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What to know about long-haul COVID

It goes by a number of different names — long COVID, long-haul COVID, chronic COVID — and the CDC now favors the term “Post-COVID conditions.” Whatever you want to call it, it’s bad news. It means that for some people, the symptoms of a COVID infection can linger for months.

One could also call it “The Post-COVID Science Swamp,” as the number of those afflicted with long-haul symptoms (perhaps 10-30% of those who’ve been infected with SARS-CoV-2) seems to far outpace our scientific understanding of what’s behind all of this. 

Grab your waders and let’s go:

Lungs are the epicenter of COVID, but other organs can become infected

SARS-CoV-2 is no average respiratory virus, but many of its primary symptoms are entirely predictable and straightforward. It’s an amazingly virulent piece of filth, and although it is capable of growing in the nose, it replicates best in the lungs. That’s because the lung cells have a lot of angiotensin converting enzyme-2 (ACE-2), a protein that SARS-CoV-2 needs to bind to gain entry into the cell. As the virus begins replicating, the immune system is alerted and the war begins. 

Think of what your schnoz goes through with a cold. With COVID-19, that same kind of inflammation and swelling is occurring deep in the lungs, making it difficult for air to move through the tiny tubules and air sacs. People cough, feel short of breath, oxygen levels fall. On X-rays and CT scans, we can see the debris piling up — clinching the diagnosis of pneumonia. 

People can become overwhelmed by any infection, a complication referred to as “sepsis.” Although any given infection might be confined to the lungs, or bladder, or colon, sometimes the interaction between the infective agent and the immune system can cause one’s blood pressure to drop, which then causes organs to fail. In other words, the widespread failure of uninfected organs sometimes comes as collateral damage to the initial infection.

We’ve seen sepsis in COVID, but there is good evidence that SARS-CoV-2 can infect the heart, kidney, and intestines directly, and cause them to fail. That’s because, like the lungs, these organs display the ACE-2 receptor that the virus requires to gain entrance. The ACE-2 receptor is also found on the cells that line our arteries. If those get infected and swell shut like your nose on Day 3 of your cold, well, very little blood will squeeze through. That’s more bad news. 

Brain dysfunction can also be seen in long-haul COVID, but at this point, there’s little evidence of direct infection of the brain. 

Recovery from any serious illness can be prolonged. But long-haul COVID seems different

For a simple infection like the common cold, once one’s immune system has killed off the virus, the cleanup begins. The nose goes back to normal and the cough is gone in a week or two. The immune system stands down, antibodies wane, but the immune system keeps a memory of that particular strain of cold virus so that it can be ready to spring into action if a person is ever re-exposed. 

Depending on the severity of the cold, it might take a week or two for one’s full energy to return — being able to sleep without coughing or mouth-breathing really helps.

For severe illness, recovery can be far more complicated. Many of those who wind up in the ICU for COVID will eventually be put on a ventilator. That means a breathing tube needs to be placed through the mouth, past the larynx (vocal cords) and into the trachea. If you’ve ever gotten a small piece of food “down the wrong pipe” and gone into a coughing fit, you can imagine what it feels like to have a plastic pipe (a tracheostomy tube) down that same “wrong pipe” — the trachea. That’s why patients on breathing machines are heavily sedated. 

Throw in pain medications, no physical activity, and very poor sleep (being “knocked out” with sedatives is NOT good sleep), and someone who is lucky enough to survive a COVID ICU stay can be messed up in all kinds of ways. They are often incredibly deconditioned and weak, and commonly their brain is scrambled. Typically, it’s not anything like a stroke, but runs the gamut from being wildly delirious to just mildly confused. 

Sometimes it can take months to recover from a serious hospitalization (from any major illness, not just infections), and sometimes the road to recovery has setbacks. Not everyone gets back to where they were before — older age and underlying health have a lot to do with that — but overall, the trend is up, and many, if not all, make a full recovery.

When does an infection become ‘long-haul COVID,’ and what are the symptoms?

The CDC says that Post-COVID conditions are a “wide range of new, returning, or ongoing health problems people can experience four or more weeks after first being infected with the virus that causes COVID-19.” It can also develop after a so-called “breakthrough infection” — after a prior-COVID infection or immunization. 

A large international study identified over 200 symptoms that may be part of the diagnosis, but here’s what the CDC lists as the most common: fatigue, fever, shortness of breath, cough, “brain fog” (problems concentrating, thinking), depression or anxiety, headache, a fast or pounding heart rate, getting lightheaded when standing, joint and muscle aches, pins-and-needles sensations, stomach pain or diarrhea, sleep problems and loss of smell or taste. Of that list, fatigue, shortness of breath, brain fog, headache and loss of smell were the most frequently reported. 

Who can get it? Anyone, of any age or sex — though it seems to be more common in women and the average age of a long-haul patient is 40. Although it might seem counter-intuitive, even someone with a “light case” of COVID can go on to have chronic problems. Most post-COVID research has tended to focus on patients who were hospitalized, but a University of Washington study found that 30% of those surveyed 6 months out from an infection had at least one post-COVID symptom, and it didn’t matter whether their infection was asymptomatic-to-mild or had landed them in the hospital (moderate to severe). 

We won’t develop any specific treatments until we understand what specifically is going on. Here are a few leading ideas.

Some who contracted SARS and MERS also had persistent symptoms

Coronaviruses have long been circulating as run-of-the-mill cold viruses, so the question is: Is this just what these newer, far more unfriendly coronaviruses do? Studies on patients who contracted the original recipe SARS or the Middle Eastern Respiratory Syndrome (MERS) showed persistent mental health issues and decreased exercise tolerance months later. In fact, a Chinese study found that fifteen years after being hospitalized with SARS, 38% of patients had reduced lung function — it was harder for oxygen and carbon dioxide to move in and out of the lung. Could some of that damage be from having been on a ventilator? Being ventilated through a tube is not natural — it forces air into the lung under positive pressure, whereas natural breathing works by creating a negative pressure that pulls air in. And so being on a ventilator for a long time can lead to permanent lung injury.

Long-haul COVID eerily similar to Chronic Fatigue Syndrome

Another historical note: Post-COVID symptoms are remarkably similar to the five criteria used to diagnose the well-recognized but still poorly understood Chronic Fatigue Syndrome (CFS). The five criteria include severe fatigue, a particular form of severe fatigue called Post Exertional Malaise (PEM), poor sleep, memory and concentration issues and a penchant for getting lightheaded upon standing.

A report from the prestigious Institute of Medicine, which renamed CFS as Systemic Exertion Intolerance Disease, grimly notes that somewhere between 830,000 and 2.5 million Americans are affected, but roughly 85-90% of those are undiagnosed. Worse yet, “Symptoms can persist for years, and most patients never regain their premorbid level of health or functioning.” CFS has been around since the 1980s (and its predecessor myalgic encephalomyelitis (ME) since the ’50s), and yet researchers still cannot uncover what’s causing it. 

“The cause of ME/CFS remains unknown, although in many cases, symptoms may be triggered by an infection or other prodromal events such as immunization, anesthetics, physical trauma, exposure to environmental pollutants, chemicals and heavy metals, and rarely blood transfusions.”

Is the COVID infection really gone, or did it just go ‘underground’?

Could there be a persistent low-level COVID infection? There’s no clear proof of this for COVID, but it’s not unprecedented for a virus to hang around for a very long time. For example, when the hepatitis C virus first infects the liver, some people will experience a few weeks of flu-like symptoms. Thereafter, the virus enters a chronic phase, where most patients have no symptoms—until they begin to develop liver cirrhosis several decades later. Still, it’s hard to square the idea that SARS-CoV-2 could still be sticking around at levels that are too low to allow us to detect its presence, and yet high enough to be causing long-haul COVID symptoms.

Is it really just an immune system problem?

Could COVID-19 have left our immune system in some kind of altered, overactive, dysfunctional state? White blood cells use inflammation to kill invaders and remove cancerous cells, but when summoned accidentally, inappropriately, they can cause a lot of damage to healthy tissue. For example, Multisystem Inflammatory Syndrome (MIS) is a rare but serious condition that can be seen during a current or recent COVID infection. It’s caused by severe inflammation, more commonly in the heart, skin, or brain. And no, we don’t understand MIS either. One thing we can say about excess inflammation and COVID is that some of the lung injury in hospitalized patients is due to an overzealous immune response, which we treat by using a type of steroid that suppresses inflammation. 

How to diagnose long-haul Covid and what to do about it

There is no lab or radiological test that can prove that someone has post-COVID symptoms. But that doesn’t mean bloodwork or an X-ray aren’t worth doing. Like many other difficult diagnoses in medicine, long-haul COVID is “a diagnosis of exclusion”: only after proving that it isn’t something else can one conclude that it’s probably long-haul COVID. For instance, symptoms of persistent shortness of breath might require testing to prove that a blood clot didn’t travel to the lungs (COVID makes the blood stickier and increases the risk of clots; lying in bed for a week also increases the risk for blood clots). It might require specific testing to see if the lungs are scarred-up and stiff, making it harder for air to move into the lungs. Patients who have had COVID still get the usual health problems too. One would not want to brush off chest pain as just being a post-COVID symptom unless one had testing that showed the heart was pumping well, and the coronary arteries were not blocked. 

There is no treatment for long-haul COVID and it is unlikely that there will be until we understand the fundamental processes that are driving it. (I will add the obvious: avoiding COVID altogether is highly effective.) In the meantime, all that patients and their health care providers can do is thoughtfully work through their symptoms and consider potential secondary treatments. Utilizing all the academic gobbledygook the CDC can muster, here is their counsel: “Providing holistic patient-centered management approaches to improve patient quality of life and function and partnering with patients to identify achievable health goals.” This is the CDC saying, “Good luck with that!”

A disclaimer: your symptoms are your symptoms

When a patient comes to the hospital or clinic with a group of symptoms, but all testing is negative and the symptoms persist, two things happen. First, the physician feels frustrated and inadequate. We like to fix things. We like to make people feel better. Second, the patient, of course, is disappointed, because they want an answer, and because they want the suffering to end.

But sometimes the message, “The tests are all normal, they’re fine,” somehow ends up sounding like “Everything is fine. There’s nothing wrong with you.” When very clearly you do not feel normal. Things are not fine. In the worst-case scenario, patients conclude (or are made to feel) that their symptoms are all in their head. They’re “crazy.” Know this: your symptoms are your symptoms. Just because we don’t have an explanation for them does not mean you are imagining things. It just means that your symptoms are unexplained. 

Having said that, it is also true that people can experience profound physical symptoms due to unresolved psychosocial issues. Stress — and there’s been a WHOLE LOT of that going around — is extremely unhealthy. It puts our bodies, minds, and immune systems on high alert, where, after a while, they can wear down. The social isolation of the pandemic has only magnified this condition. Whatever the symptoms or their sources, stress reduction is always worthy of one’s attention. 

For the above reasons, sufferers of Chronic Fatigue Syndrome and now long-haul COVID can sometimes feel dismissed, or worse yet, ridiculed by the medical system. A “Perspective” piece in the New England Journal of Medicine titled, “Confronting Our Next National Health Disaster — Long-Haul Covid” anticipates exactly that, and recommends establishing regional multi-specialty clinics that can refine and hasten our understanding of a pandemic and a virus that doesn’t seem to want to quit. In the meantime, we continue our slog through the forbidding Post-COVID Science Swamp.

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