An all-Luxembourg , led by Professors Feng Hefeng and Markus Ollert of the Infection and Immunity Department of the Luxembourg Institute of Health (LIH), analysed the functioning of the immune system of patients who had contracted the Covid-19 virus but had only mild symptoms.
Initiated in April 2020, this study analysed the immune responses of more than 100 patients during the first three days after a positive PCR test and then three weeks later. Patients were divided into three groups depending on their state: asymptomatic, mild and hospitalised.
However, this immune response varied greatly between the different groups, according to the study . Patients with mild symptoms benefit from a very early coordinated activation of the different levels of the immune system, which are disconnected in severe patients, explains Ollert in an interview with Delano’s sister publication Paperjam. Only if all branches of the immune system work together properly can the virus be defeated, the study states.
This better understanding of the immune system’s behaviour could lead to concrete applications, like a better management of patients by determining in advance how the disease will develop.
Pierre Pailler: Your study analysed the functioning of the immune system not of severely affected patients, but of patients with mild symptoms or no symptoms at all, who were therefore able to cope effectively with the Covid-19 infection. What did you learn?
Markus Ollert. - The immune response of mildly ill patients is totally different from the immune response of patients with severe symptoms. It is also different from asymptomatic people. And of course it is also different from healthy people who do not develop Covid at all, even if they have an infected person in their household.
How do these different immune responses differ?
"You have to understand that the immune system is made up of a specific arm, including antibodies and T cells, called adaptive immunity. You also have an arm of the immune system called non-specific or innate immunity. The latter is evolutionarily older--even insects have it. This one is very important to activate the whole process of immunity. Without a good initiation of the innate immune response, you will never have a successful adaptive immune response later on.
Only when all the branches of your immune system are working properly together can you defeat the virus.
Patients with mild symptoms develop a very strong innate immune response within 72 hours of infection. In contrast, this innate response is completely absent in patients with severe symptoms.”
What did you conclude from this observation?
"That a patient can only cope with the virus and get rid of it when all the different levels of the immune system are activated in a coordinated way. This is exactly what we found in patients with mild symptoms, who benefit from a very early coordinated activation of the different levels of the immune system. These seem to be disconnected in the severe patient.
So it's only when all the branches of your immune system are working properly together that you can defeat the virus. If anything goes wrong, you will have severe developments, or you may even, in the worst case, die.”
Some adults probably have such a strong local immune response that the virus can only go so far.
Why is it that some people are asymptomatic--or even not infected--despite being in contact with an infected person, for example, in their home?
"According to a study in Berlin, children can sometimes be completely asymptomatic because they have a very strong local mucosal immune response.
In our study, we found that some asymptomatic adult patients have no systemic immune response. So some adults probably have such a strong local immune response that the virus can't go any further. We didn't go into detail about this, because we didn't have enough patients of this nature. But this allows us to assume that there is also a local component to the immune response that is very important in the face of such viral infections.”
Without a good initiation of the innate immune response, you will never have a successful adaptive immune response afterwards.
What practical solutions could be developed from this study?
"You can't differentiate between severe and mild patients when you look at antibodies--they both have antibodies. The same goes for the T cells. But when you look at the whole picture, including the innate immune cells, then the mildly ill patient has a different immune signature compared to severe patients or healthy people.
So we could take a blood sample and use our data to try to determine whether a patient is going to develop severe or mild symptoms. This could allow us to pay more attention to a patient, to make the right decisions earlier, such as not sending them home and keeping them in hospital.”
Without large scale testing (LST), we would not have had the opportunity to recruit so many people with a positive PCR test and mild or asymptomatic symptoms.
This study is 100% Luxembourgish. Does the Grand Duchy have any specific features that made it possible?
"Without large scale testing (LST), we would not have had the opportunity to recruit so many people with a positive PCR test and mild or asymptomatic symptoms. This was a unique opportunity. The Luxembourg residents were also very willing to participate in this study. Without their support, this would not have been possible either.
In addition, in recent years, the LIH has developed a new strategy that positions it very strongly towards translational medicine. The LIH is a public biomedical research institution focused on precision health and invested in the mission to become a leading reference in Europe for translating scientific excellence into significant benefits for patients. Within this framework, we now have the biobank, which is part of the LIH, and numerous interactions with the University of Luxembourg, universities abroad, Luxembourg hospitals, the LNS, etc. Modern biomedical research can only succeed as a team."
This story was first published in French on . It has been translated and edited for Delano.