Circulating Type I Interferon Levels in the Early Phase of COVID-19 Are Associated With the Development of Respiratory Failure

<jats:sec><jats:title>Background</jats:title><jats:p>The role of type I interferons (IFNs) in the early phase of COVID-19 remains unclear.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>To evaluate the relationship between IFN-I levels in patients with COVID-19 and clinical presentation, SARS-CoV-2 viral load, and other major pro-inflammatory cytokines.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This prospective observational study recruited patients hospitalized with COVID-19. The levels of interferon-alpha (IFN-α), interferon-beta (IFN-β), interleukin-6 (IL-6), and C-X-C motif chemokine ligand (CXCL10) within 5 days after symptom onset were measured using an ELISA, in serum from blood collected within 5 days after the onset of symptoms. The SARS-CoV-2 viral load was determined <jats:italic>via</jats:italic> qPCR using nasal-swab specimens and serum.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The study enrolled 50 patients with COVID-19. IFN-α levels were significantly higher in patients who presented with pneumonia or developed hypoxemic respiratory failure (p &lt; 0.001). Furthermore, IFN-α levels were associated with viral load in nasal-swab specimens and RNAemia (p &lt; 0.05). In contrast, there was no significant association between IFN-β levels and the presence of pneumonia or RNAemia, despite showing a stronger association with nasal-swab viral load (p &lt; 0.001). Correlation analysis showed that the serum levels of IFN-α significantly correlated with those of IFN-β, IL-6, and CXCL10, while the levels of IFN-β did not correlate with those of IL-6 or CXCL10.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Serum IFN-I levels in the early phase of SARS-CoV-2 infection were higher in patients who developed hypoxemic respiratory failure. The association between IFN-α, IL-6, and CXCL10 may reflect the systemic immune response against SARS-CoV-2 invasion into pulmonary circulation, which might be an early predictor of respiratory failure due to COVID-19.</jats:p></jats:sec>