Multiple introductions of monkeypox virus to Ireland during the international mpox outbreak, May 2022 to October 2023.

BackgroundMpox, caused by monkeypox virus (MPXV), was considered a rare zoonotic disease before May 2022, when a global epidemic of cases in non-endemic countries led to the declaration of a Public Health Emergency of International Concern. Cases of mpox in Ireland, a country without previous mpox reports, could reflect extended local transmission or multiple epidemiological introductions.AimTo elucidate the origins and molecular characteristics of MPXV circulating in Ireland between May 2022 and October 2023.MethodsWhole genome sequencing of MPXV from 75% of all Irish mpox cases (182/242) was performed and compared to sequences retrieved from public databases (n = 3,362). Bayesian approaches were used to infer divergence time between sequences from different subclades and evaluate putative importation events from other countries.ResultsOf 242 detected mpox cases, 99% were males (median age: 35 years; range: 15-60). All 182 analysed genomes were assigned to Clade IIb and, presence of 12 distinguishable subclades suggests multiple introductions into Ireland. Estimation of time to divergence of subclades further supports the hypothesis for multiple importation events from numerous countries, indicative of extended and sustained international spread of mpox. Further analysis of sequences revealed that 92% of nucleotide mutations were from cytosine to thymine (or from guanine to adenine), leading to a high number of non-synonymous mutations across subclades; mutations associated with tecovirimat resistance were not observed.ConclusionWe provide insights into the international transmission dynamics supporting multiple introductions of MPXV into Ireland. Such information supported the implementation of evidence-informed public health control measures.

Adeno-Associated Virus 2 and Human Adenovirus F41 in Wastewater during Outbreak of Severe Acute Hepatitis in Children, Ireland.

During April-July 2022, outbreaks of severe acute hepatitis of unknown etiology (SAHUE) were reported in 35 countries. Five percent of cases required liver transplantation, and 22 patients died. Viral metagenomic studies of clinical samples from SAHUE cases showed a correlation with human adenovirus F type 41 (HAdV-F41) and adeno-associated virus type 2 (AAV2). To explore the association between those DNA viruses and SAHUE in children in Ireland, we quantified HAdV-F41 and AAV2 in samples collected from a wastewater treatment plant serving 40% of Ireland's population. We noted a high correlation between HAdV-F41 and AAV2 circulation in the community and SAHUE clinical cases. Next-generation sequencing of the adenovirus hexon in wastewater demonstrated HAdV-F41 was the predominant HAdV type circulating. Our environmental analysis showed increased HAdV-F41 and AAV2 prevalence in the community during the SAHUE outbreak. Our findings highlight how wastewater sampling could aid in surveillance for respiratory adenovirus species.

Laboratory-based testing for hepatitis C infection using dried blood spot samples: A systematic review and meta-analysis of diagnostic accuracy.

The use of dried blood spot (DBS) samples can facilitate the implementation of reflex testing by circumventing the need for centrifugation and freezing of venous blood samples. This systematic review assessed the accuracy of using DBS samples to diagnose chronic hepatitis C virus (HCV) infection. A comprehensive search was undertaken to identify articles published up to July 2020 evaluating the diagnostic accuracy of anti-HCV, HCV-RNA and HCV core antigen tests using DBS. Screening, data extraction, quality appraisal and Grading of Recommendations, Assessment, Development and Evaluations certainty of the evidence assessment were performed independently by two reviewers. Meta-analysis, meta-regression and sensitivity analyses were conducted. The evidence demonstrates that laboratory-based anti-HCV and HCV-RNA tests using DBS samples have high diagnostic accuracy. All comparisons were between DBS and venous samples. For the detection of anti-HCV, sensitivity was 95% (95% CI: 92%-97%) and specificity was 99% ([95% CI: 98%-99%]; n = 25; I2  = 81%; moderate certainty). For the detection of HCV-RNA, the sensitivity was 95% (95% CI: 93%-97%) and specificity was 97% ([95% CI: 94%-98%]; n = 20; I2  = 52%; moderate certainty). The sensitivity of HCV core antigen tests was 86% (95% CI: 79%-91%) and specificity was 98% ([95% CI: 94%-99%]; n = 5; I2  = 37%; low certainty) compared with HCV-RNA (the gold standard for detecting chronic HCV). DBS samples could facilitate diagnosis of chronic HCV infection as the necessary sequential tests (anti-HCV and then HCV-RNA or HCV core antigen) can be undertaken using the same blood sample. This could reduce loss of patient follow-up and support international efforts towards HCV elimination in both high and low prevalence settings.

Another Step Toward Hepatitis C Elimination: An Economic Evaluation of an Irish National Birth Cohort Testing Program.

OBJECTIVES: We aimed to evaluate the cost-effectiveness of offering once-off birth cohort testing for hepatitis C virus (HCV) to people in Ireland born between 1965 and 1985, the cohort with the highest reported prevalence of undiagnosed chronic HCV infection. METHODS: Systematic and opportunistic HCV birth cohort testing programs, implemented over a 4-year timeframe, were compared with the current practice of population risk-based testing only in a closed-cohort decision tree and Markov model hybrid over a lifetime time horizon. Outcomes were expressed in quality-adjusted life-years (QALYs). Costs were presented from the health system's perspective in 2020 euro (€). Uncertainty was assessed via deterministic, probabilistic, scenario, and threshold analyses. RESULTS: In the base case, systematic testing yielded the largest cost and health benefits, followed by opportunistic testing and risk-based testing. Compared with risk-based testing, the incremental cost-effectiveness ratio for opportunistic testing was €14 586 (95% confidence interval €4185-€33 527) per QALY gained. Compared with opportunistic testing, the incremental cost-effectiveness ratio for systematic testing was €16 827 (95% confidence interval €5106-€38 843) per QALY gained. These findings were robust across a range of sensitivity analyses. CONCLUSIONS: Both systematic and opportunistic birth cohort testing would be considered an efficient use of resources, but systematic testing was the optimal strategy at willingness-to-pay threshold values typically used in Ireland. Although cost-effective, any decision to introduce birth cohort testing for HCV (in Ireland or elsewhere) must be balanced with considerations regarding the feasibility and budget impact of implementing a national testing program given high initial costs and resource use.

Airborne transmission of SARS-CoV-2 via aerosols.

A key consideration in the Covid-19 pandemic is the dominant modes of transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The objective of this review was to synthesise the evidence for the potential airborne transmission of SARS-CoV-2 via aerosols. Systematic literature searches were conducted in PubMed, Embase, Europe PMC and National Health Service UK evidence up to 27 July 2020. A protocol was published and Cochrane guidance for rapid review methodology was adhered to throughout. Twenty-eight studies were identified. Seven out of eight epidemiological studies suggest aerosol transmission may occur, with enclosed environments and poor ventilation noted as possible contextual factors. Ten of the 16 air sampling studies detected SARS-CoV-2 ribonucleic acid; however, only three of these studies attempted to culture the virus with one being successful in a limited number of samples. Two of four virological studies using artificially generated aerosols indicated that SARS-CoV-2 is viable in aerosols. The results of this review indicate there is inconclusive evidence regarding the viability and infectivity of SARS-CoV-2 in aerosols. Epidemiological studies suggest possible transmission, with contextual factors noted. Viral particles have been detected in air sampling studies with some evidence of clinical infectivity, and virological studies indicate these particles may represent live virus, adding further plausibility. However, there is uncertainty as to the nature and impact of aerosol transmission of SARS-CoV-2, and its relative contribution to the Covid-19 pandemic compared with other modes of transmission.

Alternative clinical specimens for the detection of SARS-CoV-2: A rapid review.

The collection of nasopharyngeal swabs to test for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an invasive technique with implications for patients and clinicians. Alternative clinical specimens from the upper respiratory tract may offer benefits in terms of collection, comfort and infection risk. The objective of this review was to synthesise the evidence for detection of SARS-CoV-2 ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) tested saliva or nasal specimens compared with RT-PCR tested nasopharyngeal specimens. Searches were conducted in PubMed, Embase, Europe PMC and NHS evidence from December 2019 to 20 July 2020. Eighteen studies were identified; 12 for saliva, four for nasal and two included both specimen types. For saliva-based studies, the proportion of saliva samples testing positive relative to all positive samples in each study ranged from 82.9% to 100%; detection in nasopharyngeal specimens ranged from 76.7% to 100%; positive agreement between specimens for overall detection ranged from 65.4% to 100%. For nasal-based studies, the proportion of nasal swabs testing positive relative to all positive samples in each study ranged from 81.9% to 100%; detection in nasopharyngeal specimens ranged from 70% to 100%; positive agreement between specimens for overall detection ranged from 62.3% to 100%. The results indicate an inconsistency in the detection of SARS-CoV-2 RNA in the specimen types included, often with neither the index nor the reference of interest detecting all known cases. Depending on the test environment, these clinical specimens may offer a viable alternative to standard. However, at present the evidence is limited, of variable quality, and relatively inconsistent.

Multicystic Encephalomalacia: The Neuropathology of Systemic Neonatal Parechovirus Infection.

The Neuropathology of Human Parechovirus (HPeV) is not widely described due to the relatively recent discovery of the virus combined with a limited number of autopsy case reports. We report the case of an infant boy born at 38 weeks who, six days after birth, presented with fever and severe neurological dysfunction. Human Parechovirus Type 3 (HPeV3) RNA was detected in his cerebrospinal fluid (CSF) and blood. He died five days after his initial presentation. Neuropathologic examination demonstrated multicystic encephalomalacia (ME). This case report confirms that white matter pathology is dominant in HPeV3 infection. A unique feature, of HPeV encephalomalacia is absence of CSF pleocytosis and minimal inflammation in the meninges. The findings permit comment on the pathogenesis of brain injury by this virus.

The Study to Investigate COVID-19 Infection in People Living in Ireland (SCOPI): A seroprevalence study, June to July 2020.

BackgroundRobust data on SARS-CoV-2 population seroprevalence supplement surveillance data in providing evidence for public health action.AimTo conduct a SARS-CoV-2 population-based seroprevalence survey in Ireland.MethodsUsing a cross-sectional study design, we selected population samples from individuals aged 12-69 years in counties Dublin and Sligo using the Health Service Executive Primary Care Reimbursement Service database as a sampling frame. Samples were selected with probability proportional to the general population age-sex distribution, and by simple random sampling within age-sex strata. Antibodies to SARS-CoV-2 were detected using the Abbott Architect SARS-CoV-2 IgG Assay and confirmed using the Wantai Assay. We estimated the population SARS-CoV-2 seroprevalence weighted for age, sex and geographic area.ResultsParticipation rates were 30% (913/3,043) and 44% (820/1,863) in Dublin and Sligo. Thirty-three specimens had detectable SARS-CoV-2 antibodies (1.9%). We estimated weighted seroprevalences of 3.12% (95% confidence interval (CI): 2.05-4.53) and 0.58% (95% CI: 0.18-1.38) for Dublin and Sligo, and 1.69% (95% CI: 1.13-2.41) nationally. This equates to an estimated 59,482 (95% CI: 39,772-85,176) people aged 12-69 years nationally having had infection with SARS-CoV-2, 3.0 (95% CI: 2.0-4.3) times higher than confirmed notifications. Ten participants reported a previous laboratory-confirmed SARS-CoV-2 -infection; eight of these were antibody-positive. Twenty-five antibody-positive participants had not reported previous laboratory-confirmed infection.ConclusionThe majority of people in Ireland are unlikely to have been infected with SARS-CoV-2 by June-July 2020. Non-pharmaceutical public health measures remained key pending widespread availability of vaccination, and effective treatments.

Seroepidemiological and phylogenetic characterization of neurotropic enteroviruses in Ireland, 2005-2014.

Enteroviruses (EVs) are associated with a broad spectrum of clinical presentation, including aseptic meningitis (AM), encephalitis, hand, foot and mouth disease, acute flaccid paralysis, and acute flaccid myelitis. Epidemics occur sporadically and are associated with increased cases of AM in children. The present study describes the seroepidemiological analysis of circulating EVs in Ireland from 2005 to 2014 and phylogenetic characterization of echovirus 30 (E-30), enterovirus A71 (EV-A71), and enterovirus D68 (EV-D68). EV VP1 genotyping was applied to viral isolates and clinical samples, including cerebrospinal fluid (CSF), and those isolates that remained untypeable by neutralising anti-sera. An increase in AM cases from 2010 to 2014 was associated with an E-30 genogroup variant VII and sequences clustered phylogenetically with those detected in AM outbreaks in France and Italy. EV-D68 viral RNA was not detected in CSF samples and no neurological involvement was reported. Three EV-A71 positive CSF samples were identified in patients presenting with AM. A phylogenetic analysis of respiratory-associated EV-D68 and EV-A71 cases in circulation was performed to determine baseline epidemiological data. EV-D68 segregated with clades B and B(1) and EV-A71 clustered as subgenogroup C2. The EV VP1 genotyping method was more sensitive than neutralising anti-sera methods by virus culture and importantly demonstrated concordance between EV genotypes in faecal and CSF samples which should facilitate EV screening by less invasive sampling approaches in AM presentations.

Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis.

BACKGROUND: Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes. METHODS AND FINDINGS: We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05-1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06-1.25), North America (OR = 1.19; 95% CI: 1.12-1.26), Europe (OR = 1.07; 95% CI: 1.01-1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12-1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92-1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions­a proxy for recent infection­yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs­K101E, K103N, Y181C, and G190A­accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling. CONCLUSIONS: Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen.

Hepatitis C community prevalence is over-estimated: a prospective, birth cohort study.

BACKGROUND: Hepatitis C virus infection is often asymptomatic, and many patients may be unaware they are infected. Community-based, birth cohort screening has been advocated to identify these patients. It has been estimated that 0.7-1% of individuals born between 1965 and 1985 in Ireland are infected. The cost-effectiveness of screening is critically dependent on the population prevalence. AIMS: The aim is to determine the community prevalence of hepatitis C virus infection in the birth cohort 1965-1985. METHODS: Residual serum samples from blood tests ordered by community general practitioners were anonymised and analysed for the presence of hepatitis C antibody ± antigen. Twelve large general hospitals throughout the country participated. RESULTS: A total of 14,320 samples were tested, 9347 of which were from the birth cohort 1965-1985. Seventy-two samples were positive for hepatitis C antibody of which 12 were positive for hepatitis C antigen (17%). The overall prevalence of hepatitis C antigen in the birth cohort was 0.09%. A higher prevalence (0.39%) was identified in males in two urban areas of Dublin. CONCLUSIONS: Hepatitis C virus seroprevalence was much lower than previously estimated. The proportion of antibody positive patients with hepatitis C antigen was also lower than expected suggesting the effects of treatment and/or high spontaneous viral clearance. Universal birth cohort screening is unlikely to be cost-effective. Targeted birth cohort screening in high prevalence areas could be considered.

Human polyomavirus reactivation: disease pathogenesis and treatment approaches.

JC and BK polyomaviruses were discovered over 40 years ago and have become increasingly prevalent causes of morbidity and mortality in a variety of distinct, immunocompromised patient cohorts. The recent discoveries of eight new members of the Polyomaviridae family that are capable of infecting humans suggest that there are more to be discovered and raise the possibility that they may play a more significant role in human disease than previously understood. In spite of this, there remains a dearth of specific therapeutic options for human polyomavirus infections and an incomplete understanding of the relationship between the virus and the host immune system. This review summarises the human polyomaviruses with particular emphasis on pathogenesis in those directly implicated in disease aetiology and the therapeutic options available for treatment in the immunocompromised host.

D614G SARS-CoV-2 Pseudovirus Infectivity and Binding of Spike Protein to the ACE2 Receptor Inversely Correlates with Serum SARS-CoV-2-Specific IgG Levels.

Understanding the functional characteristics of antibodies produced against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will assist in the determination of disease outcomes for this virus. In this study, the ability of antibodies to inhibit viral entry into the host cell through the interaction of the receptor binding domain of the viral spike protein and the angiotensin-converting enzyme 2 receptor on the human cell surface was investigated. The SARS-CoV-2 IgG levels in 20 SARS-CoV-2 positive patients were measured using an enzyme-linked immunosorbent assay, and the samples were further analyzed using a functional binding assay. Inhibition of viral infectivity was also measured using a pseudovirus neutralization assay against a D614G SARS-CoV-2 virus strain. A significant correlation between IgG levels and neutralizing antibody 50% inhibitory concentration (IC50) titers was observed (p < 0.05). Similarly, the IC50 titers obtained in the neutralization and binding assays were significantly correlated (p < 0.001). Varying levels of IgG and IC50 titers were observed for the SARS-CoV-2 antibody-positive samples, with one sample not showing any neutralizing capability despite detectable IgG levels. Gender comparisons showed no statistical differences in any of the assays. These results suggest that increased SARS-CoV-2 IgG levels correlate with greater protection against the entry of the virus into cells; however, further investigations in larger studies are needed to confirm the correlates of protection.

Fetal Deaths in Ireland Due to SARS-CoV-2 Placentitis Caused by SARS-CoV-2 Alpha.

CONTEXT.­: A severe third wave of COVID-19 disease affected Ireland in the first 3 months of 2021. In this wave, 1 second-trimester miscarriage and 6 stillbirths were observed in the Irish population because of placental insufficiency as a result of SARS-CoV-2 placentitis. This observation was at odds with the country's previous experience with COVID-19 disease in pregnant mothers. OBJECTIVE.­: To describe the clinical and pathologic features of these pregnancy losses. DESIGN.­: Retrospective review of clinical and pathologic data of cases of second-trimester miscarriage, stillbirth, or neonatal death identified by perinatal pathologists as being due to SARS-CoV-2 placentitis during the third wave of COVID-19 in Ireland. RESULTS.­: Clinical and pathologic data were available for review in 6 pregnancies. Sequencing or genotyping of the virus identified SARS-CoV-2 alpha (B.1.1.7) in all cases. Three of the 6 cases had maternal thrombocytopenia, and fetal growth restriction was not prominent, suggesting a rapidly progressive placental disease. CONCLUSIONS.­: The identification of SARS-CoV-2 alpha in all these cases suggests that the emergence of the variant was associated with an increased risk of fetal death due to SARS-CoV-2 placentitis when compared with the original virus. Maternal thrombocytopenia may have potential as a clinical marker of placentitis, but other inflammatory markers need investigation. Three of the 6 women had been assessed for reduced fetal movements in hospital some days before the fetal deaths actually occurred; this could suggest that there may be a window for intervention in some cases.

Acute Pulmonary Exacerbation Phenotypes in Patients with Cystic Fibrosis.

Rationale: The etiology of cystic fibrosis (CF) pulmonary exacerbations (PEx) is likely multifactorial with viral, bacterial, and non-infectious pathways contributing. Objectives: To determine whether viral infection status and CRP (C-reactive protein) can classify subphenotypes of PEx that differ in outcomes and biomarker profiles. Methods: Patients were recruited at time of admission for a PEx. Nasal swabs and sputum samples were collected and processed using the respiratory panel of the FilmArray multiplex polymerase chain reaction (PCR). Serum and plasma biomarkers were measured. PEx were classified using serum CRP and viral PCR: "pauci-inflammatory" if CRP < 5 mg/L, "non-viral with systemic inflammation" if CRP ⩾ 5 mg/L and no viral infection detected by PCR and "viral with systemic inflammation" if CRP ⩾ 5 mg/L and viral infection detected by PCR. Results: Discovery cohort (n = 59) subphenotype frequencies were 1) pauci-inflammatory (37%); 2) non-viral with systemic inflammation (41%); and 3) viral with systemic inflammation (22%). Immunoglobulin G, immunoglobulin M, interleukin-10, interleukin-13, serum calprotectin, and CRP levels differed across phenotypes. Reduction from baseline in forced expiratory volume in 1 second as percent predicted (FEV1pp) at onset of exacerbation differed between non-viral with systemic inflammation and viral with systemic inflammation (-6.73 ± 1.78 vs. -13.5 ± 2.32%; P = 0.025). Non-viral with systemic inflammation PEx had a trend toward longer duration of intravenous antibiotics versus pauci-inflammation (18.1 ± 1.17 vs. 14.8 ± 1.19 days, P = 0.057). There were no differences in percent with lung function recovery to <10% of baseline FEV1pp. Similar results were seen in local and external validation cohorts comparing a pauci-inflammatory to viral/non-viral inflammatory exacerbation phenotypes. Conclusions: Subphenotypes of CF PEx exist with differences in biomarker profile, clinical presentation, and outcomes.

Deaths associated with human adenovirus-14p1 infections, Europe, 2009-2010.

Human adenovirus (HAdV) serotype 14 is rarely identified. However, an emerging variant, termed HAdV-14p1, recently has been described in the United States in association with outbreaks of acute respiratory disease with high rates of illness and death. We retrospectively analyzed specimens confirmed positive for HAdV by immunofluorescence, virus culture, or real-time PCR during July 1, 2009-July 31, 2010, and describe 9 cases of HAdV-14p1 infection with characteristic mutations in the fiber and E1A genes that are phylogenetically indistinguishable from the viruses previously detected in the United States. Three patients died; 2 were immunocompromised, and 1 was an immunocompetent adult. We propose that surveillance should be increased for HAdV-14p1 and recommend that this virus be considered in the differential diagnosis of sudden-onset acute respiratory disease, particularly fatal infections, for which an etiology is not clear.

Genomic epidemiological analysis of SARS-CoV-2 household transmission.

Family clusters have contributed significantly to the onward spread of SARS-CoV-2. However, the dynamics of viral transmission in this setting remain incompletely understood. We describe the clinical and viral-phylogenetic characteristics of a family cluster of SARS-CoV-2 infections with a high attack rate, and explore how whole-genome sequencing (WGS) can inform outbreak investigations in this context. In this cluster, the first symptomatic case was a 22-month-old infant who developed rhinorrhoea and sneezing 2 days prior to attending a family gathering. Subsequently, seven family members in attendance at this event were diagnosed with SARS-CoV-2 infections, including the infant described. WGS revealed indistinguishable SARS-CoV-2 genomes recovered from the adults at the gathering, which were closely related genetically to B.1 lineage viruses circulating in the local community. However, a divergent viral sub-lineage was recovered from the infant and another child, each harbouring a distinguishing spike substitution (N30S). This suggested that the infant was unlikely to be the primary case, despite displaying symptoms first, and additional analysis of her nasopharyngeal swab revealed a picornavirus co-infection to account for her early symptoms. Our findings demonstrate how WGS can elucidate the transmission dynamics of SARS-CoV-2 infections within household clusters and provide useful information to support outbreak investigations. Additionally, our description of SARS-CoV-2 viral lineages and notable variants circulating in Ireland to date provides an important genomic-epidemiological baseline in the context of vaccine introduction.

Parent-administered Neurodevelopmental Follow up in Children After Picornavirus CNS Infections.

BACKGROUND: Data on the neurodevelopment of children who experienced central nervous system (CNS) infections with enteroviruses (EV) or parechoviruses (hPeV) is scarce and mostly limited to follow up of short-term outcomes. METHODS: Parents of children who presented between 2014 and 2019, underwent a lumbar puncture and whose cerebrospinal fluid was polymerase chain reaction positive for EV or hPeV, were asked to complete a care-giver-administered neurodevelopmental assessment tool (The Ages and Stages Instrument [ASQ3]). Clinical data of the infective episode were collected from patient notes. RESULTS: Of 101 children, 43 (10 hPeV+, 33 EV+) submitted ASQ3 results. Median age at assessment was 38.9 months (interquartile range, 15.4-54.8), the follow-up interval 3 years (median 37 months; interquartile range, 13.9-53.1). Age, inflammatory markers, and cerebrospinal fluid pleocytosis during the infective event were not associated with ASQ3 scores. In 23 children (17 EV+, 6 hPeV+), no neurodevelopmental concerns were reported. Two more had preexisting developmental delay and were excluded. Of the remaining, 18/41 (43.9%) reported ASQ3 scores indicating need for monitoring or professional review in at least 1 category, not differing by pathogen (EV 14/31, 45.2%; hPeV 4/10, 40%; P = 0.71). Seven children will require formal review, scoring ≥2 SD below the mean in at least 1 category (6/31 EV+, 1/10 hPeV+, P = 0.7), 3 scored ≥2 SD below the mean in more than 1 area. CONCLUSIONS: Parent-administered developmental assessment of children with a history of early picornavirus infection of the CNS identified a subgroup that requires formal neurodevelopmental review. Wider application of community-based developmental screening will complement our understanding of the impact of CNS infections in early childhood.