This post was written by two ENDVOC team members: Robert Aldridge, Professor of Public Health & Data Science at UCL, and his colleague Sarah Beale. Robert Aldridge leads ENDVOC’s WP7, which focuses on the impact of viral variants on long COVID. He co-led the Virus Watch study, in which Sarah Beale also participated.
We have made huge strides in understanding, preventing, and treating coronavirus disease 2019 (COVID-19) since it was first identified in late 2019. While vaccines and treatments have greatly reduced the risk of severe illness and death from acute COVID-19, some people develop debilitating long-term symptoms after infection – commonly referred to as ‘long COVID’. As defined by the World Health Organisation (WHO), long COVID or post COVID-19 condition refers to symptoms that continue or develop within three months following infection, that last more than two months, and that cannot be explained by another cause. Common symptoms include fatigue and/or weakness, generalised pain, breathlessness, and memory problems. However, over 200 long COVID symptoms affecting different organs have been reported. Long COVID can be difficult to define because of the wide range of possible symptoms, and because different studies often measure different symptoms, making it difficult to estimate overall incidence.
Challenge 1. Estimating how many people are affected
At least 65 million people worldwide are believed to suffer from debilitating long-term symptoms following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), based on officially reported cases. However, because many infections go unreported, the number of long COVID cases is probably higher. Between 10-30% of people with mild-to-moderate COVID-19 are estimated to develop long COVID. People who are hospitalised with COVID-19 appear to be at greater risk of developing long COVID (up to 50-70%). The likelihood of developing long COVID also appears to be influenced by vaccination status and by the virus variant. People’s experience of long COVID may also change over time, with symptoms that can vary, disappear, come back, or fluctuate in their severity. Estimating the incidence of long COVID and studying how it changes over time is challenging due to the range of potential symptoms and the need to identify and follow-up COVID-19 cases – particularly as widespread community testing is no longer being done in many locations. A major focus of the END-VOC project is to use community cohorts around the world to investigate the incidence and risk factors for long COVID, how it changes over time, and how it is impacted by different virus variants.
Challenge 2. Understanding the causes
Our understanding of the processes that cause long COVID is at an early stage. The main hypotheses include persistent viral infection, reactivation of other latent viruses, tissue damage caused by inflammation or by the body’s immune system attacking its own tissues, problems with blood clotting, and disruption of microbes in the gut. In fact, it is probable that all of these processes may be at work in different cases, which may explain the large variation in symptoms, severity and duration. In short, more research is needed to understand how long COVID develops and persists, so that we can develop effective treatments.
Challenge 3. Finding effective treatments
Since our understanding of long COVID is still at an early stage, most treatments tried so far were originally used for other conditions, particularly chronic syndromes that often develop after viral infections such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Currently, no single treatment has shown broad effectiveness for long COVID. However, some treatments appear to show promise for specific clinical presentations. For example, naltrexone – which can reduce neuroinflammation and associated symptoms such as fatigue – has shown promise in case reports and is currently in Phase 2 trials. Anticoagulant medications such as sulodexide have also shown promise in early trials for reducing blood vessel complications and clotting problems in long COVID patients. Non-drug treatments, such as pacing activities to prevent fatigue, also seem to be helpful for managing the impact of long COVID. A substantial problem is that many studies of potential treatments are based on reports and not on clinical trials with comparison groups. It is therefore vital to conduct well-designed clinical trials for promising candidate treatments. Involving COVID patients as research partners is proving to be an essential approach to understand patients’ needs and to respond to them effectively.
The way forward: Involving patients in research
Because long COVID is common and can cause severe and long-term disruption to people’s health, wellbeing, and activities, there is an urgent need to better understand its causes and develop effective treatments and accessible services. Ongoing research involving scientists, healthcare professionals and long COVID patients will help us approach this complex condition from different perspectives and to tackle it effectively.