As part of my Comprehensive Review of COVID-19 series, I plan to go through the studies on Long COVID, also known as PASC, but, for now, there was a nice summary (https://www.science.org/doi/pdf/10.1126/science.adl0867) by one of the leading researchers in this area published recently that I thought I would summarize and explain for you.
- Long COVID consists of a constellation of wide-ranging symptoms reflecting the fact that the SARS-CoV-2 virus can infect and/or produce effects on almost every organ system in the body. The disease can occur in both children and adults. The prototypical (classic) form of Long Covid (with brain fog, fatigue, dysautonomia, and post-exertional malaise) is more common in younger adults and in females. Other forms of Long Covid, including those with cardiovascular and metabolic sequelae, are manifest more often in older adults and those with comorbidities.
- There are a number of mechanisms identified that appear (but are not yet proven) to explain at least part of the pathophysiology of the disease, and these different mechanisms and resulting manifestations of disease may contribute to various subtypes of disease. In other words, Long COVID may not be a single disease, but rather a spectrum of diseases for which the presentation may be influenced by the underlying mechanism of disease.
- These underlying pathogenic mechanisms include viral persistence (meaning that the body’s immune defenses are unable to rid the body of the virus) and chronic antigenic stimulation (the consequence of viral persistence in which the persistent presence of proteins of the virus [which serve as antigens] stimulate the immune system on a chronic basis and result in inflammation and immunopathology [damage from the exaggerated and/or prolonged immune response]; autoimmunity (the process by which some people, particularly females, may be genetically predisposed to develop autoimmune disorders and the infection serves as the trigger for setting this process off, in some or all cases, potentially due to molecular mimicry (meaning that the viral protein stimulating the immune response is structurally similar to proteins of the host cells, which can result in antibodies cross-reacting with or the host protein triggering an autoimmune reaction itself); mitochondrial injury and dysfunction (mitochondria are the power and energy subcellular structures of the cell, and recent studies have shown that some individuals with Long COVID suffer from dysfunctional mitochondria injured by the virus resulting in energy depletion and perhaps accounting for some of the excessive fatigue and muscle weakness seen in Long COVID and potentially contributing to a specific condition that I will write about at a future date), infection/inflammation of small blood vessels (referred to as endotheliitis, this condition can account for or contribute to the increased risk for COVID toes, limb ischemia in which blood flow can be severely restricted to an arm or leg, heart attacks, strokes, blood clots, and a host of other serious manifestations), infection/inflammation of neurons (neurons are cells of the brain), microbiome dysbiosis (our understanding of the microbiome is relatively recent and still developing. It is a reference to the usually healthy community of bacteria that line our guts that are beneficial to the metabolism and absorption of certain vitamins and food substrates, but for which we are learning that there is a quite complex interconnection to the brain, heart and potentially other organs that influences our health if the microbiome gets out of balance with the accumulation of unhealthy bacteria. Most people will be familiar with the fact that oral antibiotics can, not infrequently, cause diarrhea. Sometimes your physician will advise that you take yogurt or probiotics along with the antibiotics if you have had that problem before, or if a particularly long course of antibiotics is planned. The antibiotics can kill some of these healthy bacteria, which then clears the way for some unhealthy bacteria to take their place. We are realizing that certain infections, including COVID-19, can cause the same result); and reactivation of dormant viruses (we have seen evidence that certain herpes viruses, the zoster virus, and particularly, the Epstein-Barr virus that generally lie dormant after the initial infection [in other words in a state in which they are not replicating and infecting new cells] become activated again concurrent with the SARS-CoV-2 virus infection. Not only can these viruses cause harm in and of themselves, but the Epstein-Barr virus is an oncogenic virus [meaning that it can contribute to the development of certain cancers] and has itself been long associated with the potential for chronic fatigue.
- Long COVID risk increases with the severity of the acute infection, but as a consequence of wide-spread infections and reinfections, roughly 90% of all cases of Long COVID occur in people who reported mild illness during their acute infection.
- COVID-19 vaccination prior to infection and antiviral treatment during infection can both lessen the risks of developing Long COVID (e.g., a study of the use of Paxlovid in qualifying older adults reduces the risk for Long COVID by about 26%). The COVID-19 vaccines reduce the incidence of Long COVID somewhere between 15-75% (mean 40%).
- A recent study showed that Metformin treatment started within a week of the onset of symptoms not only reduced the risk of severe disease, but reduced the risk of developing Long COVID by about 41%.
- Reinfections result in additive risk for the development of Long COVID, and recent studies would suggest that those who developed Long COVID with prior infections are more likely to suffer a recurrence upon reinfection.
- While some persons with Long COVID do improve over time, spontaneous resolution of all symptoms and return to their prior state of health is uncommon.
- The authors conclude by stating: “Preventing infections and reinfections is the best way to prevent Long Covid and should remain the foundation of public health policy.”
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