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Background  The role of type I interferons (IFNs) in the early phase of COVID-19 remains unclear.    Objectives  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.    Methods  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  via  qPCR using nasal-swab specimens and serum.    Results  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 &amp;lt; 0.001). Furthermore, IFN-α levels were associated with viral load in nasal-swab specimens and RNAemia (p &amp;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 &amp;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.    Conclusions  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.

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