Long COVID: what are the scientific facts? (with Carmen Scheibenbogen)
Guest immunologist Carmen Scheibenbogen discusses long COVID and ME/CFS, exploring their definitions, subtypes, and potential autoimmune mechanisms. She also shares insights on effective communication, the role of psychological support, and current research into treatments and prevention.
Deep Dive Analysis
17 Topic Outline
Defining Great One-on-One Conversations
The Problem of Cached Thoughts and Expert Bias
Debates vs. Collaborative Intellectual Exchange
Cultivating a 'Scout Mindset' and Positive Conversational Vibe
Impact of Communication Medium and Emotional Vulnerability
Epstein-Barr Virus (EBV) Reactivation in Long COVID
Understanding Post-Exertional Malaise (PEM) and ME-CFS
Historical Misconceptions and Psychosomatic Views of ME-CFS
Defining Long COVID and Identifying Subtypes (ME-CFS, POTS)
Challenges in Clinical Trials and Biomarker-Driven Treatment
The Role of Psychological Support and Pacing in Management
Improving Physician Awareness and Treatment Guidelines
Promising Mechanism-Targeted Therapies for Long COVID/ME-CFS
Current Prevalence, Risk Factors, and Progression of Long COVID
Chronic Lyme Disease and Post-Infectious Illnesses
Practical Advice for Patients and Loved Ones
The Future of Autoantibody-Mediated Treatments
9 Key Concepts
Building a Tower Together
This metaphor describes a collaborative conversation where both participants contribute new ideas, like laying bricks, enabling them to reach new insights and understanding that neither could achieve alone.
Cached Ideas
These are pre-thought, memorized ideas that individuals, especially experts, tend to repeat in conversations. Relying on cached ideas hinders real-time thinking and prevents the generation of new insights, making conversations less engaging and productive.
Scout Mindset
As described by Julia Galef, this is an approach to conversation where participants are genuinely open to understanding the world and what is true. It contrasts with a 'soldier mindset,' where the goal is to convince others or win an argument.
Social Monitoring
This refers to the degree to which individuals pay attention to and evaluate the social situation during a conversation. It involves being aware of how others are feeling, how one is being perceived, and integrating these cues into the interaction.
EBV (Epstein-Barr Virus)
A common herpes family virus, almost universally present in adults, known for its ability to trigger autoreactivity. It can reactivate after other infections, such as SARS-CoV-2, and is a leading candidate for triggering autoimmunity in a subgroup of Long COVID patients.
PEM (Post-Exertional Malaise)
A hallmark symptom of ME-CFS and frequently seen in Long COVID, where even minor physical or mental exertion leads to a severe worsening of all symptoms. This debilitating crash can last for days and is thought to stem from inadequate muscle perfusion and energy production.
ME-CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome)
A severe, complex, and often chronic post-infectious disease characterized by profound fatigue, post-exertional malaise, cognitive impairment (brain fog), and orthostatic intolerance. Historically, it was often misdiagnosed as a psychiatric or psychosomatic condition, hindering research and effective treatment development.
POTS (Postural Tachycardia Syndrome)
A condition characterized by a disturbed cardiovascular regulation, often part of a broader autonomic nervous system dysfunction. Patients experience symptoms like dizziness and a significant increase in heart rate upon standing, and it represents a distinct subgroup within Long COVID.
Pacing
A crucial self-management strategy for patients with ME-CFS and Long COVID to prevent post-exertional malaise. It involves strictly limiting daily activities and making deliberate decisions about energy expenditure to stay within one's very restricted energy envelope.
15 Questions Answered
Often, participants are not on compatible pages, either discussing different things or having different goals. A common issue is people repeating 'cached ideas' they've already thought about, rather than thinking in real-time.
The ideal goal is to think together and come up with new thoughts, creating something neither person could have created alone, which fosters the biggest learning.
Debates typically involve participants repeating pre-thought 'cached thoughts' and are often performance-oriented, with little openness to changing minds. They foster a 'soldier mindset' of winning rather than a 'scout mindset' of understanding.
Before a challenging conversation, ensure both parties are in a 'scout mindset' (seeking truth, not winning). This may involve lowering the other person's defenses or reflecting on one's own defensiveness.
COVID-19 can reactivate the Epstein-Barr virus (EBV), a common herpes virus, which then induces post-infectious symptoms, potentially triggering a subgroup of Long COVID cases.
PEM is a severe worsening of all symptoms after even minor physical or mental exertion, lasting for days. It is the key symptom of ME-CFS and is thought to be caused by inadequate muscle perfusion and energy production during exertion.
For decades, ME-CFS was often misdiagnosed as a psychosomatic illness, leading to harmful recommendations like graded exercise therapy. This view hindered research, but now it's recognized as a severe, complex disease with biological mechanisms.
Many symptoms overlap, including fatigue, brain fog, and orthostatic problems. Depending on the diagnostic criteria used, between 20% to 50% of Long COVID patients meet the criteria for ME-CFS.
Many early trials were too broad, including all patients with a post-COVID definition without defining specific subgroups or using biomarkers. This likely led to missing potential benefits for specific patient subgroups.
Besides ME-CFS (about one-third of patients), another well-defined subgroup is Postural Tachycardia Syndrome (POTS), affecting about 20% of patients. Roughly 50% of patients currently have no clear diagnostic criteria but may include those with severe neurocognitive impairment.
A meta-analysis in 2023 estimated the prevalence of Long COVID to be about 5% of the population, meaning one in twenty people have lingering symptoms.
Yes, vaccination reduces the risk of Long COVID by about 50%, and also protects against more severe courses of COVID-19.
Long COVID can heal, especially in the first few months, but after six months, the risk of remaining ill increases. For ME-CFS, the risk of remaining ill is very high (90% or higher), with only a small percentage recovering over several years.
Hand grip strength is an indicator of muscle strength and metabolic health. In Long COVID, a low hand grip early in the disease is a prognostic factor for a severe and chronic course.
Long COVID is thought to be linked to an overactive immune system, which is more common in younger individuals and females. This is the opposite of what causes death in severe acute COVID, where a weaker immune system (more common in older males) increases mortality risk.
20 Actionable Insights
1. Cultivate Scout Mindset
Before challenging conversations, ensure both parties are in a “scout mindset” (seeking truth) to enable productive dialogue, rather than a “soldier mindset” (trying to win).
2. Lower Conversational Defenses
If your conversation partner is defensive, actively work to make them feel at ease and connected, showing you are not an adversary, to foster openness.
3. Self-Assess Your Defensiveness
If you find yourself in a “soldier mindset,” reflect on the root causes of your defensiveness and whether you truly wish to engage in the conversation.
4. Aim for Shared New Thoughts
In intellectual conversations, strive to collectively generate new ideas and reach conclusions neither participant could have achieved alone.
5. Seek New Angles from Experts
When conversing with experts, encourage them to explore different perspectives or delve deeper into topics, rather than simply reiterating pre-rehearsed information.
6. Embrace Emotional Vulnerability
Allow for emotional vulnerability in intellectual discussions, especially on sensitive topics, as it enables the expression of true views and facilitates genuine progress.
7. Optimize Conversational Settings
Consider environments that reduce direct eye contact, such as talking in a car or a dark room, to potentially foster greater emotional vulnerability and deeper exchanges.
8. Prioritize Conversational Vibe
Recognize that the overall “vibe” and tempo of a conversation are crucial for intellectual exchanges, aiming for a shared wavelength.
9. Utilize Micro-Expressions
Actively observe your conversation partner’s micro-expressions and reactions to gauge their understanding and engagement, allowing for more efficient communication.
10. Learn by Teaching
Engage in teaching or explaining subjects you know well, as this process helps compress information, clarify relevance, and improve your ability to articulate complex ideas.
11. Practice Pacing for PEM
If experiencing post-exertional malaise (PEM), strictly limit daily activities to a set duration (e.g., one hour) and carefully plan how to use that time to prevent symptom crashes.
12. Seek Supportive Psychotherapy
For ME/CFS or Long COVID, pursue supportive psychotherapy to help manage daily challenges, emotional distress, and learn coping strategies like pacing, avoiding therapies that promote overexertion.
13. Treat Specific Symptoms
Work with your physician to address individual Long COVID or ME/CFS symptoms like sleep disturbance, pain, or orthostatic intolerance using available and licensed medications.
14. Inform Your Physician
Proactively share reputable diagnostic and treatment guidelines for Long COVID or ME/CFS with your primary care physician to ensure they have access to the latest information.
15. Engage with Patient Organizations
Connect with well-informed patient organizations for Long COVID or ME/CFS to access information, support networks, and strategies for managing the disease’s social and practical aspects.
16. Consider Clinical Trial Participation
Participate in clinical trials for Long COVID or ME/CFS to contribute to scientific understanding, potentially access new treatments, and help advance the search for cures.
17. Mask for High-Risk Individuals
If you have a history of Long COVID or an immunodeficiency, consistently wear masks in public transport or crowded settings to significantly reduce the risk of reinfection and symptom worsening.
18. Get Vaccinated for COVID
Receive COVID-19 vaccination, especially if in a risk group (e.g., over 60), to reduce the severity of infection and lower the chance of developing Long COVID by approximately 50%.
19. Vaccinate with Long COVID/ME-CFS
If you have Long COVID or ME/CFS, get vaccinated for COVID-19 to mitigate the risk of disease deterioration from subsequent infections.
20. Strategic Masking for Healthy Individuals
For immunologically healthy individuals, wear a mask in crowded public transport or when in contact with visibly infected people, but avoid constant masking to maintain immune system training.
9 Key Quotes
The way I view conversations are that you're trying to build a kind of tower together.
Uri
My favorite episodes are always the ones where you can tell that the guest is in real time thinking and responding.
Uri
If you want the thoughts they've already had about the thing, go watch their lecture. But if you're going to watch a podcast episode with them, you want this different thing.
Spencer Greenberg
Friends don't let friends think alone.
Uri
To me, the pinnacle of good intellectual conversation matches what you're describing, like building a tower together, where you actually don't know where you're going to get by the end of the conversation.
Spencer Greenberg
I think a debate sets up like almost the exact wrong setting where you're trying to win. You're not open to new ideas. You're not open to changing your mind.
Spencer Greenberg
Even though it's an intellectual conversation, the emotional vulnerability... is really important.
Uri
ME-CFS is still not that well known among physicians. Before the pandemic, there were, I think, many, many physicians worldwide who have never, ever heard of ME-CFS.
Carmen Scheibenbogen
The risk of dying, the older you are, was most likely due to a weaker immune system... And the opposite is true for long COVID. We have the younger patients with a stronger immune system, the females.
Carmen Scheibenbogen
2 Protocols
Pacing Strategy for Post-Exertional Malaise
Carmen Scheibenbogen- Understand that you have a very limited amount of activity possible per day.
- Make conscious decisions about how to use your limited active time (e.g., one hour per day).
- Learn to say 'no' to activities, even to loved ones, to avoid overexertion.
General Advice for Long COVID/ME-CFS Patients
Carmen Scheibenbogen- Inform your physician about available guidelines for diagnosing and treating ME-CFS and Long COVID (e.g., from Charité's website).
- Work with your physician to prioritize and treat the most worrisome symptoms step-wise (e.g., sleep disturbance, pain, orthostatic intolerance).
- Practice self-management strategies like pacing to avoid post-exertional malaise.
- Explore helpful techniques such as certain breathing techniques and relaxation.
- Seek information and support from well-informed patient organizations and self-help groups.
- Consider participating in clinical trials to contribute to research and potentially access future treatments.