Covid-19: Detect severe courses of disease at an early stage

Most people who become infected with Sars-CoV-2 do not become ill or do not become seriously ill. Some patients, however, develop a very severe, life-threatening covid-19 disease. They require intensive medical care and artificial respiration, as the University of Zurich (UZH) writes in a media release. For those affected, the infection often ends fatally or leads to considerable long-term health consequences. In order to identify such patients at an early stage and treat them quickly, there is a need for measurable indicators: predictive biomarkers that can be used to predict the risk of a severe course of the disease.

 Biomarkers for severe covid 19 courses discovered for the first time

The team led by Burkhard Becher, Professor at the Institute of Experimental Immunology at the University of Zurich, together with researchers from Tübingen, Toulouse and Nantes, have now discovered such a biomarker: the number of natural killer T cells in the blood. They are a class of white blood cells and part of the early immune defence system. "Based on the number of killer T cells in the blood, a severe course of covid 19 can be predicted with a high degree of certainty - and this already on the day of hospital admission," says Becher.

More targeted therapy thanks to more precise immunopathogenesis

The new detection test helps to decide which organisational and therapeutic measures need to be taken for a Covid 19 patient, such as transfer to intensive care or normal ward, frequency of oxygen saturation measurements, therapy and start of treatment. "For such considerations, predictive biomarkers are very helpful. They help to provide the best possible care for patients with severe courses," says Stefanie Kreutmair. The results would also make it possible to explore new therapies against covid-19, according to the first author of the study.

Progress thanks to high-tech

The cause of the rapid deterioration of Covid 19 patients is an excessive response of the immune system, he said. "The enormous production of messenger substances called cytokine storm causes a massive inflammatory response in the body. Immune cells migrate en masse into the lungs, where they disrupt gas exchange," Becher explains. To determine the immune cells and cytokines in the patient samples, the UZH researchers used high-dimensional cytometry. This allows proteins on the surface and inside the cells of millions of cells to be determined simultaneously and at the single-cell level and then processed by computer algorithms.

Sars-CoV-2-specific immune signature deciphered

In addition to Sars-CoV-2, numerous other pathogens can cause pneumonia - and thus an immune response, as the UZH emphasises. The immune response of Covid 19 patients has already been intensively studied, but until now it was unclear what exactly characterises the specific immune response to Sars-CoV-2. In order to determine this, the researchers also analysed blood samples from patients with severe pneumonia triggered by pathogens other than the new coronavirus for comparison, the UZH adds: "The comparison of the immune response of Covid-19 patients with that of the comparison group made it possible to identify what is unique about the immune response to Sars-CoV-2.

"The immune responses in the different lung inflammations are very similar and part of a general inflammatory response often seen in ICU patients. However, T cells and natural killer cells behave uniquely in Covid-19 and define a kind of pattern in the immune system: the Covid-19-specific immune signature," Becher explains.

Literature: Stefanie Kreutmair, Susanne Unger, Nicolás Gonzalo Núñez, Florian Ingelfinger, et. al. Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia. Immunity (in press (PDF, 7 MB), available online from 10 May 2021).

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