In the throes of the Covid-19 outbreak, individuals and governments worldwide are turning to science for answers.
The last global outbreak to cause this much panic was the Spanish flu, which is estimated to have killed 50 million and infected 500 million people between 1918 and 1919. The cause of that disease was at the time unknown. By contrast, the viral agent of Covid-19 was discovered just weeks after the outbreak was first detected in China in December 2019. The genome sequence of the virus was made publicly available, allowing hundreds of projects to begin searching for a preventative vaccine. Potential curative drugs could also be considered based on the knowledge of viral structure that the genome sequence yielded and one, remdesivir, is showing promise in trials in China and the US.
Some publishers of scientific literature, such as Elsevier, Wiley and Springer Nature, which are often vilified for charging readers exorbitant sums of money to access their content, have lifted fees on Covid-19 related research. Thousands of scientific studies on the virus have already been published, many using the relatively new concept of “preprint”, where data is made available to readers before undergoing the peer-review process that underpins scientific rigour.
Fast-tracked publications, however, invite problems of their own. The most recent example is the publication of a paper by Chinese scientists arguing that Covid-19 had already mutated into a more virulent form. The researchers sequenced 103 Sars-Cov-2 viruses isolated from different patients infected with the disease. From this, the authors claimed to have identified two different types of the virus, based on small variations in the approximately 30,000 chemical bases called nucleotides that comprise the Covid-19 virus’s genome. One form of virus – the “L” form – was more common than the other, the so-called “S” form. Yet the “S” form appeared in some of the earlier samples. It was concluded that the mutation must have made the common “L” form more virulent.
The report gained widespread media attention and caused significant alarm among members of the public. But as researchers at the University of Glasgow’s Centre for Virus Research have pointed out, the conclusions of the study are unsound and should be read with caution. There is no solid evidence of the virus mutating to increased virulence at all.
However, it is normal for RNA (ribonucleic acid) viruses such as Sars-Cov-2 to acquire random mutations. It may be that the virus becomes less virulent as humans are increasingly exposed to it. Evolution favours those viruses that survive, which involves a complex relationship between virus replication and host immunity. Covid-19 is much more widespread than the Sars outbreak of 2002-03, because it is less virulent and more transmissible. Unlike Sars, Covid-19 spreads before causing the host serious illness or death.
The human genome also shapes the evolutionary battle between virus and host. Why are some people worse affected by Covid-19 (and other viruses) than others? Estimates of the fatality rate vary from country to country. At the time of writing it seems that in Italy, 6.2 per cent of those who become infected with coronavirus will die, while in South Korea it is 0.8 per cent.
In Iran, the trajectory of the virus has provided an explanation as to these discrepancies in mortality rates. There, during the earliest phase of the outbreak, an accurate assessment of the number of those infected was lacking. Deaths, on the other hand, were easily discerned. As more people in Iran have been diagnosed with the disease, the country’s fatality rate has fallen from an initially reported 25 per cent to 3.3 per cent today.
Indeed, given the speed with which South Korea’s government responded to the outbreak and the sophistication of its health care system, that nation’s fatality rate of 0.8 per cent is probably the most accurate calculation of the relationship between infection and death that we have.
It is possible that genetic or environmental factors play a role in distinguishing between those who become infected by Covid-19 and those who do not (and between those who survive it and those who do not). In the first instance, more men than women die (possibly linked to the fact that, especially in China, more men than women smoke and thus have compromised lungs). Elderly people are also far more likely to die than younger generations, mostly due to underlying health issues and waning immune systems.
Biological variation might also play a role in infection rates. Human genomes are full of genes where different variants exist due to the encounters our ancestors had with historic pathogens.
One gene, for example, encodes an enzyme called glucose-6-phosphate dehydrogenase (G6PD), which helps red blood cells to defend themselves against toxic chemicals derived from activated oxygen. While those lacking in G6PD are vulnerable to anaemia triggered by some drugs, its deficiency does protect against malaria. It seems the parasitic disease has been so common in West Africa for thousands of years that mutant G6PD genes emerged to protect against it. This was discovered when African Americans who were treated with the anti-malarial drug primaquine during the Korean War began suffering from anaemia. They had retained the gene variants that had protected their ancestors from malaria, even though they themselves grew up in a place lacking the disease.
Coronavirus, meanwhile, binds to specific proteins on particular cells in our respiratory tract. The key receptor is known as ACE2 (angiotensin-converting enzyme 2), which normally regulates blood pressure. Variants of the ACE2-encoding gene exist and can impact people’s blood pressure. Such divergent ACE2 variants might also bind the Covid-19 virus differently; those that bind less well are associated with a milder form of the disease.
It is possible that other features of our immune system also contribute to how different individuals respond to Covid-19 – we will soon discover what they are.
This article appears in the 11 Mar 2020 issue of the New Statesman, How the world is closing down