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Article ; Online: Dandruff lesional scalp skin exhibits epidermal T cell infiltration and a weakened hair follicle immune privilege.

Limbu, Susan L / Purba, Talveen S / Harries, Matthew / Kundu, Rhia / Bhogal, Ranjit K / Paus, Ralf

International journal of cosmetic science

2024

Abstract: Objective: Dandruff is characterised by the presence of perivascular leukocytes and mild inflammation; however, the immune microenvironment of dandruff-affected scalp skin and the potential changes to the hair follicle's (HF) physiological immune ... ...

Abstract	Objective: Dandruff is characterised by the presence of perivascular leukocytes and mild inflammation; however, the immune microenvironment of dandruff-affected scalp skin and the potential changes to the hair follicle's (HF) physiological immune privilege (HF IP) remain unknown. Here, we characterised the HF immune microenvironment and immune privilege status in dandruff-affected scalp skin. Methods: We assessed relevant key parameters in healthy versus dandruff-affected human scalp biopsies using quantitative immunohistomorphometry, laser capture microdissection, and RNA sequencing. Results: The number of epidermal CD4 Conclusion: Together, this work shows that dandruff is associated with epidermal T-cell infiltration and a weakened HF IP in the suprabulbar ORS of HFs in dandruff lesional scalp.
Language	English
Publishing date	2024-03-15
Publishing country	England
Document type	Journal Article
ZDB-ID	198917-0
ISSN	1468-2494 ; 0142-5463
ISSN (online)	1468-2494
ISSN	0142-5463
DOI	10.1111/ics.12956
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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, Vol 13, Iss 1, Pp 1-

2022 Volume 8

Abstract: While cross-reactive immunity between human coronavirus and SARS-CoV-2 may contribute to host protection, validating evidences are still scarce. Here the authors assess a cohort of 52 donors with immediate-early contact with SARS-CoV-2 to correlate ... ...

Abstract	While cross-reactive immunity between human coronavirus and SARS-CoV-2 may contribute to host protection, validating evidences are still scarce. Here the authors assess a cohort of 52 donors with immediate-early contact with SARS-CoV-2 to correlate higher frequency of cross-reactive T cells with lower infection rate.
Keywords	Science ; Q
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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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: 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.A 2322: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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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: Onset and window of SARS-CoV-2 infectiousness and temporal correlation with symptom onset: a prospective, longitudinal, community cohort study.

The Lancet. Respiratory medicine

2022 Volume 10, Issue 11, Page(s) 1061–1073

Abstract: 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- ... ...

Abstract	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 peak infectious viral load (viral RNA IQR 3-5 days, n=38; plaque-forming units IQR 3-6 days, n=35). Notably, 22 (65%) of 34 cases and eight (24%) of 34 cases continued to shed infectious virus 5 days and 7 days post-symptom onset, respectively (survival probabilities 67% and 35%). Correlation of lateral flow device (LFD) results with infectious viral shedding was poor during the viral growth phase (sensitivity 67% [95% CI 59-75]), but high during the decline phase (92% [86-96]). Infectious virus kinetic modelling suggested that the initial rate of viral replication determines the course of infection and infectiousness. Interpretation: Less than a quarter of COVID-19 cases shed infectious virus before symptom onset; under a crude 5-day self-isolation period from symptom onset, two-thirds of cases released into the community would still be infectious, but with reduced infectious viral shedding. Our findings support a role for LFDs to safely accelerate deisolation but not for early diagnosis, unless used daily. These high-resolution, community-based data provide evidence to inform infection control guidance. Funding: National Institute for Health and Care Research.
MeSH term(s)	Humans ; COVID-19/diagnosis ; COVID-19/epidemiology ; SARS-CoV-2 ; RNA, Viral ; Cohort Studies ; Prospective Studies ; Bayes Theorem
Chemical Substances	RNA, Viral
Language	English
Publishing date	2022-08-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2686754-0
ISSN	2213-2619 ; 2213-2600
ISSN (online)	2213-2619
ISSN	2213-2600
DOI	10.1016/S2213-2600(22)00226-0
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Zs.A 7041: Show issues

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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: Dandruff lesional scalp skin exhibits epidermal T cell infiltration and a weakened hair follicle immune privilege.

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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: 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: Onset and window of SARS-CoV-2 infectiousness and temporal correlation with symptom onset: a prospective, longitudinal, community cohort study.

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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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