Long COVID-19: What New Research Reveals About an Ongoing Threat

Since 2020, long COVID-19 has emerged as a widespread disabling condition, affecting the health and quality of life of millions of people worldwide. It has also cost economies billions of dollars through lower employee productivity and a reduced workforce.

The enormous scientific focus prompted by long COVID has produced more than 24,000 scientific publications, making it the most extensively studied health condition across any four-year period in recorded human history.

Long COVID describes the range of lasting health consequences caused by infection with the SARS-CoV-2 virus.

Its effects include ongoing respiratory problems, including breathlessness, as well as disabling fatigue and brain fog that can restrict people's capacity to work. It can also involve conditions including heart failure and diabetes, which are known to persist for life.

I am a physician scientist and have been closely involved in long COVID research since the earliest days of the pandemic.

I have appeared before the U.S. Senate as an expert witness on long COVID, published widely on the subject and, in 2024, was named among Time's 100 most influential people in health for my work in this field.

During the first half of 2024, a wave of reports and scientific studies brought greater understanding to this complicated condition.

In particular, they offered insights into the ways COVID-19 may continue damaging numerous organs years after the original infection, alongside growing evidence of viral persistence and immune dysfunction lasting months or years after infection.

How long COVID affects the body

A study published by my colleagues and me in the New England Journal of Medicine on 17 July 2024 found that the likelihood of developing long COVID fell as the pandemic progressed.

In 2020, when the original SARS-CoV-2 strain was dominant and vaccines were unavailable, around 10.4% of adults who contracted COVID-19 went on to develop long COVID.

By early 2022, when the omicron family of variants had become predominant, the figure had fallen to 7.7% in unvaccinated adults and 3.5% in vaccinated adults. Put another way, unvaccinated people were more than twice as likely to develop long COVID.

Researchers such as me do not yet have firm figures for the rate in mid-2024, because cases of long COVID take time to appear in the data. However, the number of new patients arriving at long COVID clinics has remained comparable with 2022.

Our research identified two main reasons for this reduction: vaccine availability and changes in the virus itself. These changes made the virus less likely to produce severe acute infection and may have weakened its ability to remain in the body long enough to cause chronic illness.

Nevertheless, even a 3.5% chance of developing long COVID is considerable. New and repeat COVID-19 infections result in millions of additional long COVID cases, adding to an already immense number of people living with the condition.

Estimates from the pandemic's first year suggest that at least 65 million people worldwide have experienced long COVID. Alongside other leading scientists, my team will shortly publish updated estimates of the worldwide burden of long COVID and its effect on the global economy through 2023.

A major new report from the National Academies of Sciences Engineering and Medicine also sets out the full range of health consequences that make up long COVID. The Social Security Administration commissioned the report to assess what long COVID means for its disability benefits.

It found that long COVID is a complex chronic condition that may cause more than 200 health effects involving several body systems. These can include the new onset or worsening of:

• heart disease
• neurological problems, including cognitive impairment, strokes and dysautonomia. This category of disorders affects the body's autonomic nervous system - the nerves controlling many vital functions, such as blood pressure, heart rate and temperature.
• post-exertional malaise, an episode of profound exhaustion that can follow even minor activity - often leaving a patient unable to function for hours, days or weeks
• gastrointestinal disorders
• kidney disease
• metabolic disorders, such as diabetes and hyperlipidaemia, or raised bad cholesterol
• immune dysfunction

Long COVID can affect people throughout life, from children to older adults, across racial and ethnic groups, and regardless of their previous health status. Crucially, more than 90% of people with long COVID had mild COVID-19 infections.

The National Academies report further found that long COVID may prevent people from returning to work or education, reduce quality of life, limit their ability to carry out everyday activities, and lower physical and cognitive functioning for months or years following the original infection.

It also notes that several effects of long COVID - including post-exertional malaise and chronic fatigue, cognitive impairment, and autonomic dysfunction - are not included in the Social Security Administration's Listing of Impairments. Yet they may substantially affect a person's ability to take part in work or education.

A long road ahead

Moreover, health issues caused by COVID-19 may continue for years after the initial infection.

A large study released in early 2024 found that even people who had experienced a mild SARS-CoV-2 infection developed new COVID-19-related health problems during the third year after their original infection.

These results reflect other research showing that the virus can persist in different organ systems for months or years after COVID-19 infection. Studies also indicate that immune responses to infection remain detectable two to three years after a mild infection.

Taken together, this research may help explain why an infection with SARS-CoV-2 years earlier can still lead to new health problems long after the original illness.

Important advances are also being made in identifying the mechanisms through which long COVID causes widespread harm in the body.

Two preliminary studies, one from the U.S. and one from the Netherlands, found that healthy mice began showing long COVID-like symptoms, including muscle weakness and poor balance, when researchers transferred auto-antibodies into them from people with long COVID. Auto-antibodies are antibodies made by a person's immune system that target their own tissues and organs.

The studies indicate that an abnormal immune response, believed to drive the production of these auto-antibodies, may be involved in long COVID. They also suggest that removing these auto-antibodies could offer promise as a potential treatment.

An ongoing threat

Despite compelling evidence of COVID-19's broad risks, much public messaging implies that it no longer poses a threat. There is no empirical evidence supporting this claim, yet the misinformation has become embedded in public discussion.

The evidence, however, presents another picture.

COVID-19 infections still exceed flu cases and cause more hospitalisations and deaths than flu. COVID-19 also produces more severe long-term health problems. Treating COVID-19 as a harmless cold, or suggesting that it is equivalent to flu, is not consistent with reality.

Ziyad Al-Aly, Chief of Research and Development, VA St. Louis Health Care System. Clinical Epidemiologist, Washington University in St. Louis

This article is republished from The Conversation under a Creative Commons licence. Read the original article.