Researchers explain how severe case of Covid-19 derail the immune system

The immune system is likely to malfunction in severe cases of Covid-19 according to a recent study published in the journal Cell .

The study was conducted by experts from Charité - Universitätsmedizin Berlin, the University of Bonn, the German Center for Neurodegenerative Diseases (DZNE), the Helmholtz Centre for Infection Research (HZI) and the German Center for Infection Research (DZIF), along with colleagues from a nationwide research network.

According to the study, in a severe case of Covid-19, “the immune response is caught in a continuous loop of activation and inhibition.”

“There is still not very much known about the causes of these severe courses of the disease. The high inflammation levels measured in those affected actually indicate a strong immune response. Clinical findings, however, rather tend to indicate an ineffective immune response. This is a contradiction,” sais Joachim Schultze, professor at the University of Bonn and research group leader at the DZNE according to an official release.

“We therefore assume that although immune cells are produced in large quantities, their function is defective. That is why we examined the blood of patients with varying degrees of COVID-19 severity,” Leif Erik Sander, Professor of Infection Immunology and Senior Physician Charité's Medical Department, Division of Infectious Diseases and Respiratory Medicine said.

‘Immature’ immune cells in severe cases

The study analysed blood samples from 53 infected men and women with from Berlin and Bonn. Their infection was classified as mild or severe according to the World Health Organisation classification.

“Blood samples from patients with other viral respiratory tract infections as well as from healthy individuals served as important controls,” the study read.

These samples were investigated with the use of single-cell OMICs technologies. Data was used to analyse the blood samples for an immune response.

“In combination with the observation of important proteins on the surface of immune cells, we were able to decipher the changes in the immune system of patients with Covid-19,” said Birgit Sawitzki, Professor at the Institute of Medical Immunology on Campus Virchow-Klinikum.

The study focused on myeloid cells, which include neutrophils and monocytes, a part of the body’s defence mechanism against diseases.

In severe Covid-19 cases, the study found that neutrophils and monocytes are only partially activated. It further found that the cells do not function properly.

“We find considerably more immature cells that have a rather inhibitory effect on the immune response,” said Sawitzki."The phenomenon can also be observed in other severe infections, although the reason for this is unclear. Many indications suggest that the immune system stands in its own way during severe courses of Covid-19. This could possibly lead to an insufficient immune response against the coronavirus, with a simultaneous severe inflammation in the lung tissue,” added Sander.

Applications in therapeutics

The study suggests can help in researching possible therapeutics for such Covid-19 cases.

Anna Aschenbrenner from the LIMES Institute at the University of Bonn said, “Our data suggest that in severe cases of Covid-19, strategies should be considered that go beyond the treatment of other viral diseases.”

“If, however, there are too many dysfunctional immune cells, as our study shows, then one would very much like to suppress or reprogramme such cells,” said Jacob Nattermann, Professor at the Medical Clinic I of the University Hospital Bonn and head of a research group at the DZIF. “Drugs that act on the immune system might be able to help. But this is a delicate balancing act. After all, it's not a matter of shutting down the immune system completely, but only those cells that slow down themselves, so to speak. In this case these are the immature cells. Possibly we can learn from cancer research. There is experience with therapies that target these cells.”

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