Chronic fatigue – classified as fatigue lasting more than six weeks – is recognised in many different clinical settings, from cancer treatment to inflammatory arthritis. It can be disabling. If 1% of the 290,000 or so people who have had COVID-19 in the UK remain under the weather at three months, this will mean thousands of people are unable to return to work. They will probably have complex needs that the NHS is ill-prepared to address at present.
COVID-19 is not the only cause of chronic fatigue. Prolonged fatigue is well recognised after other viral infections such as the Epstein-Barr virus, which causes infectious mononucleosis (also known as glandular fever). Post-viral fatigue was also seen in a quarter of those infected with the original Sars virus in Hong Kong in 2003.
When it comes to treating chronic fatigue, the emphasis previously has been on effective treatment of the underlying disease, in the belief that this would diminish the fatigue. However, for most viral infections there is no specific treatment, and because COVID-19 is so new, we don’t yet know how to manage post-COVID fatigue.
What might be causing post-COVID fatigue?
Although we know that lasting fatigue can sometimes follow other viral infections, detailed mechanistic insight is, for the most part, lacking. An ongoing viral infection in lung, brain, fat or other tissue may be one mechanism. A prolonged and inappropriate immune response after the infection has been cleared might be another.
However, a previous study has given us some insight. When a chemical called interferon-alpha was given to people as a treatment for hepatitis C, it generated a flu-like illness in many patients and post-viral fatigue in a few. Researchers have studied this “artificial infection response” as a model of chronic fatigue. They found that baseline levels of two molecules in the body that promote inflammation – interleukin-6 and interleukin-10 – predicted people’s subsequent development of chronic fatigue.
Of particular interest, these same pro-inflammatory molecules are seen in the “cytokine storm” of severely ill COVID-19 patients. This suggests there might be a pattern of immune system activation during the viral infection that is relevant to ongoing symptoms. Further support for interleukin-6 playing some sort of role comes from the successful use of tocilizumab – a treatment that lessens the impact of interleukin-6 and reduces inflammation – to treat severe COVID-19.