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On loss of smell, rehabilitation and poor predictions

On loss of smell, rehabilitation and poor predictions

Formulating research questions, obtaining funding, joining forces with other universities – before the coronavirus pandemic, these kinds of things took forever. Now, they seem to be achieved overnight. Studies related to COVID-19 and the novel coronavirus are springing up like mushrooms all over the world, although their quality sometimes leaves much to be desired. What are UM researchers currently working on?

COVID-19 patients and mechanical ventilation

Scheduling a phone interview with Marcel Ariës is not easy these days. Ariës works in the intensive care unit of the Maastricht University Medical Center+ (MUMC). It’s madness, he texted yesterday morning. Lots of patients admitted.

And, last night: Difficult, sad day in the department. Won’t be home until 8 p.m.

Before the coronavirus crisis, MUMC had 33 ICU beds. The hospital currently has more than sixty. “Eighty-five per cent of these patients are extremely ill”, says Ariës. “They’ve all developed severe pneumonia caused by the virus.”

In addition to his shifts in the ICU, Ariës – who first trained as a neurologist – is also conducting research. Together with internal medicine and intensive care specialist Bas van Bussel, he is working on a model to predict how COVID-19 will progress in patients. Will they require mechanical ventilation after being admitted to hospital, for example? Eight hospitals are taking part in the project, which was initiated by MUMC and Amsterdam UMC.

“The hospitals collected data from nine hundred COVID-19 patients over a period of two weeks”, explains Ariës. “What condition were they in before they were admitted? What about when they were in the A&E department? What department were they transferred to next?”

Using artificial intelligence and statistical analyses, the researchers hope to predict how the disease will develop in each COVID-19 patient who is hospitalized. “That’s the best-case scenario”, says Van Bussel. “We would need a lot of data, though. We’ll first restrict ourselves to conclusions about certain groups of patients: which groups are doing better than others?”

Another study currently being conducted at MUMC is looking into the best way to ventilate COVID-19 patients. According to Van Bussel, we already know that the more pressure used to push air into the lungs, the greater the lung damage. “MUMC and Erasmus MC have these meters that trained nurses can use to determine exactly how mechanical ventilation is affecting the lungs – how the air is being distributed, or whether the lungs are being overdistended. COVID-19 patients may benefit from a lower pressure setting to reduce lung damage.”

The art of prediction

The literature currently contains a lot of models that predict which people infected with the coronavirus will fall ill, which patients will end up in the ICU, and which of them will not make it at all. How reliable are these prediction models?

Laure Wynants, a researcher at UM’s Care and Public Health Research Institute (CAPHRI), is leading an international team of sixteen researchers (Oxford, Leiden, Vienna, Utrecht, Leuven). They were the first to collect and appraise these models. Their findings are described in a systematic review that will be published in the British Medical Journal (BMJ) this week.

The researchers selected a few dozen models from over 2700 articles, explains Wynants. The models turned out to be of poor quality. Most of them were developed in China and clearly produced in a hurry, says Wynants.

One problem is that predictions were partly based on incomplete patient data. “Sometimes the models only included patients who had either recovered or died, excluding patients who were still in hospital. This results in an unrepresentative picture of the patient population, causing the predictions to be incorrect as well.”

BMJ has asked the research team to provide updates every two weeks. A solid model is yet to be found.

Professor Maurice Zeegers, scientific director of CAPHRI, is also conducting a systematic review together with the Maastricht University Library, among others. Zeegers is focusing on risk factors, which include age and underlying conditions.

COVID-19 and loss of smell

COVID-19 remarkably often goes hand in hand with a loss of taste and smell. Could this be an early sign of infection? Mirjam van den Brink, a trainee research assistant at Maastricht University Campus Venlo and the Princess Máxima Center for Pediatric Oncology in Utrecht, experienced these symptoms herself about a month ago. She’d made coffee, but couldn’t smell it – or the flowers in her living room, or the scent of her own perfume. Then she lost her sense of taste. As she also had a sore throat, Van den Brink thinks she may have been infected with the coronavirus. 

Van den Brink happens to be doing her PhD research at the Princess Máxima Center on loss of taste and smell caused by chemotherapy. “We know that chemotherapy affects the sense of taste and smell in adults. It’s different for each person, though; sense of smell becomes weaker in some people and stronger in others. I want to find out whether this applies to children as well. But now there is another important question to answer: is loss of smell a symptom of COVID-19? If so, how exactly does that work?”

Van den Brink is a member of the Global Consortium for Chemosensory Research, where five hundred researchers keep each other apprised of new developments in this field. They’re conducting a global survey (Van den Brink worked on the Dutch translation) to explore the possible connection between COVID-19 and loss of taste and smell. The consortium is also developing a self-test.

In the United States and the United Kingdom, people are gradually being warned to not just stay home if they have a dry cough and a fever, but also if they’ve lost their sense of taste or smell – just in case.

Life after COVID-19

It appears that many former COVID-19 patients will never fully recover after being discharged from hospital. Pneumonia may leave scar tissue in the lungs – not just in patients who were admitted to the ICU, but also in those who didn’t really have any other symptoms. This raises the question: what is the impact of COVID-19 on quality of life?

Martijn Spruit, professor in Rehabilitation of Chronic Organ Failure at UM, also works at rehabilitation centre CIRO in Limburg. He wants to monitor all former COVID-19 patients for three months after they were discharged from hospital. How are they readjusting to everyday life? Can they go back to work? Have they recovered socio-emotionally? If not, they will need rehabilitation – preferably before those three months have passed. 

CIRO usually treats patients with chronic lung diseases like COPD and severe asthma. But since last week, the centre treats COVID-19 patients. “We currently have eight patients who were transferred from MUMC, among others”, says pulmonologist Frits Franssen, who also works at both MUMC and CIRO. “We have room for 32 patients.”

The Lung Foundation Netherlands has also announced cohort studies to monitor this new group of patients with chronic lung disease. The foundation has provisionally named the disease “Corona Obstructive Lung Disease (COLD)”.

Increase in nursing home deaths

Two weeks ago, the Netherlands went into what its Prime Minister Mark Rutte referred to as an “intelligent lockdown”. The Netherlands Ministry of Health also asked the Academic Collaborative Centres on Care for Older People – including the centre in South Limburg – to start collecting nursing home data on patients infected with the coronavirus. These data show that 281 nursing home residents have already passed away from COVID-19. This number is higher than previously thought.

In addition to this number, the data give a lot of insight into what has been happening at nursing homes during the coronavirus crisis, explains Professor Jos Schols. “How many nursing home residents have fallen ill? What symptoms did they have? Who recovered and who passed away? We will look into all of this.”

The centres would also like to read the minutes of crisis management meetings at nursing homes. Schols says, “This will give us an idea of staffing levels and sickness absence rates, as well as the effects of the ban on visitors.”

Are slum dwellers more likely to be infected with the coronavirus?

How does the coronavirus affect people who live in slums? Onno van Schayck, professor of Preventive Medicine, may set out to conduct a study on this, initiated by the Netherlands Enterprise Agency (RVO). The RVO financially supports international projects together with the Netherlands Ministry of Foreign Affairs.

India is currently on lockdown, but the people who live in its slums can’t possibly stay at home. If they don’t work, they starve, explains Van Schayck, who has been doing research on slums in India for years. “And if they stay home in their nine-square-metre slum houses, they’ll infect each other.” 

They also, often with four or five children, spend hours sitting in the smoke released during cooking. “We know that people are more likely to become infected with MERS and SARS if they smoke, but also if they are exposed to smoke from open fires, spending hours in the smoke. The harmful effects on the lungs are similar. The question is whether this means slum dwellers are more likely to become infected with the coronavirus.”

Currently, the slums are no-go areas because of the lockdown. But as soon as the lockdown is lifted, Indian researchers who have been working together with UM for years will head out there. They will work in close collaboration with the local hospitals where COVID-19 cases are diagnosed. 

Don’t use rapid tests!

What are the causes of COVID-19? Which genetic and molecular variations exist? And why does the disease progress so differently in different people? To find answers to these questions, 29 leading researchers connected with the Young Universities for the Future of Europe (YUFE) alliance have formed a consortium with Iran and China as partners. UM is represented in the consortium by Professor of Pharmacology Harald Schmidt.

The researchers will look for biomarkers – early indicators of susceptibility to the coronavirus and its life-threatening complications – to arrive at new diagnostic tests and treatments. The University of Rome Tor Vergata is leading the project and has applied for EU funding.

Meanwhile, PathoFinder, a company located on Brightlands Maastricht Health Campus, has developed a “rapid test” to detect coronavirus infections within two hours. However, UM general practitioners warn against rapid tests and strongly advise against using them as their reliability has yet to be studied by scientists. 



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