A team from the Institut Pasteur in collaboration with a French public research institute, the Alternative Energies and Atomic Energy Commission (CEA), conducted the study on lung cells in an animal model.
The results, published in the journal Nature Immunology, show not only that SARS-CoV-2 is found in the lungs of certain individuals for up to 18 months after infection, but also that its persistence appears to be linked to a failure of innate immunity, the first line of defense against pathogens.
Some viruses persist in the body in a discreet and undetectable manner after causing an infection. They remain in what are known as 'viral reservoirs', the researchers said.
This is the case for HIV, which remains latent in certain immune cells and can reactivate at any time. It could also be the case for the SARS-CoV-2 virus which causes
"We observed that inflammation persisted for long periods in primates that had been infected by SARS-CoV-2. We therefore suspected that it could be due to the presence of the virus in the body," said Michaela Muller-Trutwin, Head of the Institut Pasteur's HIV, Inflammation and Persistence Unit.
The study analysed biological samples from animal models that had been infected by the virus.
Initial results from the study indicate that viruses were found in the lungs of some individuals six to 18 months after infection, even though the virus was undetectable in the upper respiratory tract or blood.
The researchers also found that the amount of persistent virus in the lungs was lower for the Omicron strain than for the original SARS-CoV-2 strain.
"We were really surprised to find viruses in certain immune cells - alveolar macrophages - after such a long period and when regular PCR tests were negative," said Nicolas Huot, first author of the study and researcher in the Institut Pasteur's HIV, Inflammation and Persistence Unit.
"What's more, we cultured these viruses and were able to observe, using the tools we developed to study HIV, that they were still capable of replicating," Huot said.
To understand the role of innate immunity in controlling these viral reservoirs, the scientists then turned their attention to NK (natural killer) cells.
"The cellular response of innate immunity, which is the body's first line of defense, has been little studied in SARS-CoV-2 infections until now," said Muller-Trutwin.
"Yet it has long been known that NK cells play an important role in controlling viral infections," the researcher said.
The study shows that in some animals, macrophages infected with SARS-CoV-2 become resistant to destruction by NK cells, while in others, NK cells are able to adapt to infection (known as adaptive NK cells) and destroy resistant cells, in this case macrophages.
The study sheds light on a mechanism that may explain the presence of viral reservoirs.
While individuals with little or no long-term virus had adaptive NK cell production, individuals with higher levels of virus had not only an absence of adaptive NK cells, but also a reduction in NK cell activity, the researchers added.