Analysis of Serological Biomarkers of SARS-CoV-2 Infection in Convalescent Samples From Severe, Moderate and Mild COVID-19 Cases
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 P...
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2021
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oai:doaj.org-article:83c33cb02bac4ce88d2084a406ccc6802021-11-19T07:53:12ZAnalysis of Serological Biomarkers of SARS-CoV-2 Infection in Convalescent Samples From Severe, Moderate and Mild COVID-19 Cases1664-322410.3389/fimmu.2021.748291https://doaj.org/article/83c33cb02bac4ce88d2084a406ccc6802021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.748291/fullhttps://doaj.org/toc/1664-3224Precision 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.Javier Castillo-OlivaresDavid A. WellsDavid A. WellsMatteo FerrariMatteo FerrariAndrew C. Y. ChanPeter SmithAngalee NadesalingamMinna PaloniemiGeorge W. CarnellLuis OhlendorfDiego CantoniMartin Mayora-NetoPhil PalmerPaul TonksNigel J. TempertonDavid PeterhoffPatrick NeckermannRalf WagnerRalf WagnerRainer DoffingerSarah KempsterAshley D. OtterAmanda SemperTim BrooksAnna AlbeckaLeo C. JamesMark PageWilhelm SchwaebleHelen BaxendaleJonathan L. HeeneyFrontiers Media S.A.articleCOVID-19SARS-CoV-2Serological biomarkersAntibodiesWHO International StandardCorrelates of ProtectionImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
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| collection |
DOAJ |
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| topic |
COVID-19 SARS-CoV-2 Serological biomarkers Antibodies WHO International Standard Correlates of Protection Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
COVID-19 SARS-CoV-2 Serological biomarkers Antibodies WHO International Standard Correlates of Protection Immunologic diseases. Allergy RC581-607 Javier Castillo-Olivares David A. Wells David A. Wells Matteo Ferrari Matteo Ferrari Andrew C. Y. Chan Peter Smith Angalee Nadesalingam Minna Paloniemi George W. Carnell Luis Ohlendorf Diego Cantoni Martin Mayora-Neto Phil Palmer Paul Tonks Nigel J. Temperton David Peterhoff Patrick Neckermann Ralf Wagner Ralf Wagner Rainer Doffinger Sarah Kempster Ashley D. Otter Amanda Semper Tim Brooks Anna Albecka Leo C. James Mark Page Wilhelm Schwaeble Helen Baxendale Jonathan L. Heeney Analysis of Serological Biomarkers of SARS-CoV-2 Infection in Convalescent Samples From Severe, Moderate and Mild COVID-19 Cases |
| description |
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. |
| format |
article |
| author |
Javier Castillo-Olivares David A. Wells David A. Wells Matteo Ferrari Matteo Ferrari Andrew C. Y. Chan Peter Smith Angalee Nadesalingam Minna Paloniemi George W. Carnell Luis Ohlendorf Diego Cantoni Martin Mayora-Neto Phil Palmer Paul Tonks Nigel J. Temperton David Peterhoff Patrick Neckermann Ralf Wagner Ralf Wagner Rainer Doffinger Sarah Kempster Ashley D. Otter Amanda Semper Tim Brooks Anna Albecka Leo C. James Mark Page Wilhelm Schwaeble Helen Baxendale Jonathan L. Heeney |
| author_facet |
Javier Castillo-Olivares David A. Wells David A. Wells Matteo Ferrari Matteo Ferrari Andrew C. Y. Chan Peter Smith Angalee Nadesalingam Minna Paloniemi George W. Carnell Luis Ohlendorf Diego Cantoni Martin Mayora-Neto Phil Palmer Paul Tonks Nigel J. Temperton David Peterhoff Patrick Neckermann Ralf Wagner Ralf Wagner Rainer Doffinger Sarah Kempster Ashley D. Otter Amanda Semper Tim Brooks Anna Albecka Leo C. James Mark Page Wilhelm Schwaeble Helen Baxendale Jonathan L. Heeney |
| author_sort |
Javier Castillo-Olivares |
| title |
Analysis of Serological Biomarkers of SARS-CoV-2 Infection in Convalescent Samples From Severe, Moderate and Mild COVID-19 Cases |
| title_short |
Analysis of Serological Biomarkers of SARS-CoV-2 Infection in Convalescent Samples From Severe, Moderate and Mild COVID-19 Cases |
| title_full |
Analysis of Serological Biomarkers of SARS-CoV-2 Infection in Convalescent Samples From Severe, Moderate and Mild COVID-19 Cases |
| title_fullStr |
Analysis of Serological Biomarkers of SARS-CoV-2 Infection in Convalescent Samples From Severe, Moderate and Mild COVID-19 Cases |
| title_full_unstemmed |
Analysis of Serological Biomarkers of SARS-CoV-2 Infection in Convalescent Samples From Severe, Moderate and Mild COVID-19 Cases |
| title_sort |
analysis of serological biomarkers of sars-cov-2 infection in convalescent samples from severe, moderate and mild covid-19 cases |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/83c33cb02bac4ce88d2084a406ccc680 |
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