A recent review by Scripps Research scientist Eric Topol and colleagues (Nature Reviews Microbiology, 21:133-146, 2023) highlighted what we know and don’t know about “Long COVID,” a constellation of long-term symptoms that occur in at least 10% of individuals following infection with the SARS-CoV-2 virus that causes COVID. Given the huge number of reported and unreported infections, the number of people with long COVID could exceed 65 million worldwide, and some of the chronic symptoms are extremely debilitating. The probability of developing long COVID is higher in hospitalized patients and lower in vaccinated individuals, suggesting a link with how much virus is present during the primary infection.
The many symptoms involve multiple organ systems: chest pain and heart palpitations (heart); cough and shortness of breath (lungs); diabetes (pancreas); autoimmunity (immune system); abdominal pain and nausea ((gastrointestinal (GI) tract)); cognitive impairment, fatigue, sleep disorders, memory loss, ringing in the ears (neurological system); blood clots, reduced blood flow (vascular system); and changes in the autonomic nervous system that controls blood flow, breathing, heart rate, and many other functions that we are not aware of (hence, autonomic).
How might a single virus infection cause so many consequences? Current research provides some plausible suggestions, but many more studies will be required to provide a fuller explanation. The COVID virus persists in some but not all long COVID patients, and we now know that the virus can infect many different tissues, including the brain, blood vessel linings, and the GI tract. Both overactive and poor immune responses have been associated with long COVID, and some patients have evidence of autoimmunity and chronic inflammation.
Neurological and cognitive issues are a major feature of long COVID, and these could result from direct virus infection of nerve tissue, reduced blood flow and low oxygen tension due to autonomic nerve injury or inflammation, and microclots in the brain such as those seen in chronic fatigue syndrome. Whatever the cause(s), there are clear signs of damage to brain cells that lead to the impairment of function.
Some early studies show improvement in some patients with long COVID symptoms following treatment with the antiviral medication Paxlovid. Anti-histamine medications that reduce inflammation also reduce some symptoms. There have still been no large, double-blinded clinical trials to establish efficacy of any proposed treatment, and the review ends with a plea for such trials. Short synopsis for long COVID: we have a lot to learn.