475 results found
Mosscrop L, Watber P, Elliot P, et al., 2022, Evaluation of the impact of pre-analytical conditions on sample stability for the detection of SARS-CoV-2 RNA., J Virol Methods, Vol: 309
Demand for accurate SARS-CoV-2 diagnostics is high. Most samples in the UK are collected in the community and rely on the postal service for delivery to the laboratories. The current recommendation remains that swabs should be collected in Viral Transport Media (VTM) and transported with a cold chain to the laboratory for RNA extraction and RT-qPCR. This is not always possible. We aimed to test the stability of SARS-CoV-2 RNA subjected to different pre-analytical conditions. Swabs were dipped into PBS containing cultured SARS-CoV-2 and placed in either a dry tube or a tube containing either normal saline or VTM. The tubes were then stored at different temperatures (20-50 °C) for variable periods (8 h to 5 days). Samples were tested by RT-qPCR targeting SARS-CoV-2 E gene. VTM outperformed swabs in saline and dry swabs in all conditions. Samples in VTM were stable, independent of a cold chain, for 5 days, with a maximum increase in cycle threshold (Ct) of 1.34 when held at 40 °C. Using normal saline as the transport media resulted in a loss of sensitivity (increased Ct) over time and with increasing temperature (up to 7.8 cycles compared to VTM). SARS-CoV-2 was not detected in 3/9 samples in normal saline when tested after 120 h incubation. Transportation of samples in VTM provides a high level of confidence in the results despite the potential for considerable, uncontrolled variation in temperature and longer transportation periods. False negative results may be seen after 96 h in saline and viral loads will appear lower.
Chadeau-Hyam M, Tang D, Eales O, et al., 2022, Omicron SARS-CoV-2 epidemic in England during February 2022: A series of cross-sectional community surveys, LANCET REGIONAL HEALTH-EUROPE, Vol: 21, ISSN: 2666-7762
Hakki S, Zhou J, Jonnerby J, et al., 2022, Onset and window of SARS-CoV-2 infectiousness and temporal correlation with symptom onset: a prospective, longitudinal, community cohort study., Lancet Respir Med
BACKGROUND: Knowledge of the window of SARS-CoV-2 infectiousness is crucial in developing policies to curb transmission. Mathematical modelling based on scarce empirical evidence and key assumptions has driven isolation and testing policy, but real-world data are needed. We aimed to characterise infectiousness across the full course of infection in a real-world community setting. METHODS: The Assessment of Transmission and Contagiousness of COVID-19 in Contacts (ATACCC) study was a UK prospective, longitudinal, community cohort of contacts of newly diagnosed, PCR-confirmed SARS-CoV-2 index cases. Household and non-household exposed contacts aged 5 years or older were eligible for recruitment if they could provide informed consent and agree to self-swabbing of the upper respiratory tract. The primary objective was to define the window of SARS-CoV-2 infectiousness and its temporal correlation with symptom onset. We quantified viral RNA load by RT-PCR and infectious viral shedding by enumerating cultivable virus daily across the course of infection. Participants completed a daily diary to track the emergence of symptoms. Outcomes were assessed with empirical data and a phenomenological Bayesian hierarchical model. FINDINGS: Between Sept 13, 2020, and March 31, 2021, we enrolled 393 contacts from 327 households (the SARS-CoV-2 pre-alpha and alpha variant waves); and between May 24, 2021, and Oct 28, 2021, we enrolled 345 contacts from 215 households (the delta variant wave). 173 of these 738 contacts were PCR positive for more than one timepoint, 57 of which were at the start of infection and comprised the final study population. The onset and end of infectious viral shedding were captured in 42 cases and the median duration of infectiousness was 5 (IQR 3-7) days. Although 24 (63%) of 38 cases had PCR-detectable virus before symptom onset, only seven (20%) of 35 shed infectious virus presymptomatically. Symptom onset was a median of 3 days before both peak viral RNA and
Puccioni-Sohler M, Poton AR, Cabral-Castro MJ, et al., 2022, Human T Lymphotropic Virus 1-Associated Myelopathy: Overview of Human T Cell Lymphotropic Virus-1/2 Tests and Potential Biomarkers, AIDS RESEARCH AND HUMAN RETROVIRUSES, ISSN: 0889-2229
Schnell AP, Kohrt S, Aristodemou A, et al., 2022, HDAC inhibitors Panobinostat and Romidepsin enhance tax transcription in HTLV-1-infected cell lines and freshly isolated patients' T-cells, FRONTIERS IN IMMUNOLOGY, Vol: 13, ISSN: 1664-3224
Elliott P, Eales O, Bodinier B, et al., 2022, Dynamics of a national Omicron SARS-CoV-2 epidemic during January 2022 in England, Nature Communications, Vol: 13, ISSN: 2041-1723
Rapid transmission of the SARS-CoV-2 Omicron variant has led to record-breaking case incidence rates around the world. Since May 2020, the REal-time Assessment of Community Transmission-1 (REACT-1) study tracked the spread of SARS-CoV-2 infection in England through RT-PCR of self-administered throat and nose swabs from randomly-selected participants aged 5 years and over. In January 2022, we found an overall weighted prevalence of 4.41% (n=102,174), three-fold higher than in November to December 2021; we sequenced 2,374 (99.2%) Omicron infections (19 BA.2), and only 19 (0.79%) Delta, with a growth rate advantage for BA.2 compared to BA.1 or BA.1.1. Prevalence was decreasing overall (reproduction number R=0.95, 95% credible interval [CrI], 0.93, 0.97), but increasing in children aged 5 to 17 years (R=1.13, 95% CrI, 1.09, 1.18). In England during January 2022, we observed unprecedented levels of SARS-CoV-2 infection, especially among children, driven by almost complete replacement of Delta by Omicron.
Malaba TR, Nakatudde I, Kintu K, et al., 2022, 72 weeks post-partum follow-up of dolutegravir versus efavirenz initiated in late pregnancy (DolPHIN-2): an open-label, randomised controlled study., Lancet HIV, Vol: 9, Pages: e534-e543
BACKGROUND: Late initiation of antiretrovirals in pregnancy is associated with increased risk of perinatal transmission and higher infant mortality. We report the final 72-week postpartum results for efficacy and safety of dolutegravir-based compared with efavirenz-based regimens in mothers and infants. METHODS: DolPHIN-2 was a randomised, open-label trial. Pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating antiretroviral therapy in third trimester were eligible for inclusion. Eligible women were randomly assigned (1:1) to receive either dolutegravir-based (50 mg dolutegravir, 300 mg tenofovir disoproxil fumarate, and either 200 mg emtricitabine in South Africa or 300 mg lamivudine in Uganda) or efavirenz-based (fixed dose combination 600 mg tenofovir disoproxil fumarate plus either emtricitabine in South Africa or lamivudine in Uganda) therapy. The primary efficacy outcome was the time to a viral load of less than 50 copies per mL measured at 6, 12, 24, 48, and 72 weeks postpartum with a Cox model adjusting for viral load and CD4 cell count. Safety endpoints were summarised by the number of women and infants with events. This trial is registered with ClinicalTrials.gov, NCT03249181. FINDINGS: Between Jan 23 and Aug 15, 2018, 280 women were screened for inclusion, of whom 268 (96%) women were randomly assigned: 133 (50%) to the efavirenz group and 135 (50%) to the dolutegravir group. 250 (93%; 125 [50%] in the efavirenz group and 125 [50%] in the dolutegravir group) women were included in the intention-to-treat analysis of efficacy. Median time to viral load of less than 50 copies per mL was 4·1 weeks (IQR 4·0-5·1) in the dolutegravir group compared with 12·1 weeks (10·7-13·3) in the efavirenz group (adjusted hazard ratio [HR] 1·93 [95% CI 1·5-2·5]). At 72 weeks postpartum, 116 (93%) moth
Harding D, Rosadas C, Tsoti S, et al., 2022, Refining the risk of HTLV-1-associated myelopathy in people living with HTLV-1: Identification of a HAM-like phenotype in a proportion of asymptomatic carriers, Journal of NeuroVirology, ISSN: 1355-0284
Background: Up to 3.8% of human T-lymphotropic virus type-1 (HTLV-1)-infected asymptomatic carriers (AC) eventually develop HTLV-1-associated myelopathy (HAM). HAM occurs in patients with high (>1%) HTLV proviral load (PVL). However, this cut-off includes more than 50% of ACs and therefore the risk needs to be refined. As HAM is additionally characterised by an inflammatory response to HTLV-1, markers of T cell activation (TCA), β 2 -microglobulin (β 2 M) and neuronal damage were accessed for the identification of ACs at high risk of HAM. Methods: Retrospective analysis ofcross-sectional and longitudinal routine clinical data examining differences in TCA (CD4/CD25, CD4/HLA-DR, CD8/CD25 & CD8/HLA-DR), β 2 M and neurofilament light (NfL) in plasma in ACs with high or low PVL and patients with HAM. Results: Comparison between 74 low PVL ACs, 84 high PVL ACs and 58 patients with HAM revealed a significant, stepwise, increase in TCA and β 2 M. Construction of receiver operating characteristic (ROC) curves for each of these blood tests generated a profile that correctly identifies 88% of patients with HAM along with 6% of ACs. The 10 ACs with this ‘HAM-like’ profile had increased levels of NfL in plasma and two developed myelopathy during follow-up, compared to none of the 148 without this viral-immune-phenotype. Conclusions: A viral-immuno-phenotype resembling that seen in patients with HAM identifies asymptomatic carriers who are at increased risk of developing HAM and have markers of subclinical neuronal damage.
Eales O, Martins LDO, Page AJ, et al., 2022, Dynamics of competing SARS-CoV-2 variants during the Omicron epidemic in England, Nature Communications, Vol: 13, ISSN: 2041-1723
The SARS-CoV-2 pandemic has been characterised by the regular emergence of genomic variants. With natural and vaccine-induced population immunity at high levels, evolutionary pressure favours variants better able to evade SARS-CoV-2 neutralising antibodies. The Omicron variant (first detected in November 2021) exhibited a high degree of immune evasion, leading to increased infection rates worldwide. However, estimates of the magnitude of this Omicron wave have often relied on routine testing data, which are prone to several biases. Using data from the REal-time Assessment of Community Transmission-1 (REACT-1) study, a series of cross-sectional surveys assessing prevalence of SARS-CoV-2 infection in England, we estimated the dynamics of England’s Omicron wave (from 9 September 2021 to 1 March 2022). We estimate an initial peak in national Omicron prevalence of 6.89% (5.34%, 10.61%) during January 2022, followed by a resurgence in SARS-CoV-2 infections as the more transmissible Omicron sub-lineage, BA.2 replaced BA.1 and BA.1.1. Assuming the emergence of further distinct variants, intermittent epidemics of similar magnitudes may become the ‘new normal’.
Eales O, Wang H, Bodinier B, et al., 2022, SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2, BMC Infectious Diseases, Vol: 22, ISSN: 1471-2334
Background: Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape. Methods: We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September - 27 September 2021) and 15 (19 October - 5 November 2021) lineages were determined for 1322 positive individuals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month.Results: We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI, 8%-23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England.Conclusions: As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals.
Taylor G, Cook L, 2022, A new paradigm for the management in ATL, British Journal of Haematology, ISSN: 0007-1048
Eales O, de Oliveira Martins L, Page A, et al., 2022, Dynamics and scale of the SARS-CoV-2 variant Omicron epidemic in England, Nature Communications, ISSN: 2041-1723
Houston H, Hakki S, Pillay TD, et al., 2022, Broadening symptom criteria improves early case identification in SARS-CoV-2 contacts, EUROPEAN RESPIRATORY JOURNAL, Vol: 60, ISSN: 0903-1936
Barr R, Drysdale S, Boullier M, et al., 2022, A review of the prevention of mother-to-child transmission of human T-cell lymphotropic virus type 1 (HTLV-1) with a proposed management algorithm, Frontiers in Medicine, Vol: 9, Pages: 1-7, ISSN: 2296-858X
Human T cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus that is endemic in a number of regions across the world. There are an estimated 5-10 million people infected worldwide. Japan is currently the only country with a national antenatal screening programme in place. HTLV-1 is primarily transmitted sexually in adulthood, however it can be transmitted from mother-to-child perinatally. This can occur transplacentally, during the birth process or via breastmilk. If HTLV-1 is transmitted perinatally then the lifetime risk of adult T cell leukaemia/lymphoma rises from 5% to 20%, therefore prevention of mother-to-child transmission of HTLV-1 is a public health priority. There are reliable immunological and molecular tests available for HTLV-1 diagnosis during pregnancy and screening should be considered on a country by country basis. Further research on best management is needed particularly for pregnancies in women with high HTLV-1 viral load. A first step would be to establish an international registry of cases and to monitor outcomes for neonates and mothers. We have summarised key risk factors for mother-to-child transmission of HTLV-1 and subsequently propose a pragmatic guideline for management of mothers and infants in pregnancy and the perinatal period to reduce the risk of transmission. This is clinically relevant in order to reduce mother-to-child transmission of HTLV-1 and it’s complications.
Chadeau M, Tang D, Eales O, et al., 2022, Cross-sectional community surveys to monitor the Omicron SARS-CoV-2 epidemic in England during February 2022, The Lancet Regional Health Europe, ISSN: 2666-7762
Background: The Omicron wave of COVID-19 in England peaked in January 2022 resulting from the rapid transmission of the Omicron BA.1 variant. We investigate the spread and dynamics of the SARS-CoV-2 epidemic in the population of England during February 2022, by region, age and main SARS-CoV-2 sub-lineage.Methods: In the REal-time Assessment of Community Transmission-1 (REACT-1) study we obtained data from a random sample of 94,950 participants with valid throat and nose swab results by RT-PCR during round 18 (8 February to 1 March 2022).Findings: We estimated a weighted mean SARS-CoV-2 prevalence of 2.88% (95% credible interval [CrI] 2.76–3.00), with a within-round effective reproduction number (R) overall of 0.94 (0·91–0.96). While within-round weighted prevalence fell among children (aged 5 to 17 years) and adults aged 18 to 54 years, we observed a level or increasing weighted prevalence among those aged 55 years and older with an R of 1.04 (1.00–1.09). Among 1,616 positive samples with sublineages determined, one (0.1% [0.0–0.3]) corresponded to XE BA.1/BA.2 recombinant and the remainder were Omicron: N=1,047, 64.8% (62.4–67.2) were BA.1; N=568, 35.2% (32.8–37.6) were BA.2. We estimated an R additive advantage for BA.2 (vs BA.1) of 0.38 (0.34–0.41). The highest proportion of BA.2 among positives was found in London. Interpretation: In February 2022, infection prevalence in England remained high with level or increasing rates of infection in older people and an uptick in hospitalisations. Ongoing surveillance of both survey and hospitalisations data is required.Funding Department of Health and Social Care, England.
Chadeau M, Eales O, Bodinier B, et al., 2022, Breakthrough SARS-CoV-2 infections in double and triple vaccinated adults and single dose vaccine effectiveness among children in Autumn 2021 in England: REACT-1 study, EClinicalMedicine, Vol: 48, Pages: 1-14, ISSN: 2589-5370
Background: Prevalence of SARS-CoV-2 infection with Delta variant was increasing in England in late summer 2021 among children aged 5 to 17 years, and adults who had received two vaccine doses. In September 2021, a third (booster) dose was offered to vaccinated adults aged 50 years and over, vulnerable adults and healthcare/care-home workers, and a single vaccine dose already offered to 16 and 17 year-olds was extended to children aged 12 to 15 years. Methods: SARS-CoV-2 community prevalence in England was available from self-administered throat and nose swabs using reverse transcriptase polymerase chain reaction (RT-PCR) in round 13 (24 June to 12 July 2021, N= 98,233), round 14 (9 to 27 September 2021, N = 100,527) and round 15 (19 October to 5 November 2021, N = 100,112) from the REACT-1 study randomised community surveys. Linking to National Health Service (NHS) vaccination data for consenting participants, we estimated vaccine effectiveness in children aged 12 to 17 years and compared swab-positivity rates in adults who received a third dose with those who received two doses. Findings: Weighted SARS-CoV-2 prevalence was 1.57% (1.48%, 1.66%) in round 15 compared with 0.83% (0.76%, 0.89%) in round 14, and the previously observed link between infections and hospitalisations and deaths had weakened. Vaccine effectiveness against infection in children aged 12 to 17 years was estimated (round 15) at 64.0% (50.9%, 70.6%) and 67.7% (53.8%, 77.5%) for symptomatic infections. Adults who received a third vaccine dose were less likely to test positive compared to those who received two doses, with adjusted odds ratio of 0.36 (0.25, 0.53). Interpretation: Vaccination of children aged 12 to 17 years and third (booster) doses in adults were effective at reducing infection risk. High rates of vaccination, including booster doses, are a key part of the strategy to reduce infection rates in the community.
Rosadas C, Assone T, Sereno L, et al., 2022, "We need to translate research into meaningful HTLV health policies and programs": webinar HTLV World Day 2021., Frontiers in Public Health, Vol: 10, Pages: 1-5, ISSN: 2296-2565
Bradshaw D, Taylor GP, 2022, HTLV-1 transmission and HIV pre-exposure prophylaxis: a scoping review, Frontiers of Medicine, Vol: 9, ISSN: 1673-7342
HIV pre-exposure prophylaxis (HIV-PrEP) is effective in reducing the likelihood of HIV acquisition in HIV-negative people at high risk of exposure. Guidelines recommend testing for sexually transmitted infections (STIs) before starting, and periodically on PrEP, including bacterial infections, HIV, hepatitis C virus, and, for those who are non-immune, hepatitis B virus. Diagnosed infections can be promptly treated to reduce onward transmission. HTLV-1 is not mentioned; however, it is predominantly sexually transmitted, causes adult T-cell leukaemia/lymphoma (ATL) or myelopathy in 10% of those infected, and is associated with an increased risk of death in those without any classically HTLV-associated condition. The 2021 WHO Technical Report on HTLV-1 called for the strengthening of global public health measures against its spread. In this scoping review, we, therefore, (1) discuss the epidemiological context of HIV-PrEP and HTLV-1 transmission; (2) present current knowledge of antiretrovirals in relation to HTLV-1 transmission prevention, including nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and integrase strand transfer inhibitors (INSTIs); and (3) identify knowledge gaps where data are urgently required to inform global public health measures to protect HIV-PrEP users from HTLV-1 acquisition. We suggest that systematic seroprevalence studies among PrEP-using groups, including men who have sex with men (MSM), people who inject drugs (PWIDs), and female sex workers (FSWs), are needed. Further data are required to evaluate antiretroviral efficacy in preventing HTLV-1 transmission from in vitro studies, animal models, and clinical cohorts. PrEP delivery programmes should consider prioritizing the long-acting injectable INSTI, cabotegravir, in HTLV-1 endemic settings.
Cordery R, Reeves L, Zhou J, et al., 2022, Transmission of SARS-CoV-2 by children to contacts in schools and households: a prospective cohort and environmental sampling study in London, The Lancet Microbe, ISSN: 2666-5247
Background: Assessing transmission of SARS-CoV-2 by children in schools is of critical importance to inform public health action. We assessed frequency of acquisition of SARS-CoV-2 by contacts of pupils with COVID-19 in schools and households, and quantified SARS-CoV-2 shed into air and onto fomites in both settings.Methods: Incidents involving exposure to at least one index pupil with COVID-19 in 8 schools were identified between October 2020-July 2021 (prevailing variants, original, alpha and delta). Weekly PCR testing for SARS-CoV-2 was undertaken on immediate classroom contacts (the “bubble”), non-bubble school contacts, and household contacts of index pupils, supported by genome sequencing, and on surface and air samples from school and home environments.Findings: Secondary transmission of SARS-CoV-2 was not detected in 28 bubble contacts, representing 10 bubble classes (participation rate 8.8%, IQR 4.6-15.3%). Across 8 non-bubble classes, 3/62 pupils tested positive but these were unrelated to the original index case (participation rate 22.5%, IQR 9.7-32.3%). All three were asymptomatic and tested positive in one setting on the same day. In contrast, secondary transmission to previously-negative household contacts from infected index pupils was 17.1% (6/35) rising to 27.7% (13/47) when considering all potentialinfections in household contacts. Environmental contamination with SARS-CoV-2 was rare in schools; fomite SARS-CoV-2 was identified in 4/189 (2.1%) samples in bubble classrooms, 2/127 (1.6%) samples in non-bubble classrooms, and 5/130 (3.8%) samples in washrooms. This contrasted with fomites in households, where SARS-CoV-2 was identified in 60/248 (24.2%) bedroom samples, 66/241 (27.4%) communal room samples, and 21/188 (11.2%) bathroom samples. Air sampling identified SARS-CoV-2 RNA in just 1/68 (1.5%) of school air samples, compared with 21/85 (24.7%) of air samples taken in homes.Interpretation: There was no evidence of large scale SARS-Co
Vallinoto ACR, Rosadas C, Machado LFA, et al., 2022, HTLV: it is time to reach a consensus on its nomenclature., Frontiers in Microbiology, Vol: 13, Pages: 1-4, ISSN: 1664-302X
Elliott P, Eales O, Steyn N, et al., 2022, Twin peaks: the Omicron SARS-CoV-2 BA.1 and BA.2 epidemics in England
BACKGROUNDRapid transmission of the SARS-CoV-2 Omicron variant has led to record-breaking incidencerates around the world. Sub-lineages have been detected in many countries with BA.1replacing Delta and BA.2 replacing BA.1.METHODSThe REal-time Assessment of Community Transmission-1 (REACT-1) study has trackedSARS-CoV-2 infection in England using RT-PCR results from self-administered throat and noseswabs from randomly-selected participants aged 5+ years. Rounds of data collection wereapproximately monthly from May 2020 to March 2022.RESULTSIn March 2022, weighted prevalence was 6.37% (N=109,181), more than twice that inFebruary 2022 following an initial Omicron peak in January 2022. Of the lineagesdetermined by viral genome sequencing, 3,382 (99.97%) were Omicron, including 346(10.2%) BA.1, 3035 (89.7%) BA.2 and one (0.03%) BA.3 sub-lineage; the remainder (1, 0.03%)was Delta AY.4. The BA.2 Omicron sub-lineage had a growth rate advantage (compared toBA.1 and sub-lineages) of 0.11 (95% credible interval [CrI], 0.10, 0.11). Prevalence wasincreasing overall (reproduction number R=1.07, 95% CrI, 1.06, 1.09), with the greatestincrease in those aged 55+ years (R=1.12, 95% CrI, 1.09, 1.14) among whom estimatedprevalence on March 31, 2022 was 8.31%, nearly 20-fold the median prevalence since May1, 2020.CONCLUSIONSWe observed unprecedented levels of SARS-CoV-2 infection in England in March 2022 and analmost complete replacement of Omicron BA.1 by BA.2. The high and increasing prevalencein older adults may increase hospitalizations and deaths despite high levels of vaccination.(Funded by the Department of Health and Social Care in England.)
Mentzer AJ, Brenner N, Allen N, et al., 2022, Identification of host-pathogen-disease relationships using a scalable multiplex serology platform in UK Biobank., Nat Commun, Vol: 13
Certain infectious agents are recognised causes of cancer and other chronic diseases. To understand the pathological mechanisms underlying such relationships, here we design a Multiplex Serology platform to measure quantitative antibody responses against 45 antigens from 20 infectious agents including human herpes, hepatitis, polyoma, papilloma, and retroviruses, as well as Chlamydia trachomatis, Helicobacter pylori and Toxoplasma gondii, then assayed a random subset of 9695 UK Biobank participants. We find seroprevalence estimates consistent with those expected from prior literature and confirm multiple associations of antibody responses with sociodemographic characteristics (e.g., lifetime sexual partners with C. trachomatis), HLA genetic variants (rs6927022 with Epstein-Barr virus (EBV) EBNA1 antibodies) and disease outcomes (human papillomavirus-16 seropositivity with cervical intraepithelial neoplasia, and EBV responses with multiple sclerosis). Our accessible dataset is one of the largest incorporating diverse infectious agents in a prospective UK cohort offering opportunities to improve our understanding of host-pathogen-disease relationships with significant clinical and public health implications.
Khawaja A, Maughan R, Paschalaki K, et al., 2022, People living with HIV have higher frequencies of circulating endothelial colony-forming cells: steps towards patient-specific models to evaluate cardiovascular risk, Publisher: WILEY, Pages: 39-39, ISSN: 1464-2662
Chadeau-Hyam M, Wang H, Eales O, et al., 2022, SARS-CoV-2 infection and vaccine effectiveness in England (REACT-1): a series of cross-sectional random community surveys, The Lancet Respiratory Medicine, Vol: 10, Pages: 355-366, ISSN: 2213-2600
SummaryBackground England has experienced a third wave of the COVID-19 epidemic since the end of May, 2021, coincidingwith the rapid spread of the delta (B.1.617.2) variant, despite high levels of vaccination among adults. Vaccinationrates (single dose) in England are lower among children aged 16–17 years and 12–15 years, whose vaccination inEngland commenced in August and September, 2021, respectively. We aimed to analyse the underlying dynamicsdriving patterns in SARS-CoV-2 prevalence during September, 2021, in England.Methods The REal-time Assessment of Community Transmission-1 (REACT-1) study, which commenced datacollection in May, 2020, involves a series of random cross-sectional surveys in the general population of Englandaged 5 years and older. Using RT-PCR swab positivity data from 100 527 participants with valid throat and noseswabs in round 14 of REACT-1 (Sept 9–27, 2021), we estimated community-based prevalence of SARS-CoV-2 andvaccine effectiveness against infection by combining round 14 data with data from round 13 (June 24 to July 12, 2021;n=172 862).Findings During September, 2021, we estimated a mean RT-PCR positivity rate of 0·83% (95% CrI 0·76–0·89), with areproduction number (R) overall of 1·03 (95% CrI 0·94–1·14). Among the 475 (62·2%) of 764 sequenced positiveswabs, all were of the delta variant; 22 (4·63%; 95% CI 3·07–6·91) included the Tyr145His mutation in the spikeprotein associated with the AY.4 sublineage, and there was one Glu484Lys mutation. Age, region, key worker status,and household size jointly contributed to the risk of swab positivity. The highest weighted prevalence was observedamong children aged 5–12 years, at 2·32% (95% CrI 1·96–2·73) and those aged 13–17 years, at 2·55% (2·11–3·08).The SARS-CoV-2 epidemic grew in those aged 5–11 years, with an R of 1&m
Chadeau-Hyam M, Tang D, Eales O, et al., 2022, The Omicron SARS-CoV-2 epidemic in England during February 2022
Background The third wave of COVID-19 in England peaked in January 2022 resulting fromthe rapid transmission of the Omicron variant. However, rates of hospitalisations and deathswere substantially lower than in the first and second wavesMethods In the REal-time Assessment of Community Transmission-1 (REACT-1) study weobtained data from a random sample of 94,950 participants with valid throat and nose swabresults by RT-PCR during round 18 (8 February to 1 March 2022).Findings We estimated a weighted mean SARS-CoV-2 prevalence of 2.88% (95% credibleinterval [CrI] 2.76–3.00), with a within-round reproduction number (R) overall of 0.94 (0·91–0.96). While within-round weighted prevalence fell among children (aged 5 to 17 years) andadults aged 18 to 54 years, we observed a level or increasing weighted prevalence amongthose aged 55 years and older with an R of 1.04 (1.00–1.09). Among 1,195 positive sampleswith sublineages determined, only one (0.1% [0.0–0.5]) corresponded to AY.39 Deltasublineage and the remainder were Omicron: N=390, 32.7% (30.0–35.4) were BA.1; N=473,39.6% (36.8–42.5) were BA.1.1; and N=331, 27.7% (25.2–30.4) were BA.2. We estimated anR additive advantage for BA.2 (vs BA.1 or BA.1.1) of 0.40 (0.36–0.43). The highest proportionof BA.2 among positives was found in London.Interpretation In February 2022, infection prevalence in England remained high with levelor increasing rates of infection in older people and an uptick in hospitalisations. Ongoingsurveillance of both survey and hospitalisations data is required.Funding Department of Health and Social Care, England.
Aggarwal D, Page AJ, Schaefer U, et al., 2022, Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission, Nature Communications, Vol: 13, ISSN: 2041-1723
Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16–20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement.
Ye L, Taylor G, Rosadas de Oliveira C, 2022, Human T-cell lymphotropic virus type 1 and Strongyloides stercoralis co-infection: a systematic review and meta-analysis, Frontiers in Medicine, Vol: 9, Pages: 1-9, ISSN: 2296-858X
Background: The distribution of human T cell lymphotropic virus type 1 (HTLV-1) overlaps with that of Strongyloides stercoralis. S stercoralis infection has been reported to be impacted by co-infection with HTLV-1. Disseminated strongyloidiasis and hyperinfection syndrome, which are15commonly fatal, are observed in HTLV-1 co-infected patients. Reduced efficacy of anti-strongyloidiasis treatment in HTLV-1 carriers has been reported. The aim of this meta-analysis and systematic review is to better understand the association between HTLV-1 and S. stercoralis infection. Methods: PubMed, Embase, MEDLINE, Global Health, Healthcare Management Information Consortium databases were searched. Studies regarding the prevalence of S. stercoralis, those evaluating the frequency of mild or severe strongyloidiasis, and treatment response in people living with and without HTLV-1 infection were included. Data were extracted and odds ratios were calculated. Random-effect meta-analysis was used to assess the pooled OR and 95% confidence intervals. Results: Fourteen studies were included after full-text reviewing of which seven described the prevalence of S. stercoralis and HTLV-1. The odds of S. stercoralis infection were higher inHTLV-1 carriers when compared with HTLV-1 seronegative subjects (OR 3.2 95%CI 1.7-6.2). A strong association was found between severe strongyloidiasis and HTLV-1 infection (OR 59.9, 95%CI 18.1-198). Co-infection with HTLV-1 was associated with a higher rate of strongyloidiasistreatment failure (OR 5.05, 95%CI 2.5-10.1). Conclusion: S. stercoralis infection is more prevalent in people living with HTLV-1. Co-infected patients are more likely to develop severe presentation and to fail treatment. Screening for HTLV-1 and Strongyloides sp. should be routine when either isdiagnosed.
Aggarwal D, Warne B, Jahun AS, et al., 2022, Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission, Nat Commun, Vol: 13
Understanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.
Elliott P, Bodinier B, Eales O, et al., 2022, Rapid increase in Omicron infections in England during December 2021: REACT-1 study., Science, Vol: 375, Pages: eabn8347-eabn8347, ISSN: 0036-8075
The unprecedented rise in SARS-CoV-2 infections during December 2021 was concurrent with rapid spread of the Omicron variant in England and globally. We analyzed prevalence of SARS-CoV-2 and its dynamics in England from end November to mid-December 2021 among almost 100,000 participants from the REACT-1 study. Prevalence was high with rapid growth nationally and particularly in London during December 2021, and an increasing proportion of infections due to Omicron. We observed large falls in swab positivity among mostly vaccinated older children (12-17 years) compared with unvaccinated younger children (5-11 years), and in adults who received a third (booster) vaccine dose vs. two doses. Our results reinforce the importance of vaccination and booster campaigns, although additional measures have been needed to control the rapid growth of the Omicron variant.
Khan M, Rosadas C, Katsanovskaja K, et al., 2022, Simple, sensitive, specific self-sampling assay secures SARS-CoV-2 antibody signals in sero-prevalence and post-vaccine studies, Scientific Reports, Vol: 12, ISSN: 2045-2322
At-home sampling is key to large scale seroprevalence studies. Dried blood spot (DBS) self-sampling removes the need for medical personnel for specimen collection but facilitates specimen referral to an appropriately accredited laboratory for accurate sample analysis. To establish a highly sensitive and specific antibody assay that would facilitate self-sampling for prevalence and vaccine-response studies. Paired sera and DBS eluates collected from 439 sero-positive, 382 sero-negative individuals and DBS from 34 vaccine recipients were assayed by capture ELISAs for IgG and IgM antibody to SARS-CoV-2. IgG and IgM combined on DBS eluates achieved a diagnostic sensitivity of 97.9% (95%CI 96.6 to 99.3) and a specificity of 99.2% (95% CI 98.4 to 100) compared to serum, displaying limits of detection equivalent to 23 and 10 WHO IU/ml, respectively. A strong correlation (r = 0.81) was observed between serum and DBS reactivities. Reactivity remained stable with samples deliberately rendered inadequate, (p = 0.234) and when samples were accidentally damaged or 'invalid'. All vaccine recipients were sero-positive. This assay provides a secure method for self-sampling by DBS with a sensitivity comparable to serum. The feasibility of DBS testing in sero-prevalence studies and in monitoring post-vaccine responses was confirmed, offering a robust and reliable tool for serological monitoring at a population level.
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