Why was the 1918 Pandemic Fatal?

A combination of genes was responsible for the lethality

We are still living with COVID that struck us last year. COVID wasn’t the first pandemic and certainly wouldn’t be the last. The 1918 pandemic was fatal than any of the pandemics we've had in the last 100 years. The 1918 pandemic killed an estimated 50 million people across the globe and an estimated 675,000 people in the U.S. People between 15–34 years had a high death rate; life expectancy in the U.S. dropped by more than 12 years. What made the 1918 pandemic deadly? Where did the virus originate? Researchers and virus hunters looking for answers to the above questions wanted to recreate the virus.

Alaskan Village and search for the virus

Brevig Mission, a village in Alaska, contributed greatly to the 1918 virus recreation because the 1918 virus ravaged the village. Today 400 people live in Brevig Mission, but in 1918, 80 Inuit (natives) inhabited the village. From November 15–20, 1918, 72 out of 80 inhabitants died from the 1918 flu. Later, the government ordered a mass burial site for the dead.

Since Alaskan soil is permafrost, snow surrounded the buried graves. The snow helped preserve the body, the infected lungs, for a long time. Researchers went to Brevig Mission to exhume the bodies for recovering the 1918 virus from the infected lung tissues. One of the researchers went to the Alaskan village in 1951 for retrieving the 1918 virus. The attempt was unsuccessful.

In 1997, the same researcher returned to the Alaskan village, and this time the 1918 virus was successfully retrieved. The scientists were able to retrieve positive gene material for sequences from the 1997 lung tissues. Genome sequencing helped scientists to understand how different genes influenced different virus traits. Further, complete gene sequencing was necessary to reconstruct the 1918 virus.

Reconstructing the Virus

When the complete gene sequencing was done, the scientists moved to the next step: reconstructing the 1918 virus. Reconstructing the 1918 virus meant bringing the virus back to life. Reconstruction was historic. Once the scientists reconstructed the virus, they started studying the deadly virus.

Researchers infected mice with viruses to study the virus effect. Researchers infected one group of mice with the reconstructed 1918 virus and another group with different influenza viruses. The influenza viruses were created with varying gene combinations of the 1918 virus and contemporary human influenza virus, and the viruses were called “recombinant viruses.”

Researchers studied the pathogenicity of the virus; pathogenicity is the ability of a virus to cause disease and harm the host. The scientists studied the morbidity parameters (i.e., weight loss and virus replication) in infected mice.

What did the gene study tell?

The Hemagglutinin Gene (HA gene)

HA gene influences viruses’ HA surface proteins. HA surface proteins give the virus the ability to enter a host’s cell and infect it. Researchers sequencing the HA gene found that the 1918 virus was more closely related to a mammalian source, human-like or swine-like, than the avian source.

The 1918 virus didn’t have cleavage site mutations like the modern influenza viral strains. The cleavage site mutation is the genetic marker that determines the virulence of the virus. Virulence determines how severe or harmful a disease the virus will cause. The researchers inferred that more than one gene was responsible for the 1918 viruses’ virulence.

Deadly 1918 Virus

Virus count

The 1918 virus was remarkable in replicating, i.e., making copies of itself and spreading infection in the host (mice). For example, the lung tissue of mice infected with the 1918 virus had 39,000 times higher virus count than the lung tissue of mice infected with recombinant virus.

High fatality rate

Some mice died within three days of infection with the 1918 virus. Furthermore, some mice lost 13% of their weight within two days of infection with the 1918 virus. The 1918 virus was 100 times more lethal than other recombinant viruses.

The 1918 viruses’ HA gene was a big reason for its lethality. When the HA gene was swapped with a gene from a contemporary influenza gene, the resulting recombinant virus didn’t kill or cause weight loss in mice.

The 1918 virus didn’t spread to other organs of mice: brain, liver, heart but the damage to the lung was lethal and quick. The victims of the 1918 pandemic had fluid-filled lungs, severe pneumonia, and lung tissue inflammation.

The researchers pointed out that no particular gene was the reason for the viruses’ fatality and severity. Researchers remarked, “the constellation of all eight genes together created an exceptionally virulent virus.”

External reasons for the 1918 viruses’ lethality

World war-1

Troops were transported in masses and unhygienic conditions, and this facilitated the spread of the virus.

Limited medical service

30% of the physicians served the military as a result. When civilians required medical service, the doctors weren’t available.

Diagnostic tools

Health experts didn’t have a diagnostic kit to detect the virus. Many health experts misread the situation by inferring that the 1918 pandemic was caused by a bacterium called “Pfeiffer’s bacillus.”

Medical field underdeveloped

Doctors didn’t have vaccines, antibiotics, nor did they have flu anti-viral drugs. Intensive care support and mechanical ventilation were unavailable.

In another article, I will share how did the 1918 Pandemic end? Or did it really end?