scholarly journals Whole-Genome Sequencing: The Key to Unlocking a Nosocomial Outbreak of Coronavirus Disease 2019 (COVID-19)

2021 ◽  
Vol 1 (S1) ◽  
pp. s51-s51
Author(s):  
Lindsey Gottlieb ◽  
Emilia Sordillo ◽  
Harm van Bakel ◽  
Barbara Smith ◽  
Bernard Camins ◽  
...  
Keyword(s):  
New York ◽  
High Risk ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Positive Test ◽  
Contact Tracing ◽  
Whole Genome ◽  
Nosocomial Outbreak ◽  
Primary Case ◽  
Eye Protection

Background: Accurately tracing nosocomial transmission of coronavirus disease 2019 (COVID-19) is critical to developing effective infection prevention policies. Given the high prevalence and variable incubation period of SARS-CoV-2 infection, the utility of traditional contact tracing is limited. We describe a nosocomial outbreak in which whole-genome sequencing (WGS) was pivotal to identifying the primary case. Methods: This study was conducted at a New York City academic hospital. The index case was identified on August 13, 2020, and the last case on September 9, 2020. Hospital policy required all inpatients to be screened for COVID-19 on admission by SARS-CoV-2 molecular amplification testing. All healthcare workers (HCWs) were required to wear masks and eye protection for patient care. After a patient (patient 1), who tested SARS-CoV-2 negative on admission, was positive on preprocedure screening on hospital day 9, contact tracing was initiated. Two patients (patients 2 and 3) and 13 HCWs with high-risk exposures (HREs) to patient 1 were quarantined and referred for testing. Additional surveillance testing was performed on 18 inpatients and 84 HCWs on the affected unit. Patients 2 and 3 and 3 HCWs (HCW-1, -2, and -3), only 1 of whom had a high-risk exposure to patient 1, tested positive. WGS was performed to further investigate this outbreak. Results: The outbreak variant (clade 20A) was found in samples from 6 patients and 2 HCWs. Patients 2 and 3 were roommates of patient 1 in the 2 days before patient 1’s positive test, and they did not consistently wear masks in the room. HCW-1 placed a peripheral IV in patient 1 the day before patient 1’s positive test without wearing eye protection. Four additional cases in this cluster (patients 4–6 and HCW-4) were identified by surveillance WGS of positive tests. A review indicated that patient 1 was located ~3 m (~10 feet) away from patient 4 in the emergency department (ED) for 6 hours on hospital day 1, when the admission SARS-CoV-2 test from patient 4 was not positive. No epidemiologic link was found to patient 5 or 6 or HCW-4. The specimen from HCW-2 was inadequate for WGS. The specimen from HCW-3 was not linked to this cluster. Conclusions: This complex nosocomial outbreak highlights the importance of WGS in understanding transmission events. Patient 4 was not identified by traditional contact tracing but was linked to patient 1 and was recognized as the primary case through WGS, having likely infected patient 1 in the ED. Based on these findings, we focused our corrective actions on more promptly isolating suspected COVID-19 cases in the ED, increasing inpatient masking, and improving HCW adherence to universal eye protection.Funding: NoDisclosures: None

scholarly journals Unraveling a Nosocomial Outbreak of COVID-19: The Role of Whole Genome Sequence Analysis

2021 ◽  
Author(s):  
Suzy E Meijer ◽  
Noam Harel ◽  
Ronen Ben-Ami ◽  
Meital Nahari ◽  
Michal Yakubovsky ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Index Patient ◽  
Added Value ◽  
Whole Genome Sequence ◽  
Contact Tracing ◽  
Whole Genome ◽  
Nosocomial Outbreak ◽  
Multiple Introductions ◽  
The One

Abstract Background The COVID-19 pandemic poses many epidemiological challenges. The investigation of nosocomial transmission is usually performed via thorough investigation of an index case and subsequent contact tracing. Notably, this approach has a subjective component and there is accumulating evidence that whole genome sequencing of the virus may provide a more objective insight. Methods We report a large nosocomial outbreak in one of the medicine departments in our institution. Following intensive epidemiological investigation, we discovered that one of the patients involved was suffering from persistent COVID-19 while initially thought to be a recovering patient. She was therefore deemed to be the most likely source of the outbreak. We then performed whole genome sequencing of the virus of fourteen infected individuals involved in the outbreak. Results Surprisingly, the results of whole genome sequencing refuted our initial hypothesis. A phylogenetic tree of the samples showed multiple introductions of the virus into the ward, one of which led to a cluster of ten of the infected individuals. Importantly, the results pointed in the direction of a specific index patient that was different from the one that arose from our initial investigation. Conclusions These results underscore the important added value of using whole genome sequencing in epidemiological investigations as it may reveal unexpected connections between cases and aid in understanding transmission dynamics, especially in the setting of a pandemic where multiple possible index cases exist simultaneously.

scholarly journals Transmission of SARS-CoV-2 from asymptomatic and presymptomatic individuals in healthcare settings despite medical masks and eye protection

2021 ◽  
Author(s):  
Michael Klompas ◽  
Meghan A Baker ◽  
Diane Griesbach ◽  
Robert Tucker ◽  
Glen R Gallagher ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Eye Protection ◽  
Healthcare Settings

Abstract We describe 3 instances of SARS-CoV-2 transmission despite medical masks and eye protection, including transmission despite the source person being masked, transmission despite the exposed person being masked, and transmission despite both parties being masked. Whole genome sequencing confirmed perfect homology between source and exposed persons’ viruses in all cases.

scholarly journals Comprehensive Whole-Genome Sequencing and Reporting of Drug Resistance Profiles on Clinical Cases of Mycobacterium tuberculosis in New York State

2017 ◽  
Vol 55 (6) ◽  
pp. 1871-1882 ◽  
Author(s):  
Joseph Shea ◽  
Tanya A. Halse ◽  
Pascal Lapierre ◽  
Matthew Shudt ◽  
Donna Kohlerschmidt ◽  
...  
Keyword(s):  
New York ◽  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Predictive Value ◽  
New York State ◽  
Whole Genome ◽  
Content Type ◽  
York State

ABSTRACTWhole-genome sequencing (WGS) is a newer alternative for tuberculosis (TB) diagnostics and is capable of providing rapid drug resistance profiles while performing species identification and capturing the data necessary for genotyping. Our laboratory developed and validated a comprehensive and sensitive WGS assay to characterizeMycobacterium tuberculosisand otherM. tuberculosiscomplex (MTBC) strains, composed of a novel DNA extraction, optimized library preparation, paired-end WGS, and an in-house-developed bioinformatics pipeline. This new assay was assessed using 608 MTBC isolates, with 146 isolates during the validation portion of this study and 462 samples received prospectively. In February 2016, this assay was implemented to test all clinical cases of MTBC in New York State, including isolates and early positive Bactec mycobacterial growth indicator tube (MGIT) 960 cultures from primary specimens. Since the inception of the assay, we have assessed the accuracy of identification of MTBC strains to the species level, concordance with culture-based drug susceptibility testing (DST), and turnaround time. Species identification by WGS was determined to be 99% accurate. Concordance between drug resistance profiles generated by WGS and culture-based DST methods was 96% for eight drugs, with an average resistance-predictive value of 93% and susceptible-predictive value of 96%. This single comprehensive WGS assay has replaced seven molecular assays and has resulted in resistance profiles being reported to physicians an average of 9 days sooner than with culture-based DST for first-line drugs and 32 days sooner for second-line drugs.

scholarly journals Low-level rifampin resistance and rpoB mutations in Mycobacterium tuberculosis: An analysis of whole-genome sequencing and drug susceptibility test data in New York

2020 ◽  
Author(s):  
Joseph Shea ◽  
Tanya A. Halse ◽  
Donna Kohlerschmidt ◽  
Pascal Lapierre ◽  
Herns A. Modestil ◽  
...  
Keyword(s):  
New York ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Critical Concentration ◽  
Gene Sequencing ◽  
Drug Susceptibility ◽  
Whole Genome ◽  
Drug Resistant ◽  
Low Level ◽  
Indicator Tube

Rapid and reliable detection of rifampin (RIF) resistance is critical for the diagnosis and treatment of drug-resistant and multi-drug resistant (MDR) tuberculosis. Discordant RIF phenotype/genotype susceptibility results remain a challenge due to the presence of rpoB mutations which do not confer high levels of RIF resistance as have been exhibited in strains with mutations such as Ser450Leu. These strains, termed low-level RIF resistant, exhibit elevated RIF minimum inhibitory concentrations (MICs) compared to fully susceptible strains, however remain phenotypically susceptible by mycobacteria growth indicator tube (MGIT) testing and have been associated with poor patient outcomes. Here we assess RIF resistance prediction by whole-genome sequencing (WGS) among a set of 1779 prospectively tested strains by both prevalence of rpoB gene mutation and phenotype as part of routine clinical testing during a 21/2-year period. During this time, 139 strains were found to have nonsynonymous rpoB mutations, 53 of which were associated with RIF resistance, including both low-level and high-level resistance. Resistance to RIF (1.0 μg/mL in MGIT) was identified in 43 (81.1%) isolates. The remaining 10 (18.9%) strains were susceptible by MGIT, however were confirmed to be low-level RIF resistant by MIC testing. Full rpoB gene sequencing overcame the limitations of critical concentration phenotyping, probe-based genotyping, and partial-gene sequencing methods. Universal clinical WGS with concurrent phenotypic testing provided a more complete understanding of the prevalence and type of rpoB mutations and their association with RIF resistance in New York.

scholarly journals Comparison of routine field epidemiology and whole genome sequencing to identify tuberculosis transmission in a remote setting

2020 ◽  
Vol 148 ◽  
Author(s):  
J. L. Guthrie ◽  
L. Strudwick ◽  
B. Roberts ◽  
M. Allen ◽  
J. McFadzen ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Tandem Repeats ◽  
Variable Number ◽  
Yukon Territory ◽  
Contact Tracing ◽  
Whole Genome ◽  
Attitudes And Practices ◽  
Genomic Epidemiology ◽  
Recent Transmission

Abstract Yukon Territory (YT) is a remote region in northern Canada with ongoing spread of tuberculosis (TB). To explore the utility of whole genome sequencing (WGS) for TB surveillance and monitoring in a setting with detailed contact tracing and interview data, we used a mixed-methods approach. Our analysis included all culture-confirmed cases in YT (2005–2014) and incorporated data from 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) genotyping, WGS and contact tracing. We compared field-based (contact investigation (CI) data + MIRU-VNTR) and genomic-based (WGS + MIRU-VNTR + basic case data) investigations to identify the most likely source of each person's TB and assessed the knowledge, attitudes and practices of programme personnel around genotyping and genomics using online, multiple-choice surveys (n = 4) and an in-person group interview (n = 5). Field- and genomics-based approaches agreed for 26 of 32 (81%) cases on likely location of TB acquisition. There was less agreement in the identification of specific source cases (13/22 or 59% of cases). Single-locus MIRU-VNTR variants and limited genetic diversity complicated the analysis. Qualitative data indicated that participants viewed genomic epidemiology as a useful tool to streamline investigations, particularly in differentiating latent TB reactivation from the recent transmission. Based on this, genomic data could be used to enhance CIs, focus resources, target interventions and aid in TB programme evaluation.

scholarly journals Correction for Quainoo et al., “Whole-Genome Sequencing of Bacterial Pathogens: the Future of Nosocomial Outbreak Analysis”

2017 ◽  
Vol 31 (1) ◽  
Author(s):  
Scott Quainoo ◽  
Jordy P. M. Coolen ◽  
Sacha A. F. T. van Hijum ◽  
Martijn A. Huynen ◽  
Willem J. G. Melchers ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Bacterial Pathogens ◽  
Whole Genome ◽  
Nosocomial Outbreak ◽  
The Future

scholarly journals Countrywide implementation of whole genome sequencing: an opportunity to improve tuberculosis management, surveillance and contact tracing in low incidence countries

2018 ◽  
Vol 51 (6) ◽  
pp. 1800387 ◽  
Author(s):  
Andrea Maurizio Cabibbe ◽  
Alberto Trovato ◽  
Maria Rosaria De Filippo ◽  
Arash Ghodousi ◽  
Laura Rindi ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Contact Tracing ◽  
Whole Genome ◽  
Low Incidence

scholarly journals XDR-TB transmission in London: Case management and contact tracing investigation assisted by early whole genome sequencing

2016 ◽  
Vol 73 (3) ◽  
pp. 210-218 ◽  
Author(s):  
Amber Arnold ◽  
Adam A. Witney ◽  
Stephania Vergnano ◽  
Anita Roche ◽  
Catherine A. Cosgrove ◽  
...  
Keyword(s):  
Case Management ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Contact Tracing ◽  
Whole Genome
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