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Article ; Online: Dose reductions in immunoglobulin replacement are associated with increased antibiotic usage in patients with antibody deficiency.

Elhaj, Mohammed Omer / Richter, Alex G / Goddard, Sarah / Shields, Adrian M

2023 Volume 202, Issue 4, Page(s) 900–903

MeSH term(s)	Humans ; Anti-Bacterial Agents/therapeutic use ; Drug Tapering ; Immunoglobulins, Intravenous/therapeutic use ; Immunologic Deficiency Syndromes/drug therapy
Chemical Substances	Anti-Bacterial Agents ; Immunoglobulins, Intravenous
Language	English
Publishing date	2023-06-20
Publishing country	England
Document type	Letter
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.18910
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Article ; Online: Multilevel visual motion opponency in Drosophila.

Ammer, Georg / Serbe-Kamp, Etienne / Mauss, Alex S / Richter, Florian G / Fendl, Sandra / Borst, Alexander

Nature neuroscience

2023 Volume 26, Issue 11, Page(s) 1894–1905

Abstract: Inhibitory interactions between opponent neuronal pathways constitute a common circuit motif across brain areas and species. However, in most cases, synaptic wiring and biophysical, cellular and network mechanisms generating opponency are unknown. Here, ... ...

Abstract	Inhibitory interactions between opponent neuronal pathways constitute a common circuit motif across brain areas and species. However, in most cases, synaptic wiring and biophysical, cellular and network mechanisms generating opponency are unknown. Here, we combine optogenetics, voltage and calcium imaging, connectomics, electrophysiology and modeling to reveal multilevel opponent inhibition in the fly visual system. We uncover a circuit architecture in which a single cell type implements direction-selective, motion-opponent inhibition at all three network levels. This inhibition, mediated by GluClα receptors, is balanced with excitation in strength, despite tenfold fewer synapses. The different opponent network levels constitute a nested, hierarchical structure operating at increasing spatiotemporal scales. Electrophysiology and modeling suggest that distributing this computation over consecutive network levels counteracts a reduction in gain, which would result from integrating large opposing conductances at a single instance. We propose that this neural architecture provides resilience to noise while enabling high selectivity for relevant sensory information.
MeSH term(s)	Animals ; Drosophila ; Neurons/physiology ; Synapses/physiology ; Motion Perception/physiology ; Visual Pathways
Language	English
Publishing date	2023-10-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	1420596-8
ISSN	1546-1726 ; 1097-6256
ISSN (online)	1546-1726
ISSN	1097-6256
DOI	10.1038/s41593-023-01443-z
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Article ; Online: Health Care Professionals' Confidence and Preferences for Diagnostic Assays for SARS-CoV-2: A Global Study.

Shields, Adrian M / Brown, Hannah / Phillips, Neil / Drayson, Mark T / Richter, Anton A / Richter, Alex G

Frontiers in public health

2021 Volume 9, Page(s) 569315

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Adult ; COVID-19/diagnosis ; COVID-19/mortality ; COVID-19 Testing ; Female ; Global Health ; Health Personnel/statistics & numerical data ; Humans ; Male ; Polymerase Chain Reaction ; Saliva
Language	English
Publishing date	2021-02-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2021.569315
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Article ; Online: Long-term air pollution exposure and risk of SARS-CoV-2 infection: A UK-wide cohort study.

Hajmohammadi, Hajar / Talaei, Mohammad / Fecht, Daniela / Wang, Weiyi / Vivaldi, Giulia / Faustini, Sian E / Richter, Alex G / Shaheen, Seif O / Martineau, Adrian R / Sheikh, Aziz / Mudway, Ian S / Griffiths, Christopher J

Respiratory medicine

2024 Volume 224, Page(s) 107567

Abstract: Background: The association between air quality and risk of SARS-CoV-2 infection is poorly understood. We investigated this association using serological individual-level data adjusting for a wide range of confounders, in a large population-based cohort ...

Abstract	Background: The association between air quality and risk of SARS-CoV-2 infection is poorly understood. We investigated this association using serological individual-level data adjusting for a wide range of confounders, in a large population-based cohort (COVIDENCE UK). Methods: We assessed the associations between long-term (2015-19) nitrogen dioxide (NO Results: After controlling for potential confounders, we found a positive association between 5-year NO Conclusion: Our findings suggest that the long-term burden of air pollution increased the risks of SARS-CoV-2 infection and has important implications for future pandemic preparedness. This evidence strengthens the case for reducing long-term air pollution exposures to reduce the vulnerability of individuals to respiratory viruses.
MeSH term(s)	Humans ; Air Pollutants/adverse effects ; Air Pollutants/analysis ; Cohort Studies ; Nitrogen Dioxide/adverse effects ; Nitrogen Dioxide/analysis ; Environmental Exposure/adverse effects ; Environmental Exposure/analysis ; COVID-19/epidemiology ; SARS-CoV-2 ; Air Pollution/adverse effects ; Air Pollution/analysis ; Particulate Matter/adverse effects ; Particulate Matter/analysis ; United Kingdom/epidemiology
Chemical Substances	Air Pollutants ; Nitrogen Dioxide (S7G510RUBH) ; Particulate Matter
Language	English
Publishing date	2024-02-27
Publishing country	England
Document type	Journal Article
ZDB-ID	1003348-8
ISSN	1532-3064 ; 0954-6111
ISSN (online)	1532-3064
ISSN	0954-6111
DOI	10.1016/j.rmed.2024.107567
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Article ; Online: Anti-SARS-CoV-2 antibodies following vaccination are associated with lymphocyte count and serum immunoglobulins in SLE.

Reynolds, John A / Faustini, Sian E / Tosounidou, Sofia / Plant, Tim / Ubhi, Mandeep / Gilman, Rebecca / Richter, Alex G / Gordon, Caroline

Lupus

2023 Volume 32, Issue 3, Page(s) 431–437

Abstract: Objectives: Patients with Systemic Lupus Erythematosus are known to have dysregulated immune responses and may have reduced response to vaccination against COVID-19 while being at risk of severe COVID-19 disease. The aim of this study was to identify ... ...

Abstract	Objectives: Patients with Systemic Lupus Erythematosus are known to have dysregulated immune responses and may have reduced response to vaccination against COVID-19 while being at risk of severe COVID-19 disease. The aim of this study was to identify whether vaccine responses were attenuated in SLE and to assess disease- and treatment-specific associations. Methods: Patients with SLE were matched by age, sex and ethnic background to healthcare worker healthy controls (HC). Anti-SARS-CoV-2 spike glycoprotein antibodies were measured at 4-8 weeks following the second COVID-19 vaccine dose (either BNT162b2 or ChAdOx1 nCoV-19) using a CE-marked combined ELISA detecting IgG, IgA and IgM (IgGAM). Antibody levels were considered as a continuous variable and in tertiles and compared between SLE patients and HC and associations with medication, disease activity and serological parameters were determined. Results: Antibody levels were lower in 43 SLE patients compared to 40 HC ( Conclusion: Patients with SLE have lower antibody levels following 2 doses of COVID-19 vaccines compared to HC. In SLE lower lymphocyte counts and serum IgA levels are associated with lower antibody levels post vaccination, potentially identifying a subgroup of patients who may therefore be at increased risk of infection.
MeSH term(s)	Humans ; COVID-19 Vaccines ; BNT162 Vaccine ; ChAdOx1 nCoV-19 ; COVID-19 ; Lupus Erythematosus, Systemic ; Vaccination ; Lymphocyte Count ; Antibodies, Viral ; Immunoglobulin A ; Immunoglobulin M
Chemical Substances	COVID-19 Vaccines ; BNT162 Vaccine ; ChAdOx1 nCoV-19 (B5S3K2V0G8) ; Antibodies, Viral ; Immunoglobulin A ; Immunoglobulin M
Language	English
Publishing date	2023-01-11
Publishing country	England
Document type	Journal Article
ZDB-ID	1154407-7
ISSN	1477-0962 ; 0961-2033
ISSN (online)	1477-0962
ISSN	0961-2033
DOI	10.1177/09612033231151603
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Article ; Online: Clinical and laboratory characteristics of patients with symptomatic secondary immunodeficiency following the treatment of haematological malignancies.

Shields, Adrian M / Faustini, Sian E / Young, Siobhan / Terjesen, Sarah / McCarthy, Nicholas I / Anderson, Rachel L / Drayson, Mark T / Richter, Alex G

EJHaem

2023 Volume 4, Issue 2, Page(s) 339–349

Abstract: Secondary immunodeficiency (SID), manifesting as increased susceptibility to infection, is an emergent clinical problem in haematoncology. Management of SID includes vaccination, prophylactic antibiotics (pAbx) and immunoglobulin replacement therapy ( ... ...

Abstract	Secondary immunodeficiency (SID), manifesting as increased susceptibility to infection, is an emergent clinical problem in haematoncology. Management of SID includes vaccination, prophylactic antibiotics (pAbx) and immunoglobulin replacement therapy (IgRT). We report clinical and laboratory parameters of 75 individuals, treated for haematological malignancy, who were referred for immunological assessment due to recurrent infections. Forty-five were managed with pAbx while thirty required IgRT after failing to improve on pAbx. Individuals requiring IgRT had significantly more bacterial, viral and fungal infections resulting in hospitalization at least 5 years after their original haemato-oncological diagnosis. Following immunological assessment and intervention, a 4.39-fold reduction in the frequency of hospital admissions to treat infection was observed in the IgRT cohort and a 2.30-fold reduction in the pAbx cohort. Significant reductions in outpatient antibiotic use were also observed in both cohorts following immunology input. Patients requiring IgRT were more hypogammaglobulinaemic and had lower titres of pathogen-specific antibodies and smaller memory B cell populations than those requiring pAbx. Test vaccination with pneumococcal conjugate vaccine discriminated poorly between the two groups. Patients requiring IgRT could be distinguished by combining wider pathogen-specific serology with a frequency of hospital admissions for infection. If validated in larger cohorts, this approach may circumvent the need for test vaccination and enhance patient selection for IgRT.
Language	English
Publishing date	2023-04-01
Publishing country	United States
Document type	Journal Article
ISSN	2688-6146
ISSN (online)	2688-6146
DOI	10.1002/jha2.683
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Article ; Online: Saliva antiviral antibody levels are detectable but correlate poorly with serum antibody levels following SARS-CoV-2 infection and/or vaccination.

Faustini, Siân E / Cook, Alex / Hill, Harriet / Al-Taei, Saly / Heaney, Jennifer / Efstathiou, Elena / Tanner, Chloe / Townsend, Neal / Ahmed, Zahra / Dinally, Mohammad / Hoque, Madeeha / Goodall, Margaret / Stamataki, Zania / Plant, Timothy / Chapple, Iain / Cunningham, Adam F / Drayson, Mark T / Shields, Adrian M / Richter, Alex G

The Journal of infection

2023 Volume 87, Issue 4, Page(s) 328–335

Abstract: The importance of salivary SARS-CoV-2 antibodies, following infection and vaccination, has not been fully established. 875 healthcare workers were sampled during the first wave in 2020 and 66 longitudinally in response to Pfizer BioNTech 162b2 ... ...

Abstract	The importance of salivary SARS-CoV-2 antibodies, following infection and vaccination, has not been fully established. 875 healthcare workers were sampled during the first wave in 2020 and 66 longitudinally in response to Pfizer BioNTech 162b2 vaccination. We measured SARS-CoV-2 total IgGAM and individual IgG, IgA and IgM antibodies. IgGAM seroprevalence was 39.9%; however, only 34.1% of seropositive individuals also had salivary antibodies. Infection generated serum IgG antibodies in 51.4% and IgA antibodies in 34.1% of individuals. In contrast, the salivary antibody responses were dominated by IgA (30.9% and 12% generating IgA and IgG antibodies, respectively). Post 2nd vaccination dose, in serum, 100% of infection naïve individuals had IgG and 82.8% had IgA responses; in saliva, 65.5% exhibited IgG and 55.2% IgA antibodies. Prior infection enhanced the vaccine antibody response in serum but no such difference was observed in saliva. Strong neutralisation responses were seen for serum 6 months post 2nd-vaccination dose (median 87.1%) compared to low neutralisation responses in saliva (median 1%). Intramuscular vaccination induces significant serum antibodies and to a lesser extent, salivary antibodies; however, salivary antibodies are typically non-neutralising. This study provides further evidence for the need of mucosal vaccines to elicit nasopharyngeal/oral protection. Although saliva is an attractive non-invasive sero-surveillance tool, due to distinct differences between systemic and oral antibody responses, it cannot be used as a proxy for serum antibody measurement.
MeSH term(s)	Humans ; Saliva ; COVID-19/prevention & control ; Seroepidemiologic Studies ; SARS-CoV-2 ; Vaccination ; Immunoglobulin A ; Antibodies, Viral ; Immunoglobulin G
Chemical Substances	Immunoglobulin A ; Antibodies, Viral ; Immunoglobulin G
Language	English
Publishing date	2023-08-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	424417-5
ISSN	1532-2742 ; 0163-4453
ISSN (online)	1532-2742
ISSN	0163-4453
DOI	10.1016/j.jinf.2023.07.018
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Zs.A 1501: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: COVID-19 in patients with primary and secondary immunodeficiency: The United Kingdom experience.

Shields, Adrian M / Burns, Siobhan O / Savic, Sinisa / Richter, Alex G

The Journal of allergy and clinical immunology

2020 Volume 147, Issue 3, Page(s) 870–875.e1

Abstract: Background: As of November 2020, severe acute respiratory syndrome coronavirus 2 has resulted in 55 million infections worldwide and more than 1.3 million deaths from coronavirus disease 2019 (COVID-19). Outcomes following severe acute respiratory ... ...

Abstract	Background: As of November 2020, severe acute respiratory syndrome coronavirus 2 has resulted in 55 million infections worldwide and more than 1.3 million deaths from coronavirus disease 2019 (COVID-19). Outcomes following severe acute respiratory syndrome coronavirus 2 infection in individuals with primary immunodeficiency (PID) or symptomatic secondary immunodeficiency (SID) remain uncertain. Objectives: We sought to document the outcomes of individuals with PID or symptomatic SID following COVID-19 in the United Kingdom. Methods: At the start of the COVID-19 pandemic, the United Kingdom Primary Immunodeficiency Network established a registry of cases to collate the nationwide outcomes of COVID-19 in individuals with PID or symptomatic SID and determine risk factors associated with morbidity and mortality from COVID-19 in these patient groups. Results: A total of 100 patients had been enrolled by July 1, 2020, 60 with PID, 7 with other inborn errors of immunity including autoinflammatory diseases and C1 inhibitor deficiency, and 33 with symptomatic SID. In individuals with PID, 53.3% (32 of 60) were hospitalized, the infection-fatality ratio was 20.0% (12 of 60), the case-fatality ratio was 31.6% (12 of 38), and the inpatient mortality was 37.5% (12 of 32). Individuals with SID had worse outcomes than those with PID; 75.8% (25 of 33) were hospitalized, the infection-fatality ratio was 33.3% (11 of 33), the case-fatality ratio was 39.2% (11 of 28), and inpatient mortality was 44.0% (11 of 25). Conclusions: In comparison to the general population, adult patients with PID and symptomatic SID display greater morbidity and mortality from COVID-19. This increased risk must be reflected in public health guidelines to adequately protect vulnerable patients from exposure to the virus.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; COVID-19/immunology ; COVID-19/mortality ; Female ; Humans ; Male ; Middle Aged ; Primary Immunodeficiency Diseases/immunology ; Primary Immunodeficiency Diseases/mortality ; Primary Immunodeficiency Diseases/virology ; Registries ; Risk Factors ; SARS-CoV-2/immunology ; United Kingdom/epidemiology
Language	English
Publishing date	2020-12-15
Publishing country	United States
Document type	Journal Article ; Multicenter Study
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2020.12.620
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Article ; Online: Immune responses to COVID-19 booster vaccinations in intensively anti-CD38 antibody treated patients with ultra-high-risk multiple myeloma: results from the Myeloma UK (MUK) nine OPTIMUM trial.

Faustini, Sian E / Hall, Andrew / Brown, Sarah / Roberts, Sadie / Hill, Harriet / Stamataki, Zania / Jenner, Matthew W / Owen, Roger G / Pratt, Guy / Cook, Gordon / Richter, Alex / Drayson, Mark T / Kaiser, Martin F / Heaney, Jennifer L J

British journal of haematology

2023 Volume 201, Issue 5, Page(s) 845–850

Abstract: Multiple myeloma (MM) and anti-MM therapy cause profound immunosuppression, leaving patients vulnerable to coronavirus disease 2019 (COVID-19) and other infections. We investigated anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) ... ...

Abstract	Multiple myeloma (MM) and anti-MM therapy cause profound immunosuppression, leaving patients vulnerable to coronavirus disease 2019 (COVID-19) and other infections. We investigated anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies longitudinally in ultra-high-risk patients with MM receiving risk-adapted, intensive anti-CD38 combined therapy in the Myeloma UK (MUK) nine trial. Despite continuous intensive therapy, seroconversion was achieved in all patients, but required a greater number of vaccinations compared to healthy individuals, highlighting the importance of booster vaccinations in this population. Reassuringly, high antibody cross-reactivity was found with current variants of concern, prior to Omicron subvariant adapted boostering. Multiple booster vaccine doses can provide effective protection from COVID-19, even with intensive anti-CD38 therapy for high-risk MM.
MeSH term(s)	Humans ; COVID-19/prevention & control ; SARS-CoV-2 ; Multiple Myeloma/therapy ; Vaccination ; Immunity ; United Kingdom/epidemiology ; Antibodies, Viral
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2023-03-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.18714
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Article ; Online: Incidence determinants and serological correlates of reactive symptoms following SARS-CoV-2 vaccination.

Holt, Hayley / Jolliffe, David A / Talaei, Mohammad / Faustini, Sian / Vivaldi, Giulia / Greenig, Matthew / Richter, Alex G / Lyons, Ronan A / Griffiths, Christopher J / Kee, Frank / Sheikh, Aziz / Davies, Gwyneth A / Shaheen, Seif O / Martineau, Adrian R

NPJ vaccines

2023 Volume 8, Issue 1, Page(s) 26

Abstract: Prospective population-based studies investigating associations between reactive symptoms following SARS-CoV-2 vaccination and serologic responses to vaccination are lacking. We therefore conducted a study in 9003 adults from the UK general population ... ...

Abstract	Prospective population-based studies investigating associations between reactive symptoms following SARS-CoV-2 vaccination and serologic responses to vaccination are lacking. We therefore conducted a study in 9003 adults from the UK general population receiving SARS-CoV-2 vaccines as part of the national vaccination programme. Titres of combined IgG/IgA/IgM responses to SARS-CoV-2 spike (S) glycoprotein were determined in eluates of dried blood spots collected from all participants before and after vaccination. 4262 (47.3%) participants experienced systemic reactive symptoms after a first vaccine dose. Factors associating with lower risk of such symptoms included older age (aOR per additional 10 years of age 0.85, 95% CI: 0.81-0.90), male vs. female sex (0.59, 0.53-0.65) and receipt of an mRNA vaccine vs. ChAdOx1 nCoV-19 (0.29, 0.26-0.32 for BNT162b2; 0.06, 0.01-0.26 for mRNA-1273). Higher risk of such symptoms was associated with SARS-CoV-2 seropositivity and COVID-19 symptoms prior to vaccination (2.23, 1.78-2.81), but not with SARS-CoV-2 seropositivity in the absence of COVID-19 symptoms (0.94, 0.81-1.09). Presence vs. absence of self-reported anxiety or depression at enrolment associated with higher risk of such symptoms (1.24, 1.12-1.39). Post-vaccination anti-S titres were higher among participants who experienced reactive symptoms after vaccination vs. those who did not (P < 0.001). We conclude that factors influencing risk of systemic symptoms after SARS-CoV-2 vaccination include demographic characteristics, pre-vaccination SARS-CoV-2 serostatus and vaccine type. Participants experiencing reactive symptoms following SARS-CoV-2 vaccination had higher post-vaccination titres of IgG/A/M anti-S antibodies. Improved public understanding of the frequency of reactogenic symptoms and their positive association with vaccine immunogenicity could potentially increase vaccine uptake.
Language	English
Publishing date	2023-02-25
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-023-00614-0
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