scholarly journals Autoimmune anti-DNA and anti-phosphatidylserine antibodies predict development of severe COVID-19

2021 ◽  
Vol 4 (11) ◽  
pp. e202101180
Author(s):  
Claudia Gomes ◽  
Marisol Zuniga ◽  
Kelly A Crotty ◽  
Kun Qian ◽  
Nubia Catalina Tovar ◽  
...  
Keyword(s):  
Disease Severity ◽  
Cell Injury ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Predictive Biomarkers ◽  
Strong Correlations ◽  
Autoimmune Antibodies ◽  
Dna Antibodies ◽  
Common Antigens ◽  
Degrees Of Severity

High levels of autoimmune antibodies are observed in COVID-19 patients but their specific contribution to disease severity and clinical manifestations remains poorly understood. We performed a retrospective study of 115 COVID-19 hospitalized patients with different degrees of severity to analyze the generation of autoimmune antibodies to common antigens: a lysate of erythrocytes, the lipid phosphatidylserine (PS) and DNA. High levels of IgG autoantibodies against erythrocyte lysates were observed in a large percentage (up to 36%) of patients. Anti-DNA and anti-PS antibodies determined upon hospital admission correlated strongly with later development of severe disease, showing a positive predictive value of 85.7% and 92.8%, respectively. Patients with positive values for at least one of the two autoantibodies accounted for 24% of total severe cases. Statistical analysis identified strong correlations between anti-DNA antibodies and markers of cell injury, coagulation, neutrophil levels and erythrocyte size. Anti-DNA and anti-PS autoantibodies may play an important role in the pathogenesis of COVID-19 and could be developed as predictive biomarkers for disease severity and specific clinical manifestations.

scholarly journals Autoimmune anti-DNA antibodies predict disease severity in COVID-19 patients

2021 ◽  
Author(s):  
Claudia Gomes ◽  
Marisol Zuniga ◽  
Kelly A. Crotty ◽  
Kun Qian ◽  
Lawrence Hsu Lin ◽  
...  
Keyword(s):  
Disease Severity ◽  
Cell Injury ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Predictive Biomarker ◽  
Strong Correlations ◽  
Autoimmune Antibodies ◽  
Dna Antibodies ◽  
Common Antigens ◽  
Degrees Of Severity

AbstractCOVID-19 can lead to severe disease and death, however the mechanisms of pathogenesis in these patients remain poorly understood. High levels of autoimmune antibodies have been observed frequently in COVID-19 patients but their specific contribution to disease severity and clinical manifestations remain unknown.We performed a retrospective study of 115 COVID-19 hospitalized patients with different degrees of severity to analyze the generation of autoimmune antibodies to common antigens: a lysate of erythrocytes, the lipid phosphatidylserine (PS) and DNA.High levels of IgG autoantibodies against erythrocyte lysates were observed in a large percentage (up to 41%) of patients. Anti-DNA antibodies determined upon hospital admission correlated strongly with later development of severe disease, showing a positive predictive value of 89.5% and accounting for 22% of total severe cases. Statistical analysis identified strong correlations between anti-DNA antibodies and markers of cell injury, coagulation, neutrophil levels and erythrocyte size.Anti-DNA autoantibodies may play an important role in the pathogenesis of COVID-19 and could be developed as a predictive biomarker for disease severity and specific clinical manifestations.

scholarly journals The Homogeneous Multiplexed System-a New Method for Autoantibody Profile in Systemic Lupus Erythematosus

2005 ◽  
Vol 12 (2) ◽  
pp. 107-111 ◽  
Author(s):  
Gisele Zandman-Goddard ◽  
Boris Gilburd ◽  
Ora Shovman ◽  
Miri Blank ◽  
Svetlana Berdichevski ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Severity ◽  
Lupus Erythematosus ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Systemic Lupus ◽  
Autoantibody Production ◽  
Sledai Score ◽  
Autoantibody Profile ◽  
Multiplex System

Systemic lupus erythematosus (SLE) is a multi-systemic autoimmune disease leading to immunological aberrations and excessive multiple autoantibody production. The aim of this study was to investigate the prevalence of multiple autoantibodies in SLE patients utilizing the multiplex system method.We analyzed the presence of elevated titers of anti-Ro, anti-La, anti-RNP, anti-Sm, anti-Jo1, anti-centromere, anti-Scl-70, anti-histone, and anti-dsDNA antibodies in 199 serum samples (113 SLE patients, 86 healthy donors). We compared the type, level and number of autoantibodies and the correlation between the autoantibody profile and disease severity utilizing the SLEDAI score.Elevated titers of at least one autoantibody were detected in 48% of 42 SLE patients. Elevated titers of anti-Ro antibodies were most commonly detected. The distribution of specific autoantibodies was: anti-Ro- 23.8%, anti-dsDNA- 19%, anti-histone- 19%, anti-RNP- 14.2%, anti-La antibodies- 11.9%, anti-Sm- 7.1%, anti-Scl 70-4.7%, and anti-centromere- 2.4%. Utilizing ROC analysis, the sensitivity and specificity of anti-DNA antibodies at a cutoff value of 34 IU/ml were 87.1% and 79.4% respectively. Elevated titers of anti-Jo1 antibody were not detected. There was a correlation with the titer of anti-Ro antibodies and disease activity by the SLEDAI score. Seven patients harbored one autoantibody only, 15 patients harbored 2-3 autoantibodies, 3 patients harbored 4-5 autoantibodies, and one patient harbored 6 autoantibodies. A correlation between the number of autoantibodies per patient and disease severity was found. One patient with a multitude of autoantibodies had severe lupus and a myriad of clinical manifestations.In conclusion, the multiplex system is specific and sensitive, provides an autoantibody profile in a single test, and may be useful as a diagnostic test for SLE. Elevated anti-Ro antibodies are associated with severe disease. An autoantibody load may be indicative of more severe disease.

scholarly journals Clinical characteristics of foodborne botulism in the southern region of the Kyrgyz Republic

2020 ◽  
Vol 10 (3) ◽  
pp. 581-586
Author(s):  
S. T. Salieva ◽  
S. T. Zholdoshev
Keyword(s):  
Incubation Period ◽  
Disease Severity ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Acute Onset ◽  
Southern Region ◽  
Nasolabial Fold ◽  
Kyrgyz Republic ◽  
Short Incubation Period ◽  
Hands And Feet

The main factors of botulism transmission are identified as home-canned products (vegetable salads, fruit compotes, seaberry jam), pickled cucumbers and tomatoes. Botulism proceeds clinically as moderate-to-severe disease. High prevalence of type A and untypeable C. botulinum toxins along with type B species in the southern region accounts for its severe course. In our study, clinical manifestations of botulism were presented by moderate and severe clinical picture in 72.3% (47 patients) and 27.7% (18 patients) cases. No mild forms of the disease were diagnosed. Length of incubation period in examined patients on average was 13.6 hours. Upon that, a short incubation period was observed after consumption of canned fruit compote and sea buckthorn jam, cucumbers and tomatoes (16 subjects) or canned vegetables (38 subjects) on average ranging from 4 to 8 hours, 8 hours to 1 day, or 15 hours to 1.5 days, respectively. All subjects were featured with acute onset manifested as general intoxication and gastrointestinal syndromes. The former was characterized by headache, dizziness, and severe general weakness. Subfebrile temperature (37.1–37.5°C) was noted in patients with a short incubation period. Such syndrome in case of moderate disease course was also characterized by moderate severity in 70.2±6.7% cases, with acute appearance in 29.8±6.9% cases; in severe course it was featured with extremely severe course (100%), and in one case it resulted in lethal outcome. Intensity and persistence of neurological disorders clearly correlated with the disease severity, which pointed at its progression. Upon admission to the hospital, patients noted moderate and marked dry mouth in 63.1±5.9% and 36.9±5.9% cases, respectively. Ophthalmoplegic syndrome was characterized by: doubling of object contours, diplopia, limited eye movement, mydriasis, lethargy or lack of pupillary reaction to light, anisocoria, and ptosis. Phagonazoglossoneurological syndrome was early manifested by swallowing problem. Next, tongue deviation, amimia, flattened nasolabial fold, and soft palate paresis were added up. Phonolaryngology syndrome was evident depending on disease severity in a form of varying intensity of dysphonia and dysarthria. Syndrome of general myoneuroplegia was characterized by lowered strength in hands and feet.

scholarly journals Within-Host Diversity of SARS-Cov-2 in COVID-19 Patients with Variable Disease Severities

2020 ◽  
Author(s):  
Hebah A. Al Khatib ◽  
Fatiha M. Benslimane ◽  
Israa El Bashir ◽  
Asmaa A Al Thani ◽  
Hadi M. Yassine
Keyword(s):  
Disease Severity ◽  
Severe Disease ◽  
Consensus Sequence ◽  
Clinical Manifestations ◽  
Illumina Miseq ◽  
P Value ◽  
Consensus Analysis ◽  
Consensus Sequences ◽  
Host Diversity ◽  
Virus Diversity

Background: The ongoing pandemic of SARS-COV-2 has already infected more than eight million people worldwide. The majority of COVID-19 patients are either asymptomatic or have mild symptoms. Yet, about 15% of the cases experience severe complications and require intensive care. Factors determining disease severity are not yet fully characterized. Aim: Here, we investigated the within-host virus diversity in COVID-19 patients with different clinical manifestations. Methods: We compared SARS-COV-2 genetic diversity in 19 mild and 27 severe cases. Viral RNA was extracted from nasopharyngeal samples and sequenced using Illumina MiSeq platform. This was followed by deep-sequencing analyses of SARS-CoV-2 genomes at both consensus and sub-consensus sequence levels. Results: Consensus sequences of all viruses were very similar, showing more than 99·8% sequence identity regardless of the disease severity. However, the sub-consensus analysis revealed significant differences in within-host diversity between mild and severe cases. Patients with severe symptoms exhibited a significantly (p-value 0.001) higher number of variants in coding and non-coding regions compared to mild cases. Analysis also revealed higher prevalence of some variants among severe cases. Most importantly, severe cases exhibited significantly higher within-host diversity (mean= 13) compared to mild cases (mean=6). Further, higher within-host diversity was observed in patients above the age of 60 compared to the younger age group. Conclusion: These observations provided evidence that within-host diversity might play a role in the development of severe disease outcomes in COVID19 patients; however, further investigations is required to elucidate this association.

scholarly journals 483. Disease Severity and Clinical Manifestations of SARS-CoV-2 Infection Among Infants Over the First Year of the Pandemic in Canada

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S342-S343
Author(s):  
Pierre-Philippe Piché-Renaud ◽  
Luc Panetta ◽  
Daniel Farrar ◽  
Charlotte Moore Hepburn ◽  
Olivier Drouin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Disease Severity ◽  
Disease Risk ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Significant Risk ◽  
Age Group ◽  
Younger Age ◽  
The Impact ◽  
Research Grant

Abstract Background There is limited data on outcomes of SARS-CoV-2 infection among infants (< 1 year of age). In the absence of any approved vaccines for infants, understanding the risk factors for hospitalization and severe disease from COVID-19 in this age group will help inform clinical management and targeted public health interventions. The objective of this study was to describe the clinical manifestations, disease severity, and risk factors for hospitalization among infants with SARS-CoV-2 infection in Canada. Methods This is a nationwide prospective observational study using the infrastructure of the Canadian Paediatric Surveillance Program. All cases of infants aged < 1 year of age with microbiologically confirmed SARS-CoV-2 infection were reported from April 8th 2020 to May 11th 2021, and classified by disease severity, and primary cause of hospitalization. Logistic regression was performed to identify risk factors for hospitalization and severe disease. Results A total of 393 cases were reported, including 229 (58.3%) non-hospitalized and 164 (41.7%) hospitalized infants. The most common symptoms included fever (63.4%), runny nose (45.0%), cough (35.1%) and decreased oral intake (24.9%). Significant risk factors for hospitalization included younger age and presence of comorbid conditions (excluding prematurity), as shown in the Table. Among hospitalized infants, 108 (65.9%) were admitted because of COVID-19-related illness, and 52 (31.7%) were admitted for reasons other than COVID-19. A total of 31 (7.9%) infants developed severe or critical disease. Risk factors for severe disease included prematurity and younger age (Table). Conclusion We describe one of the largest cohort of infants with SARS-CoV-2 infection. Severe disease in this age group is uncommon, with younger age and prematurity being significant risk factors for severe COVID-19. Disclosures Pierre-Philippe Piché-Renaud, MD, Pfizer Global Medical Grants (Competitive grant program) (Research Grant or Support, Investigator-led project on the impact of COVID-19 on routine childhood immunizations) Olivier Drouin, MDCM MsC MPH, Covis Pharma (Research Grant or Support) Shaun Morris, MD, MPH, DTM&H, FRCPC, FAAP, GSK (Speaker’s Bureau)Pfizer (Advisor or Review Panel member)Pfizer (Grant/Research Support)

scholarly journals Comparison of three serological chemiluminescence immunoassays for SARS-CoV-2, and clinical significance of antibody index with disease severity

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253889
Author(s):  
Nuri Lee ◽  
Seri Jeong ◽  
Min-Jeong Park ◽  
Wonkeun Song
Keyword(s):  
Disease Severity ◽  
Clinical Significance ◽  
Severe Disease ◽  
Clinical Severity ◽  
Clinical Implications ◽  
Antibody Index ◽  
Clinical Markers ◽  
Strong Correlations ◽  
Igg Antibody ◽  
Molecular Tests

Background The clinical significance of the quantitative value of antibodies in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains mostly unidentified. We investigated the dynamics and clinical implications of the SARS-CoV-2 antibody over time using three automated chemiluminescence immunoassays targeting either nucleocapsids or spikes. Methods A total of 126 specimens were collected from 23 patients with confirmed and indeterminate COVID-19 identified by molecular tests. SARS-CoV-2 antibody index was measured using SARS-CoV2 IgG reagent from Alinity (Abbott) and Access (Beckman Coulter) and SARS-CoV2 Total (IgG + IgM) from Atellica (Siemens). Results Three immunoassays showed strong correlations with each other (range of Pearson’ s correlation coefficient (r) = 0.700–0.854, P < 0.001). Eleven (8.7%) specimens showed inconsistencies. SARS-CoV-2 IgG showed a statistically significantly higher value in patients with severe disease than that in non-severe disease patients (P < 0.001) and was significantly associated with clinical markers of disease severity. Conclusion The quantitative value of the SARS-CoV-2 IgG antibody measured using automated immunoassays is a significant indicator of clinical severity in patients with COVID-19.

scholarly journals Biomarkers for Disease Severity in Children Infected With Respiratory Syncytial Virus: A Systematic Literature Review

2020 ◽  
Vol 222 (Supplement_7) ◽  
pp. S648-S657 ◽  
Author(s):  
Deniz Öner ◽  
Simon B Drysdale ◽  
Calum McPherson ◽  
Gu-Lung Lin ◽  
Sophie Janet ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Disease Severity ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Risk Of Bias ◽  
Ovid Medline ◽  
Wide Range ◽  
Life Threatening ◽  
Syncytial Virus ◽  
Definition Of

Abstract Background Clinical manifestations of respiratory syncytial virus (RSV) infection vary widely from mild, self-limiting illness to severe life-threatening disease. There are gaps in knowledge of biomarkers to objectively define severe disease and predict clinical outcomes. Methods A systematic search was performed, 1945–March 2019 in databases Ovid Medline, Embase, Global health, Scopus, and Web of Science. Risk of bias was assessed using the Cochrane tool. Results A total of 25 132 abstracts were screened and studies were assessed for quality, risk of bias, and extracted data; 111 studies met the inclusion criteria. RSV severity was correlated with antibody titers, reduced T and B cells, dysregulated innate immunity, neutrophil mobilization to the lungs and blood, decreased Th1 response, and Th2 weighted shift. Microbial exposures in respiratory tract may contribute to neutrophil mobilization to the lungs of the infants with severe RSV compared with mild RSV disease. Conclusions Although a wide range of biomarkers have been associated with RSV disease severity, robust validated biomarkers are lacking. This review illustrates the broad heterogeneity of study designs and high variability in the definition of severe RSV disease. Prospective studies are required to validate biomarkers. Additional research investigating epigenetics, metabolomics, and microbiome holds promise for novel biomarkers.

scholarly journals Human Adenovirus Coinfection Aggravates the Severity of Mycoplasma pneumoniae Pneumonia in Children

2019 ◽  
Author(s):  
Jiaojiao Gao ◽  
Lili Xu ◽  
Baoping Xu ◽  
Zhengde Xie ◽  
Kunling Shen
Keyword(s):  
Disease Severity ◽  
Mycoplasma Pneumoniae ◽  
Research Group ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Severe Pneumonia ◽  
Human Adenovirus ◽  
Control Group ◽  
Children's Hospital ◽  
Children’S Hospital

Abstract Background Mycoplasma pneumoniae ( M. pneumoniae ) is an important pathogen of community-acquired pneumonia (CAP) in children. The coinfection rate of M. pneumoniae pneumonia (MPP) can reach 52% in some areas, but the effects of coinfection with different pathogens have not been clearly recognized.Methods The cases of MPP hospitalized in Beijing Children's Hospital from 1/1/2014 to 12/31/2016 were screened. MPP patients coinfected with Human adenovirus (HAdV) were categorized into the research group. Patients with single M. pneumoniae infection were categorized into the control group, matching the research group by age and admission time with a ratio of 1:3. Clinical manifestations, laboratory examinations, and disease severity were compared between these two groups.Results A total of 2,540 hospitalized MPP cases were screened in Beijing Children's Hospital, among which thirty cases were enrolled in the research group and ninety cases were enrolled in the control group. The results indicated that patients in the research group had longer hospital stays, longer fever durations and a higher rate of dyspnea, as well as a larger proportion applications of oxygen therapy and noninvasive continuous positive airway pressure (NCPAP). No obvious differences were found in lab examinations within the two groups. Regarding disease severity, the proportions of extremely severe pneumonia and severe disease defined by the clinical score system were higher in the research group than in the control group.Conclusion Compared with single M. pneumoniae infection, MPP coinfected with HAdV in children was relatively more serious.

Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF)

2016 ◽  
Vol 75 (6) ◽  
pp. 1051-1056 ◽  
Author(s):  
Erkan Demirkaya ◽  
Cengizhan Acikel ◽  
Philip Hashkes ◽  
Marco Gattorno ◽  
Ahmet Gul ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Disease Severity ◽  
Severity Score ◽  
Characteristic Curve ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Future Research ◽  
Laboratory Findings ◽  
Therapeutic Decisions ◽  
Mediterranean Fever

ObjectiveTo develop widely accepted international severity score for children and adult patients with familial Mediterranean fever (FMF) that can be easily applied, in research and clinical practice.MethodsCandidate severity criteria were suggested by several FMF expert physicians. After three rounds of Delphi survey, the candidate criteria, defined by the survey, were discussed by experts in a consensus meeting. Each expert brought data of clinical manifestations, laboratory findings and physician's global assessments (PGAs) of minimum 20 patients from their centres. We used the PGAs for disease severity as a gold standard. Logistic regression analysis was used to evaluate the predicting value of each item, and receiver operating characteristic curve analysis was performed to demonstrate the success of the criteria set.ResultsA total of 281 patients consist of 162 children and 119 adults with FMF were enrolled and available for validity analysis: Nine domains were included in the final core set of variables for the evaluation of disease severity in FMF. The International Severity Score for FMF (ISSF) may reach a maximum of 10 if all items are maximally scored. The threshold values to determine: severe disease ≥6, intermediate disease 3–5, mild disease ≤2. Area under the curve was calculated as 0.825 for this set in the whole group.ConclusionsThe initial validity of ISSF both in children and adult with FMF was demonstrated. We anticipate that it will provide a robust tool to objectively define disease severity for clinical trials, future research as well as for therapeutic decisions in managing patients with FMF.

scholarly journals Risk factors for severe PCR-positive SARS-CoV-2 infection in hospitalized children: a multicenter cohort study

2021 ◽  
Author(s):  
Tilmann Schober ◽  
Chelsea Caya ◽  
Michelle Barton ◽  
Ann Bayliss ◽  
Ari Bitnun ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Disease Severity ◽  
Neurological Disorder ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Sensitivity Analyses ◽  
Chest Imaging ◽  
Multicenter Cohort Study ◽  
Vaccination Programs

Importance: Children are less likely than adults to have severe outcomes from SARS-CoV-2 infection and the corresponding risk factors are not well established. Objective: To identify risk factors for severe disease in symptomatic children hospitalized for PCR-positive SARS-CoV-2 infection. Design: Cohort study, enrollment from February 1, 2020 until May 31, 2021 Setting 15 children's hospitals in Canada, Iran, and Costa Rica Participants: Patients <18 years of age hospitalized with symptomatic SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C) Exposures: Variables assessed for their association with disease severity included patient demographics, presence of comorbidities, clinical manifestations, laboratory parameters and chest imaging findings. Main Outcomes and Measures: The primary outcome was severe disease defined as a WHO COVID-19 clinical progression scale of ≥6, i.e., requirement of non-invasive ventilation, high flow nasal cannula, mechanical ventilation, vasopressors, or death. Multivariable logistic regression was used to evaluate factors associated with severe disease. Results: We identified 403 hospitalizations. Median age was 3.78 years (IQR 0.53-10.77). At least one comorbidity was present in 46.4% (187/403) and multiple comorbidities in 18.6% (75/403). Severe disease occurred in 33.8% (102/403). In multivariable analyses, presence of multiple comorbidities (adjusted odds ratio 2.24, 95% confidence interval 1.04-4.81), obesity (2.87, 1.19-6.93), neurological disorder (3.22, 1.37-7.56), anemia, and/or hemoglobinopathy (5.88, 1.30-26.46), shortness of breath (4.37, 2.08-9.16), bacterial and/or viral coinfections (2.26, 1.08-4.73), chest imaging compatible with COVID-19 (2.99, 1.51-5.92), neutrophilia (2.60, 1.35-5.02), and MIS-C diagnosis (3.86, 1.56-9.51) were independent risk factors for severity. Comorbidities, especially obesity (40.9% vs 3.9%, p<0.001), were more frequently present in adolescents ≥12 years of age. Neurological disorder (3.16, 1.19-8.43) in children <12 years of age and obesity (3.21, 1.15-8.93) in adolescents were the specific comorbidities associated with disease severity in age-stratified adjusted analyses. Sensitivity analyses excluding the 81 cases with MIS-C did not substantially change the identified risk factors. Conclusions and Relevance: Pediatric risk factors for severe SARS-CoV-2 infection vary according to age and can potentially guide vaccination programs and treatment approaches in children.

Sign in / Sign up

Export Citation Format

Share Document