What we know about long COVID

Research Monitor, May 5th 2021

By Dylan Barry, GCPPP staff

With vaccination campaigns gathering steam in the advanced economies, for many rich countries the end of the pandemic is in sight. But while the coronavirus itself might be brought under control, a longer-term legacy is coming into focus.

For many COVID-19 patients, infection has proved to be only the start of months of persistent and often debilitating symptoms. This continuing syndrome was initially known only from scatter reports, but vocal advocacy from sufferers—who call themselves “long haulers”—connected in online communities on the internet has brought the condition into the spotlight. This is long COVID, a mysterious condition thought to affect millions of people worldwide.

What is long COVID?

The medical community is hard at work trying to understand long COVID, also known as post-acute COVID-19 syndrome (PACS). There is not yet a universally agreed-upon definition of the condition.  The  United States Centers for Disease Control and Prevention (CDC) employs it as an umbrella term for the wide range of health consequences that are present more than four weeks post-infection with SARS-CoV-2, the virus that causes COVID-19.

The most common COVID-19 symptoms to persist post-infection are chronic fatigue, a persistent cough, headaches and muscle pain (myalgia), with 12 symptoms observed frequently enough to be tracked by the Office for National Statistics (ONS) in the United Kingdom.



There is debate over whether long COVID is a single condition or multiple overlapping ones. This is because its symptoms present themselves in three distinct clusters.

The first cluster includes cognitive and neurological symptoms, like so-called brain fog—a general sense of mental fuzziness—as well as issues with memory recall, chronic fatigue, insomnia, anxiety and depression.

The second cluster includes issues with the autonomic nervous system which governs automatic bodily functions, such as  persistent heart palpitations, issues with breathing and digestion, and dizziness.

The third cluster consists of general internal organ issues, including often severe cardiovascular and pulmonary (heart and lungs) symptoms like shortness of breath, chest pain, blood clots and a persistent cough, but also renal (kidney), endocrine (hormonal) and dermatological symptoms too.

According to the UK’s data, the syndrome appears most often in people between the ages of 35 and 69, with a median age of 45 among those who self-report as long COVID sufferers. The evidence is strong that women are more likely to suffer from long COVID than men, a surprising finding given that men are more likely to contract COVID-19 and to die of it. Finally, the condition appears to be most prevalent amongst healthcare workers and the poor.




What causes long COVID?

Because of its varied symptoms, doctors are looking into four primary mechanisms to explain long COVID.

The first is post-traumatic stress disorder (PTSD). A serious case of COVID-19 can be deeply traumatic and there is strong evidence that many COVID-19 survivors struggle with PTSD and other forms of mental ill-health in its aftermath. That might help explain symptoms of anxiety, depression and insomnia in some long COVID sufferers.

The second is that long COVID is a persistent SARS-CoV-2 infection. The premise behind this is that some patients never entirely overcome the virus. As a consequence, a lingering viral presence might last for months while the body continues to fight it off. These patients would not be infectious—the pathogens left in their systems may even be inert—but a continued viral presence might explain some persistent COVID-19 symptoms.

There is as yet no smoking gun for this hypothesis, but there is precedent. In the aftermath of viruses such as measles, dengue fever and Ebola—all RNA viruses like the coronavirus—a lingering viral presence is known to cause similar conditions. In a recent paper in Nature, researchers also showed that COVID-19 patients can continue to show traces of SARS-CoV-2 in their intestines up to four months post-infection, which shows that viral proteins can evade the immune system for that long.

The third possible explanation is that long COVID may be an autoimmune disease, a condition in which the body’s immune system mistakenly attacks itself. That could explain symptoms such as chronic fatigue, muscle pains and autonomic nervous system issues. There is weight behind this hypothesis. There is some evidence that immune cells misbehave in long COVID patients. Especially compelling is the fact that long COVID patients produce unusually high levels of auto-antibodies, cells that attack the body’s own tissues.

One possibility is that COVID-19 triggers the emergence of autoimmune diseases in people with a genetic predisposition for this. There is evidence that at least two adult patients have unexpectedly developed Grave’s disease, a disorder that produces an overactive thyroid, immediately post-infection; and COVID-19 infection also appears to precipitate Kawasaki disease, a blood-vessel disorder, in children. That women are on average more vulnerable than men to developing an autoimmune disease may also help explain why women develop long COVID at notably higher rates.

The fourth hypothesis is that long COVID is the result of irreparable damage done by the initial SARS-CoV-2 infection, mostly through inflammation. This might explain the internal organ problems in long COVID patients, especially symptoms like shortness of breath, chest pain and chronic fatigue that might be the result of severe lung damage.

It is possible that inflammation is damaging the lining of blood vessels, obstructing regular blood flow to the brain, which might also explain cognitive symptoms like brain-fog, memory loss and headaches.

How is long COVID treated?

Thus far, the single best treatment for long COVID has proven to be time. For patients who test positive for COVID-19, the probability that at least some COVID-19 symptoms will persist five weeks post-infection is 21.0%. That drops to 13.7% at twelve weeks.

This  suggests – but does not guarantee – that many long COVID patients will recover eventually. In the meantime, a recent guide in the British Medical Journal suggests offering symptomatic relief with medication like painkillers and non-steroidal anti-inflammatory drugs.

An active  treatment currently in use is rehabilitation. The same guide reports that most—but not all—patients recover well with four to six weeks of light aerobic exercise (such as walking or Pilates), gradually increasing the intensity over time. For those with chronic breathlessness, breathing exercises and guidance on better breathing techniques can make a big difference too.

For a yet-unknown number, however, the road to recovery can be a long and continuing one. The neuroscientist David Putrino, who established the United States’ first COVID long-hauler treatment centre at Mount Sinai Hospital in New York, has found that even 150 days (five months) of weekly physical therapy only reduces chronic fatigue in long COVID patients by 30-40% on average.

The real hope is that once the root causes of the syndrome are better understood, more targeted treatments will become possible. If long COVID is partly caused by a persistent viral infection, the existing gamut of antiviral treatments are likely to make for effective treatments. Treatments for specific autoimmune diseases also already exist. Once the precise nature of the autoimmune disfunctions that contribute to long COVID are pinned down, some of these will likely be transferable to treating long COVID too.

Long COVID in emerging perspective

These and other options are already being investigated in clinical trials. Nevertheless, it remains likely that some people will be scarred for life by their encounters with the coronavirus.

From surveys, the ONS estimates that at least 1.1 million people in the United Kingdom are currently living with long COVID. Of those, 697,000 first had (or suspect they had) COVID-19 more than twelve weeks ago. This duration extends beyond six months for 473,000 people and one year for 70,000 people.

Those are startling numbers, and they reflect the fact that long COVID will remain a public health challenge all over the world long after the pandemic itself is over, with a lasting impact on people’s quality of life and, conceivably, on economic productivity. To mitigate these impacts governments should consider measures to support those suffering with long COVID, including guidance to both employers and employees on how best to reintegrate long COVID patients back to work during their recovery.

Whatever governments choose to do, long COVID is likely to remain a cause for concern in the post-pandemic world. It should be treated as such.

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