Dysregulated Interferon Response Underlying Severe COVID-19.
LeAnn LopezPeter C SangYun TianYongming SangPublished in: Viruses (2020)
Innate immune interferons (IFNs), including type I and III IFNs, constitute critical antiviral mechanisms. Recent studies reveal that IFN dysregulation is key to determine COVID-19 pathogenesis. Effective IFN stimulation or prophylactic administration of IFNs at the early stage prior to severe COVID-19 may elicit an autonomous antiviral state, restrict the virus infection, and prevent COVID-19 progression. Inborn genetic flaws and autoreactive antibodies that block IFN response have been significantly associated with about 14% of patients with life-threatening COVID-19 pneumonia. In most severe COVID-19 patients without genetic errors in IFN-relevant gene loci, IFN dysregulation is progressively worsened and associated with the situation of pro-inflammation and immunopathy, which is prone to autoimmunity. In addition, the high correlation of severe COVID-19 with seniority, males, and individuals with pre-existing comorbidities will be plausibly explained by the coincidence of IFN aberrance in these situations. Collectively, current studies call for a better understanding of the IFN response regarding the spatiotemporal determination and subtype-specificity against SARS-CoV-2 infections, which are warranted to devise IFN-related prophylactics and therapies.
Keyphrases
- sars cov
- coronavirus disease
- dendritic cells
- immune response
- respiratory syndrome coronavirus
- genome wide
- early stage
- early onset
- innate immune
- copy number
- dna methylation
- intensive care unit
- transcription factor
- emergency department
- drug induced
- high resolution
- quality improvement
- neoadjuvant chemotherapy
- solid phase extraction
- adverse drug
- tandem mass spectrometry