The end of December is largely considered to be COVID-19’s beginning. It was then that the Wuhan Municipal Health Commission reported a cluster of cases of pneumonia in Wuhan, Hubei Province, China. From there, the virus was identified, sequenced, and the rest, as they say, is history. But, is this indeed when SARS-CoV-2 first emerged in humans? Or, is it possible that it was circulating in the population earlier in the year?

Researchers sought to answer this question by simulating early stages of the SARS-CoV-2 outbreak in Wuhan, China. They concluded that the virus was likely circulating earlier than has been described, possibly even in mid-October 2019. These estimates further distance the first (“index”) case from the outbreak at the Huanan Seafood Wholesale Market, which has received much attention.

This work is published in Science, in the paper, “Timing the SARS-CoV-2 index case in Hubei province.

When SARS-CoV-2 first began transmitting among humans is unknown. This new research, led by Joel Wortheim, PhD, associate adjunct professor, medicine, University of California, San Diego, suggests the first described cluster of COVID-19—associated with the Huanan Seafood Wholesale Market in late-December 2019—is unlikely to have marked the beginning of the pandemic, as COVID-19 cases from early December lacked connections to the market. What’s more, newspaper reports by the Chinese government detail daily retrospective COVID-19 diagnoses going back through November.

To better estimate the timing of the first SARS-CoV-2 case, presumably in Hubei, China, Jonathan Pekar, a PhD student at the University of California, San Diego, used a combined approach. Together with colleagues, he first applied Bayesian molecular clock phylogenetics to estimate the timing of most recent common ancestor of sampled strains of the virus. More specifically, they employed “a coalescent framework to combine retrospective molecular clock inference. They combined that with forward epidemiological simulations to determine how long SARS-CoV-2 could have circulated prior to the time of the most recent common ancestor.

Based on their simulations, the authors predicted the period between mid-October and mid-November 2019 is defined as the plausible interval when the first case of SARS-CoV-2 emerged in Hubei province.

Their simulations considered the possibility that the variant of SARS-CoV-2 that first emerged was less fit than the variant that spread widely; the authors thus simulated two-phase epidemics wherein the first case was infected with a less fit variant that went extinct, but not before giving rise to a mutant strain that persisted.

The authors noted that by characterizing the likely dynamics of the virus before it was discovered, they show that “over two-thirds of SARS-CoV-2-like zoonotic events would be self-limited, dying out without igniting a pandemic.”

The inferred prevalence of this virus was too low to permit its discovery for weeks or months, they added. By the time COVID-19 was first identified, the virus had established itself in Wuhan. The delay highlights the difficulty in surveillance for novel zoonotic pathogens with high transmissibility and moderate mortality rates.

Gaining an understanding of 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.

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