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Is this Long-COVID?

I am a Clinical Psychologist and Assistant Professor of Epidemiology and Psychiatry at the Department of Psychiatry of Amsterdam UMC in the Netherlands. In this piece, I would like to share my personal experience with Long-COVID and some thoughts on the research perspectives around it.

 

June 27th: I woke up feeling something strange in my legs. I‘m used to tiredness as I play volleyball at intense levels but this was something qualitatively different; my legs were unnaturally heavy.


In those days, I had something else exciting on my mind — I was about to leave for Berlin to meet with colleagues of the Department of Psychiatry and Psychotherapy at Charité Hospital — so I decided to simply ignore that interfering sensation (“maybe it’s just a temporary sickness” I said to myself). But the symptom did not disappear, and instead grew stronger until two weeks later I could barely climb my stairs. I slowly developed all kinds of other symptoms: general fatigue, pain in my arms and chest, and — those that scared me the most — neurocognitive symptoms such as brain fog and confusion. Furthermore, days with cognitive symptoms were also accompanied by sudden and intense states of anxiety.


Photo by Jaroslav Devia on Unsplash

The first routine health checks did not reveal any specific issues. But the symptoms were growing and reached their peak a few days later when I became extremely confused and incapable of functioning. My general practitioner referred me to the hospital to start a deeper examination, but a couple of hours after our appointment he called me back: “I was reviewing your files, I see that you actually had COVID-19 at the end of March (I had a breakthrough infection that, being fully vaccinated, resolved in a couple of days with very minor symptoms). Now you will do all the exams required by the hospital to rule out other explanations. If everything comes back negative, we will reconsider this info”. That is when I started to familiarize myself with what is commonly known as ‘Long-COVID’.


The many names of Long-COVID and its impact on public health


Several different terms and definitions have been proposed for the long-term sequelae of COVID-19 infection, among which the most commonly used is Long-COVID. More recently, the World Health Organization (WHO) formally adopted the label of “Post-COVID” and proposed a clinical case definition based on expert consensus — for the remainder of this article I will use this label.


Post-COVID occurs usually 3 months from the onset of COVID-19; the list of symptoms, which last for at least 2 months and may represent both new onset or persist from the illness, is very long and include, among others, fatigue, shortness of breath, and cognitive dysfunctions. These symptoms have an impact on daily functioning and cannot be explained by an alternative diagnosis.


The Lancet recently published a large-scale epidemiological study on more than 75,000 subjects in the Netherlands, showing that one out of eight people with COVID-19 in the general population suffers from somatic symptoms of Post-COVID such as painful muscles, heavy limbs or general fatigue. This concerningly high estimate comes from one of the most robust studies performed so far, in which the severity of Post-COVID symptoms was compared to the severity of the same type of symptoms present before the infection and in non-infected subjects.


Nevertheless, an important limitation of the study reflects our evolving comprehension of COVID-19 consequences; the studies developed in the initial phase of the pandemic did not consider including the measurement of neuropsychiatric symptoms. A new overarching review by Penninx et al. showed that neuropsychiatric consequences are instead a hallmark of COVID-19 sequelae, with cognitive impairments, anxiety, and depressive symptoms present months after the infection.

The authors of the Lancet study defined Post-COVID as “the next public health disaster in the making”. Considering the actual trend, Post-COVID is projected to have a disastrous impact on disability, healthcare costs, and lost productivity. The WHO states that it is difficult to predict how long Post-COVID will last for any given patient.


In my experience, two months after the onset of the strongest symptoms and five months after the infection, major cognitive difficulties have attenuated and I could slowly restart working. But somatic complaints such as fatigue and pain still linger; what if had a physically challenging job? Yet, my daily functioning has been disrupted: I had to re-arrange and reduce my working schedule, I had to give up volleyball, which has been an integral part of my physical activity routine and personal identity since I was a child.


Furthermore, reliable diagnostic biomarkers for Post-COVID, such as the result on a specific blood test for instance, are still unavailable; thus, I remain only with a probable clinical diagnosis that could be reached only through a long, burdensome, and expensive path of exclusion of other potential conditions.


Research perspectives


The unavailability of diagnostic biomarkers is a consequence of our lack of understanding of the underlying biological mechanisms of Post-COVID, further precluding the development of effective treatment strategies. Preliminary hypotheses and data point toward the activation of the immune system, which is the body’s main defence against infections from viruses and bacteria. In Post-COVID, the immune system activity seems unrestrained by the failure of breaking mechanisms such as cortisol (known as the ‘stress hormone’) or triggered by the awakening of latent virus, producing chronic inflammation; the author of a recent study stated that “the bodies of people with Long-COVID are actively fighting something”.


Photo by Louis Reed on Unsplash

There is an urgent need for further research on Post-COVID, measuring not only physical symptoms but also neuropsychiatric consequences, identifying its underlying pathophysiology and the segments of the population at higher risk. Such effort may also deliver useful insights for other fields. For instance, deciphering Post-COVID biological mechanisms may be relevant for psychoneuroimmunology, which studies how immuno-inflammatory dysregulations impact the development of mental disorders, and how such pathways could be targeted and modulated to ameliorate mental health.


I am personally involved in such lines of research. At Amsterdam UMC, I am co-PI, together with my colleague Femke Lamers, of the INFLAMED clinical trial testing the efficacy of anti-inflammatory add-on in the treatment of what we call immuno-metabolic depression, a form of depression characterized by signs and symptoms very similar to those I experienced such as inflammation, fatigue, and leaden paralyses (feeling that the limbs are weighed down).


These days, I’m returning to my work at INFLAMED with the only useful insight I distilled from this otherwise very difficult period: a renewed awareness of the role of immune-related mechanisms in shaping our somatic and mental health.


Photo by Külli Kittus on Unsplash

Header image by Georg Eiermann on Unsplash

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