Interferon-α2b Treatment for COVID-19 Is Associated with Improvements in Lung Abnormalities

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19), a lung disease that may progress to systemic organ involvement and in some cases, death. The identification of the earliest predictors of progressive lung disease would allow for therapeutic intervention in those cases. In an earlier clinical study, individuals with moderate COVID-19 were treated with either arbidol (ARB) or inhaled interferon (IFN)-α2b +/-ARB. IFN treatment resulted in accelerated viral clearance from the upper airways and in a reduction in the circulating levels of the inflammatory biomarkers IL-6 and C-reactive protein (CRP). We have extended the analysis of this study cohort to determine whether IFN treatment had a direct effect on virus-induced lung abnormalities and also to ascertain whether any clinical or immune parameters are associated with worsening of lung abnormalities. Evidence is provided that IFN-α2b treatment limits the development of lung abnormalities associated with COVID-19, as assessed by CT images. Clinical predictors associated with worsening of lung abnormalities include low CD8+ T cell numbers, low levels of circulating albumin, high numbers of platelets, and higher levels of circulating interleukin (IL)-10, IL-6, and C-reactive protein (CRP). Notably, in this study cohort, IFN treatment resulted in a higher percentage of CD8+ T cells, lower tumor necrosis factor (TNF)-α levels and, as reported earlier, lower IL-6 levels. Independent of treatment, age and circulating levels of albumin and CRP emerged as the strongest predictors of the severity of lung abnormalities.

Keywords: COVID-19; CT images; interferon.

Figure 1

Interferon (IFN)-α2b treatment accelerates viral clearance. Coronavirus disease 2019 (COVID-19) cases were treated with either arbidol (ARB) alone (ARB, n = 24) or IFN-α2b with or without ARB (IFN, n = 53). Data points for cases treated with IFN alone are marked as open circles. Time to viral clearance from symptom onset is indicated; p value was calculated using Wilcoxon signed-rank test. These plots are re-derived from published data employing different population parameters [5].

Figure 2

IFN-α2b treatment reduces the severity of lung abnormalities in CT scans during the course of COVID-19. (A) COVID-19 cases were treated with either ARB alone (ARB, n = 24) or IFN-α2b with or without ARB (IFN, n = 53). Data points for those cases treated with IFN alone are marked as open circles. Chest CT scores were recorded relative to treatment onset, as indicated. Each data point represents a score from a CT image; p values were calculated using thenon-parametric Mann–Whitney U test with Holm’s correction for multiple comparisons. Maximum (B), final (C), and (D) % change from peak CT scores are shown with p values calculated using Wilcoxon signed-rank test.

Figure 3

Lung CT image abnormalities correlate with many clinically relevant biomarkers of COVID-19 severity. Spearman’s correlation coefficients were calculated between blood-based biomarkers measured and CT scores. Blue-to-red heat map and dot sizes identify levels of correlation. Interleukin (IL)2, IL-2; IL4, IL-4; IL6, IL-6; IL10, IL-10; Tnfa, TNF-α; Ifng, IFN-γ; Blympho, B lymphocytes; Nkcell, NK cells; wbc, white blood cells; neut, neutrophils; lymph, lymphocytes; plt, platelets; hgb, hemoglobin; ALT, alanine transaminase; AST, aspartate aminotransferase; ALB, albumin; TBIL, total-value bilirubin; DBIL, direct bilirubin; CREA, creatinine; BUN, blood urea nitrogen; CRP, C-reactive protein.

Figure 4

The severity of lung abnormalities is associated with specific immune and clinical biomarkers. Scatterplots depicting associations between CT scores and various blood-based biomarkers. Spearman’s correlation coefficients were calculated between CT scores and (A) IL-6, (B) IL-10, (C) CD8+ T cells, (D) CRP, (E) albumin, (F) total bilirubin, (G) platelets, (H) TNF-α, and (I) IFN-γ, as indicated. Shaded areas indicate 95% confidence intervals.

Figure 5

IFN-α2b treatment regulates the levels of clinical and immune biomarkers associated with lung CT image abnormalities. COVID-19 cases were treated with either ARB alone (ARB, n = 24) or IFN-α2b with or without ARB (IFN, n = 53). % CD8+ T cells (A) and levels of IL-6 (B) and TNF-α (C) are depicted across the time course of treatment with either ARB or IFN; p values were calculated using the non-parametric Mann–Whitney U test with Holm’s correction for multiple comparisons. * p < 0.05, *** p < 0.001, **** p < 0.0001.