Researchers working on lung organoids have shown that 48 hours following infection by SARS-CoV-2, the innate immune response begins.
This group of researchers from South Korea and the UK successfully studied Mini lung organoids from tissue infected by SARS-CoV-2. The researchers detail the mechanisms underlying SARS-CoV-2 infection and the early innate immune response in the lungs.
According to the study, the alveoli is the main tissue targeted by SARS-CoV-2 and patients that develop pneumonia are a high at-risk group.
The tissue analyzed were obtained to extract human lung alveolar type 2 cells. This was achieved by reprogramming these cells back to their earlier stem cell stage, success was achieved in the growth of self-organizing alveolar-like three-dimensional (3D) structures that mimic the behavior of key lung tissue.
A combination of fluorescence imaging and single cell genetic analysis, as used to study this pre-infected mini lungs to enable study of how the cells respond to infection from the virus. Upon exposure to SARS-CoV-2 rapid replication was observed with maximum cellular infection at six hours following infection. Production of interferons was observed and subsequent initiation of the innate immune response at 48 hours was observed.
Six hours after infection, subset of alveolar cells began to disintegrate resulting in cell death and damage to the lung tissue.
Although the researchers observed changes to the lung cells within three days of infection, clinical symptoms of COVID-19 rarely occur so quickly and can sometimes take more than 10 days after exposure to appear. The team says there are several possible reasons for this. It may take several days from the virus first infiltrating the upper respiratory tract to it reaching the alveoli. It may also require a substantial proportion of alveolar cells to be infected or for further interactions with immune cells resulting in inflammation before a patient displays symptoms.
Based on this model many unanswered key questions, such as understanding genetic susceptibility to SARS-CoV-2, assessing relative infectivity of viral mutants and revealing the damage processes of the virus in human alveolar cells can be studied and most importantly, it provides the opportunity to develop and screen potential therapeutic agents against SARS-CoV-2 infection.