Long-standing COVID symptoms may improve, but healing is slow and incomplete

About 5-10% of people who contract SARS-CoV-2 experience symptoms that last well beyond the initial acute phase, a clinical syndrome we are learning more about and commonly known as long-COVID is.

Shortness of breath, brain fog, lethargy and fatigue, loss of smell or taste are common features of Long-COVID, as is the development of new conditions such as diabetes, heart disease, stroke, depression and dementia.

But how long is “long”? When and when do the symptoms subside?

A recent study looked at this in detail, following people for two years after they were infected. This and other recently published Long-COVID studies show that while symptoms resolve in many people, recovery is slow and incomplete.

What did the study find out?

The key work, led by Ziyad Al-Aly, examines the effect of SARS-CoV-2 two years after infection in a large group of US veterans.

Researchers tracked 139,000 people with COVID and nearly six million uninfected controls for two years, tracking deaths, hospitalizations and 80 long-term effects of COVID, categorized into ten organ systems.

They found that people who were initially hospitalized with COVID had a 1.3 times greater risk of dying and a 2.6 times greater risk of being hospitalized again over the two years Compared to the control group (people without COVID).

After two years, this “hospitalized” group continued to have an increased risk of 50 diseases.

People with milder COVID (who were not hospitalized with their first COVID infection) had an increased risk of dying for up to six months and an increased risk of being hospitalized for up to 18 months.

After two years, however, there was still an increased risk of 25 diseases.

So while people who were initially hospitalized for COVID experienced poorer outcomes over the two-year follow-up period, there was still a significant burden of disease in people who initially had milder COVID illness.

These included the risk of blood clots and blood disorders, lung disease, fatigue, bowel disease, muscle and joint disorders, and diabetes.

The results of other recent research have been similar

A separate cohort study tracked more than 208,000 veterans with COVID over a two-year period. It showed that 8.7% died overall, compared to 4.1% in the uninfected control group. The risk of death was concentrated in the first six months after infection.

A third, not yet peer-reviewed and smaller cohort study of 341 people with long COVID from Spain found that only 7.6% of them recovered after two years.

Another major (not yet peer-reviewed) study from the UK assessed post-COVID diabetes risk by following 15 million people in England in 2020-21.

A 30-50% increased risk of new type 2 diabetes after COVID was found. This increased risk lasted up to two years. However, the risk of type 1 diabetes did not persist.

An Australian (not yet peer-reviewed) study followed 31 people who developed long-term COVID and 31 matched controls who recovered from COVID for two years.

It turned out that most of the worrisome immunological dysfunctions that had emerged after eight months had disappeared after two years.

While nearly two-thirds of those with long-term COVID (62%) reported an improved quality of life over the two years, one-third continued to experience issues two years after their infection.

Finally, a recent whole-body positron emission tomography (PET) imaging and biopsy study demonstrated prolonged immune activation at the tissue level and viral persistence in the gut for up to a remarkable two years after COVID.

These studies have some limitations

It is important to note that the observational studies have some inherent limitations.

Almost 90% of the US veteran cohort studied by Al-Aly is male with a median age of 61, different from the groups most at risk of long-term COVID-19.

They contracted their initial infection in 2020, before Omicron, before vaccination and before therapies – all of which protect against long-COVID to some degree.

Nonetheless, Long-COVID is still common in vaccinated individuals infected with Omicron.

We’re still wearing itThere are no treatments for Long-COVID

A growing understanding of the underlying mechanisms of long-COVID, such as the involvement of persistent viruses and the impact on the mitochondria – the powerhouses of cells – may lead to treatment options that need to be explored.

In July 2023, the White House established the Office of Long COVID Research and Practice. Two randomized trials are testing whether the antiviral drug nirmatrelvir-ritonavir (Paxlovid) can be used to treat long-term COVID. Patients are currently being recruited.

A separate randomized, placebo-controlled study showed that when taken for two weeks (and within three days of testing positive for COVID), metformin, a commonly prescribed antidiabetic drug, reduced the likelihood of long-term COVID-19 by 41%.

The mechanism may involve an effect on mitochondria or directly on the virus.

But itIt is still important to prevent COVID (re)infections

Collectively, these long-COVID longevity studies contribute significantly to accelerating the development of interventions and therapies to prevent and/or cure the disease.

In the meantime, preventing (re)infections in the first place is crucial to reduce the future burden of long-lived COVID, which is already estimated to be affecting more than 65 million people worldwide.

Breathe clean air by making sure indoor spaces are well ventilated. In poorly ventilated or crowded spaces, wear a well-fitting, good quality mask (a P2, KN95, or N95 mask) and/or use air filtration equipment appropriate for the space you are in.

Stay up to date with boosters. And get tested so you can get antiviral treatment if you qualify.

If you suspect you have Long-COVID, discuss this with your GP, who may refer you to specialized services or multidisciplinary treatment.

Written by Suman Majumdar, Brendan Crabb. The conversation.

If you care about your health, please read studies showing that vitamin D can reduce inflammation and that vitamin K could reduce your risk of heart disease by a third.

For more health information, check out recent studies on new ways to stop excess inflammation and the results showing that foods can cause inflammation.

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