Was the "Russian flu" caused by a zoonotic coronavirus crossover?
You probably don’t spend a lot of time thinking about the virus HCoV-OC43, a close relative of the SARS-Cov-2 virus that’s dominated global attention for the past 18 months. But it’s one of the four coronaviruses that circulate widely in human beings and have for a long time, and that today are often responsible for what people normally call the common cold.
Dennis Wat’s literature review on the common cold estimates that endemic coronaviruses are responsible for about 10 to 15% of cases. According to Wat, the largest share of colds are caused by various rhinoviruses, and between five and 15% of colds are actually mild influenza infections.
This reflects a very modern way of speaking about illness. Biologically speaking, the common cold is not a single disease or even necessarily a cluster of particularly similar diseases. It’s just that when a respiratory infection strikes and it’s not too severe, we tend to call it a cold. The fact that a rhinovirus, HCoV-OC43, and a mild case of the flu might all produce similar symptoms doesn’t change the fact that these are actually three different illnesses, and the “common cold” is just a loose way of talking about them.
By the same token, in today’s understanding, “the flu” is by definition caused by an infection of one of the influenza viruses. Some other infections might cause “flu-like symptoms,” but it’s not the flu unless it’s the influenza virus.
But back in the 1880s, the idea of a virus was just speculation. Louis Pasteur inferred that the causative agent of rabies had to be some kind of microbe that was much smaller than a bacteria, but it wasn’t until the 1890s that scientists began to actually detect these microbes, and no images existed until 1931.
So in 1889, when people in St. Petersburg started coming down with something, there was no distinction between flu-like symptoms and the flu. The idea that something might “really” or “not really” be influenza didn’t make sense in the context of the time. Russians had flu-like symptoms, so it was the Russian Flu, and as it spread across western Europe and then into the United States, people called it influenza or “la grippe.” And it killed a lot of people. By New Year’s Day 1890, the New York City health department was reporting its second-highest daily death total on record, “ample proof that the influenza or ‘grip’ is a serious factor.”
But what if the Russian Flu was not what we would today call the flu? What if it was a coronavirus, HCoV-OC43, making the leap from animals to humans and infecting a population that had simply never been exposed to it before? It could be the case that a quarter of colds caused by coronaviruses today are what we might call Covid-1899, the modern-day symptomatic manifestation of what used to be a much more serious illness — one that’s simply not a big deal now due to a mix of evolution and acquired immunity.
A somewhat unusual flu
By 1918, a new flu pandemic — one that scientists are certain was caused by an influenza virus — was upon the world, so people were naturally interested in looking back at the 1899 outbreak. Researchers in the American Journal of Public Health published a detailed look at the mortality burden in Chicago and found “the greatest increase above the expected was in death of persons over 60,” whereas young children not only had a low absolute number of deaths but a low relative increase in deaths compared to older cohorts.
This is not a typical pattern for the flu, which generally strikes the elderly hardest, followed by little kids.
That’s one reason Danish epidemiologist Lone Simonsen gives for thinking the Russian flu wasn’t influenza at all. Another suggestive element is that some medical professionals reported the loss of a sense of taste as one of the symptoms of the illness.
In her qualitative research on the pandemic’s course in Hamilton, Ontario, Vanessa Colasanti reports on a debate that sounds very similar to today’s “long Covid” controversies. Some Russian Flu sufferers reported long-term neurological symptoms, while others doubted the connection was real or thought it might be psychosomatic.
Although reports on depression and other mental illnesses are difficult to find in late nineteenth-century Hamilton, observers elsewhere noticed that the Russian Influenza had long-term effects. For instance, a notable sudden increase in suicides occurred in 1890-1894 in London, Norfolk, and Dublin, for which approximately half of the coroners’ reports listed influenza as a primary cause (Smith 1995:71). Explanations for post-influenza mental illnesses varied. Some doctors favoured neurological models, arguing that influenza “runs up and down” the nervous system, causing disorder and pain in different parts of the body. Others favoured psychological and psychodynamic interpretations. A few doctors doubted a causal relationship between influenza and mental disorders (Honigsbaum 2010:311)
It is difficult to establish a relationship between influenza, depression, and suicide in Hamilton during the 1889-90 Russian Influenza pandemic. Newspaper articles discuss the possibility of a relationship between influenza, depression, and suicide, such as “Death’s Russian Grip” (The Hamilton Herald 1890c), which notes that physicians were alarmed to observe profound depression resulting from the aching head and body during influenza. The article indicates that the theory is supported by recent suicides in New York of people known to have been suffering from the disease. On 9 January, 1890 “Not Death’s Grip” mentions depression and influenza: “Pains in the back, chest, and head and a general feeling of depression are the symptoms of which all complain” (The Hamilton Herald 1890j).
I want to be totally clear that while I find this symptom spelunking to be interesting, it’s hardly ironclad. The mortality patterns of flu pandemics have varied, and post-viral syndromes are just very poorly understood.
The main point is that there was never any particular scientific basis for believing the Russian Flu was caused by an influenza virus. The meaning of the word “flu” just changed after scientists learned about viruses, and it came to mean “the disease caused by influenza viruses” rather than “any serious respiratory ailment.”
What we do know is that HCoV-OC43 exists, and there is suggestive evidence that it arose around the time of the Russian Flu.
The cows of Bukhara
The Russian Flu spread into Western Europe from St. Petersburg, but it was understood at the time to have actually originated in what is known today as Uzbekistan, specifically the historic city of Bukhara.
Back in 2005, a Belgian research team did a complete genomic sequencing of HCoV-OC43 and found that it is similar to Bovine Coronavirus (BCoV), which causes respiratory ailments in cows. Geneticists can look at how two species differ and estimate the point of divergence, and they have concluded that these two viruses split around 1890.
And that, more than the symptom-snooping, is the case for Covid-1889.
We know that some kind of virus caused a respiratory pandemic starting in 1889.
We know that the respiratory virus HCoV-OC43 diverged from its bovine relative around 1890.
It is, of course, possible that there was a flu outbreak in 1889 and that, at around the same time, a coronavirus crossed over from cows and started causing mild respiratory symptoms that were not serious enough to warrant much attention.
But I think that if nobody had ever used the phrase “Russian Flu,” and instead the 1889 pandemic was a mystery ailment called “The Grip,” we would say the most parsimonious explanation is that molecular analysis strongly suggests it was caused by the breakthrough of a new coronavirus from cows to humans, possibly in the Bukhara area. The pandemic would have then spread very rapidly because railroads and steamships connected the world efficiently, killing large numbers of older people and leaving many survivors with neurological symptoms, but largely sparing the young.
From the grip to the common cold
The question, of course, is how could a common cold virus have caused a deadly pandemic?
In an article for Microbial Biotechnology, Harald Brüssow and Lutz Brüssow note that neutralizing antibodies for common cold coronaviruses are found in 50% of school-age kids and 80% of adults. And neutralizing antibodies are just one of the mechanisms through which people acquire immunity through past viral exposure.
The basic theory is that when Covid-1889 originally struck, it did a lot of damage because it was hitting middle-aged and older people who had no prior exposure to the disease. It then circulated for several years, with medical records indicating elevated mortality into the mid-1890s. But it eventually became an endemic virus that people probably got multiple times over the course of their first two or three decades on the planet.
To this day, elderly and immunocompromised people do die of the common cold, so it’s not like there’s some totalizing conceptual barrier between “it’s just a cold” and “now you have pneumonia and can’t breathe.” It does on some level come down to immune response. It’s just that by now, the vast majority of cases of Covid-1889 are not particularly noteworthy. Little kids get it and they have the sniffles. Then over time, you get various breakthrough infections, especially in the winter when these viruses are spreading more efficiently.
Mostly I think this is just an interesting historical puzzle. Hopefully, someday we’ll get more direct scientific evidence about the pathogen responsible for the Russian flu.
But if the Covid-1889 theory is true, I think that helps illustrate some themes we should think about going forward. Realization seems to be spreading that even with vaccines available, it is very unlikely that we are going to reach Covid Zero. For context, Mark Honigsbaum and Lakshmi Krishnan wrote in The Lancet that “although H. Franklin Parsons, the medical investigator for England's Local Government Board, completed his final report on the ‘1889–92 epidemic’ in 1893, further severe recrudescences were observed in 1893, 1895, 1898, and 1899–1900.”
That is a frustratingly long time. And obviously, it was not possible then and would not be possible today to keep things shut down across a decade of variants and new strains and breakthrough infections. Individual people might want to raise their personal level of caution. But in terms of a society-wide response, the only thing that makes sense is acting to “bend the curve” to prevent outbreaks from becoming so large that they stress hospital capacity.
The good news, though, is that even though Covid-1889 never really ended, it also obviously did end.
After kicking around the human population for long enough, the 1889 virus — whatever it was — stopped being a big deal. Very possibly, it’s still with us, and we’re now so adapted that we barely notice. And these days we do have vaccines that we know accelerate that process of rendering Covid-19 less harmful; booster shots could further speed that process. So could increasing the pace at which we get shots into arms in poor countries. Anything we can do to boost vaccine production is good in terms of saving lives and helping restore normalcy.
But to some extent, we’ve probably got to just take the L on this. The common cold is not a huge deal and neither is seasonal flu, but they’re both not nothing. If you could reduce cold incidence by 5% by eliminating HCoV-OC43, that would be pretty awesome. And even if SARS-Cov-2 does calm down and becomes just another cold virus, that’s still not great. But it’s something we’re going to have to learn to live with on some level.