35 results on '"Shields, Adrian M"'
Search Results
2. SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study
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Shields, Adrian M., Faustini, Sian E., Hill, Harriet J., Al-Taei, Saly, Tanner, Chloe, Ashford, Fiona, Workman, Sarita, Moreira, Fernando, Verma, Nisha, Wagg, Hollie, Heritage, Gail, Campton, Naomi, Stamataki, Zania, Klenerman, Paul, Thaventhiran, James E. D., Goddard, Sarah, Johnston, Sarah, Huissoon, Aarnoud, Bethune, Claire, Elcombe, Suzanne, Lowe, David M., Patel, Smita Y., Savic, Sinisa, Burns, Siobhan O., and Richter, Alex G.
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- 2022
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3. Resolution of Persistent COVID-19 After Convalescent Plasma in a Patient with B Cell Aplasia
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McKemey, Emily, Shields, Adrian M., Faustini, Sian E., Hill, Harriet J., Barnskaya, Aliaksandra, Stamataki, Zania, Gompertz, Simon, Richter, Alex G., Dosanjh, Davinder, and Madathil, Shyam
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- 2021
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4. Sensitive Detection of SARS-CoV-2-Specific Antibodies in Dried Blood Spot Samples
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Morley, Gabriella L., Taylor, Stephen, Jossi, Sian, Perez-Toledo, Marisol, Faustini, Sian E., Marcial-Juarez, Edith, Shields, Adrian M., Goodall, Margaret, Allen, Joel D., Watanabe, Yasunori, Newby, Maddy L., Crispin, Max, Drayson, Mark T., Cunningham, Adam F., Richter, Alex G., and OShea, Matthew K.
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Blood -- Medical examination ,Serodiagnosis -- Methods ,Health - Abstract
A confirmed diagnosis of acute coronavirus disease (COVID-19) depends on the detection of RNA from the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In contrast, although serologic testing [...]
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- 2020
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5. A Novel, Heterozygous Three Base-Pair Deletion in CARD11 Results in B Cell Expansion with NF-κB and T Cell Anergy Disease
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Shields, Adrian M., Bauman, Bradly M., Hargreaves, Chantal E., Pollard, Andrew J., Snow, Andrew L., and Patel, Smita Y.
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- 2020
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6. The primary immunodeficiency disorders
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Shields, Adrian M. and Patel, Smita Y.
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- 2017
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7. Correction to: Resolution of Persistent COVID-19 After Convalescent Plasma in a Patient with B Cell Aplasia
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McKemey, Emily, Shields, Adrian M., Faustini, Sian E., Hill, Harriet J., Baranskaya, Aliaksandra, Stamataki, Zania, Gompertz, Simon, Richter, Alex G., Dosanjh, Davinder, and Madathil, Shyam
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- 2021
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8. Dose reductions in immunoglobulin replacement are associated with increased antibiotic usage in patients with antibody deficiency.
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Elhaj, Mohammed Omer, Richter, Alex G., Goddard, Sarah, and Shields, Adrian M.
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PELVIC inflammatory disease ,PLASMA cell diseases ,PRIMARY immunodeficiency diseases ,PLASMA products - Abstract
.83 ht 1 Abbreviations: IgG, immunoglobulin G; IgRT, immunoglobulin replacement therapy; IQR, interquartile range. We demonstrate that, in previously stable patients, IgRT dose reductions lead to a reduction in trough IgG, which is associated with an increased frequency of infections requiring outpatient antibiotic use. [Extracted from the article]
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- 2023
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9. SARS-CoV-2 infection is associated with anti-desmoglein 2 autoantibody detection.
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Ward, Kerensa E, Steadman, Lora, Karim, Abid R, Reynolds, Gary M, Pugh, Matthew, Chua, Winnie, Faustini, Sian E, Veenith, Tonny, Thwaites, Ryan S, Openshaw, Peter J M, Drayson, Mark T, Shields, Adrian M, Cunningham, Adam F, Wraith, David C, and Richter, Alex G
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AUTOANTIBODIES ,CONVALESCENT plasma ,COVID-19 ,SARS-CoV-2 ,BLOOD proteins ,AUTOIMMUNE diseases - Abstract
Post-acute cardiac sequelae, following SARS-CoV-2 infection, are well recognized as complications of COVID-19. We have previously shown the persistence of autoantibodies against antigens in skin, muscle, and heart in individuals following severe COVID-19; the most common staining on skin tissue displayed an inter-cellular cement pattern consistent with antibodies against desmosomal proteins. Desmosomes play a critical role in maintaining the structural integrity of tissues. For this reason, we analyzed desmosomal protein levels and the presence of anti-desmoglein (DSG) 1, 2, and 3 antibodies in acute and convalescent sera from patients with COVID-19 of differing clinical severity. We find increased levels of DSG2 protein in sera from acute COVID-19 patients. Furthermore, we find that DSG2 autoantibody levels are increased significantly in convalescent sera following severe COVID-19 but not in hospitalized patients recovering from influenza infection or healthy controls. Levels of autoantibody in sera from patients with severe COVID-19 were comparable to levels in patients with non-COVID-19-associated cardiac disease, potentially identifying DSG2 autoantibodies as a novel biomarker for cardiac damage. To determine if there was any association between severe COVID-19 and DSG2, we stained post-mortem cardiac tissue from patients who died from COVID-19 infection. This confirmed DSG2 protein within the intercalated discs and disruption of the intercalated disc between cardiomyocytes in patients who died from COVID-19. Our results reveal the potential for DSG2 protein and autoimmunity to DSG2 to contribute to unexpected pathologies associated with COVID-19 infection. We find raised levels of anti-DSG2 autoantibodies in sera from individuals following severe COVID-19. Staining of post-mortem cardiac tissue from individuals that died from COVID-19 with an anti-DSG2 antibody revealed disruption of the intercalated disc between cardiomyocytes that was consistent with separation of the DSG2 protein homodimer. Our results reveal the potential for DSG2 protein and autoimmunity to DSG2 to contribute to unexpected pathologies associated with COVID-19 infection. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Clinical and laboratory characteristics of patients with symptomatic secondary immunodeficiency following the treatment of haematological malignancies.
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Shields, Adrian M., Faustini, Sian E., Young, Siobhan, Terjesen, Sarah, McCarthy, Nicholas I., Anderson, Rachel L., Drayson, Mark T., and Richter, Alex G.
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- 2023
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11. Correlation Between Postvaccination Anti-Spike Antibody Titers and Protection Against Breakthrough Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Population-Based Longitudinal Study.
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Vivaldi, Giulia, Jolliffe, David A, Faustini, Sian, Shields, Adrian M, Holt, Hayley, Perdek, Natalia, Talaei, Mohammad, Tydeman, Florence, Chambers, Emma S, Cai, Weigang, Li, Wenhao, Gibbons, Joseph M, Pade, Corinna, McKnight, Áine, Shaheen, Seif O, Richter, Alex G, and Martineau, Adrian R
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COVID-19 ,SARS-CoV-2 ,ANTIBODY titer ,BREAKTHROUGH infections - Abstract
In this population-based cohort of 7538 adults, combined immunoglobulin (Ig) G, IgA, and IgM (IgG/A/M) anti-spike titers measured after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination were predictive of protection against breakthrough SARS-CoV-2 infection. Discrimination was significantly improved by adjustment for factors influencing risk of SARS-CoV-2 exposure, including household overcrowding, public transport use, and visits to indoor public places. Anti-spike IgG/A/M titers showed positive correlation with neutralizing antibody titers (rs = 0.80 [95% confidence interval, .72-.86]; P < .001) and S peptide-stimulated interferon-γ concentrations (rs = 0.31 [.13-.47]; P < .001). [ABSTRACT FROM AUTHOR]
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- 2022
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12. Impact of vaccination on hospitalization and mortality from COVID-19 in patients with primary and secondary immunodeficiency: The United Kingdom experience.
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Shields, Adrian M., Tadros, Susan, Al-Hakim, Adam, Nell, Jeremy M., Me Me Nay Lin, Chan, Michele, Goddard, Sarah, Dempster, John, Dziadzio, Magdalena, Patel, Smita Y., Elkalifa, Shuayb, Huissoon, Aarnoud, Duncan, Christopher J. A., Herwadkar, Archana, Khan, Sujoy, Bethune, Claire, Elcombe, Suzanne, Thaventhiran, James, Klenerman, Paul, and Lowe, David M.
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COVID-19 ,PRIMARY immunodeficiency diseases ,PELVIC inflammatory disease ,VACCINATION ,COVID-19 vaccines ,SARS-CoV-2 Omicron variant - Abstract
Background: Individuals with primary and secondary immunodeficiency (PID/SID) were showntobeat riskofpooroutcomesduringtheearly stagesoftheSARS-CoV-2pandemic. SARS-CoV-2 vaccines demonstrate reduced immunogenicity in these patients. Objectives: To understand whether the risk of severe COVID-19 in individuals with PID or SID has changed following the deployment of vaccination and therapeutics in the context of the emergence of novel viral variants of concern. Methods: The outcomes of two cohorts of patients with PID and SID were compared: the first, infected between March and July 2020, prior to vaccination and treatments, the second after these intervention became available between January 2021 and April 2022. Results: 22.7% of immunodeficient patients have been infected at least once with SARS-CoV-2 since the start of the pandemic, compared to over 70% of the general population. Immunodeficient patients were typically infected later in the pandemic when the B.1.1.529 (Omicron) variant was dominant. This delay was associated with receipt of more vaccine doses and higher pre-infection seroprevalence. Compared to March-July 2020, hospitalization rates (53.3% vs 17.9%, p<0.0001) and mortality (Infection fatality rate 20.0% vs 3.4%, p=0.0003) have significantly reduced for patients with PID but remain elevated compared to the general population. The presence of a serological response to vaccination was associated with a reduced duration of viral detection by PCR in the nasopharynx. Early outpatient treatment with antivirals or monoclonal antibodies reduced hospitalization during the Omicron wave. Conclusions: Most individuals with immunodeficiency in the United Kingdom remain SARS-CoV-2 infection naïve. Vaccination, widespread availability of outpatient treatments and, possibly, the emergence of the B.1.1.529 variant have led to significant improvements in morbidity and mortality followings SARS-CoV-2 infection since the start of the pandemic. However, individuals with PID and SID remain at significantly increased risk of poor outcomes compared to the general population; mitigation, vaccination and treatment strategies must be optimized to minimize the ongoing burden of the pandemic in these vulnerable cohorts. [ABSTRACT FROM AUTHOR]
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- 2022
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13. Outcomes following SARS-CoV-2 infection in patients with primary and secondary immunodeficiency in the UK.
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Shields, Adrian M, Anantharachagan, Ariharan, Arumugakani, Gururaj, Baker, Kenneth, Bahal, Sameer, Baxendale, Helen, Bermingham, William, Bhole, Malini, Boules, Evon, Bright, Philip, Chopra, Charu, Cliffe, Lucy, Cleave, Betsy, Dempster, John, Devlin, Lisa, Dhalla, Fatima, Diwakar, Lavanya, Drewe, Elizabeth, Duncan, Christopher, and Dziadzio, Magdalena
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PRIMARY immunodeficiency diseases , *INFECTION , *SARS-CoV-2 , *CONVALESCENT plasma , *LYMPHOCYTE count , *PELVIC inflammatory disease - Abstract
In March 2020, the United Kingdom Primary Immunodeficiency Network (UKPIN) established a registry of cases to collate the outcomes of individuals with PID and SID following SARS-CoV-2 infection and treatment. A total of 310 cases of SARS-CoV-2 infection in individuals with PID or SID have now been reported in the UK. The overall mortality within the cohort was 17.7% (n = 55/310). Individuals with CVID demonstrated an infection fatality rate (IFR) of 18.3% (n = 17/93), individuals with PID receiving IgRT had an IFR of 16.3% (n = 26/159) and individuals with SID, an IFR of 27.2% (n = 25/92). Individuals with PID and SID had higher inpatient mortality and died at a younger age than the general population. Increasing age, low pre-SARS-CoV-2 infection lymphocyte count and the presence of common co-morbidities increased the risk of mortality in PID. Access to specific COVID-19 treatments in this cohort was limited: only 22.9% (n = 33/144) of patients admitted to the hospital received dexamethasone, remdesivir, an anti-SARS-CoV-2 antibody-based therapeutic (e.g. REGN-COV2 or convalescent plasma) or tocilizumab as a monotherapy or in combination. Dexamethasone, remdesivir, and anti-SARS-CoV-2 antibody-based therapeutics appeared efficacious in PID and SID. Compared to the general population, individuals with PID or SID are at high risk of mortality following SARS-CoV-2 infection. Increasing age, low baseline lymphocyte count, and the presence of co-morbidities are additional risk factors for poor outcome in this cohort. [ABSTRACT FROM AUTHOR]
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- 2022
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14. SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement Activation.
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Lamerton, Rachel E., Marcial-Juarez, Edith, Faustini, Sian E., Perez-Toledo, Marisol, Goodall, Margaret, Jossi, Siân E., Newby, Maddy L., Chapple, Iain, Dietrich, Thomas, Veenith, Tonny, Shields, Adrian M., Harper, Lorraine, Henderson, Ian R., Rayes, Julie, Wraith, David C., Watson, Steve P., Crispin, Max, Drayson, Mark T., Richter, Alex G., and Cunningham, Adam F.
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COMPLEMENT activation ,SARS-CoV-2 ,COMPLEMENT (Immunology) ,VIRAL antigens ,IMMUNOGLOBULINS - Abstract
Antibodies specific for the spike glycoprotein (S) and nucleocapsid (N) SARS-CoV-2 proteins are typically present during severe COVID-19, and induced to S after vaccination. The binding of viral antigens by antibody can initiate the classical complement pathway. Since complement could play pathological or protective roles at distinct times during SARS-CoV-2 infection we determined levels of antibody-dependent complement activation along the complement cascade. Here, we used an ELISA assay to assess complement protein binding (C1q) and the deposition of C4b, C3b, and C5b to S and N antigens in the presence of antibodies to SARS-CoV-2 from different test groups: non-infected, single and double vaccinees, non-hospitalised convalescent (NHC) COVID-19 patients and convalescent hospitalised (ITU-CONV) COVID-19 patients. C1q binding correlates strongly with antibody responses, especially IgG1 levels. However, detection of downstream complement components, C4b, C3b and C5b shows some variability associated with the subject group from whom the sera were obtained. In the ITU-CONV, detection of C3b-C5b to S was observed consistently, but this was not the case in the NHC group. This is in contrast to responses to N, where median levels of complement deposition did not differ between the NHC and ITU-CONV groups. Moreover, for S but not N, downstream complement components were only detected in sera with higher IgG1 levels. Therefore, the classical pathway is activated by antibodies to multiple SARS-CoV-2 antigens, but the downstream effects of this activation may differ depending the disease status of the subject and on the specific antigen targeted. [ABSTRACT FROM AUTHOR]
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- 2022
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15. Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study.
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Shields, Adrian M., Faustini, Sian E., Hill, Harriet J., Al-Taei, Saly, Tanner, Chloe, Ashford, Fiona, Workman, Sarita, Moreira, Fernando, Verma, Nisha, Wagg, Hollie, Heritage, Gail, Campton, Naomi, Stamataki, Zania, Drayson, Mark T., Klenerman, Paul, Thaventhiran, James E. D., Elkhalifa, Shuayb, Goddard, Sarah, Johnston, Sarah, and Huissoon, Aarnoud
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ANTIBODY formation ,PRIMARY immunodeficiency diseases ,SARS-CoV-2 ,COVID-19 vaccines ,IMMUNIZATION - Abstract
Background: Patients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity. Objectives: To determine the immunogenicity of the third primary SARS-CoV-2 immunisation in a heterogeneous cohort of patients with antibody deficiency. Methods: Participants enrolled in the COV-AD study were sampled before and after their third vaccine dose. Serological and cellular responses were determined using ELISA, livevirus neutralisation and ELISPOT assays. Results: Following a two-dose schedule, 100% of healthy controls mounted a serological response to SARS-CoV-2 vaccination, however, 38.6% of individuals with antibody deficiency remained seronegative. A third primary SARS-CoV-2 vaccine significantly increased anti-spike glycoprotein antibody seroprevalence from 61.4% to 76.0%, the magnitude of the antibody response, its neutralising capacity and induced seroconversion in individuals who were seronegative after two vaccine doses. Vaccine-induced serological responses were broadly cross-reactive against the SARS-CoV-2 B.1.1.529 variant of concern, however, seroprevalence and antibody levels remained significantly lower than healthy controls. No differences in serological responses were observed between individuals who received AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 during their initial two-dose vaccine schedule. SARS-CoV-2 infectionnaive participants who had received a heterologous vaccine as a third dose were significantly more likely to have a detectable T cell response following their third vaccine dose (61.5% vs 11.1%). Conclusion: These data support the widespread use of third primary immunisations to enhance humoral immunity against SARS-CoV-2 in individuals with antibody deficiency. [ABSTRACT FROM AUTHOR]
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- 2022
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16. SARS-CoV-2 vaccine responses following CD20-depletion treatment in patients with haematological and rheumatological disease: a West Midlands Research Consortium study.
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Shields, Adrian M, Venkatachalam, Srinivasan, Shafeek, Salim, Paneesha, Shankara, Ford, Mark, Sheeran, Tom, Kelly, Melanie, Qureshi, Iman, Salhan, Beena, Karim, Farheen, De Silva, Neelakshi, Stones, Jacqueline, Lee, Sophie, Khawaja, Jahanzeb, Kaudlay, Praveen Kumar, Whitmill, Richard, Kakepoto, Ghulam Nabi, Parry, Helen M, Moss, Paul, and Faustini, Sian E
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VACCINE effectiveness , *COVID-19 vaccines , *BOOSTER vaccines , *CONSORTIA , *B cells , *IMMUNE reconstitution inflammatory syndrome , *AUTOIMMUNE diseases - Abstract
B-cell-depleting agents are among the most commonly used drugs to treat haemato-oncological and autoimmune diseases. They rapidly induce a state of peripheral B-cell aplasia with the potential to interfere with nascent vaccine responses, particularly to novel antigens. We have examined the relationship between B-cell reconstitution and SARS-CoV-2 vaccine responses in two cohorts of patients previously exposed to B-cell-depleting agents: a cohort of patients treated for haematological B-cell malignancy and another treated for rheumatological disease. B-cell depletion severely impairs vaccine responsiveness in the first 6 months after administration: SARS-CoV-2 antibody seroprevalence was 42.2% and 33.3% in the haemato-oncological patients and rheumatology patients, respectively and 22.7% in patients vaccinated while actively receiving anti-lymphoma chemotherapy. After the first 6 months, vaccine responsiveness significantly improved during early B-cell reconstitution; however, the kinetics of reconstitution was significantly faster in haemato-oncology patients. The AstraZeneca ChAdOx1 nCoV-19 vaccine and the Pfizer BioNTech 162b vaccine induced equivalent vaccine responses; however, shorter intervals between vaccine doses (<1 m) improved the magnitude of the antibody response in haeamto-oncology patients. In a subgroup of haemato-oncology patients, with historic exposure to B-cell-depleting agents (>36 m previously), vaccine non-responsiveness was independent of peripheral B-cell reconstitution. The findings have important implications for primary vaccination and booster vaccination strategies in individuals clinically vulnerable to SARS-CoV-2. B cell depleting drugs including rituximab are commonly used to treat haematological malignancy and autoimmune diseases but may impair the immunological response to vaccination. This study investigates SARS-CoV-2 vaccine responses in individuals with haematological and rheumatological disease with previously exposure to B cell depleting agents. Vaccination within the first 6 months of B cell depletion is associated with significant impairment of vaccine responsiveness; however, rheumatology and haemato-oncological patients display different kinetics of B cell reconstitution corresponding to differential vaccine responsiveness over time. [ABSTRACT FROM AUTHOR]
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- 2022
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17. Pro-resolution immunological networks: binding immunoglobulin protein and other resolution-associated molecular patterns
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Shields, Adrian M., Thompson, Stephen J., Panayi, Gabriel S., and Corrigall, Valerie M.
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- 2012
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18. Development of a high‐sensitivity ELISA detecting IgG, IgA and IgM antibodies to the SARS‐CoV‐2 spike glycoprotein in serum and saliva.
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Faustini, Sian E., Jossi, Sian E., Perez‐Toledo, Marisol, Shields, Adrian M., Allen, Joel D., Watanabe, Yasunori, Newby, Maddy L., Cook, Alex, Willcox, Carrie R., Salim, Mahboob, Goodall, Margaret, Heaney, Jennifer L., Marcial‐Juarez, Edith, Morley, Gabriella L., Torlinska, Barbara, Wraith, David C., Veenith, Tonny V., Harding, Stephen, Jolles, Stephen, and Ponsford, Mark J.
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IMMUNOGLOBULIN G ,SARS-CoV-2 ,IMMUNOGLOBULIN A ,SALIVA ,IMMUNOGLOBULINS - Abstract
Detecting antibody responses during and after SARS‐CoV‐2 infection is essential in determining the seroepidemiology of the virus and the potential role of antibody in disease. Scalable, sensitive and specific serological assays are essential to this process. The detection of antibody in hospitalized patients with severe disease has proven relatively straightforward; detecting responses in subjects with mild disease and asymptomatic infections has proven less reliable. We hypothesized that the suboptimal sensitivity of antibody assays and the compartmentalization of the antibody response may contribute to this effect. We systematically developed an ELISA, optimizing different antigens and amplification steps, in serum and saliva from non‐hospitalized SARS‐CoV‐2‐infected subjects. Using trimeric spike glycoprotein, rather than nucleocapsid, enabled detection of responses in individuals with low antibody responses. IgG1 and IgG3 predominate to both antigens, but more anti‐spike IgG1 than IgG3 was detectable. All antigens were effective for detecting responses in hospitalized patients. Anti‐spike IgG, IgA and IgM antibody responses were readily detectable in saliva from a minority of RT‐PCR confirmed, non‐hospitalized symptomatic individuals, and these were mostly subjects who had the highest levels of anti‐spike serum antibodies. Therefore, detecting antibody responses in both saliva and serum can contribute to determining virus exposure and understanding immune responses after SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]
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- 2021
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19. Establishing the prevalence of common tissue‐specific autoantibodies following severe acute respiratory syndrome coronavirus 2 infection.
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Richter, Alex G., Shields, Adrian M., Karim, Abid, Birch, David, Faustini, Sian E., Steadman, Lora, Ward, Kerensa, Plant, Timothy, Reynolds, Gary, Veenith, Tonny, Cunningham, Adam F., Drayson, Mark T., and Wraith, David C.
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COVID-19 , *AUTOANTIBODIES , *VIRUS diseases , *RESPIRATORY infections , *SARS-CoV-2 - Abstract
Summary: Coronavirus 19 (COVID‐19) has been associated with both transient and persistent systemic symptoms that do not appear to be a direct consequence of viral infection. The generation of autoantibodies has been proposed as a mechanism to explain these symptoms. To understand the prevalence of autoantibodies associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, we investigated the frequency and specificity of clinically relevant autoantibodies in 84 individuals previously infected with SARS‐CoV‐2, suffering from COVID‐19 of varying severity in both the acute and convalescent setting. These were compared with results from 32 individuals who were on the intensive therapy unit (ITU) for non‐COVID reasons. We demonstrate a higher frequency of autoantibodies in the COVID‐19 ITU group compared with non‐COVID‐19 ITU disease control patients and that autoantibodies were also found in the serum 3–5 months post‐COVID‐19 infection. Non‐COVID patients displayed a diverse pattern of autoantibodies; in contrast, the COVID‐19 groups had a more restricted panel of autoantibodies including skin, skeletal muscle and cardiac antibodies. Our results demonstrate that respiratory viral infection with SARS‐CoV‐2 is associated with the detection of a limited profile of tissue‐specific autoantibodies, detectable using routine clinical immunology assays. Further studies are required to determine whether these autoantibodies are specific to SARS‐CoV‐2 or a phenomenon arising from severe viral infections and to determine the clinical significance of these autoantibodies. [ABSTRACT FROM AUTHOR]
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- 2021
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20. SARS‐CoV‐2‐specific IgG1/IgG3 but not IgM in children with Pediatric Inflammatory Multi‐System Syndrome.
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Perez‐Toledo, Marisol, Faustini, Sian E., Jossi, Sian E., Shields, Adrian M., Marcial‐Juarez, Edith, Kanthimathinathan, Hari Krishnan, Allen, Joel D., Watanabe, Yasunori, Goodall, Margaret, Willcox, Benjamin E., Willcox, Carrie R., Salim, Mahboob, Wraith, David C., Veenith, Tonny V., Syrimi, Eleni, Drayson, Mark T., Jyothish, Deepthi, Al‐Abadi, Eslam, Chikermane, Ashish, and Welch, Steven B.
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COVID-19 ,CHILD patients ,TOXIC shock syndrome ,MEDICAL personnel ,VIRAL antibodies - Abstract
Although anti-S IgA and IgG were more similar in children and adult COVID-19 patients, anti-N IgA and IgG antibodies were higher in ITU patients (Figure 1C,D). Since antibody isotypes can reflect recent infection (IgM), or more historic infections (IgG and IgA), we examined individual antibody isotypes and presented these results as area under the curve (AUC). Therefore, children with Kawasaki-like inflammatory syndrome, negative by PCR, can have IgG1, IgG3, and IgA antibody levels to SARS-CoV-2 in the absence of maintained IgM responses. Screening of sera, diluted 1:40, to detect IgG, IgA, and IgM demonstrated that all children had antibodies against the SARS-CoV-2 S glycoprotein (Figure 1A). [Extracted from the article]
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- 2021
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21. T cell response to SARS-CoV-2 infection in humans: A systematic review.
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Shrotri, Madhumita, van Schalkwyk, May C. I., Post, Nathan, Eddy, Danielle, Huntley, Catherine, Leeman, David, Rigby, Samuel, Williams, Sarah V., Bermingham, William H., Kellam, Paul, Maher, John, Shields, Adrian M., Amirthalingam, Gayatri, Peacock, Sharon J., and Ismail, Sharif A.
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SARS-CoV-2 ,T cells ,HERD immunity ,COVID-19 ,VACCINE development ,ANTIBODY formation - Abstract
Background: Understanding the T cell response to SARS-CoV-2 is critical to vaccine development, epidemiological surveillance and disease control strategies. This systematic review critically evaluates and synthesises the relevant peer-reviewed and pre-print literature published from 01/01/2020-26/06/2020. Methods: For this systematic review, keyword-structured literature searches were carried out in MEDLINE, Embase and COVID-19 Primer. Papers were independently screened by two researchers, with arbitration of disagreements by a third researcher. Data were independently extracted into a pre-designed Excel template and studies critically appraised using a modified version of the MetaQAT tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results: 61 articles were included. 55 (90%) studies used observational designs, 50 (82%) involved hospitalised patients with higher acuity illness, and the majority had important limitations. Symptomatic adult COVID-19 cases consistently show peripheral T cell lymphopenia, which positively correlates with increased disease severity, duration of RNA positivity, and non-survival; while asymptomatic and paediatric cases display preserved counts. People with severe or critical disease generally develop more robust, virus-specific T cell responses. T cell memory and effector function has been demonstrated against multiple viral epitopes, and, cross-reactive T cell responses have been demonstrated in unexposed and uninfected adults, but the significance for protection and susceptibility, respectively, remains unclear. Conclusion: A complex pattern of T cell response to SARS-CoV-2 infection has been demonstrated, but inferences regarding population level immunity are hampered by significant methodological limitations and heterogeneity between studies, as well as a striking lack of research in asymptomatic or pauci-symptomatic individuals. In contrast to antibody responses, population-level surveillance of the T cell response is unlikely to be feasible in the near term. Focused evaluation in specific sub-groups, including vaccine recipients, should be prioritised. [ABSTRACT FROM AUTHOR]
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- 2021
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22. Serological responses to SARS-CoV-2 following non-hospitalised infection: clinical and ethnodemographic features associated with the magnitude of the antibody response.
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Shields, Adrian M., Faustini, Sian E., Perez-Toledo, Marisol, Jossi, Sian, Allen, Joel D., Al-Taei, Saly, Backhouse, Claire, Dunbar, Lynsey A., Ebanks, Daniel, Emmanuel, Beena, Faniyi, Aduragbemi A., Garvey, Mark, Grinbergs, Annabel, McGinnell, Golaleh, O'Neill, Joanne, Yasunori Watanabe, Crispin, Max, Wraith, David C., Cunningham, Adam F., and Drayson, Mark T.
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- 2021
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23. Antibody response to SARS-CoV-2 infection in humans: A systematic review.
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Post, Nathan, Eddy, Danielle, Huntley, Catherine, van Schalkwyk, May C. I., Shrotri, Madhumita, Leeman, David, Rigby, Samuel, Williams, Sarah V., Bermingham, William H., Kellam, Paul, Maher, John, Shields, Adrian M., Amirthalingam, Gayatri, Peacock, Sharon J., and Ismail, Sharif A.
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ANTIBODY formation ,IMMUNOGLOBULIN M ,SARS-CoV-2 ,CONVALESCENT plasma ,HUMORAL immunity - Abstract
Background: Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. Assessment of the full range of evidence generated to date to understand the characteristics of the antibody response, its dynamics over time, its determinants and the immunity it confers will have a range of clinical and policy implications for this novel pathogen. This review comprehensively evaluated evidence describing the antibody response to SARS-CoV-2 published from 01/01/2020-26/06/2020. Methods: Systematic review. Keyword-structured searches were carried out in MEDLINE, Embase and COVID-19 Primer. Articles were independently screened on title, abstract and full text by two researchers, with arbitration of disagreements. Data were double-extracted into a pre-designed template, and studies critically appraised using a modified version of the Public Health Ontario Meta-tool for Quality Appraisal of Public Health Evidence (MetaQAT) tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results: 150 papers were included. Most studies (113 or 75%) were observational in design, were based wholly or primarily on data from hospitalised patients (108, 72%) and had important methodological limitations. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, up to around three months from disease onset, but the picture regarding correlates of the antibody response was inconsistent. IgM was consistently detected before IgG in included studies, peaking at weeks two to five and declining over a further three to five weeks post-symptom onset depending on the patient group; IgG peaked around weeks three to seven post-symptom onset then plateaued, generally persisting for at least eight weeks. Neutralising antibodies were detectable within seven to 15 days following disease onset, with levels increasing until days 14–22 before levelling and then decreasing, but titres were lower in those with asymptomatic or clinically mild disease. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross-reactivity but limited cross-neutralisation with other human coronaviridae was reported. Evidence for protective immunity in vivo was limited to small, short-term animal studies, showing promising initial results in the immediate recovery phase. Conclusions: Literature on antibody responses to SARS-CoV-2 is of variable quality with considerable heterogeneity of methods, study participants, outcomes measured and assays used. Although acute phase antibody dynamics are well described, longer-term patterns are much less well evidenced. Comprehensive assessment of the role of demographic characteristics and disease severity on antibody responses is needed. Initial findings of low neutralising antibody titres and possible waning of titres over time may have implications for sero-surveillance and disease control policy, although further evidence is needed. The detection of potent neutralising antibodies in convalescent plasma is important in the context of development of therapeutics and vaccines. Due to limitations with the existing evidence base, large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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24. Classical and Non-classical Presentations of Complement Factor I Deficiency: Two Contrasting Cases Diagnosed via Genetic and Genomic Methods.
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Shields, Adrian M., Pagnamenta, Alistair T., Pollard, Andrew J., Taylor, Jenny C., Allroggen, Holger, Patel, Smita Y., Knight, Samantha J. L., Popitsch, Niko, Camps, Carme, Pentony, Melissa M., Kvikstad, Erika M., Lange, Lukas, Hashim, Mona, Harris, Steve, Tilley, Mark, Vavoulis, Dimitris, Kaisaki, Pamela, Ragoussis, Vassilis, Feral, Matteo, and Schuh, Anna H.
- Subjects
NEUROLOGICAL disorders ,DIAGNOSIS ,BACTERIAL diseases ,GENETICS ,RARE diseases - Abstract
Deficiency of complement factor I is a rare immunodeficiency that typically presents with increased susceptibility to encapsulated bacterial infections. However, non-infectious presentations including rheumatological, dermatological and neurological disease are increasingly recognized and require a high-index of suspicion to reach a timely diagnosis. Herein, we present two contrasting cases of complement factor I deficiency: one presenting in childhood with invasive pneumococcal disease, diagnosed using conventional immunoassays and genetics and the second presenting in adolescence with recurrent sterile neuroinflammation, diagnosed via a genomic approach. Our report and review of the literature highlight the wide spectrum of clinical presentations associated with CFI deficiency and the power of genomic medicine to inform rare disease diagnoses. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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25. Improved monitoring of clinical response in Systemic Lupus Erythematosus by longitudinal trend in soluble vascular cell adhesion molecule-1.
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Lewis, Myles J., Vyse, Simon, Shields, Adrian M., Lu Zou, Khamashta, Munther, Gordon, Patrick A., Pitzalis, Costantino, Vyse, Timothy J., and D'Cruz, David P.
- Published
- 2016
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26. RESOURCE UTILISATION ASSOCIATED WITH SINGLE DIGIT DUPUYTREN'S CONTRACTURE TREATED WITH EITHER SURGERY OR INJECTION OF COLLAGENASE CLOSTRIDIUM HISTOLYTICUM.
- Author
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Povlsen, Bo, Shields, Adrian M., and Bhabra, Gev S.
- Subjects
- *
TREATMENT of Dupuytren's contracture , *COLLAGENASES , *INJECTIONS , *HAND abnormality patients , *FINGER surgery , *FOLLOW-up studies (Medicine) , *MEDICAL decision making , *THERAPEUTICS - Abstract
The gold standard treatment for Dupuytren's contracture is surgical excision of the cord. A non-surgical treatment with collagenase clostridium histolyticum injection is available but appears costly. Objectives: To provide data on resource consumption related to surgical and non-surgical treatment for Dupuytren's contracture. Design and Participants: Twenty patients with a single digit Dupuytren's contracture, 10 treated with surgical excision, and 10 treated with a single injection of collagenase. Measurements: Minutes spent in theatre, number of follow-up appointments, time to skin healing, and patients return to normal activities of daily living. Results: The injection group was significantly better regarding theatre time (p < 0.0001), follow-up appointments (p = 0.048), skin healing time (p < 0.001), and return to normal activities of daily living (p = 0.02) than the operated group. Conclusions: There are significant personal and health economic differences between the two methods of treatment which may influence local choice. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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27. COVID-19 in patients with primary and secondary immunodeficiency: The United Kingdom experience.
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Shields, Adrian M., Burns, Siobhan O., Savic, Sinisa, and Richter, Alex G.
- Abstract
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. We sought to document the outcomes of individuals with PID or symptomatic SID following COVID-19 in the United Kingdom. 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. 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). 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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28. UBE2L3 Polymorphism Amplifies NF-κB Activation and Promotes Plasma Cell Development, Linking Linear Ubiquitination to Multiple Autoimmune Diseases.
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Lewis, Myles J., Vyse, Simon, Shields, Adrian M., Boeltz, Sebastian, Gordon, Patrick A., Spector, Timothy D., Lehner, Paul J., Walczak, Henning, and Vyse, Timothy J.
- Subjects
- *
GENETIC polymorphisms , *NF-kappa B , *BLOOD plasma , *CELL growth , *UBIQUITINATION , *AUTOIMMUNE diseases , *DISEASE susceptibility , *SYSTEMIC lupus erythematosus - Abstract
UBE2L3 is associated with increased susceptibility to numerous autoimmune diseases, but the underlying mechanism is unexplained. By using data from a genome-wide association study of systemic lupus erythematosus (SLE), we observed a single risk haplotype spanning UBE2L3 , consistently aligned across multiple autoimmune diseases, associated with increased UBE2L3 expression in B cells and monocytes. rs140490 in the UBE2L3 promoter region showed the strongest association. UBE2L3 is an E2 ubiquitin-conjugating enzyme, specially adapted to function with HECT and RING-in-between-RING (RBR) E3 ligases, including HOIL-1 and HOIP, components of the linear ubiquitin chain assembly complex (LUBAC). Our data demonstrate that UBE2L3 is the preferred E2 conjugating enzyme for LUBAC in vivo, and UBE2L3 is essential for LUBAC-mediated activation of NF-κB. By accurately quantifying NF-κB translocation in primary human cells from healthy individuals stratified by rs140490 genotype, we observed that the autoimmune disease risk UBE2L3 genotype was correlated with basal NF-κB activation in unstimulated B cells and monocytes and regulated the sensitivity of NF-κB to CD40 stimulation in B cells and TNF stimulation in monocytes. The UBE2L3 risk allele correlated with increased circulating plasmablast and plasma cell numbers in SLE individuals, consistent with substantially elevated UBE2L3 protein levels in plasmablasts and plasma cells. These results identify key immunological consequences of the UBE2L3 autoimmune risk haplotype and highlight an important role for UBE2L3 in plasmablast and plasma cell development. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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29. Vitamin D status: a U-shaped relationship for SARS-CoV-2 seropositivity in UK healthcare workers.
- Author
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Lugg ST, Mackay WR, Faniyi AA, Faustini SE, Webster C, Duffy JE, Hewison M, Shields AM, Parekh D, Richter AG, Scott A, and Thickett DR
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- Female, Health Personnel, Humans, Male, SARS-CoV-2, State Medicine, United Kingdom epidemiology, Vitamin D, COVID-19 epidemiology, Vitamin D Deficiency epidemiology
- Abstract
Background: There is increasing evidence that vitamin D (VD) deficiency may increase individuals' risk of COVID-19 infection and susceptibility. We aimed to determine the relationship between VD deficiency and sufficiency and COVID-19 seropositivity within healthcare workers., Methods: The study included an observational cohort of healthcare workers who isolated due to COVID-19 symptoms from 12 May to 22 May 2020, from the University Hospitals Birmingham National Health Service Foundation Trust. Data collected included SARS-CoV-2 seroconversion status, serum 25(OH)D
3 levels, age, body mass index (BMI), sex, ethnicity, job role and comorbidities. Participants were grouped into four VD categories: (1) Severe VD deficiency (VD<30 nmol/L); (2) VD deficiency (30 nmol/L ≤VD<50 nmol/L); (3) VD insufficiency (50 nmol/L ≤VD<75 nmol/L); (4) VD sufficiency (VD≥75 nmol/L)., Results: When VD levels were compared against COVID-19 seropositivity rate, a U-shaped curve was identified. This trend repeated when participants were split into subgroups of age, sex, ethnicity, BMI and comorbidity status. Significant difference was identified in the COVID-19 seropositivity rate between VD groups in the total population and between groups of men and women; black, Asian and minority ethnic (BAME) group; BMI<30 (kg/m2 ); 0 and +1 comorbidities; the majority of which were differences when the severely VD deficient category were compared with the other groups. A larger proportion of those within the BAME group (vs white ethnicity) were severely VD deficient (p < 0.00001). A larger proportion of the 0 comorbidity subgroup were VD deficient in comparison to the 1+ comorbidity subgroup (p=0.046)., Conclusions: Our study has shown a U-shaped relationship for COVID-19 seropositivity in UK healthcare workers. Further investigation is required to determine whether high VD levels can have a detrimental effect on susceptibility to COVID-19 infection. Future randomised clinical trials of VD supplementation could potentially identify 'optimal' VD levels, allowing for targeted therapeutic treatment for those at risk., Competing Interests: Competing interests: MH reports personal fees from Thornton Ross, outside the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2022
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30. Health Care Professionals' Confidence and Preferences for Diagnostic Assays for SARS-CoV-2: A Global Study.
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Shields AM, Brown H, Phillips N, Drayson MT, Richter AA, and Richter AG
- Subjects
- Adult, Female, Humans, Male, Polymerase Chain Reaction, Saliva, COVID-19 diagnosis, COVID-19 mortality, COVID-19 Testing, Global Health, Health Personnel statistics & numerical data
- Abstract
Background: The COVID-19 pandemic has led to an urgent requirement for novel diagnostic tests that determine infection with SARS-CoV-2 and the development of an immune response against it. The perspective of end users on the characteristics and clinical use of these assays has not been previously considered. Methods: We surveyed 17,186 health care professions (HCPs) in 29 countries to gauge opinion on the design, use, diagnostic impact and diagnostic accuracy of COVID-19 tests. Results were correlated with national statistics on the burden of disease and testing in individual countries. Results: HCPs overwhelmingly recognized the importance of COVID-19 tests but 37.1% were unsure of the appropriate timing of investigations relative to disease symptoms. Confidence in the diagnostic accuracy of assays varied inversely with COVID-19-related mortality in individual countries but had no relationship with the total number of tests performed. There was global consensus that the most important impact of positive antigen and antibody testing was confidence in returning to work following recovery. Saliva was the preferred sampling fluid for COVID-19 diagnostic tests in all groups surveyed. Conclusions: HCP input can ensure novel assays are fit for purpose in varied global health care settings, but HCPs may require support to effectively use novel diagnostics thus minimizing waste when supplies are limited., Competing Interests: MD reports personal fees from Abingdon Health, outside the submitted work. HB, NP, and AAR are employees of M3 Global Research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shields, Brown, Phillips, Drayson, Richter and Richter.)
- Published
- 2021
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31. Serological responses to SARS-CoV-2 following non-hospitalised infection: clinical and ethnodemographic features associated with the magnitude of the antibody response.
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Shields AM, Faustini SE, Perez-Toledo M, Jossi S, Allen JD, Al-Taei S, Backhouse C, Dunbar L, Ebanks D, Emmanuel B, Faniyi AA, Garvey MI, Grinbergs A, McGinnell G, O'Neill J, Watanabe Y, Crispin M, Wraith DC, Cunningham AF, Drayson MT, and Richter AG
- Abstract
Objective: To determine clinical and ethnodemographic correlates of serological responses against the SARS-CoV-2 spike glycoprotein following mild-to-moderate COVID-19., Design: A retrospective cohort study of healthcare workers who had self-isolated due to COVID-19., Setting: University Hospitals Birmingham NHS Foundation Trust, UK (UHBFT)., Participants: 956 health care workers were recruited by open invitation via UHBFT trust email and social media., Intervention: Participants volunteered a venous blood sample that was tested for the presence of anti-SARS-CoV-2 spike glycoprotein antibodies. Results were interpreted in the context of the symptoms of their original illness and ethnodemographic variables., Results: Using an assay that simultaneously measures the combined IgG, IgA and IgM response against the spike glycoprotein (IgGAM), the overall seroprevalence within this cohort was 46.2% (n=442/956). The seroprevalence of immunoglobulin isotypes was 36.3%, 18.7% and 8.1% for IgG, IgA and IgM respectively. IgGAM identified serological responses in 40.6% (n=52/128) of symptomatic individuals who reported a negative SARS-CoV-2 PCR test. Increasing age, non-white ethnicity and obesity were independently associated with greater IgG antibody response against the spike glycoprotein. Self-reported fever and fatigue were associated with greater IgG and IgA responses against the spike glycoprotein. The combination of fever and/or cough and/or anosmia had a positive predictive value of 92.3% for seropositivity., Conclusions and Relevance: Assays employing combined antibody detection demonstrate enhanced seroepidemiological sensitivity and can detect prior viral exposure even when PCR swabs have been negative. We demonstrate an association between known ethnodemographic risk factors associated with mortality from COVID-19 and the magnitude of serological responses in mild-to-moderate disease. The combination of cough, and/or fever and/or anosmia identifies the majority of individuals who should self-isolate for COVID-19.
- Published
- 2020
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32. Detection of antibodies to the SARS-CoV-2 spike glycoprotein in both serum and saliva enhances detection of infection.
- Author
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Faustini SE, Jossi SE, Perez-Toledo M, Shields AM, Allen JD, Watanabe Y, Newby ML, Cook A, Willcox CR, Salim M, Goodall M, Heaney JL, Marcial-Juarez E, Morley GL, Torlinska B, Wraith DC, Veenith TV, Harding S, Jolles S, Ponsford MJ, Plant T, Huissoon A, O'Shea MK, Willcox BE, Drayson MT, Crispin M, Cunningham AF, and Richter AG
- Abstract
Background: Detecting antibody responses during and after SARS-CoV-2 infection is essential in determining the seroepidemiology of the virus and the potential role of antibody in disease. Scalable, sensitive and specific serological assays are essential to this process. The detection of antibody in hospitalized patients with severe disease has proven straightforward; detecting responses in subjects with mild disease and asymptomatic infections has proven less reliable. We hypothesized that the suboptimal sensitivity of antibody assays and the compartmentalization of the antibody response may contribute to this effect., Methods: We systemically developed an ELISA assay, optimising different antigens and amplification steps, in serum and saliva from symptomatic and asymptomatic SARS-CoV-2-infected subjects., Results: Using trimeric spike glycoprotein, rather than nucleocapsid enabled detection of responses in individuals with low antibody responses. IgG1 and IgG3 predominate to both antigens, but more anti-spike IgG1 than IgG3 was detectable. All antigens were effective for detecting responses in hospitalized patients. Anti-spike, but not nucleocapsid, IgG, IgA and IgM antibody responses were readily detectable in saliva from non-hospitalized symptomatic and asymptomatic individuals. Antibody responses in saliva and serum were largely independent of each other and symptom reporting., Conclusions: Detecting antibody responses in both saliva and serum is optimal for determining virus exposure and understanding immune responses after SARS-CoV-2 infection., Funding: This work was funded by the University of Birmingham, the National Institute for Health Research (UK), the NIH National Institute for Allergy and Infectious Diseases, the Bill and Melinda Gates Foundation and the University of Southampton.
- Published
- 2020
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33. Serology confirms SARS-CoV-2 infection in PCR-negative children presenting with Paediatric Inflammatory Multi-System Syndrome.
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Perez-Toledo M, Faustini SE, Jossi SE, Shields AM, Kanthimathinathan HK, Allen JD, Watanabe Y, Goodall M, Wraith DC, Veenith TV, Drayson MT, Jyothish D, Al-Abadi E, Chikermane A, Welch SB, Masilamani K, Hackett S, Crispin M, Scholefield BR, Cunningham AF, and Richter AG
- Abstract
Background: During the COVID-19 outbreak, reports have surfaced of children who present with features of a multisystem inflammatory syndrome with overlapping features of Kawasaki disease and toxic shock syndrome - Paediatric Inflammatory Multisystem Syndrome- temporally associated with SARS-CoV-2 pandemic (PIMS-TS). Initial reports find that many of the children are PCR-negative for SARS-CoV-2, so it is difficult to confirm whether this syndrome is a late complication of viral infection in an age group largely spared the worst consequences of this infection, or if this syndrome reflects enhanced surveillance., Methods: Children hospitalised for symptoms consistent with PIMS-TS between 28 April and 8 May 2020, and who were PCR-negative for SARS-CoV-2, were tested for antibodies to viral spike glycoprotein using an ELISA test., Results: Eight patients (age range 7-14 years, 63% male) fulfilled case-definition for PIMS-TS during the study period. Six of the eight patients required admission to intensive care. All patients exhibited significant IgG and IgA responses to viral spike glycoprotein. Further assessment showed that the IgG isotypes detected in children with PIMS-TS were of the IgG1 and IgG3 subclasses, a distribution similar to that observed in samples from hospitalised adult COVID-19 patients. In contrast, IgG2 and IgG4 were not detected in children or adults. IgM was not detected in children, which contrasts with adult hospitalised adult COVID-19 patients of whom all had positive IgM responses., Conclusions: Strong IgG antibody responses can be detected in PCR-negative children with PIMS-TS. The low detection rate of IgM in these patients is consistent with infection having occurred weeks previously and that the syndrome onset occurs well after the control of SARS-CoV-2 viral load. This implies that the disease is largely immune-mediated. Lastly, this indicates that serology can be an appropriate diagnostic tool in select patient groups.
- Published
- 2020
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34. A New-Age for Biologic Therapies: Long-Term Drug-Free Therapy with BiP?
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Shields AM, Panayi GS, and Corrigall VM
- Abstract
Heat shock proteins (HSPs) and other members of the much broader stress protein family have been shown to play important roles in coordinating multiple phases of immunological reactions; from facilitating immunological recognition, to promoting and regulating immunological responses and finally augmenting the resolution of inflammation and return to immunological homeostasis. In this review, we consider the challenges facing the stress protein field as we enter 2012; in particular we consider the role that HSPs and stress proteins may play in the initiation and termination of immunological responses. Special attention is afforded to the resolution-associated molecular pattern, binding immunoglobulin protein (BiP, also known as glucose regulated protein-78). We review the evidence that resolution-promoting proteins such as BiP may herald a new generation of biologics for inflammatory disease and reflect on the challenges of achieving clinical remission in rheumatoid arthritis with novel therapeutics and correlating clinical remission with immunological parameters of resolution of inflammation.
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- 2012
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35. Right ventricular metastasis of transitional cell carcinoma of the renal pelvis: successful single stage surgical treatment.
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Shields AM, Pomplun S, Deshpande R, and Whitaker DC
- Subjects
- Biopsy, Needle, Cardiac Surgical Procedures methods, Echocardiography, Doppler, Female, Follow-Up Studies, Heart Neoplasms diagnosis, Heart Ventricles pathology, Heart Ventricles surgery, Humans, Immunohistochemistry, Kidney Neoplasms pathology, Magnetic Resonance Imaging methods, Middle Aged, Nephrectomy methods, Rare Diseases, Risk Assessment, Tomography, X-Ray Computed methods, Treatment Outcome, Carcinoma, Transitional Cell secondary, Carcinoma, Transitional Cell surgery, Heart Neoplasms secondary, Heart Neoplasms surgery, Kidney Neoplasms surgery
- Abstract
A 58-year-old female presented with symptoms mimicking infective endocarditis and was diagnosed with a right ventricular metastasis from a transitional cell carcinoma (TCC) of the left renal pelvis. The patient was treated with concurrent removal of the cardiac tumour and radical left nephrectomy followed by adjuvant gemcitabine-cisplatin chemotherapy. To our knowledge, this is the 14th report of cardiac metastases from TCC and the only case where one-stage surgical management of primary and cardiac metastases from TCC has been successfully completed.
- Published
- 2011
- Full Text
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