MRC-University of Glasgow Centre for Virus Research

Virus evolution poses a continual threat to human health, allowing viruses to escape from the protective immunity we build up through vaccination and previous cases of infection.  During the early stages of the COVID-19 pandemic, one of the surprising features of virus evolution was the sudden appearance of new viral variants, such as Alpha and Omicron, which differed substantially from SARS-CoV-2 viruses we had seen before.  One hypothesis is that longer cases of infection in immunocompromised patients, provided the conditions necessary for rapid virus evolution. 

In a new paper, researchers from the MRC-University of Glasgow Centre for Virus Research developed a new statistical method to measure the rate of virus evolution in nine cases of long-term SARS-CoV-2 infection in hospitalised patients, with at least three weeks in between the first and last positive test.  In contrast to previous approaches, the new method considered a phenomenon known as compartmentalisation, where viruses form multiple distinct populations in different parts of the body. 

Using this new method, researchers found evidence for compartmentalisation in five of the nine individuals.  This evidence was more likely to be found in patients who were severely immunocompromised, for example due to having a form of blood cancer, or having received an organ transplant.  Viruses in different compartments evolved in different directions, and sometimes at significantly different rates in the same person.  While rates of virus evolution were highly variable, this method identified faster rates of virus evolution than would otherwise be found, supporting the idea that longer cases of infection may have seeded the emergence of new SARS-CoV-2 variants.

This study did not consider whether or not compartmentalisation makes a case of infection more or less serious.  Compartmentalisation may be a common feature of SARS-CoV-2 infection, albeit one which is usually hard to observe.  A better understanding of virus evolution may lead to improved treatments for virus infection, or may simply mean that we are less surprised next time around.

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First published: 2 May 2025