Timing the SARS-CoV-2 Index Case in Hubei Province
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Abstract
Understanding when SARS-CoV-2 emerged is critical to evaluating our current approach to monitoring novel zoonotic pathogens and understanding the failure of early containment and mitigation efforts for COVID-19. We employed a coalescent framework to combine retrospective molecular clock inference with forward epidemiological simulations to determine how long SARS-CoV-2 could have circulated prior to the time of the most recent common ancestor. Our results define the period between mid-October and mid-November 2019 as the plausible interval when the first case of SARS-CoV-2 emerged in Hubei province. By characterizing the likely dynamics of the virus before it was discovered, we show that over two-thirds of SARS-CoV-2-like zoonotic events would be self-limited, dying out without igniting a pandemic. Our findings highlight the shortcomings of zoonosis surveillance approaches for detecting highly contagious pathogens with moderate mortality rates.
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SciScore for 10.1101/2020.11.20.392126: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources To facilitate convergence, (i) a hard lower bound of 1×10-5 substitutions/site/year was placed on the clock rate and (ii) we initiated the MCMC using the maximum likelihood phylogeny that had been transformed into a chronogram via TempEst v1.5.3 (38). TempEstsuggested: (TempEst, RRID:SCR_017304)Convergence and mixing was assessed in Tracer v1.7.1 (39) and chains were combined in LogCombiner, such that all ESS values were >200. Tracersuggested: (Tracer, RRID:SCR_019121)Epidemic Simulation: To explore the evolutionary dynamics at play during the beginning of the COVID-19 pandemic, we … SciScore for 10.1101/2020.11.20.392126: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources To facilitate convergence, (i) a hard lower bound of 1×10-5 substitutions/site/year was placed on the clock rate and (ii) we initiated the MCMC using the maximum likelihood phylogeny that had been transformed into a chronogram via TempEst v1.5.3 (38). TempEstsuggested: (TempEst, RRID:SCR_017304)Convergence and mixing was assessed in Tracer v1.7.1 (39) and chains were combined in LogCombiner, such that all ESS values were >200. Tracersuggested: (Tracer, RRID:SCR_019121)Epidemic Simulation: To explore the evolutionary dynamics at play during the beginning of the COVID-19 pandemic, we performed a series of epidemic simulations using FAVITES v1.2.6 (21) First, we generated static contact networks in FAVITES under a preferential-attachment model using the Barabási-Albert algorithm (40). FAVITESsuggested: NoneMutation analysis: To approximate the number of mutations that separated the index case virus from that represented by the most recent common ancestor of all 583 analyzed SARS-CoV-2 genomes, we calculated the time between the date of index case and the tMRCA after rejection sampling (Fig. 3) and multiplied that time (in years) by the corresponding mean substitution rate from the posterior sample from BEAST. BEASTsuggested: (BEAST, RRID:SCR_010228)Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2020.11.20.392126: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources To facilitate convergence, (i) a hard lower bound of 1x10-5 substitutions/site/year was placed on the clock rate and (ii) we initiated the MCMC using the maximum likelihood phylogeny that had been transformed into a chronogram via TempEst v1.5.3 (38) . TempEstsuggested: (TempEst, RRID:SCR_017304)Convergence and mixing was assessed in Tracer v1.7.1 (39) and chains were combined in LogCombiner, such that all ESS values were >200. …SciScore for 10.1101/2020.11.20.392126: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources To facilitate convergence, (i) a hard lower bound of 1x10-5 substitutions/site/year was placed on the clock rate and (ii) we initiated the MCMC using the maximum likelihood phylogeny that had been transformed into a chronogram via TempEst v1.5.3 (38) . TempEstsuggested: (TempEst, RRID:SCR_017304)Convergence and mixing was assessed in Tracer v1.7.1 (39) and chains were combined in LogCombiner, such that all ESS values were >200. Tracersuggested: (Tracer, RRID:SCR_019121)W e explored the sensitivity of the rejection sampling approach to different molecular clocks in the BEAST inference. BEASTsuggested: (BEAST, RRID:SCR_010228)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
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