24 results on '"Cutino-Moguel, Teresa"'
Search Results
2. The origins of new SARS-COV-2 variants in immunocompromised individuals.
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Riddell AC and Cutino-Moguel T
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- Humans, SARS-CoV-2 genetics, Immunocompromised Host, COVID-19, HIV Infections
- Abstract
Purpose of Review: To explore the origins of new severe acute respiratory coronavirus 2 (SARS-CoV-2) variants in immunocompromised individuals and whether the emergence of novel mutations in these individuals is responsible for the development of variants of concern (VOC)., Recent Findings: Next generation sequencing of samples from chronically infected immunocompromised patients has enabled identification of VOC- defining mutations in individuals prior to the emergence of these variants worldwide. Whether these individuals are the source of variant generation is uncertain. Vaccine effectiveness in immunocompromised individuals and with respect to VOCs is also discussed., Summary: Current evidence on chronic SARS-CoV-2 infection in immunocompromised populations is reviewed including the relevance of this to the generation of novel variants. Continued viral replication in the absence of an effective immune response at an individual level or high levels of viral infection at the population level are likely to have contributed to the appearance of the main VOC., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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3. Generation of Novel Severe Acute Respiratory Syndrome Coronavirus 2 Variants on the B.1.1.7 Lineage in 3 Patients With Advanced Human Immunodeficiency Virus-1 Disease.
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Riddell AC, Kele B, Harris K, Bible J, Murphy M, Dakshina S, Storey N, Owoyemi D, Pade C, Gibbons JM, Harrington D, Alexander E, McKnight Á, and Cutino-Moguel T
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- Humans, SARS-CoV-2 genetics, HIV-1 genetics, COVID-19, Graft vs Host Disease
- Abstract
The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is of public health concern in case of vaccine escape. Described are 3 patients with advanced human immunodeficiency virus (HIV)-1 and chronic SARS-CoV-2 infection in whom there is evidence of selection and persistence of novel mutations that are associated with increased transmissibility and immune escape., Competing Interests: Potential conflicts of interest. M. M. reports an honorarium to self for a presentation for ViiV, February 2020, and for an HIV workshop for Janssen in November 2018 and support for attendance at the 17th EACS Conference, November 2019, from Gilead; registration for the EACS Conference, October 2021, from ViiV; and registration for the International AIDS Conference, July 2021, from ViiV. S. D. reports receiving support for attending the EACS Conference from ViiV (virtual conference) in October 2021. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2022
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4. Improving the accuracy of clinical interpretation of serological testing for the diagnosis of acute hepatitis a infection.
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Rycroft JA, Mullender CM, Hopkins M, and Cutino-Moguel T
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- Acute Disease, Hepatitis A Antibodies, Humans, Immunoglobulin M, Hepatitis A diagnosis
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Background: Hepatitis A (HA) remains a common infection globally that results in a self-limiting hepatitis with gastrointestinal and systemic symptoms. Direct detection of the virus in blood or stool is often not possible once symptomatic. Serological testing is frequently performed to investigate abnormal liver function tests - and interpretation of equivocal and low-level positive anti-hepatitis A virus (HAV) IgM is difficult even in the context of accurate epidemiological and clinical information., Objectives: The aim of this project was to characterise the association between low-level reactive anti-HAV IgM results and clinical disease., Study Design: Anti-HAV serology results recorded over 22 months were analysed. Equivocal and positive Architect anti-HAV IgM results were matched with available clinical and demographical data to identify confirmed and probable cases of acute HAV infection., Results: Reactive anti-HAV IgM results were recorded for 88/7661 (1.15%) samples. Using clinical and laboratory data, 35 patients were confirmed to have acute HAV infection. Acute HA was associated with a mean Architect anti-HAV IgM value of 9.4 (SD 6.8-12.0). Cases of HA had a mean peak ALT value of 1920 (SD 682-3158). All confirmed cases (35/35) of acute HAV were associated with at least one clinical indicator, with 28/31 cases (90%) having a documented jaundice. All 35 (100%) cases of acute HAV infection had anti-HAV IgM > 4.0. A diagnosis other than acute HA was identified in 7/11 (63.6%) of low-level reactive anti-HAV IgM results (clinical data unavailable for further 4/11, 36.3%). Where clinical information was available, acute HA was excluded in all 31 patients with equivocal or low-level reactive anti-HAV IgM results., Conclusions: The accuracy of reports sent out to the clinician showed room for improvement. An interpretive algorithm is proposed including a clinically significant cut-off value for anti-HAV IgM., (Copyright © 2022. Published by Elsevier B.V.)
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- 2022
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5. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Placental Infection Is Associated With Massive Perivillous Fibrin Deposition at the Maternal-Fetal Interface: A Preliminary Study.
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Kotiloglu-Karaa E, Kele B, Kulasegaran-Shylini R, Broad CE, Owoyemi D, Martin J, MacPhail G, Iliodromiti S, Riddell A, Alexander E, and Cutino-Moguel T
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- Female, Fibrin analysis, Humans, Placenta, Pregnancy, SARS-CoV-2, COVID-19, Pregnancy Complications, Infectious
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We observed an increased frequency of massive perivillous fibrin deposition (MPFD) during the second coronavirus disease 2019 (COVID-19) pandemic wave dominated by the Alpha variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MPFD associated with 100% reverse transcription polymerase chain reaction (RT-PCR) positivity for SARS-CoV-2 and detection by immunohistochemistry. The Alpha variant was identified in all placentas with MPFD that could be sequenced., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
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- 2022
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6. 2022 update on the clinical outcome of coronavirus disease 2019 in haemato-oncology patients.
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Bradwell S, Hone L, Thorneycroft K, Lambourne J, Aries JA, Davies JK, Cutino-Moguel T, and Riches JC
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- Humans, COVID-19, Hematologic Neoplasms complications, Hematologic Neoplasms therapy, Neoplasms complications, Neoplasms therapy
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- 2022
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7. Immune boosting by B.1.1.529 ( Omicron) depends on previous SARS-CoV-2 exposure.
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Reynolds CJ, Pade C, Gibbons JM, Otter AD, Lin KM, Muñoz Sandoval D, Pieper FP, Butler DK, Liu S, Joy G, Forooghi N, Treibel TA, Manisty C, Moon JC, Semper A, Brooks T, McKnight Á, Altmann DM, Boyton RJ, Abbass H, Abiodun A, Alfarih M, Alldis Z, Altmann DM, Amin OE, Andiapen M, Artico J, Augusto JB, Baca GL, Bailey SNL, Bhuva AN, Boulter A, Bowles R, Boyton RJ, Bracken OV, O'Brien B, Brooks T, Bullock N, Butler DK, Captur G, Carr O, Champion N, Chan C, Chandran A, Coleman T, Couto de Sousa J, Couto-Parada X, Cross E, Cutino-Moguel T, D'Arcangelo S, Davies RH, Douglas B, Di Genova C, Dieobi-Anene K, Diniz MO, Ellis A, Feehan K, Finlay M, Fontana M, Forooghi N, Francis S, Gibbons JM, Gillespie D, Gilroy D, Hamblin M, Harker G, Hemingway G, Hewson J, Heywood W, Hickling LM, Hicks B, Hingorani AD, Howes L, Itua I, Jardim V, Lee WJ, Jensen M, Jones J, Jones M, Joy G, Kapil V, Kelly C, Kurdi H, Lambourne J, Lin KM, Liu S, Lloyd A, Louth S, Maini MK, Mandadapu V, Manisty C, McKnight Á, Menacho K, Mfuko C, Mills K, Millward S, Mitchelmore O, Moon C, Moon J, Muñoz Sandoval D, Murray SM, Noursadeghi M, Otter A, Pade C, Palma S, Parker R, Patel K, Pawarova M, Petersen SE, Piniera B, Pieper FP, Rannigan L, Rapala A, Reynolds CJ, Richards A, Robathan M, Rosenheim J, Rowe C, Royds M, Sackville West J, Sambile G, Schmidt NM, Selman H, Semper A, Seraphim A, Simion M, Smit A, Sugimoto M, Swadling L, Taylor S, Temperton N, Thomas S, Thornton GD, Treibel TA, Tucker A, Varghese A, Veerapen J, Vijayakumar M, Warner T, Welch S, White H, Wodehouse T, Wynne L, Zahedi D, Chain B, and Moon JC
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- Animals, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, Cross Reactions, Humans, Mice, Spike Glycoprotein, Coronavirus genetics, Spike Glycoprotein, Coronavirus immunology, B-Lymphocytes immunology, BNT162 Vaccine immunology, BNT162 Vaccine therapeutic use, COVID-19 immunology, COVID-19 prevention & control, Immunization, Secondary, SARS-CoV-2 genetics, SARS-CoV-2 immunology, T-Lymphocytes immunology
- Abstract
The Omicron, or Pango lineage B.1.1.529, variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection against severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple BioNTech BNT162b2 messenger RNA-vaccinated health care workers (HCWs) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple-vaccinated individuals, but the magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCWs who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529.
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- 2022
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8. Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants.
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Reynolds CJ, Gibbons JM, Pade C, Lin KM, Sandoval DM, Pieper F, Butler DK, Liu S, Otter AD, Joy G, Menacho K, Fontana M, Smit A, Kele B, Cutino-Moguel T, Maini MK, Noursadeghi M, Brooks T, Semper A, Manisty C, Treibel TA, Moon JC, McKnight Á, Altmann DM, and Boyton RJ
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- Adult, Antibodies, Neutralizing blood, Antibodies, Neutralizing immunology, Antibodies, Viral blood, Antibodies, Viral immunology, Antigens, Viral immunology, BNT162 Vaccine administration & dosage, COVID-19 Vaccines immunology, Coronavirus Nucleocapsid Proteins immunology, Cross Protection, Female, Health Personnel, Humans, Longitudinal Studies, Male, Memory B Cells immunology, Mutation, Phosphoproteins immunology, Protein Domains, SARS-CoV-2 genetics, Spike Glycoprotein, Coronavirus chemistry, Spike Glycoprotein, Coronavirus immunology, T-Lymphocytes immunology, Vaccination, Vaccine Potency, BNT162 Vaccine immunology, COVID-19 immunology, COVID-19 virology, SARS-CoV-2 immunology
- Abstract
The impact of the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecting strain on downstream immunity to heterologous variants of concern (VOCs) is unknown. Studying a longitudinal healthcare worker cohort, we found that after three antigen exposures (infection plus two vaccine doses), S1 antibody, memory B cells, and heterologous neutralization of B.1.351, P.1, and B.1.617.2 plateaued, whereas B.1.1.7 neutralization and spike T cell responses increased. Serology using the Wuhan Hu-1 spike receptor binding domain poorly predicted neutralizing immunity against VOCs. Neutralization potency against VOCs changed with heterologous virus encounter and number of antigen exposures. Neutralization potency fell differentially depending on targeted VOCs over the 5 months from the second vaccine dose. Heterologous combinations of spike encountered during infection and vaccination shape subsequent cross-protection against VOC, with implications for future-proof next-generation vaccines.
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- 2022
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9. The Alpha variant was not associated with excess nosocomial SARS-CoV-2 infection in a multi-centre UK hospital study.
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Boshier FAT, Venturini C, Stirrup O, Guerra-Assunção JA, Alcolea-Medina A, Becket AH, Byott M, Charalampous T, Filipe ADS, Frampton D, Glaysher S, Khan T, Kulasegara-Shylini R, Kele B, Monahan IM, Mollett G, Parker M, Pelosi E, Randell P, Roy S, Taylor JF, Weller SJ, Wilson-Davies E, Wade P, Williams R, Copas AJ, Cutino-Moguel T, Freemantle N, Hayward AC, Holmes A, Hughes J, Mahungu TW, Nebbia G, Nastouli E, Partridge DG, Pope CF, Price JR, Robson SC, Saeed K, Shin GY, de Silva TI, Snell LB, Thomson EC, Witney AA, and Breuer J
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- Hospitals, Humans, SARS-CoV-2, United Kingdom epidemiology, COVID-19, Cross Infection epidemiology
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Objectives: Recently emerging SARS-CoV-2 variants have been associated with an increased rate of transmission within the community. We sought to determine whether this also resulted in increased transmission within hospitals., Methods: We collected viral sequences and epidemiological data of patients with community and healthcare associated SARS-CoV-2 infections, sampled from 16th November 2020 to 10th January 2021, from nine hospitals participating in the COG-UK HOCI study. Outbreaks were identified using ward information, lineage and pairwise genetic differences between viral sequences., Results: Mixed effects logistic regression analysis of 4184 sequences showed healthcare-acquired infections were no more likely to be identified as the Alpha variant than community acquired infections. Nosocomial outbreaks were investigated based on overlapping ward stay and SARS-CoV-2 genome sequence similarity. There was no significant difference in the number of patients involved in outbreaks caused by the Alpha variant compared to outbreaks caused by other lineages., Conclusions: We find no evidence to support it causing more nosocomial transmission than previous lineages. This suggests that the stringent infection prevention measures already in place in UK hospitals contained the spread of the Alpha variant as effectively as other less transmissible lineages, providing reassurance of their efficacy against emerging variants of concern., (Copyright © 2021. Published by Elsevier Ltd.)
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- 2021
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10. Confirmed Reinfection With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variant VOC-202012/01.
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Harrington D, Kele B, Pereira S, Couto-Parada X, Riddell A, Forbes S, Dobbie H, and Cutino-Moguel T
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- Humans, Reinfection diagnosis, SARS-CoV-2, COVID-19 diagnosis, COVID-19 virology, Reinfection virology
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- 2021
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11. Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study.
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Gupta RK, Rosenheim J, Bell LC, Chandran A, Guerra-Assuncao JA, Pollara G, Whelan M, Artico J, Joy G, Kurdi H, Altmann DM, Boyton RJ, Maini MK, McKnight A, Lambourne J, Cutino-Moguel T, Manisty C, Treibel TA, Moon JC, Chain BM, and Noursadeghi M
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- Adolescent, Adult, Biomarkers, Case-Control Studies, Female, Humans, Male, Middle Aged, Prospective Studies, SARS-CoV-2 genetics, Sensitivity and Specificity, COVID-19 diagnosis
- Abstract
Background: We hypothesised that host-response biomarkers of viral infections might contribute to early identification of individuals infected with SARS-CoV-2, which is critical to breaking the chains of transmission. We aimed to evaluate the diagnostic accuracy of existing candidate whole-blood transcriptomic signatures for viral infection to predict positivity of nasopharyngeal SARS-CoV-2 PCR testing., Methods: We did a nested case-control diagnostic accuracy study among a prospective cohort of health-care workers (aged ≥18 years) at St Bartholomew's Hospital (London, UK) undergoing weekly blood and nasopharyngeal swab sampling for whole-blood RNA sequencing and SARS-CoV-2 PCR testing, when fit to attend work. We identified candidate blood transcriptomic signatures for viral infection through a systematic literature search. We searched MEDLINE for articles published between database inception and Oct 12, 2020, using comprehensive MeSH and keyword terms for "viral infection", "transcriptome", "biomarker", and "blood". We reconstructed signature scores in blood RNA sequencing data and evaluated their diagnostic accuracy for contemporaneous SARS-CoV-2 infection, compared with the gold standard of SARS-CoV-2 PCR testing, by quantifying the area under the receiver operating characteristic curve (AUROC), sensitivities, and specificities at a standardised Z score of at least 2 based on the distribution of signature scores in test-negative controls. We used pairwise DeLong tests compared with the most discriminating signature to identify the subset of best performing biomarkers. We evaluated associations between signature expression, viral load (using PCR cycle thresholds), and symptom status visually and using Spearman rank correlation. The primary outcome was the AUROC for discriminating between samples from participants who tested negative throughout the study (test-negative controls) and samples from participants with PCR-confirmed SARS-CoV-2 infection (test-positive participants) during their first week of PCR positivity., Findings: We identified 20 candidate blood transcriptomic signatures of viral infection from 18 studies and evaluated their accuracy among 169 blood RNA samples from 96 participants over 24 weeks. Participants were recruited between March 23 and March 31, 2020. 114 samples were from 41 participants with SARS-CoV-2 infection, and 55 samples were from 55 test-negative controls. The median age of participants was 36 years (IQR 27-47) and 69 (72%) of 96 were women. Signatures had little overlap of component genes, but were mostly correlated as components of type I interferon responses. A single blood transcript for IFI27 provided the highest accuracy for discriminating between test-negative controls and test-positive individuals at the time of their first positive SARS-CoV-2 PCR result, with AUROC of 0·95 (95% CI 0·91-0·99), sensitivity 0·84 (0·70-0·93), and specificity 0·95 (0·85-0·98) at a predefined threshold (Z score >2). The transcript performed equally well in individuals with and without symptoms. Three other candidate signatures (including two to 48 transcripts) had statistically equivalent discrimination to IFI27 (AUROCs 0·91-0·95)., Interpretation: Our findings support further urgent evaluation and development of blood IFI27 transcripts as a biomarker for early phase SARS-CoV-2 infection for screening individuals at high risk of infection, such as contacts of index cases, to facilitate early case isolation and early use of antiviral treatments as they emerge., Funding: Barts Charity, Wellcome Trust, and National Institute of Health Research., Competing Interests: We declare no competing interests., (© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)
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- 2021
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12. Evaluation of 2 commercial anti-SARS-CoV-2 antibody assays in an immunocompetent and immunocompromised inpatient population with COVID-19.
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Harrington D, Azim T, Rosmarin C, Cutino-Moguel T, and Hopkins M
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- Adult, Aged, Aged, 80 and over, COVID-19 diagnosis, Female, Humans, Immunocompromised Host, Kinetics, Male, Middle Aged, SARS-CoV-2 isolation & purification, Sensitivity and Specificity, Seroconversion, Antibodies, Viral blood, COVID-19 immunology, COVID-19 Serological Testing, SARS-CoV-2 immunology
- Abstract
Introduction: During the COVID-19 pandemic, widespread introduction of SARS-CoV-2 antibody testing was introduced without a full understanding of the assays performance or the antibody kinetics following infection with SARS-CoV-2., Methods: We performed an evaluation of 2 anti-SARS-CoV-2 antibody assays with a more detailed look into the effect of immune status on antibody sensitivity., Results: Both assays demonstrated 100% specificity. The overall sensitivity of the Roche was 92.1% at ≥14 days and 94.8% at ≥21 days, and the overall sensitivity of the Abbott was 94.4% at ≥14 days and 98.2% at ≥21 days. 7/41 (17%) of patients included in this cohort were immunocompromised. Seroconversion was seen less commonly in the immunocompromised (4/7 [57.1%] seroconverted) and after excluding these patients 100% sensitivity was seen in both assays at ≥21 days., Discussion: Performance of both assays in the immunocompetent appeared excellent after 21 days postsymptom onset. Both assays are highly specific., Competing Interests: Declaration of competing interests The authors report no conflicts of interest relevant to this article., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)
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- 2021
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13. The difference in mortality between adult patients with laboratory documented influenza A and B, a single centre retrospective observational study.
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Mabayoje DA, Cutino-Moguel T, Haigh J, Wilks M, Welch CA, and Melzer M
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- Adult, Aged, Aged, 80 and over, Disease Outbreaks, Female, Hospitalization statistics & numerical data, Humans, Influenza, Human diagnosis, Influenza, Human virology, Male, Middle Aged, RNA, Viral genetics, Retrospective Studies, Seasons, United Kingdom epidemiology, Young Adult, Clinical Laboratory Techniques statistics & numerical data, Influenza A virus genetics, Influenza B virus genetics, Influenza, Human epidemiology, Influenza, Human mortality
- Abstract
Background: Seasonal influenza is an annual occurrence that leads to large community outbreaks and increased hospitalization. A number of studies have suggested that influenza A (FLUAV) is associated with increased rates of hospitalization and mortality compared with influenza B (FLUBV). This study compared demographic and clinical variables in patients diagnosed with FLUAV or FLUBV during the 2017-2018 UK Influenza season., Methods: Patient demographic and clinical information were obtained by accessing medical records of patients testing FLUAV or FLUBV positive using the Cepheid GXP. We used the χ
2 test to compare variables in patients with laboratory-confirmed FLUAV and FLUBV., Results: One hundred and twenty-seven adult patients had confirmed Influenza, 71 (55.9%) had FLUAV, and 56 (44.1%) FLUBV. There was no significant difference between severity at presentation, admission to HDU/ITU or median length of stay. The overall mortality was 6 (4.5%) and 9 (7.1%) at 7 and 30 days, respectively. There was a statistically significant difference in 7-day mortality between patients with FLUAV and FLUBV, 1 (1.4%) versus 5 (8.9%), respectively, p = .047) although this became nonsignificant at 30 days., Conclusions: With the exception of mortality, we did not observe significant differences between patients with FLUAV and FLUBV. Seven-day mortality in patients with FLUBV was significantly higher with FLUAV, although this was was not apparent at 30 days., (© 2020 Wiley Periodicals LLC.)- Published
- 2021
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14. Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose.
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Reynolds CJ, Pade C, Gibbons JM, Butler DK, Otter AD, Menacho K, Fontana M, Smit A, Sackville-West JE, Cutino-Moguel T, Maini MK, Chain B, Noursadeghi M, Brooks T, Semper A, Manisty C, Treibel TA, Moon JC, Valdes AM, McKnight Á, Altmann DM, and Boyton R
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SARS-CoV-2 vaccine rollout has coincided with the spread of variants of concern. We investigated if single dose vaccination, with or without prior infection, confers cross protective immunity to variants. We analyzed T and B cell responses after first dose vaccination with the Pfizer/BioNTech mRNA vaccine BNT162b2 in healthcare workers (HCW) followed longitudinally, with or without prior Wuhan-Hu-1 SARS-CoV-2 infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 and B.1.351. By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 and B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Single dose vaccination with BNT162b2 in the context of prior infection with a heterologous variant substantially enhances neutralizing antibody responses against variants., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)
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- 2021
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15. Disparities of SARS-CoV-2 Nucleoprotein-Specific IgG in Healthcare Workers in East London, UK.
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Choudhry N, Drysdale K, Usai C, Leighton D, Sonagara V, Buchanan R, Nijjar M, Thomas S, Hopkins M, Cutino-Moguel T, Gill US, Foster GR, and Kennedy PT
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Introduction: SARS-CoV-2 antibody detection serves as an important diagnostic marker for past SARS-CoV-2 infection and is essential to determine the spread of COVID-19, monitor potential COVID-19 long-term effects, and to evaluate possible protection from reinfection. A study was conducted across three hospital sites in a large central London NHS Trust in the UK, to evaluate the prevalence and duration of SARS-CoV-2 IgG antibody positivity in healthcare workers. Methods: A matrix equivalence study consisting of 228 participants was undertaken to evaluate the Abbott Panbio™ COVID-19 IgG/IgM rapid test device. Subsequently, 2001 evaluable healthcare workers (HCW), representing a diverse population, were enrolled in a HCW study between June and August 2020. A plasma sample from each HCW was evaluated using the Abbott Panbio™ COVID-19 IgG/IgM rapid test device, with confirmation of IgG-positive results by the Abbott Architect
TM SARS-CoV-2 IgG assay. 545 participants, of whom 399 were antibody positive at enrolment, were followed up at 3 months. Results: The Panbio™ COVID-19 IgG/IgM rapid test device demonstrated a high concordance with laboratory tests. SARS-CoV-2 antibodies were detected in 506 participants (25.3%) at enrolment, with a higher prevalence in COVID-19 frontline (28.3%) than non-frontline (19.9%) staff. At follow-up, 274/399 antibody positive participants (68.7%) retained antibodies; 4/146 participants negative at enrolment (2.7%) had seroconverted. Non-white ethnicity, older age, hypertension and COVID-19 symptoms were independent predictors of higher antibody levels (OR 1.881, 2.422-3.034, 2.128, and 1.869 respectively), based on Architect™ index quartiles; participants in the first three categories also showed a greater antibody persistence at 3 months. Conclusion: The SARS-CoV-2 anti-nucleocapsid IgG positivity rate among healthcare staff was high, declining by 31.3% during the 3-month follow-up interval. Interestingly, the IgG-positive participants with certain risk factors for severe COVID-19 illness (older age, Black or Asian Ethnicity hypertension) demonstrated greater persistence over time when compared to the IgG-positive participants without these risk factors., Competing Interests: The authors declare that this study received funding from Abbott Rapid Diagnostics. The funder had the following involvement in the study: study concept, data analysis, statistical analysis, admin/technical support, ethics and critical review of manuscript, Electronic Data Capture database development and management, statistical programming., (Copyright © 2021 Choudhry, Drysdale, Usai, Leighton, Sonagara, Buchanan, Nijjar, Thomas, Hopkins, Cutino-Moguel, Gill, Foster and Kennedy.)- Published
- 2021
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16. Delayed-onset myocarditis following COVID-19.
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Bajaj R, Sinclair HC, Patel K, Low B, Pericao A, Manisty C, Guttmann O, Zemrak F, Miller O, Longhi P, Proudfoot A, Lams B, Agarwal S, Marelli-Berg FM, Tiberi S, Cutino-Moguel T, Carr-White G, and Mohiddin SA
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- Adult, Biomarkers blood, COVID-19 diagnosis, COVID-19 immunology, COVID-19 virology, COVID-19 Nucleic Acid Testing, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Myocarditis blood, Myocarditis diagnosis, Myocarditis mortality, RNA, Viral isolation & purification, SARS-CoV-2 genetics, SARS-CoV-2 isolation & purification, Shock, Cardiogenic blood, Shock, Cardiogenic diagnosis, Shock, Cardiogenic mortality, Systemic Inflammatory Response Syndrome blood, Systemic Inflammatory Response Syndrome diagnosis, Systemic Inflammatory Response Syndrome mortality, Time Factors, Young Adult, COVID-19 complications, Myocarditis immunology, SARS-CoV-2 immunology, Shock, Cardiogenic immunology, Systemic Inflammatory Response Syndrome immunology
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- 2021
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17. Persistence of antibody response to SARS-CoV-2 in a cohort of haemodialysis patients with COVID-19.
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Forbes S, Davari M, Gnanasampanthan S, Roth N, Young G, Rajakariar R, Cove-Smith A, Yaqoob MM, Cutino-Moguel T, Mahalingasivam V, and McCafferty K
- Abstract
Background: Haemodialysis patients are extremely vulnerable to COVID-19. Their immune response after infection is unclear. We have found high seroconversion rates in this population with 95% developing antibodies. It is unclear if and how long these antibodies persist. Here we investigate this with serial antibody testing., Methods: We identified haemodialysis patients who had confirmed SARS-CoV-2 between March-May 2020 and measured monthly antibodies (IgG/IgM) in those who survived. We used a semi-quantitative cut-off index (COI) to create a qualitative result and plotted optical density (OD) over time. We used linear regression to examine the slope, as well as noting peak OD and time to peak OD. We correlated these against baseline demographics, markers of illness severity, and comorbidities., Results: 122 patients were analysed. All remained antibody positive during follow-up; for a minimum of 148 days. 71% had a positive gradient indicating increasing antibody positivity over time. We found that age (p = 0.01), duration of PCR positivity (p = 0.06) and presence of symptoms (p = 0.05) were associated with a longer time to peak OD. Immunosuppression did not alter peak OD but did lead to a non-significant increase in time to peak OD and more patients had a subsequent fall in Ab levels (p = 0.02). Diabetic patients were more likely to have a positive slope (OR 2.26)., Conclusions: These results indicate that haemodialysis patients have a robust and sustained antibody response after confirmed COVID-19 infection with no suggestion that immunosuppression weakens this response. Although unclear what protection these antibodies confer, this encouraging that haemodialysis patients should respond to vaccination., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)
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- 2021
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18. Time series analysis and mechanistic modelling of heterogeneity and sero-reversion in antibody responses to mild SARS‑CoV-2 infection.
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Manisty C, Treibel TA, Jensen M, Semper A, Joy G, Gupta RK, Cutino-Moguel T, Andiapen M, Jones J, Taylor S, Otter A, Pade C, Gibbons J, Lee J, Bacon J, Thomas S, Moon C, Jones M, Williams D, Lambourne J, Fontana M, Altmann DM, Boyton R, Maini M, McKnight A, Chain B, Noursadeghi M, and Moon JC
- Subjects
- Antibodies, Neutralizing immunology, Antibodies, Viral immunology, COVID-19 diagnosis, Health Personnel statistics & numerical data, Humans, Immunoglobulin A blood, Immunoglobulin G blood, Phosphoproteins immunology, Protein Domains immunology, Antibodies, Neutralizing blood, Antibodies, Viral blood, COVID-19 blood, Coronavirus Nucleocapsid Proteins immunology, SARS-CoV-2 immunology, Spike Glycoprotein, Coronavirus immunology
- Abstract
Background: SARS-CoV-2 serology is used to identify prior infection at individual and at population level. Extended longitudinal studies with multi-timepoint sampling to evaluate dynamic changes in antibody levels are required to identify the time horizon in which these applications of serology are valid, and to explore the longevity of protective humoral immunity., Methods: Healthcare workers were recruited to a prospective cohort study from the first SARS-CoV-2 epidemic peak in London, undergoing weekly symptom screen, viral PCR and blood sampling over 16-21 weeks. Serological analysis (n =12,990) was performed using semi-quantitative Euroimmun IgG to viral spike S1 domain and Roche total antibody to viral nucleocapsid protein (NP) assays. Comparisons were made to pseudovirus neutralizing antibody measurements., Findings: A total of 157/729 (21.5%) participants developed positive SARS-CoV-2 serology by one or other assay, of whom 31.0% were asymptomatic and there were no deaths. Peak Euroimmun anti-S1 and Roche anti-NP measurements correlated (r = 0.57, p<0.0001) but only anti-S1 measurements correlated with near-contemporary pseudovirus neutralising antibody titres (measured at 16-18 weeks, r = 0.57, p<0.0001). By 21 weeks' follow-up, 31/143 (21.7%) anti-S1 and 6/150 (4.0%) anti-NP measurements reverted to negative. Mathematical modelling revealed faster clearance of anti-S1 compared to anti-NP (median half-life of 2.5 weeks versus 4.0 weeks), earlier transition to lower levels of antibody production (median of 8 versus 13 weeks), and greater reductions in relative antibody production rate after the transition (median of 35% versus 50%)., Interpretation: Mild SARS-CoV-2 infection is associated with heterogeneous serological responses in Euroimmun anti-S1 and Roche anti-NP assays. Anti-S1 responses showed faster rates of clearance, more rapid transition from high to low level production rate and greater reduction in production rate after this transition. In mild infection, anti-S1 serology alone may underestimate incident infections. The mechanisms that underpin faster clearance and lower rates of sustained anti-S1 production may impact on the longevity of humoral immunity., Funding: Charitable donations via Barts Charity, Wellcome Trust, NIHR., Competing Interests: Declaration of Competing Interests DA and RB report consultancy fees from Oxford Immunotec, RKG reports grants from NIHR, during the conduct of the study; CM reports grants from Barts Charity during the conduct of the study; MN reports grants from Wellcome Trust, during the conduct of the study; DW reports personal fees from Barts Health NHS Trust during the conduct of the study. The authors declare no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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19. Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection.
- Author
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Reynolds CJ, Swadling L, Gibbons JM, Pade C, Jensen MP, Diniz MO, Schmidt NM, Butler DK, Amin OE, Bailey SNL, Murray SM, Pieper FP, Taylor S, Jones J, Jones M, Lee WJ, Rosenheim J, Chandran A, Joy G, Di Genova C, Temperton N, Lambourne J, Cutino-Moguel T, Andiapen M, Fontana M, Smit A, Semper A, O'Brien B, Chain B, Brooks T, Manisty C, Treibel T, Moon JC, Noursadeghi M, Altmann DM, Maini MK, McKnight Á, and Boyton RJ
- Subjects
- Antibodies, Neutralizing blood, Antibodies, Viral blood, Antibodies, Viral immunology, Case-Control Studies, Cross-Sectional Studies, Humans, SARS-CoV-2 immunology, Antibodies, Neutralizing immunology, Asymptomatic Infections, COVID-19 immunology, T-Lymphocytes immunology
- Abstract
Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection., (Copyright © 2020, American Association for the Advancement of Science.)
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- 2020
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20. Asymptomatic health-care worker screening during the COVID-19 pandemic - Authors' reply.
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Treibel TA, Manisty C, Andiapen M, Pade C, Jensen M, Fontana M, Couto-Parada X, Cutino-Moguel T, Noursadeghi M, and Moon JC
- Subjects
- Betacoronavirus, COVID-19, COVID-19 Testing, Clinical Laboratory Techniques, Humans, London, Polymerase Chain Reaction, SARS-CoV-2, Asymptomatic Diseases, Coronavirus Infections diagnosis, Health Personnel, Pandemics prevention & control, Pneumonia, Viral
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- 2020
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21. Healthcare Workers Bioresource: Study outline and baseline characteristics of a prospective healthcare worker cohort to study immune protection and pathogenesis in COVID-19.
- Author
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Augusto JB, Menacho K, Andiapen M, Bowles R, Burton M, Welch S, Bhuva AN, Seraphim A, Pade C, Joy G, Jensen M, Davies RH, Captur G, Fontana M, Montgomery H, O'Brien B, Hingorani AD, Cutino-Moguel T, McKnight Á, Abbass H, Alfarih M, Alldis Z, Baca GL, Boulter A, Bracken OV, Bullock N, Champion N, Chan C, Couto-Parada X, Dieobi-Anene K, Feehan K, Figtree G, Figtree MC, Finlay M, Forooghi N, Gibbons JM, Griffiths P, Hamblin M, Howes L, Itua I, Jones M, Jardim V, Kapil V, Jason Lee WY, Mandadapu V, Mfuko C, Mitchelmore O, Palma S, Patel K, Petersen SE, Piniera B, Raine R, Rapala A, Richards A, Sambile G, Couto de Sousa J, Sugimoto M, Thornton GD, Artico J, Zahedi D, Parker R, Robathan M, Hickling LM, Ntusi N, Semper A, Brooks T, Jones J, Tucker A, Veerapen J, Vijayakumar M, Wodehouse T, Wynne L, Treibel TA, Noursadeghi M, Manisty C, and Moon JC
- Abstract
Background : Most biomedical research has focused on sampling COVID-19 patients presenting to hospital with advanced disease, with less focus on the asymptomatic or paucisymptomatic. We established a bioresource with serial sampling of health care workers (HCWs) designed to obtain samples before and during mainly mild disease, with follow-up sampling to evaluate the quality and duration of immune memory. Methods : We conducted a prospective study on HCWs from three hospital sites in London, initially at a single centre (recruited just prior to first peak community transmission in London), but then extended to multiple sites 3 weeks later (recruitment still ongoing, target n=1,000). Asymptomatic participants attending work complete a health questionnaire, and provide a nasal swab (for SARS-CoV-2 RNA by RT-PCR tests) and blood samples (mononuclear cells, serum, plasma, RNA and DNA are biobanked) at 16 weekly study visits, and at 6 and 12 months. Results : Preliminary baseline results for the first 731 HCWs (400 single-centre, 331 multicentre extension) are presented. Mean age was 38±11 years; 67% are female, 31% nurses, 20% doctors, and 19% work in intensive care units. COVID-19-associated risk factors were: 37% black, Asian or minority ethnicities; 18% smokers; 13% obesity; 11% asthma; 7% hypertension and 2% diabetes mellitus. At baseline, 41% reported symptoms in the preceding 2 weeks. Preliminary test results from the initial cohort (n=400) are available: PCR at baseline for SARS-CoV-2 was positive in 28 of 396 (7.1%, 95% CI 4.9-10.0%) and 15 of 385 (3.9%, 2.4-6.3%) had circulating IgG antibodies. Conclusions : This COVID-19 bioresource established just before the peak of infections in the UK will provide longitudinal assessments of incident infection and immune responses in HCWs through the natural time course of disease and convalescence. The samples and data from this bioresource are available to academic collaborators by application https://covid-consortium.com/application-for-samples/., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Augusto JB et al.)
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- 2020
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22. Healthcare Workers Bioresource: Study outline and baseline characteristics of a prospective healthcare worker cohort to study immune protection and pathogenesis in COVID-19.
- Author
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Augusto JB, Menacho K, Andiapen M, Bowles R, Burton M, Welch S, Bhuva AN, Seraphim A, Pade C, Joy G, Jensen M, Davies RH, Captur G, Fontana M, Montgomery H, O'Brien B, Hingorani AD, Cutino-Moguel T, McKnight Á, Abbass H, Alfarih M, Alldis Z, Baca GL, Boulter A, Bracken OV, Bullock N, Champion N, Chan C, Couto-Parada X, Dieobi-Anene K, Feehan K, Figtree G, Figtree MC, Finlay M, Forooghi N, Gibbons JM, Griffiths P, Hamblin M, Howes L, Itua I, Jones M, Jardim V, Kapil V, Jason Lee WY, Mandadapu V, Mfuko C, Mitchelmore O, Palma S, Patel K, Petersen SE, Piniera B, Raine R, Rapala A, Richards A, Sambile G, Couto de Sousa J, Sugimoto M, Thornton GD, Artico J, Zahedi D, Parker R, Robathan M, Hickling LM, Ntusi N, Semper A, Brooks T, Jones J, Tucker A, Veerapen J, Vijayakumar M, Wodehouse T, Wynne L, Treibel TA, Noursadeghi M, Manisty C, and Moon JC
- Abstract
Background : Most biomedical research has focused on sampling COVID-19 patients presenting to hospital with advanced disease, with less focus on the asymptomatic or paucisymptomatic. We established a bioresource with serial sampling of health care workers (HCWs) designed to obtain samples before and during mainly mild disease, with follow-up sampling to evaluate the quality and duration of immune memory. Methods : We conducted a prospective observational study on HCWs from three hospital sites in London, initially at a single centre (recruited just prior to first peak community transmission in London), but then extended to multiple sites 3 weeks later (recruitment still ongoing, target n=1,000). Asymptomatic participants attending work complete a health questionnaire, and provide a nasal swab (for SARS-CoV-2 RNA by RT-PCR tests) and blood samples (mononuclear cells, serum, plasma, RNA and DNA are biobanked) at 16 weekly study visits, and at 6 and 12 months. Results : Preliminary baseline results for the first 731 HCWs (400 single-centre, 331 multicentre extension) are presented. Mean age was 38±11 years; 67% are female, 31% nurses, 20% doctors, and 19% work in intensive care units. COVID-19-associated risk factors were: 37% black, Asian or minority ethnicities; 18% smokers; 13% obesity; 11% asthma; 7% hypertension and 2% diabetes mellitus. At baseline, 41% reported symptoms in the preceding 2 weeks. Preliminary test results from the initial cohort (n=400) are available: PCR at baseline for SARS-CoV-2 was positive in 28 of 396 (7.1%, 95% CI 4.9-10.0%) and 15 of 385 (3.9%, 2.4-6.3%) had circulating IgG antibodies. Conclusions : This COVID-19 bioresource established just before the peak of infections in the UK will provide longitudinal assessments of incident infection and immune responses in HCWs through the natural time course of disease and convalescence. The samples and data from this bioresource are available to academic collaborators by application https://covid-consortium.com/application-for-samples/., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Augusto JB et al.)
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- 2020
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23. COVID-19: PCR screening of asymptomatic health-care workers at London hospital.
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Treibel TA, Manisty C, Burton M, McKnight Á, Lambourne J, Augusto JB, Couto-Parada X, Cutino-Moguel T, Noursadeghi M, and Moon JC
- Subjects
- Betacoronavirus, COVID-19, COVID-19 Testing, Hospitals, Humans, London, Nose virology, Pandemics, SARS-CoV-2, Clinical Laboratory Techniques statistics & numerical data, Coronavirus Infections diagnosis, Personnel, Hospital statistics & numerical data, Pneumonia, Viral diagnosis, Polymerase Chain Reaction
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- 2020
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24. The Role of Phylogenetics as a Tool to Predict the Spread of Resistance.
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Zhukova A, Cutino-Moguel T, Gascuel O, and Pillay D
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- Drug Resistance, Viral genetics, HIV drug effects, HIV Infections drug therapy, HIV Infections virology, Humans, Mutation genetics, Phylogeny, Anti-HIV Agents therapeutic use, HIV genetics, HIV Infections epidemiology
- Abstract
Drug resistance mutations emerge in genetic sequences of HIV through drug-selective pressure. Drug resistance can be transmitted. In this review we discuss phylogenetic methods used to study the emergence of drug resistance and the spread of resistant viruses., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2017
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