The US is nearing the bleak milestone of 100,000 confirmed coronavirus deaths. But the actual death toll will probably have hit that figure days before the official tallies reflect it. And despite scientists’ best efforts, that date may for ever go unmarked.

Coronavirus was probably spreading through the US before the Trump administration restricted travel from China, before the US had a reliable supply of diagnostic tests, and before the disease caused by the virus was even named. Models of the Covid-19 outbreak estimate that the virus was making its way through America’s major cities, undetected, weeks before a California woman in early February became the first American known to have died of related causes.

Researchers are now doing detective work, revisiting autopsies from early this year and studying how the virus has subtly evolved to try to trace when Covid-19 may have first sickened and killed people in the US. Infectious disease experts caution, however, that finding a “patient zero”, or even figuring out exactly how many Americans were infected and died before testing was available, will be nearly impossible.

The first ‘first case’

The first report of coronavirus in the US came on 21 January, when a man in Washington state who had traveled to Wuhan, China, tested positive. The Seattle area soon became a hotspot, with cases soaring after an outbreak at a nursing home outside the city. On 29 February, Washington state reported what at the time was believed to be the nation’s first death from Covid-19.

Coronavirus cases were also identified in California in late January, initially among those who had recently travelled to Wuhan. By late February, California’s governor, Gavin Newsom, said officials were monitoring more than 8,400 patients – but the state had only 200 testing kits.

Tests were difficult to come by across the nation, after the Centers for Disease Control and Prevention (CDC) had botched the rollout of diagnostic kits and delayed allowing private and academic labs to develop their own. Initially, only the most severely ill patients were being tested, and those who had recently travelled were prioritized.

It was only by looking back that California officials realized that the virus may have been spreading through the state and killing residents earlier than they had thought. Large hospitals and academic medical centers routinely preserve and store tissue samples from autopsies for six months to a year. In April, an analysis of samples from the autopsy of a 57-year-old Santa Clara woman who died suddenly in her home on 6 February revealed that she succumbed to the disease. The woman probably contracted the virus at least a week or two before she died. The fact that she had not travelled outside the country means that coronavirus was spreading within the community by mid-to-late January.

Recently, Washington officials have been looking into the cases of two patients with symptoms typical of Covid-19 in late December, after they recently tested positive for antibodies to the virus. These patients could have suffered from a severe flu or other respiratory illness, and contracted the coronavirus later – but more research and widespread serological tests could help clear up whether some severe cases in late December or January that appeared to be cold or flu were in fact Covid-19.

“Absolutely there’s a chance that there were more infections that resulted in death, at a time when we didn’t know about this novel coronavirus,” said Andrew Badley, chair of the Mayo Clinic’s Covid-19 research task force. “As we do more testing, I think it would be quite likely that we will find cases that go back several months in North America.”

‘We’re not going to exhume bodies’

But much about these early cases is – and will remain – unclear.

Newsom, the California governor, ordered coroners in the state to review autopsies back to December, and the Mayo Clinic is one of many academic medical centers giving cases of pneumonia and flu-like illness a second look. But because only a fraction of deaths at a given medical center are autopsied, and because of the small number of coronavirus infections, even widespread reviews of preserved tissues would not fill in the full picture.

“I mean, we’re not going to exhume bodies and test them,” said George Rutherford, an epidemiologist at the University of California, San Francisco.

At Stanford University, researchers who tested batches of samples collected before mid-February found that only two of nearly 3,000 people with respiratory disease symptoms were infected with coronavirus. While researchers know that there were sporadic cases early on, more research is needed to figure out how widely the virus was circulating in January and February, according to Stanford’s Benjamin Pinsky, who led the testing effort.

That the US saw a late, severe flu season makes it even trickier to tease apart whether it was the flu or coronavirus that was making people sick in January and February, said Rutherford. He wouldn’t be surprised if more early cases turned up, but he said it was unclear why, if the virus was circulating early, patients were not overwhelming hospitals early on. “The big mystery is why don’t we have even more cases now, if it was spreading before we had shelter in place and all that,” he said.

Elsewhere, researchers are hoping to learn more by studying the virus’s genetic makeup. “All viruses have the ability to mutate and change a little bit over time,” said Badley. By tracing different strains of the virus, and working out the rate at which the virus tends to change, researchers can estimate when each strain was introduced to a region, Bradley explained. But the process is tricky and requires that the older strains of the virus still be around – either preserved in tissue samples or spreading through the population.

A genetic analysis found at least eight lineages of the coronavirus circulating in northern California, suggesting that the virus was introduced to the region several times from different sources. That research has yet to be peer-reviewed and published in a scientific journal, but these early findings support what many epidemiologists believe: that there wasn’t a single “patient zero” who sparked the outbreak in the US.

Definitely interesting, but useful?

“I see this fascination with finding who the patient zero was, both in the US or even globally,” Pinsky said, with a chuckle. “But I’m not sure how much we’d gain by actually finding that out.”

Researchers are more interested in grappling with the present and future of the pandemic, ramping up testing, and preparing for a potential seasonal surge in the fall, Pinsky said. “Looking for the first case or death is an interesting, but not so useful, exercise.”

If previous epidemics are to be a guide, there were multiple patient zeros, said Stephen Morse, an epidemiologist at the Columbia University medical center focused on developing early disease warning systems. “There was probably more than one introduction of the virus from Wuhan to the US, and then other introductions from Europe,” Morse said. “Even if we eventually figure it out and are able to trace the route the virus took, it’ll be information that’s more of intellectual interest than scientific interest.”

A better understanding of the path the virus took early on in the US could help states better prepare for a potential second surge of cases in the fall, and it could help smaller countries that have yet to be significantly impacted by the pandemic to protect themselves.

The real lesson here, experts said, is that the US government should have paid attention to early warning signs when they initially cropped up. “I’m heartbroken and disheartened,” Morse said. “I’ve worked for the past 30 years trying to prevent the sort of catastrophe we’re seeing right now.”

The US could have begun testing for coronavirus soon after it started to spread in Wuhan, especially given the amount of travel between the US and China, Morse noted. Countries could have better coordinated their responses and worked together to track and trace early cases.

“Of course my hope is that as we trace back this pandemic, we’ll learn something,” Morse said. “But this time we didn’t learn from past outbreaks. And my suspicion is that by the time another one comes around, years from now, nobody remembers the lessons.”

From: Maanvi Singh


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