scholarly journals SARS-CoV-2 antibody magnitude and detectability are driven by disease severity, timing, and assay

2021 ◽  
Author(s):  
Michael J. Peluso ◽  
Saki Takahashi ◽  
Jill Hakim ◽  
J. Daniel Kelly ◽  
Leonel Torres ◽  
...  
Keyword(s):  
Disease Severity ◽  
Antibody Responses ◽  
Binding Assays ◽  
Oxygen Requirement ◽  
Test Characteristics ◽  
Clinical Presentations ◽  
Antibody Assays ◽  
Previous Infection ◽  
Antibody Titers ◽  
Infection Timing

ABSTRACTSerosurveillance studies are critical for estimating SARS-CoV-2 transmission and immunity, but interpretation of results is currently limited by poorly defined variability in the performance of antibody assays to detect seroreactivity over time in individuals with different clinical presentations. We measured longitudinal antibody responses to SARS-CoV-2 in plasma samples from a diverse cohort of 128 individuals over 160 days using 14 binding and neutralization assays. For all assays, we found a consistent and strong effect of disease severity on antibody magnitude, with fever, cough, hospitalization, and oxygen requirement explaining much of this variation. We found that binding assays measuring responses to spike protein had consistently higher correlation with neutralization than those measuring responses to nucleocapsid, regardless of assay format and sample timing. However, assays varied substantially with respect to sensitivity during early convalescence and in time to seroreversion. Variations in sensitivity and durability were particularly dramatic for individuals with mild infection, who had consistently lower antibody titers and represent the majority of the infected population, with sensitivities often differing substantially from reported test characteristics (e.g., amongst commercial assays, sensitivity at 6 months ranged from 33% for ARCHITECT IgG to 98% for VITROS Total Ig). Thus, the ability to detect previous infection by SARS-CoV-2 is highly dependent on the severity of the initial infection, timing relative to infection, and the assay used. These findings have important implications for the design and interpretation of SARS-CoV-2 serosurveillance studies.

scholarly journals SARS-CoV-2 antibody magnitude and detectability are driven by disease severity, timing, and assay

2021 ◽  
Vol 7 (31) ◽  
pp. eabh3409
Author(s):  
Michael J. Peluso ◽  
Saki Takahashi ◽  
Jill Hakim ◽  
J. Daniel Kelly ◽  
Leonel Torres ◽  
...  
Keyword(s):  
Disease Severity ◽  
Antibody Responses ◽  
Plasma Samples ◽  
Oxygen Requirement ◽  
Clinical Presentations ◽  
Antibody Assays ◽  
Previous Infection ◽  
Antibody Titers ◽  
Protein Versus ◽  
Over Time

Interpretation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveillance studies is limited by poorly defined performance of antibody assays over time in individuals with different clinical presentations. We measured antibody responses in plasma samples from 128 individuals over 160 days using 14 assays. We found a consistent and strong effect of disease severity on antibody magnitude, driven by fever, cough, hospitalization, and oxygen requirement. Responses to spike protein versus nucleocapsid had consistently higher correlation with neutralization. Assays varied substantially in sensitivity during early convalescence and time to seroreversion. Variability was dramatic for individuals with mild infection, who had consistently lower antibody titers, with sensitivities at 6 months ranging from 33 to 98% for commercial assays. Thus, the ability to detect previous infection by SARS-CoV-2 is highly dependent on infection severity, timing, and the assay used. These findings have important implications for the design and interpretation of SARS-CoV-2 serosurveillance studies.

scholarly journals Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1390
Author(s):  
Anwar M. Hashem ◽  
Abdullah Algaissi ◽  
Sarah A. Almahboub ◽  
Mohamed A. Alfaleh ◽  
Turki S. Abujamel ◽  
...  
Keyword(s):  
Disease Severity ◽  
Neutralizing Antibodies ◽  
Humoral Response ◽  
Mortality Rates ◽  
Antibody Responses ◽  
High Morbidity ◽  
Clinical Presentations ◽  
Specific Igg ◽  
Almost All ◽  
Kinetics Of

The Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, continues to spread globally with significantly high morbidity and mortality rates. Antigen-specific responses are of unquestionable value for clinical management of COVID-19 patients. Here, we investigated the kinetics of IgM, IgG against the spike (S) and nucleoproteins (N) proteins and their neutralizing capabilities in hospitalized COVID-19 patients with different disease presentations (i.e., mild, moderate or severe), need for intensive care units (ICU) admission or outcomes (i.e., survival vs death). We show that SARS-CoV-2 specific IgG, IgM and neutralizing antibodies (nAbs) were readily detectable in almost all COVID-19 patients with various clinical presentations. Interestingly, significantly higher levels of nAbs as well as anti-S1 and -N IgG and IgM antibodies were found in patients with more severe symptoms, patients requiring admission to ICU or those with fatal outcomes. More importantly, early after symptoms onset, we found that the levels of anti-N antibodies correlated strongly with disease severity. Collectively, these findings provide new insights into the kinetics of antibody responses in COVID-19 patients with different disease severity.

scholarly journals Analysis of Serological Biomarkers of SARS-CoV-2 Infection in Convalescent Samples From Severe, Moderate and Mild COVID-19 Cases

2021 ◽  
Vol 12 ◽  
Author(s):  
Javier Castillo-Olivares ◽  
David A. Wells ◽  
Matteo Ferrari ◽  
Andrew C. Y. Chan ◽  
Peter Smith ◽  
...  
Keyword(s):  
Large Scale ◽  
World Health Organisation ◽  
Epidemiological Studies ◽  
Antibody Responses ◽  
Clinical Severity ◽  
World Health ◽  
Binding Assays ◽  
Neutralising Antibodies ◽  
Antibody Assays ◽  
Binding Antibody

Precision monitoring of antibody responses during the COVID-19 pandemic is increasingly important during large scale vaccine rollout and rise in prevalence of Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2) variants of concern (VOC). Equally important is defining Correlates of Protection (CoP) for SARS-CoV-2 infection and COVID-19 disease. Data from epidemiological studies and vaccine trials identified virus neutralising antibodies (Nab) and SARS-CoV-2 antigen-specific (notably RBD and S) binding antibodies as candidate CoP. In this study, we used the World Health Organisation (WHO) international standard to benchmark neutralising antibody responses and a large panel of binding antibody assays to compare convalescent sera obtained from: a) COVID-19 patients; b) SARS-CoV-2 seropositive healthcare workers (HCW) and c) seronegative HCW. The ultimate aim of this study is to identify biomarkers of humoral immunity that could be used to differentiate severe from mild or asymptomatic SARS-CoV-2 infections. Some of these biomarkers could be used to define CoP in further serological studies using samples from vaccination breakthrough and/or re-infection cases. Whenever suitable, the antibody levels of the samples studied were expressed in International Units (IU) for virus neutralisation assays or in Binding Antibody Units (BAU) for ELISA tests. In this work we used commercial and non-commercial antibody binding assays; a lateral flow test for detection of SARS-CoV-2-specific IgG/IgM; a high throughput multiplexed particle flow cytometry assay for SARS-CoV-2 Spike (S), Nucleocapsid (N) and Receptor Binding Domain (RBD) proteins); a multiplex antigen semi-automated immuno-blotting assay measuring IgM, IgA and IgG; a pseudotyped microneutralisation test (pMN) and an electroporation-dependent neutralisation assay (EDNA). Our results indicate that overall, severe COVID-19 patients showed statistically significantly higher levels of SARS-CoV-2-specific neutralising antibodies (average 1029 IU/ml) than those observed in seropositive HCW with mild or asymptomatic infections (379 IU/ml) and that clinical severity scoring, based on WHO guidelines was tightly correlated with neutralisation and RBD/S antibodies. In addition, there was a positive correlation between severity, N-antibody assays and intracellular virus neutralisation.

scholarly journals Heterogeneity in response to serological exposure markers of recent Plasmodium vivax infections in contrasting epidemiological contexts

2021 ◽  
Vol 15 (2) ◽  
pp. e0009165
Author(s):  
Jason Rosado ◽  
Michael T. White ◽  
Rhea J. Longley ◽  
Marcus Lacerda ◽  
Wuelton Monteiro ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Antibody Responses ◽  
Blood Stage ◽  
Linear Regression Models ◽  
Low Transmission ◽  
Infected People ◽  
Previous Infection ◽  
Antibody Titers ◽  
Study Sites

Background Antibody responses as serological markers of Plasmodium vivax infection have been shown to correlate with exposure, but little is known about the other factors that affect antibody responses in naturally infected people from endemic settings. To address this question, we studied IgG responses to novel serological exposure markers (SEMs) of P. vivax in three settings with different transmission intensity. Methodology We validated a panel of 34 SEMs in a Peruvian cohort with up to three years’ longitudinal follow-up using a multiplex platform and compared results to data from cohorts in Thailand and Brazil. Linear regression models were used to characterize the association between antibody responses and age, the number of detected blood-stage infections during follow-up, and time since previous infection. Receiver Operating Characteristic (ROC) analysis was used to test the performance of SEMs to identify P. vivax infections in the previous 9 months. Principal findings Antibody titers were associated with age, the number of blood-stage infections, and time since previous P. vivax infection in all three study sites. The association between antibody titers and time since previous P. vivax infection was stronger in the low transmission settings of Thailand and Brazil compared to the higher transmission setting in Peru. Of the SEMs tested, antibody responses to RBP2b had the highest performance for classifying recent exposure in all sites, with area under the ROC curve (AUC) = 0.83 in Thailand, AUC = 0.79 in Brazil, and AUC = 0.68 in Peru. Conclusions In low transmission settings, P. vivax SEMs can accurately identify individuals with recent blood-stage infections. In higher transmission settings, the accuracy of this approach diminishes substantially. We recommend using P. vivax SEMs in low transmission settings pursuing malaria elimination, but they are likely to be less effective in high transmission settings focused on malaria control.

scholarly journals Evaluation of commercial anti-SARS-CoV-2 antibody assays and comparison of standardized titers in vaccinated healthcare workers

2021 ◽  
Author(s):  
Kahina Saker ◽  
Vanessa Escuret ◽  
Virginie Pitiot ◽  
Amélie Massardier-Pilonchéry ◽  
Stéphane Paul ◽  
...  
Keyword(s):  
Healthcare Workers ◽  
Conversion Factor ◽  
Internal Standard ◽  
World Health ◽  
Detection Assay ◽  
Significant Difference ◽  
Antibody Assays ◽  
Previous Infection ◽  
Antibody Titers ◽  
Health Organization

AbstractWith the availability of vaccines, commercial assays detecting anti-SARS-CoV-2 antibodies (Ab) evolved towards quantitative assays directed to the spike glycoprotein or its receptor binding domain (RBD). The main objective of the present study was to compare the Ab titers obtained with quantitative commercial binding Ab assays, after 1 dose (convalescent individuals) or 2 doses (naive individuals) of vaccine, in healthcare workers (HCW).Antibody titers were measured in 263 sera (from 150 HCW) with 5 quantitative immunoassays (Abbott RBD IgG II quant, bioMerieux RBD IgG, DiaSorin Trimeric spike IgG, Siemens Healthineers RBD IgG, Wantai RBD IgG). One qualitative total antibody anti RBD detection assay (Wantai) was used to detect previous infection before vaccination. The results are presented in binding Ab units (BAU)/mL after application, when possible, of a conversion factor provided by the manufacturers and established from a World Health Organization (WHO) internal standard.There was a 100% seroconversion with all assays evaluated after two doses of vaccine. With assays allowing BAU/ml correction, Ab titers were correlated (ρ= 0.84-0.99). However, a significant difference between values persisted. The titer differences varied by a mean 3.04% between Siemens and bioMerieux assays to 50.54% between Siemens and DiaSorin assays.Titer harmonization is still to be improved despite better results were obtained between assays detecting the same Ab against the same antigen. The next step towards a true standardization of the assays would be to include the International Standard in the calibration of each assays to express the results in IU/mL.

scholarly journals Evaluation of commercial anti-SARS-CoV-2 antibody assays and comparison of standardized titers in vaccinated healthcare workers.

2021 ◽  
Author(s):  
Kahina Saker ◽  
Vanessa Escuret ◽  
Virginie Pitiot ◽  
Amélie Massardier-Pilonchéry ◽  
Stéphane Paul ◽  
...  
Keyword(s):  
Healthcare Workers ◽  
Conversion Factor ◽  
Pearson Correlation ◽  
Internal Standard ◽  
World Health ◽  
Detection Assay ◽  
Antibody Assays ◽  
Previous Infection ◽  
Antibody Titers ◽  
Health Organization

With the availability of vaccines, commercial assays detecting anti-SARS-CoV-2 antibodies (Ab) evolved towards quantitative assays directed to the spike glycoprotein or its receptor binding domain (RBD). The main objective of the present study was to compare the Ab titers obtained with quantitative commercial binding Ab assays, after 1 dose (convalescent individuals) or 2 doses (naïve individuals) of vaccine, in healthcare workers (HCW). Antibody titers were measured in 255 sera (from 150 HCW) with 5 quantitative immunoassays (Abbott RBD IgG II quant, bioMérieux RBD IgG, DiaSorin Trimeric spike IgG, Siemens Healthineers RBD IgG, Wantai RBD IgG). One qualitative total antibody anti RBD detection assay (Wantai) was used to detect previous infection before vaccination. The results are presented in binding Ab units (BAU)/mL after application, when possible, of a conversion factor provided by the manufacturers and established from a World Health Organization (WHO) internal standard. There was a 100% seroconversion with all assays evaluated after two doses of vaccine. With assays allowing BAU/ml correction, Ab titers were correlated (Pearson correlation coefficient, ρ, range: 0.85-0.94). The titer differences varied by a mean of 10.6% between Siemens and bioMérieux assays to 60.9% between Abbott and DiaSorin assays. These results underline the importance of BAU conversion for the comparison of Ab titer obtained with the different quantitative assays. However, significant differences persist, notably, between kits detecting Ab against the different antigens. A true standardization of the assays would be to include the International Standard in the calibration of each assays to express the results in IU/mL

scholarly journals Towards Internationally standardised humoral Immune Correlates of Protection from SARS CoV 2 infection and COVID-19 disease

2021 ◽  
Author(s):  
Javier Castillo-Olivares ◽  
David Wells ◽  
Matteo Ferrari ◽  
Andrew Chan ◽  
Peter Smith ◽  
...  
Keyword(s):  
Large Scale ◽  
Antibody Responses ◽  
Clinical Severity ◽  
World Health ◽  
Binding Assays ◽  
Neutralising Antibodies ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Antibody Assays ◽  
Binding Antibody

Precision monitoring of antibody responses during the COVID-19 pandemic is increasingly important during large scale vaccine rollout and rise in prevalence of Severe Acute Respiratory Syndrome- related Coronavirus-2 (SARS-CoV-2) variants of concern (VOC). Equally important is defining Correlates of Protection (CoP) for SARS-CoV-2 infection and COVID-19 disease. Data from epidemiological studies and vaccine trials identified virus neutralising antibodies (VNab) and SARS- CoV-2 antigen-specific (notably RBD, and S) binding antibodies as candidate CoP. In this study, we used the World Health Organisation (WHO) international standard to benchmark neutralising antibody responses and a large panel of binding antibody assays to compare convalescent sera obtained from: a) COVID-19 patients; b) SARS-CoV-2 seropositive healthcare workers (HCW) and c) seronegative HCW. The ultimate aim of this study, was to identify biomarkers of humoral immunity that could be used as candidate CoP in internationally accepted unitage. Whenever suitable, the antibody levels of the samples studied were expressed in International Units (INU) for virus neutralisation assays or International Binding Antibody Units (BAU) for ELISA tests. In this work we used commercial and non-commercial antibody binding assays; a lateral flow test for detection of SARS-CoV-2-specific IgG / IgM; a high throughput multiplexed particle flow cytometry assay for SARS-CoV-2 Spike (S), Nucleocapsid (N) and Receptor Binding Domain (RBD) proteins); a multiplex antigen semi-automated immuno-blotting assay measuring IgM, IgA and IgG; a pseudotyped microneutralisation test (pMN) and electroporation-dependent neutralisation assay (EDNA). Our results indicate that overall, severe COVID-19 patients showed statistically significantly higher levels of SARS-CoV-2-specific neutralising antibodies (average 1029 IU/ml) than those observed in seropositive HCW with mild or asymptomatic infections (379 IU/ml) and that clinical severity scoring, based on WHO guidelines was tightly correlated with neutralisation and RBD / S binding assays. In addition, there was a positive correlation between severity, N-antibody assays and intracellular virus neutralisation.

scholarly journals Evolution of anti-Trypanosoma cruzi antibody production in patients with chronic Chagas disease: Correlation between antibody titers and development of cardiac disease severity

2017 ◽  
Vol 11 (7) ◽  
pp. e0005796 ◽  
Author(s):  
Ingebourg Georg ◽  
Alejandro Marcel Hasslocher-Moreno ◽  
Sergio Salles Xavier ◽  
Marcelo Teixeira de Holanda ◽  
Eric Henrique Roma ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Disease Severity ◽  
Chagas Disease ◽  
Antibody Production ◽  
Cardiac Disease ◽  
Antibody Titers ◽  
Chronic Chagas Disease

Evaluation of Two Tetravalent (ACYW135) Meningococcal Vaccines in Infants and Small Children: A Clinical Study Comparing Immunogenicity of O-Acetyl-Negative and O-Acetyl-Positive Group C Polysaccharides

PEDIATRICS ◽  
1985 ◽  
Vol 76 (1) ◽  
pp. 91-96
Author(s):  
Heikki Peltola ◽  
Assad Safary ◽  
Helena Käyhty ◽  
Viena Karanko ◽  
Francis E. André
Keyword(s):  
Clinical Study ◽  
Elevated Temperatures ◽  
Age Groups ◽  
Antibody Responses ◽  
Meningococcal Vaccine ◽  
Small Children ◽  
Positive Group ◽  
Systemic Reactions ◽  
Antibody Titers ◽  
Group A

Two different tetravalent polysaccharide vaccines against group A, C, Y, and W135 meningococci were given to 118 infants aged 6 to 23 months; the same vaccines were administered in a second dose 12 months later to those infants aged 6 to 11 months at first vaccination. Forty of the infants received vaccine containing the nonacetylated group C polysaccharide C(OAc-) and 78 the acetylated group C polysaccharide C(OAc+) together with group A, Y, and W135 polysaccharides. All polysaccharides, at a dose of 30 µg, induced antibody responses after administration of both vaccines in all age groups although the responses were better in the older infants. Acetylation of the sialic acid of the group C polysaccharide did not significantly influence the response. Rapid decreases in the antibody titers after the first vaccination stressed the need for one or more revaccinations. Vaccination elicited mild local and systemic reactions. Elevated temperatures were more common in the youngest infants but only four developed fever exceeding 38.5°C (101.3°F). We conclude that tetravalent (ACYW135) meningococcal vaccine is safe and immunologically effective in children younger than age 2 years. However, revaccinations may be required to maintain immunity.

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