, 28-4-2021, Steven Novella

Part of the challenge of the COVID-19 pandemic is (to borrow a commonly used metaphor) we are building the plane as we are flying it. We entered the pandemic with zero knowledge of SARS-CoV-2 and the infection it causes, and have been learning as we go. It is a testament to our modern institutions of science that we have come so far in just 17 months.

One of the features of COVID-19 that has emerged over time is being called “long COVID” – when chronic symptoms persist after the infection itself has resolved. Right now we are in the phase of this medical condition of just gathering data, and hoping that some patterns emerge. But we still know very little about this complication. Most of the published literature on long COVID is case reports – front line observations that may lead to hypotheses that can later be tested. A recent review of these reports summarized the results:

Fatigue, cough, chest tightness, breathlessness, palpitations, myalgia and difficulty to focus are symptoms reported in long COVID. It could be related to organ damage, post viral syndrome, post-critical care syndrome and others.

From these symptoms it seems that the brain, heart, and lungs are the most affected organs. It could be that all organs are equally affected, but these are the ones that cause chronic noticeable symptoms. As neurologists are one of the specialists to whom these patients might be referred for evaluation, I have started to see long COVID patients myself. Fatigue and “brain fog” are the most common symptoms of those patients referred to me. The cognitive symptoms are extremely similar to patients who have post-concussive syndrome or traumatic brain injury. I have also seen patients over the years who survived a serious brain infection, and they too are similar.

What this means is that these symptoms are non-specific. They don’t point to a particular part of the brain or to a particular mechanism of injury. They may simply reflect the fact that the brain has undergone some diffuse stress and has not yet recovered. For brain injury the mechanism is most likely “diffuse axonal injury” – the connections among brain cells have been partially disrupted. This means the brain has a harder time communicating with itself, which further means that those tasks which require heavy brain processing power are the most affected. People with TBI therefore have a hard time multi-tasking and concentrating, and they cannot keep up with changing or complex sensory input. Sometimes they feel like they just don’t have complete control over their movements, so things that used to be easy, like walking, are now challenging.

The cardiac and pulmonary symptoms are likewise nonspecific – breathlessness could be many things. Therefore researchers have many clues to track down. There is some reason to suspect that the virus itself, particularly the spike protein that allows it to infect cells, causes cellular damage. However, the body’s immune response is also part of the equation. This is perhaps why steroids are one of the most effective treatments for severe COVID – it suppresses the host’s immune respond to limit resulting damage.

Post-infectious syndromes are not uncommon – a severe long term infection can takes its toll on the body. Some people never recover back to their prior baseline. There is also no specific treatment, which is limited to symptom management and trying to generically optimize recovery. We are in the same situation with long COVID, giving sufferers what amounts to supportive care (physical therapy, speech therapy, and breathing exercises) and so called “tincture of time”. For this reason I don’t suspect we will find any specific treatment for long COVID anytime soon.

Research is likely to help in predicting who is most likely to get it, and perhaps in treatments during the active infection that will reduce the chance of developing long COVID. For now just treating the infection itself is our best bet.

We are starting to see the scope of long COVID. An NHS survey in the UK from April 2020 to March 2021 found that 25% of patients from 35-69 years old complained of chronic symptoms more than 5 weeks following the presumed date of infection onset. This is not a small problem. It is important to include long COVID when we consider the toll of this pandemic. Much reporting focuses on the death toll, which of course is the worst outcome, but when considering the burden of an illness we need to include morbidity with mortality. Long COVID means millions of people will be affected, with lost productivity and increased health-care costs. Any “cost-benefit” analysis of steps taken to mitigate the pandemic needs to include long COVID in the equation.

It is also imperative for the medical community to pay close attention to long COVID – to find out as much as we can, and optimize management as much as possible. The situation is ripe for exploitation by the existing quack infrastructure. Pretty soon every existing snake oil treatment will become a treatment for long COVID and people who never even had COVID will be diagnosed with it to explain their symptoms and justify the snake oil. Victims of long COVID will then just be harmed again, extracting their time, energy, and limited funds and perhaps even exposing them to harmful interventions. Symptoms of long COVID tend to wax and wane, with good days and weeks and bad stretches of time – a setup for placebo effects to give the illusion that any intervention works. It’s coming, I have no doubt, and we’ll just have to stay on top of it as much as possible.