Millions of people worldwide may have experienced long covid, with some having symptoms that have lingered for several years. However, while the number of cases is exceptional, the syndrome itself is not.
Long covid is one of many chronic conditions that can be triggered, at least in part, by infections, mostly by viruses. A surge of interest in long covid has helped us gain an improved understanding of what causes some of these conditions, from the role of herpes viruses in myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) to different viruses鈥� potential effects in the onset of fibromyalgia, a condition that causes chronic pain throughout the body as well as other symptoms, like fatigue.
The scale of the long covid pandemic is staggering. A recent analysis of multiple studies, led by at the Patient-Led Research Collaborative in New York, offered a 鈥渃onservative鈥� estimate that caused by the SARS-CoV-2 coronavirus result in long covid. Given there have been , this implies at least 75 million incidences of long covid.
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Possible causes of long covid
Long covid causes a wide range of symptoms, including brain fog, shortness of breath and post-exertional malaise. Exactly why it occurs is unknown, but there are multiple potential causes. Many people with long covid have ongoing disruption to their immune system, whether it be overactive or suppressed, which may contribute to the symptoms. Microscopic blood clots have been seen in some people, which may block and damage the smallest blood vessels, potentially explaining their fatigue. And some people may have persistent coronavirus infections that remain in the body.
This array of potential causes may mean there are several kinds of long covid 鈥� including post-intensive care and post-viral fatigue syndromes 鈥� each involving different mechanisms and combinations of symptoms. But long covid itself didn鈥檛 come as a surprise. 鈥淚 think it was quite reasonable to expect SARS-CoV-2 to cause chronic problems,鈥� says at Brunel University London. That is because other coronaviruses, such as those that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), have triggered long-term problems.
Nevertheless, long covid has drawn researchers鈥� attention to other conditions that can commonly occur after a viral infection, some of which have been neglected for decades.
Viral triggers for ME/CFS
One condition that was garnering increased scientific attention before the covid-19 pandemic is ME/CFS 鈥� and long covid has raised its profile further. The most common include near-constant tiredness, even after sleep, and taking a long time to recover following exercise. This has considerable overlap with long covid: a study published in 2022 of 465 people with long covid found that met the criteria for ME/CFS.
鈥淚f you ask any ME/CFS patient, they always say it started with flu-like or cold-like symptoms鈥�
Some have long suspected that ME/CFS is triggered by a viral infection, but pinning down the culprit has been hard, says at the University of W眉rzburg, Germany. 鈥淚f you ask any patient, they always say it started with flu-like or cold-like symptoms,鈥� he says. But by the time ME/CFS has developed and doctors are investigating, there is no trace of the original virus.
Prusty thinks ME/CFS originates in early childhood, when most people are infected by human betaherpesvirus 6B (HHV-6B), which causes a mild illness lasting a few days. 鈥淎fterwards, the virus stays in our body for the rest of our lives,鈥� says Prusty. Later in life, the virus can become reactivated 鈥� and it is this that Prusty and some others believe causes ME/CFS.
In a 2021 study, Cliff and her colleagues took monthly saliva samples from 30 people with ME/CFS and 14 people who didn鈥檛 have the condition. Those with ME/CFS had higher levels of HHV-6B and another herpes virus, HHV-7, than those without. In people whose symptoms fluctuated over time, more severe symptoms were .
In 2022, Prusty and his colleagues from three people who had been diagnosed with ME/CFS, plus three who hadn鈥檛. They only found signs of HHV-6B activity in the brain and spinal cord of those who鈥檇 had ME/CFS.
鈥淭he virus doesn鈥檛 have to be completely active [and] doesn鈥檛 have to produce viral particles,鈥� says Prusty, who describes what the team saw as localised infections. This limited viral activity seems to be enough to cause chronic symptoms.
Prusty thinks reactivated herpes viruses may also be a factor in long covid, specifically in cases where symptoms last beyond three months or even for years. In line with this, in 2022, Eirini Apostolou at Link枚ping University, Sweden, and her colleagues showed that people EBV, HHV6 and HERV-K in their saliva three to six months after becoming infected with SARS-CoV-2, suggesting that the herpes viruses were reactivated after they caught the coronavirus. This was particularly true for those who also had ME/CFS.
Fibromyalgia鈥檚 multiple triggers
Just as long covid and ME/CFS overlap, so do ME/CFS and fibromyalgia. In 2022, at the National Institute of Cardiology Mexico in Mexico City and his colleagues showed that .
Unlike ME/CFS, where viruses may be responsible, in fibromyalgia they could be one of multiple causes. 鈥淚nfection induces fibromyalgia in a subgroup of fibromyalgia patients,鈥� says Mart铆nez-Lav铆n. 鈥淧sychological stress, physical trauma and autoimmune illnesses are other recognised triggers.鈥�
But a picture is forming of how viruses may give rise to the condition. Mart铆nez-Lav铆n thinks the key to fibromyalgia lies in the dorsal root ganglia, a set of 31 nerve clusters dotted along the spine. Many pathogens are able to infect them, including herpes viruses, the hepatitis C virus and SARS-CoV-2.
When the neurons鈥� normal function is disrupted, Mart铆nez-Lav铆n thinks they may send erroneous signals to the brain, causing the sensation of pain where no tissue damage exists. Studies have found correlations between , and a small study in 2022 suggested that antiviral drugs targeting chronic hepatitis C in some people.
Rethinking chronic conditions
While the mechanisms of conditions like long covid, ME/CFS and fibromyalgia are becoming clearer, many questions remain unanswered. We don鈥檛 know why certain viral infections are more likely to cause chronic conditions than others or what makes some people more susceptible to developing these conditions.
A long-standing challenge has been the lack of diagnostic tests that can reliably distinguish people who have chronic fatigue and pain conditions from people who don鈥檛 by measuring a particular molecule in a person鈥檚 blood or a similar bodily substance.
In the longer term, digging into the physiological mechanisms of these conditions should suggest the best treatment options. In the meantime, Cliff says sociological change is the most important preventative step we can take.
鈥淚 think personally there needs to be a bit of a groundswell change in the way we view illness,鈥� she says. 鈥淭here is evidence that overexertion early on after an acute infection is more likely to lead to chronic ill health than recovery.鈥� In other words, when we are ill we should take time to rest rather than rushing back to work or school while still unwell. 鈥淚 don鈥檛 think that enables us to get better,鈥� says Cliff.
Article amended on 1 March 2023
This article has been changed to correctly define ME.
