Since the Renaissance, the world has faced multiple influenza pandemics, punctuated by lulls lasting a few decades. “Influenza” has been defined by the sudden onset of respiratory signs with fever and high contagiousness in the population. In the 19th century, several pandemics originating in the East were reported, including 1831–1833, 1847–1848 and, finally, from 1889 to 1894, the so-called “Russian flu”, which spread throughout Europe and then the world. This episode was well-documented in many countries in several official reports, medical sources, and numerous press articles that covered the pandemic on a daily basis.
The first cases were reported in May 1889 in the city of Bukhara in Turkestan; curiously, a few cases were also reported in the city of Athabasca in Western Canada and in Greenland. In mid-October 1889, influenza reached the Russian Empire. It was reported in Tomks in western Siberia, Ufa (100 km from the Ural Mountains), Kazan on the Volga River in western Russia (700 km east of Moscow), Jekaterynoslav on the Dnieper River in Ukraine, and Novgorod near St. Petersburg. Kiev was stricken, as was the entire region of Lake Baikal, and then Siberia up to the island of Sakhalin. The capital of the Empire was severely hit in November 1889, with 20,000 cases. The flu afflicted all levels of society, including Tsar Alexander III himself. By the beginning of December, one third of hospital beds were occupied by flu patients. Economic activity ground to a halt, factories were closed, as were barracks and schools; 25–50% of soldiers and children had fallen ill. The peak of the epidemic occurred on December 1, 1889 in St. Petersburg. The first wave lasted five weeks with a total of 180,000 victims in a city of one million inhabitants.
From St. Petersburg, the Baltic ports were contaminated, notably Stockholm and the rest of Sweden, where the flu infected 60% of the population for eight weeks, and then Copenhagen and Oslo. The German Empire was affected in December, particularly in Poznań, Warsaw and Lodz. The epidemic resulted in 150,000 cases in Berlin for a population of 1.5 million.
What to do? Almost everywhere the unprepared authorities recommended hygienic measures such as ventilation, disinfection of public places and patients’ rooms, prohibition of public gatherings, isolation at home… Needless to say, there was no effective treatment at the time. Quinine was used to treat fever, but without success, as well as treatments such as strychnine, phenol inhalation, carbonic smoke ball that were dangerous… or fanciful (castor oil, electric current, brandy, oysters…). Commercial activity likewise collapsed, and schools, colleges, universities, public services, transportation and factories were shut down: a true disaster! Numerous eminent personalities – the President of the Republic, ministers, deputies – were stricken.
From mid-December 1889, the same scenario played out in the United Kingdom. In January 1890, there were 2258 deaths in London, including 1070 from pneumonia, far exceeding the seasonal average. The disease spread to other cities, including Edinburgh, Glasgow, Birmingham (50,000 cases) and Dublin.
The epidemic soon crossed the Atlantic, and the first cases in the United States were reported on 18 December 1889. The wave lasted five weeks, reaching a peak on 12 January 1890. The epidemic spread along the East Coast before reaching Chicago, Kansas City and San Francisco. Soon afterwards, from Mexico City to Buenos Aires, Latin America was likewise contaminated. In spring 1890, the pandemic spread widely in Africa and Asia. If Africans called it “the white man’s disease”, it was because they had apparently never previously known influenza.
Compared to the previous pandemics of the 19th century, the rapid spread of influenza was surprising. How can it be explained? In 1890, at the outset of the Pastorian era, the proponents of contagion still clashed with those of the miasma theory, which explained the rapid spread by air. In reality, the first wave did not progress steadily from east to west. It first hit successively the major European cities and capitals, which were closely connected by railroads, before disseminating to regions; this explains its predominantly urban impact. The pandemic also moved upstream, along the rivers; in addition, numerous grouped family cases were reported, indicating that influenza spreads directly through human-to-human contact. There is little doubt that influenza was borne by the European railroads, which were constantly expanding, with 202,887 km of track, and by the ever more rapid steamboats plying the waterways and seas. From May 1889 onwards, influenza was transported from Central Asia to the Russian Empire by the Transcaspian line to Samarkand in August, and then to Tomsk, 3200 km away, in October. The spread towards the East was slower because the Trans-Siberian Railway did not yet exist. St. Petersburg was afflicted in November 1889 via the Volga River trade routes.
Which agent was responsible for the pandemic? Needless to say, during the Pastorian revolution search for the germ of Russian flu became a priority, but the search began with a 50-year mistake. In the 1890s, viruses were still unknown. In November 1891, the German Richard Pfeiffer isolated a previously undescribed bacillus, which grew only on blood agar, from patients’ nasopharyngeal samples. Terming it Bacillus influenzae (now Haemophilus influenzae), on January 4, 1892 he announced that he had discovered the agent responsible for influenza. Unfortunately, he was unable to reproduce the disease experimentally in animals and did not fullfill the Koch’s postulates, which might have established a causal link. He hypothesized that the agent was a very specific human pathogen, comparable to those of leprosy or cholera. As the bacillus was repeatedly isolated during cases of flu, Pfeiffer’s observations seemed to be corroborated. In the years following the discovery, however, the bacillus was also found independently of any epidemic in otitis, mastoiditis, meningitis and pneumopathy. This is in contradiction with the existence of a specific germ at the origin of influenza. During the Spanish flu of 1918, this bacterium was once again incriminated, and many unsuccessful attempts were made to vaccinate against H. influenzae. At present, we know that it is a superinfection germ often present in nasopharyngeal samples.
While the Covid-19 pandemic resembles the other influenza pandemics, the SARS-CoV-2 coronavirus was identified by sequencing a few weeks after its onset. There are seven coronaviruses pathogenic to humans: three are highly pathogenic and epidemic: SARS-CoV-1 (9% mortality), MERS-CoV (30% mortality) and the current pandemic virus, SARS-CoV-2 (0.6%−2% mortality); four are the cause of 15–30% of common colds and have been circulating in populations for decades: HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1. These benign viruses are of animal origin (bats or rodents) and evolve in small seasonal epidemics every three to four years during the autumn and the winter, conferring short-term immunity.
In 2005, Belgian researchers sequenced the entire genome of a laboratory strain of HCoV-OC43 (which had undergone multiple passages in culture), demonstrating its phylogenetic proximity to another beta-coronavirus of bovine origin, BCoV, which originated from rodents and yields acute diarrhea in calves. The nucleotide sequence of HCoV-OC43 is almost identical to BCov, from which it was derived in about 1890. These investigators confirmed their discovery by comparing different sequences of wild-type HCoV-OC43 strains isolated from patients with acute rhinitis. They also found these viruses to be close to PHEV, a coronavirus causing porcine hemagglutinating encephalomyelitis. In light of the Covid-19 pandemic, these phylogenic observations raise the question of the role of a coronavirus in Russian influenza and make HCoV-OC43 an unexpectedly plausible candidate.
The emergence of the SARS-CoV-2 pandemic prompts a revisiting of the cause of past influenza pandemics. It should be remembered that there exist many wild reservoirs of coronaviruses, including bats, rodents, and birds, in whom the viruses are not (or only weakly) pathogenic. As many as 5000 types of coronaviruses have been identified, including 500 in bats, which may be the cause of many animal infections and epizootics. Could the loss of virulence be due to the natural evolution of pandemic viruses, an avatar of Darwinian selection of variants well-adapted to the species and persisting in the form of benign diseases or asymptomatic carriage, as in wild reservoirs? Chiropterans that appeared 50 million years ago, most of them asymptomatic carriers of many viruses, may have survived iterative lethal epidemics since the dawn of time. A balance was conceivably found between host-adapted viruses and hosts that developed specific and original defense systems conferring “natural” resistance to viruses.
Clinical, epidemiological and phylogenetic clues point to a coronavirus that caused the Russian influenza pandemic, as occurred in Covid-19, with its flu-like symptoms. Could there exist a historical precedent of a pandemic due to a coronavirus ? Could the benign coronaviruses encountered in human populations be the relics of ancient epidemics yielding mild viruses that are perpetuated in the human species? This alternative hypothesis deserves further investigation.
Source: Science Direct
