Usefulness and Limitations of Anti-S IgG Assay in Detecting Previous SARS-CoV-2 Breakthrough Infection in Fully Vaccinated Healthcare Workers
Introduction: The anti-spike (S) IgG assay is the most widely used method to assess the immunological response to COVID-19 vaccination. Several studies showed that subjects with perivaccination infection have higher anti-S IgG titers. However, a cut-off has not yet been identified so far for disting...
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MDPI AG
2022-09-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/12/9/2152 |
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| author | Gianluca Spiteri Maria Grazia Lourdes Monaco Gulser Caliskan Angela Carta Maria Diletta Pezzani Giuseppe Lippi Davide Gibellini Giuseppe Verlato Stefano Porru |
| author_facet | Gianluca Spiteri Maria Grazia Lourdes Monaco Gulser Caliskan Angela Carta Maria Diletta Pezzani Giuseppe Lippi Davide Gibellini Giuseppe Verlato Stefano Porru |
| author_sort | Gianluca Spiteri |
| collection | DOAJ |
| description | Introduction: The anti-spike (S) IgG assay is the most widely used method to assess the immunological response to COVID-19 vaccination. Several studies showed that subjects with perivaccination infection have higher anti-S IgG titers. However, a cut-off has not yet been identified so far for distinguishing infected subjects after vaccination. This study thus evaluates the performance of the anti-S IgG assay in identifying subjects with breakthrough infections (BIs) and its potential usefulness for screening healthcare workers (HCWs). Methods: Out of 6400 HCWs of the University Hospital of Verona vaccinated with two doses of BNT162b2, 4462 never infected before subjects who had completed primary vaccination were tested for IgG anti-S 6 to 9 months after the second dose. Of these, 59 (1.3%) had a BI. The discriminant power of IgG anti-S in detecting previous breakthrough infection was tested by constructing receiver operating characteristic (ROC) curves. Results: The discriminant power for BI was rather good (area under the curve (AUC), 0.78) and increased with decreasing time elapsed between antibody titer assessment and previous SARS-CoV-2 infection. Accuracy (AUC) sensitivity increased from 0.78 (95% CI 0.70–0.85) for BI in the previous six months to 0.83 (95% CI 0.67–0.99) for those in the previous two months, and from 0.68 to 0.80, respectively. The specificity (0.86) and optimal cut-off (935 BAU/mL) remained unchanged. However, BI were rather rare (1.3%), so the positive predictive value (PPV) was low. Only 40 of the 664 HCWs with antibody titer > 935 BAU/mL had previously confirmed BI, yielding a PPV of only 6.0%. When adopting as cut-off the 90th percentile (1180 BAU/mL), PPV increased to 7.9% (35/441). Conclusions: The anti-S IgG assay displayed good sensitivity and specificity in discriminating subjects with BI, especially in recent periods. However, BIs were rare among HCWs, so that the anti-S IgG assay may have low PPV in this setting, thus limiting the usefulness of this test as a screening tool for HCWs. Further studies are needed to identify more effective markers of a previous infection in vaccinated subjects. |
| first_indexed | 2024-03-10T00:17:27Z |
| format | Article |
| id | doaj.art-ee691bc70d7e48f78f18df7294819e87 |
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| language | English |
| last_indexed | 2024-03-10T00:17:27Z |
| publishDate | 2022-09-01 |
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| series | Diagnostics |
| spelling | doaj.art-ee691bc70d7e48f78f18df7294819e872023-11-23T15:49:34ZengMDPI AGDiagnostics2075-44182022-09-01129215210.3390/diagnostics12092152Usefulness and Limitations of Anti-S IgG Assay in Detecting Previous SARS-CoV-2 Breakthrough Infection in Fully Vaccinated Healthcare WorkersGianluca Spiteri0Maria Grazia Lourdes Monaco1Gulser Caliskan2Angela Carta3Maria Diletta Pezzani4Giuseppe Lippi5Davide Gibellini6Giuseppe Verlato7Stefano Porru8Occupational Medicine Unit, University Hospital of Verona, 37134 Verona, ItalyOccupational Medicine Unit, University Hospital of Verona, 37134 Verona, ItalyUnit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, ItalyOccupational Medicine Unit, University Hospital of Verona, 37134 Verona, ItalyInfectious Diseases Unit, University Hospital of Verona, 37134 Verona, ItalySection of Clinical Biochemistry, Department of Neuroscience, Biomedicine and Movement, University of Verona, 37134 Verona, ItalySection of Microbiology, Department of Diagnostics and Public Health, University of Verona, 37129 Verona, ItalyUnit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, ItalyOccupational Medicine Unit, University Hospital of Verona, 37134 Verona, ItalyIntroduction: The anti-spike (S) IgG assay is the most widely used method to assess the immunological response to COVID-19 vaccination. Several studies showed that subjects with perivaccination infection have higher anti-S IgG titers. However, a cut-off has not yet been identified so far for distinguishing infected subjects after vaccination. This study thus evaluates the performance of the anti-S IgG assay in identifying subjects with breakthrough infections (BIs) and its potential usefulness for screening healthcare workers (HCWs). Methods: Out of 6400 HCWs of the University Hospital of Verona vaccinated with two doses of BNT162b2, 4462 never infected before subjects who had completed primary vaccination were tested for IgG anti-S 6 to 9 months after the second dose. Of these, 59 (1.3%) had a BI. The discriminant power of IgG anti-S in detecting previous breakthrough infection was tested by constructing receiver operating characteristic (ROC) curves. Results: The discriminant power for BI was rather good (area under the curve (AUC), 0.78) and increased with decreasing time elapsed between antibody titer assessment and previous SARS-CoV-2 infection. Accuracy (AUC) sensitivity increased from 0.78 (95% CI 0.70–0.85) for BI in the previous six months to 0.83 (95% CI 0.67–0.99) for those in the previous two months, and from 0.68 to 0.80, respectively. The specificity (0.86) and optimal cut-off (935 BAU/mL) remained unchanged. However, BI were rather rare (1.3%), so the positive predictive value (PPV) was low. Only 40 of the 664 HCWs with antibody titer > 935 BAU/mL had previously confirmed BI, yielding a PPV of only 6.0%. When adopting as cut-off the 90th percentile (1180 BAU/mL), PPV increased to 7.9% (35/441). Conclusions: The anti-S IgG assay displayed good sensitivity and specificity in discriminating subjects with BI, especially in recent periods. However, BIs were rare among HCWs, so that the anti-S IgG assay may have low PPV in this setting, thus limiting the usefulness of this test as a screening tool for HCWs. Further studies are needed to identify more effective markers of a previous infection in vaccinated subjects.https://www.mdpi.com/2075-4418/12/9/2152SARS-CoV-2 vaccinationSARS-CoV-2 breakthrough infectionCOVID-19anti-S IgGhealthcare workers |
| spellingShingle | Gianluca Spiteri Maria Grazia Lourdes Monaco Gulser Caliskan Angela Carta Maria Diletta Pezzani Giuseppe Lippi Davide Gibellini Giuseppe Verlato Stefano Porru Usefulness and Limitations of Anti-S IgG Assay in Detecting Previous SARS-CoV-2 Breakthrough Infection in Fully Vaccinated Healthcare Workers Diagnostics SARS-CoV-2 vaccination SARS-CoV-2 breakthrough infection COVID-19 anti-S IgG healthcare workers |
| title | Usefulness and Limitations of Anti-S IgG Assay in Detecting Previous SARS-CoV-2 Breakthrough Infection in Fully Vaccinated Healthcare Workers |
| title_full | Usefulness and Limitations of Anti-S IgG Assay in Detecting Previous SARS-CoV-2 Breakthrough Infection in Fully Vaccinated Healthcare Workers |
| title_fullStr | Usefulness and Limitations of Anti-S IgG Assay in Detecting Previous SARS-CoV-2 Breakthrough Infection in Fully Vaccinated Healthcare Workers |
| title_full_unstemmed | Usefulness and Limitations of Anti-S IgG Assay in Detecting Previous SARS-CoV-2 Breakthrough Infection in Fully Vaccinated Healthcare Workers |
| title_short | Usefulness and Limitations of Anti-S IgG Assay in Detecting Previous SARS-CoV-2 Breakthrough Infection in Fully Vaccinated Healthcare Workers |
| title_sort | usefulness and limitations of anti s igg assay in detecting previous sars cov 2 breakthrough infection in fully vaccinated healthcare workers |
| topic | SARS-CoV-2 vaccination SARS-CoV-2 breakthrough infection COVID-19 anti-S IgG healthcare workers |
| url | https://www.mdpi.com/2075-4418/12/9/2152 |
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