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Sequela: Long after a pandemic is 'over,' new and terrible symptoms can appear

Brexiter

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“Sequela” is a word that few Americans recognize today. Unfortunately, it’s a word that is much more likely to become familiar over the next few years… even decades. A sequela is a long-term pathological effect resulting from exposure to a disease. When the pandemic ends, the damage is not going to be over.

There’s often a tendency in the media—and in social media—to try to frame the damage of COVID-19 to an either-or situation. Someone gets sick for a few days, and they either recover and are fine, or they die and count among the ever-growing total deaths. It’s that sort of all-or-nothing approach that allows people to say things like, “Well, the survival rate is 99.9%, so …” Add more nines to the end of that number, depending on how many right-wing news programs you watch.

Nationally, the actual survival rate is something closer to 98.8%, but that’s not the point. Studies have already indicated that 43% of those who have had at least one symptomatic COVID-19 infection tend to have issues that persist over an extended period. For those who have required hospitalization, the number jumps to 57%. In the United States alone, that’s something over 15 million people who are now suffering protracted illness due to a single, nonlethal infection from COVID-19.

Those suffering these persistent symptoms aren’t really going through a never-ending infection with SARS-CoV-2. “Long COVID” is a sequela—a long-term pathological effect resulting from exposure to COVID-19. For some of these 15 million, the damage is minor and transient. For others, it is debilitating and possibly lifelong.

Many sequelae aren’t obvious. And they may not show up for years.


What kind of long-term effects can be generated by an infection is difficult to predict. As an example, mumps is a viral infection that’s mostly focused on the salivary glands. The primary symptoms include pain on the sides of the face, difficulty in swallowing, fever, headache, and fatigue.

But mumps can also cause temporary or permanent hearing loss. That loss can be subtle. It can be severe. It can affect one ear. It can affect both. Most importantly, hearing loss can have an onset that begins at the same time as other symptoms of the disease, but it can also not appear until months after other symptoms have passed.

Shingles may be one of the best-known sequela. Unusual in that it represents a continuous infection of the herpes zoster virus over a period of years or decades, shingles can even produce its own sequela in the form of postherpetic neuralgia: debilitating pain that persists for months or years after the typical shingles rash has disappeared.

Similarly, highly infectious measles is primarily a viral infection of the respiratory system. However, it can generate horrific damage to the central nervous system that doesn’t become evident for years. Among the possible consequences of a measles infection is subacute sclerosing panencephalitis (SSP), which is described as “a progressive, disabling, and deadly brain disorder.” This disorder is relatively rare, but when it does appear in measles patients, the SSP comes seven to 10 years after that first infection.

An infectious disease places an enormous strain on the body. In the case of a viral disease, cells in the affected area are hijacked to produce millions of copies of the invading virus. Then those cells are torn apart as the virus particles escape. It’s also not unusual for this replication process to fail, leaving behind fragmentary bits, proteins, and the contents of all those exploded cells. In the case of a large, rapid mutation—like the omicron variant—a virus may generate a large number of transcription errors, resulting in a lot of “junk” floating around the system.

The long-term results of tissue damage, viral fragments, and the efforts of the body’s own systems attempting to control the infection are hard to judge. But this much should be clear: A large-scale pandemic has consequences that can appear well after the infection itself has been brought under control. In the case of a novel virus that suddenly infects a large portion of the population in a short period, the resulting sequelae can be expected to be significant, both in terms of the number of cases, and their effect on every aspect of society.

In particular, neurological sequelae are frequently associated with epidemics and pandemics.

Nervous system infection or dysfunction during pandemics is common and its enduring consequences, especially among vulnerable populations, are frequently forgotten.

After the 1918 flu pandemic, whole new waves of symptoms appeared in flu survivors years after the immediate threat was past. One of the first sequela to be noticed in the United States was a big increase in miscarriages, stillbirths, premature delivery, and maternal mortality that peaked a year after the flu was gone.

More mysteriously, the years after the 1918 flu saw a wave of fatigue and depression that spread around the world. Sometimes, the symptoms were easy to miss—after all, this was a society just moving on from World War I—and there was a tendency to connect the cases that appeared afterward with similar symptoms that had happened years before.

But the wave of what would come to be known as “La Von Economo’s encephalitis lethargica,” which peaked in 1923, went beyond some kind of international weltschmerz or even an outbreak of depression. Those suffering the disorder presented with a whole spectrum of symptoms, among which was a sleepiness so profound that patients would drift into a fugue at any time of the day. After a week or two, patients improved. Or they got worse, tumbling toward coma and death. Those affected were described as having “corpse-like” faces that were rigid and devoid of emotion, 50% of those affected died.

In some areas, the wave of encephalitis lethargica generated a secondary wave of famine because the “debilitating lethargy” left people unable to plant and harvest crops.

How far into the future can the sequelae from the COVID-19 pandemic stretch? The consequences will literally be with us for the lifetimes of all those infected. Possibly longer. Male babies born during the 1918-1919 flu pandemic were at increased risk of heart disease six decades later.

Calculating the loss of lives, much less quality of lives, seems impossible.


What kind of sequelae can we expect from this pandemic? We don’t know. Studying those suffering “long COVID” may provide some clues. So should a look at the consequences of past pandemics. But because the SARS-CoV-2 virus infects so many parts of the body, nasty surprises can be expected for a long time.


The problem with such a broad pandemic is that even rare side effects can generate enormous numbers. Encephalitis affects 1 out of 1000 mumps patients. But with 73 million COVID-19 cases in the U.S. alone, a rare problem is going to be way too common. Any planning for health care in the future should be made based on the assumption that the 2020-2022 pandemic is going to cast a long shadow down the decades, one that will extend through generations.

Oh, and … wear a mask.
 
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