Lead researcher Prof. Anke-Hilse Maitland – van der Zee wants to use the P4O2 project to find treatments that can prevent and repair lung damage
The collaborative project ‘Precision Medicine for More Oxygen’ (P4O2) consists of a large collection of different studies. Including research that tries to find targets for treatments for long COVID. Four researchers share the latest developments.
Lead researcher Prof. Anke-Hilse Maitland – van der Zee wants to use the P4O2 project to find treatments that can prevent and repair lung damage (see also www.p4o2.org). The project is divided into several parts, including a COPD and long COVID part. All conditions within the P4O2 project are investigated from different angles. Both in the laboratory and in people. The first results are now emerging from research into long COVID.
Multidisciplinary research
The lung COVID researchers want to get a complete picture of the condition by investigating different perspectives. This is also called multidisciplinary research. For example, within a group of a hundred people with long COVID complaints, lung function, fatigue, environmental factors and the functioning of the nasal cells were examined.
Distinguish three groups
PhD student Jelle Blankestijn from Amsterdam UMC participated in the lung COVID research. Blankestijn looked for groups of participants that matched each other based on various medical characteristics. In the clinic it can be seen that long COVID manifests itself differently in people. Therefore, there may be different underlying causes for the complaints per group. This means that treatments may work differently for different groups,” Blankestijn explains. The participants were ultimately divided based on data into a group with mild lung COVID complaints, more serious complaints, and a group with lung problems. The groups also differ in their medical history and patient characteristics.
Reduced lung function after corona infection
‘The lung function of participants with lung problems is greatly reduced compared to that of the other two groups,’ says Blankestijn. ‘A decrease in lung function can mean that you can absorb less oxygen from the air you breathe, causing shortness of breath,’ explains co-researcher and PhD student Merel Cornelissen from Amsterdam UMC. Six months after a corona infection, the researchers found reduced lung function in about half of the participants. More than half of them still had lower lung function after a year.
Fatigue after corona infection
Six months after a corona infection, about three-quarters of the participants suffered from fatigue. After a year, this number was still just over half. “This decrease means that fatigue does not necessarily have to be permanent for everyone,” says Cornelissen. The participants’ fatigue complaints were compared with those of people with long-term fatigue, also called chronic fatigue. There appeared to be many similarities between both groups. ‘This shows that more research into long COVID and chronic fatigue is important to find better treatments,’ says Cornelissen.
Inflammation in the nose
Co-researcher and PhD student Nadia Baalbaki from Amsterdam UMC has examined the nasal cells of people with long COVID. Possible medications were also examined. In the laboratory study, cells from the participants’ noses were tested for the production of inflammatory factors. This showed that a number of participants produce more inflammatory factors after a corona infection than healthy people. This can cause a leaky barrier between the nasal cells. This makes it easier for bacteria and viruses, for example, to enter the body through the nose. “So your filter is actually broken, which can also be seen with allergies such as hay fever and other respiratory diseases,” Baalbaki explains. This leaky barrier in the nose has also been found in people with long COVID. For people who suffer from this, there is a medicine that may help to inhibit the inflammatory response in the nasal cells. Whether this medicine really works for long COVID remains to be investigated.
Effect of RNA on nasal cells
Baalbaki has also examined the RNA of people with long COVID. RNA consists of copies of your DNA, which is a kind of code for all the information in your body. RNA is important for making proteins, which ensure that your body works properly. Baalbaki shows in her research that the RNA of some participants indicates persistent inflammation in the nose. What was also striking was that a number of participants with abnormalities on their lung X-rays had more RNA. This can ensure that they have a higher production of a substance that partly regulates inflammation in the nose. This substance can cause the formation of scar tissue in the lungs. It is not yet known to what extent the increased amount of RNA in the nose can say something about the development of respiratory complaints in people with long COVID. It is therefore important to do more research into this. An existing medicine may also be able to help here.
Differences in immune response after corona infection
In addition to differences in the RNA in the nose cells, there also appears to be a difference in the RNA in the blood of participants. A difference in RNA can indicate a disruption of body processes, such as the immune system. This may cause physical complaints. “We may have seen a different immune response in a small number of participants,” Blankestijn notes. It may therefore be that the body of those participants responds differently to damage from the coronavirus. To help this group, they may need different treatment than the rest.
The effect of environmental factors
“It appears that people with long COVID who are exposed to a higher amount of particulate matter have reduced lung function,” notes co-researcher and PhD student Laura Houweling from Utrecht University. In addition to the body, the environment can also play a role in the development of long COVID complaints. Houweling is therefore investigating the effect of various environmental factors, such as particulate matter, on the occurrence and development of long COVID.
Not only lung function appears to be lower in participants who were more exposed to particulate matter. They may also feel more tired and their quality of life seems lower. Houweling: ‘There certainly seem to be links between exposure to particulate matter and the complaints after a coronavirus infection.’
Particulate matter measurements
Two devices were used to measure the amount of particulate matter. The ‘UPAS’, which the participants wore with them for 24 hours to measure personal particulate matter. And the ‘Sniffer sensor’, which was attached to the outside of the house to measure the particulate matter in the environment. These measurements are now combined with all medical information from the participants, such as lung function and blood values.
A few puzzle pieces further
‘Many studies into long COVID are currently being conducted all over the world. These are all little pieces of the puzzle,” Baalbaki describes. The long COVID research in the P4O2 project also adds small pieces to the puzzle. This creates an increasingly better picture of the long COVID disease. Baalbaki: ‘Based on this research, new studies can further determine which processes in the body exactly cause the various complaints. In this way, new medicines can be developed for people with long COVID.’
The results from this study are not yet hard evidence. The group of participants is still too small for this and the effects found are sometimes still too modest. ‘But the fact that certain effects can be seen is a promising step for further research in larger populations,’ says Houweling hopefully. It is especially important to know that people with long COVID are not all the same, but that each patient requires personalized treatment.
The P4O2 project
The long COVID research is part of the P4O2 project. This project aims to develop prevention and treatment methods for lung diseases. In addition to people with long COVID, people with COPD are also being examined. Furthermore, a large group of healthy adults is being studied, some of whom have a high risk of developing lung disease. The results of this will follow.
The collaborative project P4O2 (Precision Medicine for more Oxygen) is co-financed with the PPP allowance. This allowance has been made available by the Top Sector Life Sciences & Health to Longfonds, to stimulate public-private partnerships. The consortium consists of top researchers from across the country, private parties and patient representatives who strive for an international leading position for the Netherlands in the field of lung research.
Source: Long Fund
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