This is a question that I am asked more frequently by patients, friends and colleagues as we go into the second year of the Covid pandemic. Not surprising, since more than 100 million people will be asking themselves this question over the next year!

How can that be? Current research estimates at least 1 in 10 people with Covid will have prolonged symptoms that continue more than 6 months. This condition has been called “long Covid.” The CDC estimates that nearly 1 in 4 Americans have had Covid by January and the WHO estimates that more than 1 in 10 people globally have had COVID by last October. These estimates translate to a minimum of 8 million Americans and 100 million people globally that will develop long Covid, with further growth depending on how the pandemic plays out.

Since fall 2020, there have been a number of insightful published studies that give us insights into what people are experiencing. Follow-up data from patients in Wuhan China highlights that if you are sick enough to be hospitalized, you have a 70%+ chance of having significant symptoms six months later. Data published in the Lancet shows:

• Fatigue and post exertional malaise were experienced by more than 70% of people.
• Brain fog, headache and memory were experienced by more than 50% of people.
• Sleeping problems, shortness of breath and palpitations were experienced by more than 40% of people.

These symptoms are remarkably similar to those experienced by patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) and patients who have had chronic Lyme / tick-borne disease. As a result, many of the clinical and research insights from those areas should prove to be extremely useful for long Covid patients. 

The complication is that those 2 areas have been historically extremely controversial in medicine, with many critics doubting the existence of those conditions and attributing it to psychological issues instead! Patients with both of these conditions have historically experienced significant trauma because their symptoms were not accepted as valid and downplayed by a majority of clinicians. This has started to change… Very slowly. The National Academy of Medicine validated the research behind ME/ CFS in 2015 with a seminal report. Similarly, the Department of Health and Human Services helped to endorse the existence of chronic Lyme in a critical report in 2018. 

The research in these 2 areas, along with the initial first wave of research into long Covid shows there are 3 potential mechanisms that could be contributing to symptoms:

Persistent chronic infection – the virus is still active and replicating, although it may be at a level that is difficult to detect. This is a concept proved to be highly controversial in the infectious disease community when it came to Lyme and triggered the so-called “Lyme Wars”, even though animal and human data in the last few years have conclusively demonstrated that infections can persist in humans despite prolonged antibiotics. It will be important that researchers do not bring pre existing biases and downplay this potential mechanism.

Persistent inflammation, autoimmunity that results in tissue destruction in the body including blood vessels and the brain through direct damage or through activation of other mechanisms such as blood clotting. It may be that the viral infection is gone but the body’s response to the prior infection cannot be readily turned off. If there is tissue destruction in the brain, this can create a whole host of unexplained symptoms that can be readily interpreted as psychiatric symptoms. Patients can be told “it is in their head” and indeed it is, but it is through a biologic cause rather than a psychiatric one.

Reactivation of latent or stealth infections. There are multiple infections such as Lyme, Epstein Barr or herpes viruses that can be dormant in the body and when the immune system weakens, they may be reactivated. Determining this potential mechanism requires careful testing and good clinical judgment.  

Because of these mechanisms, there are likely to be 3 major categories of treatments that could be helpful to patients with long Covid. They include: 

• Treatment of infections both against Covid and any latent or stealth infections.
• Support of the immune system and treatment of potential immune dysregulation and autoimmunity with pharmaceuticals and nutraceuticals. 
• Addressing inflammation, autoimmunity and clotting with appropriate interventions.

Proper research in this area will be critical. The US Congress funded more than 1 billion of research for Long Covid in December 2020 and in late February 2021 the National Institutes of Health announced the details on the first wave of research that will be funded including research that will explore how integrative medicine approaches can help.

The ME/CFS experience has also shown us that avoiding setbacks is a critical component of treatment.  Many people with post exertional malaise, cannot recover quickly from exertion and exercise because of problems with their mitochondrial metabolism. The best intended episode of over-exertion can lead to “crashing” the next day and potential permanent damage to the mitochondria. Patients need to be taught how to understand their “energy envelope” and to NOT try to exercise their way out of fatigue.

What can you do today if you think you have long Covid? I have 3 practical suggestions:

1. See a clinician who has experience and capabilities in fatiguing illnesses, such as ME/CFS or chronic infections such as Lyme and Bartonella. This has not been an area in which most primary care practitioners have had training so seeing a specialized clinic is the answer. Ideally this clinician would be connected to the upcoming NIH cohort studies or other clinical networks on Covid. While there is no FDA approved treatment it does not mean that healing cannot occur with the assistance of appropriate care. If you can’t find someone locally, telehealth is always an option. 
2. Be prepared to advocate for yourself. Since there are no immediate answers or approved protocols for post Covid, the clinician will need to bring their best clinical judgment and you need to articulate your values and preferences. Avoiding nihilism is essential – there can be interventions with a safe track record that can fall in the category of good clinical judgment. It is OK to do a “N of 1” trial with interventions that have a safe track record. Getting enrolled in a clinical study is another option. Don’t wait for “approved” recommendations to get converted into formal health policy before you take action because you will be waiting a long time. For example, the potential benefit of Vitamin D in the prevention and treatment of Covid has been documented in research since the early stages of the epidemic, but official US policy is still silent on the use and benefit of Vitamin D long after most of the world has adopted a policy promoting Vitamin D.
3. Maintain hope! The natural history of viral induced fatiguing illnesses is that a majority of people do recover within the first year. There is more focused research on Covid than has happened on any other major illness in our lifetime. The vaccine came in a record time of 12 months from sequence to delivery and hopefully by this time next year, there will also be record new insights and treatments into post Covid.

References:

1.   Huang et al. 6 month consequences of Covid-19 in patients discharged from hospital: a cohort study. Lancet January 2021 http://doi.org/10.1016/S0140-6736(20)32656-8

2.   David et al. Characterizing Long Covid in an International Cohort: 7 months of symptoms and their impact: MedRxiv https://doi.org/10.1101/2020.12.24.20248802

3.   Tremblay M, Madore C et al. Neuropathobiology of Covid 19: The role for Glia. Front. Cell. Neurosci., 11 November 2020. https://doi.org/10.3389/fncel.2020.592214

4.   Bergamaschi et al. Early immune pathology and persistent dysregulation characterize severe Covid-19. MedRxiv preprint.  https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3757074

5.   Wang et al. Diverse Functional Autoantibodies in Patients with Covid 19.  https://doi.org/10.1101/2020.12.10.20247205

6.   Naess H, Sundal E, Myhr K-M, Nyland HI. Postinfectious and chronic fatigue syndromes: clinical experience from a tertiary referral center in Norway. In Vivo. 2010;24(2):185-188. http://iv.iiarjournals.org/content/24/2/185.long

7.   Lyons D, Frampton M, Naqvi S, Donohoe D, Adams G, Glynn K. Fallout from the COVID-19 pandemic – should we prepare for a tsunami of post-viral depression? . Ir J Psychol Med. 2020;1-6. http://doi:10.1017/ipm.2020.40