May 17, 2020
Interferon-α2b Treatment for COVID-19
Posted by Omuterema Akhahenda in categories: biotech/medical, chemistry, genetics
The global pandemic of COVID-19 cases caused by infection with SARS-CoV-2 is ongoing, with no approved antiviral intervention. We describe here the effects of treatment with interferon (IFN)-α2b in a cohort of confirmed COVID-19 cases in Wuhan, China. In this uncontrolled, exploratory study, 77 adults hospitalized with confirmed COVID-19 were treated with either nebulized IFN-α2b (5 mU b.i.d.), arbidol (200 mg t.i.d.) or a combination of IFN-α2b plus arbidol. Serial SARS-CoV-2 testing along with hematological measurements, including cell counts, blood biochemistry and serum cytokine levels, and temperature and blood oxygen saturation levels, were recorded for each patient during their hospital stay. Treatment with IFN-α2b with or without arbidol significantly reduced the duration of detectable virus in the upper respiratory tract and in parallel reduced duration of elevated blood levels for the inflammatory markers IL-6 and CRP. These findings suggest that IFN-α2b should be further investigated as a therapy in COVID-19 cases.
In December 2019, an outbreak of pneumonia was reported in Wuhan, Hubei province, China, resulting from infection with a novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2. SARS-CoV-2 is a novel, enveloped betacoronavirus with phylogenetic similarity to SARS-CoV (1). Unlike the coronaviruses HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU, that are pathogenic in humans and are associated with mild clinical symptoms, SARS-CoV-2 resembles both SARS-CoV and Middle East respiratory syndrome (MERS), with the potential to cause more severe disease. A critical distinction is that CoVs that infect the upper respiratory tract tend to cause a mild disease, whereas CoVs that infect both upper and lower respiratory tracts (such as SARS-CoV-2 appears to be) may cause more severe disease. Coronavirus disease (COVID)-19, the disease caused by SARS-CoV-2, has since spread around the globe as a pandemic.
In the absence of a SARS-CoV-2-specific vaccine or an approved antiviral, a number of antivirals are currently being evaluated for their therapeutic effectiveness. Type I IFNs-α/β are broad spectrum antivirals, exhibiting both direct inhibitory effects on viral replication and supporting an immune response to clear virus infection (2). During the 2003 SARS-CoV outbreak in Toronto, Canada, treatment of hospitalized SARS patients with an IFN-α, resulted in accelerated resolution of lung abnormalities (3). Arbidol (ARB) (Umifenovir) (ethyl-6-bromo-4-[(dimethylamino)methyl]-5-hydroxy-1-methyl-2 [(phenylthio)methyl]-indole-3-carboxylate hydrochloride monohydrate), a broad spectrum direct-acting antiviral, induces IFN production and phagocyte activation. ARB displays antiviral activity against respiratory viruses, including coronaviruses (4).
Young blood plasma is known to confer beneficial effects on various organs in mice. However, it was not known whether young plasma rejuvenates cells and tissues at the epigenetic level; whether it alters the epigenetic clock, which is a highly-accurate molecular biomarker of aging. To address this question, we developed and validated six different epigenetic clocks for rat tissues that are based on DNA methylation values derived from n=593 tissue samples. As indicated by their respective names, the rat pan-tissue clock can be applied to DNA methylation profiles from all rat tissues, while the rat brain-, liver-, and blood clocks apply to the corresponding tissue types. We also developed two epigenetic clocks that apply to both human and rat tissues by adding n=850 human tissue samples to the training data. We employed these six clocks to investigate the rejuvenation effects of a plasma fraction treatment in different rat tissues. The treatment more than halved the epigenetic ages of blood, heart, and liver tissue. A less pronounced, but statistically significant, rejuvenation effect could be observed in the hypothalamus. The treatment was accompanied by progressive improvement in the function of these organs as ascertained through numerous biochemical/physiological biomarkers and behavioral responses to assess cognitive functions. Cellular senescence, which is not associated with epigenetic aging, was also considerably reduced in vital organs. Overall, this study demonstrates that a plasma-derived treatment markedly reverses aging according to epigenetic clocks and benchmark biomarkers of aging.
