scholarly journals Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Avidity Maturation and Association with Disease Severity

2020 ◽  
Author(s):  
Yiqi Ruben Luo ◽  
Indrani Chakraborty ◽  
Cassandra Yun ◽  
Alan H B Wu ◽  
Kara L Lynch
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Disease Severity ◽  
Symptom Onset ◽  
Strong Correlation ◽  
Label Free ◽  
Antibody Avidity ◽  
Mild Disease ◽  
Igg Avidity ◽  
Kinetics Of ◽  
Avidity Maturation

Abstract The kinetics of IgG avidity maturation during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was studied. The IgG avidity assay, using a novel label-free immunoassay technology, revealed a strong correlation between IgG avidity and days since symptom onset. Peak readings were significantly higher in severe than mild disease cases.

scholarly journals Kinetics of SARS-CoV-2 Antibody Avidity Maturation and Association with Disease Severity

2020 ◽  
Author(s):  
Yiqi Ruben Luo ◽  
Indrani Chakraborty ◽  
Cassandra Yun ◽  
Alan H.B. Wu ◽  
Kara Lake Lynch
Keyword(s):  
Disease Severity ◽  
Symptom Onset ◽  
Strong Correlation ◽  
Label Free ◽  
Antibody Avidity ◽  
Mild Disease ◽  
Avidity Assay ◽  
Igg Avidity ◽  
Kinetics Of ◽  
Avidity Maturation

The kinetics of IgG avidity maturation during SARS-CoV-2 infection was studied. The IgG avidity assay used a novel label-free immunoassay technology. It was found that there was a strong correlation between IgG avidity and days since symptom onset, and peak readings were significantly higher in severe than mild disease cases.

scholarly journals Longitudinal Study of SARS-CoV-2 Antibody Characteristics Using Label-Free Immunoassays

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S32-S32
Author(s):  
Y R Luo ◽  
C Yun ◽  
A H Wu ◽  
K L Lynch ◽  
I Chakraborty
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibody ◽  
Label Free ◽  
Serum Samples ◽  
Neutralization Activity ◽  
Antibody Avidity ◽  
Avidity Assay ◽  
Initial Rise ◽  
Igg Avidity ◽  
Antibody Titers

Abstract Introduction/Objective Since the start of the COVID-19 pandemic, much research has focused on the kinetics and magnitude of humoral immune response. With the advantages of monitoring real-time immunoreactions, label-free immunoassay (LFIA) is becoming a powerful tool in serology studies. We have developed LFIAs to measure SARS- CoV-2 antibody avidity and neutralization activity in a cohort of COVID-19 patients and determine if they correlate with antibody concentration. Serial serum samples collected from mild to severe COVID-19 patients were measured out to 8 months post-symptom onset to determine the durability of the neutralizing antibody response. Methods/Case Report Based on thin-film interferometry technology, we established a label-free IgG avidity assay and a label-free surrogate virus neutralization test (LF-sVNT). For measurement, sensing probes pre-coated with receptor-binding domain (RBD) of SARS-CoV-2 spike protein are applied to serum samples containing SARS-CoV-2 antibodies. The label-free IgG avidity assay measures the binding strength between RBD and IgG under urea dissociation. The LF-sVNT analyzes the binding ability of RBD to ACE2 after neutralizing RBD with antibodies. Results (if a Case Study enter NA) IgG avidity indices and neutralizing antibody titers (IC50) were determined from serum samples (n=246) from COVID-19 patients (n=113). IgG concentrations were measured using a fluorescent immunoassay. The neutralizing antibody titers showed a weak correlation with IgG concentrations and no correlation with IgG avidity indices. Over the time course up to 8 months post-symptom onset, IgG concentrations and neutralizing antibody titers presented similar trends: an initial rise, plateau and then in some cases a gradual decline after 40 days. The IgG avidity indices, in the same cases, plateaued after the initial rise. Conclusion The results demonstrated that LFIA could be used an excellent solution in the determination of SARS- CoV-2 antibody characteristics. The study found that IgG concentration and neutralizing antibody titer declined over time, while IgG avidity index remained constant after reaching a plateau. The decline of antibody neutralization activity can be attributed to the reduction in antibody quantity rather than the deterioration of antibody quality, as measured by antibody avidity.

scholarly journals Time to negative PCR from symptom onset in COVID-19 patients on Hydroxychloroquine and Azithromycin - A real world experience

2020 ◽  
Author(s):  
Sarfraz A Saleemi ◽  
Abdulrahman Alrajhi ◽  
Mohammed Alhajji ◽  
Areej Alfattani ◽  
Faisal Albaiz
Keyword(s):  
Disease Severity ◽  
Median Time ◽  
Symptom Onset ◽  
Viral Clearance ◽  
P Value ◽  
Nasopharyngeal Swab ◽  
Multivariate Regression Model ◽  
Mild Disease ◽  
Virus Clearance

Background: The role of hydroxychloroquine (HCQ) and azithromycin in the treatment of COVID-19 and its effect on SARS-CoV-2 viral clearance is not known. Methods: This is a retrospective observational study to assess the effect of HCQ and Azithromycin on duration from symptom onset to negative SARS-CoV-2 PCR using nasopharyngeal swab in hospitalized patient with COVID-19. Eighty-five patients were included in the study, 65 in HCQ (Hydroxychloroquine + Azithromycin) and 20 in non-HCQ group. Measurement of duration from symptom onset to negative PCR and effect of gender, age and disease severity on time to viral clearance was measured. Results: Median time to negative PCR in HCQ group was 23 days (IQR: 9, Mean 24+8, N=65) compared with non-HCQ group, 19 days (IQR: 8, Mean 18+6, N=20), (p <0.05). Forty-one (63%) patients in HCQ group and all patients (100%) in non-HCQ group had mild disease. Multivariate regression model (F=6.8, P<0.002, R2=0.20) shows that being in HCQ group would delay the time to negative PCR by 7 days (95%CI: 2-12) and with every year increase in the age, the time to negative PCR would be delayed by 0.12 days (95%CI: 0.017-0.22). Among HCQ sub-groups, gender and disease severity had no effect on duration (p 0.142 and 0.156 respectively) but older patients >60 year had longer duration compared to patients <60 year of age although p value did not reach significance (p 0.073). Median time to negative PCR in mild-HCQ group (23 days, IQR: 9, Mean 23+8, N=41) was longer when compared with non-HCQ group (p <0.05). On day 28, all patients in non-HCQ group had negative PCR while only 50/65 (77%) were negative in HCQ group. Conclusion: Hydroxychloroquine (HCQ) and azithromycin delay SARS-CoV-2 virus clearance in hospitalized patients with COVID-19 and it is correlated with older age. Larger studies are needed to confirm this finding.

scholarly journals Magnitude and Kinetics of Anti–Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Responses and Their Relationship to Disease Severity

2020 ◽  
Author(s):  
Kara L Lynch ◽  
Jeffrey D Whitman ◽  
Noreen P Lacanienta ◽  
Erica W Beckerdite ◽  
Shannon A Kastner ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Antibody Response ◽  
Disease Severity ◽  
Dynamic Range ◽  
Vaccine Development ◽  
High Sensitivity ◽  
Immunoglobulin M ◽  
Viral Neutralization ◽  
Mild Disease ◽  
Protein Receptor

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can be detected indirectly by measuring the host immune response. For some viruses, antibody concentrations correlate with host protection and viral neutralization, but in rare cases, antiviral antibodies can promote disease progression. Elucidation of the kinetics and magnitude of the SARS-CoV-2 antibody response is essential to understand the pathogenesis of coronavirus disease 2019 (COVID-19) and identify potential therapeutic targets. Methods Sera (n = 533) from patients with real-time polymerase chain reaction–confirmed COVID-19 (n = 94 with acute infections and n = 59 convalescent patients) were tested using a high-throughput quantitative immunoglobulin M (IgM) and immunoglobulin G (IgG) assay that detects antibodies to the spike protein receptor binding domain and nucleocapsid protein. Individual and serial samples covered the time of initial diagnosis, during the disease course, and following recovery. We evaluated antibody kinetics and correlation between magnitude of the response and disease severity. Results Patterns of SARS-CoV-2 antibody production varied considerably. Among 52 patients with 3 or more serial specimens, 44 (84.6%) and 42 (80.8%) had observed IgM and IgG seroconversion at a median of 8 and 10 days, respectively. Compared to those with milder disease, peak measurements were significantly higher for patients admitted to the intensive care unit for all time intervals between 6 and 20 days for IgM, and all intervals after 5 days for IgG. Conclusions High-sensitivity assays with a robust dynamic range provide a comprehensive picture of host antibody response to SARS-CoV-2. IgM and IgG responses were significantly higher in patients with severe than mild disease. These differences may affect strategies for seroprevalence studies, therapeutics, and vaccine development.

scholarly journals A SARS-CoV-2 Label-Free Surrogate Virus Neutralization Test and a Longitudinal Study of Antibody Characteristics in COVID-19 Patients

2021 ◽  
Author(s):  
Yiqi Ruben Luo ◽  
Cassandra Yun ◽  
Indrani Chakraborty ◽  
Alan H.B. Wu ◽  
Kara L. Lynch
Keyword(s):  
Symptom Onset ◽  
Neutralization Test ◽  
Neutralizing Antibody ◽  
Virus Neutralization Test ◽  
Virus Neutralization ◽  
Label Free ◽  
Serum Samples ◽  
Initial Rise ◽  
Igg Avidity ◽  
Antibody Titers

AbstractBackgroundThe laboratory-based methods to measure the SARS-CoV-2 humoral response include virus neutralization tests (VNTs) to determine antibody neutralization potency. For ease of use and universal applicability, surrogate virus neutralization tests (sVNTs) based on antibody-mediated blockage of molecular interactions have been proposed.MethodsA surrogate virus neutralization test established on a label-free immunoassay platform (LF-sVNT). The LF-sVNT analyzes the binding ability of RBD to ACE2 after neutralizing RBD with antibodies in serum.ResultsThe LF-sVNT neutralizing antibody titers (IC50) were determined from serum samples (n=246) from COVID-19 patients (n=113), as well as the IgG concentrations and the IgG avidity indices. Although there is variability in the kinetics of the IgG concentrations and neutralizing antibody titers between individuals, there is an initial rise, plateau and then in some cases a gradual decline at later timepoints after 40 days post-symptom onset. The IgG avidity indices, in the same cases, plateau after the initial rise and did not show a decline.ConclusionsThe LF-sVNT can be a valuable tool in clinical laboratories for the assessment of the presence of neutralizing antibodies to COVID-19. This study is the first to provide longitudinal neutralizing antibody titers beyond 200 days post-symptom onset. Despite the decline of IgG concentration and neutralizing antibody titer, IgG avidity index increases, reaches a plateau and then remains constant up to 8 months post-infection. The decline of antibody neutralization potency can be attributed to the reduction in antibody quantity rather than the deterioration of antibody avidity, a measure of antibody quality.SummaryA surrogate virus neutralization test established on a label-free immunoassay platform (LF-sVNT). Using the LF-sVNT and other assays, 246 serum samples from 113 COVID-19 patients were measured. We observed the time course of antibody characteristics beyond 200 days post-symptom onset.

scholarly journals Antibody Avidity Maturation during Severe Acute Respiratory Syndrome–Associated Coronavirus Infection

2005 ◽  
Vol 192 (1) ◽  
pp. 166-169 ◽  
Author(s):  
Paul K. S. Chan ◽  
Pak‐Leong Lim ◽  
Esther Y. M. Liu ◽  
Jo L. K. Cheung ◽  
Danny T. M. Leung ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Antibody Avidity ◽  
Coronavirus Infection ◽  
Avidity Maturation

scholarly journals A SARS-CoV-2 Label-Free Surrogate Virus Neutralization Test and a Longitudinal Study of Antibody Characteristics in COVID-19 Patients

2021 ◽  
Author(s):  
Yiqi Ruben Luo ◽  
Cassandra Yun ◽  
Indrani Chakraborty ◽  
Alan H.B. Wu ◽  
Kara L. Lynch
Keyword(s):  
Symptom Onset ◽  
Neutralization Test ◽  
Neutralizing Antibody ◽  
Virus Neutralization Test ◽  
Virus Neutralization ◽  
Label Free ◽  
Neutralization Activity ◽  
Initial Rise ◽  
Igg Avidity ◽  
Antibody Titers

Methods designed to measure SARS-CoV-2 humoral response include virus neutralization tests to determine antibody neutralization activity. For ease of use and universal applicability, surrogate virus neutralization tests (sVNTs) based on antibody-mediated blockage of molecular interactions have been proposed. A surrogate virus neutralization test was established on a label-free immunoassay platform (LF-sVNT). The LF-sVNT analyzes the binding ability of SARS-CoV-2 spike protein receptor-binding domain (RBD) to ACE2 after neutralizing RBD with antibodies in serum. The LF-sVNT neutralizing antibody titers (IC50) were determined from serum samples (n=246) from COVID-19 patients (n=113), as well as the IgG concentrations and the IgG avidity indices. Although there was variability in the kinetics of the IgG concentrations and neutralizing antibody titers between individuals, there was an initial rise, plateau and then in some cases a gradual decline at later timepoints after 40 days post-symptom onset. The IgG avidity indices, in the same cases, plateaued after an initial rise and did not show a decline. The LF-sVNT can be a valuable tool in research and clinical laboratories for the assessment of the presence of neutralizing antibodies to COVID-19. This study is the first to provide longitudinal neutralizing antibody titers beyond 200 days post-symptom onset. Despite the decline of IgG concentration and neutralizing antibody titer, IgG avidity index increases, reaches a plateau and then remains constant up to 8 months post-infection. The decline of antibody neutralization activity can be attributed to the reduction in antibody quantity rather than the deterioration of antibody quality, as measured by antibody avidity.

scholarly journals Genomic Characterization of SARS-CoV-2 Isolated from Patients with Distinct Disease Outcomes in Mexico

2022 ◽  
Author(s):  
Celia Boukadida ◽  
Blanca Taboada ◽  
Marina Escalera-Zamudio ◽  
Pavel Isa ◽  
José Ernesto Ramírez-González ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Ambulatory Care ◽  
Disease Severity ◽  
Severe Disease ◽  
Mild Disease ◽  
Disease Outcomes ◽  
Distinct Disease ◽  
Genomic Characterization ◽  
Clinical Conditions

The genetic association of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with different clinical conditions remains unclear and needs further investigation. In this study, we characterized 57 complete SARS-CoV-2 genomes from patients in Mexico with distinct disease severity outcomes: mild disease or ambulatory care, severe disease or hospitalized, and deceased.

scholarly journals Investigation of Four Clusters of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Rwanda, 2020

2021 ◽  
Vol 18 (13) ◽  
pp. 7018
Author(s):  
Olivier Nsekuye ◽  
Edson Rwagasore ◽  
Marie Aime Muhimpundu ◽  
Ziad El-Khatib ◽  
Daniel Ntabanganyimana ◽  
...  
Keyword(s):  
High Risk ◽  
Severe Acute Respiratory Syndrome ◽  
Symptom Onset ◽  
Attack Rate ◽  
Positive Sample ◽  
Contact Tracing ◽  
Face To Face ◽  
Laboratory Confirmation ◽  
Closed Environment ◽  
Index Cases

We reported the findings of the first Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) four clusters identified in Rwanda. Case-investigations included contact elicitation, testing, and isolation/quarantine of confirmed cases. Socio-demographic and clinical data on cases and contacts were collected. A confirmed case was a person with laboratory confirmation of SARS-CoV-2 infection (PCR) while a contact was any person who had contact with a SARS-CoV-2 confirmed case within 72 h prior, to 14 days after symptom onset; or 14 days before collection of the laboratory-positive sample for asymptomatic cases. High risk contacts were those who had come into unprotected face-to-face contact or had been in a closed environment with a SARS-CoV-2 case for >15 min. Forty cases were reported from four clusters by 22 April 2020, accounting for 61% of locally transmitted cases within six weeks. Clusters A, B, C and D were associated with two nightclubs, one house party, and different families or households living in the same compound (multi-family dwelling). Thirty-six of the 1035 contacts tested were positive (secondary attack rate: 3.5%). Positivity rates were highest among the high-risk contacts compared to low-risk contacts (10% vs. 2.2%). Index cases in three of the clusters were imported through international travelling. Fifteen of the 40 cases (38%) were asymptomatic while 13/25 (52%) and 8/25 (32%) of symptomatic cases had a cough and fever respectively. Gatherings in closed spaces were the main early drivers of transmission. Systematic case-investigations contact tracing and testing likely contributed to the early containment of SARS-CoV-2 in Rwanda.

scholarly journals CD169/SIGLEC1 is expressed on circulating monocytes in COVID-19 and expression levels are associated with disease severity

Infection ◽  
2021 ◽  
Author(s):  
Jan-Moritz Doehn ◽  
Christoph Tabeling ◽  
Robert Biesen ◽  
Jacopo Saccomanno ◽  
Elena Madlung ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Disease Severity ◽  
Clinical Studies ◽  
Viral Infections ◽  
Severe Disease ◽  
Type I Interferons ◽  
Type I ◽  
Interferon Signaling ◽  
Expression Levels

AbstractCoronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Type I interferons are important in the defense of viral infections. Recently, neutralizing IgG auto-antibodies against type I interferons were found in patients with severe COVID-19 infection. Here, we analyzed expression of CD169/SIGLEC1, a well described downstream molecule in interferon signaling, and found increased monocytic CD169/SIGLEC1 expression levels in patients with mild, acute COVID-19, compared to patients with severe disease. We recommend further clinical studies to evaluate the value of CD169/SIGLEC1 expression in patients with COVID-19 with or without auto-antibodies against type I interferons.

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