A patient at a London hospital tested positive for COVID-19 for 505 days before dying, according to evidence presented this week at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Lisbon, Portugal.

Aside from representing the longest known COVID-19 infection, this extraordinary case highlights the capacity of the SARS-CoV-2 virus to persist within immunocompromised patients, where it may be able to mutate and adapt.

At present, there are three leading theories as to how new variants of the virus arise, one of which posits that the pathogen can linger and evolve in patients with compromised immune systems, such as those undergoing treatment for cancer or HIV. Another hypothesis states that the virus changes as mutations accumulate during the chain of person-to-person infections, while the third theory suggests that adaptations occur as the pathogen jumps between people and animals.

Researchers analyzed genetic changes within the SARS-CoV-2 virus in immunocompromised patients who had tested positive for at least eight continuous weeks. Between March 2020 and December 2021, the team identified nine individuals in London who met these criteria, four of whom later died.

Patients tested positive for an average of 73 days, with the shortest infection lasting for 56 days and the longest 505 days. One patient – who remains alive – carried the virus for 412 days at the time of their last check-up in early 2022, and could well set a new record by the time their next check comes around.

Importantly, the researchers found that the SARS-CoV-2 virus developed mutations associated with variants of concern in five of the nine patients. These included mutations altering the nature of the spike protein that the virus uses to enter cells, and which have given rise to new variants like Alpha, Delta, and Omicron.

The virus from one patient contained ten mutations that would later arise separately in some of these new variants. In a statement, study author Dr Luke Blagdon Snell explained that “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,” he said.

“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.”

The researchers also report the detection of the first known case of an occult COVID-19 infection, whereby the virus persisted within a patient who was thought to have cleared the pathogen. The person in question was initially infected with the Alpha variant before recovering and testing negative for the virus – only to test positive once again after developing symptoms several months later.

Intriguingly, this second infection was also caused by the Alpha strain, despite the fact that the variant had been eliminated from the UK by this time. Based on this observation, the researchers say the virus must have remained within the patient’s body undetected since their initial infection.

Earlier this week, doctors reported the quickest known COVID-19 reinfection after a 31-year-old female healthcare worker caught the illness twice in the space of 20 days. Collectively, findings like these are helping scientists understand how the virus adapts in order to evade vaccines and become more infectious.