Long-Haul COVID Syndrome

By Dr. David M. Brady and Danielle Moyer

It has been over a year since the COVID-19 virus unleashed a pandemic onto the world. We have witnessed the catastrophic effects of the virus on the individual, varying case-by-case. Some were asymptomatic, some only got mildly sick, some had severe cases with acute illness or respiratory distress syndrome, and some sadly succumbed to the disease. A year later, there exists a large group of COVID victims that have not been as recognized as they so rightfully deserve – the COVID long-haulers.

“Long-haulers” refers to those who had COVID-19 and have recovered from the acute symptoms of the virus. Yet, they experience long-term symptoms that extend far beyond the two-week viral infection period or what the “normal” time of recovery would be. These symptoms could last for weeks or, in some cases, more than 6 months after initial  COVID-19 infection [1].

Long-haul COVID is not well-defined or understood, as research limitations can only evolve as time progresses. The symptoms are sometimes vague and nonspecific, and the variety and commonality of them make it hard to make a confirmed COVID-related diagnosis. These non-specific symptoms are often described as intermittent, where improvement in health is quickly followed by recurring suffering [1].

I have witnessed these long haulers in my medical practice and personal life. In fact, my lovely wife is one of them.

At the World Health Organization’s international “Long-COVID Forum” on December 9, 2020, it was proposed that probably more than five million people on the planet have long-haul COVID. “Many of (the five million) are living and suffering in the U.S.” [1]. One study looked at all the COVID-19 hospitalizations in Bergamo, Italy, and revealed that more than 50% of the patients reported ongoing chronic symptoms significant enough to alter their daily lives months after being infected [2]. A more recent, larger study surveying thousands of patients from 56 countries now suggests that this chronic dysfunction is experienced by an even larger percentage of those who have had COVID than in the Bergamo study. This includes those who never had a positive COVID test despite showing all the hallmark symptoms of COVID-19. In fact, 96% of respondents in this study had some remaining symptoms after 90 days [3].

King’s College in London created a self-reporting app from the health-sciences company ZOE, where 4 million users in the UK tracked and monitored their COVID-symptoms over time. Since March 24, 2020, data from this app and similar studies have been used to study the patterns and durations of COVID-19 symptoms. The researchers state that their understanding of long-haul COVID is still in the early stages, but provided the following as the most common reported symptoms cited in various studies from a few days to a few months post infection [4].

• Excessive fatigue and exhaustion (the most commonly reported long-haul symptom)
• Breathlessness
• Headache
• Insomnia
• Muscle fatigue/pains
• Chest pains
• Persistent cough
• Loss of taste and smell
• Intermittent fevers
• Skin rashes
• Post-exercise malaise (overtraining leads to symptoms coming back)

There are some fewer common symptoms that have been self-reported by long-haul sufferers that have yet to be confirmed in studies [4]…

• Hearing problems
• Cognitive issues, such as “brain fog”
• Mental-health problems
• Hair loss

In my practice, I have seen my long-haul patients with the symptoms above, as well as specifically…

• Inflammatory pain. Predominantly in the small joints of the hands, fingers, and wrists, as well as the rib cage
• An electric, buzzing sensation in the body, which is quite strange and unique to COVID-19
• Excessive fatigue
• Tachycardia, or intermittent, rapid heartbeat

For the patients who have experienced erratic heartbeats, some echograms and stress tests of patients show seemingly normal function. However, despite its label as a respiratory disease, we know that the virus can also impact organs beyond just the lungs. It has a particular affinity for the heart. After COVID-19, one can see a physical or physiological change to the cardiac muscle, or myocardium. Damage to the heart from the virus can help to explain some of the frequently reported long-haul COVID symptoms, such as shortness of breath, chest pain, and heart palpitations [4].

The King’s College self-reporting app interestingly found that a person’s COVID-19 experiences during the active two-week viral stage can correlate to how likely they are to experience long-haul COVID symptoms as well. For example, if a person experienced a “persistent cough, hoarse voice, headache, diarrhea, loss of appetite and shortness of breath in the first week,” they were two to three times more likely to get long-haul COVID symptoms [4]. The researchers also determined that long-haul COVID syndrome is twice as common in women as in men, and the average age of a long hauler is 45 years old, though young people can be long haulers too. One study from the US found that one in five people between the ages of 18 to 34 years old without preexisting chronic medical conditions reported cases of long-haul COVID after their initial infection [4].

Through self-reporting, these sufferers are demonstrating that long-haul COVID is real and can cause chronic health manifestations. The symptoms can be debilitating, and have been shown to affect mental health, physical function, and ability to work [3].

What are these long-haulers doing? Due to the limited research, the answer can be boiled down to “trying their best”. Often, they find solace in online support groups on Facebook [1]. Here they can share their stories, discuss what has been helping their symptoms, report what hasn’t been helping, and simply, feel less alone in their experiences. There is one Facebook support group called “Long Covid Support Group'' with 35.1K members as of February 2021 [5] . 

There are multiple different theories on the origin of long-haul COVID syndrome. Most agree that it is not an active COVID-19 infection, but rather it is a re-programmed immune response that occurred because of the virus. The initial infection of the virus changes immunity patterns, which can put someone into a more aggressive immunity stance. Some have even speculated (and I would not be surprised if it were true) that the virus has created an autoimmune attack of the body against its own tissues. The exact pathophysiology is unknown.

Currently, there are no proven treatments for long-haul COVID syndrome. We are learning and rushing to figure out the best way to  provide relief to those who are suffering. The sheer number of long haulers is terrifying and will only continue to grow,  indicating that this pandemic will remain in us much longer than hoped. Potentially, ailments may remain for a lifetime in those affected. The toll this takes on our healthcare system is incalculable at this time.

Right now, I want to share what I am using with my patients and my wife to help with some of their long-haul symptoms. This is not intended to be direct advice on what to do or what to take. One must really work with their doctor or healthcare provider. Instead, I offer these suggestions to discuss with your provider as options to explore in the hopes that they may help you.

Studies have shown that it is possible for the SARS-CoV-2 virus to directly impair mitochondrial energy metabolism by targeting the action of oxygen availability and utilization in the cell [6]. This can cause a breakdown in energy production, particularly around a pathway involving NAD+, or nicotinamide adenine dinucleotide [6-10].

To address this, we are using NAD+ precursors to rebalance this energy biochemistry and respiration in the body at a cellular level. This includes administering products containing nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN) to assist in mitochondrial production. Other well-known nutrients that support mitochondrial energy production are Co-enzyme Q10 (CoQ10) and ribose. CoQ10 is especially helpful for the cardiac muscle, which is beneficial for the rhythm or beating of the heart.

When a patient is experiencing shortness of breath, lung irritation, or respiratory issues, we are using nebulized glutathione or oral glutathione, or a medicinal peptide called Thymosin-Alpha-1. Thymosin-Alpha-1 is a prescription peptide that has been previously used in autoimmune conditions and in immune deregulatory symptoms. Essentially, it talks to the immune system to get it back on track, quelling any hyper response of the immunity system.  

If you are a long hauler suffering, I hope this article serves as acknowledgement and recognition of you. Many of us in the medical and health fields are doing everything we can to figure this out and trying to find viable ways to make your experience better. In the meantime, I highly encourage you to get involved with the online support groups. You will learn from others and will not feel so isolated in your experience.

Please listen to the video I made on “Long-Haul” if you have any interest in the topic, knowing that it was recorded with all of those who are suffering in mind: https://www.youtube.com/watch?v=lHewi7W1Qps&mc_cid=a542e9bc89&mc_eid=afada787fe

To read more information about Long-Haul COVID, please see this excellent article in Scientific American: https://www.scientificamerican.com/article/the-problem-of-long-haul-covid/

Again, if any of you are suffering from COVID in the short or long term, we are thinking of you. 

References: 

1. Barber C. The Problem of ‘Long Haul’ COVID. Scientific American website. https://www.scientificamerican.com/article/the-problem-of-long-haul-covid/. Published December 29, 2020. Accessed February 10, 2021. 
2. Harlan C, Pitrelli S. Italy’s Bergamo is calling back coronavirus survivors. About half say they haven’t fully recovered. The Washington Post website. https://www.washingtonpost.com/world/2020/09/08/bergamo-italy-covid-longterm/?arc404=true. Published September 8, 2020. Accessed February 10, 2021. 
3. Davis HE, Assaf GS, McCorkell L, et al. Characterizing Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact. medRxiv. Published online December 27, 2020:2020.12.24.20248802. doi:10.1101/2020.12.24.20248802
4. Sleat D, Wain R, Miller B. Long Covid: Reviewing the Science and Assessing the Risk. :18.
5. Long Covid Support Group. Facebook website. https://www.facebook.com/groups/longcovid/. Accessed February 10, 2021. 
6. Stefano GB, Ptacek R, Ptackova H, Martin A, Kream RM. Selective Neuronal Mitochondrial Targeting in SARS-CoV-2 Infection Affects Cognitive Processes to Induce ‘Brain Fog’ and Results in Behavioral Changes that Favor Viral Survival. Med Sci Monit. 2021;27:e930886-1-e930886-4. doi:10.12659/MSM.930886
7. Omran HM, Almaliki MS. Influence of NAD+ as an ageing-related immunomodulator on COVID 19 infection: A hypothesis. Journal of Infection and Public Health. 2020;13(9):1196-1201. doi:10.1016/j.jiph.2020.06.004
8. Kouhpayeh S, Shariati L, Boshtam M, et al. The Molecular Story of COVID-19; NAD+ Depletion Addresses All Questions in this Infection. Published online March 23, 2020. doi:10.20944/preprints202003.0346.v1
9. Heer CD, Sanderson DJ, Voth LS, et al. Coronavirus infection and PARP expression dysregulate the NAD Metabolome: an actionable component of innate immunity. bioRxiv. Published online October 6, 2020:2020.04.17.047480. doi:10.1101/2020.04.17.047480
10. Miller R, Wentzel AR, Richards GA. COVID-19: NAD+ deficiency may predispose the aged, obese and type2 diabetics to mortality through its effect on SIRT1 activity. Medical Hypotheses. 2020;144:110044. doi:10.1016/j.mehy.2020.110044

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