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1.
Gigascience ; 112022 05 28.
Article in English | MEDLINE | ID: covidwho-1873910

ABSTRACT

BACKGROUND: The Syrian hamster (Mesocricetus auratus) has been suggested as a useful mammalian model for a variety of diseases and infections, including infection with respiratory viruses such as SARS-CoV-2. The MesAur1.0 genome assembly was generated in 2013 using whole-genome shotgun sequencing with short-read sequence data. Current more advanced sequencing technologies and assembly methods now permit the generation of near-complete genome assemblies with higher quality and greater continuity. FINDINGS: Here, we report an improved assembly of the M. auratus genome (BCM_Maur_2.0) using Oxford Nanopore Technologies long-read sequencing to produce a chromosome-scale assembly. The total length of the new assembly is 2.46 Gb, similar to the 2.50-Gb length of a previous assembly of this genome, MesAur1.0. BCM_Maur_2.0 exhibits significantly improved continuity, with a scaffold N50 that is 6.7 times greater than MesAur1.0. Furthermore, 21,616 protein-coding genes and 10,459 noncoding genes are annotated in BCM_Maur_2.0 compared to 20,495 protein-coding genes and 4,168 noncoding genes in MesAur1.0. This new assembly also improves the unresolved regions as measured by nucleotide ambiguities, where ∼17.11% of bases in MesAur1.0 were unresolved compared to BCM_Maur_2.0, in which the number of unresolved bases is reduced to 3.00%. CONCLUSIONS: Access to a more complete reference genome with improved accuracy and continuity will facilitate more detailed, comprehensive, and meaningful research results for a wide variety of future studies using Syrian hamsters as models.


Subject(s)
Chromosomes, Mammalian , Mesocricetus , Animals , Chromosomes, Mammalian/genetics , Genome , High-Throughput Nucleotide Sequencing/methods , Mesocricetus/genetics , Whole Genome Sequencing
2.
Sci Transl Med ; : eabm4908, 2022 May 17.
Article in English | MEDLINE | ID: covidwho-1846321

ABSTRACT

The SARS-CoV-2 B.1.621 (Mu) variant emerged in January 2021 and was categorized as a variant of interest by the World Health Organization in August 2021. This designation prompted us to study the sensitivity of this variant to antibody neutralization. In a live virus neutralization assay with serum samples from individuals vaccinated with the Pfizer/BioNTech or Moderna mRNA vaccines, we measured neutralization antibody titers against B.1.621, an early isolate (spike 614D), and a variant of concern (B.1.351, beta variant). We observed reduced neutralizing antibody titers against the B.1.621 variant (3.4 to 7-fold reduction, depending on the serum sample and time after the second vaccination) compared to the early isolate and a similar reduction when compared to B.1.351. Likewise, convalescent serum from hamsters previously infected with an early isolate neutralized B.1.621 to a lower degree. Despite this antibody titer reduction, hamsters could not be efficiently re-challenged with the B.1.621 variant, suggesting the immune response to the first infection is adequate to provide protection against a subsequent infection with the B.1.621 variant.

3.
J Biomol Tech ; 32(3): 228-275, 2021 09.
Article in English | MEDLINE | ID: covidwho-1687373

ABSTRACT

As the second year of the COVID-19 pandemic begins, it remains clear that a massive increase in the ability to test for SARS-CoV-2 infections in a myriad of settings is critical to controlling the pandemic and to preparing for future outbreaks. The current gold standard for molecular diagnostics is the polymerase chain reaction (PCR), but the extraordinary and unmet demand for testing in a variety of environments means that both complementary and supplementary testing solutions are still needed. This review highlights the role that loop-mediated isothermal amplification (LAMP) has had in filling this global testing need, providing a faster and easier means of testing, and what it can do for future applications, pathogens, and the preparation for future outbreaks. This review describes the current state of the art for research of LAMP-based SARS-CoV-2 testing, as well as its implications for other pathogens and testing. The authors represent the global LAMP (gLAMP) Consortium, an international research collective, which has regularly met to share their experiences on LAMP deployment and best practices; sections are devoted to all aspects of LAMP testing, including preanalytic sample processing, target amplification, and amplicon detection, then the hardware and software required for deployment are discussed, and finally, a summary of the current regulatory landscape is provided. Included as well are a series of first-person accounts of LAMP method development and deployment. The final discussion section provides the reader with a distillation of the most validated testing methods and their paths to implementation. This review also aims to provide practical information and insight for a range of audiences: for a research audience, to help accelerate research through sharing of best practices; for an implementation audience, to help get testing up and running quickly; and for a public health, clinical, and policy audience, to help convey the breadth of the effect that LAMP methods have to offer.


Subject(s)
COVID-19 , Nucleic Acid Amplification Techniques , SARS-CoV-2 , COVID-19/diagnosis , COVID-19 Nucleic Acid Testing , Humans , Molecular Diagnostic Techniques , Pandemics , RNA, Viral , SARS-CoV-2/isolation & purification
4.
J Biomol Tech ; 32(3): 137-147, 2021 09.
Article in English | MEDLINE | ID: covidwho-1626499

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) control in the United States remains hampered, in part, by testing limitations. We evaluated a simple, outdoor, mobile, colorimetric reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay workflow where self-collected saliva is tested for SARS-CoV-2 RNA. From July 16, 2020, to November 19, 2020, surveillance samples (n = 4704) were collected from volunteers and tested for SARS-CoV-2 at 5 sites. Twenty-one samples tested positive for SARS-CoV-2 by RT-LAMP; 12 were confirmed positive by subsequent quantitative reverse-transcription polymerase chain reaction (qRT-PCR) testing, whereas 8 tested negative for SARS-CoV-2 RNA, and 1 could not be confirmed because the donor did not consent to further molecular testing. We estimated the false-negative rate of the RT-LAMP assay only from July 16, 2020, to September 17, 2020 by pooling residual heat-inactivated saliva that was unambiguously negative by RT-LAMP into groups of 6 or fewer and testing for SARS-CoV-2 RNA by qRT-PCR. We observed a 98.8% concordance between the RT-LAMP and qRT-PCR assays, with only 5 of 421 RT-LAMP-negative pools (2493 total samples) testing positive in the more-sensitive qRT-PCR assay. Overall, we demonstrate a rapid testing method that can be implemented outside the traditional laboratory setting by individuals with basic molecular biology skills and that can effectively identify asymptomatic individuals who would not typically meet the criteria for symptom-based testing modalities.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19 Testing , Humans , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , RNA, Viral/genetics , Sensitivity and Specificity
5.
Open Forum Infect Dis ; 8(11): ofab518, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1528171

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has had high incidence rates at institutions of higher education (IHE) in the United States, but the transmission dynamics in these settings are poorly understood. It remains unclear to what extent IHE-associated outbreaks have contributed to transmission in nearby communities. METHODS: We implemented high-density prospective genomic surveillance to investigate these dynamics at the University of Michigan and the surrounding community during the Fall 2020 semester (August 16-November 24). We sequenced complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from 1659 individuals, including 468 students, representing 20% of cases in students and 25% of total cases in Washtenaw County over the study interval. RESULTS: Phylogenetic analysis identified >200 introductions into the student population, most of which were not related to other student cases. There were 2 prolonged student transmission clusters, of 115 and 73 individuals, that spanned multiple on-campus residences. Remarkably, <5% of nonstudent genomes were descended from student clusters, and viral descendants of student cases were rare during a subsequent wave of infections in the community. CONCLUSIONS: The largest outbreaks among students at the University of Michigan did not significantly contribute to the rise in community cases in Fall 2020. These results provide valuable insights into SARS-CoV-2 transmission dynamics at the regional level.

6.
Non-conventional in English | [Unspecified Source], Grey literature | ID: grc-750514

ABSTRACT

Evidence-based public health approaches that minimize the introduction and spread of new SARS-CoV-2 transmission clusters are urgently needed in the United States and other countries struggling with expanding epidemics. Here we analyze 247 full-genome SARS-CoV-2 sequences from two nearby communities in Wisconsin, USA, and find surprisingly distinct patterns of viral spread. Dane County had the 12th known introduction of SARS-CoV-2 in the United States, but this did not lead to descendant community spread. Instead, the Dane County outbreak was seeded by multiple later introductions, followed by limited community spread. In contrast, relatively few introductions in Milwaukee County led to extensive community spread. We present evidence for reduced viral spread in both counties, and limited viral transmission between counties, following the statewide Safer-at-Home public health order, which went into effect 25 March 2020. Our results suggest that early containment efforts suppressed the spread of SARS-CoV-2 within Wisconsin.

7.
AIDS Res Hum Retroviruses ; 2021 Nov 25.
Article in English | MEDLINE | ID: covidwho-1486408

ABSTRACT

The HIV Research for Prevention (HIVR4P) conference catalyzes knowledge sharing on biomedical HIV prevention interventions such as HIV vaccines, antibody infusions, pre-exposure prophylaxis, and microbicides in totality-from the molecular details and delivery formulations to the behavioral, social, and structural underpinnings. HIVR4P // Virtual was held over the course of 2 weeks on January 27-28 and February 3-4, 2021 as the COVID-19 pandemic continued to inflict unprecedented harm globally. The HIVR4P community came together with 1,802 researchers, care providers, policymakers, implementers, and advocates from 92 countries whose expertise spanned the breadth of the HIV prevention pipeline from preclinical to implementation. The program included 113 oral and 266 poster presentations. This article presents a brief summary of the conference highlights. Complete abstracts, webcasts, and daily rapporteur summaries may be found on the conference website (https://www.hivr4p.org/).

8.
Emerg Infect Dis ; 27(11): 2776-2785, 2021 11.
Article in English | MEDLINE | ID: covidwho-1444021

ABSTRACT

University settings have demonstrated potential for coronavirus disease (COVID-19) outbreaks; they combine congregate living, substantial social activity, and a young population predisposed to mild illness. Using genomic and epidemiologic data, we describe a COVID-19 outbreak at the University of Wisconsin-Madison, Madison, Wisconsin, USA. During August-October 2020, a total of 3,485 students, including 856/6,162 students living in dormitories, tested positive. Case counts began rising during move-in week, August 25-31, 2020, then rose rapidly during September 1-11, 2020. The university initiated multiple prevention efforts, including quarantining 2 dormitories; a subsequent decline in cases was observed. Genomic surveillance of cases from Dane County, in which the university is located, did not find evidence of transmission from a large cluster of cases in the 2 quarantined dorms during the outbreak. Coordinated implementation of prevention measures can reduce COVID-19 spread in university settings and may limit spillover to the surrounding community.


Subject(s)
COVID-19 , Universities , Disease Outbreaks , Humans , SARS-CoV-2 , Wisconsin/epidemiology
9.
Clin Infect Dis ; 73(6): e1329-e1336, 2021 09 15.
Article in English | MEDLINE | ID: covidwho-1411883

ABSTRACT

BACKGROUND: Healthcare personnel (HCP) are at increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We posit that current infection control guidelines generally protect HCP from SARS-CoV-2 infection in a healthcare setting. METHODS: In this retrospective case series, we used viral genomics to investigate the likely source of SARS-CoV-2 infection in HCP at a major academic medical institution in the Upper Midwest of the United States between 25 March and 27 December 2020. We obtained limited epidemiological data through informal interviews and review of the electronic health record and combined this information with healthcare-associated viral sequences and viral sequences collected in the broader community to infer the most likely source of infection in HCP. RESULTS: We investigated SARS-CoV-2 infection clusters involving 95 HCP and 137 possible patient contact sequences. The majority of HCP infections could not be linked to a patient or coworker (55 of 95 [57.9%]) and were genetically similar to viruses circulating concurrently in the community. We found that 10.5% of HCP infections (10 of 95) could be traced to a coworker. Strikingly, only 4.2% (4 of 95) could be traced to a patient source. CONCLUSIONS: Infections among HCP add further strain to the healthcare system and put patients, HCP, and communities at risk. We found no evidence for healthcare-associated transmission in the majority of HCP infections evaluated. Although we cannot rule out the possibility of cryptic healthcare-associated transmission, it appears that HCP most commonly become infected with SARS-CoV-2 via community exposure. This emphasizes the ongoing importance of mask wearing, physical distancing, robust testing programs, and rapid distribution of vaccines.


Subject(s)
COVID-19 , SARS-CoV-2 , Delivery of Health Care , Health Personnel , Humans , Retrospective Studies , United States/epidemiology
10.
PLoS Pathog ; 17(8): e1009849, 2021 08.
Article in English | MEDLINE | ID: covidwho-1369568

ABSTRACT

The emergence of divergent SARS-CoV-2 lineages has raised concern that novel variants eliciting immune escape or the ability to displace circulating lineages could emerge within individual hosts. Though growing evidence suggests that novel variants arise during prolonged infections, most infections are acute. Understanding how efficiently variants emerge and transmit among acutely-infected hosts is therefore critical for predicting the pace of long-term SARS-CoV-2 evolution. To characterize how within-host diversity is generated and propagated, we combine extensive laboratory and bioinformatic controls with metrics of within- and between-host diversity to 133 SARS-CoV-2 genomes from acutely-infected individuals. We find that within-host diversity is low and transmission bottlenecks are narrow, with very few viruses founding most infections. Within-host variants are rarely transmitted, even among individuals within the same household, and are rarely detected along phylogenetically linked infections in the broader community. These findings suggest that most variation generated within-host is lost during transmission.


Subject(s)
COVID-19/virology , Genetic Variation , SARS-CoV-2/genetics , Acute Disease , COVID-19/transmission , Evolution, Molecular , Genome, Viral , Humans , Phylogeny , SARS-CoV-2/pathogenicity , Time Factors
11.
Immunohorizons ; 5(6): 466-476, 2021 06 17.
Article in English | MEDLINE | ID: covidwho-1359325

ABSTRACT

Lasting immunity will be critical for overcoming COVID-19. However, the factors associated with the development of high titers of anti-SARS-CoV-2 Abs and how long those Abs persist remain incompletely defined. In particular, an understanding of the relationship between COVID-19 symptoms and anti-SARS-CoV-2 Abs is limited. To address these unknowns, we quantified serum anti-SARS- CoV-2 Abs in clinically diverse COVID-19 convalescent human subjects 5 wk (n = 113) and 3 mo (n = 79) after symptom resolution with three methods: a novel multiplex assay to quantify IgG against four SARS-CoV-2 Ags, a new SARS-CoV-2 receptor binding domain-angiotensin converting enzyme 2 inhibition assay, and a SARS-CoV-2 neutralizing assay. We then identified clinical and demographic factors, including never-before-assessed COVID-19 symptoms, that consistently correlate with high anti-SARS-CoV-2 Ab levels. We detected anti-SARS-CoV-2 Abs in 98% of COVID-19 convalescent subjects 5 wk after symptom resolution, and Ab levels did not decline at 3 mo. Greater disease severity, older age, male sex, higher body mass index, and higher Charlson Comorbidity Index score correlated with increased anti-SARS-CoV-2 Ab levels. Moreover, we report for the first time (to our knowledge) that COVID-19 symptoms, most consistently fever, body aches, and low appetite, correlate with higher anti-SARS-CoV-2 Ab levels. Our results provide robust and new insights into the development and persistence of anti-SARS-CoV-2 Abs.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Immunoglobulin G/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/epidemiology , COVID-19/virology , Cohort Studies , Female , Hospitalization/statistics & numerical data , Humans , Immunoglobulin G/blood , Linear Models , Male , Middle Aged , Multivariate Analysis , Pandemics , SARS-CoV-2/physiology , Severity of Illness Index , Time Factors
12.
Clin Infect Dis ; 73(Suppl 1): S45-S53, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1315688

ABSTRACT

BACKGROUND: High-frequency, rapid-turnaround severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, 2 SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester, despite mandatory directly observed daily antigen testing. METHODS: During the fall 2020 semester, athletes and staff in both programs were tested daily using Quidel's Sofia SARS Antigen Fluorescent Immunoassay, with positive antigen results requiring confirmatory testing with real-time reverse-transcription polymerase chain reaction. We used genomic sequencing to investigate transmission dynamics in these 2 outbreaks. RESULTS: In the first outbreak, 32 confirmed cases occurred within a university athletics program after the index patient attended a meeting while infectious, despite a negative antigen test on the day of the meeting. Among isolates sequenced from that outbreak, 24 (92%) of 26 were closely related, suggesting sustained transmission following an initial introduction event. In the second outbreak, 12 confirmed cases occurred among athletes from 2 university programs that faced each other in an athletic competition, despite receipt of negative antigen test results on the day of the competition. Sequences from both teams were closely related and distinct from viruses circulating in the community for team 1, suggesting transmission during intercollegiate competition in the community for team 2. CONCLUSIONS: These findings suggest that antigen testing alone, even when mandated and directly observed, may not be sufficient as an intervention to prevent SARS-CoV-2 outbreaks in congregate settings, and they highlight the importance of vaccination to prevent SARS-CoV-2 outbreak in congregate settings.


Subject(s)
COVID-19 , Sports , Humans , Immunologic Tests , SARS-CoV-2 , Universities
13.
Nat Commun ; 12(1): 4317, 2021 07 14.
Article in English | MEDLINE | ID: covidwho-1310803

ABSTRACT

The COVID-19 pandemic exposed difficulties in scaling current quantitative PCR (qPCR)-based diagnostic methodologies for large-scale infectious disease testing. Bottlenecks include lengthy multi-step processes for nucleic acid extraction followed by qPCR readouts, which require costly instrumentation and infrastructure, as well as reagent and plastic consumable shortages stemming from supply chain constraints. Here we report an Oil Immersed Lossless Total Analysis System (OIL-TAS), which integrates RNA extraction and detection onto a single device that is simple, rapid, cost effective, and requires minimal supplies and infrastructure to perform. We validated the performance of OIL-TAS using contrived SARS-CoV-2 viral particle samples and clinical nasopharyngeal swab samples. OIL-TAS showed a 93% positive predictive agreement (n = 57) and 100% negative predictive agreement (n = 10) with clinical SARS-CoV-2 qPCR assays in testing clinical samples, highlighting its potential to be a faster, cheaper, and easier-to-deploy alternative for infectious disease testing.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , COVID-19 Nucleic Acid Testing/economics , COVID-19 Nucleic Acid Testing/instrumentation , Equipment Design , Humans , Molecular Diagnostic Techniques , Nasopharynx/virology , Nucleic Acid Amplification Techniques , RNA, Viral/genetics , RNA, Viral/isolation & purification , Reproducibility of Results , SARS-CoV-2/genetics , Sensitivity and Specificity , Time Factors , Virion/genetics , Virion/isolation & purification
14.
PLoS Biol ; 19(6): e3001265, 2021 06.
Article in English | MEDLINE | ID: covidwho-1278162

ABSTRACT

The search for potential antibody-based diagnostics, vaccines, and therapeutics for pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused almost exclusively on the spike (S) and nucleocapsid (N) proteins. Coronavirus membrane (M), ORF3a, and ORF8 proteins are humoral immunogens in other coronaviruses (CoVs) but remain largely uninvestigated for SARS-CoV-2. Here, we use ultradense peptide microarray mapping to show that SARS-CoV-2 infection induces robust antibody responses to epitopes throughout the SARS-CoV-2 proteome, particularly in M, in which 1 epitope achieved excellent diagnostic accuracy. We map 79 B cell epitopes throughout the SARS-CoV-2 proteome and demonstrate that antibodies that develop in response to SARS-CoV-2 infection bind homologous peptide sequences in the 6 other known human CoVs. We also confirm reactivity against 4 of our top-ranking epitopes by enzyme-linked immunosorbent assay (ELISA). Illness severity correlated with increased reactivity to 9 SARS-CoV-2 epitopes in S, M, N, and ORF3a in our population. Our results demonstrate previously unknown, highly reactive B cell epitopes throughout the full proteome of SARS-CoV-2 and other CoV proteins.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Viral Proteins/immunology , Antibodies, Viral/blood , COVID-19/pathology , Coronavirus/immunology , Cross Reactions , Epitopes, B-Lymphocyte , Humans , Immunodominant Epitopes , Immunoglobulin G/blood , Immunoglobulin G/immunology , Proteome/immunology , Severity of Illness Index
15.
Proc Natl Acad Sci U S A ; 118(27)2021 07 06.
Article in English | MEDLINE | ID: covidwho-1276013

ABSTRACT

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a key role in viral infectivity. It is also the major antigen stimulating the host's protective immune response, specifically, the production of neutralizing antibodies. Recently, a new variant of SARS-CoV-2 possessing multiple mutations in the S protein, designated P.1, emerged in Brazil. Here, we characterized a P.1 variant isolated in Japan by using Syrian hamsters, a well-established small animal model for the study of SARS-CoV-2 disease (COVID-19). In hamsters, the variant showed replicative abilities and pathogenicity similar to those of early and contemporary strains (i.e., SARS-CoV-2 bearing aspartic acid [D] or glycine [G] at position 614 of the S protein). Sera and/or plasma from convalescent patients and BNT162b2 messenger RNA vaccinees showed comparable neutralization titers across the P.1 variant, S-614D, and S-614G strains. In contrast, the S-614D and S-614G strains were less well recognized than the P.1 variant by serum from a P.1-infected patient. Prior infection with S-614D or S-614G strains efficiently prevented the replication of the P.1 variant in the lower respiratory tract of hamsters upon reinfection. In addition, passive transfer of neutralizing antibodies to hamsters infected with the P.1 variant or the S-614G strain led to reduced virus replication in the lower respiratory tract. However, the effect was less pronounced against the P.1 variant than the S-614G strain. These findings suggest that the P.1 variant may be somewhat antigenically different from the early and contemporary strains of SARS-CoV-2.


Subject(s)
COVID-19/virology , SARS-CoV-2/physiology , SARS-CoV-2/pathogenicity , Virus Replication , Animals , Antibodies, Neutralizing , COVID-19/diagnostic imaging , COVID-19/pathology , Cricetinae , Humans , Immunogenicity, Vaccine , Lung/pathology , Mesocricetus , Mice , Spike Glycoprotein, Coronavirus/genetics , X-Ray Microtomography
16.
Clin Infect Dis ; 73(Suppl 1): S45-S53, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1225623

ABSTRACT

BACKGROUND: High-frequency, rapid-turnaround severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, 2 SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester, despite mandatory directly observed daily antigen testing. METHODS: During the fall 2020 semester, athletes and staff in both programs were tested daily using Quidel's Sofia SARS Antigen Fluorescent Immunoassay, with positive antigen results requiring confirmatory testing with real-time reverse-transcription polymerase chain reaction. We used genomic sequencing to investigate transmission dynamics in these 2 outbreaks. RESULTS: In the first outbreak, 32 confirmed cases occurred within a university athletics program after the index patient attended a meeting while infectious, despite a negative antigen test on the day of the meeting. Among isolates sequenced from that outbreak, 24 (92%) of 26 were closely related, suggesting sustained transmission following an initial introduction event. In the second outbreak, 12 confirmed cases occurred among athletes from 2 university programs that faced each other in an athletic competition, despite receipt of negative antigen test results on the day of the competition. Sequences from both teams were closely related and distinct from viruses circulating in the community for team 1, suggesting transmission during intercollegiate competition in the community for team 2. CONCLUSIONS: These findings suggest that antigen testing alone, even when mandated and directly observed, may not be sufficient as an intervention to prevent SARS-CoV-2 outbreaks in congregate settings, and they highlight the importance of vaccination to prevent SARS-CoV-2 outbreak in congregate settings.


Subject(s)
COVID-19 , Sports , Humans , Immunologic Tests , SARS-CoV-2 , Universities
17.
PLoS Pathog ; 17(2): e1009373, 2021 02.
Article in English | MEDLINE | ID: covidwho-1105836

ABSTRACT

The evolutionary mechanisms by which SARS-CoV-2 viruses adapt to mammalian hosts and, potentially, undergo antigenic evolution depend on the ways genetic variation is generated and selected within and between individual hosts. Using domestic cats as a model, we show that SARS-CoV-2 consensus sequences remain largely unchanged over time within hosts, while dynamic sub-consensus diversity reveals processes of genetic drift and weak purifying selection. We further identify a notable variant at amino acid position 655 in Spike (H655Y), which was previously shown to confer escape from human monoclonal antibodies. This variant arises rapidly and persists at intermediate frequencies in index cats. It also becomes fixed following transmission in two of three pairs. These dynamics suggest this site may be under positive selection in this system and illustrate how a variant can quickly arise and become fixed in parallel across multiple transmission pairs. Transmission of SARS-CoV-2 in cats involved a narrow bottleneck, with new infections founded by fewer than ten viruses. In RNA virus evolution, stochastic processes like narrow transmission bottlenecks and genetic drift typically act to constrain the overall pace of adaptive evolution. Our data suggest that here, positive selection in index cats followed by a narrow transmission bottleneck may have instead accelerated the fixation of S H655Y, a potentially beneficial SARS-CoV-2 variant. Overall, our study suggests species- and context-specific adaptations are likely to continue to emerge. This underscores the importance of continued genomic surveillance for new SARS-CoV-2 variants as well as heightened scrutiny for signatures of SARS-CoV-2 positive selection in humans and mammalian model systems.


Subject(s)
COVID-19/veterinary , Cat Diseases/virology , SARS-CoV-2/physiology , Adaptation, Biological , Animals , Biological Evolution , COVID-19/transmission , COVID-19/virology , Cats , Evolution, Molecular , Genetic Variation , Humans , Phylogeny , Selection, Genetic
18.
PLoS One ; 15(12): e0244882, 2020.
Article in English | MEDLINE | ID: covidwho-1004475

ABSTRACT

SARS-CoV-2 testing is crucial to controlling the spread of this virus, yet shortages of nucleic acid extraction supplies and other key reagents have hindered the response to COVID-19 in the US. Several groups have described loop-mediated isothermal amplification (LAMP) assays for SARS-CoV-2, including testing directly from nasopharyngeal swabs and eliminating the need for reagents in short supply. Frequent surveillance of individuals attending work or school is currently unavailable to most people but will likely be necessary to reduce the ~50% of transmission that occurs when individuals are nonsymptomatic. Here we describe a fluorescence-based RT-LAMP test using direct nasopharyngeal swab samples and show consistent detection in clinically confirmed primary samples with a limit of detection (LOD) of ~625 copies/µl, approximately 100-fold lower sensitivity than qRT-PCR. While less sensitive than extraction-based molecular methods, RT-LAMP without RNA extraction is fast and inexpensive. Here we also demonstrate that adding a lysis buffer directly into the RT-LAMP reaction improves the sensitivity of some samples by approximately 10-fold. Furthermore, purified RNA in this assay achieves a similar LOD to qRT-PCR. These results indicate that high-throughput RT-LAMP testing could augment qRT-PCR in SARS-CoV-2 surveillance programs, especially while the availability of qRT-PCR testing and RNA extraction reagents is constrained.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19 , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , RNA, Viral/genetics , SARS-CoV-2/genetics , COVID-19/diagnosis , COVID-19/genetics , DNA Primers/chemistry , DNA Primers/genetics , Humans , Limit of Detection , Nasopharynx/virology
19.
Nat Commun ; 11(1): 5558, 2020 11 03.
Article in English | MEDLINE | ID: covidwho-910229

ABSTRACT

Evidence-based public health approaches that minimize the introduction and spread of new SARS-CoV-2 transmission clusters are urgently needed in the United States and other countries struggling with expanding epidemics. Here we analyze 247 full-genome SARS-CoV-2 sequences from two nearby communities in Wisconsin, USA, and find surprisingly distinct patterns of viral spread. Dane County had the 12th known introduction of SARS-CoV-2 in the United States, but this did not lead to descendant community spread. Instead, the Dane County outbreak was seeded by multiple later introductions, followed by limited community spread. In contrast, relatively few introductions in Milwaukee County led to extensive community spread. We present evidence for reduced viral spread in both counties following the statewide "Safer at Home" order, which went into effect 25 March 2020. Our results suggest patterns of SARS-CoV-2 transmission may vary substantially even in nearby communities. Understanding these local patterns will enable better targeting of public health interventions.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Genome, Viral/genetics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , COVID-19 , Coronavirus Infections/prevention & control , Geography , Humans , Mass Screening/methods , Molecular Epidemiology/methods , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Psychological Distance , Respiratory Protective Devices , SARS-CoV-2 , United States/epidemiology , Wisconsin/epidemiology
20.
Nat Rev Immunol ; 20(12): 727-738, 2020 12.
Article in English | MEDLINE | ID: covidwho-899931

ABSTRACT

The rapid scale-up of research on coronavirus disease 2019 (COVID-19) has spawned a large number of potential vaccines and immunotherapies, accompanied by a commensurately large number of in vitro assays and in vivo models to measure their effectiveness. These assays broadly have the same end-goal - to predict the clinical efficacy of prophylactic and therapeutic interventions in humans. However, the apparent potency of different interventions can vary considerably between assays and animal models, leading to very different predictions of clinical efficacy. Complete harmonization of experimental methods may be intractable at the current pace of research. However, here we analyse a selection of existing assays for measuring antibody-mediated virus neutralization and animal models of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and provide a framework for comparing results between studies and reconciling observed differences in the effects of interventions. Finally, we propose how we might optimize these assays for better comparison of results from in vitro and animal studies to accelerate progress.


Subject(s)
COVID-19 Serological Testing/methods , COVID-19/immunology , Immunoassay/methods , Animals , COVID-19/drug therapy , COVID-19/prevention & control , Disease Models, Animal , Humans , Neutralization Tests , Pre-Exposure Prophylaxis
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