When COVID-19 arrived in the Netherlands almost 3 years ago, Dr Merel Hellemons was working as a respiratory specialist. Worried about the long-term effects of lung injury in her hospitalized patients, she and her colleagues at the Erasmus University Medical Centre in Rotterdam set up a post-COVID-19 clinic to chart how 650 patients hospitalized for COVID-19 from the first and second wave in 2020 were recovering.
What they saw took them by surprise.
“One of the things that we noticed early on in these patients was that lung injury was there, but it was resolving most of the time, and only a fraction of them had severe lung injury,” noted Dr Hellemons. “But it became apparent that so many patients were unable to return to work and suffered from lots of weird symptoms, like cognitive problems and memory loss.”
The clinic soon started to receive calls from general practitioners (GPs) describing patients who had not been ill enough to require hospital admission but were nonetheless suffering a range of similar symptoms.
“In retrospect, it was a misconception not to include this group in the original study plan. We never imagined that patients who had initially experienced COVID-19 less severely would also have residual symptoms.”
They have now also included these patients in a research programme which aims to increase understanding and find workable treatments for post COVID-19 condition, the complex syndrome now commonly known as “long COVID”.
Understanding the complexity of long COVID
Based on background research into ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome – a serious, long-term illness that affects many body systems), the Erasmus team hypothesized that persistent post COVID-19 symptoms may be due to immune disruption triggered by viral infection. Putting this hypothesis to the test, they compared the changes in the immune system of study participants who had had COVID-19 which led to persistent fatigue 6 months after hospital discharge, with those who did not develop this ongoing fatigue. This has revealed some interesting differences, which the research team are now investigating further.
“We found a wide variety of immune abnormalities, with differing immune-profiles in different patients. There are different sorts of immune disruption and what we cannot yet determine is how these findings in the immune system relate to symptoms. What we do see, however, is probable targets for therapy and that this should be tailored to the patients.”
The Erasmus team have taken physical function measurements, such as walking ability and hand-grip strength that can point to improvements in a patient’s physical recovery over time and can help identify those who need rehabilitation. However, cognitive measurements, and investigation into quality of life, return to work, stress, depression and anxiety symptoms reveal considerable, long-lasting impacts.
The Erasmus team is also coordinating the CO-FLOW study involving patients from 8 other regional hospitals and rehabilitation sites in the Netherlands. Due to the high prevalence of these residual symptoms in the 650 people enrolled in the study, the team plan to extend their research for a further period to better understand these impacts in the longer-term.
Angelique Hasselbaink is one of those enrolled in the study. She was hospitalized with COVID-19 and has returned to the centre 4 times to participate in tests. Like most participants, she is keen to contribute to the understanding of long COVID. “The people in the hospital, the medical staff, they were there for me. So I think it’s my obligation to give back to the public. To help.”
Another participant is Justine Pelmelay, a singer who has previously represented the Netherlands in the Eurovision Song Contest. She was hospitalized with COVID-19 in 2020 and has experienced a big impact on her subsequent health: “The first time after COVID I had to perform I was crying on stage because my condition was terrible”. Her motivation to enrol was also to help others, so they will not have to go through what she did.
A patient-centred approach
Dr Hellemons acknowledges that for those suffering ongoing symptoms, finding treatment is a pressing priority, and that many are frustrated by the wait for a full understanding of the disease. She therefore proposes more urgent research into progressive forms of treatment.
“We as doctors don’t like to take too many risks. On the other hand, rather than patients privately trialling unproven techniques, we would rather try safer treatments that we can really learn from regarding the effects, in a controlled setting, with informed consent, in co-creation with the patient. No 2 long COVID patients are the same. Based on variety in symptoms and the differences in immune disturbances, each patient needs to be treated differently, and that’s what we’re going to focus on next. We are planning to establish a clinical study where we carry out immune profiling of patients and based on this, we propose pragmatic treatments. There are several drugs that we already know work well with other diseases that are safe, have limited side effects and are affordable.”
The team are also hoping to collaborate with the patient advocacy group Long COVID Europe, with whom WHO/Europe partners.
“They, the patients, are the experts. They collaborate so much, they exchange so much. We can learn so much from them,” says Dr Hellemons.
Despite the prevalence of long COVID in Europe, Dr Hellemons believes that the condition is still mostly unrecognized, leaving many sufferers with unmet needs. She also mentions widespread misconceptions about treatment, such as a belief that it can be solved by exercise, or that symptoms can be attributed purely to psychological factors.
The role of GPs
To dispel misconceptions about long COVID, Dr Hellemons and her team deliver lectures and workshops, physically and online, to GPs across the Netherlands, bringing them new insights into how to support their patients. In turn, they hear from GPs about successful long COVID management strategies.
“We are involving GPs in our project to see which patients should be treated by which speciality, because you need to divide the burden equally and have the right treatment, in the right place and at the right time. There are some patients that need an internal medicine doctor or a lung specialist for treatment, but there are other patients that will need to see a physiotherapist.”
While anything resembling a “cure” for long COVID still seems a long way off, Dr Hellemons is optimistic that the research undertaken at Erasmus University Medical Centre will help find forms of successful treatment for at least some people.
The determination of the Erasmus team to make a difference to the lives of those coping with this little understood condition is summed up in Dr Hellemons’ parting words – words which she hopes will also be a trigger for others in the region and globally.
“It’s time for action. We have a lot of work ahead of us.”
WHO/Europe and post COVID-19 condition (long COVID)
WHO/Europe remains committed to learning more about the medium- and long-term outcomes for people with post-COVID-19 condition and has developed 3 goals in collaboration with Long COVID Europe, jointly calling for governments and health authorities to focus attention on the condition and those affected by it through greater:
- recognition and knowledge-sharing
- research and reporting
- rehabilitation.