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1.
PLoS One ; 17(5): e0267853, 2022.
Article in English | MEDLINE | ID: covidwho-1846931

ABSTRACT

BACKGROUND: Prior to direct-acting antivirals (DAAs), HCV incidence rose among men who have sex with men (MSM) living with HIV infection in Germany despite high hepatitis C virus (HCV) treatment rates. We establish a HCV elimination modeling framework to evaluate whether existing treatment rates can achieve the World Health Organization (WHO) incidence target among MSM living with HIV in Germany. METHODS: To evaluate progress towards HCV elimination in Germany, we adapted a previously published HCV transmission model among MSM living with diagnosed HIV. We modelled HCV incidence and prevalence until 2030 (relative to 2015) under existing treatment and DAA scale-up and explored potential impacts of disruptions in treatment and behavioral risk reduction due to the COVID-19 pandemic. RESULTS: Continuing current treatment rates will result in stable HCV incidence among MSM living with HIV in Germany between 2015-2030. The WHO HCV incidence target is achievable under DAA scale-up to 100% treatment combined with treatment of those previously diagnosed and untreated (at a rate of 15%/year) and would result in greater reductions with early treatment (3 vs 6 months) reducing incidence from 4.0/100person-years to 0.8/100person-years by 2030. A 12-month disruption to HCV treatment (20% reduction) and risk behaviors (25%,50%,75% reduction) during the COVID-19 pandemic would result in a 15% relative increase in total HCV incidence in 2030 compared to that expected under the status quo. CONCLUSIONS: HCV elimination among MSM living with HIV in Germany requires further DAA scale-up among those newly diagnosed combined with efforts to treat those previously diagnosed but untreated. Prospective monitoring will establish whether Germany is on track for HCV microelimination.


Subject(s)
COVID-19 , HIV Infections , Hepatitis C, Chronic , Hepatitis C , Sexual and Gender Minorities , Antiviral Agents/therapeutic use , COVID-19/epidemiology , Germany/epidemiology , HIV Infections/drug therapy , HIV Infections/epidemiology , Hepacivirus , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepatitis C, Chronic/drug therapy , Homosexuality, Male , Humans , Incidence , Male , Pandemics , Prospective Studies
3.
Cell ; 184(20): 5189-5200.e7, 2021 09 30.
Article in English | MEDLINE | ID: covidwho-1401295

ABSTRACT

The independent emergence late in 2020 of the B.1.1.7, B.1.351, and P.1 lineages of SARS-CoV-2 prompted renewed concerns about the evolutionary capacity of this virus to overcome public health interventions and rising population immunity. Here, by examining patterns of synonymous and non-synonymous mutations that have accumulated in SARS-CoV-2 genomes since the pandemic began, we find that the emergence of these three "501Y lineages" coincided with a major global shift in the selective forces acting on various SARS-CoV-2 genes. Following their emergence, the adaptive evolution of 501Y lineage viruses has involved repeated selectively favored convergent mutations at 35 genome sites, mutations we refer to as the 501Y meta-signature. The ongoing convergence of viruses in many other lineages on this meta-signature suggests that it includes multiple mutation combinations capable of promoting the persistence of diverse SARS-CoV-2 lineages in the face of mounting host immune recognition.


Subject(s)
COVID-19/epidemiology , Evolution, Molecular , Mutation , Pandemics , SARS-CoV-2/genetics , Amino Acid Sequence/genetics , COVID-19/immunology , COVID-19/transmission , COVID-19/virology , Codon/genetics , Genes, Viral , Genetic Drift , Host Adaptation/genetics , Humans , Immune Evasion , Phylogeny , Public Health
5.
Cell ; 184(19): 4848-4856, 2021 09 16.
Article in English | MEDLINE | ID: covidwho-1363914

ABSTRACT

Since the first reports of a novel severe acute respiratory syndrome (SARS)-like coronavirus in December 2019 in Wuhan, China, there has been intense interest in understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the human population. Recent debate has coalesced around two competing ideas: a "laboratory escape" scenario and zoonotic emergence. Here, we critically review the current scientific evidence that may help clarify the origin of SARS-CoV-2.


Subject(s)
SARS-CoV-2/physiology , Animals , Biological Evolution , COVID-19/virology , Humans , Laboratories , SARS-CoV-2/genetics , Zoonoses/virology
6.
Syst Biol ; 71(2): 426-438, 2022 02 10.
Article in English | MEDLINE | ID: covidwho-1358488

ABSTRACT

Phylogenetic trees from real-world data often include short edges with very few substitutions per site, which can lead to partially resolved trees and poor accuracy. Theory indicates that the number of sites needed to accurately reconstruct a fully resolved tree grows at a rate proportional to the inverse square of the length of the shortest edge. However, when inferred trees are partially resolved due to short edges, "accuracy" should be defined as the rate of discovering false splits (clades on a rooted tree) relative to the actual number found. Thus, accuracy can be high even if short edges are common. Specifically, in a "near-perfect" parameter space in which trees are large, the tree length $\xi$ (the sum of all edge lengths) is small, and rate variation is minimal, the expected false positive rate is less than $\xi/3$; the exact value depends on tree shape and sequence length. This expected false positive rate is far below the false negative rate for small $\xi$ and often well below 5% even when some assumptions are relaxed. We show this result analytically for maximum parsimony and explore its extension to maximum likelihood using theory and simulations. For hypothesis testing, we show that measures of split "support" that rely on bootstrap resampling consistently imply weaker support than that implied by the false positive rates in near-perfect trees. The near-perfect parameter space closely fits several empirical studies of human virus diversification during outbreaks and epidemics, including Ebolavirus, Zika virus, and SARS-CoV-2, reflecting low substitution rates relative to high transmission/sampling rates in these viruses.[Ebolavirus; epidemic; HIV; homoplasy; mumps virus; perfect phylogeny; SARS-CoV-2; virus; West Nile virus; Yule-Harding model; Zika virus.].


Subject(s)
COVID-19 , Zika Virus Infection , Zika Virus , Humans , Models, Genetic , Phylogeny , SARS-CoV-2
7.
Nat Commun ; 12(1): 4886, 2021 08 09.
Article in English | MEDLINE | ID: covidwho-1349666

ABSTRACT

Wide-scale SARS-CoV-2 genome sequencing is critical to tracking viral evolution during the ongoing pandemic. We develop the software tool, Variant Database (VDB), for quickly examining the changing landscape of spike mutations. Using VDB, we detect an emerging lineage of SARS-CoV-2 in the New York region that shares mutations with previously reported variants. The most common sets of spike mutations in this lineage (now designated as B.1.526) are L5F, T95I, D253G, E484K or S477N, D614G, and A701V. This lineage was first sequenced in late November 2020. Phylodynamic inference confirmed the rapid growth of the B.1.526 lineage. In concert with other variants, like B.1.1.7, the rise of B.1.526 appears to have extended the duration of the second wave of COVID-19 cases in NYC in early 2021. Pseudovirus neutralization experiments demonstrated that B.1.526 spike mutations adversely affect the neutralization titer of convalescent and vaccinee plasma, supporting the public health relevance of this lineage.


Subject(s)
COVID-19/virology , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , COVID-19/epidemiology , Genome, Viral , Humans , Models, Molecular , Mutation , New York/epidemiology , Phylogeny , SARS-CoV-2/genetics , Software , Spike Glycoprotein, Coronavirus/genetics
8.
Science ; 372(6540): 412-417, 2021 04 23.
Article in English | MEDLINE | ID: covidwho-1199748

ABSTRACT

Understanding when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged is critical to evaluating our current approach to monitoring novel zoonotic pathogens and understanding the failure of early containment and mitigation efforts for COVID-19. We used a coalescent framework to combine retrospective molecular clock inference with forward epidemiological simulations to determine how long SARS-CoV-2 could have circulated before the time of the most recent common ancestor of all sequenced SARS-CoV-2 genomes. Our results define the period between mid-October and mid-November 2019 as the plausible interval when the first case of SARS-CoV-2 emerged in Hubei province, China. By characterizing the likely dynamics of the virus before it was discovered, we show that more than two-thirds of SARS-CoV-2-like zoonotic events would be self-limited, dying out without igniting a pandemic. Our findings highlight the shortcomings of zoonosis surveillance approaches for detecting highly contagious pathogens with moderate mortality rates.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Genome, Viral , Pandemics , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Animals , COVID-19/transmission , China/epidemiology , Computer Simulation , Evolution, Molecular , Genetic Fitness , Humans , Models, Theoretical , Phylogeny , Retrospective Studies , Viral Zoonoses
9.
bioRxiv ; 2020 Nov 24.
Article in English | MEDLINE | ID: covidwho-955722

ABSTRACT

Understanding when SARS-CoV-2 emerged is critical to evaluating our current approach to monitoring novel zoonotic pathogens and understanding the failure of early containment and mitigation efforts for COVID-19. We employed a coalescent framework to combine retrospective molecular clock inference with forward epidemiological simulations to determine how long SARS-CoV-2 could have circulated prior to the time of the most recent common ancestor. Our results define the period between mid-October and mid-November 2019 as the plausible interval when the first case of SARS-CoV-2 emerged in Hubei province. By characterizing the likely dynamics of the virus before it was discovered, we show that over two-thirds of SARS-CoV-2-like zoonotic events would be self-limited, dying out without igniting a pandemic. Our findings highlight the shortcomings of zoonosis surveillance approaches for detecting highly contagious pathogens with moderate mortality rates.

10.
Science ; 370(6516): 564-570, 2020 10 30.
Article in English | MEDLINE | ID: covidwho-760215

ABSTRACT

Accurate understanding of the global spread of emerging viruses is critical for public health responses and for anticipating and preventing future outbreaks. Here we elucidate when, where, and how the earliest sustained severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission networks became established in Europe and North America. Our results suggest that rapid early interventions successfully prevented early introductions of the virus from taking hold in Germany and the United States. Other, later introductions of the virus from China to both Italy and Washington state, United States, founded the earliest sustained European and North America transmission networks. Our analyses demonstrate the effectiveness of public health measures in preventing onward transmission and show that intensive testing and contact tracing could have prevented SARS-CoV-2 outbreaks from becoming established in these regions.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Phylogeny , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Air Travel , COVID-19 , China/epidemiology , Computer Simulation , Contact Tracing , Coronavirus Infections/prevention & control , Evolution, Molecular , Genome, Viral , Germany/epidemiology , Humans , Italy/epidemiology , Mass Screening , Mutation , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , SARS-CoV-2 , Washington/epidemiology
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