Researchers demonstrate SARS-CoV-2 infection in human lung bronchioalveolar tissue model

The development of an in vitro human tissue model to study viral infection and disease progression in the alveolar cells of the lungs responsible for the exchange of oxygen and carbon dioxide with the blood could allow the study of possible therapies for acute respiratory distress syndrome (ARDS) triggered by SARS-CoV-2. Researchers in the Netherlands have shown that SARS-CoV-2 replicates efficiently in their model resembling the human bronchioalveolar system which is thought to play a critical role in the progression of infection to pneumonia and ARDS.

It is already established that in people infected with COVID-19 or other respiratory viruses, alveolar damage can trigger a cascade of events leading to ARDS, limiting the transport of oxygen in the blood to dangerously low levels . There is also growing evidence that the epithelium lining the alveoli plays a major role in the progression of COVID-19. However, in vitro models to replicate disease progression in the alveoli of the human lungs have proven difficult to establish, especially models that are also permissive for SARS-CoV-2 infection. This has significantly limited our understanding of COVID-19.

The Dutch team has now remedied this deficiency by applying models of self-renewing organoids containing stem cells capable of differentiating into cell types relevant for the study of disease processes. Organoids are tiny 3D tissues about 2mm in diameter taken from stem cells to reflect the complex structures of an organ, or at least to express certain aspects of it in order to meet a given biomedical research goal. These organoids can then provide continuous sources of 2D tissues that more precisely mimic the geometry or cell alignment of the structures studied.

A self-renewing organoid model for the gas-conducting airway epithelium has already been developed by the same team, but the alveolar epithelium has proven to be a greater challenge to generate so far. The Dutch team overcame this challenge and developed a 2D “air interface” system comprising a basal layer of stem cells in contact with the culture media and an upper layer exposed to air as it would be in the lungs.

Several cultures have been successfully generated and infected with SARS-CoV-2 primarily targeting type II alveolar cells, known as ATII-L, confirmed by transmission electron microscopy (TEM), surface markers and sequencing. single cells. The study then shed light on the sequence of events following infection.

The study also identified, through analysis of the expression of messenger RNA, a cellular immune response to the virus by infected cells. When cultures were treated with the antiviral signaling molecule lambda interferon at the onset of infection, the replication of SARS-CoV-2 was almost completely blocked, indicating that – when properly programmed – interferon lambda could be an effective treatment. These results also indicate that these cultures could be useful for the development of a therapeutic intervention against acute respiratory distress syndrome (ARDS) from COVID-19.