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. FINDINGS: In 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. CONCLUSION: WGS 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.

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 0-1 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 simultaneous 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.

Routine screening for hepatitis C in pregnancy is cost-effective in a large urban population in Ireland: a retrospective study.

OBJECTIVE: To investigate whether risk factor-based screening in pregnancy is failing to identify women with hepatitis C virus (HCV) infection and to assess the cost-effectiveness of universal screening. DESIGN: Retrospective study and model-based economic evaluation. SETTING: Two urban tertiary referral maternity units, currently using risk factor-based screening for HCV infection. POPULATION: Pregnant women who had been tested for hepatitis B, HIV but not HCV. METHODS: Anonymised sera were tested for HCV antibody. Positive sera were tested for HCV antigen. A cost-effectiveness analysis of a change to universal screening was performed using a Markov model to simulate disease progression and Monte Carlo simulations for probabilistic sensitivity analysis. MAIN OUTCOME MEASURES: Presence of HCV antigen and cost per quality-adjusted life year (QALY). RESULTS: In all, 4655 samples were analysed. Twenty had HCV antibodies and five HCV antigen. This gives an active infection rate of 5/4655, or 0.11%, compared with a rate of 0.15% in the risk-factor group. This prevalence is 65% lower than a previous study in the same hospitals from 2001 to 2005. The calculated incremental cost-effectiveness ratio (ICER) for universal screening was €3,315 per QALY gained. CONCLUSION: This study showed that the prevalence of HCV infection in pregnant women in the Dublin region has declined by 65% over the past two decades. Risk factor-based screening misses a significant proportion of infections. A change to universal maternal screening for hepatitis C would be cost-effective in our population. TWEETABLE ABSTRACT: Universal maternal screening for hepatitis C is cost-effective in this urban Irish population.

Indirect impact of rotavirus vaccination on viral causes of acute gastroenteritis in the elderly.

BACKGROUND: Rotavirus is considered a childhood infection causing acute gastroenteritis however, it also causes disease in adults which may be underestimated due to less frequent testing in this age-group. OBJECTIVES: To determine if paediatric rotavirus vaccination, introduced into Ireland in December 2016, affected the viral aetiology in those aged ≥65 yrs presenting with gastroenteritis in the pre- and post-vaccination years. Additionally, rotavirus genotypes in this age-group will be described. METHODS: Faecal samples from 2015 to 2019 for the investigation of gastroenteritis were tested by real-time (RT-) PCR for norovirus, adenovirus, rotavirus, Rotarix, astrovirus and sapovirus. Rotaviruses were genotyped by multiplex real-time RT-PCR or hemi-nested RT-PCR and a proportion confirmed by sequencing. RESULTS: 22,593 samples from adults aged ≥65 yrs were tested and 2566 (11 %) had ≥1 virus detected. Of 2566 positive samples, norovirus was detected in 82 %, rotavirus 9 %, sapovirus 6 %, astrovirus 3 % and adenovirus 1 %. Rotavirus and norovirus infections decreased between pre and post-vaccine year groups p < 0.001, whereas sapovirus, astrovirus and adenovirus remained unchanged. Between 2015-16 and 2018-19, G2P[4] increased and G4P[8] decreased, p < 0.001. In 2015-2019 there were 37 rotavirus outbreaks. Five geriatric outbreaks were genotyped and caused by G4P[8] (n = 1), G1P[8] (n = 1), G2P[4] (n = 2) and G12P[8] (n = 1). CONCLUSION: Rotavirus causes acute gastroenteritis in older people. Paediatric vaccination may have contributed to a decline in infections in the elderly; nevertheless, rotavirus continued to circulate in older people following vaccine introduction. Genotype distribution changed between the pre- and post-vaccine era however genotypes in outbreak and endemic settings were comparable.

Diagnostic Limitations in Congenital Zika Virus Infection.

This is the first documented case of an infant with congenital Zika virus infection (ZVI) born in Ireland. A term infant was delivered with an antenatal diagnosis of severe microcephaly. First trimester bloods confirmed maternal ZVI and although the infant did not have Zika virus RNA or Zika-specific IgM in her blood or urine, she had multiple clinical features of congenital ZVI and Zika virus RNA was present in the placenta.

The role of rhinovirus infections in young children with cystic fibrosis.

Rhinovirus (RV) is an important virus in children with chronic respiratory conditions such as asthma; however, little is known about its role in CF. Our aim was to examine the prevalence and clinical impact of different RV species in young children with CF. We collected clinical data and nasal swabs on patients at home and in the hospital setting. Parents filled out symptom diaries and collected nasal swabs when their children were symptomatic and asymptomatic. A novel RV typing PCR assay was used to determine the RV species present. We collected 55 nasal swab samples from ten preschool CF patients over a six month period. The quality of parent collected samples at home was sufficient for PCR analysis. RV was the most common virus detected in young children with CF. There was no difference in the frequency of RV species between symptomatic and asymptomatic subjects. However, parental home-sampling is an acceptable and feasible approach to monitoring young children with CF.

Integration of a recent infection testing algorithm into HIV surveillance in Ireland: improving HIV knowledge to target prevention.

Recent infection testing algorithms (RITA) for HIV combine serological assays with epidemiological data to determine likely recent infections, indicators of ongoing transmission. In 2016, we integrated RITA into national HIV surveillance in Ireland to better inform HIV prevention interventions. We determined the avidity index (AI) of new HIV diagnoses and linked the results with data captured in the national infectious disease reporting system. RITA classified a diagnosis as recent based on an AI < 1.5, unless epidemiological criteria (CD4 count <200 cells/mm3; viral load <400 copies/ml; the presence of AIDS-defining illness; prior antiretroviral therapy use) indicated a potential false-recent result. Of 508 diagnoses in 2016, we linked 448 (88.1%) to an avidity test result. RITA classified 12.5% of diagnoses as recent, with the highest proportion (26.3%) amongst people who inject drugs. On multivariable logistic regression recent infection was more likely with a concurrent sexually transmitted infection (aOR 2.59; 95% CI 1.04-6.45). Data were incomplete for at least one RITA criterion in 48% of cases. The study demonstrated the feasibility of integrating RITA into routine surveillance and showed some ongoing HIV transmission. To improve the interpretation of RITA, further efforts are required to improve completeness of the required epidemiological data.

Diagnosis of rotavirus infection in a vaccinated population: Is a less sensitive immunochromatographic method more suitable for detecting wild-type rotavirus than real-time RT-PCR?

BACKGROUND: Diagnosis of wild-type rotavirus disease may be complicated by the detection of vaccine-derived virus which can be detected in stool samples following immunisation. We evaluate an immunochromatographic assay and real-time RT-PCR to determine which is more suitable for the detection of wild-type rotavirus. OBJECTIVES: To compare the Ct values of wild-type rotavirus and Rotarix determined by real-time RT-PCR. To establish the Ct value corresponding to the limit of detection of the immunochromatographic Combi-Strip method (Coris, BioConcept). STUDY DESIGN: Retrospective review of real-time RT-PCR Ct values was performed on 100 samples tested by a pan-rotavirus assay (n = 50 wild-type, n = 50 Rotarix). Secondly the limit of detection of the Combi-Strip assay was determined by testing; wild-type rotavirus (n = 33, Ct range 6.85-34.26) samples, Rotarix (n = 9, Ct range 20.86-34.26) samples and rotavirus negative (n = 21) samples. RESULTS: The median Ct of 50 wild-type rotavirus was Ct 12.43; range 6.11-32.66 compared with the median of 50 Rotarix, Ct 29.09; range 18.91-35.28, p=<0.0001. The limit of detection of the Combi-Strip method was approximately Ct 18. The 21 rotavirus negative samples were negative by real-time RT-PCR and Combi-Strip. CONCLUSIONS: We found the Ct value was significantly lower, and therefore the viral load higher, for wild-type rotavirus compared to detectable Rotarix. The Combi-Strip assay detects most wild-type infections; however, it lacks sensitivity to detect low-level wild-type rotavirus and, beneficially, is unlikely to detect Rotarix. It is not a more suitable method than real-time RT-PCR when a definitive rotavirus result is required.

Transfusion-transmitted hepatitis B virus (HBV) infection from an individual-donation nucleic acid (ID-NAT) non-reactive donor.

Lookback was initiated upon notification of an acute HBV infection in a repeat Irish donor, 108 days post-donation. The donation screened non-reactive by individual-donation nucleic acid testing (ID-NAT) using the Procleix Ultrio Elite multiplex assay and again when the archived sample was retested, but the discriminatory assay for HBV was reactive. The immunocompromised recipient of the implicated red cell component was tested 110 days post-transfusion, revealing a HBV DNA viral load of 470 IU/ml. Genotype C2 sequences identical across two regions of the HBV genome were found in samples from the donor and recipient.

Circulating rotavirus genotypes in the Irish paediatric population prior to the introduction of the vaccination programme.

BACKGROUND: Rotavirus is the leading cause of viral gastroenteritis in children, and it is anticipated that the introduction of the Rotarix™ vaccine (GlaxoSmithKline Biologicals S.A., Rixensart, Belgium) into the Irish immunisation schedule will result in a significant reduction of rotavirus-associated disease. In the pre- and post-vaccination eras, it is important to determine circulating strains of rotavirus to assess vaccine effectiveness, to monitor vaccine failures, and to detect potential emerging strains. AIM: This study was a collaboration between the Temple Street Children's University Hospital (TSCUH), Dublin, and the National Virus Reference Laboratory (NVRL), Dublin, to determine the then circulating rotavirus strains in a paediatric hospital. METHOD: In the 2015/2016 period (July 2015-June 2016) 89 faecal samples from paediatric patients (53 from TSCUH, 36 from other hospitals) were characterised. RESULTS: The results showed G1P[8] to be the predominant genotype (57%), followed by G9P[8] (34%), G4P[8] (6%), G2P[4] (2%), and G12P[8] (1%). CONCLUSION: This distribution of genotypes is comparable to those found in other European countries prior to vaccination suggesting that the vaccine should be highly efficacious in the Irish population.

Effectiveness of interferon-free therapy for the treatment of HCV-patients with compensated cirrhosis treated through the Irish early access program.

BACKGROUND: We investigated the real-world effectiveness of interferon-free regimens for the treatment of patients with compensated cirrhosis infected with hepatitis C virus (HCV). METHOD: Using the Irish national HCV treatment registry, the effectiveness and safety of interferon-free regimens for HCV-infected patients treated between April 2015 and August 2016, was determined. RESULTS: A SVR12 was achieved in 86% of subjects treated with sofosbuvir/ledipasvir ± ribavirin (SOF/LDV±RBV), 93% treated with paritaprevir, ombitasvir and ritonavir combined with dasabuvir ± ribavirin (3D±RBV) and 89% treated with sofosbuvir/daclatasvir ± ribavirin (SOF/DCV±RBV). The discontinuation rate was 5% and the on-treatment mortality rate was 1%. CONCLUSION: The availability of interferon-free regimens represents a significant breakthrough for the treatment of HCV infection. Treatments options, with high SVR12 rates, are now available for patients with compensated cirrhosis who were unsuitable for treatment with interferon-based regimens. Data obtained from studies conducted in real world practice provide robust information fundamental for input into future economic evaluations for agents used for the treatment of HCV infection.

Is universal screening for hepatitis C infection prior to commencing antitumour necrosis factor-α therapy necessary?

BACKGROUND: Screening for hepatitis C virus (HCV) prior to the commencement of antitumour necrosis factor (anti-TNF)-α therapies for dermatological disease is recommended for all patients. OBJECTIVES: To determine the incidence of HCV infection among dermatology patients who were screened for HCV infection prior to commencing anti-TNF-α therapies. METHODS: We reviewed the HCV infection status of all patients attending our dermatology department who had been tested for evidence of HCV infection between January 2005 and November 2012. We identified patients who had been tested as part of routine screening prior to commencing anti-TNF-α therapy using dermatology departmental records. RESULTS: In total, 215 patients were screened for HCV infection prior to commencing anti-TNF-α therapies. Among this group, 143 patients (66·5%) were male and 72 (33·5%) were female. None of these patients tested positive for active HCV infection. One patient tested positive for HCV antibody with negative HCV antigen and HCV RNA. This indicated previous HCV infection that had cleared. This patient had abnormal liver function tests and a history of alcohol excess. CONCLUSIONS: There were no cases of active HCV infection diagnosed through pretreatment anti-TNF-α screening in our department, which is located in a low-prevalence area for HCV infection. In view of the lack of evidence of harm associated with anti-TNF-α use in HCV-infected patients, we propose that screening for HCV infection in low-prevalence areas should be targeted to those with pre-existing risk factors. This is consistent with current guidelines from the Royal College of General Practitioners. Targeted screening rather than universal screening may be a safe and cost-effective option among patients being evaluated for anti-TNF-α therapies.

First reported cases of human adenovirus serotype 14p1 infection, Ireland, October 2009 to July 2010.

We report the first nine confirmed cases of human adenovirus 14p1 infection (HAdV-14p1), identified at different locations in Ireland between October 2009 and July 2010. These were the first notifications in Ireland and all were sporadic cases. Following these notifications, the Health Protection Surveillance Centre set up an enhanced surveillance system for HAdV-14p1 infection. Seven cases were male and five were aged less than one year. Three patients died, giving a case fatality rate of 33%. It should be noted that cases presented here were diagnosed on presentation to hospital and may represent the severe end of the spectrum of HAdV 14 disease in Ireland.