) due to lack of accessibility to PCR tests. These limitations, combined with SARS-CoV-2s propensity for asymptomatic transmission, raise the question how reliable was contact tracing for COVID-19 in the United States? We answered this question using a Markov model to examine the efficiency with which transmission could be detected based on the design and response rates of contact tracing studies in the United States. Our results suggest that contact tracing protocols in the U.S. are unlikely to have identified more than 1.65% (95% uncertainty interval: 1.62%-1.68%) of transmission events with PCR testing and 0.88% (95% uncertainty interval 0.86%-0.89%) with rapid antigen testing. When considering an optimal scenario, based on compliance rates in East Asia with PCR testing, this increases to 62.7% (95% uncertainty interval: 62.6%-62.8%). These findings highlight the limitations in interpretability for studies of SARS-CoV-2 disease spread based on U.S. contact tracing and underscore the vulnerability of the population to future disease outbreaks, for SARS-CoV-2 and other pathogens.
Keywords	covid19
Language	English
Publishing date	2023-03-29
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.03.27.23287812
Database	COVID19

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