An estimated 10-40 percent of patients worldwide report experiencing persistent health issues associated with COVID for weeks, months, or even years after recovering from their infection. The condition – commonly called Long COVID – has caused much discussion and debate in healthcare communities worldwide as clinicians and health organizations attempt to determine what constitutes Long COVID, what causes it, and how best to diagnose and treat it.

The official definition of Long COVID is still in flux. Some clinicians consider it symptoms lasting four weeks or more, while others believe symptoms should last three months or longer. We do know that Long COVID can occur in anyone, even otherwise healthy people and those who experienced mild symptoms during their initial COVID infection. All variants of the virus appear to cause Long COVID, though studies have found the occurrence of Long COVID increased slightly as we went from the ‘wild-type’ virus to the Alpha variant. From there, researchers noticed a drop as Delta became the dominant strain (also around the time vaccines became available). Omicron and its descendant, the BA1.12.1 variant appear to cause Long COVID at half the rate of delta, and are not causing the same number of hospitalizations and deaths as earlier variants.

Symptoms of Long COVID

Long COVID can include a wide variety of symptoms that differ from patient to patient, though the most prevalent symptoms are fatigue, dyspnea (or shortness of breath), and brain fog. Many patients report feeling drained, with fatigue increasing dramatically after attempting to perform even simple tasks.

Other commonly reported symptoms include:

• Depression, anxiety
• Loss of smell
• Dizziness
• Coughing
• Hair loss
• Headaches
• Heart palpitations or fluctuations in heart rate (racing, then normalizing)
• Stomach pain
• Diarrhea
• Body and joint aches
• Skin rashes
• Swollen lymph nodes
• Sleep disturbances
• Tingling sensation

What Causes Long COVID?

It’s the million-dollar question: What causes Long COVID? Though there is no definitive answer, there are several strong hypotheses with solid data supporting each theory. Dr. David Strain shared three theories in a recent MDBriefCase webinar, The Other Pandemic – The Impact of Long COVID on Patients.

1. Persistent Viral Load

Much like Shingles, the COVID virus appears able to remain hidden in our bodies – some preferred locations being brain tissue and elsewhere in the nervous system. Studies have also discovered the virus can linger for months within the gut. It’s believed that patients experience local inflammation where the virus hides, e.g. brain tissue, which causes Long COVID symptoms like brain fog and fatigue. It’s also possible that the virus is occasionally releasing into the system – not at levels that would make a person infectious – but enough to cause small blood clots which cause many common Long COVID symptoms.

2. Blood Clots

Patients who had acute COVID experienced a tremendous increase in blood clots – pulmonary embolisms, strokes, and heart attacks all increased during the first waves of the pandemic. As a result, it’s believed Long COVID patients could have an abundance of amyloid-based microclots that could impair blood flow to the lungs and restrict oxygen exchange, and therefore cause some of the breathing problems, cardiac inflammation, and other common symptoms patients experience.

3. Mitochondrial Dysfunction

The COVID virus enters the body through the angiotensin-converting enzyme 2 or ACE2 enzyme. In a healthy human, the ACE2 enzyme is one of the pathways that stimulates mitochondrial assembly. When that pathway is blocked, mitochondria are adversely affected, and because they are the power source of every cell, when they fail, every cell in our bodies starts to shrivel. The cells that were most impacted during the initial COVID infection could account for why different people get different symptoms, e.g. tingling, rashes, hair loss, brain fog, fatigue.

This theory could also explain why fatigue is occurring in otherwise healthy people who experienced mild symptoms during their initial infection. Humans normally burn two types of fuel for energy:

• Glucose (short term, does not need oxygen, generates lactate)
• Fatty acids (uses oxygen, used more for long-term energy)

It’s believed that the virus ‘flips a switch,’ so patients are mainly burning glucose for energy instead of fatty acids. This process generates a lot of lactic acid, which is why patients run out of fuel quickly with minimal exertion.

Remember, these are only theories. There is still much research to be done to truly understand Long COVID, however, one thing is certain: there is no one-size-fits-all with the virus. As we learn more about Long COVID, it’s entirely possible we might discover it’s not one single condition, but one of three or more conditions requiring different approaches to care.

Diagnosing Patients

Because there are so many symptoms and unknowns surrounding Long COVID, it can be quite difficult to diagnose. Patients are also unlikely to make an appointment saying they have Long COVID – rather they will explain they are experiencing many of the symptoms associated with Long COVID. It’s up to clinicians to make the connection and determine if the patient previously had COVID and determine the best course of action from there.

Learn more about Long COVID, its symptoms, possible causes and treatments in this MDBriefCase webinar, The Other Pandemic – The Impact of Long COVID on Patients. The webinar features insights from a panel of COVID-19 experts, including Dr. Peter Lin, Dr. David Strain, and Dr. Vivien Brown.

Healthcare providers: Stay current on the latest COVID-19 updates and treatment best practices. Watch theStraight Talk on COVID-19 series for free on MDBriefCase. Join today.

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