Long COVID: symptoms experienced during infection may predict lasting illness

Earlier in the pandemic, it appeared that the majority of people infected with the coronavirus experienced mild-to-moderate symptoms and generally recovered within two to three weeks, depending on the severity of their illness. However, as time has passed, it’s become clear that some people, regardless of the severity of their disease, continue to experience symptoms beyond the acute phase of infection. This has become known as “long COVID”.

Emerging evidence suggests that these patients experience a range of persistent symptoms and health complications. These may have a significant impact on their quality of life, physical and mental health, and ability to return to work.

But understanding long COVID is difficult. Its reported symptoms are highly varied, making it difficult to define. Many sufferers also weren’t hospitalised during the acute phase of their infection, and so weren’t tested for the coronavirus during the first wave of the pandemic. This makes it more difficult to understand what the potential causes of their long-lasting symptoms are, and also how these relate to symptoms that patients had during the early stages of infection.

We and other researchers from the Therapies for Long COVID (TLC) Study Group at the University of Birmingham therefore decided to try to build a clearer picture of what long COVID is and what influences it by pooling data from lots of separate studies. This gave us a view of the prevalence of reported symptoms, and better allowed us to see what the impacts and complications of long COVID are. Here’s what we discovered.

Symptoms of long COVID

Our review showed just how varied long COVID is. Patients may experience symptoms related to any system in the body – including respiratory, neurological and gastroenterological symptoms. Our pooled data showed that the ten most commonly reported symptoms in long COVID are fatigue, shortness of breath, muscle pain, cough, headache, joint pain, chest pain, an altered sense of smell, diarrhoea and altered taste.

Other common symptoms include “brain fog” – when thinking is fuzzy and sluggish – memory loss, disordered sleep, heart palpitations and a sore throat. Rare but important outcomes include thoughts of self-harm and suicide and even seizures.

Most long COVID patients complain of symptoms experienced during their acute infection persisting beyond it, with the number of symptoms experienced tending to decline as patients move from acute to long COVID. Some, though, report developing new symptoms during their long COVID illness, while some also report symptoms reoccuring that had previously resolved themselves.

One of the studies we included in our review described two main symptom clusters of long COVID: those comprising exclusively of fatigue, headache and upper respiratory complaints; and those that are multi-system complaints, including ongoing fever and gastroenterological symptoms. This division encapsulates the difficulty of trying to pin long COVID down – it is a wide-ranging condition containing many types of complaints.

The mid-term and long-term effects and impacts of long COVID are yet to be fully understood. However, the evidence we reviewed suggests that people with long COVID may experience significant reductions in their quality of life, difficulties carrying out their daily activities or returning to full-time employment, as well as mental health issues.

One study reported that nearly a quarter of previously hospitalised COVID-19 patients suffered from anxiety or depression six months after the onset of their symptoms. People with long COVID often report being dismissed by healthcare professionals and receiving little or no support for the management of their condition – underlining the need for better treatments.

What increases the likelihood of long COVID?

We found that a range of factors are associated with developing long COVID. For instance, one study reported that the presence of more than five symptoms of COVID-19 in the first week of infection was significantly associated with developing long COVID, irrespective of age or gender.

In addition, being older, female and hospitalised at symptom onset were found to be significantly associated with an increased risk of developing long COVID. However, several studies showed that for a significant number of patients, developing long COVID didn’t seem to be tied to the severity of their initial illness.

Experiencing certain symptoms during the acute phase of infection – such as initial breathlessness, chest pain or abnormal heart sounds – was also strongly associated with developing long-lasting symptoms. Having co-morbidities, particularly asthma, also raised the risk.

What the huge variability of long COVID suggests is that it actually comprises a number of different syndromes, potentially with different underlying causes. A better understanding of the underlying biological and immunological mechanisms of long COVID is therefore urgently needed if we’re to develop effective treatments for it.

The impacts that patients report – on their lives, work and mental health – make it clear that better ways of caring for people with long COVID patients are urgently needed. As well as evaluating symptoms and investigating the underlying mechanisms of long COVID, our TLC Study Group was set up to identify potential interventions for treating long COVID that could be evaluated in clinical trials. Armed with the knowledge from this research, this is what we’re aiming to work towards next.

Olalekan Lee Aiyegbusi receives funding from the National Institute for Health Research (NIHR) and UK Research and Innovation (UKRI) (grant number COV-LT-0013). He also receives funding from the NIHR Birmingham Biomedical Research Centre (BRC), NIHR Applied Research Centre (ARC) West Midlands at the University of Birmingham and University Hospitals Birmingham NHS Foundation, Innovate UK (part of UK Research and Innovation), Gilead Sciences Ltd, and Janssen Pharmaceuticals, Inc. Olalekan Lee Aiyegbusi declares personal fees from Gilead Sciences Ltd, GlaxoSmithKline (GSK) and Merck outside the submitted work.

Shamil Haroon receives funding from the National Institute for Health Research (NIHR) and UK Research and Innovation (UKRI) (grant number COV-LT-0013). He also receives funding from the West Midlands NIHR Clinical Research Network.