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.