Framing Post-COVID in an interdisciplinary way: neurological approaches

Long and post-COVID are complex diseases requiring interdisciplinary cooperation, explains Prof. Dr. Peter Berlit at the DGIM Congress in Germany.

75% incidence of long and post-COVID after severe infection

According to Prof. Berlit, the prevalence of long and post-COVID should not be underestimated.1 Data from 1.2 million COVID sufferers from 22 countries gave an indication of symptoms that persist for at least three months after the acute infection. These include at least one symptom of fatigue, persistent respiratory problems or cognitive impairment. At least one of these symptoms was found in 6.2% of the people studied; the median duration of symptoms was 9 months in hospitalised people and only 4 months in non-hospitalised people.2

Similarly, the incidence of long- and post-COVID differs depending on the intensity of the acute infection: if this was mild, 10-20% suffer from long-COVID. However, if the COVID-19 course was severe, three quarters of this group had post-COVID-19 symptoms.3,4

However, these sequelae can also last significantly longer than 9 months. The population-based Linköping COVID-19 study from Sweden (DOI: 10.1016/j.lanepe.2023.100595) is the first study to conduct a 2-year follow-up in people affected by long-COVID.5 At the beginning of the longitudinal study, 40% (185 of 433) subjects had symptoms four months after the initial COVID infection. Two years later, 84% (139 out of 165) were still experiencing at least one symptom or persistent limitations in daily life. These were mainly cognitive, sensorimotor and fatigue symptoms, but no significant differences were found between the main disease requiring intensive care and the main disease not requiring intensive care.5

Neurological manifestations in post-COVID

In his lecture, Prof. Berlit discussed the neurological manifestations of post-COVID and named the following:

According to Prof. Berlit, cognitive deficits after COVID-19 affect neurological executive functions, i.e. planning thinking, concentration, memory and/or language performance. These long-term symptoms can also occur after mild corona.1

The first systematic review on post-COVID examined 57 studies with over 250,000 COVID-19 survivors, 79% of whom were hospitalised. Of these, 54% had long-term symptoms, most commonly pulmonary and neuropsychiatric symptoms.6

Up to one year after a Corona infection, there is an increased cardiovascular risk, the probability of a stroke, for example, is increased by a factor of 4, and the risk of suffering atrial fibrillation is also 10 times higher.7

What risk factors increase the likelihood of developing post- or long-COVID infection?

There are some factors that increase the risk of developing post- or long-COVID infection. These include biographical factors (female gender, middle age, Caucasian ethnicity) as well as pre-existing conditions such as bronchial asthma, poor mental health, diabetes mellitus, hypertension and obesity. In addition, the severity of corona infections influences the prevalence of long-term symptoms: more than five acute symptoms, a high acute viral load, low baseline IgG against SARS-CoV-2, diarrhoea and a negative vaccination status tend to result more often in a post-COVID infection. Autoimmune diseases, allergic diseases and depression in particular are significantly associated with long-COVID. This is also the case when the severity of acute SARS-CoV-2 infection is taken into account.1

However, according to Prof. Berlit, care must always be taken when diagnosing post- or long-term COVID to distinguish it from "post-intensive care syndrome" (PICS). This is because patients with an intensive care course during an acute infection can also show clinical symptoms in the context of PICS. In this case, there are also cognitive deficits, muscle weakness in the sense of critical illness polyneuropathy and myopathy (CIP/CIM), post-traumatic stress disorder (PTSD), depression and anxiety disorders.1

Interdisciplinarity is essential in the treatment of long COVID

The symptoms of long-COVID are manifold, which is why their therapy cannot be covered by medical specialists from one single discipline. Therefore, Prof. Berlit pleads for interdisciplinary collaboration, especially between the fields of pneumology and neurology, with the inclusion of psychosomatic experts. This collaboration should manifest itself in a dual treatment concept that covers both somatic and psychological aspects. Ideally, this should be supported by an individually adapted physical stress programme and neurocognitive training. Telemedical patient care is also essential for those affected by long- or post-COVID. Regarding the pathophysiology of post-COVID symptoms, Prof. Berlit sees neurotransmitter-mediated changes, immune-mediated mechanisms, post-infectious persisting coagulopathy, and psychological factors as particularly relevant for further research.1

Here, Prof. Berlit emphatically mentioned the Post-Corona Virus Immune Treatment Trial,8 which will investigate the effect of methylprednisolone vs. placebo in patients with cognitive deficits, and the results of which he is extremely curious about. Further controlled studies on treatment and prevalence of long and post-COVID symptoms are essential in his view.

References:
  1. Session in German only: Berlit, Peter. "Post-Covid-Erkrankung und ihre Facetten aus neurologischer Sicht". Session: Post-Covid-Erkrankung und ihre Facetten. DGIM 2023. 
  2. Hanson SW, Abbafati C, Aerts JG et al. Global Burden of Disease Long COVID Collaborators. Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021. JAMA 2022 Oct 10. https://jamanetwork.com/journals/jama/fullarticle/2797443
  3. Augustin M. et.al,, Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study, Lancet Reg Health Eur. 2021
  4. Akbarialiabad H et.al., Long COVID, a comprehensive systematic scoping review. Infection. 2021
  5. Wahlgren C, Forsberg G, Divanoglou A et al. Two-year-follow-up of patients with post-COVID-19 condition in Sweden: a prospective cohort study. Lancet Reg Helath Eur 2023 Feb 24; 100595 doi:10.1016/j.lanepe.2023.100595. Online ahead of print. https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(23)00013-3/fulltext
  6. Groff D, Sun A, Ssentongo AE et al. Short-term and Long-term Rates of Postacute Sequelae of SARS-CoV-2 Infection: A Systematic Review. JAMA Netw Open 2023; 4(10): e2128568. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2784918
  7. Xie Y, Xu E, Bowe B et al.: Longterm cardiovascular outcomes of COVID-19. Nat Med 2022. https://doi.org/10.1038/s41591-022-01689-3
  8. Link in German only: https://cfc.charite.de/klinische_studien/nksg/studie_pocovit/