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COVID Long Haulers: Symptoms and Connections to Post Viral Fatigue and Organ Damage

December 22, 2020
Long COVID is not easily defined. Here's what clinicians need to know about patient subsets, potential organ damage. Plus, how post COVID fatigue resembles CFS and other symptoms seen in previous infectious disease outbreaks.

with medical review by Don L. Goldenberg


Defining Long COVID: 3 Distinct Patient Groups

The terms “COVID long haulers,” “long COVID,” and “Post COVID Syndrome,” have all been used interchangeably in recent months to describe individuals who have been infected with the SARS-CoV-2 and continue to experience symptoms after “recovery.” However, these terms may be misleading to healthcare providers, patients, and even the media as they represent three different patient subsets with prolonged symptoms, usually defined as greater than 1 month after COVID-19 infection.

As described in the fast-tracked book by PPM Editorial Board Advisor Don L. Goldenberg, How the COVID-19 Pandemic is Affecting You and Your Healthcare (Armin Lear Press), these subsets include:

  1. Critically-ill patients, almost all who have been admitted to intensive care, who, are expected to have a lengthy recovery period (often months) and may have permanent organ damage, particularly in the lung.
  2. An undetermined number of patients, following mild or severe infection, who have organ damage/dysfunction, such as myocarditis or an encephalopathy. The long-range consequences are unclear. (More on cardiovascular risks in COVID long haulers)
  3. Many patients, in some series estimated up to 10%,1 have prolonged, multisystem symptoms with no evidence of organ damage or dysfunction. These patients most often have severe exhaustion, headaches, myalgias, and mood and cognitive disturbances with normal physical and laboratory findings. This is the subset experiencing symptoms most similar to post-viral fatigue syndrome (PVFS), chronic fatigue syndrome (CFS) – also termed benign myalgic encephalomyelitis (BME) in the UK, fibromyalgia and other related, poorly understood disorders associated with chronic fatigue and pain. In these conditions, there has been no strong evidence for organ damage or persistent and significant immune/inflammatory abnormalities.

The confusion and controversy playing out online and among support groups for the third subset of patients mirrors the misunderstandings of CFS over the past 40 years in both the United States and the United Kingdom.2,3

COVID long haulers may be broken into three patient groups depending on organ damage and other key symptoms. (iStock)

What we do know, so far, is that this broad group of COVID-19 survivors does not seem to fully recover and that there are significant differences between those who experience organ damage and those who do not.

We also know that, while COVID-19 has killed more men than women, long haulers seem to be predominantly female. Physicians at a Paris Hospital recently reported that among the long hauler patients they treated between mid-May and late July 2020, women outnumbered men 4:1 – the same rate by which women outnumber men in CFS.1

As the medical community works to understand the acute stage of COVID-19, long-term consequences pose a further challenge for understanding how this virus persists. Here, we look at what clinicians and researchers are finding in COVID-19 patients with regard to potential organ damage following COVID-19 infection and how chronic post-viral fatigue is playing out.


Severe Post COVID Syndrome and Organ Damage

As noted above, some patients with mild or moderate COVID infection do develop organ damage (subsets 1 and 2), most notably myocarditis or an encephalopathy. In some patients with sustained organ damage or dysfunction, there may be a vascular connection, according to William Li, MD, founder of the Angiogenesis Foundation (AF), which is currently dedicated to research on the novel coronavirus, particularly its long-term consequences.4

Dr. Li and an international team of researchers noticed something atypical for a respiratory virus − it was infecting vascular endothelial cells and damaging the endothelium. The team compared autopsies on the lungs of patients who died from COVID-19 with those of patients who died from influenza. The COVID-19 lungs had nine times as many microthrombi as the influenza lungs.

Dr. Li believes there may be three main components at play: microvascular damage, persistent inflammation, which may have an autoimmune component, and neuropathy. It is important to note Dr. Li's findings are based on patients who died of COVID-infection, not those living with long COVID.


Long COVID and Post Viral Fatigue

As noted, up to 10% of patients recovering from COVID infection1 seem to experience prolonged symptoms that appear to resemble PVFS or CFS (subset 3). Clinicians may recall that both fatigue syndromes have connections to prior infectious disease outbreaks. For example:

  • 2003 SARS

o   Doctors observed PVFS in patients after the 2003 SARS outbreak (also a coronavirus), which affected 8,096 people worldwide.5

o   This SARS-CoV virus resulted in reports of PVFS up to 1 year following diagnosis in more than half of recovered patients; the symptoms often occurred with sleep difficulties.5

o   A 4-year follow-up evaluation of people recovering from SARS in Hong Kong found that 40.3% reported chronic fatigue and that 27.1% met the diagnostic criteria for CFS.6

  • 1918 Spanish Influenza

o   There was evidence of high rates of PVFS/CFS after the 1918 influenza A (H1N1) pandemic, with fatigue being the most common long-term symptom.7

  • 2009 Influenza A (H1N1)

o   Researchers in Norway studying the lasting symptoms of this influenza pandemic and found that the infection was associated with a greater than wo-fold increased risk of CFS. The researchers did not observe an increased risk for CFS following vaccination.8

There have also been reports of post viral fatigue in Ebola virus patients. A cross-sectional study estimated that 28% of people who recovered from the Ebola virus experienced unusual fatigue post recovery. Symptoms of Post-Ebola Syndrome also included joint pain, muscle pain, headaches, eye problems, and sleep disturbances. Finally, there have been some reports attempting to associate Epstein-Barr virus (EBV), the human herpes virus that can lead to infectious mononucleosis, with the novel coronavirus and autoimmune response but conclusive data is still needed.9-11

Overlapping Symptoms: Post COVID Syndrome and Post Viral Fatigue Syndrome

Many clinicians and researchers are comparing the post-acute effects of today’s coronavirus with PVFS and CFS. Natalie Lambert, PhD, associate professor and director of the Lambert Lab at the Indiana University School of Medicine, has published in collaboration with Survivor Corps, a long-hauler support group, a Long-Hauler Symptom Survey. The survey includes reports from more than 4,000 COVID-19 patients.12 The most common symptoms her team uncovered were exhaustion (both physical and mental), other cognitive disturbances, headaches, myalgias, dyspnea, gastrointestinal, sleep and mood disturbances.12

These symptoms are similar to those reported in PVFS or CFS. However, dyspnea and loss of taste and smell appear to be much more common in Post COVID Syndrome patients.


Practical Takeaways

While PVFS is not new to the medical community, there is no clear path to treatment. More important, there is still not enough knowledge about the exact causes or repercussions of post-viral fatigue in recovering COVID-19 patients.

Ongoing symptoms reported by those recovering from COVID-19 infection should be taken seriously and addressed accordingly. As stated by Dr. Anthony Fauci in July 2020, “Anecdotally, there’s no question that there are a considerable number of individuals who have a post viral syndrome that really, in many respects, can incapacitate them for weeks and weeks following so-called recovery and clearing of the virus, highly suggestive of myalgic encephalomyelitis/chronic fatigue syndrome.”1

John Brooks, MD, chief medical officer of the CDC’s COVID response team, predicted that “long COVID would affect on the order of tens of thousands in the United States and possibly hundreds of thousands.”13


More on our COVID resource page.

Plus, the January/February 2021 issue of PPM focuses on how to conduct telemedicine exams (and prescribe) for pain, rheumatic disease, and chronic headache. Plus, what to watch for in those recovering from COVID-19 infection, including cardiac risks.



Last updated on: January 5, 2021
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