Hunting for Covid-19 Origins

iStock

By Mary Carpenter

ON THE TRAIL of mysterious illnesses, The Medical Detectives — the title of collected New Yorker articles dating from the late 1940s by Berton Roueché —must diagnose puzzling symptoms and afterwards pinpoint the origin. Their work becomes especially urgent if symptoms begin to worsen or spread—to prevent an epidemic and to forestall future outbreaks.

Searching for the origin of the novel coronavirus, hundreds of researchers around the world continue to pursue two trails, both starting in Wuhan, China: a “lab leak” from biological researchers studying coronaviruses and “natural spillover” from wet markets selling live animals.

The search for Patient Zero, however, is ongoing and extends as far away and back in time as Italy, September 2019, when more than 10% of blood samples collected for a cancer-screening trial tested positive for coronavirus antibodies. Although the WHO requested retesting by a different laboratory in the Netherlands, results have not yet become available.

In Roueché’s “Eleven Blue Men,” the source of cyanotic (blue) coloring— indicating insufficient oxygen in the blood— in 11 sick men turned out to be the salt sprinkled on oatmeal from a single shaker in a public cafeteria, which had had been mistakenly filled with sodium nitrite— familiar as a meat curing agent but poisonous in high doses.

But origins can remain forever unverifiable, as in “The Liberace Room,” where investigators looking into high fever and other symptoms in elementary school students and one teacher in Missouri first suspected bird-borne psittacosis from the class parakeet named Liberace. But when the diagnosis turned out to be the fungal infection histoplasmosis, suspicions centered on a load of coal deposited close to the window of the most-infected classroom—and a recent cave-in at the local strip mine buried any potential evidence.

Unresolved investigations give rise to finger-pointing and sometimes to conspiracy-like theories—that have included lab leaks. Michael C. Carroll’s Lab 257 traces the emergence of Lyme disease to a poorly secured, biological-weapons research lab on Plum Island, New York.  The lab, staffed in the 1940s and ’50s by Russian scientists who specialized in tick-borne diseases, appears close to the epicenter on some early Lyme disease maps.

Close to the center for SARS-CoV-2 on some early maps is the Wuhan Institute of Virology (W.I.V.), where scientists have been studying coronaviruses for years and where safety lapses were the focus of a November 19, 2019, meeting, although the institute has not responded to questions about the lapses or whether these led to accidents.

Fueling suspicions were rumors about W.I.V. coronavirus studies involving “gain of function” —altering a virus’s genotype in ways that could make it more contagious and more virulent, with the goal of better understanding virus-host interactions and the virus’s ability to replicate — especially after the U.S. State Department prohibited mention of U.S. funding for this research, reported by Vanity Fair.

In a related theory of the novel coronavirus’s origin, a W.I.V. researcher might have contracted the virus on a field expedition to study bats, or while processing a virus at the lab, according to Rutgers molecular biologist Richard Ebright.

But University of Arizona virologist Michael Worobey insists that there were “no early cases cluster anywhere near the W.I.V.” Worobey recently switched his support to the natural spillover theory after researchers found that the Wuhan wet market sold civets and raccoon dogs, which can act as intermediate hosts for coronaviruses moving from bats to humans.

Also, Worobey points to the animal market’s location “right at the epicenter of the outbreak.”  (Other scientists including Ebright, however, disagree about the significance of both the recent animal studies and the locations involved.)

But the strongest evidence for the natural spillover theory may be the “uncanny similarity” between the Covid and SARS pandemics, according to UC San Diego virologist Joel Wertheim.  Both viruses emerged in China in late fall, with early cases occurring close to animal markets in cities —Wuhan for Covid and Shenzhen for SARS.

In the search for Patient Zero, researchers at France’s National Institute for Health and Medical Research along with other institutes found seven serum samples testing positive for the coronavirus in a retrospective examination of more than 9,000 samples collected starting in November 2019, and banked as part of a public health project.

Also, beginning in October 2019, China was in the midst of its “worst flu season in more than a decade,” leading to suspicions that early Covid-19 cases could have been missed. Around the same time in October 2019, Wuhan hosted the Military World Games—for which blood samples were collected but no information has yet been made available, despite requests from the WHO.

While some experts doubt that the virus could have circulated for long enough to include these early samples—especially those from France and Italy—others explain that early appearances of new viruses can “fizzle out,” which happened two-thirds of the time in simulations of early Covid-19 outbreaks.

“We have entered a new pandemic era,” write tropical medicine and virus experts collaborating on the September, 2020 paper ,“The Origin of Covid-19 and Why It Matters.” With recent emergences and re-emergences of Ebola fever, Lassa fever, chikungunya, Zika, HIV and other diseases, they warn that “future coronavirus transmissions into humans are not only possibly but likely.”

While science has the ability to control pandemic viral emergencies within 2 to 3 years, it is “dramatically insufficient to prevent and control their emergences in the first place,” the scientists warn. To lower future risks, they call for more aggressive surveillance of coronavirus hot spots and of human behaviors that “bring us into contact with bats, including risks from wet markets, bat cave tourism, and capturing and eating bats.”

To establish the provenance and early infection path of a new disease can take years under the best conditions—and to date China’s government has limited access to biological samples and original records, even from the WHO–which in turn has been slow to release information, according to the Post. U.S. intelligence agencies are now working on an end-of-summer deadline to report to President Biden.

—Mary Carpenter keeps track of continuing developments in research on Covid-19.