One study found that the SARS-CoV-2 virus can persist in the lungs for up to 18 months after infection, casting doubt on the idea that the virus is undetectable after initial recovery. This persistence is associated with a malfunction of the innate immune system. This study confirms the existence of "viral reservoirs" similar to those of HIV and highlights the role of NK cells in controlling these reservoirs. This discovery is critical to understanding Long-COVID and the mechanisms by which the virus persists.
A groundbreaking study reveals that due to a failure of the innate immune system, SARS-CoV-2 can lie dormant in the lungs for months, undetected, and may cause Long-COVID.
One to two weeks after COVID infection, the SARS-CoV-2 virus is generally undetectable in the upper respiratory tract. But does this mean the virus no longer exists in the human body? To find out, the Institut Pasteur's HIV/AIDS specialist group, in collaboration with the French public research agency the Commission for Alternative Energies and Atomic Energy (CEA), studied lung cells from animal models. The findings show that not only does SARS-CoV-2 persist in some people's lungs for up to 18 months, but its persistence appears to be related to a breakdown in innate immunity, the first line of defense against pathogens. The research was published in the journal Nature Immunology.
Viral reservoir discovered in COVID-19
Some viruses remain in the body in a subtle and undetectable way after causing an infection. They are called "virus databases". This is the case with HIV, which lies dormant in certain immune cells and can reactivate at any time. This may also be the case with the SARS-CoV-2 virus that causes COVID-19. At least, that's the hypothesis proposed in 2021 by a team of scientists from the Pasteur Institute, and has now been confirmed in preclinical models in non-human primates.
"We observed that inflammation persists for a long time in primates infected with SARS-CoV-2. We therefore suspected that this could be due to the presence of the virus in the body," explains Michaela Müller-Trutwin, head of the HIV, inflammation and persistence research group at the Pasteur Institute.
Research results
To study the persistence of the SARS-CoV-2 virus, scientists from the Institut Pasteur, in collaboration with CEA's IDMIT (Infectious Disease Modeling for Innovative Therapeutics) Center, analyzed biological samples from animal models infected with the virus. Preliminary results from the study show that although the virus was not detectable in the upper respiratory tract or blood, it was found in the lungs of some people six to 18 months after infection. Another finding was that the Omicron strain persisted in lower amounts of virus in the lungs than the original SARS-CoV-2 strain.
Nicolas Huot, first author of the study and a researcher in the HIV, Inflammation and Persistence Research Group at the Pasteur Institute, said: "We were very surprised to find that after such a long time, the virus was found in certain immune cells - alveolar macrophages - where conventional PCR tests were negative. What's more, we cultured these viruses and observed that they were still able to replicate using the tools we developed to study HIV."
To understand the role of innate immunity in controlling these viral reservoirs, scientists then turned their attention to NK (natural killer) cells. Michaela Müller-Trutwin says: "The cellular response of innate immunity is the body's first line of defense, but until now SARS-CoV-2 infection has been poorly studied. However, it has long been known that NK cells play an important role in controlling viral infections. This Research shows that in some animals, macrophages infected with SARS-CoV-2 are resistant to destruction by NK cells, while in others, NK cells are able to adapt to the infection (called adaptive NK cells) and destroy resistant cells, in this case macrophages."
Therefore, this study reveals a mechanism that may explain the existence of a "viral reservoir": people infected with viruses for a long time or with very few viruses will produce adaptive NK cells, while people infected with more viruses not only have no adaptive NK cells, but also have reduced NK cell activity. Therefore, innate immunity appears to play a role in controlling persistent SARS-CoV-2 viruses.
"We will start studying people infected with SARS-CoV-2 at the beginning of the pandemic to determine whether the viral reservoirs and mechanisms discovered are relevant to long-term COVID cases. But the results here already represent an important step towards understanding the nature of the viral reservoir and the mechanisms that regulate virus persistence," says Michaela Müller-Trutwin. "
Reference "SARS-CoV-2 virus persistence in alveolar macrophages is controlled by IFN-γ and NK cells", authors: Nicolas Huot, Cyril Planchais, Pierre Rosenbaum, Vanessa Contreras, BeatriceJ acquelin, Caroline Petitdemange, Marie Lazzerini, Emma Beaumont, Aurelio Orta-Resendiz, Félix A. Rey, R. Keith Rey, Félix A. Rosenbaum. Rey, R. Keith Reeves, Roger LeGrand, Hugo Mouquet, and Michaela Müller-Trutwin, November 2, 2023, Nature Immunology.
DOI:10.1038/s41590-023-01661-4
Compiled source: ScitechDaily