New strain emerges from world’s longest case of COVID-19

A man in the Netherlands, who was infected with COVID-19 for almost two years, has been presented as the world’s longest known case of COVID-19 at this week’s European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Global Conference in Barcelona.
 
Initially admitted to Amsterdam University Medical Centre with a positive COVID test in February 2022, the 72-year-old remained infected for a total of 613 days, during which time the virus mutated into a variant resistant to certain COVID-19 treatments.
 
The man had previously undergone allogenic stem cell transplantation for treatment for myelodysplastic and myeloproliferative overlap syndrome.
 
However, his blood cancer treatment was complicated by the development of post-transplant lymphoma, requiring treatment with rituximab immune therapy, which depleted all of his immune B-cells, including those that would normally produce anti-COVID-19 antibodies.
 
This left him in an immunocompromised state highly susceptible to severe COVID-19 infections.
 
Interestingly, this man had previously received multiple COVID-19 vaccinations but his weakened immune system meant that his response was still unmeasurable when he was admitted to hospital at the start of 2022.
 
In hospital, he also received the anti-COVID-19 antibody, sotrovimab, anti-IL6 antibody, sarilumab, and dexamethasone. Again, his impaired immune system failed to clear the infection, with COVID-19-sequencing tests showed that the virus actually developed a sotrovimab-resistant mutation (S:E340K) within the host, 21 days after receiving the antiviral medicine.
 
Unfortunately, the man required multiple hospital admissions over the next two years, prolonged periods of isolation and reported a greatly reduced quality of life. He died from a relapse of his haematological condition, remaining COVID-19 positive with high viral loads for a total of 613 days.
 
Full genome sequencing was performed on a total of 27 nasopharyngeal specimens obtained from the man between February 2022 and September 2023. They confirmed that the initial virus strain had mutated into an alarmingly immune-evasive variant.
 
The study’s author, Magda Vergouwe is currently researching other cases of prolonged infection in immunocompromised patients and the potential public health threat posed if these extensively-mutated variants are transmitted to the broader community.
 
Her team, from the University of Amsterdam, emphasises the importance of continuing close genomic surveillance of COVID-19 evolution in immunocompromised hosts and advocates for early diagnostic tests for symptomatic contacts.
 
While there was no documented transmission of the highly mutated variant to secondary community cases in this instance, Ms Vergouwe further qualifies that not every new variant ends up being a new variant of concern.
 
‘The duration of SARS-CoV-2 infection in this described case is extreme, but prolonged infections in immunocompromised patients are much more common compared to the general community,’ she said.
 
‘However, from the viewpoint of the general public, prolonged infections remain rare as the immunocompromised population is only a very small percentage of the total population.’
 
Professor Dale Godfrey, from the Doherty Institute for Infection and Immunity, says it is difficult to determine the level of threat posed to the overall community by variants originating in immunocompromised individuals.
 
‘We still don’t know enough about the mechanics of how these variants are generated and survive,’ he told newsGP.
 
He explains that, with any virus, mutations and variants only occur within their hosts as they cannot proliferate on their own. In this sense, what has been observed in this individual is similar to what has happened for all variants we know of and probably for many more we will never know about.

However, if the virus is in the host for two years, there is a lot more opportunity for it to mutate compared to someone who is infected for only a week.
 
‘The variant that arose managed to overcome this man’s compromised  immune system,’ Professor Godfrey said.
 
‘That doesn’t mean that somebody with a completely healthy immune system, throwing lots of different antibodies at it, would also be susceptible.
 
‘Not to say that this variant is harmless, it’s just hard to know whether any given variant is likely to be a threat to the community versus a threat to just the individual, especially when that individual is immunocompromised.’
 
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