Chronic Covid-19 and convalescent plasma may increase the risk of mutation

Photographer: Omar Marques / Getty Images

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British doctors who spent 102 days treating a cancer survivor for Covid-19 have documented how the virus mutated after the man was treated with convalescent plasma.

The case study suggests that the use of blood plasma donated by Covid-19 survivors may have put enough pressure on the virus to force it to evolve. The result: less sensitivity to the immune system’s antibodies that normally fight infection, according to the report published Friday in the journal Nature.

Although convalescent plasma does not appear to harm the patient, it offers no clear benefit, the lead author said. Ravindra Gupta, professor of clinical microbiology at the Cambridge Institute of Therapeutic Immunology and Infectious Disease. It should be used with caution in people with chronic immune diseases, he said, preferably in clinical trials or in carefully controlled environments.

The report also suggests that many mutations can emerge in patients who have both weakened immune systems and chronic infections.

“When the virus has a chance to sit in a person for a long time and replicate for weeks and months, it learns to fight the immune system,” Gupta said. It’s all about “pressure on the virus”.

The patient did not develop the exact variant that has now become the dominant form of the virus circulating in the UK, according to the report, but he had some things in common. “It just illustrates that someone like him is probably zero patient,” Gupta said.

Slow mutations

Overall, Covid-19 mutates relatively slowly. This is because it is a fast-growing virus that leaves it little time to evolve. In this case, however, the patient and his doctors battled the virus for 102 days from when he was diagnosed until his death, Gupta said.

The patient was diagnosed with Covid-19 at a local hospital in the spring of 2020, when the first wave of the virus was reaching crisis levels in the UK, and was then taken to Cambridge University Hospitals for more intensive care.

The team there tested him twice a week to see if any treatments he was receiving, including Gilead Sciences Inc.’s remdesivir lowered his viral load. They were not.

Genetic profiling

At the same time, the samples were sent for genetic profiling. This resulted in a snapshot of how the virus mutated over time, allowed researchers to determine where, how and when the pathogen changed over the months.

There was little change in the virus after receiving two courses of remdesivir in the first two months, the researchers said. However, after the administration of convalescent plasma, there were large dynamic changes in the viral population, including in the key spike protein, which the virus uses to attach to and infect healthy cells.

The variants then presented evidence of reduced sensitivity to the neutralizing antibodies that normally control the virus.

Large study

The case study comes almost a month after a A large national study in the UK examining convalescent plasma as therapy was halted after it was discovered that the treatment touted by US President Donald Trump is not working.

The The research from the University of Oxford was part of a clinical trial called Recovery that studies different Covid-19 treatments. The other arms of the study are in progress.

The results come after more than 100,000 Americans were treated with convalescent plasma after its use was cleared by US regulators on an emergency basis.