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COVID-19 is an emerging and rapidly evolving disease. We hypothesize that young patients without risk factors admitted to intensive care units due to very severe COVID-19 or due to multisystem inflammatory disease triggered by COVID-19 carry inborn errors of immunity to this virus. Monogenic immune disorders unravel, as a proof-of-principle, the ultimate relevance of a component of the immune system in human biology.

At the University Children’s Hospital Zurich, we have established a workflow to investigate patients with suspected novel monogenic immunodeficiencies. Since 2015, we have been recruiting patients with suspected novel primary immunodeficiencies to the Genetic Study for Immunodeficiency ID: NCT02735824.


Our laboratory is furthermore the only one in Switzerland routinely performing functional tests of cytotoxic lymphocytes used for diagnostic purposes in patients with cytokine storm diseases. Using our workflow for patients with suspected monogenic diseases, we perform a combined genomic, phenotypic and functional approach to define the inborn error(s) underlying very severe COVID-19 in children. The identification of gene defects in patients with very severe COVID-19 without risk factors and the subsequent functional characterization of the gene products will give unique insights in the defence mechanism of the human immune system.


The data generated by this approach may fundamentally change the way we conceptualize COVID-19, providing prognostic biomarkers, and also by underscoring signalling pathways amenable to therapeutic targeting.

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