Tag: Spanish Flu

Scientists Reconstruct the Genome of the 1918 Influenza Virus

Genetic analysis of the early pandemic virus shows key adaptations to humans.

Creative artwork featuring colourised 3D prints of influenza virus (surface glycoprotein hemagglutinin is blue and neuraminidase is orange; the viral membrane is a darker orange). Note: Not to scale. Credit: NIAID

Researchers from the universities of Basel and Zurich have used a historical specimen from UZH’s Medical Collection to decode the genome of the virus responsible for the 1918-1920 influenza pandemic in Switzerland. The genetic material of the virus reveals that it had already developed key adaptations to humans at the outset of what became the deadliest influenza pandemic in history.

New viral epidemics pose a major challenge to public health and society. Understanding how viruses evolve and learning from past pandemics are crucial for developing targeted countermeasures. The so-called Spanish flu of 1918-1920 was one of the most devastating pandemics in history, claiming some 20 to 100 million lives worldwide. And yet, until now, little has been known about how that influenza virus mutated and adapted over the course of the pandemic.

More than 100-year-old flu virus sequenced

An international research team led by Verena Schünemann, a paleogeneticist and professor of archaeological science at the University of Basel (formerly at the University of Zurich) has now reconstructed the first Swiss genome of the influenza virus responsible for the pandemic of 1918-1920. For their study, the researchers used a more than 100-year-old virus taken from a formalin-fixed wet specimen sample in the Medical Collection of the Institute of Evolutionary Medicine at UZH. The virus came from an 18-year-old patient from Zurich who had died during the first wave of the pandemic in Switzerland and underwent autopsy in July 1918.

Three key adaptations in Swiss virus genome

“This is the first time we’ve had access to an influenza genome from the 1918-1920 pandemic in Switzerland. It opens up new insights into the dynamics of how the virus adapted in Europe at the start of the pandemic,” says last author Verena Schünemann. By comparing the Swiss genome with the few influenza virus genomes previously published from Germany and North America, the researchers were able to show that the Swiss strain already carried three key adaptations to humans that would persist in the virus population until the end of the pandemic.

Two of these mutations made the virus more resistant to an antiviral component in the human immune system – an important barrier against the transmissions of avian-like flu viruses from animals to humans. The third mutation concerned a protein in the virus’s membrane that improved its ability to bind to receptors in human cells, making the virus more resilient and more infectious.

New genome-sequencing method

Unlike adenoviruses, which cause common colds and are made up of stable DNA, influenza viruses carry their genetic information in the form of RNA, which degrades much faster. “Ancient RNA is only preserved over long periods under very specific conditions. That’s why we developed a new method to improve our ability to recover ancient RNA fragments from such specimens,” says Christian Urban, the study’s first author from UZH. This new method can now be used to reconstruct further genomes of ancient RNA viruses and enables researchers to verify the authenticity of the recovered RNA fragments.

Invaluable archives

For their study, the researchers worked hand in hand with UZH’s Medical Collection and the Berlin Museum of Medical History of the Charité University Hospital. “Medical collections are an invaluable archive for reconstructing ancient RNA virus genomes. However, the potential of these specimens remains underused,” says Frank Rühli, co-author of the study and head of the Institute of Evolutionary Medicine at UZH.

The researchers believe the results of their study will prove particularly important when it comes to tackling future pandemics. “A better understanding of the dynamics of how viruses adapt to humans during a pandemic over a long period of time enables us to develop models for future pandemics,” Verena Schünemann says. “Thanks to our interdisciplinary approach that combines historico-epidemiological and genetic transmission patterns, we can establish an evidence-based foundation for calculations,” adds Kaspar Staub, co-author from UZH. This will require further reconstructions of virus genomes as well as in-depth analyses that include longer intervals.

Source: University of Zurich

Another COVID-scale Pandemic in 59 Years ‘Statistically Likely’

Photo by Edwin Hooper on Unsplash

A new study based on 400 years of historical records asserts that extreme pandemic events such as COVID are more common than believed.

The Duke University study, published in Proceedings of the National Academy of Sciences, used records of past outbreaks to estimate the intensity of those events and the yearly probability of them recurring.

It found the probability of a pandemic with similar impact to COVID is about 2% in any year, meaning that someone born in the year 2000 by now would have about a 38% chance of experiencing one. That probability is only increasing, highlighting the need to adjust perceptions of pandemic risks and expectations for preparedness, the researchers said.

“The most important takeaway is that large pandemics like COVID and the Spanish flu are relatively likely,” said study co-author William Pan, PhD, associate professor of global environmental health at Duke. The understanding that pandemics are not so rare should raise the priority of future prevention and control efforts, he said.

The study employed new statistical methods to measure the scale and frequency of disease outbreaks for which there was no immediate medical intervention over the past four centuries. Their analysis, including deadly pathogens including plague, smallpox, cholera, typhus and novel influenza viruses, found pandemics occurred with great variability in the past. But they also identified patterns that allowed them to describe the probabilities of similar-scale events happening again.

In the case of a pandemic like the Spanish flu, which killed more than 30 million people between 1918 and 1920, the probability of a pandemic of similar magnitude occurring ranged from 0.3% to 1.9% per year over the time period studied. Taken together, it is statistically likely that such a massive pandemic would occur within the next 400 years.

However, the data also show that the risk of intense outbreaks is increasing rapidly. Based on the increasing rate at which novel pathogens such as SARS-CoV-2 have broken loose in human populations in the past 50 years, the study estimates that the probability of novel disease outbreaks will likely triple in the next few decades.

With this increased risk factor, the researchers estimate that a COVID-scale pandemic is likely within a span of 59 years (by the year 2090), a result they write is “much lower than intuitively expected.” Although not included in the paper, they also calculated the probability of a pandemic capable of eliminating all human life, finding it statistically likely within the next 12 000 years. 

That does not mean it will be 59 years before the next COVID-like pandemic, nor that the Spanish flu for another 300 years. Such events are equally probable in any year during the span, said Duke University Professor Gabriel Katul, another of the paper’s authors.

“When a 100-year flood occurs today, one may erroneously presume that one can afford to wait another 100 years before experiencing another such event. This impression is false. One can get another 100-year flood the next year,” explained Prof Katul.

Dr Pan noted that population growth, changes in food systems, environmental degradation and more frequent contact between humans and disease-harboring animals all may be significant factors for increasing frequency of pandemics. However, he stresses that the statistical techniques are not to explain the pandemics.

However, he hopes the study will spark deeper exploration of the factors that may be making devastating pandemics more likely – and how to counteract them.

“This points to the importance of early response to disease outbreaks and building capacity for pandemic surveillance at the local and global scales, as well as for setting a research agenda for understanding why large outbreaks are becoming more common,” Dr Pan said.

Source: Duke University