Researchers are deploying Simoa technology from Quanterix, Billerica, Mass, to profile innate immune response in covid-19 patients, with the aim of identifying indicators associated with poor outcomes and opening new avenues for targeted therapies. New studies suggest that a reduction of interferon (IFN) type I in the blood may provide a means for detecting patients at the greatest risk for dysregulation of the inflammatory response and detection of a cytokine storm earlier in the disease cascade.1,2 The research also provides a rationale for new early intervention and treatment strategies.

“Through our collaborations with Powering Precision Health’s global network and leading experts on the frontlines of the pandemic response, we’ve learned that our ultra-sensitive Simoa assays act like ‘a radar system’ for important inflammatory molecules and can be used to predict disease progression and cytokine storms that traditional systems cannot detect,” says Kevin Hrusovsky, chairman and chief executive officer, Quanterix and founder, Powering Precision Health. “These studies represent important advances in detecting life-threatening immune reactions before they occur. Such early detection presents an opportunity to proactively intervene and treat covid-19 patients with targeted immune modulation therapies, which could save countless lives. We are excited to see these advances being made using Simoa in the fight against covid-19.”

An estimated one in five patients will develop a severe or critical form of covid-19. Experts believe this can be traced to an overproduction of immune molecules, known as a cytokine storm, and attribute many of the crisis’s fatalities to this rampant immune reaction. Emerging research suggests that assessment of interferon response, including blood levels of the cytokine IFN-α—which is considered to be one of the earliest indicators of dysregulation of the anti-viral immune response—IL-6 and several other inflammatory biomarkers are among the most promising prognostic markers for severe disease expression.

To further evaluate this theory, two research teams—one from the Institut Pasteur and another on behalf of the International Center for Research in Infectious Diseases in Lyon, France—deployed Quanterix’ highly sensitive Simoa technology to quantify and profile telltale markers, including inflammatory cytokines, in covid-19 patients with a range of disease severity. Findings in both studies suggest a correlation between disease severity and low interferon production, suggesting that quantification of IFN production could be a promising strategy for identifying high-risk individuals and informing therapeutic response.

The Institut Pasteur, Institut Imagine, Inserm, Université de Paris and Assistance publique–Hôpitaux de Paris  (AP-HP) conducted an integrated immune analysis that included in-depth phenotypical profiling of immune cells, whole-blood transcriptomic, and cytokine quantification on a cohort of 50 covid-19 patients with a range of disease severity. Patients were tested 8 to 12 days following their first symptoms and in the absence of anti-inflammatory therapy. Findings illustrate a profoundly impaired IFN type I response characterized by a low interferon production and activity, with consequent downregulation of interferon-stimulated genes. Moreover, the team found this to be associated with persistent blood virus load and characterized by increased IL-6 production and innate immune chemokines.

“Like SARS and MERS before it, covid-19 has proven capable of restricting the body’s natural response to a viral invasion. This can lead to a dysregulation of interferon and compromise the chain of immune response mechanisms that follow,” says Darragh Duffy, scientist and member of the Immunobiology of dendritic cells Unit, Institut Pasteur, Inserm. “Because IFN-α concentrations in blood are quite low, it can be difficult to detect, much less quantify. Simoa’s high fidelity was instrumental in this effort and enabled us to uncover important correlations among our cohort that could have considerable implications for healthcare workers and their patients.”

Although preliminary, the research demonstrates the potential utility of a test for type-I IFN deficiency in the blood to help stratify covid-19 patients and support earlier intervention for those most likely to experience an acute reaction. Furthermore, findings from both studies offer new insights into the innate immune response and covid-19 associated deficiencies that could inform ongoing therapeutic development and treatment decisions in clinical settings.

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1. Hadjadj J, Yatim N, Barnabei L, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020;369(6504):718-724. doi: 10.1126/science.abc6027.

2. Trouillet-Assant S, Viel S, Gaymard A, et al. Type I IFN Immunoprofiling in covid-19 patients. J Allergy Clin Immunol. 2020;146(1):206-208.e2. doi: 10.1016/j.jaci.2020.04.029.

Featured image: Type I IFN immunoprofiling in COVID-19 patients: Plasma IFN-α2, IL-6, CRP, and IP-10 concentrations in COVID-19 critically ill patient cohort (n = 26). A, Plasma IFN-α concentrations (fg/mL) were determined by single-molecule array (Simoa). Fit Loess curve represents local polynomial regression performed with Loess method. CI at 95% was indicated (orange area). B-D, CRP (µg/mL), IL-6, and IP-10 (pg/mL) concentrations were measured using a multiplexed assay with the Ella platform. Normal values for healthy volunteers were indicated by grey area. Vertical bar indicates the median delay between symptom onset and intensive care unit admission.

© 2020 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.