CST faculty searching for "patient zero"

The first case of COVID-19 human transmission has yet to be identified. However, it won’t be long now, if eight Temple researchers have anything to say about it, that is.

With funding from two awards from the National Science Foundation and the National Institutes of Health, the team is taking advantage of an unprecedented number of virus genomes sequenced by researchers from around the world to trace the pandemic’s spread back to the likely genetic common ancestor of all the infections—the so-called progenitor genome, the first combination of genetic material to create the virus. In other words, they’re seeking the “mother” of all COVID-19 cases.

Among their findings, which were published in the May issue of Molecular Biology and Evolution journal: Multiple coronavirus infections in China and the U.S. harbored the identifying characteristics of the progenitor in January 2020 and later. This discovery suggests that the virus was spreading worldwide months before the first reported cases of COVID-19 in China.

According to the researchers, the progenitor genome actually differs from genomes of the first coronaviruses sampled in China by three mutations—implying that none of the earliest patients represent the first case that gave rise to all the human infections.

Indeed, they estimate that the SARS-CoV-2 progenitor was already circulating in late October 2019, at least six to eight weeks prior to the first genome sequenced in Wuhan, China.

“Our findings have shifted the conversation regarding SARS-CoV-2’s origins and spread to times much before the first major recognized outbreak in Wuhan, China,” said the paper’s lead author, Sudhir Kumar, Carnell Professor of Biology and director of Temple’s Institute for Genomics and Evolutionary Medicine.

Pond, a professor of biology who focuses on evolutionary genomics, and his laboratory have extensive experience using powerful computers and computational methods to sift through big data sets, including those of viruses. Kumar’s laboratory has developed and investigated many techniques for analyzing genetic data from tumors in cancer patients. In a novel approach to unraveling the evolution of the coronavirus, the research team adapted those cancer techniques to analyze thousands of the more than one million SARS-CoV-2 sequenced genomes.

“The ‘real-time’ nature of the COVID-19 pandemic, with thousands of genome sequences made public daily, created volumes of data and resulted in rapid discoveries never before seen,” said Pond. As a result, the Temple researchers were able to build a trail of mutations that automatically traces back to the progenitor.

“Their innovative methods of using computations to look at the past enables them also to extrapolate the future, allowing us to anticipate changing occurrences,” said Masucci. “This team exemplifies how Temple researchers are pushing the envelope and leading in their fields.”

As to whether the progenitor evolved naturally or was the result of a laboratory leak—a recently revived theory—they lean toward the former hypothesis. “To be able to prove the pandemic was triggered by a lab leak, we would need to be able to compare genomes of lab strains with those found in the lab’s vicinity,” noted Kumar. “Since no such data from lab strains exist, the lab-origin hypothesis remains speculative.”

The team continues to push further back in time to learn about “patient zero” through evolutionary analytics.

“It has been very fulfilling, professionally and personally, to be contributing to the fight against this scourge of humanity by inventing new ways to tame this truly big data,” said Kumar.

-Bruce E. Beans

Learn more about how Temple investigators are studying the pandemic from all angles here.

October 28, 2021