Current DateSeptember 24, 2021

Covid-19: how the immune system affects the course of the disease

Infection with Sars-CoV-2 leads to severe covid-19 symptoms in 10 to 20 percent of cases, while other sufferers remain completely symptomless. Several research teams have now examined crucial information on the role of individual immune response for these differences.

According to two recent studies, there appear to be three immune types among patients – and these immune types are closely linked to the severity of the infection. They differ mainly in the type and quantity of activated immune cells. In addition, patients with severe histories differ from the outset in which and how many immune messengers are released.

From previous experience during the Corona pandemic, it is now clear that certain risk factors can promote a severe course of Covid-19 These include old age, pre-existing conditions such as diabetes, kidney problems, high blood pressure or other cardiovascular conditions, but also obesity.

However, there are also younger, healthy infected people who fall seriously ill without these risk factors, and in some people from the risk groups, Covid-19 is surprisingly mild. In the search for causes, scientists have already identified two genetic factors. Differences in the immune response have also been suspected for some time. Many patients who need to be artificially ventilated or die from Covid-19 show a particularly strong release of inflammatory messenger substances, which indicates an overreaction of the immune system.

Differences in messenger substances

To get to the bottom of immunological differences, two groups of researchers have now examined different aspects of the immune response in more detail. Jérome Hadjadj of the University of Paris and his team in their study focused on immune messengers such as interferons and the activity of genes regulating their release.

Some interferons play a crucial role in fighting viral and bacterial pathogens, while others, such as interferon-6, can also trigger excessive inflammatory reactions such as the so-called “cytokine storm”. For their study, the researchers analyzed the concentrations of messengers in the blood and gene activity of 50 Covid-19 patients and 18 healthy controls.

When comparing patients with mild and critical histories, they actually found significant differences: In seriously ill patients, significantly lower concentrations of the so-called type 1 interferons were found in the blood, including interferon alpha. “Low plasma levels of interferon-alpha-2 were significantly correlated with an increased risk of aggravation to critical status,” Hadjadj and his team report.

The genes that stimulate the production of these messenger substances were also significantly less active in these severe trajectories, as the analyses showed. For this purpose, the production of the inflammatory messenger substances TNF-Alpha and Interleukin-6 was significantly upregulated in these Covid-19 patients. According to the scientists, this reveals clear immunological differences between the rather mild and severe cases of Covid-19.

The profile of a severe, usually fatal infection is therefore characterized by a lack of alpha interferons and at the same time an excessive production of interleukin-6 and TNF-alpha.

“The interesting thing is that we observed that low plasma levels of interferon alpha occurred even before the worsening of the clinical condition and the transfer to the intensive care unit,” the scientists say. This knowledge could therefore perhaps be suitable for recognizing an imminent change to critical courses at an early stage.

Cell analysis reveals three immune types

The second team of researchers, led by Divij Mathew of the University of Pennsylvania in Philadelphia, focused their study on the response of immune cells to acute coronavirus infection. To do this, they analyzed which cell types were present and in what amounts in 125 inpatient Covid-19 patients, in recovering patients with only mild histories, and in healthy control subjects. The analysis was carried out by means of flow cytometry, a process in which the cell-containing liquid is passed past electrodes and light sensors. This revealed differences in the quantity and type of some T cells. These immune cells include the infected cells, CD8+ killer cells, but also CD4+ cells that regulate the release of immune messengers.

Mathew and his team have identified three immune types related to these cells. In the third immune type, the immune cells show little reaction to the infection. “This immune type 3 is negatively linked to disease severity,” the researchers said. “This suggests that a less robust immune response in Covid-19 is also associated with less severe progressions.”

Immune types 1 and 2, on the other hand, were common in patients who needed hospital treatment. Typical for immune type 1 was a significant activation of CD4+ cells, but a lack of certain CD8+ cells. This type of immune response was particularly often associated with typical inflammation, organ failure and kidney damage, as Mathew and his colleagues report.

In immune type 2, on the other hand, CD4+ activation was weaker, but certain CD8+ cells were more strongly represented. For this type of immune, the researchers found no association with the severity of disease symptoms, but with the presence of pre-existing immunodeficiency and also increased mortality. According to the researchers, identifying these immune types could potentially help treat Covid-19 sufferers better and perhaps even predict the course of the disease.