Addressing the Mystery of Long Hauler COVID: The Time is Now

As we learn more about inflammatory syndromes, we may get better at using laboratory tests to identify and isolate the actual cellular and chemical processes that drive them.

Long COVID is one of the most challenging and enigmatic aspects of the COVID-19 pandemic. It can be completely different from person to the next. It can seem to wane, then suddenly reappear.

And although long COVID is more likely in older people and those who had severe infections, it also appears in those who started with a mild illness. So, what is it?

It turns out, you might have long COVID without even realizing it. In many cases, long COVID manifests as lingering symptoms of the initial infection—a cough, ongoing loss of smell, or fatigue and weakness that goes on for weeks or months.

It may improve over time, which makes it similar to other post-viral symptoms that we’ve known from other viral infections. The difference in COVID-19 is how common it is—more than half of COVID-19 cases produce ongoing issues, such as continued tiredness or coughing after a month. But that’s only part of the long COVID story—other manifestations of it are much stranger.

They include concerning problems, such as severe, debilitating fatigue that lasts for months or years. They include depression, anxiety, brain fog, muscle and joint pain, recurring headaches, hair loss, rapid pulse or other signs that may not show up until after the individual recovered from the initial illness.

Inflammation is the missing link

As confusing as these syndromes may be, they all share a common thread that can explain them from a scientific perspective. That is, these issues are all related to inflammation. The way they come and go, or surge after certain triggers, is a familiar pattern found in other immune-related diseases.

The core of the problem is that the same immune system response that exists to fight off a dangerous infection can sometimes fail to wind down after an infection is gone. In some cases, that viral infection might trick the immune system into attacking the body itself, and the immune system may continue doing so even after the virus is destroyed.

It can simmer down to a low level of activity, then flare up any time the immune system becomes active for other reasons. We don’t know all the reasons the immune system makes these counter-productive moves, but we’ve seen it happen repeatedly in inflammatory disorders we’ve been studying and treating for many decades.

Nobody’s immune system is perfect

How do long-term immune problems begin? Few of us are born with them, but then again, we’re born vulnerable to all sorts of infections because our immune system doesn’t recognize anything yet. As we grow up and build resistance to threats our bodies encounter in the environment, almost everybody develops a few cases in which the immune system goes off track.

The most common example is an allergy, whether a serious life-threatening reaction or just mild seasonal allergies. But countless other health concerns, from dandruff to diabetes, have known, well-established links to inflammatory processes.

The older we get, and the more complexity our immune systems have dealt with in the world, the more errors appear in its instructions. So, when we look at long COVID—more likely to occur in older people, in women, and in those whose blood tests show a higher count of auto-antibodies—there’s a lot of overlap with those who are most vulnerable to developing new inflammatory diseases. That’s a further sign that long COVID is, itself, a disease of runaway inflammation, sparked in the chaos of a viral illness our bodies were not fully prepared for.

Looking for solutions

As we learn more about inflammatory syndromes, we may get better at using laboratory tests to identify and isolate the actual cellular and chemical processes that drive them. I think it would be validating for patients to know their fatigue, trouble concentrating, new anxiety issues or mysterious aches and pains, which can be hard to observe, are in fact driven by real, verifiable processes in their bodies.

That knowledge may also point towards new therapies to edit or reset the immune system’s script and get it to work more predictably. In the meantime, we need to find ways to address the symptoms of long COVID in the millions of people suffering from it today.

One lingering question is whether the extended inflammatory response is truly a rogue immune system, or if there is still a bit of live virus hiding somewhere in the body that it is overreacting to. If there’s live virus, it may mean a steroid drug, which bluntly suppresses the immune system and affects all sorts of other functions, is a risky treatment option we hopefully won't need to turn to in most cases.

Other drugs, like antihistamines and non-steroidal anti-inflammatories, are more likely to shut off peripheral immune functions (fevers, hives, aches, and runny noses) rather than the immune system’s core function of attacking germs or making antibodies. These drugs don’t seem to weaken our ability to fight illness, so I think that’s the place to start.

About the Author

Jackie Iversen, RPh, MS, Founder and Head of Clinical Development Sen-Jam Pharmaceutical. Check us out on WeFunder.