scholarly journals Anti-prothrombin autoantibodies enriched after infection with SARS-CoV-2 and influenced by strength of antibody response against SARS-CoV-2 proteins

2021 ◽  
Author(s):  
Marc Emmenegger ◽  
Sreedhar Saseendran Kumar ◽  
Vishalini Emmenegger ◽  
Thomas Buettner ◽  
Peter Schierack ◽  
...  
Keyword(s):  
Antibody Response ◽  
Disease Severity ◽  
Viral Infections ◽  
Igg Antibody ◽  
Mixed Effect ◽  
Pregnancy Morbidity ◽  
Glycoprotein I ◽  
Mixed Effect Models ◽  
Number Of Patients ◽  
Potential Pathogenicity

Antiphospholipid antibodies (aPL), assumed to cause antiphospholipid syndrome (APS), are notorious for their heterogeneity and detect phospholipids and phospholipid-binding proteins. The persistent presence of Lupus anticoagulant and/or aPL against cardiolipin and/or β2 glycoprotein I have been shown to be independent risk factors for vascular thrombosis and pregnancy morbidity in APS. Among others, viral infections have been proposed to trigger the production of aPL while mostly being considered non-pathogenic. Yet, the potential pathogenicity of infection-associated aPL has gained momentum since an increasing number of patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been described with coagulation abnormalities and hyperinflammation, together with the presence of aPL. Here, we present data from a multicentric, mixed-severity study including three cohorts of individuals who contracted SARS-CoV-2 as well as non-infected blood donors. We simultaneously measured 10 different criteria and non-criteria aPL (IgM and IgG) by using a line immunoassay. Further, IgG antibody response against three SARS-CoV-2 proteins was investigated using tripartite automated blood immunoassay technology. Our analyses revealed that select non-criteria aPL are enriched concomitant to or after an infection with SARS-CoV-2. Linear mixed-effect models suggest an association of aPL to prothrombin (PT) with the strength of the antibody response against SARS-CoV-2 and further influenced by SARS-CoV-2 disease severity and sex of the individuals. In conclusion, our study is the first to report an association between disease severity, anti-SARS-CoV-2 immunoreactivity and aPL against PT in patients with SARS-CoV-2.

scholarly journals Anti-prothrombin autoantibodies enriched after infection with SARS-CoV-2 and influenced by strength of antibody response against SARS-CoV-2 proteins

2021 ◽  
Vol 17 (12) ◽  
pp. e1010118
Author(s):  
Marc Emmenegger ◽  
Sreedhar Saseendran Kumar ◽  
Vishalini Emmenegger ◽  
Tomas Malinauskas ◽  
Thomas Buettner ◽  
...  
Keyword(s):  
Antibody Response ◽  
Disease Severity ◽  
Viral Infections ◽  
Igg Antibody ◽  
Infected Blood ◽  
Pregnancy Morbidity ◽  
Glycoprotein I ◽  
Number Of Patients ◽  
Independent Risk Factors ◽  
Potential Pathogenicity

Antiphospholipid antibodies (aPL), assumed to cause antiphospholipid syndrome (APS), are notorious for their heterogeneity in targeting phospholipids and phospholipid-binding proteins. The persistent presence of Lupus anticoagulant and/or aPL against cardiolipin and/or β2 glycoprotein I have been shown to be independent risk factors for vascular thrombosis and pregnancy morbidity in APS. aPL production is thought to be triggered by–among other factors–viral infections, though infection-associated aPL have mostly been considered non-pathogenic. Recently, the potential pathogenicity of infection-associated aPL has gained momentum since an increasing number of patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been described with coagulation abnormalities and hyperinflammation, together with the presence of aPL. Here, we present data from a multicentric, mixed-severity study including three cohorts of individuals who contracted SARS-CoV-2 as well as non-infected blood donors. We simultaneously measured 10 different criteria and non-criteria aPL (IgM and IgG) by using a line immunoassay. Further, IgG antibody response against three SARS-CoV-2 proteins was investigated using tripartite automated blood immunoassay technology. Our analyses revealed that selected non-criteria aPL were enriched concomitant to or after an infection with SARS-CoV-2. Linear mixed-effects models suggest an association of aPL with prothrombin (PT). The strength of the antibody response against SARS-CoV-2 was further influenced by SARS-CoV-2 disease severity and sex of the individuals. In conclusion, our study is the first to report an association between disease severity, anti-SARS-CoV-2 immunoreactivity, and aPL against PT in patients with SARS-CoV-2.

scholarly journals Significantly Low Levels of IgG Antibodies Against Oncogenic Merkel Cell Polyomavirus in Sera From Females Affected by Spontaneous Abortion

2021 ◽  
Vol 12 ◽  
Author(s):  
Chiara Mazziotta ◽  
Giulia Pellielo ◽  
Mauro Tognon ◽  
Fernanda Martini ◽  
John Charles Rotondo
Keyword(s):  
Antibody Response ◽  
Spontaneous Abortion ◽  
Viral Infections ◽  
Merkel Cell Polyomavirus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Merkel Cell ◽  
Igg Antibodies ◽  
Igg Antibody ◽  
The Impact

Merkel cell polyomavirus (MCPyV) is a small DNA tumor virus ubiquitous in humans. MCPyV establishes a clinically asymptomatic lifelong infection in healthy immunocompetent individuals. Viral infections are considered to be risk factors for spontaneous abortion (SA), which is the most common adverse complication of pregnancy. The role of MCPyV in SA remains undetermined. Herein, the impact of MCPyV infection in females affected by SA was investigated. Specifically, an indirect enzyme-linked immunosorbent assay (ELISA) method with two linear synthetic peptides/mimotopes mimicking MCPyV antigens was used to investigate immunoglobulin G (IgG) antibodies against MCPyV in sera from 94 females affected by SA [mean ± standard deviation (SD) age 35 ± (6) years] and from 96 healthy females undergoing voluntary pregnancy interruption [VI, mean (±SD) age 32 ± (7) years]. MCPyV seroprevalence and serological profiles were analyzed. The overall prevalence of serum IgG antibodies against MCPyV was 35.1% (33/94) and 37.5% (36/96) in SA and VI females, respectively (p > 0.05). Notably, serological profile analyses indicated lower optical densities (ODs) in females with SA compared to those undergoing VI (p < 0.05), thus indicating a reduced IgG antibody response in SA females. Circulating IgGs were identified in sera from SA and VI females. Our immunological findings indicate that a relatively reduced fraction of pregnant females carry serum anti-MCPyV IgG antibodies, while SA females presented a more pronounced decrease in IgG antibody response to MCPyV. Although yet to be determined, this immunological decrease might prompt an increase in MCPyV multiplication events in females experiencing abortive events. The role of MCPyV in SA, if present, remains to be determined.

scholarly journals Clinical characteristics and antibody response to SARS-CoV-2 spike 1 protein using VITROS Anti-SARS-CoV-2 antibody tests in COVID-19 patients in Japan

2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Mayu Nagura-Ikeda ◽  
Kazuo Imai ◽  
Katsumi Kubota ◽  
Sakiko Noguchi ◽  
Yutaro Kitagawa ◽  
...  
Keyword(s):  
Antibody Response ◽  
Disease Severity ◽  
Clinical Utility ◽  
Clinical Characteristics ◽  
Igg Antibody ◽  
Laboratory Findings ◽  
Disease Prognosis ◽  
Antibody Assays ◽  
Clinical Records ◽  
Antibody Tests

Introduction. Serological tests for COVID-19 are important in providing results for surveillance and supporting diagnosis. Investigating the serological response in COVID-19 patients with different disease severity is important for assessing the clinical utility of serological assays. Gap Statement. However, few studies have investigated the clinical utility of antibody assays for COVID-19 or differences in antibody response in association with disease severity. Aim. The study aimed to evaluate the clinical characteristics and clinical utility of VITROS SARS-CoV-2 antibody tests according to COVID-19 severity in patients in Japan. Methodology. We analysed 255 serum specimens from 130 COVID-19 patients and examined clinical records and laboratory data. Presence of total (IgA, IgM, and IgG) and specific IgG antibody for the spike 1 antigen of SARS-CoV-2 was determined using VITROS Anti-SARS-CoV-2 antibody tests. Results. Overall, 98 (75.4 %) and 32 (24.6 %) patients had mild and severe COVID-19, respectively. On admission, 76 (58.5 %) and 45 (34.6 %) patients were positive for total and IgG antibody assays. Among 91 patients at discharge, 90 (98.9 %) and 81 (89.0 %) were positive for total and IgG antibody, respectively. Clinical background and laboratory findings on admission, but not the prevalence or concentration of total or IgG antibody, were associated with disease prognosis. Total and IgG antibody intensities were significantly higher in severe cases than in mild cases in serum collected >11 days after onset, but not within 10 days. Conclusion. VITROS Anti-SARS-CoV-2 total and IgG assays will be useful as supporting diagnostic and surveillance tools and for evaluation of humoral immune response to COVID-19. Optimal prediction of disease prognosis is made from considering both clinical history and laboratory findings.

scholarly journals The Study of Humoral Immunity in Healthсare Workers Exposed to COVID-19 Patients

2021 ◽  
pp. 70-74
Author(s):  
EP Sizova ◽  
MA Patyashina ◽  
LV Stavropolskaya ◽  
GG Badamshina ◽  
LM Fatkhutdinova
Keyword(s):  
Antibody Response ◽  
Humoral Immunity ◽  
Nucleocapsid Protein ◽  
Healthcare Workers ◽  
Viral Infections ◽  
Igg Antibodies ◽  
Igg Antibody ◽  
Scientific Center ◽  
Response Index ◽  
Test Kit

Introduction: Today, the novel coronavirus disease (hereinafter referred to as COVID-19) is spreading very quickly, and the healthcare workers exposed to COVID-19 patients represent the most vulnerable occupational cohort at risk of this contagious disease. Issues of immunological protection and health monitoring in medical personnel are of special interest and importance during the pandemic. The objective of our study was to assess humoral immunity in healthcare professionals by the presence of class G (IgG) antibodies to the nucleocapsid protein of SARS-CoV-2. Methods: We selected 345 healthcare workers of different specialties who might have been exposed to COVID-19 patients in hospitals and 72 age- and sex-matched controls (engineers, IT-personnel, and accountants) working elsewhere. Blood immunoglobulins G to the nucleocapsid protein of SARS-CoV-2 were tested by enzyme immunoassay using the commercial test kit produced by the Scientific Center for Applied Microbiology and Biotechnology, Obolensk, Russian Federation. The presence of IgG antibodies was established by the SARS-CoV-2 IgG antibody response index (index of positivity) calculated as the ratio of the optical density of the sample to the cut-off level of the assay. Results: The average IgG antibody response index value was significantly higher in the healthcare workers compared to the controls (p < 0.05). IgG antibodies to SARS-CoV-2 were more prevalent in nurses than in physicians (42.2 ± 3.6 % vs 31.0 ± 3.7 %, p < 0.05) and controls (42.2 ± 3.6 % vs 27.8 ± 5.3 %, p < 0.05) and their index values were higher than in the comparison group (p < 0.05). Conclusion: Our findings demonstrate a high prevalence of diagnostically important SARS-CoV-2 IgG antibody response and higher index values in nurses possibly related to prolonged contacts with COVID-19 patients. IgG antibodies found in 37.1 ± 2.6 % of the healthcare workers may be a consequence of both symptomatic and asymptomatic diseases and requires further study. According to the generally accepted opinion about the mechanisms of immune response to viral infections, we could assume the presence of protective immunity against COVID-19, but this issue requires further investigation. In the current epidemic situation, however, detection of IgG antibodies to SARS-CoV-2 can be used for implementation of preventive strategies among healthcare workers.

scholarly journals Influenza and other respiratory viral infections associated with absence from school among schoolchildren in Pittsburgh, Pennsylvania, USA: a cohort study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jonathan M. Read ◽  
Shanta Zimmer ◽  
Charles Vukotich ◽  
Mary Lou Schweizer ◽  
David Galloway ◽  
...  
Keyword(s):  
Cohort Study ◽  
Viral Infections ◽  
Influenza Infection ◽  
Respiratory Viruses ◽  
Influenza B ◽  
Mixed Effect ◽  
School Aged Children ◽  
Respiratory Viral Infections ◽  
Day Programs ◽  
K 12

Abstract Background Information on the etiology and age-specific burden of respiratory viral infections among school-aged children remains limited. Though school aged children are often recognized as driving the transmission of influenza as well as other respiratory viruses, little detailed information is available on the distribution of respiratory infections among children of different ages within this group. Factors other than age including gender and time spent in school may also be important in determining risk of infection but have been little studied in this age group. Methods We conducted a cohort study to determine the etiology of influenza like illness (ILI) among 2519 K–12 students during the 2012–13 influenza season. We obtained nasal swabs from students with ILI-related absences. Generalized linear mixed-effect regressions determined associations of outcomes, including ILI and laboratory-confirmed respiratory virus infection, with school grade and other covariates. Results Overall, 459 swabs were obtained from 552 ILI–related absences. Respiratory viruses were found in 292 (63.6%) samples. Influenza was found in 189 (41.2%) samples. With influenza B found in 134 (70.9%). Rates of influenza B were significantly higher in grades 1 (10.1, 95% CI 6.8–14.4%), 2 (9.7, 6.6–13.6%), 3 (9.3, 6.3–13.2%), and 4 (9.9, 6.8–13.8%) than in kindergarteners (3.2, 1.5–6.0%). After accounting for grade, sex and self-reported vaccination status, influenza B infection risk was lower among kindergarteners in half-day programs compared to kindergarteners in full-day programs (OR = 0.19; 95% CI 0.08–0.45). Conclusions ILI and influenza infection is concentrated in younger schoolchildren. Reduced infection by respiratory viruses is associated with a truncated school day for kindergarteners but this finding requires further investigation in other grades and populations.

scholarly journals Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Anna C. Aschenbrenner ◽  
◽  
Maria Mouktaroudi ◽  
Benjamin Krämer ◽  
Marie Oestreich ◽  
...  
Keyword(s):  
Immune System ◽  
Disease Severity ◽  
Whole Blood ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Target Prediction ◽  
Data Driven ◽  
Host Responses ◽  
Drug Candidates ◽  
Drug Target Prediction

Abstract Background The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system. Methods In order to dissect COVID-19-driven immune host responses, we performed RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Additionally, publicly available data was used to show the distinction from COVID-19 to other diseases. Reverse drug target prediction was used to identify known or novel drug candidates based on finding from data-driven findings. Results Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 16 COVID-19 patients (44 samples). Comparison of COVID-19 blood transcriptomes with those of a collection of over 3100 samples derived from 12 different viral infections, inflammatory diseases, and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host. Conclusions Our study provides novel insights in the distinct molecular subgroups or phenotypes that are not simply explained by clinical parameters. We show that whole blood transcriptomes are extremely informative for COVID-19 since they capture granulocytes which are major drivers of disease severity.

scholarly journals Antibiotic Use Prior to Hospital Presentation Among Individuals With Suspected Enteric Fever in Nepal, Bangladesh, and Pakistan

2020 ◽  
Vol 71 (Supplement_3) ◽  
pp. S285-S292
Author(s):  
Krista Vaidya ◽  
Kristen Aiemjoy ◽  
Farah N Qamar ◽  
Samir K Saha ◽  
Dipesh Tamrakar ◽  
...  
Keyword(s):  
Blood Culture ◽  
Disease Severity ◽  
Enteric Fever ◽  
Clinical Care ◽  
Prevalence Ratio ◽  
Antibiotic Use ◽  
Urine Samples ◽  
Mixed Effect ◽  
Culture Positivity ◽  
Blood Culture Positivity

Abstract Background Antibiotic use prior to seeking care at a hospital may reduce the sensitivity of blood culture for enteric fever, with implications for both clinical care and surveillance. The Surveillance for Enteric Fever in Asia Project (SEAP) is a prospective study of enteric fever incidence in Nepal, Bangladesh, and Pakistan. Nested within SEAP, we evaluated the accuracy of self-reported antibiotic use and investigated the association between antibiotic use and blood culture positivity. Methods Between November 2016 and April 2019, we collected urine samples among a subset of SEAP participants to test for antibiotic use prior to the hospital visit using an antibacterial activity assay. All participants were asked about recent antibiotic use and had a blood culture performed. We used mixed-effect logit models to evaluate the effect of antimicrobial use on blood culture positivity, adjusted for markers of disease severity. Results We enrolled 2939 patients with suspected enteric fever. Antibiotics were detected in 39% (1145/2939) of urine samples. The correlation between measured and reported antibiotic use was modest (κ = 0.72). After adjusting for disease severity, patients with antibiotics in their urine were slightly more likely to be blood culture positive for enteric fever; however, the effect was not statistically significant (prevalence ratio, 1.22 [95% confidence interval, .99–1.50]). Conclusions The reliability of self-reported prior antibiotic use was modest among individuals presenting with fever to tertiary hospitals. While antibiotics are likely to reduce the sensitivity of blood culture, our findings indicate that there is still considerable value in performing blood culture for individuals reporting antibiotic use.

scholarly journals A hierarchical bivariate meta-analysis of diagnostic test accuracy to provide direct comparisons of immunoassays vs. indirect immunofluorescence for initial screening of connective tissue diseases

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Michelle Elaine Orme ◽  
Carmen Andalucia ◽  
Sigrid Sjölander ◽  
Xavier Bossuyt
Keyword(s):  
Connective Tissue ◽  
Indirect Immunofluorescence ◽  
Meta Analysis ◽  
Connective Tissue Diseases ◽  
Test Accuracy ◽  
Initial Screening ◽  
Case Control Studies ◽  
Cross Sectional ◽  
Mixed Effect ◽  
Mixed Effect Models

AbstractObjectivesTo compare indirect immunofluorescence (IIF) for antinuclear antibodies (ANA) against immunoassays (IAs) as an initial screening test for connective tissue diseases (CTDs).MethodsA systematic literature review identified cross-sectional or case-control studies reporting test accuracy data for IIF and enzyme-linked immunosorbent assays (ELISA), fluorescence enzyme immunoassay (FEIA), chemiluminescent immunoassay (CLIA) or multiplex immunoassay (MIA). The meta-analysis used hierarchical, bivariate, mixed-effect models with random-effects by test.ResultsDirect comparisons of IIF with ELISA showed that both tests had good sensitivity (five studies, 2321 patients: ELISA: 90.3% [95% confidence interval (CI): 80.5%, 95.5%] vs. IIF at a cut-off of 1:80: 86.8% [95% CI: 81.8%, 90.6%]; p = 0.4) but low specificity, with considerable variance across assays (ELISA: 56.9% [95% CI: 40.9%, 71.5%] vs. IIF 1:80: 68.0% [95% CI: 39.5%, 87.4%]; p = 0.5). FEIA sensitivity was lower than IIF sensitivity (1:80: p = 0.005; 1:160: p = 0.051); however, FEIA specificity was higher (seven studies, n = 12,311, FEIA 93.6% [95% CI: 89.9%, 96.0%] vs. IIF 1:80 72.4% [95% CI: 62.2%, 80.7%]; p < 0.001; seven studies, n = 3251, FEIA 93.5% [95% CI: 91.1%, 95.3%] vs. IIF 1:160 81.1% [95% CI: 73.4%, 86.9%]; p < 0.0001). CLIA sensitivity was similar to IIF (1:80) with higher specificity (four studies, n = 1981: sensitivity 85.9% [95% CI: 64.7%, 95.3%]; p = 0.86; specificity 86.1% [95% CI: 78.3%, 91.4%]). More data are needed to make firm inferences for CLIA vs. IIF given the wide prediction region. There were too few studies for the meta-analysis of MIA vs. IIF (MIA sensitivity range 73.7%–86%; specificity 53%–91%).ConclusionsFEIA and CLIA have good specificity compared to IIF. A positive FEIA or CLIA test is useful to support the diagnosis of a CTD. A negative IIF test is useful to exclude a CTD.

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