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  • 1
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    Online Resource
    1959. Lower B-Cell Responses Rather Than Circulating Antibody Titres Are Associated With SARS-CoV-2 Infection Post Third Dose COVID-19 Vaccination
    Oxford University Press (OUP) ; 2022
    In:  Open Forum Infectious Diseases Vol. 9, No. Supplement_2 ( 2022-12-15)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: Which components of the immune response to SARS-CoV-2 vaccination best protect against subsequent infection remains unclear. We explored SARS-CoV-2 specific antibody and B-cell responses post 3rd dose vaccine and their relationship to subsequent SARS-CoV-2 infection. Methods In a multicentre prospective cohort, adult subjects provided samples before and 14 days (d14) post 3rd dose vaccine with Pfizer-BioNTech 162b2. At 18-22 weeks post vaccine, subjects self-reported SARS-CoV-2 infection (confirmed by PCR or antigen test). We used electrochemiluminescence assays to quantify antibodies to SARS-CoV-2 spike subunit 1 (S1), subunit 2 (S2) and receptor-binding domain (RBD) in plasma (reported in WHO IU/mL). In a subset of subjects, we assessed SARS-CoV-2 specific differentiated B-cell (plasma cell) and memory B-cell responses from peripheral blood mononuclear cells. Unstimulated plasma cells, and memory B cells stimulated with R848 and IL2, were seeded on plates coated with RBD or full Spike antigen and antigen-specific responses measured by ELISpot (Mabtech ELISpot, Sweden). We compared between group differences by Wilcoxon signed rank or Mann–Whitney tests. Data are median [IQR] unless specified. Results Of 133 subjects (age 43 [32-50], 81.2% female (table 1), 77 subjects in the B-cell subgroup (table 2)), 47 (35.3%) reported SARS-CoV-2 infection post 3rd vaccine. Antibody titres, plasma cell and memory B-cell responses all increased significantly at d14 post 3rd vaccine (Table 1 & 2, all P & lt; 0.001). Although d14 antibody titres did not differ in those with and without subsequent infection (table 1), those reporting subsequent infection had significantly lower d14 RBD-specific plasma cells and a lower proportion of RBD-specific memory B-cells (Figure 1a-b, both P & lt; 0.05). Similar results were observed with full-spike-specific memory B-cell responses (Figure 1d). The differences persisted when the non-infected group was restricted only to those reporting a confirmed close contact (n=26). Conclusion Infection following 3rd dose vaccine is associated with lower d14 circulating and memory B cell responses, but not antibody titres, suggesting B-cell responses better predict protection against subsequent SARS-CoV-2 infection. Disclosures All Authors: No reported disclosures.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofac492.1585
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 2
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    Identification of Distinct Long COVID Clinical Phenotypes Through Cluster Analysis of Self-Reported Symptoms
    Oxford University Press (OUP) ; 2022
    In:  Open Forum Infectious Diseases Vol. 9, No. 4 ( 2022-04-01)
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    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. 4 ( 2022-04-01)
    Abstract: We aimed to describe the clinical presentation of individuals presenting with prolonged recovery from coronavirus disease 2019 (COVID-19), known as long COVID. Methods This was an analysis within a multicenter, prospective cohort study of individuals with a confirmed diagnosis of COVID-19 and persistent symptoms & gt;4 weeks from onset of acute symptoms. We performed a multiple correspondence analysis (MCA) on the most common self-reported symptoms and hierarchical clustering on the results of the MCA to identify symptom clusters. Results Two hundred thirty-three individuals were included in the analysis; the median age of the cohort was 43 (interquartile range [IQR], 36–54) years, 74% were women, and 77.3% reported a mild initial illness. MCA and hierarchical clustering revealed 3 clusters. Cluster 1 had predominantly pain symptoms with a higher proportion of joint pain, myalgia, and headache; cluster 2 had a preponderance of cardiovascular symptoms with prominent chest pain, shortness of breath, and palpitations; and cluster 3 had significantly fewer symptoms than the other clusters (2 [IQR, 2–3] symptoms per individual in cluster 3 vs 6 [IQR, 5–7] and 4 [IQR, 3–5] in clusters 1 and 2, respectively; P  & lt; .001). Clusters 1 and 2 had greater functional impairment, demonstrated by significantly longer work absence, higher dyspnea scores, and lower scores in SF-36 domains of general health, physical functioning, and role limitation due to physical functioning and social functioning. Conclusions Clusters of symptoms are evident in long COVID patients that are associated with functional impairments and may point to distinct underlying pathophysiologic mechanisms of disease.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofac060
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 3
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    Temporal trends in COVID-19 outcomes in people with rheumatic diseases in Ireland: data from the COVID-19 Global Rheumatology Alliance registry
    Oxford University Press (OUP) ; 2022
    In:  Rheumatology Vol. 61, No. SI2 ( 2022-06-28), p. SI151-SI156
    Details
    In: Rheumatology, Oxford University Press (OUP), Vol. 61, No. SI2 ( 2022-06-28), p. SI151-SI156
    Abstract: Although evidence is accumulating globally, data on outcomes in rheumatic disease and COVID-19 in Ireland are limited. We used data from the COVID-19 Global Rheumatology Alliance (C19-GRA) to describe time-varying COVID-19 outcomes for people with rheumatic disease in Ireland. Methods Data entered into the C19-GRA provider registry from Ireland between 24 March 2020 and 9 July 2021 were analysed. Differences in the likelihood of hospitalization and mortality according to demographic and clinical variables were investigated using Chi-squared test or Fisher’s exact test, as appropriate. Trends in odds of hospitalization and mortality over time were investigated using logistic regression with the time period as a categorical variable. Results Of 212 cases included, 59.4% were female and median age was 58.0 years (range 13–96). Of the 212 cases, 92 (43%) were hospitalized and 22 (10.4%) died. Increasing age, a diagnosis of gout, ever smoking, glucocorticoid use, having comorbidities and specific comorbidities of cancer, cardiovascular and pulmonary disease were more common in those hospitalized. A diagnosis of inflammatory arthritis, csDMARD and/or b/tsDMARD use were less frequent in those hospitalized. Increasing age, a diagnosis of gout, ever smoking, having comorbidities and specific comorbidities of obesity, cardiovascular and pulmonary disease were more common in those who died. Odds of hospitalization or mortality did not change over time. Conclusion No temporal trend was observed in either COVID-19-related hospitalization or mortality outcomes for people with rheumatic disease in Ireland.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    URL: Article
    DOI: 10.1093/rheumatology/keac142
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1474143-X
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  • 4
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    Dynamic platelet function: A novel biomarker in inflammatory arthritis?
    Public Library of Science (PLoS) ; 2022
    In:  PLOS ONE Vol. 17, No. 1 ( 2022-1-25), p. e0261825-
    Details
    In: PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 1 ( 2022-1-25), p. e0261825-
    Abstract: Patients with inflammatory arthritis die prematurely of cardiovascular disease. Inflammation activates platelets. Since treatment of inflammatory arthritis is associated with reduced mortality, and decreased platelet reactivity reduces cardiovascular events, we hypothesised that platelet reactivity as measured by dynamic platelet function (DPF) would be increased in patients with inflammatory arthritis and that reactivity could be reduced with therapeutic intervention. Objectives To characterise platelet function using a validated physiological assay in patients with inflammatory arthritis before and after disease improvement. Methods 22 patients were recruited and treated as per local protocol. DPF was measured at baseline and after clinical improvement. Video microscopy was utilised to measure dynamic platelet behaviour in microliters of blood perfused over von Willebrand factor (VWF) at arterial shear rates (1500 s-1). Motion-analysis software measured the number of platelets interacting with VWF, translocating across VWF, the speed and distance platelets travelled across VWF, and stably adhering to the surface. Platelet parameters at baseline and following improvement were compared using Wilcoxon signed rank test and paired student t-test. Changes in platelet function were correlated to inflammatory disease markers by Pearson Correlation. Results 18 patients completed the study. Platelet adhesion decreased and platelet motion increased following treatment. Tender joint count correlated with platelet adhesion (Pearson r = 0.616, p≤0.01) while CRP correlated with velocity of platelet movement (Pearson r = 0.563, p≤0.01). Conclusions Improvement in clinical markers of inflammation is associated with a corresponding change in platelet function. Given the association between reduced mortality and decreased platelet reactivity our results suggest that an appropriate assay of platelet function could guide future therapy of patients with inflammatory arthritis.
    Type of Medium: Online Resource
    ISSN: 1932-6203
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1371/journal.pone.0261825
    DOI: 10.1371/journal.pone.0261825.g001
    DOI: 10.1371/journal.pone.0261825.g002
    DOI: 10.1371/journal.pone.0261825.t001
    DOI: 10.1371/journal.pone.0261825.t002
    DOI: 10.1371/journal.pone.0261825.t003
    DOI: 10.1371/journal.pone.0261825.s001
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2022
    detail.hit.zdb_id: 2267670-3
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