The discovery of SARS-CoV-2 mutations evolving in an immunocompromised patient treated with convalescent plasma has been revealed by Ravindra Gupta, MD, PhD, of University of Cambridge in England, and team.
“We have documented a repeated evolutionary response by SARS-CoV-2 in the presence of antibody therapy during the course of a persistent infection in an immunocompromised host,” the authors wrote.
Previous research has shown that immunosuppressed patients could serve as reservoirs for norovirus variants.
Although they did not claim the UK variant was created by that particular case, Gupta’s group speculated that the plasma therapy could have unleashed the resistant variants, and could do so in other immunosuppressed patients too.
They wrote that, in such patients, “the antibodies administered [in plasma] have little support from cytotoxic T cells, thereby reducing chances of clearance and theoretically raising the potential for escape mutations.”
They cautioned that convalescent plasma use should be limited, and only with appropriate infection control in monitoring in immunosuppressed patients.
A man in his 70s, who had received immunotoxic chemotherapy to treat lymphoma eight years previously, was initially hospitalised in May with neutropenic sepsis, and, about a week later, tested positive for SARS-CoV-2. He was discharged later in May, but in late June was readmitted with cough and breathlessness.
His condition worsened and he received dexamethasone and two 10-day courses of remdesivir 5 days apart. On two days around July 20, convalescent plasma was administered; more remdesivir and convalescent plasma was administered about 4 weeks later. He died shortly afterward.
Gupta and team took viral samples from this patient on 23 occasions, and over the first 57 days, they observed little change in viral population upon treatment with remdesivir, but after the July round of convalescent plasma, a shift in viral genotype occurred.
Initially the patient’s viral serotype showed a mutation first reported in China. However, in late July, a variant was observed with two alterations in the spike protein, including the deletion seen in the B.1.1.7 variant. Testing showed a twofold reduced susceptibility to the antibodies in the convalescent plasma.
The team wrote that this sort of evolution is unlikely to emerge in immunocompetent patients. They cautioned against using convalescent plasma in severe COVID patients, and especially those who were immunosuppressed.
The study’s limitations included being only a single case, and samples were taken from the upper respiratory tract and not the lower respiratory tract.
Given South Africa’s large HIV positive population, if viral evolution is driven by convalescent plasma in immunosuppressed patients, this raises questions for the country’s COVID strategy.
Source: MedPage Today
Journal information: Kemp SA, et al “SARS-CoV-2 evolution during treatment of chronic infection” Nature 2021; DOI: 10.1038/s41586-021-03291-y.
