新冠疫情到底何时结束？参考一下百年前的“俄罗斯流感”

Patients suffering from respiratory and neurological symptoms, including loss of taste and smell.

Long-haul sufferers who struggle to muster the energy to return to work.

A pandemic with a penchant for attacking the elderly and obese with particular force.

Sounds a lot like COVID, right?

It’s not.

Rather, it’s the “Russian Flu,” the world’s first well-documented pandemic, occurring as modern germ theory rose to prominence and miasma theory dispelled, ushering in the era of modern medical science and public health.

A quick check of the textbooks—the few that actually mention the thing—will inform you that the pandemic, which killed an estimated 1 million worldwide, lasted from 1889 to 1890.

Experts will tell you it likely hung around much longer—and might still lurk, in some form, today.

Predating the now oft-discussed “Spanish Flu” pandemic of 1918, which killed an estimated 50 million worldwide, the Russian Flu likely wasn’t a flu at all, some contend.

Instead, its symptoms more closely resemble a coronavirus—a category of viruses named for their crown-like appearance under a microscope, of which COVID-19 is a member.

Coronaviruses typically cause mild to moderate upper-respiratory infections in humans and are responsible for a handful of common colds. But some have turned deadly, including COVID-19; SARS (Severe Acute Respiratory Syndrome), an epidemic that emerged in 2002 and killed hundreds; and MERS (Middle Eastern respiratory syndrome), another epidemic that emerged in 2012 and killed hundreds.

“The epidemiology and clinical symptoms of the Russian Flu are much more in line with COVID than what we know about influenza pandemics,” said Dr. Harald Bruessow, editor of Microbial Biotechnology and a guest professor at KU Leuven in Belgium who has studied and published extensively on the esoteric ailment.

“You have respiratory infection, but at the same time there are strong neurologic symptoms,” he said of both the Russian Flu and COVID. “There’s also something like Long COVID that was observed following the Russian Flu pandemic. These people were incapacitated for a really long time, with an increase in suicide rate and an inability to return to full work capacity.

“All this stuff makes one think that one is dealing with a coronavirus infection in the 1880s.”

Let’s say the so-called “Russian Flu” was a coronavirus. Does it serve as a better lens through which to view the current pandemic than the Spanish Flu? What lessons can we learn? Does it offer any clues to how the COVID-19 pandemic might end—or linger, rather, as viruses tend to?

"If we say maybe the Russian Flu went extinct by a deus ex machina event, the odds are much lower for COVID," Dr. Arijit Chakravarty, Fractal Therapeutics CEO and COVID researcher, told Fortune.

"We're past that point."

The forgotten “flu”

When "nobody really dared to predict the trajectory of the COVID pandemic, how it will develop or end"—frustrated by short-term computer simulations with a tendency toward inaccuracy—and looking to glimpse into a COVID-19 crystal ball, Bruessow turned to the past.

What pandemic might serve as the best paradigm for COVID? He first examined the Spanish Flu—but that was a different virus, he reasoned. Traveling backward in history from there, his options were limited, with the Russian Flu being the next chronological option—and, ironically, the first pandemic for which data was collected en masse.

As it turns out, it was a great fit.

“The Russian Flu was actually the best case I could figure out of a respiratory pandemic of a comparable size to COVID that was sufficiently medically documented,” Bruessow said of the disease, thought to have originated in cattle in Turkestan before enveloping the Russian empire and sweeping the world.

While considered a flu at the time, scientists did not yet have a solid grasp on what caused disease, with germ theory arising nearly simultaneously and duking it out with the miasma theory, the pre-scientific notion that disease was caused by "bad air" rising from the ground.

In one of his articles on the ailment, Bruessow refers to a 344-page doctors’ report from 1891 London, which describes Russian Flu patients as suffering from a “hard, dry cough,” fevers of 100-105 degrees, “frontal headache of special severity,” “pains in the eyeballs,” “general feeling of misery and weakness, and great depression of spirits,” and “weeping, nervous restlessness, inability to sleep, and occasional delirium.”

As with COVID, children seemed relatively spared, often only mildly affected, if they fell ill at all. Those who were elderly—in addition to those with pre-existing conditions like heart disease, tuberculosis, or diabetes—were more apt to take a fatal course, Bruessow wrote.

And there’s more: Nearly 10% of cases saw continued symptoms, referred to by European doctors of the time as “long enduring evil effects.”

As with COVID, it was noted that patients were likely infectious before developing symptoms, and were occasionally reinfected, as was the case with a patient who fell ill with the “flu” in December 1889 in France, and then again a month later in January 1890 in England.

Dr. Tom Ewing, a history professor and associate dean at Virginia Tech who has published extensively on the topic, considered the Russian Flu an apt comparison during the first three months of the COVID pandemic due to its quick spread and global efforts to track symptoms.

He now considers the Spanish Flu to be a better comparison due to the body count: It's thought to have killed about 650,000 people in the U.S. in eight months, and COVID has killed nearly a million in the U.S. in a little over two years. In contrast, the Russian Flu is thought to have killed a million worldwide, in sum.

"I think where the useful comparisons are is, how do people react?" Ewing said. "How do they respond to first reports? How do physicians deal with a new threatening scale of disease? What we're all living with right now—at what point do you say it's all over?

Is the “Russian Flu” still a killer?

The Russian Flu is typically considered to have lasted from 1889 through 1890, but in reality, it lasted much longer—through 1894, according to the U.S. National Institutes of Health National Library of Medicine—and nearly a decade, depending on whom you talk to. Major mortality peaks, as seen in public health data from the United Kingdom, continued through 1899 or 1900, Bruessow said, adding that the mortality peaks in England during that period are nearly as high as they were during what was likely the first phase of the Russian Flu.

It is unknown if later deaths were from additional waves of the Russian Flu or something else. But reports of symptoms from potential later waves, found in The Lancet and other British medical journals, are “strikingly similar,” and contemporary researchers were “formulating the suspicion” of an up-flair, he said.

All this “makes me think that we should consider the possibility that the Russian Flu agent was evolving and hanging around and even causing a major mortality peak in the United Kingdom and elsewhere,” he concluded.

While it’s unknown if the Russian Flu was indeed a coronavirus, some believe it lives on today as OC43, a common human coronavirus that often causes upper-respiratory track illness, according to the U.S. Centers for Disease Control and Prevention. While its presentation is often mild, the pathogen is known to cause bronchitis, bronchiolitis, and pneumonia in children and the elderly, as well as immunosuppressed patients, and its presentation may be easily confused with that of COVID-19, according to a 2021 article in The Southwest Respiratory and Critical Care Chronicles.

The thought that the Russian Flu endures as OC43 is a “fascinating hypothesis,” developed when scientists realized how genetically similar OC43 is to bovine coronavirus and projected a common ancestor arising around 1890—the Russian Flu era, and a time of major cattle pandemics that may have spread to humans.

If they’re correct, the Russian Flu is still circulating, and it's still occasionally deadly—a 2021 study published in Nature found a 9.1% mortality rate for those hospitalized with confirmed cases of OC43, though it only tracked 77 patients between 2012 and 2017 at one Korean hospital.

The Russian Flu may indeed be "still killing people off, and we're just not paying attention to it, which is totally plausible," Chakravarty said. "We used to think the Epstein-Barr Virus was harmless," and now we know it raises the risk of developing multiple sclerosis by more than 30 times.

"There's a lot of sort of 'dark matter' in the infectious disease world that we haven't fully mapped out."

Such a future may await COVID, Bruessow contends.

“This is what virologists working in the viral evolution field are thinking we should expect from SARS-CoV2,” he said regarding the potential of COVID to persist well into the future. “Some people think the Omicron variant that dominates now is already going a bit in this direction, because this variant is much less affecting the lung and much more targeting the upper respiratory tract.”

Bruessow hopes Omicron is “the last hoorah” of COVID-19’s acute phase—the Russian Flu’s lasted about three years—but he’s well aware this may not be the case.

“Personally, I would be a bit skeptical” that Omicron would be the end of this, he said. “The virus will still occupy our societies for a while.”

Even if the Russian Flu eventually became less severe, there’s no reason to necessarily think COVID-19 will go the same route, Bruessow cautions, nor is the Russian Flu's presumed attenuation necessarily permanent.

“Viral evolution is really neutral with respect to virulence," he said. "The indication is that [COVID-19] will try to escape from the immune response, simply to infect the maximum number of people, and the virus with the highest efficiency will replace less efficient viral types.

“This is the dynamic we are seeing, of increasing transmission. There’s no guarantee that the next wave won’t be a virus that has, once again, increased virulence, like Delta.”

“Pandemic-era” life for more than a century

Among Chakravarty's take-aways from the Russian Flu: "The body count can still pile up" over several years, even if a disease isn't incredibly transmissible and has a relatively low fatality rate, as was the case with the Russian Flu.

Even so, "mortality bounced around," he said. "There wasn't a steady decrease toward endemicity."

Regardless, COVID is "much more contagious" than the Russian Flu was, Chakravarty cautions—and the world is much better connected than it was in the industrial era, allowing for greater ease of disease spread.

COVID has a "screamingly high" transmission rate—one person with Omicron infects, on average, eight to nine others, making it nearly as infectious as mumps—and the duration of immunity is low, he cautioned.

"You can sneeze in Wuhan in the morning and someone can be really ill the next day in Frankfurt."

The potential Russian Flu wave of 1900 is the last mention of the illness Bruessow sees in medical literature. There seem to have been seasonal, legitimate influenza outbreaks up until the onset of the Spanish Flu in 1918, after which major respiratory pandemics “were all influenza related.”

“After that, there’s no indication of a coronavirus causing a major epidemic in the 20th century," he said.

It's possible that a "very mild" coronavirus continued to circulate throughout the 20th century but was less impactful due to improvements in public health and quality of life, Ewing said.

During the early 20th century "health was getting better, mortality rates were decreasing, life expectancy was going up." This, in addition to tuberculous public health campaigns encouraging people to beware of coughing, sneezing, and spitting in public, may have blunted any circulating coronaviruses, he said.

While the Spanish Flu may not be the best lens through which to view COVID-19, it does contain pertinent lessons, Bruessow contends.

While the Spanish Flu is generally thought to have subsided in 1919 after three waves, later waves occurred periodically in the late 1920s into the 1940s—some as virulent as the initial Spanish Flu, with even higher mortality, he contends.

As U.S. COVID czar Dr. Anthony Fauci and colleagues pointed out in a 2009 New England Journal of Medicine article, "It is not generally appreciated that descendants of the H1N1 influenza A virus that caused the catastrophic and historic pandemic of 1918-1919 have persisted in humans for more than 90 [now 100] years and have continued to contribute their genes to new viruses, causing new pandemics," including the 2009 H1N1 "swine flu."

"We are living in a pandemic era that began around 1918," they wrote 13 years ago—long before the advent of COVID-19.

Bruessow agrees with Fauci and his colleagues that “viruses do not simply disappear."

"They change and hopefully they adapt and behave," Bruessow said. "But there are still some escapes, and we might see a return with higher virulence. Vigilance is indicated.”

Chakravarty is of a similar mindset but cautions that one can't draw too many inferences from any particular pandemic, regardless of similarities.

"Each new pandemic, new plague is a new chapter in the history books," he said. "Your mileage may vary."

But one thing remains constant.

"There's no two-year timeline for pandemics," he warned.