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Antigen lateral flow devices (LFDs) have been widely used to control SARS-CoV-2. We aimed to improve understanding of LFD performance with changes in variant infections, vaccination, viral load, and LFD use, and in the detection of infectious individuals. In this diagnostic study, paired LFD and RT-PCR test results were prospectively collected from asymptomatic and symptomatic participants in the UK between Nov 4, 2020, and March 21, 2022, to support the National Health Service (NHS) England's Test and Trace programme. The LFDs evaluated were the Innova SARS-CoV-2 Antigen Rapid Qualitative Test, the Orient Gene Rapid Covid-19 (Antigen) Self-Test, and the Acon Flowflex SARS-CoV-2 Antigen Rapid Test (Self-Testing). Test results were collected across various community testing settings, including predeployment testing sites, routine testing centres, homes, schools, universities, workplaces, targeted community testing, and from health-care workers. We used multivariable logistic regression to analyse LFD sensitivity and specificity using RT-PCR as a reference standard, adjusting for viral load, LFD manufacturer, test setting, age, sex, test assistance, symptom status, vaccination status, and SARS-CoV-2 variant. National contact tracing data from NHS Test and Trace (Jan 1, 2021, to Jan 11, 2022) were used to estimate the proportion of transmitting index patients (with ≥1 RT-PCR-positive or LFD-positive contact) potentially detectable by LFDs (specifically Innova, as the most widely used LFD) with time, accounting for index viral load, variant, and symptom status. We assessed 75 382 pairs of LFD and RT-PCR tests. Of these, 4131 (5·5%) were RT-PCR-positive. LFD sensitivity versus RT-PCR was 63·2% (95% CI 61·7–64·6) and specificity was 99·71% (95% CI 99·66–99·74). Increased viral load was independently associated with being LFD positive (adjusted odds ratio [aOR] 2·85 [95% CI 2·66–3·06] per 1 log 10 copies per mL increase; p<0·0001). There was no evidence that LFD sensitivity differed for delta (B.1.617.2) infections versus alpha (B.1.1.7) or pre-alpha (B.1.177) infections (aOR 1·00 [0·69–1·45]; p=0·99), whereas omicron (BA.1 or BA.2) infections appeared more likely to be LFD positive (aOR 1·63 [1·02–2·59]; p=0·042). Sensitivity was higher in symptomatic participants (68·7% [95% CI 66·9–70·4]) than in asymptomatic participants (52·8% [50·1–55·4]). Among 347 374 unique index patients with probable onward transmission, 78·3% (95% CI 75·3–81·2) were estimated to have been detectable with LFDs (Innova), and this proportion was mostly stable with time and for successive variants. Overall, the estimated proportion of infectious index patients detectable by the Innova LFD was lower in asymptomatic patients (57·6% [53·6–61·9]) versus symptomatic patients (79·7% [76·7–82·5]). LFDs remained able to detect most SARS-CoV-2 infections throughout vaccine roll-out and across different viral variants. LFDs can potentially detect most infections that transmit to others and reduce the risk of transmission. However, performance is lower in asymptomatic individuals than in symptomatic individuals. UK Health Security Agency, the UK Government Department of Health and Social Care, National Institute for Health Research (NIHR) Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, and the University of Oxford NIHR Biomedical Research Centre. [ABSTRACT FROM AUTHOR]

• Self-testing by LFD is only marginally less sensitive than professional LFD testing. • LFD self-testing tends to be associated with a higher void rate. • LFD exhibits consistent performance across different age groups and sex. • Sensitivity of LFDs significantly increases when symptoms are present. The advent of lateral flow devices (LFDs) for SARS-CoV-2 detection enabled widespread use of rapid self-tests during the pandemic. While self-testing using LFDs is now common, whether self-testing provides comparable performance to professional testing was a key question that remained important for pandemic planning. Three prospective multi-centre studies were conducted to compare the performance of self- and professional testing using LFDs. Participants tested themselves or were tested by trained (professional) testers at community testing sites in the UK. Corresponding qRT-PCR test results served as reference standard. The performance of Innova, Orient Gene and SureScreen LFDs by users (self) and professional testers was assessed in terms of sensitivity, specificity, and kit failure (void) rates. Impact of age, sex and symptom status was analysed using logistic regression modelling. 16,617 participants provided paired tests, of which 15,418 were included in the analysis. Self-testing with Innova, Orient Gene or SureScreen LFDs achieved sensitivities of 50 %, 53 % or 72 %, respectively, compared to qRT-PCR. Self and professional LFD testing showed no statistically different sensitivity with respect to corresponding qRT-PCR testing. Specificity was consistently equal to or higher than 99 %. Sex and age had no or only marginal impact on LFD performance while sensitivity was significantly higher for symptomatic individuals. Sensitivity of LFDs increased strongly to up to 90 % with higher levels of viral RNA measured by qRT-PCR. Our results support SARS-CoV-2 self-testing with LFDs, especially for the detection of individuals whose qRT-PCR tests showed high viral concentrations. [ABSTRACT FROM AUTHOR]

• Pooling at source does not require changes in high-throughput testing pipeline. • High concordance (> 97%) of results for pooled and individual samples. • Positive individual samples undetected in pools have very low viral burden. • Sensitivity of pooled testing over 99% for samples with > 400 viral copies/mL. • Pooling at source is a viable pandemic preparedness testing strategy. The challenges of rapid upscaling of testing capacity were a major lesson from the COVID-19 pandemic response. The need for process adjustments in high-throughput testing laboratories made sample pooling a challenging option to implement. This study aimed to evaluate whether pooling samples at source (swab pooling) was as effective as qRT-PCR testing of individuals in identifying cases of SARS-CoV-2 in real-world community testing conditions using the same high-throughput pipeline. Two cohorts of 10 (Pool10: 1,030 participants and 103 pools) and 6 (Pool6: 1,284 participants and 214 pools) samples per pool were tested for concordance, sensitivity, specificity, and Ct value differences with individual testing as reference. Swab pooling allowed unmodified application of an existing high-throughput SARS-Cov-2 testing pipeline with only marginal loss of accuracy. For Pool10, concordance was 98.1% (95% Confidence interval: 93.3–99.8%), sensitivity was 95.7% (85.5–99.5%), and specificity was 100.0% (93.6–100.0%). For Pool6, concordance was 97.2% (94.0–99.0%), sensitivity was 97.5% (93.7–99.3%), and specificity was 96.4% (87.7–99.6%). Differences of outcomes measure between pool size were not significant. Most positive individual samples, which were not detected in pools, had very low viral concentration. If only individual samples with a viral concentration > 400 copies/ml (i.e. Ct value < 30) were considered positive, the overall sensitivity of pooling increased to 99.5%. The study demonstrated high sensitivity and specificity by swab pooling and the immediate capability of high-throughput laboratories to implement this method making it an option in planning of rapid upscaling of laboratory capacity for future pandemics. [Display omitted] [ABSTRACT FROM AUTHOR]

Post-transplant lymphoproliferative disorder (PTLD) is a rare, serious complication following solid organ transplantation, with an incidence of 2.6 cases per 1000 patient years. Optimal treatment strategies and risk stratifications specific to kidney transplantation are lacking and PTLD mortality remains high. This study investigated survival and prognosis in 89 cases of PTLD presenting over 44 years at Manchester Royal Infirmary. Patient survival following diagnosis was 72% at 6 months, 67% at 1 year and 54% at 3 years. In multivariate analysis, a poorer 3 year survival was associated with acute kidney injury at diagnosis (p= 0.0001), impaired renal function (p= 0.04), early onset (p= 0.02), T cell disease (p= 0.02) and previous treatment with anti-thymocyte globulin (p= 0.04). The inclusion of graft function adds prognostic value to risk stratification and should be explored further. Strategies to improve survival should include timing and choice of immuno-chemotherapy, preparation for dialysis and aggressive surveillance for sepsis and treatment toxicity. [ABSTRACT FROM PUBLISHER]

Presents a study that describes the association of human herpes virus 6 with cases of fetal hydrops. Methods; Results; Conclusions.

Electron microscopy (EM), real-time polymerase chain reaction (PCR) and conventional PCR were used to identify viruses associated with infection in 2 transplantation patients. An autologous haematopoietic stem cell, liver and renal transplant recipient was found to be positive for simian virus 40 (SV40). Dual BK virus and SV40 infection was found in a heart and renal transplantation patient. SV40 infection can occur in immunocompromised patients. [ABSTRACT FROM AUTHOR]

• A European Network on Next-Generation Sequencing (ENNGS) has been established. • Recommendations for the implementation of viral metagenomic high-throughput sequencing (mHTS) in diagnostic laboratories are provided, focusing on the wet lab (Part I). • Recommendations for implementation and validation of the bioinformatic procedure of viral mHTS warrants separate recommendations (Part II). • In the current manuscript, practical recommendations on facility requirements, extraction of nucleic acid, viral enrichment, library preparation, controls and assay validation are provided. Metagenomic high-throughput sequencing (mHTS) is a hypothesis-free, universal pathogen detection technique for determination of the DNA/RNA sequences in a variety of sample types and infectious syndromes. mHTS is still in its early stages of translating into clinical application. To support the development, implementation and standardization of mHTS procedures for virus diagnostics, the European Society for Clinical Virology (ESCV) Network on Next-Generation Sequencing (ENNGS) has been established. The aim of ENNGS is to bring together professionals involved in mHTS for viral diagnostics to share methodologies and experiences, and to develop application recommendations. This manuscript aims to provide practical recommendations for the wet lab procedures necessary for implementation of mHTS for virus diagnostics and to give recommendations for development and validation of laboratory methods, including mHTS quality assurance, control and quality assessment protocols. [ABSTRACT FROM AUTHOR]