scholarly journals Early and Strong Antibody Responses to SARS-CoV-2 Predict Disease Severity in COVID-19 Patients

2022 ◽  
Author(s):  
Jānis Plūme ◽  
Artis Galvanovskis ◽  
Sindija Šmite ◽  
Nadezda Romanchikova ◽  
Pawel Zayakin ◽  
...  
Keyword(s):  
Cell Activation ◽  
Severe Disease ◽  
Prognostic Significance ◽  
Serum Levels ◽  
Epidemiological Studies ◽  
Antibody Responses ◽  
Mast Cell Activation ◽  
N Protein ◽  
Mild Disease ◽  
Severity Of The Disease

Abstract Background Antibody response to SARS-CoV-2 is a valuable biomarker for the assessment of the spread of the virus in a population and evaluation of the vaccine candidates. Recent data suggest that antibody levels also may have a prognostic significance in COVID-19. Most of the serological studies so far rely on testing antibodies against spike (S) or nucleocapsid (N) protein, however antibodies can be directed against other structural and nonstructural proteins of the virus, whereas their frequency, biological and clinical significance is unknown. Methods A novel antigen array comprising 30 SARS-CoV-2 antigens or their fragments was developed and used to examine IgG, IgA, IgE and IgM responses to SARS-CoV-2 in sera from 103 patients with COVID-19 including 34 patients for whom sequential samples were available, and 20 pre-pandemic healthy controls. Results Antibody responses to various antigens are highly correlated and the frequencies and peak levels of antibodies are higher in patients with severe/moderate disease than in those with mild disease. This finding supports the idea that antibodies against SARS-CoV-2 may exacerbate the severity of the disease via antibody-dependent enhancement. Moreover, early IgG and IgA responses to full length S protein may be used as an additional biomarker for the identification of patients who are at risk of developing severe disease. Importantly, this is the first study reporting that SARS-CoV-2 elicits IgE responses and their serum levels positively correlate with the severity of the disease thus suggesting a link between high levels of antibodies and mast cell activation. Conclusions This is the first study assessing the prevalence and dynamics IgG, IgA, IgE and IgM responses to multiple SARS-CoV-2 antigens simultaneously. Results provide important insights into the pathogenesis of COVID-19 and have implications in planning and interpreting antibody-based epidemiological studies.

scholarly journals Defining Antibody Seroprevalence and Duration of Humoral Responses to SARS-CoV-2 Infection and/or Vaccination in a Greek Community

2021 ◽  
Vol 19 (1) ◽  
pp. 407
Author(s):  
Ourania S. Kotsiou ◽  
Dimitrios Papagiannis ◽  
Evangelos C. Fradelos ◽  
Dimitra I. Siachpazidou ◽  
Garifallia Perlepe ◽  
...  
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Severe Disease ◽  
Vaccination Status ◽  
Antibody Responses ◽  
Antibody Testing ◽  
Mild Disease ◽  
Antibody Titers ◽  
Humoral Responses ◽  
Pandemic Wave

Background: In this work we aimed to evaluate antibody-response longevity to SARS-CoV-2 infection and/or vaccination in one of the Greek communities that was worst hit by the pandemic, Deskati, five months after a previous serosurveillance and nine months after the pandemic wave initiation (October 2020). Methods: The SARS-CoV-2 IgG II Quant method (Architect, Abbott, IL, USA) was used for antibody testing. Results: A total of 69 subjects, who previously tested positive or negative for COVID-19 antibodies, participated in the study. We found that 48% of participants turned positive due to vaccination and 27% of participants were both previously infected and vaccinated. All previously infected participants retained antibodies to the virus, irrespective of their vaccination status. The antibody titers were significantly higher in previously infected participants that had been vaccinated than those who were unvaccinated and in those that had been previously hospitalized for COVID-19 than those with mild disease. Conclusions: Antibody responses to SARS-CoV-2 infection were maintained nine months after the pandemic. Vaccination alone had generated an immune response in almost half of the population. Higher antibody titers were found in the case of vaccination in previously infected subjects and especially in those with severe disease leading to hospitalization

Enhancement of apoptosis with loss of cellular adherence in the villus epithelium of the small intestine after infection with the nematode Nippostrongylus brasiliensis in rats

Parasitology ◽  
1999 ◽  
Vol 119 (2) ◽  
pp. 199-207 ◽  
Author(s):  
Y. HYOH ◽  
M. NISHIDA ◽  
T. TEGOSHI ◽  
M. YAMADA ◽  
R. UCHIKAWA ◽  
...  
Keyword(s):  
Mast Cell ◽  
Small Intestine ◽  
Epithelial Cell ◽  
Adhesion Molecule ◽  
Cell Activation ◽  
Serum Levels ◽  
Mast Cell Activation ◽  
Nippostrongylus Brasiliensis ◽  
Villus Atrophy ◽  
Labelling Method

It has been reported that infection with Nippostrongylus brasiliensis induces villus atrophy with various histological alterations. In N. brasiliensis-infected rats, villus length in the jejunum was reduced significantly at day 10 p.i., when serum levels of rat mast cell protease (RMCP) II had increased significantly. To determine whether the villus atrophy is associated with enhancement of apoptosis, apoptotic nuclei were labelled using the nick end-labelling method. Numbers of labelled cells were markedly increased in the villus epithelium at 7–10 days p.i., while the numbers returned to normal 14 days p.i. when worms were rejected from the intestine and villus length became normal. Examination of the expression of the adhesion molecule E-cadherin showed granular immunoreactivity in the cytoplasm of atrophic villus epithelium with loss of normal localization to epithelial cell borders. In mast cell-deficient Ws/Ws rats, villus length was reduced as significantly as in +/+ counterparts at day 10 p.i. with marked increases in the numbers of apoptotic cells. These results suggested that villus atrophy was closely associated with enhanced apoptosis and loss of adhesion in epithelial cells. Mast cell activation appears not to be involved in these alterations.

scholarly journals Cell type-specific immune dysregulation in severely ill COVID-19 patients

2020 ◽  
Author(s):  
Changfu Yao ◽  
Stephanie A Bora ◽  
Tanyalak Parimon ◽  
Tanzira Zaman ◽  
Oren A Friedman ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Ventilatory Support ◽  
Adaptive Immune Response ◽  
Disease Course ◽  
B Cell Activation ◽  
Peripheral Blood Mononuclear ◽  
Mild Disease

Coronavirus disease 2019 (COVID-19) has quickly become the most serious pandemic since the 1918 flu pandemic. In extreme situations, patients develop a dysregulated inflammatory lung injury called acute respiratory distress syndrome (ARDS) that causes progressive respiratory failure requiring mechanical ventilatory support. Recent studies have demonstrated immunologic dysfunction in severely ill COVID-19 patients. To further delineate the dysregulated immune response driving more severe clinical course from SARS-CoV-2 infection, we used single-cell RNA sequencing (scRNAseq) to analyze the transcriptome of peripheral blood mononuclear cells (PBMC) from hospitalized COVID-19 patients having mild disease (n = 5), developing ARDS (n = 6), and recovering from ARDS (n = 6). Our data demonstrated an overwhelming inflammatory response with select immunodeficiencies within various immune populations in ARDS patients. Specifically, their monocytes had defects in antigen presentation and deficiencies in interferon responsiveness that contrasted the higher interferon signals in lymphocytes. Furthermore, cytotoxic activity was suppressed in both NK and CD8 lymphocytes whereas B cell activation was deficient, which is consistent with the delayed viral clearance in severely ill COVID-19 patients. Finally, we identified altered signaling pathways in the severe group that suggests immunosenescence and immunometabolic changes could be contributing to the dysfunctional immune response. Our study demonstrates that COVID-19 patients with ARDS have an immunologically distinct response when compared to those with a more innocuous disease course and show a state of immune imbalance in which deficiencies in both the innate and adaptive immune response may be contributing to a more severe disease course in COVID-19.

scholarly journals CORRELATION BETWEEN SERUM C-REACTIVE PROTEIN LEVEL WITH SEVERITY OF THE DISEASE IN COVID-19 PATIENTS

2021 ◽  
Vol 5 (11) ◽  
Author(s):  
Sangeeta Gahlot ◽  
Surendra Yadav ◽  
Makkhan Lal Saini
Keyword(s):  
Severe Disease ◽  
Serum Levels ◽  
Cross Sectional Study ◽  
P Value ◽  
C Reactive Protein ◽  
Cross Sectional ◽  
Reactive Protein ◽  
Group I ◽  
Moderate Disease ◽  
Severity Of The Disease

Background: To find the levels of serum CRP in confirmed Covid-19 patients and to compare their levels in patients with mild to moderate disease and patients with severe disease who required ICU care for management. Methods: A Cross sectional study was carried out on 100 confirmed cases of Covid-19, in whom Serum levels of Random sugar (RBS), Creatinine, Urea, C- reactive protein (CRP) were measured. Results: The levels of serum Urea, Creatinine were significantly increased in group II when compared to group 1, and the levels of CRP were significantly increased with p value <0.0001 in group IIwhen compared to group I. Conclusion: Findings of our study suggest that determination of biochemical parameters like CRP at the time of hospitalization helps in predicting the severity of disease and need for ICU for better treatment management and prevention of adverse outcome. Keywords: Severe acute respiratory syndrome, Covid-19, C- reactive protein, Intensive care unit.

scholarly journals Clinical influence of maternal serum homocysteine, folate and vitamin B12 in the development of pre-eclampsia

Pteridines ◽  
2019 ◽  
Vol 30 (1) ◽  
pp. 48-53 ◽  
Author(s):  
Hongyan Zhao ◽  
Xu Zeng
Keyword(s):  
Vitamin B12 ◽  
Gestational Hypertension ◽  
Severe Disease ◽  
Serum Levels ◽  
Maternal Serum ◽  
Control Group ◽  
Mild Disease ◽  
Serum Homocysteine ◽  
Folate And Vitamin B12 ◽  
Serological Biomarkers

Abstract Background: The aim of this study was to investigate the correlation between maternal serum homocysteine (Hcy), folate, vitamin B12 (VitB12) and the development of pre-eclampsia (PE). Methods: Seventy-eight normal pregnant women (without hypertension and proteinuria during their pregnancy (control group)), 66 cases of gestational hypertension (GH group) and 82 cases of pre-eclampsia (PE group, with 56 cases of mild disease and 26 cases of severe disease) were include in this study. The maternal serum Hcy, folate and VitB12 level of the included cases were examined between 11 to 13 weeks gestation and compared between each group. Results: The serum levels of VitB12 were significantly different between the control, GH and PE groups (p<0.05). The serum levels of Hcy in the PE group were significantly higher than those of the control group (p<0.05). However, the serum levels of folate in the PE group were significantly lower than those of control group (p<0.05). Significant statistical differences in the maternal serum Hcy and folate were found between mild and severe PE patient groups (p<0.05). A significant correlation was found between maternal serum Hcy and VitB12 (r=-0.34, p=0.001). Conclusion: Hcy, folate and VitB12 may play an important role in the development of PE and could be potential serological biomarkers for early PE diagnosis.

scholarly journals Clinical asthma phenotypes in the real world: opportunities and challenges

Breathe ◽  
2015 ◽  
Vol 11 (3) ◽  
pp. 186-193 ◽  
Author(s):  
Clementine Bostantzoglou ◽  
Vicky Delimpoura ◽  
Konstantinos Samitas ◽  
Eleftherios Zervas ◽  
Frank Kanniess ◽  
...  
Keyword(s):  
Severe Disease ◽  
Asthma Management ◽  
Airflow Limitation ◽  
List Type ◽  
Asthma Treatment ◽  
Future Planning ◽  
Phenotypic Characteristics ◽  
Asthmatic Patients ◽  
Mild Disease ◽  
Severity Of The Disease

Key PointsAsthma is a heterogeneous syndrome ranging from mild disease with barely noticeable symptoms to very severe disease with constant symptoms that may greatly hinder patients’ quality of life.The aim of asthma treatment is control of asthma and the prevention of risk of exacerbations and fixed airflow limitation.Asthma management must be individualised; tailored not only to the severity of the disease but importantly, to the phenotypic characteristics of the patient and modified according to response to treatment.Educational AimsTo inform readers about the current understanding on the treatment of asthma.To highlight the usefulness of phenotypes in treating asthmatic patients, especially those with severe disease.To introduce the issues of severe asthma management and future planning.Asthma is a common, chronic and heterogeneous syndrome, affecting people of all ages, all races and both sexes. It may range from mild disease with barely noticeable symptoms, to very severe disease with constant symptoms that greatly hinder the life of the patient. Guidelines issued by various medical societies provide guidance on how to diagnose and manage asthmatic patients. It is now increasingly recognised that asthma management must be individualised, tailored not only to the severity of the disease but to the phenotypic characteristics of each patient. The aim of asthma treatment is control of asthma and the prevention of risk of exacerbations and fixed airflow limitation. Asthma control can be easily assessed clinically through simple screening tools such as the use of validated questionnaires and spirometry. The use of inflammatory biomarkers can be an alternative approach that, however, requires more time and resources. Asthma treatment involves the use of controllers, mainly inhaled corticosteroids and long-acting β2-agonists, and relievers, mainly rapid-acting β2-agonists. Controller medications reduce airway inflammation, lead to better symptom control and reduce the risk of future exacerbations. Reliever (rescue) medications alleviate symptoms and prevent exercise-induced bronchoconstriction. Treatment must be based on a “stepwise approach” in order to achieve good control of symptoms and to minimise future risks of exacerbations. That is, less treatment for mild disease, more treatment for severe, uncontrolled disease. Once good asthma control has been achieved and maintained, treatment should be stepped down. In severe asthmatics, phenotypic characterisation becomes more clinically useful and add-on treatment such as anti-immunoglobulin E monoclonal antibodies may be required. Despite our better understanding of asthma, there are still patients who will not respond to treatment and remain symptomatic. Dissemination of guidelines and national plans allowing early diagnosis of asthma as well as access to specialised primary and secondary care for asthmatic patients, personalised treatment and continuity of care may lead to excellence in care and controlled asthma for the majority of patients. Education of the patient in asthma is also very important, as in every chronic disease, as the patients live with the disease every day while they visit a healthcare professional a few times a year. Future planning for new treatments should focus on the needs of such severe asthma patients.

scholarly journals Antibody kinetics and clinical course of COVID-19 a prospective observational study

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248918
Author(s):  
Anna Bläckberg ◽  
Nils Fernström ◽  
Emma Sarbrant ◽  
Magnus Rasmussen ◽  
Torgny Sunnerhagen
Keyword(s):  
Observational Study ◽  
Prospective Observational Study ◽  
Severe Disease ◽  
Antibody Responses ◽  
University Hospital ◽  
Spike Protein ◽  
Serological Response ◽  
Igg Antibody ◽  
Mild Disease ◽  
Antibody Levels

Background Serological response and association to clinical manifestation is important for understanding the pathogenesis of COVID-19. Materials and methods A prospective observational study was conducted where antibody responses of IgG and IgA towards SARS-CoV-2 spike protein were studied over time in patients with COVID-19. Possible associations between antibody titers and outcome were analyzed. Results Forty patients with COVID-19, hospitalized at Skåne University hospital, Sweden, between April and June 2020 were included. IgG antibody responses were detected for all patients with the highest levels four weeks after COVID-19 diagnosis. Levels of IgA were generally higher at diagnosis and decreased towards baseline 4 weeks after confirmed COVID-19. Patients with severe COVID-19 had higher levels of antibodies directed against SARS-CoV-2 spike protein compared with patients with mild disease. Conclusion IgG and IgA antibodies towards the spike protein follow different kinetics during COVID-19 and patients with severe disease develop higher antibody levels.

scholarly journals Detection of antibodies to the SARS-CoV-2 spike glycoprotein in both serum and saliva enhances detection of infection

2020 ◽  
Author(s):  
Sian E. Faustini ◽  
Sian E. Jossi ◽  
Marisol Perez-Toledo ◽  
Adrian M. Shields ◽  
Joel D. Allen ◽  
...  
Keyword(s):  
Severe Disease ◽  
Hospitalized Patients ◽  
Antibody Responses ◽  
Spike Glycoprotein ◽  
Mild Disease ◽  
Antibody Assays ◽  
Gates Foundation ◽  
Asymptomatic Individuals ◽  
The University

AbstractBackgroundDetecting 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.MethodsWe systemically developed an ELISA assay, optimising different antigens and amplification steps, in serum and saliva from symptomatic and asymptomatic SARS-CoV-2-infected subjects.ResultsUsing 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.ConclusionsDetecting antibody responses in both saliva and serum is optimal for determining virus exposure and understanding immune responses after SARS-CoV-2 infection.FundingThis 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.

scholarly journals Antibody responses to SARS-CoV2 are distinct in children with MIS-C compared to adults with COVID-19

2020 ◽  
Author(s):  
Stuart P Weisberg ◽  
Thomas Connors ◽  
Yun Zhu ◽  
Matthew Baldwin ◽  
Wen-Hsuan Lin ◽  
...  
Keyword(s):  
Distress Syndrome ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Serological Response ◽  
The Novel ◽  
N Protein ◽  
Mild Disease ◽  
Patient Groups ◽  
Novel Coronavirus ◽  
Inflammatory Syndrome

Clinical manifestations of COVID-19 caused by the novel coronavirus SARS-CoV-2 are associated with age. While children are largely spared from severe respiratory disease, they can present with a SARS-CoV-2-associated multisystem inflammatory syndrome (MIS-C) similar to Kawasaki's disease. Here, we show distinct antibody (Ab) responses in children with MIS-C compared to adults with severe COVID-19 causing acute respiratory distress syndrome (ARDS), and those who recovered from mild disease. There was a reduced breadth and specificity of anti-SARS-CoV-2-specific antibodies in MIS-C patients compared to the COVID patient groups; MIS-C predominantly generated IgG Abs specific for the Spike (S) protein but not for the nucleocapsid (N) protein, while both COVID-19 cohorts had anti-S IgG, IgM and IgA Abs, as well as anti-N IgG Abs. Moreover, MIS-C patients had reduced neutralizing activity compared to COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children and adults who develop severe disease, with implications for optimizing treatments based on symptom and age.

scholarly journals Familial aggregation of COVID-19 severity suggests a genetic component to host infection response

2021 ◽  
Vol 2 (2) ◽  
Author(s):  
Alexandre R Vieira ◽  
Keyword(s):  
Familial Aggregation ◽  
Severe Disease ◽  
Case Series ◽  
Genetic Component ◽  
Mild Disease ◽  
Individual Host ◽  
Disease Pattern ◽  
Infection Response ◽  
Severity Of The Disease ◽  
Host Infection

Familial aggregation of COVID-19 cases suggest transmission occurs by contact but can also be evidence of a genetic component to the disease presentation. The goal of this work was to evaluate the disease pattern in families that many individuals have been affected by the disease. A case series analysis of six families that had many individuals affected by COVID-19 and the pattern of the severity of the disease is reported. Families were from two densely populated cities in Brazil. Participants included family members of six unrelated families, with some individuals that showed signs of COVID-19. The exposure was SARS-CoV-2 in the same household. The main outcomes and measures were disease affection and severity, including mortality. From the six families, two had mild cases only, whereas the other four families showed severe disease and death in the same sibship. The two families that had mild disease could be followed for six months and one showed reinfection after six months. This cases series suggest that disease severity aggregates in families, which suggests a genetic component for individual host response to SARS-CoV-2 infection.

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