Following COVID infection, the SARS-CoV-2 virus typically becomes undetectable in the upper respiratory tract one to two weeks later. However, this absence does not necessarily indicate the virus is entirely eradicated from the body. To explore this, scientists from the Institut Pasteur, specializing in HIV, collaborated with the French Alternative Energies and Atomic Energy Commission (CEA), conducting a study on lung cells in an animal model.
The findings, published in Nature Immunology, reveal that SARS-CoV-2 persists in the lungs of certain individuals for up to 18 months post-infection. Notably, this persistence seems linked to a failure of innate immunity, the body's initial defense against pathogens. This revelation draws parallels with other viruses, like HIV, which maintains latent reservoirs within immune cells and can reactivate at any time.
In 2021, the Institut Pasteur proposed the hypothesis that SARS-CoV-2 might establish viral reservoirs, a theory now substantiated in a non-human primate preclinical model. Michaela Müller-Trutwin, Head of the Institut Pasteur's HIV, Inflammation, and Persistence Unit, notes the prolonged inflammation in primates infected with SARS-CoV-2, leading to suspicions of viral presence.
To delve into the virus's persistence, scientists at the Institut Pasteur, collaborating with CEA's IDMIT center, scrutinized biological samples from infected animal models. Surprisingly, the study revealed the presence of the virus in the lungs, even when undetectable in the upper respiratory tract or blood, lasting 6 to 18 months post-infection. Notably, the omicron strain showed lower persistence than the original SARS-CoV-2 strain.
Nicolas Huot, lead author of the study, highlights the unexpected discovery of viruses in immune cells (alveolar macrophages) after extensive periods, capable of replicating even when standard PCR tests were negative. This led to the investigation of the role of innate immunity, particularly NK (natural killer) cells, in controlling these viral reservoirs.
Innate immunity, the body's initial line of defense, has been understudied in SARS-CoV-2 infections. The study unravels that infected macrophages can become resistant to NK cell destruction, while adaptive NK cells in some individuals can overcome this resistance and eliminate infected cells. Conversely, individuals with higher viral levels not only lack adaptive NK cells but also experience reduced NK cell activity.
These findings suggest a crucial role for innate immunity in controlling persistent SARS-CoV-2 viruses. Michaela Müller-Trutwin emphasizes the next step involves studying a cohort infected at the pandemic's onset to understand if the identified viral reservoirs and mechanisms correlate with cases of long COVID. Nonetheless, these results signify a significant stride in comprehending viral reservoirs and the mechanisms governing viral persistence.
Source: Pasteur Institute