Researchers from the Amsterdam University Medical Center have discovered an important mechanism responsible for fatigue in people with Long COVID. They show that essentially it is an energy availability problem within the muscles, rather than hypoxia due to clots blocking tiny blood vessels as previously thought. The results were published in Nature Communications on January 4, 2024.
Studies conducted in India have revealed that 5.3% to 37.3% of individuals with COVID-19 either experience persistent health issues or develop new symptoms that last for well over three months. Fatigue, shortness of breath and brain fog are prominent among the new symptoms occurring in previously healthy people. This constellation of lingering symptoms has collectively been called Long COVID. Various hypotheses have been proposed to explain these.
The commonest symptom is extreme tiredness or fatigue that is worse after even mild exertion. For instance, walking a few steps might result in the same level of fatigue as climbing six flights of stairs, necessitating an immediate rest afterward.
The Amsterdam study primarily addressed this symptom. The researchers studied a group of 25 previously healthy, socially active people who developed Long COVID following a bout of mild disease. They were compared to a group of similar individuals who recovered completely from mild COVID-19. Being able to compare like versus like adds credibility to their findings.
The researchers performed blood tests and muscle biopsies in both groups before and after subjecting them to stationary cycling exercise. They discovered both structural and functional damage to muscles in Long COVID, likely from a deranged immune response. The cause of tiredness was identified as muscle cells not receiving sufficient energy from mitochondria. This is somewhat like using an old mobile phone with a weak battery and low charge, where even a brief conversation triggers a complete shutdown. Similarly, even a slight exertion led to excessive fatigue in the muscle cells.
When Long COVID was initially reported in 2020, many of these patients were subjected to extreme scepticism to the extent of dismissal, with accusations of their symptoms being “all in the mind”, and “not different from any other viral infection”. However, while typical viral infections might leave a person feeling tired for a few days to a couple of weeks at most, Long COVID stands out as the symptoms persist for more than three to six months, often varying in severity without any apparent cause. Moreover, new symptoms appear in previously healthy people.
Over a dozen studies have reported the risk of developing this condition among the Indian population. A study on non-hospitalised COVID-19 patients conducted by AIIMS Delhi revealed a 28% incidence at 28 days, while AIIMS Bhubaneswar reported a 9.2% incidence at six months. In a study of predominantly non-hospitalised individuals who got COVID-19 in spite of vaccination, Dr. Dipu T.S. and others from Amrita Institute of Medical Sciences and Research Centre, Kerala, reported a 10.1% incidence of Long COVID at three months. This indicates that Long COVID may occur even after mild initial disease and despite being vaccinated. Since the arrival of Omicron and its sublineages, the incidence of Long COVID has decreased, possibly due to reduced severity of initial illness.
Recent papers have looked at the post Delta era. A large study from Malaysia shows that 11.2% of people with symptomatic Omicron infection went on to develop Long COVID, defined as persistent symptoms beyond three months. A study from BJ Medical College Pune led by Dr. Rajesh Karyakarte shows that 5.3% of those with Omicron infection got Long COVID, compared to 12.4% during the Delta period. This study found that none of the individuals who had asymptomatic infection developed Long COVID.
Unlike deaths, Long COVID has received less attention, probably due to gradual, insidious changes that individuals suffer from. Long COVID is also perceived to be rare as routine investigations at times do not reveal anything abnormal and sometimes because the symptoms get wrongly attributed to other common conditions. As a result, the actual burden of Long COVID is not known.
The Amsterdam study which uncovers the actual reason for Long COVID will hopefully pave the way for scientific remedies. Supportive care and selected medications for subsets of patients remain the mainstay of treatment.
(Rajeev Jayadevan is co-chairman of the National IMA COVID task Force)
