A hallmark of severe COVID-19 pneumonia is SARS-CoV-2 infection of the facultative progenitors of lung alveoli, the alveolar epithelial type 2 cells (AT2s). However, inability to access these cells from patients, particularly at early stages of disease, limits an understanding of disease inception.
Now, a team of infectious disease, pulmonary and regenerative medicine researchers at Boston University, studying human stem cell-derived lung cells called type 2 pneumocytes, infected with SARS-CoV-2, have shown that the virus initially suppresses the lung cells’ ability to call in the help of the immune system with interferons to fight off the viral invaders and instead activates an inflammatory pathway called NFkB.
According to the researchers, the inflammatory signals initiated by the infected pneumocytes attract an army of immune cells into lung tissue laden with infected and already dead and dying cells. Their data confirms that SARS-CoV-2 blocks cells from activating one of the anti-viral branches of the immune system early on after infection has set in. The signal the cells would typically send out, a tiny protein called interferon that they exude under threat of disease, are instead delayed for several days, giving SARS-CoV-2 plenty of time to spread and kill cells, triggering a buildup of dead cell debris and other inflammation.
References: Jessie Huang et al. SARS-CoV-2 Infection of Pluripotent Stem Cell-derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response, Cell Stem Cell (2020). DOI: 10.1016/j.stem.2020.09.013