SARS-CoV2. Figure by CDC, Public Domain
(Click on the following link to listen to an audio version of this blog … Long covid
As we have discussed in the three previous blogs, SARS-CoV2 (the virus that causes the disease COVID-19) infects the body primarily by attaching to cells via a very common cell membrane surface protein called ACE2 (“angiotensin converting enzyme 2”). This surface protein is very abundant on the lining epithelial cells of the respiratory organs, and, so, SARS-CoV2 typically enters the body via the upper respiratory tract and generates a wide range of respiratory symptoms when it triggers a COVID-19 infection (everything from a stuffy nose, to a cough, to a sore throat to pneumonia).
ACE2 proteins, though, are found on cells in many other organs of the body. In addition to its presence on the oral and nasal mucosa, the nasopharynx and the lungs, ACE2 is found in the heart, the lining epithelium (the “endothelium”) of blood vessels throughout the body, the stomach, small intestine, large intestine, gall bladder, liver, brain, kidneys and testis. If the SARS-Cov2 virus enters the blood stream (which can occur if it overwhelms the non-specific immune defenses of the respiratory tract) it could encounter and infect any of these ACE2 possessing organs. The complex and highly individualized matrix of organ involvement and symptoms seen in COVID-19 patients with “Multisystem Inflammatory Syndrome” (MIS) reflects this broad distribution of ACE2 receptors! COVID-19, though, is typically an acute illness of limited duration that is most commonly confined to the respiratory system.
The first official case of COVID-19 was reported from Wuhan, China on December 31, 2019. A month later, though, it was detected in the United States and in a numerous sites around the world. It quickly spread and in 15 months had infected over a hundred million people and caused almost 3 million deaths.
By Spring, 2020, there was a significant population of people around the world who had had COVID-19 and had recovered from the acute phase of the disease. Some of these COVID-19 survivors, though, reported that they had persisting, and often debilitating, disease symptoms. The medical community was initially quite skeptical of these assertions of lingering COVID-19 symptoms and put it down to anxiety or hysteria. The sheer number of these cases, though, forced medical providers and researchers to concede that something was going on that stretched beyond the time frame of acute COVID-19.
Symptoms of persisting COVID-19 included fatigue (seen in 67% of these patients), and headache (in about 50% of these patients). There were also a broad cluster of sensory disorders (loss of taste, loss of smell), attention/cognition disorders (“brain fogs”), hair loss, shortness of breath, cough, rapid breathing and joint pain. About 25% of the chronic patients exhibited at least some of these additional symptoms. Other neurological problems, lung problems and heart problems were also observed. Currently there are lists in the medical literature of over 200 persisting symptoms that have been found in these chronic COVID-19 patients.
The people experiencing these persisting symptoms coined a number of names for their condition including: long COVID, long-haul COVID, post-acute COVID-19, post-acute sequelae of SARS-CoV-2 infection (PASC), long-term effects of COVID and chronic COVID. Most authoritative references now use the terms “Long COVID” or “Post-COVID conditions” (PCC) to refer to this syndrome.
One of the problems in the study of Long COVID has been a disagreement about the description of the syndrome’s symptoms and time frame. The acute phase of COVID-19 can last for up to four weeks. So, symptoms persisting after this one month time period are generally considered to be part of Long COVID. These Long COVID symptoms may then last for weeks or months and may, quite rarely, persist for such a long period of time and in such severe forms that the individual becomes disabled. In fact, as of July, 2021, Long COVID was added to the list of considered disabilities covered under the federal “Americans with Disabilities Act” (ADA).
The journal Nature reported that 80% of post-acute COVID patients had at least one, persisting Long COVID symptom. A recent New York Times article cited a Scottish study that indicated that 40% of post-acute COVID patients had symptoms that reached into the time requirements of Long COVID. A UCLA study indicated that 30% of acute COVID patients still had symptoms 60 to 90 days after infection. The University of Michigan found 43% of all acute COVID patients experienced Long COVID and 57% of hospitalized COVID patients had persisting symptoms. A Penn State study found 50% of the post-acute COVID patients had symptoms up to six months after infection.
The Center for Disease Control (CDC) summarized these studies and many more and determined that Long COVID occurs in 13.3% of all patients after one month, in 2.5% of all patients after three months and in 30% of hospitalized patients after six months.
The CDC has also summarized the symptoms of Long COVID: General Symptoms are fatigue, fever and a worsening of symptoms when the patient undergoes either physical or mental exertions (“post-exertional malaise”). Overlaying these general symptoms are persisting respiratory problems (cough, shortness of breath) cardiovascular problems (chest pains, heart palpations), neurological problems (“brain fog,” headache, sleep problems, depression, anxiety, altered senses of taste and smell), diarrhea, joint pain, muscle pain. The time frame for these persisting symptoms may be weeks, months or longer. As we mentioned above, in some patients these persisting symptoms can be debilitating and life changing. Also, often, these symptoms cannot be monitored or explained by standard medical testing.
Fundamentally, the more severe the acute COVID-19 case is, the more likely that a significant Long COVID case will develop. COVID patients who had to be hospitalized are much more likely to have severe Long COVID symptoms. Patients who experienced MIS (mentioned above) are more likely to experience severe Long COVID symptoms. Patients who had severe underlying health conditions prior to their becoming infected with SARS-CoV2 also are more likely to experience severe Long COVID symptoms.
Many of these above factors are not easily controlled by an individual. One factor, though, that is under the control of every individual and has been clearly shown to reduce the chances of severe acute COVID-19 disease and also Long Covid is getting vaccinated and boosted against the disease. Vaccination not only reduces the chance that you will “catch” SARS-CoV2 but also significantly reduces the severity of the disease even if the virus does enter your body.
How does this acute viral infection cause such long-term illness? There are currently four main hypotheses that explain Long COVID:
- Out of control inflammation. “Cytokine storms” triggering tissue and organ damage throughout the body.
- Activation of dormant autoimmune disorders which begin to attack and destroy “self” tissues and organs.
- The SARS-CoV2 virus persists in the tissues and organs of the body. A recent study, published in Nature, isolated the virus from heart and brain autopsy tissues from patients 230 days after they had first been infected. These persisting viruses may directly damage body tissues or trigger immune reactions that lead to tissue damage.
- Micro-clots disrupting blood flow in tissues and organs. Endothelial damage from SARS-CoV2 infections trigger the formation of blood clots which embolize causing extensive tissue damage throughout the body.
It is likely that Long COVID is caused by several or possibly all of these mechanisms in reaction to the stress of an overwhelming viral infection.
Long COVID is not a unique feature of a SARS-CoV2 infection. Many other viruses also cause chronic disease syndromes. The 1918 Spanish flu epidemic generated a significant population of flu survivors who had “nervous complications,” persisting muscular weakness, sleeplessness and depression. Epstein-Barr viruses are correlated with Chronic Fatigue Syndromes and, most recently, Multiple Sclerosis. Varicella zoster viruses cause chicken-pox in children and also can persist in the sensory ganglia of the body where they can trigger the disease shingles later in life. West Nile virus, polio, Dengue fever, measles, MERS-CoV and SARS-CoV1 all have well described “long” syndromes.
The United States Government Accounting Office (GAO) estimates that there are between 7.7 and 23 million people in the United States who have Long COVID. Many of these people are so ill that they are unable to work and will need to be supported, possibly, for the rest of their lives. COVID-19 has extracted a steep social and economic toll since SARS-CoV2 exploded across our world. Its acute impacts and chronic legacies will remain with us for many generations to come!