Researchers from Cape Peninsula University of Technology (CPUT) and the University of Cape Town’s Neuroscience Institute at Groote Schuur Hospital hope to document the cognitive and emotional symptoms of long Covid, the post-viral syndrome linked to Covid-19. Dr Donné Minné from CPUT and Altay Yüce Turan from UCT, who are involved in this research, tell us more.
(The study is currently running and will be ongoing until April 2023. Minné and Turan are seeking participants to enroll in their study – find out how you can get involved below.)
People who develop severe Covid-19 have a much higher risk of ongoing neurological and mood-related disorders, particularly if they were hospitalized. These effects have been linked to pathological events in the body as a result of the virus, including system-wide inflammation, blood vessel changes, alterations in the blood-brain barrier, loss of oxygen to the brain, and the consequences of mechanical ventilation.
However, long Covid presents more of an enigma. Not long after the first wave of pandemic infections, a number of people recovering from even mild Covid-19 started to report hard-to-place symptoms, sometimes up to six months after their infection. They called themselves Covid “long-haulers” and the now widely accepted term “long Covid” was born.
‘Mrs S’ was a typical case. Previously an active, high-functioning individual, she now described feeling foggy and unable to concentrate, very unlike her usual self. Her memory of her was patchy, and she was terribly tired all the time. She struggled to keep track of conversations and had gradually begun avoiding social interaction.
She was experiencing heart palpitations and breathlessness after minor exertions, and most of the time these episodes were accompanied by a ringing in her ears. Unable to work as a result of these symptoms, she was on indefinite sick leave, filled with anxiety about her precarious employment status. Some days were better than others, but ever since her mild bout of Covid-19 eight months earlier, Mrs S had forgotten what she felt like to be herself.
READ | Living with long Covid: From an induced coma to learning how to walk again – ‘I will fight’
Different profiles of long Covid: Explained
Generally speaking, long Covid is the post-viral syndrome associated with Covid-19. Individual experiences of long Covid vary widely, however. In some cases, Covid symptoms persist long after a negative test. In others, an entirely new symptom profile emerges, either immediately following the initial acute phase of the illness, or after a variable window of time. In all cases, though, the SARS-CoV2 virus does not show up in diagnostic tests. The original infection is no longer present.
Cases such as that of Mrs S – where an initial viral infection appears to trigger another prolonged period of illness – are not unprecedented. Readers of writer-neurologist Oliver Sacks will be reminded of the encephalitis lethargica epidemic he describes in his book and film awakeningsand the strange post-viral syndrome it left in its wake.
Between 1915 and 1926, encephalitis lethargica spread swiftly across the world, killing half a million people before vanishing almost overnight. Apparently caused by an enterovirus (a type of RNA virus that usually lives in the gastrointestinal tract), encephalitis lethargica was described by Sacks as a “hydra with a thousand heads” on account of the unpredictable and complex ways it would manifest.
Its distinctive mark was a kind of sleeping sickness, interrupted in some by agitation and insomnia. Most disturbing, however, was the post-viral syndrome associated with this disease. After a period of recovery – brief in some patients, years-long in others – symptoms would suddenly return. Often these were the same symptoms that had originally presented, but sometimes a severe and unusual form of Parkinson’s disease emerged instead.
Are long haulers in for the grim ride of post-encephalitis Parkinson’s?
Why encephalitis lethargica led to these extreme forms of post-encephalitic syndrome is a mystery that has never been solved. Doctors were unable to detect any sign of lingering infection in sufferers, and their order remains medically unexplained even today.
While the parallels between Covid-19’s post-viral syndrome and the one associated with encephalitis lethargica may seem alarming, there is little evidence to suggest that long Covid sufferers are in for the grim ride of post-encephalitis Parkinsonism.
Parkinson’s disease is a motor disorder of the central nervous system (CNS), and we’re not seeing many signs of this specific type of CNS disturbance in long Covid. Rather, long Covid symptoms have a more diffuse nature. They generally include fatigue, headache, brain fog, breathlessness, loss of smell or taste, and depression. Heart palpitations, anxiety, dizziness upon standing, sleep disturbances, and pins-and-needles are also frequently reported. Symptom profiles differ from patient to patient, but almost all patients report fatigue.
Fatigue following infection with other viruses
Fatigue symptoms and syndromes following infections are not especially rare. In addition to the post-encephalitis syndrome already described, syndromes have emerged following infection with Epstein-Barr virus, the Ebola virus, the human herpesvirus, the West Nile virus, and Dengue virus, among many other viruses. It’s hard to know why these syndromes occur in some individuals but not others.
A recent large-scale study on long Covid found that, during the acute stage of Covid-19, five symptoms, in particular, are predictive of whether one develops the post-viral syndrome: fatigue, headache, breathlessness, hoarse voice, and muscle pain. A great deal more research into the phenomenon is needed before any real conclusions can be drawn.
No one really knows why post-viral syndromes occur, but what they all have in common is that they begin with an infection – with a period of sickness, in other words. But what happens in the body during periods of sickness, and how is this experience both a physical and an emotional one?
We need only think back to the last time we were ill ourselves to understand the way illness hijacks our body and mind. When we are ill, we feel drained of energy, our body aches, and our desire to socialize diminishes. We feel woozy and sluggish. Passions of all varieties fade. We lose our appetite and usually retreat, forlorn, to a warm, safe spot.
Scientists coined the phrase “sickness behaviour” in the 1980s to refer to the dampened motivational state that accompanies infection. It is believed to be orchestrated, at the neural level, by inflammatory cytokines that turn down the activity of several neurotransmitters – including dopamine and serotonin – while at the same time increasing the turnover of hormones in the central stress pathway, which spans the hypothalamus, the pituitary gland, and the adrenal glands. These mechanisms have one shared purpose: combatting the infection.
Technically, our body could fight this internal battle without us being the least bit aware of it. But sickness doesn’t work like that, and for good reason. We experience sickness consciously because the feeling of being sick has a function. Feelings are the workhorses of the mind. They make us do what needs to be done to support the body, which in the case of illness is to do not very much at all.
In the academic literature, sickness is widely accepted as an evolved strategy for overhauling motivational priorities in order to redirect energy resources towards the fight against infection. In other words, you are meant to feel tired and listless; this feeling ensures that you don’t expend unnecessary energy. The body is commanding you to stop and rest.
What could be happening with LC and other post-viral syndromes?
Since inflammation in the body is closely intertwined with dopamine, serotonin, and other neurotransmitters that regulate mood, motivation, and emotion, it should not surprise us that physical illness so often co-occurs with anxiety and depression. While purely speculative, what could be happening with long Covid and other post-viral syndromes is that, even though the body is no longer infected with the virus, the immune system is still switched on, in battle mode. Inflammatory processes in certain brain regions may persist, mood and emotion remain off-kilter, and intense fatigue continues to govern daily life.
Studies on neuropsychological outcomes – a branch of psychology that deals with how the brain controls mental functions such as thoughts and feelings – have shown that long Covid patients often experience forgetfulness, difficulties with concentration and motivation, and trouble following conversations or finding the right words.
READ | Long Covid concentration and memory issues common, could impact working population – study
This can feel disorienting and overwhelming. Symptoms like these pose a major challenge to independent living and general wellbeing, and are likely to heavily impact mental health. One consequence is that people tend to experience anxiety and might prefer to self-isolate. Fatigue is very common and can be debilitating.
Having a clear-cut definition
While the global research community is committed to better understanding the syndrome, idiosyncratic symptom profiles of long Covid has meant that the syndrome is hard to define. Without clear-cut definitions, it is difficult to design research studies that can adequately compare patient and control groups.
Before we can untangle the possible causes of the syndrome, it will be important to properly classify the spectrum of complaints that we are seeing from patients. This will involve a lot of careful listening.
Scientific reports on long Covid are being churned out on an impressive scale, and while this should be reassuring, it is somehow not. According to the research team from Cape Town, much of the available research on long Covid lacks nuance and tends to capture symptom profiles with broad brush strokes.
Take fatigue, for example. Fatigue is similar to tiredness, but it is not just tiredness. It can feel like drowsiness or weakness or boredom, but it’s much more than any of those things. It can engulf you post-feast, post-nap, or at random. Fatigue can be felt in the body or in the mind, or in both places at once. If we want to be particular about who is most vulnerable to fatigue, and why, then we should also get specific about what we really mean by this term.
And we need to listen to our patients for that. Similar problems crop up when one talks about brain fog. This is a worrisome term, but it is also not very meaningful in and of itself. It doesn’t form part of the clinical nomenclature. It might be possible to eradicate the fear in an intimidating phrase like brain fog if we knew, for instance, that it could be explained almost entirely by its co-occurrence with fatigue. It is also important to define brain fog in terms of established cognitive functions, such as attention or memory, and so on. These are the sorts of questions our research is hoping to unravel.
Vaccination and long Covid
Studies suggest that while vaccination does offer protection against the risk of developing post-Covid syndrome, it may only offer partial protection. Insufficient knowledge and understanding of long Covid has meant that many sufferers have resorted to self-medication.
Appropriate care – especially psychological support, to address the trauma and loss associated with brain injury – is a key part of the rehabilitation process. “In many cases, we find that when the emotional disturbances are attended to, the brain is freed up to process information better and this can lead in some cases to an improvement in cognition.”
If you have had Covid-19 or think you are suffering from Long Covid and would like to participate in the research taking place in Cape Town, send an email to firstname.lastname@example.org
The views expressed in this article represent the opinions of the authors and not those of their affiliated institutions.
Written by Donné Minné & Altay Yüce Turan.
Donné Minné is a clinical neuropsychologist based in Cape Town and a postdoctoral fellow at the Applied Microbial and Health Biotechnology Institute at Cape Peninsula University of Technology. Altay Yüce Turan is a neuropsychology master’s candidate at the University of Cape Town. Her research focuses on characterizing the mental aspects of long Covid fatigue and is supervised by Prof Mark Solms and Dr Donné Minne.