While reports of the mysterious condition known as long COVID are rising, less is known about its prevalence, risk factors or whether it is possible to predict. Defined as displaying coronavirus symptoms for longer than four weeks with no other cause, long COVID can have devastating effects on health. It is therefore helpful to know the symptoms to look out for. New research suggests that it is possible to predict those most at risk of developing long COVID after coronavirus infection, identifying those in need of targeted treatment.

Diverse symptoms

Coronavirus or COVID-19 effects individuals differently, with its consequences ranging from asymptomatic to fatal. The duration of symptoms can also vary [1]. After initial infection, individuals can develop symptoms including fever, fatigue, headache, dry cough and change in taste or smell. The body’s immune system responds to invading pathogens like the SARS-CoV-2 virus and works to reduce viral replication, causing inflammation and activating molecules specific to coronavirus like immunoglobulin M (IgM), IgA and IgG antibodies. After about three weeks, most infected people will fully recover and their symptoms will clear. However, a third of people experience continued coronavirus symptoms for more than four weeks after initial infection, a condition that is now known as long COVID. If you have previously been infected with coronavirus and are experiencing long lasting symptoms that cannot be explained by anything else, it is most likely due to long COVID.
The long COVID symptoms reported most frequently include:

• Fatigue
• Cognitive impairment ‘brain fog’ that presents as reduced concentration and memory loss.
• Change in smell or taste
• Aches and pains [2].

Long COVID initially confused the medical community due to the heterogenous nature of its symptoms. As the pandemic continues, long COVID is becoming recognised as having a serious, long-term impact on health and identifying those who are at risk of developing it after infection is integral. The underlying cause of these prolonged symptoms is uncertain but thought to be related to an overreaction of the body’s immune response to the coronavirus infection. This produces inflammation and can cause cytokine storms, seen in patients with severe COVID-19 cases. Despite being part of the immune response, this can have the opposite effect and actually inflict damage on the body. Indeed, infections can cause long term damage when they effect the brain; for example, chronic fatigue symptoms (CFS) and myalgic encephalitis (ME) can develop following a neurological viral infection [3].
Read more about COVID-19 and immune health here.

Predicting the risk of long COVID

Similarly to the risk of developing severe COVID-19, it is thought that those most at risk of long COVID include older people and those with underlying health conditions, as well as those who developed more symptoms during initial coronavirus infection [1].
Now, new research published in Nature Communications holds future potential for a blood test that can predict a person’s risk of developing long COVID. In a prospective cohort study, researchers followed individuals who had been previously been infected with coronavirus for one year following infection and compared them to individuals without coronavirus. They found that an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, in those who had COVID-19 could predict the risk of developing long COVID. The development of long COVID is related to this distinct Ig signature, in addition to patient age, history of asthma and number of symptoms experienced during primary infection. The researchers used this finding to develop a model known as post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) score and used it on the cohort. They found that the PACS score could identify those at risk of developing long COVID no matter the timepoint of testing, and performed better than symptom-based scores and did not require specialised tests like SARS-CoV-2-specific immunoassays.
It has been previously thought that women are more likely to develop COVID as they have an increased infection rate compared to men. However, the study found no evidence for this and in fact male sex is associated with worse acute COVID-19 outcomes. The study recommended that the prediction score be sex-independent.
The research suggests that there is another possible mechanism by which long COVID can develop, distinct from increased inflammation from activating the immune system. Unlike inflammatory makers that increase during infection, unspecific Ig levels remain stable over time. This increases the possibility of using them as biomarkers. The research signposts the ability to measure Igs in the blood in order to predict which individuals with coronavirus are at risk of developing long COVID, particularly in hospital patients, and highlights the need for targeted treatments [2].
Long COVID is one of the many effects of the ongoing pandemic that will have long-term consequences. Spotting its symptoms, as well as using future predictive tools, can help limit its impact on health and lifespan.