SARS-CoV-2 Virus Culture, Genomic and Subgenomic RNA Load, and Rapid Antigen Test in Experimentally Infected Syrian Hamsters

Zhang, Cheng; Guo, Zhendong; Chen, Zhaoliang; Yan, Fang; Li, Yuanguo; Liu, Juxiang; Gao, Yuwei; Zhang, Chunmao

doi:10.1128/jvi.01034-22

Cited by 7 publications

(4 citation statements)

References 27 publications

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“…While the quantitative results of our models should not be used directly to predict culture results for any host-pathogen system besides non-human primates and SARS-CoV-2, the general framework could be adapted easily to generate similar predictions for other host species, other viruses, or other assays. For example, our model could be modified to robustly compare the relationships among antigen tests, PCR, and viral culture, which has recently garnered interest [ 14 , 15 , 82 , 83 ] and would benefit from the increased sample size and cofactor coverage possible with meta-analytical treatment. Notably, when applying the framework to other scenarios, careful model development is still necessary, especially given that different viruses and assays may have other defining characteristics that could affect their relationships, which should influence the choice of candidate cofactors.…”

Section: Discussionmentioning

confidence: 99%

Predicting the presence of infectious virus from PCR data: A meta-analysis of SARS-CoV-2 in non-human primates

Snedden,

Lloyd-Smith

2024

PLoS Pathog

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Researchers and clinicians often rely on molecular assays like PCR to identify and monitor viral infections, instead of the resource-prohibitive gold standard of viral culture. However, it remains unclear when (if ever) PCR measurements of viral load are reliable indicators of replicating or infectious virus. The recent popularity of PCR protocols targeting subgenomic RNA for SARS-CoV-2 has caused further confusion, as the relationships between subgenomic RNA and standard total RNA assays are incompletely characterized and opinions differ on which RNA type better predicts culture outcomes. Here, we explore these issues by comparing total RNA, subgenomic RNA, and viral culture results from 24 studies of SARS-CoV-2 in non-human primates (including 2167 samples from 174 individuals) using custom-developed Bayesian statistical models. On out-of-sample data, our best models predict subgenomic RNA positivity from total RNA data with 91% accuracy, and they predict culture positivity with 85% accuracy. Further analyses of individual time series indicate that many apparent prediction errors may arise from issues with assay sensitivity or sample processing, suggesting true accuracy may be higher than these estimates. Total RNA and subgenomic RNA showed equivalent performance as predictors of culture positivity. Multiple cofactors (including exposure conditions, host traits, and assay protocols) influence culture predictions, yielding insights into biological and methodological sources of variation in assay outcomes–and indicating that no single threshold value applies across study designs. We also show that our model can accurately predict when an individual is no longer infectious, illustrating the potential for future models trained on human data to guide clinical decisions on case isolation. Our work shows that meta-analysis of in vivo data can overcome longstanding challenges arising from limited sample sizes and can yield robust insights beyond those attainable from individual studies. Our analytical pipeline offers a framework to develop similar predictive tools in other virus-host systems, including models trained on human data, which could support laboratory analyses, medical decisions, and public health guidelines.

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Section: Discussionmentioning

confidence: 99%

Predicting the presence of infectious virus from PCR data: A meta-analysis of SARS-CoV-2 in non-human primates

Snedden,

Lloyd-Smith

2024

PLoS Pathog

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“…The SARS-CoV-2 pandemic has been ongoing for three years, and safe and effective vaccines are essential to prevent and reduce the spread of the disease ( Zhang et al, 2022a ). Currently, several SARS-CoV-2 vaccines have primarily been used worldwide.…”

Section: Discussionmentioning

confidence: 99%

A Trim-RBD-GEM vaccine candidate protects mice from SARS-CoV-2

Shi

et al. 2023

Virology

Self Cite

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“…While we developed this model to analyze PCR and viral culture data from non-human primate experiments, the framework can be adapted easily to other animal models or other viral assays. For example, our model could robustly compare the relationships among antigen tests, PCR, and viral culture, which has recently gained interest 9,10,74,75 and would benefit from the increased sample size and cofactor coverage possible with definitive meta-analytical treatment. The framework also shows particular potential for clinical diagnostics, where it offers a straightforward, standardized pipeline to predict whether an individual is infectious based on PCR results, which is a clear need.…”

Section: Discussionmentioning

confidence: 99%

PCR data accurately predict infectious virus: a characterization of SARS-CoV-2 in non-human primates

Snedden

Lloyd‐Smith

2023

Preprint

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Researchers and clinicians often rely on molecular assays like PCR to identify and monitor viral infections instead of the resource-prohibitive gold standard of viral culture. However, it remains unclear when (if ever) PCR measurements of viral load are reliable indicators of replicating or infectious virus. Here, we compare total RNA, subgenomic RNA, and viral culture results from 24 studies of SARS-CoV-2 in non-human primates using bespoke statistical models. On out-of-sample data, our best models predict subgenomic RNA from total RNA with 91% accuracy, and they predict culture positivity with 85% accuracy. Total RNA and subgenomic RNA showed equivalent performance as predictors of culture positivity. Multiple cofactors, including exposure conditions and host traits, influence culture predictions for total RNA quantities spanning twelve orders of magnitude. Our model framework can be adapted to compare any assays, in any host species, and for any virus, to support laboratory analyses, medical decisions, and public health guidelines.

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SARS-CoV-2 Virus Culture, Genomic and Subgenomic RNA Load, and Rapid Antigen Test in Experimentally Infected Syrian Hamsters

Cited by 7 publications

References 27 publications

Predicting the presence of infectious virus from PCR data: A meta-analysis of SARS-CoV-2 in non-human primates

Predicting the presence of infectious virus from PCR data: A meta-analysis of SARS-CoV-2 in non-human primates

A Trim-RBD-GEM vaccine candidate protects mice from SARS-CoV-2

PCR data accurately predict infectious virus: a characterization of SARS-CoV-2 in non-human primates

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