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

Abstract

BackgroundThe role of type I interferons (IFNs) in the early phase of COVID-19 remains unclear.ObjectivesTo 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.MethodsThis 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.ResultsThe 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 < 0.001). Furthermore, IFN-α levels were associated with viral load in nasal-swab specimens and RNAemia (p < 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 < 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.ConclusionsSerum 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.

Revealing the characteristics of ZIKV infection through tissue-specific transcriptome sequencing analysis

“…6 b, Supplementary Table 14 ). These observations show that ZIKV induced overt but delayed type I IFN responses when infecting placenta, which was similar to SAR-COV-2 in the airway epithelial cell line [ 54 – 56 ], suggesting that ZIKV infection perturbed host immune responses and provided mechanistic insights into the immune evasion.…”

Effect of Casirivimab/Imdevimab Treatment on Serum Type I Interferon Levels in SARS-CoV-2 Infection

“…However, this study could include various unvaccinated patients in the same endemic period, which would minimize bias due to vaccine- or strain-dependent SARS-CoV-2 virulence. Further, because the methodology measuring each IFN/cytokine had been confirmed as reported in the previous study [ 30 ], we believe that these limitations would not have significantly affected our outcomes.…”

“…IFN-α is mainly produced by circulating hematopoietic cells, whereas IFN-β is produced by a broad range of cell types [ 29 ]. Previously, we reported that serum IFN-α levels were elevated in patients in the early phase (clinical day ≤ 5) of mild to moderate SARS-CoV-2 infection, which is highly associated with the development of hypoxemic respiratory failure and viremia [ 30 ]. Considering the distribution of drug delivery, C/I might strongly neutralize the virion in the blood compared to those in the nasopharynx or other organs.…”

Effect of Cytomegalovirus Reactivation on Inflammatory Status and Mortality of Older COVID-19 Patients

“…Previous findings suggested that an impaired IFN-I response could be an important contributor to the disease severity in SARS-CoV-2 infection [ 45 , 46 , 47 ]. However, recent evidence shows that serum IFN-I levels in the early phase of SARS-CoV-2 infection are increased in patients who develop hypoxemic respiratory failure [ 48 ]. In our study, the levels of cytokines in serum were measured within one week after symptom onset, therefore the increased early IFN-α response in CMV positive patients could contribute to disease severity.…”