Whole-genome sequencing to investigate transmission of SARS-CoV-2 in the acute healthcare setting: a systematic review

Background: Whole-genome sequencing (WGS) has been used widely to elucidate transmission of SARS-CoV-2 in acute healthcare settings, and to guide infection, prevention,and control (IPC) responses.Aim: To systematically appraise available literature, published between January 1st, 2020 and June 30th, 2022, describing the implementation of WGS in acute healthcare settings to characterize nosocomial SARS-CoV-2 transmission.Methods: Searches of the PubMed, Embase, Ovid MEDLINE, EBSCO MEDLINE, and Cochrane Library databases identified studies in English reporting the use of WGS to investigate SARS-CoV-2 transmission in acute healthcare environments. Publications involved data collected up to December 31st, 2021, and findings were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.FindingsIn all, 3088 non-duplicate records were retrieved; 97 met inclusion criteria, involving 62 outbreak analyses and 35 genomic surveillance studies. No publications from low-income countries were identified. In 87/97 (90%), WGS supported hypotheses for nosocomial transmission, while in 46 out of 97 (47%) suspected transmission events were excluded. An IPC intervention was attributed to the use of WGS in 18 out of 97 (18%); however, only three (3%) studies reported turnaround times ≤7 days facilitating near real-time IPC action, and none reported an impact on the incidence of nosocomial COVID-19 attributable to WGS.ConclusionWGS can elucidate transmission of SARS-CoV-2 in acute healthcare settings to enhance epidemiological investigations. However, evidence was not identified to support sequencing as an intervention to reduce the incidence of SARS-CoV-2 in hospital or to alter the trajectory of active outbreaks.</p

Repeated transmission of SARS-CoV-2 in an overcrowded Irish emergency department elucidated by whole-genome sequencing

Aim: To provide a detailed genomic-epidemiological description of a complex multi-ward SARS-CoV-2 outbreak, which originated in the crowded emergency department (ED) in our hospital during the third wave of the COVID-19 pandemic, and was elucidated promptly by local whole-genome sequencing (WGS).Methods: SARS-CoV-2 was detected by reverse transcriptase real-time polymerase chain reaction on viral RNA extracted from nasopharyngeal swabs. WGS was performed using an Oxford MinION Mk1C instrument following the ARTIC v3 sequencing protocol. High-quality consensus genomes were assembled with the artic-ncov2019 bioinformatics pipeline and viral phylogenetic trees were built, inferred by maximum-likelihood. Clusters were defined using a threshold of 0e1 single nucleotide polymorphisms (SNPs) between epidemiologically linked sequences.Results: In April 2021, outbreaks of COVID-19 were declared on two wards at University Hospital Limerick after 4 healthcare-associated SARS-CoV-2 infections were detected by post-admission surveillance testing. Contact tracing identified 12 further connected cases; all with direct or indirect links to the ED ‘COVID Zone’. All sequences were assigned to the Pangolin B.1.1.7 lineage by WGS, and SNP-level analysis revealed two distinct but simul?taneous clusters of infections. Repeated transmission in the ED was demonstrated, involving patients accommodated on trolleys in crowded areas, resulting in multiple generations of infections across three inpatient hospital wards and subsequently to the local community. These findings informed mitigation efforts to prevent cross-transmission in the ED.Conclusion: Cross-transmission of SARS-CoV-2 occurred repeatedly in an overcrowded emergency department. Viral WGS elucidated complex viral transmission networks in our hospital and informed infection, prevention and control practice.</p

Identification of in vivo-expressed antigens of Staphylococcus aureus and their use in vaccinations for protection against nasal carriage

A spectrum of in vivo-expressed Staphylococcus aureus antigens was identified by probing bacteriophage expression libraries of S. aureus with serum samples from infected and uninfected individuals. Eleven recombinant antigenic proteins were produced, and specific antibody titers in a large collection of human serum samples were determined. Significantly increased concentrations of reactive immunoglobulin G (IgG) to 7 antigens were found in serum samples from ill individuals, compared with those in healthy individuals. Significantly higher concentrations of reactive IgG to 4 antigens, including iron-responsive surface determinant (Isd) A and IsdH, were found in serum samples from healthy individuals who were not nasal carriers of S. aureus, compared with those in healthy carriers. Vaccination of cotton rats with IsdA or IsdH protected against nasal carriage. Also, IsdA is involved in adherence of S. aureus to human desquamated nasal epithelial cells and is required for nasal colonization in the cotton rat model. Thus, vaccination with these antigens may prevent S. aureus carriage and reduce the prevalence of human disease.</p

Low prevalence of SARS-CoV-2 detected in symptomatic children admitted to hospital

Aims Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China in 2019 and is responsible for the condition known as COVID-19. COVID-19 was first reported in Ireland in February 2020 with University Hospital Limerick’s (UHL) first paediatric case reported on 4th March 2020. Studies have shown clinical manifestations of children’s cases are generally less severe than those of adults. UHL serves a catchment population of approximately 100,000 children. We aimed to describe the clinical presentation, and prevalence of SARS-CoV-2, in children requiring inpatient hospitalization during the initial phase of the pandemic in Ireland. Methods Data were examined relating to all inpatients aged 0 – 16 years admitted with a queried or confirmed diagnosis of COVID-19 from 8 th February 2020 to 8th June 2020. Emergency Department notes and inpatient records along with laboratory and radiology records were reviewed. Results 220 paediatric inpatients were tested by PCR for SARS-CoV-2 during this period; 101 (45.9%) were female. Ninety-five (43.2%) were diagnosed with ‘viral illnesses’. Seven (3.2%) had laboratory confirmed SARS-CoV-2, with an average age of 8.1 years (range: 0.59 years to 13.77 years). There were two Kawasaki-like illnesses admitted; both tested negative for SARS-CoV-2 on PCR. In our SARS-CoV-2 positive cohort, there was no associated significant morbidity and no associated mortality. Conclusion During the initial phase of the COVID-19 pandemic, prevalence of confirmed SARS-CoV-2 in symptomatic hospitalised children was low at 3.2