For more than three months the patient struggled against Covid-19. His immune system was already in a bad way when he caught the virus – he had been receiving a drug treatment for lymphoma, a type of blood cancer, that depleted some of his immune cells. With fewer of the usual defences against infection, the virus was able to spread in his body relatively unchecked.
As doctors tried to help the elderly patient fight the virus, they gave him blood plasma collected from people who had already recovered from Covid-19. Contained within this milky-brown liquid – also known as convalescent plasma – were antibodies against the virus that might help to neutralise it.
Over the course of 101 days as they treated the man, clinicians at Addenbrookes Hospital in Cambridge, UK, took 23 swab samples as he fought against the disease. Each swab was sent off to a nearby laboratory to be analysed. But when virologists looked at the virus’s genetic material in the samples, they noticed something astonishing – Covid-19 was evolving before their eyes.
“We saw some remarkable changes in the virus over that time,” says Ravinda Gupta, an infectious diseases consultant at the hospital and a clinical microbiologist at the University of Cambridge who analysed the patient’s samples. “We saw mutations that seemed to suggest the virus was showing signs of adaptation to avoid the antibodies in the convalescent plasma treatment. It was the first time we had seen something like this happening in a person in real time.”
Nearly a year after the global Covid-19 pandemic started, the issue of mutations looms large. New variants capable of spreading faster are emerging and leading to inevitable questions about whether they will make the newly approved vaccines less effective. To date, there is little evidence they are, but scientists are already starting to explore how the Covid-19 virus will mutate in the future and whether they might be able to head it off. In the first of a two part series looking at Covid-19 mutations, we look at what they have learned so far.
Among the mutations Gupta and his colleagues identified was a deletion of two amino acids – known as H69 and V70 – in the spike protein sitting on the outside of the Covid-19 virus. This protein plays a key role in the ability of the coronavirus to infect cells.
The oily capsule that surrounds most of the virus is studded with these spikes sticking outwards, making it look like a crown when viewed through an electron microscope. It is this appearance that gives the coronavirus family its name – corona is Latin for crown. The spikes are also the main way Covid-19 recognises the cells it can infect and helps the virus penetrate them.
When Gupta and his team looked closer at the spike protein deletion they had spotted, it produced worrying results. “We did some infection experiments using artificial viruses and they showed that the H69/V70 deletion mutation increases the infectivity by twofold,” says Gupta. This prompted the researchers to scour the international genetic databases of Covid-19. There they found that something more alarming was taking place.
“We wanted to see what was happening worldwide and we stumbled upon this big expanding group of [H69/V70 deletion] sequences in the UK,” says Gupta. “When we looked more closely, we found that there was a new variant causing a big outbreak.”
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