Published on 10/15/2020
COVID-19 Genomics and Precision Public Health Weekly Update Content
Pathogen and Human Genomics Studies
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Detection of SARS-CoV-2 with SHERLOCK One-Pot Testing.
Joung Julia et al. The New England journal of medicine 2020 Oct (15) 1492-1494We describe a simple test for detection of SARS-CoV-2. The sensitivity of this test is similar to that of reverse-transcription–quantitative polymerase-chain-reaction (RT-qPCR) assays. STOP (SHERLOCK testing in one pot) is a streamlined assay that combines simplified extraction of viral RNA with isothermal amplification and CRISPR-mediated detection. This test can be performed at a single temperature in less than an hour and with minimal equipment. -
SARS-CoV-2 disrupts splicing, translation, and protein trafficking to suppress host defenses
AK Banerjee et al, Cell, October 8, 2020We define the interactions between SARS-CoV-2 proteins and human RNAs. NSP16 binds to the mRNA recognition domains of the U1 and U2 splicing RNAs and acts to suppress global mRNA splicing upon SARS-CoV-2 infection. NSP1 binds to 18S ribosomal RNA in the mRNA entry channel of the ribosome and leads to global inhibition of mRNA translation upon infection. Finally, NSP8 and NSP9 bind to the 7SL RNA in the Signal Recognition Particle and interfere with protein trafficking to the cell membrane upon infection. Disruption of each of these essential cellular functions acts to suppress the interferon response to viral infection. Our results uncover a multipronged strategy utilized by SARS-CoV-2 to antagonize essential cellular processes to suppress host defenses. -
Large-scale Multi-omic Analysis of COVID-19 Severity
KA Overmeyer et al, Cell Systems, October 7, 2020We surveyed biomolecules in 102 COVID-19 and 26 non-COVID-19 patient blood samples. We found 219 biomolecules strongly associated with COVID-19 status and severity. We observed pronounced dysregulation of lipid transport and neutrophil degranulation. -
Clinical impact of molecular point-of-care testing for suspected COVID-19 in hospital (COV-19POC): a prospective, interventional, non-randomised, controlled study
NJ Brendish et al, Lancet Resp Medicine, October 8, 2020This is a prospective, interventional, non-randomized, controlled study of molecular point-of-care testing in patients aged 18 years or older presenting with suspected COVID-19. Point-of-care testing was associated with large reductions in time to results and could lead to improvements in infection control measures and patient flow compared with centralized laboratory PCR testing. -
Evaluation of a genetic risk score for severity of COVID-19 using human chromosomal-scale length variation.
Toh Christopher et al. Human genomics 2020 Oct (1) 36We compared 981 patients from the UK Biobank dataset who had a severe reaction to SARS-CoV-2 infection before 27 April 2020 to a similar number of age-matched patients drawn for the general UK Biobank population. For each patient, we built a profile of 88 numbers characterizing the chromosomal-scale length variability of their germ line DNA. -
Rapid, sensitive and specific SARS coronavirus-2 detection: a multi-center comparison between standard qRT-PCR and CRISPR based DETECTR.
Brandsma Eelke et al. The Journal of infectious diseases 2020 OctDETECTR, a combination of isothermal reverse transcriptase loop mediated amplification (RT-LAMP) and subsequent Cas12 bystander nuclease activation by amplicon targeting ribonucleoprotein complexes, could be a faster and cheaper alternative to qRT-PCR without sacrificing sensitivity/specificity. -
Genomic evidence for reinfection with SARS-CoV-2: a case study
RL Tillet et al, Lancet Inf Diseases, October 12, 2020A 25-year-old man who was a resident of Washoe County in the US state of Nevada presented to health authorities on two occasions with symptoms of viral infection. The patient had two positive tests for SARS-CoV-2, separated by two negative tests done during follow-up. Genomic analysis of SARS-CoV-2 showed genetically significant differences between each variant associated with each instance of infection. -
SARS-CoV-2 sequencing reveals rapid transmission from college student clusters resulting in morbidity and deaths in vulnerable populations
CS Richmond et al, MEDRXIV, October 14, 2020La Crosse County, Wisconsin experienced a substantial SARS-CoV-2 outbreak (2,002 cases in September 2020) that coincided with the return to in-person instruction at three local academic institutions. Genomic sequencing found rapid expansion of two viral substrains. Although the majority of cases were among college-age individuals, from a total of 111 genomes sequenced we identified rapid transmission of the virus into more vulnerable populations. -
Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates
EE Walsh et al, NEJM, October 15, 2020195 participants underwent randomization. In each of 13 groups of 15 participants, 12 participants received vaccine and 3 received placebo. BNT162b2 was associated with a lower incidence and severity of systemic reactions than BNT162b1. The vaccine candidates elicited similar dose-dependent neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of convalescent serum samples.
Non-Genomics Precision Health Studies
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Detection of SARS-CoV-2 with SHERLOCK One-Pot Testing.
Joung Julia et al. The New England journal of medicine 2020 Oct (15) 1492-1494We describe a simple test for detection of SARS-CoV-2. The sensitivity of this test is similar to that of reverse-transcription–quantitative polymerase-chain-reaction (RT-qPCR) assays. STOP (SHERLOCK testing in one pot) is a streamlined assay that combines simplified extraction of viral RNA with isothermal amplification and CRISPR-mediated detection. This test can be performed at a single temperature in less than an hour and with minimal equipment. -
SARS-CoV-2 disrupts splicing, translation, and protein trafficking to suppress host defenses
AK Banerjee et al, Cell, October 8, 2020We define the interactions between SARS-CoV-2 proteins and human RNAs. NSP16 binds to the mRNA recognition domains of the U1 and U2 splicing RNAs and acts to suppress global mRNA splicing upon SARS-CoV-2 infection. NSP1 binds to 18S ribosomal RNA in the mRNA entry channel of the ribosome and leads to global inhibition of mRNA translation upon infection. Finally, NSP8 and NSP9 bind to the 7SL RNA in the Signal Recognition Particle and interfere with protein trafficking to the cell membrane upon infection. Disruption of each of these essential cellular functions acts to suppress the interferon response to viral infection. Our results uncover a multipronged strategy utilized by SARS-CoV-2 to antagonize essential cellular processes to suppress host defenses. -
Large-scale Multi-omic Analysis of COVID-19 Severity
KA Overmeyer et al, Cell Systems, October 7, 2020We surveyed biomolecules in 102 COVID-19 and 26 non-COVID-19 patient blood samples. We found 219 biomolecules strongly associated with COVID-19 status and severity. We observed pronounced dysregulation of lipid transport and neutrophil degranulation. -
Clinical impact of molecular point-of-care testing for suspected COVID-19 in hospital (COV-19POC): a prospective, interventional, non-randomised, controlled study
NJ Brendish et al, Lancet Resp Medicine, October 8, 2020This is a prospective, interventional, non-randomized, controlled study of molecular point-of-care testing in patients aged 18 years or older presenting with suspected COVID-19. Point-of-care testing was associated with large reductions in time to results and could lead to improvements in infection control measures and patient flow compared with centralized laboratory PCR testing. -
Evaluation of a genetic risk score for severity of COVID-19 using human chromosomal-scale length variation.
Toh Christopher et al. Human genomics 2020 Oct (1) 36We compared 981 patients from the UK Biobank dataset who had a severe reaction to SARS-CoV-2 infection before 27 April 2020 to a similar number of age-matched patients drawn for the general UK Biobank population. For each patient, we built a profile of 88 numbers characterizing the chromosomal-scale length variability of their germ line DNA. -
Rapid, sensitive and specific SARS coronavirus-2 detection: a multi-center comparison between standard qRT-PCR and CRISPR based DETECTR.
Brandsma Eelke et al. The Journal of infectious diseases 2020 OctDETECTR, a combination of isothermal reverse transcriptase loop mediated amplification (RT-LAMP) and subsequent Cas12 bystander nuclease activation by amplicon targeting ribonucleoprotein complexes, could be a faster and cheaper alternative to qRT-PCR without sacrificing sensitivity/specificity. -
Genomic evidence for reinfection with SARS-CoV-2: a case study
RL Tillet et al, Lancet Inf Diseases, October 12, 2020A 25-year-old man who was a resident of Washoe County in the US state of Nevada presented to health authorities on two occasions with symptoms of viral infection. The patient had two positive tests for SARS-CoV-2, separated by two negative tests done during follow-up. Genomic analysis of SARS-CoV-2 showed genetically significant differences between each variant associated with each instance of infection. -
SARS-CoV-2 sequencing reveals rapid transmission from college student clusters resulting in morbidity and deaths in vulnerable populations
CS Richmond et al, MEDRXIV, October 14, 2020La Crosse County, Wisconsin experienced a substantial SARS-CoV-2 outbreak (2,002 cases in September 2020) that coincided with the return to in-person instruction at three local academic institutions. Genomic sequencing found rapid expansion of two viral substrains. Although the majority of cases were among college-age individuals, from a total of 111 genomes sequenced we identified rapid transmission of the virus into more vulnerable populations. -
Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates
EE Walsh et al, NEJM, October 15, 2020195 participants underwent randomization. In each of 13 groups of 15 participants, 12 participants received vaccine and 3 received placebo. BNT162b2 was associated with a lower incidence and severity of systemic reactions than BNT162b1. The vaccine candidates elicited similar dose-dependent neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of convalescent serum samples.
News, Reviews and Commentaries
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Detection of SARS-CoV-2 with SHERLOCK One-Pot Testing.
Joung Julia et al. The New England journal of medicine 2020 Oct (15) 1492-1494We describe a simple test for detection of SARS-CoV-2. The sensitivity of this test is similar to that of reverse-transcription–quantitative polymerase-chain-reaction (RT-qPCR) assays. STOP (SHERLOCK testing in one pot) is a streamlined assay that combines simplified extraction of viral RNA with isothermal amplification and CRISPR-mediated detection. This test can be performed at a single temperature in less than an hour and with minimal equipment. -
SARS-CoV-2 disrupts splicing, translation, and protein trafficking to suppress host defenses
AK Banerjee et al, Cell, October 8, 2020We define the interactions between SARS-CoV-2 proteins and human RNAs. NSP16 binds to the mRNA recognition domains of the U1 and U2 splicing RNAs and acts to suppress global mRNA splicing upon SARS-CoV-2 infection. NSP1 binds to 18S ribosomal RNA in the mRNA entry channel of the ribosome and leads to global inhibition of mRNA translation upon infection. Finally, NSP8 and NSP9 bind to the 7SL RNA in the Signal Recognition Particle and interfere with protein trafficking to the cell membrane upon infection. Disruption of each of these essential cellular functions acts to suppress the interferon response to viral infection. Our results uncover a multipronged strategy utilized by SARS-CoV-2 to antagonize essential cellular processes to suppress host defenses. -
Large-scale Multi-omic Analysis of COVID-19 Severity
KA Overmeyer et al, Cell Systems, October 7, 2020We surveyed biomolecules in 102 COVID-19 and 26 non-COVID-19 patient blood samples. We found 219 biomolecules strongly associated with COVID-19 status and severity. We observed pronounced dysregulation of lipid transport and neutrophil degranulation. -
Clinical impact of molecular point-of-care testing for suspected COVID-19 in hospital (COV-19POC): a prospective, interventional, non-randomised, controlled study
NJ Brendish et al, Lancet Resp Medicine, October 8, 2020This is a prospective, interventional, non-randomized, controlled study of molecular point-of-care testing in patients aged 18 years or older presenting with suspected COVID-19. Point-of-care testing was associated with large reductions in time to results and could lead to improvements in infection control measures and patient flow compared with centralized laboratory PCR testing. -
Evaluation of a genetic risk score for severity of COVID-19 using human chromosomal-scale length variation.
Toh Christopher et al. Human genomics 2020 Oct (1) 36We compared 981 patients from the UK Biobank dataset who had a severe reaction to SARS-CoV-2 infection before 27 April 2020 to a similar number of age-matched patients drawn for the general UK Biobank population. For each patient, we built a profile of 88 numbers characterizing the chromosomal-scale length variability of their germ line DNA. -
Rapid, sensitive and specific SARS coronavirus-2 detection: a multi-center comparison between standard qRT-PCR and CRISPR based DETECTR.
Brandsma Eelke et al. The Journal of infectious diseases 2020 OctDETECTR, a combination of isothermal reverse transcriptase loop mediated amplification (RT-LAMP) and subsequent Cas12 bystander nuclease activation by amplicon targeting ribonucleoprotein complexes, could be a faster and cheaper alternative to qRT-PCR without sacrificing sensitivity/specificity. -
Genomic evidence for reinfection with SARS-CoV-2: a case study
RL Tillet et al, Lancet Inf Diseases, October 12, 2020A 25-year-old man who was a resident of Washoe County in the US state of Nevada presented to health authorities on two occasions with symptoms of viral infection. The patient had two positive tests for SARS-CoV-2, separated by two negative tests done during follow-up. Genomic analysis of SARS-CoV-2 showed genetically significant differences between each variant associated with each instance of infection. -
SARS-CoV-2 sequencing reveals rapid transmission from college student clusters resulting in morbidity and deaths in vulnerable populations
CS Richmond et al, MEDRXIV, October 14, 2020La Crosse County, Wisconsin experienced a substantial SARS-CoV-2 outbreak (2,002 cases in September 2020) that coincided with the return to in-person instruction at three local academic institutions. Genomic sequencing found rapid expansion of two viral substrains. Although the majority of cases were among college-age individuals, from a total of 111 genomes sequenced we identified rapid transmission of the virus into more vulnerable populations. -
Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates
EE Walsh et al, NEJM, October 15, 2020195 participants underwent randomization. In each of 13 groups of 15 participants, 12 participants received vaccine and 3 received placebo. BNT162b2 was associated with a lower incidence and severity of systemic reactions than BNT162b1. The vaccine candidates elicited similar dose-dependent neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of convalescent serum samples.
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