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Probabilistic class...
Probabilistic classification of anti-SARS-CoV-2 antibody responses improves seroprevalence estimates
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- Castro Dopico, Xaquin (författare)
- Karolinska Institutet
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- Muschiol, Sandra (författare)
- Karolinska Institutet
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- Grinberg, Nastasiya F. (författare)
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, United Kingdom
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- Aleman, Soo (författare)
- Karolinska Institutet
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- Sheward, Daniel J. (författare)
- Karolinska Institutet
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- Hanke, Leo (författare)
- Karolinska Institutet
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- Ahl, Marcus (författare)
- Department of Infectious Diseases, Karolinska University Hospital, Huddinge, Sweden
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- Vikström, Linnea (författare)
- Umeå universitet,Institutionen för klinisk mikrobiologi
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- Forsell, Mattias N. E. (författare)
- Umeå universitet,Institutionen för klinisk mikrobiologi
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- Coquet, Jonathan M. (författare)
- Karolinska Institutet
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- McInerney, Gerald (författare)
- Karolinska Institutet
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- Dillner, Joakim (författare)
- Karolinska Institutet
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- Bogdanovic, Gordana (författare)
- Karolinska Institutet
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- Murrell, Ben (författare)
- Karolinska Institutet
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- Albert, Jan (författare)
- Karolinska Institutet
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- Wallace, Chris (författare)
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, United Kingdom; Medical Research Council Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom
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- Karlsson Hedestam, Gunilla B. (författare)
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
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(creator_code:org_t)
- 2022-03-02
- 2022
- Engelska.
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Ingår i: Clinical & Translational Immunology (CTI). - : John Wiley & Sons. - 2050-0068. ; 11:3
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://onlinelibrar...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
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- Objectives: Population-level measures of seropositivity are critical for understanding the epidemiology of an emerging pathogen, yet most antibody tests apply a strict cutoff for seropositivity that is not learnt in a data-driven manner, leading to uncertainty when classifying low-titer responses. To improve upon this, we evaluated cutoff-independent methods for their ability to assign likelihood of SARS-CoV-2 seropositivity to individual samples. Methods: Using robust ELISAs based on SARS-CoV-2 spike (S) and the receptor-binding domain (RBD), we profiled antibody responses in a group of SARS-CoV-2 PCR+ individuals (n = 138). Using these data, we trained probabilistic learners to assign likelihood of seropositivity to test samples of unknown serostatus (n = 5100), identifying a support vector machines-linear discriminant analysis learner (SVM-LDA) suited for this purpose. Results: In the training data from confirmed ancestral SARS-CoV-2 infections, 99% of participants had detectable anti-S and -RBD IgG in the circulation, with titers differing > 1000-fold between persons. In data of otherwise healthy individuals, 7.2% (n = 367) of samples were of uncertain serostatus, with values in the range of 3-6SD from the mean of pre-pandemic negative controls (n = 595). In contrast, SVM-LDA classified 6.4% (n = 328) of test samples as having a high likelihood (> 99% chance) of past infection, 4.5% (n = 230) to have a 50–99% likelihood, and 4.0% (n = 203) to have a 10–49% likelihood. As different probabilistic approaches were more consistent with each other than conventional SD-based methods, such tools allow for more statistically-sound seropositivity estimates in large cohorts. Conclusion: Probabilistic antibody testing frameworks can improve seropositivity estimates in populations with large titer variability.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Nyckelord
- antibody responses
- antibody testing
- COVID-19
- probability
- SARS-CoV-2
- serology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Castro Dopico, X ...
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Muschiol, Sandra
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Grinberg, Nastas ...
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Aleman, Soo
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Sheward, Daniel ...
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Hanke, Leo
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Ahl, Marcus
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Vikström, Linnea
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Forsell, Mattias ...
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Coquet, Jonathan ...
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McInerney, Geral ...
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Dillner, Joakim
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Bogdanovic, Gord ...
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Murrell, Ben
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Albert, Jan
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Wallace, Chris
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Karlsson Hedesta ...
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Umeå universitet
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