Prognostic value of upper respiratory tract microbes in children presenting to primary care with respiratory infections:a prospective cohort study

BACKGROUND: The association between upper respiratory tract microbial positivity and illness prognosis in children is unclear. This impedes clinical decision-making and means the utility of upper respiratory tract microbial point-of-care tests remains unknown. We investigated for relationships between pharyngeal microbes and symptom severity in children with suspected respiratory tract infection (RTI). METHODS: Baseline characteristics and pharyngeal swabs were collected from 2,296 children presenting to 58 general practices in Bristol, UK with acute cough and suspected RTI between 2011–2013. Post-consultation, parents recorded the severity of six RTI symptoms on a 0–6 scale daily for ≤28 days. We used multivariable hurdle regression, adjusting for clinical characteristics, antibiotics and other microbes, to investigate associations between respiratory microbes and mean symptom severity on days 2–4 post-presentation. RESULTS: Overall, 1,317 (57%) children with complete baseline, microbiological and symptom data were included. Baseline characteristics were similar in included participants and those lacking microbiological data. At least one virus was detected in 869 (66%) children, and at least one bacterium in 783 (60%). Compared to children with no virus detected (mean symptom severity score 1.52), adjusted mean symptom severity was 0.26 points higher in those testing positive for at least one virus (95% CI 0.15 to 0.38, p<0.001); and was also higher in those with detected Influenza B (0.44, 0.15 to 0.72, p = 0.003); RSV (0.41, 0.20 to 0.60, p<0.001); and Influenza A (0.25, -0.01 to 0.51, p = 0.059). Children positive for Enterovirus had a lower adjusted mean symptom severity (-0.24, -0.43 to -0.05, p = 0.013). Children with detected Bordetella pertussis (0.40, 0.00 to 0.79, p = 0.049) and those with detected Moraxella catarrhalis (-0.76, -1.06 to -0.45, p<0.001) respectively had higher and lower mean symptom severity compared to children without these bacteria. CONCLUSIONS: There is a potential role for upper respiratory tract microbiological point-of-care tests in determining the prognosis of childhood RTIs

Detecting SARS-CoV-2 variants with SNP genotyping.

Tracking genetic variations from positive SARS-CoV-2 samples yields crucial information about the number of variants circulating in an outbreak and the possible lines of transmission but sequencing every positive SARS-CoV-2 sample would be prohibitively costly for population-scale test and trace operations. Genotyping is a rapid, high-throughput and low-cost alternative for screening positive SARS-CoV-2 samples in many settings. We have designed a SNP identification pipeline to identify genetic variation using sequenced SARS-CoV-2 samples. Our pipeline identifies a minimal marker panel that can define distinct genotypes. To evaluate the system, we developed a genotyping panel to detect variants-identified from SARS-CoV-2 sequences surveyed between March and May 2020 and tested this on 50 stored qRT-PCR positive SARS-CoV-2 clinical samples that had been collected across the South West of the UK in April 2020. The 50 samples split into 15 distinct genotypes and there was a 61.9% probability that any two randomly chosen samples from our set of 50 would have a distinct genotype. In a high throughput laboratory, qRT-PCR positive samples pooled into 384-well plates could be screened with a marker panel at a cost of < £1.50 per sample. Our results demonstrate the usefulness of a SNP genotyping panel to provide a rapid, cost-effective, and reliable way to monitor SARS-CoV-2 variants circulating in an outbreak. Our analysis pipeline is publicly available and will allow for marker panels to be updated periodically as viral genotypes arise or disappear from circulation

Detecting SARS-CoV-2 variants with SNP genotyping.

Tracking genetic variations from positive SARS-CoV-2 samples yields crucial information about the number of variants circulating in an outbreak and the possible lines of transmission but sequencing every positive SARS-CoV-2 sample would be prohibitively costly for population-scale test and trace operations. Genotyping is a rapid, high-throughput and low-cost alternative for screening positive SARS-CoV-2 samples in many settings. We have designed a SNP identification pipeline to identify genetic variation using sequenced SARS-CoV-2 samples. Our pipeline identifies a minimal marker panel that can define distinct genotypes. To evaluate the system, we developed a genotyping panel to detect variants-identified from SARS-CoV-2 sequences surveyed between March and May 2020 and tested this on 50 stored qRT-PCR positive SARS-CoV-2 clinical samples that had been collected across the South West of the UK in April 2020. The 50 samples split into 15 distinct genotypes and there was a 61.9% probability that any two randomly chosen samples from our set of 50 would have a distinct genotype. In a high throughput laboratory, qRT-PCR positive samples pooled into 384-well plates could be screened with a marker panel at a cost of < £1.50 per sample. Our results demonstrate the usefulness of a SNP genotyping panel to provide a rapid, cost-effective, and reliable way to monitor SARS-CoV-2 variants circulating in an outbreak. Our analysis pipeline is publicly available and will allow for marker panels to be updated periodically as viral genotypes arise or disappear from circulation

Relationship between microbiology of throat swab and clinical course among primary care patients with acute cough: a prospective cohort study.

BACKGROUND: Acute lower respiratory tract infections (ALRTIs) account for most antibiotics prescribed in primary care despite lack of efficacy, partly due to clinician uncertainty about aetiology and patient concerns about illness course. Nucleic acid amplification tests could assist antibiotic targeting. METHODS: In this prospective cohort study, 645 patients presenting to primary care with acute cough and suspected ALRTI, provided throat swabs at baseline. These were tested for respiratory pathogens by real-time polymerase chain reaction and classified as having a respiratory virus, bacteria, both or neither. Three hundred fifty-four participants scored the symptoms severity daily for 1 week in a diary (0 = absent to 4 = severe problem). RESULTS: Organisms were identified in 346/645 (53.6%) participants. There were differences in the prevalence of seven symptoms between the organism groups at baseline. Those with a virus alone, and those with both virus and bacteria, had higher average severity scores of all symptoms combined during the week of follow-up than those in whom no organisms were detected [adjusted mean differences 0.204 (95% confidence interval 0.010 to 0.398) and 0.348 (0.098 to 0.598), respectively]. There were no differences in the duration of symptoms rated as moderate or severe between organism groups. CONCLUSIONS: Differences in presenting symptoms and symptoms severity can be identified between patients with viruses and bacteria identified on throat swabs. The magnitude of these differences is unlikely to influence management. Most patients had mild symptoms at 7 days regardless of aetiology, which could inform patients about likely symptom duration

Young infants exhibit robust functional antibody responses and restrained IFN-γ production to SARS-CoV-2

Severe COVID-19 appears rare in children. This is unexpected, especially in young infants, who are vulnerable to severe disease caused by other respiratory viruses. We evaluate convalescent immune responses in four infants under 3 months old with confirmed COVID-19 who presented with mild febrile illness, alongside their parents, and adult controls recovered from confirmed COVID-19. Although not statistically significant, compared to seropositive adults, infants have high serum levels of IgG and IgA to SARS-CoV-2 spike protein with corresponding functional ability to block SARS-CoV-2 cellular entry. Infants also exhibit robust saliva anti-spike IgG and IgA responses. Spike-specific IFN-γ production by infant peripheral blood mononuclear cells appears restrained, but the frequency of spike-specific IFN-γ and/or TNF-ɑ producing T cells is comparable between infants and adults. On principal component analysis, infant immune responses appear distinct from their parents. Robust functional antibody responses alongside restrained IFN-γ production may help protect infants from severe COVID-19

Increased reports of severe myocarditis associated with enterovirus infection in neonates, United Kingdom, 27 June 2022 to 26 April 2023

Enteroviruses are a common cause of seasonal childhood infections. The vast majority of enterovirus infections are mild and self-limiting, although neonates can sometimes develop severe disease. Myocarditis is a rare complication of enterovirus infection. Between June 2022 and April 2023, twenty cases of severe neonatal enteroviral myocarditis caused by coxsackie B viruses were reported in the United Kingdom. Sixteen required critical care support and two died. Enterovirus PCR on whole blood was the most sensitive diagnostic test. We describe the initial public health investigation into this cluster and aim to raise awareness among paediatricians, laboratories and public health specialists

Detecting SARS-CoV-2 variants with SNP genotyping

Tracking genetic variations from positive SARS-CoV-2 samples yields crucial information about the number of variants circulating in an outbreak and the possible lines of transmission but sequencing every positive SARS-CoV-2 sample would be prohibitively costly for population-scale test and trace operations. Genotyping is a rapid, high-throughput and low-cost alternative for screening positive SARS-CoV-2 samples in many settings. We have designed a SNP identification pipeline to identify genetic variation using sequenced SARSCoV-2 samples. Our pipeline identifies a minimal marker panel that can define distinct genotypes. To evaluate the system, we developed a genotyping panel to detect variants-identified from SARS-CoV-2 sequences surveyed between March and May 2020 and tested this on 50 stored qRT-PCR positive SARS-CoV-2 clinical samples that had been collected across the South West of the UK in April 2020. The 50 samples split into 15 distinct genotypes and there was a 61.9% probability that any two randomly chosen samples from our set of 50 would have a distinct genotype. In a high throughput laboratory, qRT-PCR positive samples pooled into 384-well plates could be screened with a marker panel at a cost of < £1.50 per sample. Our results demonstrate the usefulness of a SNP genotyping panel to provide a rapid, cost-effective, and reliable way to monitor SARS-CoV-2 variants circulating in an outbreak. Our analysis pipeline is publicly available and will allow for marker panels to be updated periodically as viral genotypes arise or disappear from circulation

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine