Broadening research on long COVID syndrome

Broadening research on long COVID syndrome

Understanding long COVID syndrome is vital for ensuring those affected can receive the best possible care. Aranka Ballering, first author of a study that compared groups of uninfected and COVID-19-positive participants explains how such research can help inform the healthcare response.

For many people who contract COVID-19, symptoms will ease within one to two weeks, much like the common cold. However, for others, the effects of the SARS-CoV-2 infection can last for much longer and have a significant impact on their daily lives. Researchers are now trying to unearth vital information and patterns for so-called long COVID or post-COVID syndrome whereby the condition persists for longer than 12 weeks. Common traits of the condition include fatigue, muscle aches and a loss of smell, but there is a range of other symptoms that can be attributable to long COVID.

A recent Dutch study published in The Lancet investigated the prevalence of long-COVID symptoms in adults by comparing infected persons with an uninfected population. This is one of the first studies that has compared results from the two groups, therefore giving greater insight into how long COVID syndrome is distinguishable from other conditions that present in a similar way.

Researchers found that 21.4% of people who contracted the virus, compared to 8.7% of the control group, experienced at least one new or severely increased symptom three to five months post-infection. This suggested that one in eight COVID-19-positive people (12.7%) in the general population experience long-term symptoms. To find out more about the study, and where further research is needed to better understand long COVID syndrome, Lorna Rothery spoke to the study’s first author, Aranka Ballering.

Why is it important that we explore the potential effects of long COVID on population health and how can this research help to inform the healthcare response?

Long COVID syndrome can affect daily functioning and may also have a significant effect on the economy, as well as on society as a whole. To ensure an adequate healthcare response, we need to understand the disease at hand and what kind of symptoms are involved. We also need to understand who the most at-risk groups are so that we can create effective treatments for them.

Long COVID syndrome research should firstly focus on understanding long COVID syndrome and then we may be able to move on to adequate treatments.

What were the key benefits of including uninfected populations in your study? How does your research compare to other studies on long COVID syndrome so far?

Some studies have compared long COVID syndrome symptoms with uninfected populations. That is of course important because the symptoms that are associated with long COVID syndrome are pretty common in the regular population. We all experience a headache from time to time or sneeze or have a sore throat, especially when it is hay fever season, but some of these may be attributable to COVID and some to other conditions like hay fever. If you can compare with the uninfected population, you can firstly account for symptoms that are just present in a regular population and secondly account for symptoms that are due to, for example, seasonal changes.

Some other studies have included uninfected control participants, but there were no studies yet that detailed the health of people before they got COVID. A lot of researchers simply ask if participants are still experiencing symptoms, prompting a ‘yes’ or ‘no’ answer, however, what we did was gather data from weeks and months before people contracted COVID, so we could better understand their symptom severity and whether symptoms three to five months after COVID were a continuation of pre-existing symptoms, new or really severe symptoms. That is the most unique part of this study.

What external factors such as age, environment, or previous conditions have to be considered in a study of this nature?

You need to make sure that your infected population is suitably comparable to your uninfected population. So, for example, you cannot have 60% of your COVID-positive people be female, and then compare that to a population that is 75% male. You need to ensure your population is comparable with regard to sex and age and you may also want to check for comorbidities. Our study only included sex and age as key factors. In this kind of analysis, you also want to consider whether certain factors predispose you to long COVID syndrome.

Did you experience any challenges or limitations during the course of your research?

All in all, our study is still quite basic; it is only exploratory. Saying that we thought a lot about whom to include as a control population and whether we needed to include the control population of uninfected people if we already compared people’s health before they got COVID. We needed to understand why it was necessary so there were a lot of pretty challenging considerations.

LifeLines is a relatively old population, and it is 98% white people in the north of the Netherlands so we do not really know whether we can extrapolate these findings to other settings. There are no children in this cohort study so we cannot say anything about paediatric long COVID syndrome.

What other areas need to be explored to help us fully understand the impact of long COVID?

To fully understand the impact of long COVID, we first need to understand the long COVID syndrome, and COVID itself. We are now seeing studies that hypothesise that there are different pathophysiological mechanisms underlying different symptoms, so there are people who are only suffering from symptoms of the cardiopulmonary system, and there are people who are mainly suffering from cognitive dysfunction.

There has been a study recently that showed that there is grey matter loss in the brain after COVID and in people suffering from long COVID. I think we first need to understand which symptoms cluster with each other and may form one category or subtype of long COVID syndrome. We can then figure out what the underlying mechanism is. That would allow us to give more tailored, personalised treatments and anticipate what the longer-term issues of long COVID could be.

What is next for your research in this area?

We are now trying to do cluster analyses to understand which symptoms can cluster together and what the risk factors for these subtypes are. Because we were able to identify who these people with long COVID syndrome were, we are asking them to do physiological tests and we will assess their blood pressure and will also assess their blood for certain proteins.

There are two strands to our research, one is epidemiological and the other biomedical.

Aranka Ballering
PhD candidate
University of Groningen 

This article is from issue 22 of Health Europa Quarterly. Click here to get your free subscription today.


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