New variants of SARS-CoV-2, the virus that causes COVID-19, have emerged throughout the pandemic. Some of these variants transmit more easily between people, cause more severe disease, or make the vaccines less effective. One theory is that these viral variants evolve in individuals whose immune systems are weakened from illness or medical treatments like chemotherapy, who can have persistent infection with SARS-CoV-2.
First author, Dr Luke Blagdon Snell from the School of Immunology & Microbial Sciences
22 April 2022
UK patient had COVID for 505 days
Researchers from King’s and Guy’s and St Thomas’ NHS Foundation Trust have described the longest known COVID-19 infection.
The anonymised patient tested positive for the virus for 505 continuous days before their death. The previous longest known PCR confirmed case is believed to be 335 days.
The researchers, who present their findings in an abstract this weekend at this year’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Portugal, were interested in how SARS-CoV-2 changes over time in immunocompromised individuals.
He added: “We wanted to investigate which mutations arise, and if variants evolve, in these people with persistent infection.”
The study involved nine immunocompromised patients who tested positive for the virus for at least eight weeks. Infections persisted for 73 days, on average, but two patients had persistent infections for more than a year.
The patients, who were studied between March 2020 and December 2021, had weakened immune systems due to organ transplantation, HIV, cancer, or medical therapies for other illnesses.
Regular sampling and genetic analysis of the virus showed that five of the nine patients developed at least one mutation seen in variants of concern. Some individuals developed multiple mutations associated with variants of concern, such as the Alpha, Delta and Omicron variants.
Dr Snell said: “This provides evidence that mutations found in variants of concern do arise in immunocompromised patients and so supports the idea that new variants of the viruses may develop in immunocompromised individuals.
“It is important to note, however, that none of the individuals in our work developed new variants that became widespread variants of concern.
“Additionally, whilst this work shows variants could arise in immunocompromised individuals, whether the previous variants of concern like Alpha, Delta and Omicron arose in this manner remains unknown.”
Five of the nine patients survived. Two of those five did not have treatment for SARS-CoV-2 infection, two cleared the infection after treatment with antibody therapies and antivirals, and one individual has ongoing infection.
Immunocompromised patients with persistent infection have poor outcomes, and new treatment strategies are urgently needed to clear their infection. This may also prevent the emergence of variants.
Dr Gaia Nebbia, co-author from the School of Life Course & Population Sciences
The researchers also report one of the first cases of an occult COVID-19 infection. Occult infection means someone who tested negative on PCR for COVID despite having an ongoing infection. In this case, the patient was symptomatic and testing positive with the Alpha variant in 2021, and then the symptoms subsided and they tested negative at multiple time points. The patient developed COVID symptoms several months later. Genome sequencing of the virus at this later point showed the infection was caused by the Alpha variant, which had been eliminated from the UK, suggesting the virus had been lurking in the body undetected.
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Clinical Research Fellow