A major loss: no more sense of smell after COVID-19

Dr Sanne Boesveldt of Wageningen University & Research and Dr Digna Kamalski at UMC Utrecht are conducting research into both the causes and the treatment of this disturbed sense of smell. Sanne looks at the natural course of loss of smell and smell changes, and she also examines the brains of patients with loss of smell in the COVORTS study. Digna tests anti-inflammatories as a treatment within the COCOS study.

Digna: ‘You only miss your sense of smell once you no longer have it. That is the experience of many patients who have lost their sense of smell for many months. For example, as soon as they returned to their parental home and could no longer smell the familiar smells, they experienced the loss of this important sense. Therefore, experiencing a loss of smell for many months is a major loss. We treated the patients who came to me with anti-inflammatory drugs. In addition, they also received an intensive sense of smell training. For most of them, the smell score increased after a period, and you could clearly see what an enormous relief that was. It also helped considerably that the patient felt heard.’

Digna: ‘We do not know why one person experiences a loss of smell but another does not. However, the COVID-19 variant you were infected with seems to make a difference. During the first COVID-19 wave, it quickly became clear that many people experienced a loss of smell following a COVID-19 infection. Later in the pandemic, with the Omicron variant, fewer patients experienced a loss of smell. Our research started during the first COVID-19 wave, so we observed the peak of the Delta variant. That was, at the same time, a blessing in disguise too: as a result, it was possible to allow many patients to participate in the study and we quickly obtained results. That allowed us to test our medication under a large group of patients who experienced an olfactory disorder.’

Sanne: ‘Initially, we were going to follow patients for a period of one year. However, we quickly noticed that we would miss an important group of patients, who had already been experiencing olfactory complaints for some time. Therefore we will now follow patients more extensively, namely for two years so that we can have a longer follow-up period. That will allow us to test whether the ability to taste and smell changes over time. We do see a very limited improvement over the course of time, but this is much more limited than in other cohorts. That might be because we have offered no treatment whereas Digna, for example, offered olfactory trainings too.’

Sanne: ‘I examine the brain processes to determine what exactly has caused the loss of smell or change in smell. What happens in the brain, and which information do we see in the brain in the case of olfactory disorders? We examine this using imaging techniques such as a functional MRI scan or PET scan. That is a rather intensive research trajectory, also because people sometimes find these imaging techniques frightening or burdensome. We think that’s why finding people who want to participate in this study is more difficult. Patients must go to the Gelderse Vallei Hospital in Ede or Amsterdam UMC for the imaging techniques. In addition, we visit people at home to question them about their experiences over the last months. We make a house visit every three months and perform taste and smell tests to objectify the symptoms. It is quite a considerable logistics operation to regularly visit 75 patients but we do plan this smartly per region.

Digna: ‘In November 2021, our research into anti-inflammatory drugs as a treatment for olfactory disorders was published. Because we saw that an inflammatory reaction of a nasal nerve played a role in patients with an olfactory disorder, we treated a group with prednisolone. The other group received a placebo. Unfortunately, prednisolone did not result in an improved sense of smell. This is an important outcome that helps us gain a better understanding of the clinical picture. We still do not have any drugs available to treat the loss of smell following a COVID-19 infection. We first of all want to go back to basics: what happens at the cell level? Where does the drug need to intervene?”

By measuring at multiple moments what the loss of smell does and how it proceeds, we can better understand how to effect a possible recovery. Ultimately, we want to be able to easily predict how quickly the loss of smell will recover, so that we can better advise patients about what they can expect.

The patients from the first and second COVID-19 waves still experience daily symptoms because they have little or no sense of smell. We probably need to approach this problem more comprehensively for a possible treatment. For example, which other symptoms do these patients have and whether there is relationship with other Long COVID symptoms. Examples are concentration problems and tiredness. In brief, we still do not know much about this interesting subject. We will therefore continue to try and further unravel the secrets of the sense of smell.’

• Long Covid
• Blog series "I'm researching long COVID"