RESUMEN
We identified an emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California, a state in the western United States. Named B.1.427/B.1.429 to denote its two lineages, the variant emerged in May 2020 and increased from 0% to >50% of sequenced cases from September 2020 to January 2021, showing 18.6%-24% increased transmissibility relative to wild-type circulating strains. The variant carries three mutations in the spike protein, including an L452R substitution. We found 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation common to variants B.1.1.7, B.1.351, and P.1. Antibody neutralization assays revealed 4.0- to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California exhibiting decreased antibody neutralization warrants further investigation.
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Anticuerpos Neutralizantes/inmunología , COVID-19/inmunología , COVID-19/transmisión , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/inmunología , Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Humanos , Mutación/genética , Secuenciación Completa del Genoma/métodosRESUMEN
The highly transmissible B.1.1.7 variant of SARS-CoV-2, first identified in the United Kingdom, has gained a foothold across the world. Using S gene target failure (SGTF) and SARS-CoV-2 genomic sequencing, we investigated the prevalence and dynamics of this variant in the United States (US), tracking it back to its early emergence. We found that, while the fraction of B.1.1.7 varied by state, the variant increased at a logistic rate with a roughly weekly doubling rate and an increased transmission of 40%-50%. We revealed several independent introductions of B.1.1.7 into the US as early as late November 2020, with community transmission spreading it to most states within months. We show that the US is on a similar trajectory as other countries where B.1.1.7 became dominant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.
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COVID-19 , Modelos Biológicos , SARS-CoV-2 , COVID-19/genética , COVID-19/mortalidad , COVID-19/transmisión , Femenino , Humanos , Masculino , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidad , Estados Unidos/epidemiologíaRESUMEN
We combined viral genome sequencing with contact tracing to investigate introduction and evolution of severe acute respiratory syndrome coronavirus 2 lineages in Santa Clara County, California, from 27 January to 21 March 2020. From 558 persons with coronavirus disease 2019, 101 genomes from 143 available clinical samples comprised 17 lineages, including SCC1 (nâ =â 41), WA1 (nâ =â 9; including the first 2 reported deaths in the United States, with postmortem diagnosis), D614G (nâ =â 4), ancestral Wuhan Hu-1 (nâ =â 21), and 13 others (nâ =â 26). Public health intervention may have curtailed the persistence of lineages that appeared transiently during February and March. By August, only D614G lineages introduced after 21 March were circulating in Santa Clara County.
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COVID-19/epidemiología , COVID-19/transmisión , SARS-CoV-2/genética , Adulto , Anciano , COVID-19/prevención & control , California/epidemiología , Trazado de Contacto , Femenino , Variación Genética , Genoma Viral/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Factores de Riesgo , SARS-CoV-2/clasificación , Viaje , Adulto JovenRESUMEN
In early-to-mid March 2020, 20 of 46 (43%) COVID-19 cases at a tertiary care hospital in San Francisco, California were travel related. Cases were significantly associated with travel to either Europe (odds ratio, 6.1) or New York (odds ratio, 32.9). Viral genomes recovered from 9 of 12 (75%) cases co-clustered with lineages circulating in Europe.
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COVID-19 , Europa (Continente) , Humanos , New York , SARS-CoV-2 , San Francisco/epidemiología , Viaje , Enfermedad Relacionada con los ViajesRESUMEN
BACKGROUND: Streptococcus pneumoniaeis a major cause of community-acquired pneumonia and septicemia in adults. The global drug-susceptible capsular serotype 12F, clonal complex 218 caused several outbreaks in the United States between 1989 and 2008, as well as a recent large outbreak in Manitoba, Canada, that resulted in 36 cases of septicemia and 3 deaths. The evolutionary origin of the Canadian outbreak strain and its relationship to the historical US outbreak strains are not known. METHODS: Whole-genome deep sequencing was performed on isolates from the Canadian outbreak (n = 36), the US outbreaks (n = 9), and nonoutbreak surveys (n = 21). Phylogenomic analysis and comparative genomics were used to assess evolutionary relationships and to detect gene content differences between the isolates. RESULTS: The Canadian outbreak was closely related to sporadic cases that occurred preoutbreak in cross-border geographic regions in Manitoba, North Dakota, and Iowa. The emerging Canadian strain differed from US strains by acquisition of a cell-surface protein and macrolide resistance determinants via incorporation of a 5.3-kb mega cassette harboringmsrDandmefE Furthermore, during 11 months of transmission, this clone evolved rapidly and acquired fluoroquinolone resistance through precise stepwise mutations in bothparCandgyrA, and putative compensatory mutations inuraAorIMPDHunder drug selection. Alarmingly, this drug-resistant clone appears to have spread quickly to other regions of Canada and the United States, and replaced drug-susceptible strains. CONCLUSIONS: Whole-genome sequencing revealed an independent emergence and secondary adaptation of a new virulent and drug-resistant pneumococcal epidemic clone. Ongoing molecular surveillance is required, and measures to prevent its spread should be developed.
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Evolución Biológica , Farmacorresistencia Bacteriana/genética , Genoma Bacteriano , Análisis de Secuencia de ADN , Serogrupo , Streptococcus pneumoniae/genética , Antibacterianos/uso terapéutico , Canadá , Brotes de Enfermedades , Humanos , Infecciones Neumocócicas/tratamiento farmacológico , Infecciones Neumocócicas/genética , Streptococcus pneumoniae/efectos de los fármacos , Estados UnidosRESUMEN
BACKGROUND: In 2010, Winnipeg, Canada, experienced a doubling of invasive pneumococcal disease (IPD) rates, with a significant increase in the number of cases due to Streptococcus pneumoniae serotype 12F, which previously had accounted for very few cases each year. METHODS: All serotype 12F IPD cases reported between September 2009 and January 2011 were reviewed. Pulsed-field gel electrophoresis (PFGE) and multilocus variable number tandem repeat analysis (MLVA) were conducted on all isolates. PFGE and MLVA patterns identified several possible clusters. Additional interviews were conducted to obtain information on risk factors and outcomes. RESULTS: Between September 2009 and January 2011, 169 cases of IPD were identified. The number of IPD cases due to 12F serotype increased sharply from about 3-4 cases per year (6% of IPD cases) in 2007-2009 to 28 (29%) in 2010. All 12F isolates belonged to a single sequence type (ST218), and they were generally susceptible to penicillin and fluoroquinolones but not to erythromycin. Compared with cases caused by other serotypes, patients with serotype 12F were more likely to be homeless, reside in low-income inner-city communities, and engage in substance abuse, including intravenous and crack cocaine use. Subclusters identified using MLVA had even higher rates of homelessness and substance use. CONCLUSIONS: An immunization campaign targeting high-risk groups was undertaken with pneumococcal polysaccharide vaccine, and subsequently rates of serotype 12F decreased. To our knowledge, this is the largest documented community outbreak of serotype 12F IPD and the first report of an outbreak of IPD serotype 12F in a marginalized urban population in Canada.
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Brotes de Enfermedades , Infecciones Neumocócicas/epidemiología , Pobreza , Streptococcus pneumoniae/clasificación , Adolescente , Adulto , Anciano , Canadá/epidemiología , Niño , Electroforesis en Gel de Campo Pulsado , Femenino , Personas con Mala Vivienda , Humanos , Masculino , Persona de Mediana Edad , Infecciones Neumocócicas/microbiología , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/inmunología , Serogrupo , Serotipificación , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/aislamiento & purificación , Trastornos Relacionados con Sustancias , Población Urbana , Vacunación , Adulto JovenRESUMEN
BACKGROUND: Antimicrobial resistance (AMR) is rising at an alarming rate and complicating the management of infectious diseases including lower respiratory tract infections (LRTI). Metagenomic next-generation sequencing (mNGS) is a recently established method for culture-independent LRTI diagnosis, but its utility for predicting AMR has remained unclear. We aimed to assess the performance of mNGS for AMR prediction in bacterial LRTI and demonstrate proof of concept for epidemiological AMR surveillance and rapid AMR gene detection using Cas9 enrichment and nanopore sequencing. METHODS: We studied 88 patients with acute respiratory failure between 07/2013 and 9/2018, enrolled through a previous observational study of LRTI. Inclusion criteria were age ≥ 18, need for mechanical ventilation, and respiratory specimen collection within 72 h of intubation. Exclusion criteria were decline of study participation, unclear LRTI status, or no matched RNA and DNA mNGS data from a respiratory specimen. Patients with LRTI were identified by clinical adjudication. mNGS was performed on lower respiratory tract specimens. The primary outcome was mNGS performance for predicting phenotypic antimicrobial susceptibility and was assessed in patients with LRTI from culture-confirmed bacterial pathogens with clinical antimicrobial susceptibility testing (n = 27 patients, n = 32 pathogens). Secondary outcomes included the association between hospital exposure and AMR gene burden in the respiratory microbiome (n = 88 patients), and AMR gene detection using Cas9 targeted enrichment and nanopore sequencing (n = 10 patients). RESULTS: Compared to clinical antimicrobial susceptibility testing, the performance of respiratory mNGS for predicting AMR varied by pathogen, antimicrobial, and nucleic acid type sequenced. For gram-positive bacteria, a combination of RNA + DNA mNGS achieved a sensitivity of 70% (95% confidence interval (CI) 47-87%) and specificity of 95% (CI 85-99%). For gram-negative bacteria, sensitivity was 100% (CI 87-100%) and specificity 64% (CI 48-78%). Patients with hospital-onset LRTI had a greater AMR gene burden in their respiratory microbiome versus those with community-onset LRTI (p = 0.00030), or those without LRTI (p = 0.0024). We found that Cas9 targeted sequencing could enrich for low abundance AMR genes by > 2500-fold and enabled their rapid detection using a nanopore platform. CONCLUSIONS: mNGS has utility for the detection and surveillance of resistant bacterial LRTI pathogens.
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Infecciones Bacterianas , Infecciones del Sistema Respiratorio , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Enfermedad Crítica , Farmacorresistencia Bacteriana/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Metagenómica/métodos , ARN , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/microbiología , Sensibilidad y EspecificidadRESUMEN
Associations between vaccine breakthrough cases and infection by different SARS coronavirus 2 (SARS-CoV-2) variants have remained largely unexplored. Here we analysed SARS-CoV-2 whole-genome sequences and viral loads from 1,373 persons with COVID-19 from the San Francisco Bay Area from 1 February to 30 June 2021, of which 125 (9.1%) were vaccine breakthrough infections. Vaccine breakthrough infections were more commonly associated with circulating antibody-resistant variants carrying ≥1 mutation associated with decreased antibody neutralization (L452R/Q, E484K/Q and/or F490S) than infections in unvaccinated individuals (78% versus 48%, P = 1.96 × 10-8). Differences in viral loads were non-significant between unvaccinated and fully vaccinated cases overall (P = 0.99) and according to lineage (P = 0.09-0.78). Symptomatic vaccine breakthrough infections had comparable viral loads (P = 0.64), whereas asymptomatic breakthrough infections had decreased viral loads (P = 0.023) compared with infections in unvaccinated individuals. In 5 cases with serial samples available for serologic analyses, vaccine breakthrough infections were found to be associated with low or undetectable neutralizing antibody levels attributable to an immunocompromised state or infection by an antibody-resistant lineage. Taken together, our results show that vaccine breakthrough infections are overrepresented by antibody-resistant SARS-CoV-2 variants, and that symptomatic breakthrough infections may be as efficient in spreading COVID-19 as unvaccinated infections, regardless of the infecting lineage.
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Anticuerpos Antivirales/sangre , Vacuna BNT162/inmunología , COVID-19/epidemiología , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Adolescente , Adulto , Anciano , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Vacuna BNT162/administración & dosificación , COVID-19/inmunología , Vacunas contra la COVID-19/inmunología , Estudios de Cohortes , Femenino , Genoma Viral , Humanos , Masculino , Persona de Mediana Edad , Mutación , Filogenia , San Francisco/epidemiología , Vacunación , Carga Viral/estadística & datos numéricos , Secuenciación Completa del Genoma , Adulto JovenRESUMEN
We developed a metagenomic next-generation sequencing (mNGS) test using cell-free DNA from body fluids to identify pathogens. The performance of mNGS testing of 182 body fluids from 160 patients with acute illness was evaluated using two sequencing platforms in comparison to microbiological testing using culture, 16S bacterial PCR and/or 28S-internal transcribed ribosomal gene spacer (28S-ITS) fungal PCR. Test sensitivity and specificity of detection were 79 and 91% for bacteria and 91 and 89% for fungi, respectively, by Illumina sequencing; and 75 and 81% for bacteria and 91 and 100% for fungi, respectively, by nanopore sequencing. In a case series of 12 patients with culture/PCR-negative body fluids but for whom an infectious diagnosis was ultimately established, seven (58%) were mNGS positive. Real-time computational analysis enabled pathogen identification by nanopore sequencing in a median 50-min sequencing and 6-h sample-to-answer time. Rapid mNGS testing is a promising tool for diagnosis of unknown infections from body fluids.
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Bacterias/aislamiento & purificación , Líquidos Corporales/microbiología , Hongos/aislamiento & purificación , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Metagenómica , Adulto , Anciano , Bacterias/genética , Ácidos Nucleicos Libres de Células/análisis , Ácidos Nucleicos Libres de Células/genética , Femenino , Hongos/genética , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To describe epidemiologic and genomic characteristics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a large skilled-nursing facility (SNF), and the strategies that controlled transmission. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted during March 22-May 4, 2020, among all staff and residents at a 780-bed SNF in San Francisco, California. METHODS: Contact tracing and symptom screening guided targeted testing of staff and residents; respiratory specimens were also collected through serial point prevalence surveys (PPSs) in units with confirmed cases. Cases were confirmed by real-time reverse transcription-polymerase chain reaction testing for SARS-CoV-2, and whole-genome sequencing (WGS) was used to characterize viral isolate lineages and relatedness. Infection prevention and control (IPC) interventions included restricting from work any staff who had close contact with a confirmed case; restricting movement between units; implementing surgical face masking facility-wide; and the use of recommended PPE (ie, isolation gown, gloves, N95 respirator and eye protection) for clinical interactions in units with confirmed cases. RESULTS: Of 725 staff and residents tested through targeted testing and serial PPSs, 21 (3%) were SARS-CoV-2 positive: 16 (76%) staff and 5 (24%) residents. Fifteen cases (71%) were linked to a single unit. Targeted testing identified 17 cases (81%), and PPSs identified 4 cases (19%). Most cases (71%) were identified before IPC interventions could be implemented. WGS was performed on SARS-CoV-2 isolates from 4 staff and 4 residents: 5 were of Santa Clara County lineage and the 3 others were distinct lineages. CONCLUSIONS: Early implementation of targeted testing, serial PPSs, and multimodal IPC interventions limited SARS-CoV-2 transmission within the SNF.
Asunto(s)
COVID-19 , Instituciones de Cuidados Especializados de Enfermería , Estudios de Cohortes , Brotes de Enfermedades , Humanos , SARS-CoV-2 , San Francisco/epidemiologíaRESUMEN
We identified a novel SARS-CoV-2 variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California. Named B.1.427/B.1.429 to denote its 2 lineages, the variant emerged around May 2020 and increased from 0% to >50% of sequenced cases from September 1, 2020 to January 29, 2021, exhibiting an 18.6-24% increase in transmissibility relative to wild-type circulating strains. The variant carries 3 mutations in the spike protein, including an L452R substitution. Our analyses revealed 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation found in the B.1.1.7, B.1.351, and P.1 variants. Antibody neutralization assays showed 4.0 to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California associated with decreased antibody neutralization warrants further investigation.
RESUMEN
As of January of 2021, the highly transmissible B.1.1.7 variant of SARS-CoV-2, which was first identified in the United Kingdom (U.K.), has gained a strong foothold across the world. Because of the sudden and rapid rise of B.1.1.7, we investigated the prevalence and growth dynamics of this variant in the United States (U.S.), tracking it back to its early emergence and onward local transmission. We found that the RT-qPCR testing anomaly of S gene target failure (SGTF), first observed in the U.K., was a reliable proxy for B.1.1.7 detection. We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, detection of the variant increased at a logistic rate similar to those observed elsewhere, with a doubling rate of a little over a week and an increased transmission rate of 35-45%. By performing time-aware Bayesian phylodynamic analyses, we revealed several independent introductions of B.1.1.7 into the U.S. as early as late November 2020, with onward community transmission enabling the variant to spread to at least 30 states as of January 2021. Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.
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Although the first HIV circulating recombinant form (CRF01_AE) is the predominant strain in many Asian countries, it is uncommonly found in the Congo Basin from where it first originated. To fill the gap in the evolutionary history of this important strain, we sequenced near complete genomes from HIV samples with subgenomic CRF01_AE regions collected in Cameroon and the Democratic Republic of the Congo from 2001 to 2006. HIV genomes were generated from N = 13 plasma specimens by next-generation sequencing of metagenomic libraries prepared with spiked primers targeting HIV, followed by Sanger gap-filling. Genome sequences were aligned to reference strains, including Asian and African CRF01_AE sequences, and evaluated by phylogenetic and recombinant analysis to identify four CRF01_AE strains from Cameroon. We also identified two CRF02, one CRF27, and six unique recombinant form genomes (01|A1|G, 01|02|F|U, F|G|01, A1|D|01, F|G|01, and A1|G|01). Phylogenetic analysis, including the four new African CRF01_AE genomes, placed these samples as a bridge between basal Central African Republic CRF01_AE strains and all Asian, European, and American CRF01_AE strains. Molecular dating confirmed previous estimates indicating that the most recent common CRF01_AE ancestor emerged in the early 1970s (1968-1970) and spread beyond Africa around 1980 to Asia. The new sequences and analysis presented in this study expand the molecular history of the CRF01_AE clade, and are illustrated in an interactive Next Strain phylogenetic tree, map, and timeline at (https://nextstrain.org/community/EduanWilkinson/hiv-1_crf01).
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Genoma Viral , VIH-1/genética , VIH-1/aislamiento & purificación , Filogenia , Recombinación Genética , República Democrática del Congo/epidemiología , Variación Genética , Genotipo , Infecciones por VIH/sangre , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Humanos , FilogeografíaRESUMEN
An outbreak of novel betacoronavirus, SARS-CoV-2 (formerly named 2019-nCoV), began in Wuhan, China in December 2019 and the COVID-19 disease associated with infection has since spread rapidly to multiple countries. Here we report the development of SARS-CoV-2 DETECTR, a rapid (~30 min), low-cost, and accurate CRISPR-Cas12 based lateral flow assay for detection of SARS-CoV-2 from respiratory swab RNA extracts. We validated this method using contrived reference samples and clinical samples from infected US patients and demonstrated comparable performance to the US CDC SARS-CoV-2 real-time RT-PCR assay.
RESUMEN
An outbreak of betacoronavirus severe acute respiratory syndrome (SARS)-CoV-2 began in Wuhan, China in December 2019. COVID-19, the disease associated with SARS-CoV-2 infection, rapidly spread to produce a global pandemic. We report development of a rapid (<40 min), easy-to-implement and accurate CRISPR-Cas12-based lateral flow assay for detection of SARS-CoV-2 from respiratory swab RNA extracts. We validated our method using contrived reference samples and clinical samples from patients in the United States, including 36 patients with COVID-19 infection and 42 patients with other viral respiratory infections. Our CRISPR-based DETECTR assay provides a visual and faster alternative to the US Centers for Disease Control and Prevention SARS-CoV-2 real-time RT-PCR assay, with 95% positive predictive agreement and 100% negative predictive agreement.
Asunto(s)
Betacoronavirus/aislamiento & purificación , Sistemas CRISPR-Cas , Técnicas de Laboratorio Clínico , Técnicas de Amplificación de Ácido Nucleico/métodos , Betacoronavirus/genética , COVID-19 , Prueba de COVID-19 , Vacunas contra la COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , Humanos , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/virología , ARN Guía de Kinetoplastida/genética , SARS-CoV-2 , Factores de TiempoRESUMEN
Metagenomic next-generation sequencing (mNGS), the shotgun sequencing of RNA and DNA from clinical samples, has proved useful for broad-spectrum pathogen detection and the genomic surveillance of viral outbreaks. An additional target enrichment step is generally needed for high-sensitivity pathogen identification in low-titre infections, yet available methods using PCR or capture probes can be limited by high cost, narrow scope of detection, lengthy protocols and/or cross-contamination. Here, we developed metagenomic sequencing with spiked primer enrichment (MSSPE), a method for enriching targeted RNA viral sequences while simultaneously retaining metagenomic sensitivity for other pathogens. We evaluated MSSPE for 14 different viruses, yielding a median tenfold enrichment and mean 47% (±16%) increase in the breadth of genome coverage over mNGS alone. Virus detection using MSSPE arboviral or haemorrhagic fever viral panels was comparable in sensitivity to specific PCR, demonstrating 95% accuracy for the detection of Zika, Ebola, dengue, chikungunya and yellow fever viruses in plasma samples from infected patients. Notably, sequences from re-emerging and/or co-infecting viruses that have not been specifically targeted a priori, including Powassan and Usutu, were successfully enriched using MSSPE. MSSPE is simple, low cost, fast and deployable on either benchtop or portable nanopore sequencers, making this method directly applicable for diagnostic laboratory and field use.
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Genoma Viral , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Metagenoma , Metagenómica/métodos , Virus/genética , Virus/aislamiento & purificación , Virus Chikungunya/genética , Virus Chikungunya/aislamiento & purificación , Biología Computacional , ADN Viral/genética , Dengue/diagnóstico , Virus del Dengue/genética , Virus del Dengue/aislamiento & purificación , Ebolavirus/genética , Ebolavirus/aislamiento & purificación , Fiebre Hemorrágica Ebola/diagnóstico , Humanos , Reacción en Cadena de la Polimerasa , ARN Viral/genética , ARN Viral/aislamiento & purificación , Virosis/diagnóstico , Fiebre Amarilla/diagnóstico , Virus Zika/genética , Infección por el Virus Zika/diagnósticoRESUMEN
After its emergence in Wuhan, China, in late November or early December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus rapidly spread globally. Genome sequencing of SARS-CoV-2 allows the reconstruction of its transmission history, although this is contingent on sampling. We analyzed 453 SARS-CoV-2 genomes collected between 20 February and 15 March 2020 from infected patients in Washington state in the United States. We find that most SARS-CoV-2 infections sampled during this time derive from a single introduction in late January or early February 2020, which subsequently spread locally before active community surveillance was implemented.
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Betacoronavirus/genética , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Genoma Viral , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Teorema de Bayes , COVID-19 , Humanos , Funciones de Verosimilitud , Pandemias , Filogenia , SARS-CoV-2 , Washingtón/epidemiologíaRESUMEN
BACKGROUND: Most data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have been presented as case series without comparison to patients with other acute respiratory illnesses. METHODS: We examined emergency department patients between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared clinical presentation, diagnostics, treatment, and outcomes. FINDINGS: Among 316 patients, 33 tested positive for SARS-CoV-2; 31 without COVID-19 tested positive for another respiratory virus. Among patients with additional viral testing (27/33), no SARS-CoV-2 co-infections were identified. Compared to those who tested negative, patients with COVID-19 reported longer symptoms duration (median 7d vs. 3d, p < 0.001). Patients with COVID-19 were more often hospitalized (79% vs. 56%, p = 0.014). When hospitalized, patients with COVID-19 had longer hospitalizations (median 10.7d vs. 4.7d, p < 0.001) and more often developed ARDS (23% vs. 3%, p < 0.001). Most comorbidities, medications, symptoms, vital signs, laboratories, treatments, and outcomes did not differ by COVID-19 status. INTERPRETATION: While we found differences in clinical features of COVID-19 compared to other acute respiratory illnesses, there was significant overlap in presentation and comorbidities. Patients with COVID-19 were more likely to be admitted to the hospital, have longer hospitalizations and develop ARDS, and were unlikely to have co-existent viral infections. FUNDING: National Center for Advancing Translational Sciences, National Heart Lung Blood Institute, National Institute of Allergy and Infectious Diseases, Chan Zuckerberg Biohub, Chan Zuckerberg Initiative.
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The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, with >365,000 cases in California as of 17 July 2020. We investigated the genomic epidemiology of SARS-CoV-2 in Northern California from late January to mid-March 2020, using samples from 36 patients spanning nine counties and the Grand Princess cruise ship. Phylogenetic analyses revealed the cryptic introduction of at least seven different SARS-CoV-2 lineages into California, including epidemic WA1 strains associated with Washington state, with lack of a predominant lineage and limited transmission among communities. Lineages associated with outbreak clusters in two counties were defined by a single base substitution in the viral genome. These findings support contact tracing, social distancing, and travel restrictions to contain the spread of SARS-CoV-2 in California and other states.
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Betacoronavirus/genética , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Genoma Viral , Filogenia , Neumonía Viral/epidemiología , Neumonía Viral/virología , COVID-19 , California/epidemiología , Infecciones por Coronavirus/transmisión , Monitoreo Epidemiológico , Humanos , Pandemias , Neumonía Viral/transmisión , SARS-CoV-2 , Alineación de Secuencia , Navíos , Viaje , WashingtónRESUMEN
BACKGROUND: Emerging data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have largely been presented as case series. Few studies have compared these clinical features and outcomes of COVID-19 to other acute respiratory illnesses. METHODS: We examined all patients presenting to an emergency department in San Francisco, California between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared demographics, comorbidities, symptoms, vital signs, and laboratory results including viral diagnostics using PCR and mNGS. Among those hospitalized, we determined differences in treatment (antibiotics, antivirals, respiratory support) and outcomes (ICU admission, ICU interventions, acute respiratory distress syndrome, cardiac injury). FINDINGS: In a cohort of 316 patients, 33 (10%) tested positive for SARS-CoV-2; 31 patients, all without COVID-19, tested positive for another respiratory virus (16%). Among patients with additional viral testing, no co-infections with SARS-CoV-2 were identified by PCR or mNGS. Patients with COVID-19 reported longer symptoms duration (median 7 vs. 3 days), and were more likely to report fever (82% vs. 44%), fatigue (85% vs. 50%), and myalgias (61% vs 27%); p<0.001 for all comparisons. Lymphopenia (55% vs 34%, p=0.018) and bilateral opacities on initial chest radiograph (55% vs. 24%, p=0.001) were more common in patients with COVID-19. Patients with COVID-19 were more often hospitalized (79% vs. 56%, p=0.014). Of 186 hospitalized patients, patients with COVID-19 had longer hospitalizations (median 10.7d vs. 4.7d, p<0.001) and were more likely to develop ARDS (23% vs. 3%, p<0.001). Most comorbidities, home medications, signs and symptoms, vital signs, laboratory results, treatment, and outcomes did not differ by COVID-19 status. INTERPRETATION: While we found differences in clinical features of COVID-19 compared to other acute respiratory illnesses, there was significant overlap in presentation and comorbidities. Patients with COVID-19 were more likely to be admitted to the hospital, have longer hospitalizations and develop ARDS, and were unlikely to have co-existent viral infections. These findings enhance understanding of the clinical characteristics of COVID-19 in comparison to other acute respiratory illnesses. .