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Article ; Online: Protocol for the challenge non-typhoidal

Smith, Christopher / Smith, Emma / Rydlova, Anna / Varro, Robert / Hinton, Jay C D / Gordon, Melita A / Choy, Robert K M / Liu, Xinxue / Pollard, Andrew J / Chiu, Christopher / Cooke, Graham S / Gibani, Malick M

BMJ open

2024 Volume 14, Issue 1, Page(s) e076477

Abstract: Introduction: Invasive non-typhoidal : Methods and analysis: This double-blind, safety and dose-escalation study will randomise 40-80 healthy UK participants aged 18-50 to receive oral challenge with one of two strains of : Ethics and dissemination! ...

Abstract	Introduction: Invasive non-typhoidal Methods and analysis: This double-blind, safety and dose-escalation study will randomise 40-80 healthy UK participants aged 18-50 to receive oral challenge with one of two strains of Ethics and dissemination: Ethical approval has been obtained from the NHS Health Research Authority (London-Fulham Research Ethics Committee 21/PR/0051; IRAS Project ID 301659). The study findings will be disseminated in international peer-reviewed journals and presented at national/international stakeholder meetings. Study outcome summaries will be provided to both funders and participants. Trial registration number: NCT05870150.
MeSH term(s)	Humans ; Singing ; Salmonella ; Typhoid Fever ; London ; Vaccines ; Randomized Controlled Trials as Topic
Chemical Substances	Vaccines
Language	English
Publishing date	2024-01-10
Publishing country	England
Document type	Clinical Trial Protocol ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2023-076477
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Article ; Online: Rapid emergence of transmissible SARS-CoV-2 variants in mild community cases.

Microbiology spectrum

2024 Volume 12, Issue 4, Page(s) e0363423

MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2/genetics
Language	English
Publishing date	2024-03-14
Publishing country	United States
Document type	Letter
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.03634-23
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Article ; Online: Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts.

Nature communications

2022 Volume 13, Issue 1, Page(s) 80

Abstract: Cross-reactive immune responses to SARS-CoV-2 have been observed in pre-pandemic cohorts and proposed to contribute to host protection. Here we assess 52 COVID-19 household contacts to capture immune responses at the earliest timepoints after SARS-CoV-2 ... ...

Abstract	Cross-reactive immune responses to SARS-CoV-2 have been observed in pre-pandemic cohorts and proposed to contribute to host protection. Here we assess 52 COVID-19 household contacts to capture immune responses at the earliest timepoints after SARS-CoV-2 exposure. Using a dual cytokine FLISpot assay on peripheral blood mononuclear cells, we enumerate the frequency of T cells specific for spike, nucleocapsid, membrane, envelope and ORF1 SARS-CoV-2 epitopes that cross-react with human endemic coronaviruses. We observe higher frequencies of cross-reactive (p = 0.0139), and nucleocapsid-specific (p = 0.0355) IL-2-secreting memory T cells in contacts who remained PCR-negative despite exposure (n = 26), when compared with those who convert to PCR-positive (n = 26); no significant difference in the frequency of responses to spike is observed, hinting at a limited protective function of spike-cross-reactive T cells. Our results are thus consistent with pre-existing non-spike cross-reactive memory T cells protecting SARS-CoV-2-naïve contacts from infection, thereby supporting the inclusion of non-spike antigens in second-generation vaccines.
MeSH term(s)	Adult ; Antibodies, Viral/immunology ; COVID-19/epidemiology ; COVID-19/immunology ; COVID-19/virology ; Contact Tracing/methods ; Coronavirus/immunology ; Coronavirus/physiology ; Cross Reactions/immunology ; Epitopes, T-Lymphocyte/immunology ; Female ; Humans ; Male ; Memory T Cells/immunology ; Memory T Cells/metabolism ; Memory T Cells/virology ; Middle Aged ; Pandemics/prevention & control ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; SARS-CoV-2/physiology ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/immunology ; Spike Glycoprotein, Coronavirus/metabolism ; Viral Proteins/genetics ; Viral Proteins/immunology ; Viral Proteins/metabolism ; Young Adult
Chemical Substances	Antibodies, Viral ; Epitopes, T-Lymphocyte ; Spike Glycoprotein, Coronavirus ; Viral Proteins ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-01-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-27674-x
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Article ; Online: Broadening symptom criteria improves early case identification in SARS-CoV-2 contacts.

Houston, Hamish / Hakki, Seran / Pillay, Timesh D / Madon, Kieran / Derqui-Fernandez, Nieves / Koycheva, Aleksandra / Singanayagam, Anika / Fenn, Joe / Kundu, Rhia / Conibear, Emily / Varro, Robert / Cutajar, Jessica / Quinn, Valerie / Wang, Lulu / Narean, Janakan S / Tolosa-Wright, Mica R / Barnett, Jack / Kon, Onn Min / Tedder, Richard /

Taylor, Graham / Zambon, Maria / Ferguson, Neil / Dunning, Jake / Deeks, Jonathan J / Lalvani, Ajit

The European respiratory journal

2022 Volume 60, Issue 1

Abstract: Background: The success of case isolation and contact tracing for the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission depends on the accuracy and speed of case identification. We assessed whether inclusion of ... ...

Abstract	Background: The success of case isolation and contact tracing for the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission depends on the accuracy and speed of case identification. We assessed whether inclusion of additional symptoms alongside three canonical symptoms (CS), Methods: Two prospective longitudinal London (UK)-based cohorts of community SARS-CoV-2 contacts, recruited within 5 days of exposure, provided independent training and test datasets. Infected and uninfected contacts completed daily symptom diaries from the earliest possible time-points. Diagnostic information gained by adding symptoms to the CS was quantified using likelihood ratios and area under the receiver operating characteristic curve. Improvements in sensitivity and time to detection were compared with penalties in terms of specificity and number needed to test. Results: Of 529 contacts within two cohorts, 164 (31%) developed PCR-confirmed infection and 365 (69%) remained uninfected. In the training dataset (n=168), 29% of infected contacts did not report the CS. Four symptoms (sore throat, muscle aches, headache and appetite loss) were identified as early-predictors (EP) which added diagnostic value to the CS. The broadened symptom criterion "≥1 of the CS, or ≥2 of the EP" identified PCR-positive contacts in the test dataset on average 2 days earlier after exposure (p=0.07) than "≥1 of the CS", with only modest reduction in specificity (5.7%). Conclusions: Broadening symptom criteria to include individuals with at least two of muscle aches, headache, appetite loss and sore throat identifies more infections and reduces time to detection, providing greater opportunities to prevent SARS-CoV-2 transmission.
MeSH term(s)	COVID-19/diagnosis ; Headache/diagnosis ; Humans ; Pain ; Pharyngitis/diagnosis ; Prospective Studies ; SARS-CoV-2
Language	English
Publishing date	2022-07-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639359-7
ISSN	1399-3003 ; 0903-1936
ISSN (online)	1399-3003
ISSN	0903-1936
DOI	10.1183/13993003.02308-2021
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Zs.MO 292: Show issues

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Article ; Online: Risk factors and vectors for SARS-CoV-2 household transmission: a prospective, longitudinal cohort study.

Derqui, Nieves / Koycheva, Aleksandra / Zhou, Jie / Pillay, Timesh D / Crone, Michael A / Hakki, Seran / Fenn, Joe / Kundu, Rhia / Varro, Robert / Conibear, Emily / Madon, Kieran J / Barnett, Jack L / Houston, Hamish / Singanayagam, Anika / Narean, Janakan S / Tolosa-Wright, Mica R / Mosscrop, Lucy / Rosadas, Carolina / Watber, Patricia /

Anderson, Charlotte / Parker, Eleanor / Freemont, Paul S / Ferguson, Neil M / Zambon, Maria / McClure, Myra O / Tedder, Richard / Barclay, Wendy S / Dunning, Jake / Taylor, Graham P / Lalvani, Ajit

The Lancet. Microbe

2023 Volume 4, Issue 6, Page(s) e397–e408

Abstract: Background: Despite circumstantial evidence for aerosol and fomite spread of SARS-CoV-2, empirical data linking either pathway with transmission are scarce. Here we aimed to assess whether the presence of SARS-CoV-2 on frequently-touched surfaces and ... ...

Abstract	Background: Despite circumstantial evidence for aerosol and fomite spread of SARS-CoV-2, empirical data linking either pathway with transmission are scarce. Here we aimed to assess whether the presence of SARS-CoV-2 on frequently-touched surfaces and residents' hands was a predictor of SARS-CoV-2 household transmission. Methods: In this longitudinal cohort study, during the pre-alpha (September to December, 2020) and alpha (B.1.1.7; December, 2020, to April, 2021) SARS-CoV-2 variant waves, we prospectively recruited contacts from households exposed to newly diagnosed COVID-19 primary cases, in London, UK. To maximally capture transmission events, contacts were recruited regardless of symptom status and serially tested for SARS-CoV-2 infection by RT-PCR on upper respiratory tract (URT) samples and, in a subcohort, by serial serology. Contacts' hands, primary cases' hands, and frequently-touched surface-samples from communal areas were tested for SARS-CoV-2 RNA. SARS-CoV-2 URT isolates from 25 primary case-contact pairs underwent whole-genome sequencing (WGS). Findings: From Aug 1, 2020, until March 31, 2021, 620 contacts of PCR-confirmed SARS-CoV-2-infected primary cases were recruited. 414 household contacts (from 279 households) with available serial URT PCR results were analysed in the full household contacts' cohort, and of those, 134 contacts with available longitudinal serology data and not vaccinated pre-enrolment were analysed in the serology subcohort. Household infection rate was 28·4% (95% CI 20·8-37·5) for pre-alpha-exposed contacts and 51·8% (42·5-61·0) for alpha-exposed contacts (p=0·0047). Primary cases' URT RNA viral load did not correlate with transmission, but was associated with detection of SARS-CoV-2 RNA on their hands (p=0·031). SARS-CoV-2 detected on primary cases' hands, in turn, predicted contacts' risk of infection (adjusted relative risk [aRR]=1·70 [95% CI 1·24-2·31]), as did SARS-CoV-2 RNA presence on household surfaces (aRR=1·66 [1·09-2·55]) and contacts' hands (aRR=2·06 [1·57-2·69]). In six contacts with an initial negative URT PCR result, hand-swab (n=3) and household surface-swab (n=3) PCR positivity preceded URT PCR positivity. WGS corroborated household transmission. Interpretation: Presence of SARS-CoV-2 RNA on primary cases' and contacts' hands and on frequently-touched household surfaces associates with transmission, identifying these as potential vectors for spread in households. Funding: National Institute for Health Research Health Protection Research Unit in Respiratory Infections, Medical Research Council.
MeSH term(s)	Humans ; SARS-CoV-2/genetics ; COVID-19/diagnosis ; COVID-19/epidemiology ; Prospective Studies ; RNA, Viral/genetics ; Longitudinal Studies ; Risk Factors ; Cohort Studies
Chemical Substances	RNA, Viral
Language	English
Publishing date	2023-04-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-5247
ISSN (online)	2666-5247
DOI	10.1016/S2666-5247(23)00069-1
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Article ; Online: Rapid emergence of transmissible SARS-CoV-2 variants in mild community cases

Crone, Michael Andrew / Hakki, Seran / Zhou, Jie / Rosadas de Oliveira, Carolina / Madon, Kieran J / Koycheva, Aleksandra V / Badhan, Anjna / Jonnerby, Jakob / Fenn, Joe / Kundu, Rhia / Barnett, Jack L / Nevin, Sean / Conibear, Emily / Derqui-Fernandez, Nieves / Pillay, Timesh D / Varro, Robert / Luca, Constanta / Quinn, Valerie / Shazaad, Ahmad /

Zambon, Maria / Barclay, Wendy / Dunning, Jake / Freemont, Paul S / Taylor, Graham P / Lalvani, Ajit

medRxiv

Abstract: SARS-CoV-2 immune-escape variants have only been observed to arise in immunosuppressed COVID-19 cases, during prolonged viral shedding. Through daily longitudinal RT-qPCR, quantitative viral culture and sequencing, we observe for the first time the ... ...

Abstract	SARS-CoV-2 immune-escape variants have only been observed to arise in immunosuppressed COVID-19 cases, during prolonged viral shedding. Through daily longitudinal RT-qPCR, quantitative viral culture and sequencing, we observe for the first time the evolution of transmissible variants harbouring mutations consistent with immune-escape in mild community cases within 2 weeks of infection.
Keywords	covid19
Language	English
Publishing date	2023-02-23
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.02.15.23285923
Database	COVID19

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Article ; Online: Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study.

The Lancet. Infectious diseases

2021 Volume 22, Issue 2, Page(s) 183–195

Abstract: Background: The SARS-CoV-2 delta (B.1.617.2) variant is highly transmissible and spreading globally, including in populations with high vaccination rates. We aimed to investigate transmission and viral load kinetics in vaccinated and unvaccinated ... ...

Abstract	Background: The SARS-CoV-2 delta (B.1.617.2) variant is highly transmissible and spreading globally, including in populations with high vaccination rates. We aimed to investigate transmission and viral load kinetics in vaccinated and unvaccinated individuals with mild delta variant infection in the community. Methods: Between Sept 13, 2020, and Sept 15, 2021, 602 community contacts (identified via the UK contract-tracing system) of 471 UK COVID-19 index cases were recruited to the Assessment of Transmission and Contagiousness of COVID-19 in Contacts cohort study and contributed 8145 upper respiratory tract samples from daily sampling for up to 20 days. 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. We analysed transmission risk by vaccination status for 231 contacts exposed to 162 epidemiologically linked delta variant-infected index cases. We compared viral load trajectories from fully vaccinated individuals with delta infection (n=29) with unvaccinated individuals with delta (n=16), alpha (B.1.1.7; n=39), and pre-alpha (n=49) infections. Primary outcomes for the epidemiological analysis were to assess the secondary attack rate (SAR) in household contacts stratified by contact vaccination status and the index cases' vaccination status. Primary outcomes for the viral load kinetics analysis were to detect differences in the peak viral load, viral growth rate, and viral decline rate between participants according to SARS-CoV-2 variant and vaccination status. Findings: The SAR in household contacts exposed to the delta variant was 25% (95% CI 18-33) for fully vaccinated individuals compared with 38% (24-53) in unvaccinated individuals. The median time between second vaccine dose and study recruitment in fully vaccinated contacts was longer for infected individuals (median 101 days [IQR 74-120]) than for uninfected individuals (64 days [32-97], p=0·001). SAR among household contacts exposed to fully vaccinated index cases was similar to household contacts exposed to unvaccinated index cases (25% [95% CI 15-35] for vaccinated vs 23% [15-31] for unvaccinated). 12 (39%) of 31 infections in fully vaccinated household contacts arose from fully vaccinated epidemiologically linked index cases, further confirmed by genomic and virological analysis in three index case-contact pairs. Although peak viral load did not differ by vaccination status or variant type, it increased modestly with age (difference of 0·39 [95% credible interval -0·03 to 0·79] in peak log Interpretation: Vaccination reduces the risk of delta variant infection and accelerates viral clearance. Nonetheless, fully vaccinated individuals with breakthrough infections have peak viral load similar to unvaccinated cases and can efficiently transmit infection in household settings, including to fully vaccinated contacts. Host-virus interactions early in infection may shape the entire viral trajectory. Funding: National Institute for Health Research.
MeSH term(s)	Adult ; COVID-19/epidemiology ; COVID-19/prevention & control ; COVID-19/transmission ; COVID-19/virology ; Cohort Studies ; England/epidemiology ; Female ; Humans ; Kinetics ; Longitudinal Studies ; Male ; Middle Aged ; Prospective Studies ; SARS-CoV-2/physiology ; United Kingdom/epidemiology ; Vaccination ; Vaccination Coverage ; Viral Load/physiology
Language	English
Publishing date	2021-10-29
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(21)00648-4
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Article ; Online: Protocol for the challenge non-typhoidal

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Article ; Online: Rapid emergence of transmissible SARS-CoV-2 variants in mild community cases.

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Article ; Online: Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts.

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Article ; Online: Broadening symptom criteria improves early case identification in SARS-CoV-2 contacts.

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Article ; Online: Risk factors and vectors for SARS-CoV-2 household transmission: a prospective, longitudinal cohort study.

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Article ; Online: Rapid emergence of transmissible SARS-CoV-2 variants in mild community cases

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Article ; Online: Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study.

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