A study by Petter Brodin’s group at the Karolinska Institute in Stockholm has used a longitudinal, systems-level approach to characterize immune responses at both the cellular and protein level in severe COVID-19, and during the transition from acute disease to the recovery phase.
Overview of the systems immunology approach used in the study. Image courtesy of Dr. Petter Brodin.
The systems-level immune-monitoring combined mass cytometry with Olink protein biomarker analysis (180 proteins) and produced the following key findings:
Identified an IFNγ – eosinophil axis as an important factor in lung hyperinflammation
Observed patterns of immune cell coregulation that differ among four different stages of the disease
Showed that basophils and hyperinflammation modulate humoral responses to the virus
Demonstrated a shared trajectory of immunological recovery in severe COVID-19, with characteristics that could potentially serve as future biomarkers of disease progression
Decreases in the proteins IL-6, MCP3, KRT19, CXCL10, AREG and IFNγ
Increases in the classical and non-classical monocytes, CD56dim NK cells, Eosinophils and γδT-cells,
This study is available as a preprint online: Rodriguezet. al. (2020) medRxiv 2020.06.03.20121582 – view the article
About the principle investigator on this study
Petter Brodin studied medicine at Karolinska Institutet and graduated in 2011, when he also defended his PhD thesis in immunology at the same institution. He subsequently joined the Mark Davis laboratory at Stanford University, California. There he studied human immune system variation and the influences of heritable and non-heritable factors (Brodin et al, Cell 2015).
In 2013, he was recruited back to Sweden and the newly established Science for Life Laboratory in Solna to build up a national facility for Mass cytometry and form his own research group. Brodin and his team members have since continued to develop methods to profile human immune systems at the system level in health and disease.
He also specializes in pediatrics and has more recently focused on early human immune systems development, and the influences of environmental factors. (Photograph of Petter kindly provided by Ulf Sirborn)
Petter’s thoughts on the approach taken for this COVID-19 study
“The power of longitudinal monitoring is that patients captured at different stages of their disease course can be analyzed and compared. Longitudinal monitoring also allow for co-regulated features to be inferred and the systems-level perspective adds greater understanding of the immune cell and protein interactions that underlie the disease process“.
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