Innate immune response may predict Covid severity

COVID-19 disease severity seems to be affected by the characteristics of white blood cells called granulocytes, which are part of the innate immune system. Combined measurements of granulocytes and well-known biomarkers in the blood can predict the severity of the disease, according to a new study from Karolinska Institutet in Sweden. The results are published in the journal PNAS and may eventually contribute to more tailored treatments for COVID-19 patients.

Granulocytes are a family of white blood cells that include neutrophils, eosinophils and basophils. They are part of the so-called innate immune system, which is the body’s first line of defence against pathogens. There are many studies on how SARS-CoV-2 affects various components of the immune system, but there is still a lack of knowledge about the role of granulocytes in COVID-19.

Researchers at Karolinska Institutet have now investigated the characteristics of granulocytes in the blood during the early phase of SARS-CoV-2 infection in a total of 26 hospitalised patients with COVID-19 at the Karolinska University Hospital. They also performed follow-up analyses four months after hospital discharge and compared these with analyses of healthy uninfected individuals.

Significantly altered characteristics

Magda Lourda

Magda Lourda. Photo: private

“Our study shows significantly altered characteristics of all granulocyte subsets in COVID-19 patients and this can be linked to the severity of the disease”, says lead author Magda Lourda, who is a researcher at the Department of Medicine, Huddinge, at Karolinska Institutet.

Combined measurements of granulocyte characteristics and widely used biomarkers in the blood called C-reactive protein (CRP) and creatinine, could predict key clinical features such as respiratory function and multiorgan failure.

“The finding needs to be taken with caution considering the limited size of our study cohort, but our hope is that these combined measurements can be used to predict the severity of the disease, resulting in more tailored treatments for COVID-19 patients,” says Magda Lourda.

Part of a large COVID-19 project

The study is part of the Karolinska KI/K COVID-19 Immune Atlas project, which was initiated in April 2020, aiming at providing a comprehensive overview of the immune response to SARS-CoV-2 in hospitalised patients with moderate or severe COVID-19.

The study was supported by grants from Nordstjernan AB, Knut and Alice Wallenberg Foundation, the Swedish Governmental Agency for Innovation Systems, the Swedish Research Council, the Swedish Cancer Foundation, Clas Groschinsky Foundation, the Center for Innovative Medicine at Karolinska Institutet, the Swedish Children’s Cancer Foundation, Dr Åke Olsson Foundation and Karolinska Institutet’s research foundation. Part of the data handling and analysis was enabled by resources provided by the Swedish National Infrastructure for Computing.

Co-author Karl-Johan Malmberg is a scientific advisor and has a research grant from Fate Therapeutics and is a member of the scientific advisory board of Vycellix Inc. Hans-Gustaf Ljunggren is a member of the board of XNK Therapeutics AB and Vycellix Inc. Jan-Inge Henter serves as consultant for Sobi AB.

Publication

“High-dimensional profiling reveals phenotypic heterogeneity and disease-specific alterations of granulocytes in COVID-19”. Magda Lourda, Majda Dzidic, Laura Hertwig, Helena Bergsten, Laura M. Palma Medina, Indranil Sinha, Egle Kvedaraite, Puran Chen, Jagadeeswara R. Muvva, Jean-Baptiste Gorin, Martin Cornillet, Johanna Emgård, Kirsten Moll, Marina García, Kimia T. Maleki, Jonas Klingström, Jakob Michaëlsson, Malin Flodström-Tullberg, Susanna Brighenti, Marcus Buggert, Jenny Mjösberg, Karl-Johan Malmberg, Johan K. Sandberg, Jan-Inge Henter, Elin Folkesson, Sara Gredmark-Russ, Anders Sönnerborg, Lars I. Eriksson, Olav Rooyackers, Soo Aleman, Kristoffer Strålin, Hans-Gustaf Ljunggren, Niklas K. Björkström, Mattias Svensson, Andrea Ponzetta, Anna Norrby-Teglund, Benedict J. Chambers, and Karolinska KI/K COVID-19 Study Group. PNAS, online 21 September 2021, doi: 10.1073/pnas.2109123118.

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