Distinct airway epithelial immune responses after infection with SARS-CoV-2 compared to H1N1

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• Airway epithelial cells are crucial for early viral defense.
• Children generally experience less severe SARS-CoV-2 symptoms than adults.
• Influenza A H1N1 severity varies with age, particularly in the very young and elderly.

Purpose of the Study:

• To investigate viral replication and immune responses in paediatric and adult bronchial epithelial cells infected with SARS-CoV-2.
• To compare cellular responses to SARS-CoV-2 versus Influenza A H1N1 infection.
• To determine age-related differences in epithelial cell responses to SARS-CoV-2.

Main Methods:

• Primary bronchial epithelial cells were isolated from paediatric (2.5-5.6 years) and adult (47-63 years) donors.
• Cells were infected with SARS-CoV-2 or Influenza A H1N1.
• Viral replication, interferon responses (IFNB1, IFNL1), inflammatory proteins (IL-6, IL-8), and epithelial barrier integrity were assessed.
• Expression of SARS-CoV-2 entry factors (FURIN, NRP1) was measured.

Main Results:

• Both viruses induced interferon responses, but SARS-CoV-2 elicited significantly lower levels of interferons and inflammatory proteins compared to H1N1.
• Only H1N1 infection disrupted the epithelial cell layer.
• H1N1 infection led to sustained upregulation of FURIN and NRP1.
• No significant differences were observed in the epithelial response to SARS-CoV-2 between paediatric and adult cells.
• SARS-CoV-2 demonstrated reduced replication and immune-evoking potential in bronchial epithelial cells compared to H1N1.

Conclusions:

• SARS-CoV-2 has a diminished capacity to replicate and trigger immune responses in airway epithelial cells compared to Influenza A H1N1.
• Airway epithelial cells from children and adults exhibit similar responses to SARS-CoV-2 infection.
• These findings highlight differential viral pathogenesis at the cellular level.