27 June 2023

The understanding of why some people experience lingering symptoms following COVID-19 has increased rapidly since the outbreak of the pandemic. Swedish researchers have now published an overview of research findings on breathing and heart function problems in post-COVID condition patients. The LiU researchers behind the article study post-COVID from different perspectives.

COVID-19, which is caused by SARS-Cov-2 virus infection, no longer meets the criteria for being considered a public health emergency of international concern, according to the World Health Organization, WHO. But this does not mean that the research community will stop seeking answers to all the questions that have arisen in the wake of the pandemic. Many people still have remaining or late symptoms long after infection, i.e. post-COVID condition.Kristofer Hedman, researcher and specialist in clinical physiology Kristofer Hedman, researcher and specialist in clinical physiology Photo credit Gunilla Pravitz

“Symptoms can in many cases drag on for a very long time, so we may not even have reached the summit in terms of post-COVID condition sufferers yet. We see more and more health care cases where people experience major problems in their everyday lives. And unfortunately this is probably not the last pandemic. It’s very important to ensure that health care can be better prepared for this type of persistent health issues next time,” says Kristofer Hedman, physician and associate professor in the Department of Health, Medicine and Caring Sciences.

Abnormal breathing pattern during exercise

Relatively early in the pandemic, the Department of Clinical Physiology at Linköping University Hospital, where Kristofer Hedman works as a physician, received many referrals from other health care providers.Man on bicycle being supervised by male physician.Extensive tests of patients’ lung function and of how their bodies reacted to physical exercise has been carried out in the form of bicycle exercise tolerance tests.. Photo credit Charlotte Perhammar

In an agreement with the then post-COVID care centre, the clinic carried out extensive tests of patients’ lung function and of how their bodies reacted to physical exercise in the form of bicycle exercise tolerance tests.

“We didn’t expect that so much would be normal in these tests, with patients having quite explicit symptoms. But what we did see that surprised us, and which we seldom see, was a disrupted breathing pattern during exercise”, he says.

Normally, breathing should increase stably in response to increasing exercise. But many of those referred for lingering symptoms after COVID-19 had a fluctuating breathing pattern, similar, but not identical, to a pattern previously linked only to heart failure. This uneven breathing pattern aroused the researchers’ interest.

In healthy individuals, breathing is automatically regulated by the autonomic nervous system. But this seems to have been disrupted in some people with post-COVID. Linköping researchers have looked more closely at this disruption, also known as autonomic dysfunction. The researchers followed a group of patients for a set period of time to see whether these problems would pass. Their preliminary results, which have not yet been published, indicate that one year later, around half of the patients have a normal breathing pattern.

“Half of the patients still have this abnormal breathing pattern. Also, those who still have these problems in many cases seem to have a somewhat milder form, so we’re hoping this will go away over time,” says Kristofer Hedman.

Heart and breathing commonly affected

Disruption of autonomic nervous system regulation is not in itself a new phenomenon. But it does however seem to be a prominent feature in the post-COVID group. One of the most common symptoms associated with the heart is a strong unwarranted increase in heart rate when standing up. This phenomenon is known as POTS (an abbreviation of postural orthostatic tachycardia syndrome). As for the breathing function, an abnormal breathing pattern and hyperventilation are examples of post-COVID symptoms.Woman in white lab coat in a laboratory.Maria Lerm. Photo credit Charlotte Perhammar

Kristofer Hedman is one of the authors behind an article that summarises the research findings concerning disruption of the autonomic nervous system in post-COVID sufferers. The initiative for this article came from Professor Maria Lerm at LiU, who gathered researchers at Linköping University, Karolinska Institutet, the University of Gothenburg and Uppsala University with expertise in for instance pulmonary medicine, infectious diseases, cardiac medicine and cell biology. In their article, the researchers address several issues: What actually happens in the body? What do the symptoms look like? What treatment options are there?Young woman using a pipette in a laboratory.The researchers investigate changes in gene regulation as a potential underlying cause of disruptions in the autonomous nervous system. Photo credit Charlotte Perhammar

Explanations for this disruption could possibly be found in the individual organs, but it is also possible that it could be due to gene regulation. Maria Lerm has led a study of a small group of people with lingering symptoms, and has followed them for more than a year. The LiU researchers were the first in the world to report that post-COVID condition seems to be linked to changed gene regulation, known as epigenetic reprogramming. Frida Nikesjö is a doctoral student involved in this research:

“Cells can reprogramme their genes to change protein production to fight and withstand infection. One theory is that this genetic reprogramming is disrupted in post-COVID,” she says.

“In this article, we present many different theories on underlying causes of post-COVID. But this is a very attractive explanation for how symptoms can linger in certain patients, that this might be due to reprogramming of how some genes are used,” says Kristofer Hedman.

Important to demystify post-COVID

With increasing knowledge of a particular condition, it often turns out that the patient group is not as homogenous as may initially have been imagined. It has turned out that there are post-COVID condition subgroups too. This poses a challenge for researchers. In Kristofer Hedman’s opinion, it is important to distinguish between subgroups.

“If people who have been very seriously ill thereafter suffer from severe long-lingering symptoms, this could be due to the infection as such, but it could also be because they’ve been hospitalised for a long time. And then we have the group of patients that have had a very mild infection, and who sometimes haven’t even noticed the acute infection, but who for some reason develop lingering symptoms,” says Kristofer Hedman. Photo credit Charlotte Perhammar

Finding specific treatment for post-COVID condition is also a challenge. Treatment for some symptoms is currently available, such as physiotherapy rehabilitation in cases of disrupted breathing patterns. But finding treatments that tackle the root of the problems requires that researchers and drug developers understand the biological mechanisms.

“Many patients find it frustrating that much of the treatment cannot cure them. I think that for many patients – not all, but many – it may also be important that we succeed in demystifying the disease,” says Frida Nikesjö.

Kristofer Hedman thinks that many post-COVID condition patients may find their condition a bit easier to handle if they feel that science and the doctors they see at least know what is wrong and believe what their patients are saying. He says:

“At the outset of the pandemic, when this was something completely new, it was a common problem that people seeking medical care for this condition were not taken seriously. This happens a lot less now, although I’m sure it still happens. We’re beginning to understand post-COVID better now. We’re still far from understanding everything, but we’re slowly approaching some sort of core. That’s very satisfying.”

The article: Cardiorespiratory dysautonomia in post-COVID-19 condition: manifestations, mechanisms and management, Artur Fedorowski, Monika Fagevik Olsén, Frida Nikesjö, Christer Janson, Judith Bruchfeld, Maria Lerm and Kristofer Hedman, (2023), Journal of Internal Medicine, published online 14 May 2023, doi: 10.1111/joim.13652

Translation by Anneli Mosell

How common is post-COVID?

What is it?
Lingering health issues three months after acute COVID-19 infection or symptoms appearing no earlier than three months after acute infection and lasting for at least two months may be post-COVID.
• How many people have contracted post-COVID?
There are no completely reliable statistics on post-COVID, and the estimates made differ greatly. The above definition has been used in many studies now, with an occurrence of between 5 and 30 per cent of all people having had COVID-19. It is estimated that the occurrence is somewhere between 5 and 10 per cent. The estimate is greatly affected by the selection of patients included.
Does the vaccine make any difference?
Yes, it is quite evident that the vaccine protects not only from contracting severe COVID-19, but also the risk of developing post-COVID is significantly lower for those who have been vaccinated.

Source: Kristofer Hedman, assistant professor in the Department of Health, Medicine and Caring Sciences, and physician

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