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1.
J Clin Invest ; 131(18)2021 09 15.
Article in English | MEDLINE | ID: covidwho-1533156

ABSTRACT

The efficacy of COVID-19 mRNA vaccines is high, but breakthrough infections still occur. We compared the SARS-CoV-2 genomes of 76 breakthrough cases after full vaccination with BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), or JNJ-78436735 (Janssen) to unvaccinated controls (February-April 2021) in metropolitan New York, including their phylogenetic relationship, distribution of variants, and full spike mutation profiles. The median age of patients in the study was 48 years; 7 required hospitalization and 1 died. Most breakthrough infections (57/76) occurred with B.1.1.7 (Alpha) or B.1.526 (Iota). Among the 7 hospitalized cases, 4 were infected with B.1.1.7, including 1 death. Both unmatched and matched statistical analyses considering age, sex, vaccine type, and study month as covariates supported the null hypothesis of equal variant distributions between vaccinated and unvaccinated in χ2 and McNemar tests (P > 0.1), highlighting a high vaccine efficacy against B.1.1.7 and B.1.526. There was no clear association among breakthroughs between type of vaccine received and variant. In the vaccinated group, spike mutations in the N-terminal domain and receptor-binding domain that have been associated with immune evasion were overrepresented. The evolving dynamic of SARS-CoV-2 variants requires broad genomic analyses of breakthrough infections to provide real-life information on immune escape mediated by circulating variants and their spike mutations.


Subject(s)
COVID-19/genetics , COVID-19/immunology , Evolution, Molecular , Immune Evasion/genetics , Mutation , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Adult , Aged , Aged, 80 and over , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Female , Humans , Male , Middle Aged , New York City , Protein Domains , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
2.
PLoS Pathog ; 17(5): e1009571, 2021 05.
Article in English | MEDLINE | ID: covidwho-1236598

ABSTRACT

During the first phase of the COVID-19 epidemic, New York City rapidly became the epicenter of the pandemic in the United States. While molecular phylogenetic analyses have previously highlighted multiple introductions and a period of cryptic community transmission within New York City, little is known about the circulation of SARS-CoV-2 within and among its boroughs. We here perform phylogeographic investigations to gain insights into the circulation of viral lineages during the first months of the New York City outbreak. Our analyses describe the dispersal dynamics of viral lineages at the state and city levels, illustrating that peripheral samples likely correspond to distinct dispersal events originating from the main metropolitan city areas. In line with the high prevalence recorded in this area, our results highlight the relatively important role of the borough of Queens as a transmission hub associated with higher local circulation and dispersal of viral lineages toward the surrounding boroughs.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , SARS-CoV-2/genetics , Genome, Viral/genetics , Humans , New York City/epidemiology , Phylogeny , Phylogeography , Prevalence , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification
3.
Emerg Microbes Infect ; 10(1): 51-65, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1066197

ABSTRACT

COVID-19 is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and declared by the World Health Organization a global public health emergency. Among the severe outbreaks across South America, Uruguay has become known for curtailing SARS-CoV-2 exceptionally well. To understand the SARS-CoV-2 introductions, local transmissions, and associations with genomic and clinical parameters in Uruguay, we sequenced the viral genomes of 44 outpatients and inpatients in a private healthcare system in its capital, Montevideo, from March to May 2020. We performed a phylogeographic analysis using sequences from our cohort and other studies that indicate a minimum of 23 independent introductions into Uruguay, resulting in five major transmission clusters. Our data suggest that most introductions resulting in chains of transmission originate from other South American countries, with the earliest seeding of the virus in late February 2020, weeks before the borders were closed to all non-citizens and a partial lockdown implemented. Genetic analyses suggest a dominance of S and G clades (G, GH, GR) that make up >90% of the viral strains in our study. In our cohort, lethal outcome of SARS-CoV-2 infection significantly correlated with arterial hypertension, kidney failure, and ICU admission (FDR < 0.01), but not with any mutation in a structural or non-structural protein, such as the spike D614G mutation. Our study contributes genetic, phylodynamic, and clinical correlation data about the exceptionally well-curbed SARS-CoV-2 outbreak in Uruguay, which furthers the understanding of disease patterns and regional aspects of the pandemic in Latin America.


Subject(s)
COVID-19/complications , Mutation , SARS-CoV-2/genetics , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/virology , Disease Outbreaks , Female , Humans , Male , Middle Aged , Phylogeny , Polymorphism, Single Nucleotide , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Uruguay/epidemiology , Young Adult
4.
Genome Res ; 30(12): 1781-1788, 2020 12.
Article in English | MEDLINE | ID: covidwho-889658

ABSTRACT

Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epidemiological parameters. Here, we report the analysis of 864 SARS-CoV-2 sequences from cases in the New York City metropolitan area during the COVID-19 outbreak in spring 2020. The majority of cases had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that early transmission was most linked to cases from Europe. Our data are consistent with numerous seeds from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of genomic surveillance in addition to traditional epidemiological indicators.


Subject(s)
COVID-19 , Genome, Viral , Pandemics , Phylogeny , SARS-CoV-2/genetics , Whole Genome Sequencing , COVID-19/epidemiology , COVID-19/genetics , COVID-19/transmission , Female , Humans , Male , New York City
5.
medRxiv ; 2020 Aug 19.
Article in English | MEDLINE | ID: covidwho-828498

ABSTRACT

Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epidemiological parameters. Here, we report the analysis of 864 SARS-CoV-2 sequences from cases in the New York City metropolitan area during the COVID-19 outbreak in Spring 2020. The majority of cases had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that early transmission was most linked to cases from Europe. Our data are consistent with numerous seeds from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of genomic surveillance in addition to traditional epidemiological indicators.

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