The Mystery of Long COVID and Why We Still Don’t Fully Understand Its Human Impact

September 2, 2023

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Unlocking the mysteries of Long COVID — Research is slowly beginning to understand why COVID-19 is different from previous coronaviruses and what happens to people who suffer from Long COVID. (Image credit: The Business Standard)

Why do so many who are first infected with the COVID-19 virus in its many forms, end up with long-term symptoms? What makes this coronavirus different from others like a predecessor that caused the SARS pandemic from 2002 to 2004?

Before we tackle this subject it would be good to have a definition. What is Long COVID? It describes COVID-19 symptoms that persist beyond 12 weeks. The average gestation for COVID-19 with resolution of symptoms lasts up to 4 weeks. But when symptoms persist without any alternative explanation, the individual who has had COVID is deemed to be suffering from Long COVID.

From a study on population groups, the U.S. National Institute of Health (NIH) has come up with a list of 37 discrete COVID-19 symptoms that include post-exertional malaise (the worsening of symptoms after physical or mental activity), fatigue, brain fog, dizziness, gut symptoms, heart palpitations, sexual problems, change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements such as muscle twitching or jerking. Of these 12 have appeared to be persistent in individuals suffering from what we call Long COVID.

These 12 break down into four categories that produce symptoms in different parts of the body such as:

Heart, kidney and circulatory problems.
Lung complications, sleep disruptions and anxiety.
Muscle pain, and nervous and connective tissue symptoms.
Digestive and respiratory symptoms.

Researchers have tried to create a method of scoring these various Long COVID symptoms to allow for differentiation. The NIH research shows that symptoms of Long COVID appear to be more common before the arrival of the Omicron variant of the virus, and in those who have never been vaccinated. And those in the Omicron era who have been infected again are also seen as more susceptible to Long COVID.

States Andrea Foulkes a doctor at Massachusetts General Hospital who has been a senior researcher at NIH, “One of the big takeaways is [that] long COVID is not just one syndrome; it’s a syndrome of syndromes.” Within the four clusters as described above are other Long COVID symptoms that include dry mouth, weakness, headaches, tremors, muscle and abdominal pain, fever, sweats, chills, and sleep disturbances.

Many studies over the last two years have identified immune cell abnormalities and tiny blood clots that persist beyond 8 months after an initial infection.

An Australian research study has identified persistent signs of inflammation associated with abnormal circulation.

A study out of Italy shows cells associated with blood flow appear to be damaged by the COVID-19 virus in patients suffering from long-term symptoms. States Danilo Buonsenso, a pediatric infectious disease doctor working at Italy’s Gemelli University Hospital, in assessing circulatory abnormalities in Long COVID, “In some patients, we have specific areas where no blood flow comes in.”

Now adding to our understanding comes research from the Children’s Hospital of Philadelphia (CHOP) and the COVID-19 International Research Team (COV-IRT) that shows the virus causes genetic impairments to the mitochondria in cells. Infected mitochondria in host cells when activating immune defences, cause malfunctions that can result in serious complications such as organ failure.

Mitochondria are organelles found in every living cell in our bodies. The genes responsible for them are contained within the DNA in the main cell body as well as separately within the mitochondria organelles themselves. Studies show COVID-19 proteins within infected cells bind to mitochondrial proteins which explains the malfunctions.

At CHOP, autopsies showed that mitochondria in lungs recovered from COVID-19, but normal function in the heart, kidneys and liver exhibited malfunctions. Long COVID even showed the suppression of normal mitochondrial function in the cerebellum even when COVID was not found in brain tissue.

Douglas C. Wallace, Director of the Center for Mitochondrial and Epigenomic Medicine at CHOP states that there is “strong evidence that we need to stop looking at COVID-19 as strictly an upper respiratory disease and start viewing it as a systemic disorder that impacts multiple organs…The continued dysfunction we observed in organs other than the lungs suggests that mitochondrial dysfunction could be causing long-term damage to internal organs.”