SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells

This study, titled “SARS-CoV-2 Viral Persistence in Lung Alveolar Macrophages is Controlled by IFN-γ and NK Cells,” published in Nature Immunology, provides significant insights into the persistence of SARS-CoV-2 in the body and the mechanisms regulating it.

The key findings of the study are:

  1. Persistence of SARS-CoV-2: The study used a macaque model to investigate SARS-CoV-2 persistence. It was found that replication-competent SARS-CoV-2 could be detected in bronchioalveolar lavage (BAL) macrophages beyond six months post-infection, indicating long-term viral presence.
  2. Study Design: 25 cynomolgus macaques were infected with either wild-type SARS-CoV-2 or Omicron variants (BA.1 and BA.2), alongside six noninfected macaques as controls. Viral RNA loads peaked in nasal and tracheal swabs at day 3 post-infection, but all macaques tested negative by day 21 and remained so up to 18 months post-infection. The immune responses, including plasma immunoglobulin G (IgG) and IgA reactivities, were assessed, showing lasting inflammation.
  3. Macrophage Phenotype and Inflammation: The study revealed significant long-term alterations in macrophage phenotype due to SARS-CoV-2 infection. This included increased expression of CD206, CD4, CD11c, MHC-E, and IL-10, and decreased expression of CD16 and CXCR4, suggesting an alternative activation of alveolar macrophages potentially linked to lung contusion and pneumonia.
  4. Viral Replication in Macrophages: Further investigation showed that SARS-CoV-2 could replicate in macrophages. This was evidenced by the detection of spike protein and the expression of double-stranded RNA and nonstructural protein 3 (NSP3) in BAL macrophages, suggesting cell-to-cell viral propagation.
  5. Gene Expression Alterations: The study also analyzed the transcriptome of BAL macrophages and found 138 differentially regulated genes compared to healthy controls. Notably, there was an enrichment of genes associated with lipid binding and a decrease in those related to cytokine activity and chemotaxis, indicating a change in macrophage function due to SARS-CoV-2 infection.

The study underscores the complex interplay between immune cells and the SARS-CoV-2 virus, highlighting the persistence of the virus in lung macrophages and its implications for long-term immune response and inflammation.

Read More:

Leave a comment