COVID-19: lambda interferon against viral load and hyperinflammation

Abstract

Coronavirus disease 2019 (COVID-19), triggered by the betacoronavirus SARS-CoV-2, has become one of the worst pandemics of our time that has already caused more than 250,000 deaths (JHU data-05/06/2020, https://coronavirus.jhu.edu/). Effective therapeutic approaches are urgently needed to reduce the spread of the virus and its death toll. Here, we assess the possibility of using interferon-lambda (IFNλ), a third type of interferon sharing low homology with type I IFNs and IL-10, for treating COVID-19 patients. We discuss the unique role of IFNλ in fine-tuning antiviral immunity in the respiratory tract to achieve optimal protection and minimal host damage and review early evidence that SARS-CoV-2 may impair IFNλ induction, leading to a delayed type I IFN-dominated response that triggers hyperinflammation and severe disease. We also consider the potential windows of opportunity for therapeutic intervention with IFNλ and potential safety considerations. We conclude that IFNλ constitutes a promising therapeutic agent for reducing viral presence and hyperinflammation in a single shot to prevent the devastating consequences of COVID-19 such as pneumonia and acute respiratory distress syndrome (ARDS).

Keywords: COVID-19; cytokine storm; hyperinflammation; interferon; viral infection.

Figure 1. Immunopathogenesis of COVID‐19 and potential windows of opportunity for therapeutic intervention with IFNλ

Schematic showing the disease course of COVID‐19 in relation to its clinical and immunopathological characteristics. The thick blue line indicates the progressive incline in disease severity in vulnerable patient populations when untreated. Therapeutic intervention with a single or repeated dose of IFNλ in patients with mild disease (marked with red), or later on in patients with various degrees of pneumonia severity (marked with purple) appears to be the most promising approach. ARDS: Acute Respiratory Distress Syndrome; Mon, monocytes; Neu, neutrophils.