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the small and large vessels throughout the body. It causes septic shock: a system-wide drop in blood pressure with inflammation that can lead to damage in the extremities that may require amputation, or to multiple organ failure, and ultimately to death. The precipitating factors for this outsized inflammatory reaction are the subject of ongoing study. If we can identify what causes some people to have such extreme reactions while others have milder infections, we may be able to prevent this life-threatening consequence of COVID-19. PASC: A Post-Viral Syndrome As we've said, long COVID or PASC is a condition some patients develop in the weeks and months after their initial infection—it is a post-viral syndrome. The phenomenon of developing long-term problems after an infection is not unique to SARS-CoV-2; other infections also sometimes show lingering post-infectious consequences. Flu viruses sometimes do this, and it has been well documented among Ebola survivors. In the November/December 2021 issue of Massage & Bodywork ("Sepsis: The Hidden Crisis," page 38), I discussed post- sepsis syndrome, which, although it usually involves bacterial rather than viral infection, has a lot in common with what COVID long haulers describe. And another condition appears to be a post-viral issue, at least some of the time, and it has a lot of overlap with symptoms of long COVID: chronic fatigue syndrome (CFS). We will address connections between long COVID and CFS shortly. Long COVID affects a lot of people, but at this point, the condition itself is difficult to define. There are no agreed-upon diagnostic criteria to help identify who has long COVID versus any other health issues, and the pathophysiology of this condition is still a mystery. This means we can't count how many people have it—we can only guess at who is most at risk, and our ability to treat it is limited to the management of symptoms. Who Gets Long COVID? One of the many frustrating things about trying to understand this condition is the wide variety of ways researchers have begun to gather data—especially regarding timing. Long COVID has been documented in elders, middle-aged people, young adults, and children. Men are more likely to have very severe COVID-19 infections, but women are up to four times more likely to report having long COVID symptoms. Some studies survey patients at six weeks post-diagnosis; others look at six months or more. Consequently, estimates of what percentage of patients develop this condition range from 5 to 80 percent. That said, several studies have landed on estimates in the neighborhood of 30–40 percent as the proportion of patients who have symptoms at six months or more after their diagnosis. Long COVID seems to be most common in people who had severe infections that required hospitalization, but one study reported that about one-third of the people with long COVID nine months after their infection had no symptoms at the time of their diagnosis. This suggests that people with mild or even asymptomatic infections can develop long COVID. Long COVID Pathophysiology What causes long COVID? What functional changes produce these signs and symptoms that last for weeks, or months, or longer? This question is under active investigation, but so far, we have seen many theories and not much confirmation. As with most complicated health issues, long COVID is almost certainly multifactorial. And because it looks so different in one person from another—and in one person from day to day—we will probably eventually find several contributing factors join to create the whole syndrome. Some of the theories about the pathophysiology of PASC getting the most attention include these: Maybe the virus was never fully cleared. Some specialists propose that small colonies of SARS-CoV-2 may find ways to hide in the body, causing continuing symptoms and immune system activity. Other viruses have this capacity: the Herpesviridae that cause cold sores, chickenpox, and shingles can hide from immune system activity, and human immunodeficiency virus (HIV ) is notorious for this behavior. Alternatively, it is possible that while intact viruses have been eradicated, viral particles and debris may linger and continue to elicit an immune system response, with accompanying symptoms. Maybe latent pathogens wake up. When our immune system is stretched thin or overwhelmed, latent infectious agents can sometimes reactivate. We see this with shingles (a resurgence of herpes zoster) and some other pathogens. Some experts suggest that long COVID is the result of this process as well, and Epstein-Barr virus, the causative agent for mononucleosis, is a potential culprit. 38 m a s s a g e & b o d y wo r k j a n u a r y/ fe b r u a r y 2 0 2 2