scholarly journals Systemic and mucosal antibody secretion specific to SARS-CoV-2 during mild versus severe COVID-19

2020 ◽  
Author(s):  
Carlo Cervia ◽  
Jakob Nilsson ◽  
Yves Zurbuchen ◽  
Alan Valaperti ◽  
Jens Schreiner ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Healthcare Workers ◽  
Immunoglobulin A ◽  
Antibody Responses ◽  
Patient Age ◽  
Mild Disease ◽  
Specific Serum ◽  
Patient Âgé ◽  
Serum Iga ◽  
Very High

AbstractBackgroundInfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an acute illness termed coronavirus disease 2019 (COVID-19). Humoral immune responses likely play an important role in containing SARS-CoV-2, however, the determinants of SARS-CoV-2-specific antibody responses are unclear.MethodsUsing immunoassays specific for the SARS-CoV-2 spike protein, we determined SARS-CoV-2-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) in sera and mucosal fluids of two cohorts, including patients with quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR)-confirmed SARS-CoV-2 infection (n = 56; median age 61 years) with mild versus severe COVID-19, and SARS-CoV-2-exposed healthcare workers (n = 109; median age 36 years) with or without symptoms and tested negative or positive by RT-qPCR.FindingsOn average, SARS-CoV-2-specific serum IgA titers in mild COVID-19 cases became positive eight days after symptom onset and were often transient, whereas serum IgG levels remained negative or reached positive values 9–10 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers as a function of duration since symptom onset, independent of patient age and comorbidities. Very high levels of SARS-CoV-2-specific serum IgA correlated with severe acute respiratory distress syndrome (ARDS). Interestingly, some of the SARS-CoV-2-exposed healthcare workers with negative SARS-CoV-2-specific IgA and IgG serum titers had detectable SARS-CoV-2-specific IgA antibodies in their nasal fluids and tears. Moreover, SARS-CoV-2-specific IgA levels in nasal fluids of these healthcare workers were inversely correlated with patient age.InterpretationThese data show that systemic IgA and IgG production against SARS-CoV-2 develops mainly in severe COVID-19, with very high IgA levels seen in patients with severe ARDS, whereas mild disease may be associated with transient serum titers of SARS-CoV-2-specific antibodies but stimulate mucosal SARS-CoV-2-specific IgA secretion. The findings suggest four grades of antibody responses dependent on COVID-19 severity.

scholarly journals Immune Response Characterization after Controlled Infection with Lyophilized Shigella sonnei 53G

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Kristen A. Clarkson ◽  
Robert W. Frenck ◽  
Michelle Dickey ◽  
Akamol E. Suvarnapunya ◽  
Lakshmi Chandrasekaran ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Antibody Responses ◽  
Memory B Cell ◽  
Content Type ◽  
Cell Responses ◽  
Specific Serum ◽  
Serum Iga ◽  
Risk Of Disease ◽  
Reduced Risk

ABSTRACT Shigella is a major cause of moderate to severe diarrhea largely affecting children (<5 years old) living in low- and middle-income countries. Several vaccine candidates are in development, and controlled human infection models (CHIMs) can be useful tools to provide an early assessment of vaccine efficacy and potentially support licensure. A lyophilized strain of S. sonnei 53G was manufactured and evaluated to establish a dose that safely and reproducibly induced a ≥60% attack rate. Samples were collected pre- and postchallenge to assess intestinal inflammatory responses, antigen-specific serum and mucosal antibody responses, functional antibody responses, and memory B cell responses. Infection with S. sonnei 53G induced a robust intestinal inflammatory response as well as antigen-specific antibodies in serum and mucosal secretions and antigen-specific IgA- and IgG-secreting B cells positive for the α4β7 gut-homing marker. There was no association between clinical disease outcomes and systemic or functional antibody responses postchallenge; however, higher lipopolysaccharide (LPS)-specific serum IgA- and IgA-secreting memory B cell responses were associated with a reduced risk of disease postchallenge. This study provides unique insights into the immune responses pre- and postinfection with S. sonnei 53G in a CHIM, which could help guide the rational design of future vaccines to induce protective immune responses more analogous to those triggered by infection. IMPORTANCE Correlate(s) of immunity have yet to be defined for shigellosis. As previous disease protects against subsequent infection in a serotype-specific manner, investigating immune response profiles pre- and postinfection provides an opportunity to identify immune markers potentially associated with the development of protective immunity and/or with a reduced risk of developing shigellosis postchallenge. This study is the first to report such an extensive characterization of the immune response after challenge with S. sonnei 53G. Results demonstrate an association of progression to shigellosis with robust intestinal inflammatory and mucosal gut-homing responses. An important finding in this study was the association of elevated Shigella LPS-specific serum IgA and memory B cell IgA responses at baseline with reduced risk of disease. The increased baseline IgA responses may contribute to the lack of dose response observed in the study and suggests that IgA responses should be further investigated as potential correlates of immunity.

scholarly journals High National Rates of High-Dose Dopamine Agonist Prescribing for RLS

SLEEP ◽  
2021 ◽  
Author(s):  
John W Winkelman
Keyword(s):  
Dopamine Agonist ◽  
Daily Maximum ◽  
High Dose ◽  
Patient Age ◽  
Dose Rates ◽  
Patient Âgé ◽  
Related Symptom ◽  
Icd 10 ◽  
High Doses ◽  
Very High

Abstract Study Objectives Long-term dopamine agonist (DA) use in restless legs syndrome (RLS) is associated with augmentation, a dose-related symptom worsening leading to further dose escalation to manage RLS. This study investigated rates and factors of high-dose DA prescribing in US RLS patients. Methods This retrospective analysis examined data from a US longitudinal prescriptions database (October 2017–September 2018). Patients diagnosed with RLS (ICD-10 G255.81) without Parkinson’s disease who were prescribed ropinirole, pramipexole, and/or rotigotine were included. Daily DA dosage was categorized: LOW/MID (FDA-approved/guideline or slightly above FDA-approved [pramipexole]); HIGH (101%–149%); VERY HIGH (&gt;150%). Patient counts were converted to US national estimates. Logistic regression of patient counts evaluated factors associated with HIGH/VERY HIGH DA dosing. Results Of 670,404 RLS patients (131,289,331 therapy days), 58.8% were prescribed DA therapy. Overall, 19.1% of RLS patients were prescribed DAs above maximum FDA-approved/guideline daily doses—over half of these were &gt;150% maximum recommended doses; 67.6% of HIGH/VERY HIGH-dose prescriptions were pramipexole (OR [95% CI] pramipexole vs ropinirole, 5.8 [5.7–6.0]). The highest 1% of DA prescriptions were ≥10× the FDA-recommended maximum daily dose. Rates of HIGH/VERY HIGH DA dosing increased with patient age. Twice as many neurologists (31.1%) prescribed HIGH/VERY HIGH doses vs other specialties (OR [95%CI], 2.1 [1.2–2.0]). Conclusions Approximately 20% of DA-treated RLS patients were prescribed doses above the approved and guideline daily maximum. Pramipexole, Neurology as specialty, and patient age were independently associated with HIGH/VERY HIGH DA dosing. Increased education is warranted regarding risks of high-dose DA exposure in RLS.

The predictive relationship of food-specific serum IgE concentrations to challenge outcomes for egg and milk varies by patient age

2007 ◽  
Vol 119 (5) ◽  
pp. 1272-1274 ◽  
Author(s):  
Takatsugu Komata ◽  
Lars Söderström ◽  
Magnus P. Borres ◽  
Hiroshi Tachimoto ◽  
Motohiro Ebisawa
Keyword(s):  
Patient Age ◽  
Serum Ige ◽  
Specific Serum ◽  
Patient Âgé ◽  
Relationship Of ◽  
Predictive Relationship

scholarly journals Longitudinal Development of Antibody Responses in COVID-19 Patients of Different Severity with ELISA, Peptide, and Glycan Arrays: An Immunological Case Series

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 438
Author(s):  
Jasmin Heidepriem ◽  
Christine Dahlke ◽  
Robin Kobbe ◽  
René Santer ◽  
Till Koch ◽  
...  
Keyword(s):  
Immunoglobulin A ◽  
Case Series ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Longitudinal Development ◽  
Vaccination Programs ◽  
Mild Disease ◽  
Peptide Microarrays ◽  
Epitope Spread ◽  
Over Time

The current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). A better understanding of its immunogenicity can be important for the development of improved diagnostics, therapeutics, and vaccines. Here, we report the longitudinal analysis of three COVID-19 patients with moderate (#1) and mild disease (#2 and #3). Antibody serum responses were analyzed using spike glycoprotein enzyme linked immunosorbent assay (ELISA), full-proteome peptide, and glycan microarrays. ELISA immunoglobulin A, G, and M (IgA, IgG, and IgM) signals increased over time for individuals #1 and #2, whereas #3 only showed no clear positive IgG and IgM result. In contrast, peptide microarrays showed increasing IgA/G signal intensity and epitope spread only in the moderate patient #1 over time, whereas early but transient IgA and stable IgG responses were observed in the two mild cases #2 and #3. Glycan arrays showed an interaction of antibodies to fragments of high-mannose and core N-glycans, present on the viral shield. In contrast to protein ELISA, microarrays allow for a deeper understanding of IgA, IgG, and IgM antibody responses to specific epitopes of the whole proteome and glycans of SARS-CoV-2 in parallel. In the future, this may help to better understand and to monitor vaccination programs and monoclonal antibodies as therapeutics.

Gestion orthopédique d’une ankylose de l’ATM chez l’enfant

2020 ◽  
Vol 54 (4) ◽  
pp. 407-418
Author(s):  
Pamela Villalon-Pooley ◽  
Camila Hernandez-Veliz ◽  
Maria Fernanda Pinto-Chavez ◽  
Pierre Bourdiol
Keyword(s):  
Patient Age ◽  
Patient Âgé

Parmi les fractures cranio-faciales, celles affectant le condyle mandibulaire font partie des fractures les plus souvent rencontrées chez le patient en âge pédiatrique. L’évolution sans traitement peut produire une ankylose temporo-mandibulaire entraînant troubles fonctionnels et asymétrie de la croissance cranio-faciale. Le traitement traditionnellement chirurgical est d’un pronostic généralement réservé. Dans cet article est présenté le cas d’un patient, âgé de quatre ans, atteint d’ankylose fibreuse de l’articulation temporo-mandibulaire gauche, suite probable d’une fracture du col du condyle non-diagnostiquée. La libération fonctionnelle de la fibro-ankylose articulaire a été l’objectif de la première étape thérapeutique. Celle-ci a été suivie, à l’âge de sept ans, d’une distraction articulaire obtenue au moyen de butées occlusales controlatérales disposées côté droit. Ceci a produit un ajustement de la croissance dento-alvéolaire assurant à la fois un rattrapage du déficit de croissance unilatéral de départ et une néoformation condylienne par remodelage de l’articulation temporo-mandibulaire gauche. Quatre années après la mise en route de la phase orthopédique initiale, la fonction articulaire restaurée et l’équilibre facial obtenu restent stables chez ce jeune patient

Hemmkörperentwicklung bei Hämophilie-Patienten nach Präparate wechsel

2012 ◽  
Vol 32 (S 01) ◽  
pp. S39-S42 ◽  
Author(s):  
S. Kocher ◽  
G. Asmelash ◽  
V. Makki ◽  
S. Müller ◽  
S. Krekeler ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Observational Study ◽  
Retrospective Observational Study ◽  
Frequent Change ◽  
Patient Age ◽  
Treatment Regimens ◽  
Patient Âgé ◽  
The Relationship ◽  
Observation Period

SummaryThe retrospective observational study surveys the relationship between development of inhibitors in the treatment of haemophilia patients and risk factors such as changing FVIII products. A total of 119 patients were included in this study, 198 changes of FVIII products were evaluated. Results: During the observation period of 12 months none of the patients developed an inhibitor, which was temporally associated with a change of FVIII products. A frequent change of FVIII products didn’t lead to an increase in inhibitor risk. The change between plasmatic and recombinant preparations could not be confirmed as a risk factor. Furthermore, no correlation between treatment regimens, severity, patient age and comorbidities of the patients could be found.

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