Abstract
The COVID-19 pandemic was unprecedented in the number of people affected from all cultures and countries. It posed immediate challenges of how to counter the Severe Acute Respiratory Syndrome-Coronovirus-2 that was causing fatalities, overburdening hospitals, and to develop effective vaccines and antivirals to complement the public health measures. The ribonucleic acid technology used to develop a novel class of vaccines proved highly successful in reducing the severe case numbers and fatalities. More challenging were the secondary long lasting effects from the viral infection in a relatively high proportion of patients now estimated to be in the range of 5-15%. The post viral condition, termed publicly Long COVID, and clinically Post Acute Sequelae of COVID-19 surprised many clinicians with its intractability. However, it mirrored previous experiences of patients suffering from ongoing post-viral (stressor) conditions, covered by the umbrella term, Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome. From over 775 million worldwide COVID-19 infections reported to date there has arisen an estimated 60 million cases of Long COVID. Long COVID is a hetergeneous condition with ~50% having a classic Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-like syndrome with over 200 similar symptoms to those reported for this syndrome, but in addition ~25% are debilitated following the specific acute effects of the virus on body organs like the lungs, heart, and kidneys. This heterogeneity highlights the challenges of developing future management strategies, and treatments for the group as a whole to at least lessen the burden for all, and to reverse the fatigue syndrome post-viral condition for those with that clinical phenotype. Opportunities to understand Long COVID as a model of post-viral conditions are possible because the condition has arisen with such a large number of cases specific from this single stressor at the same time. Meaningful longitudinal patient studies can now be initiated and its immediacy and frequency has caught the attention of clinicians and scientists worldwide. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome cases by contrast have arisen constantly as a ‘drip feed’ in small numbers from boutique infectious outbreaks like the first Severe Acute Respiratory Syndrome virus epidemic in 2003 where there were only ~ 9000 infections, or from endemic viruses like Epstein-Barr virus (glandular fever) from which ~5-10% develop a post-viral condition, but additionally from other major stressors. Widespread interest and investment in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome research has been lacking. Long COVID has now many talented scientists and clinicians researching its pathophysiology, and there has been significant investment, spearheaded in the United States through the ‘Recover Initiative’. It is hoped promising treatments can now be developed and tested in clinical trials. This gives hope for the ‘missing millions’ of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients worldwide, many of whom have had their condition neglected for decades. Beyond the core symptoms that define the clinical case definitions for both Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome it is becoming clear the broader symptoms of an individual patient can not only reflect their previous health histories and co-morbidities, but also their specific genetic background. The major challenge ahead is there will likely need an individual-focused treatment strategy to improve the quality of life for these patients. Fundamental advances are still needed like simple accessible diagnostic tests based on molecular markers that can rapidly confirm the condition, follow its progress, and identify those at risk.