Understanding Long COVID: Symptoms, Management, and Research Insights

Introduction

Long COVID is a phenomenon that has become the subject of increased attention. In this article, we explore the condition, its symptoms, and strategies for its management and discuss the latest research on the topic.

What is Long COVID?

Long COVID refers to a set of symptoms experienced by individuals who have been infected with the SARS-CoV-2 (COVID-19) infection, in which symptom persistence has lasted for weeks, months or even years after the initial infection.¹ This set of symptoms is distinct from the commonly developed symptoms caused by the initial infection, which is known as acute COVID, which causes symptoms such as cough, shortness of breath, fever, joint pain, headache, fatigue, abdominal pain, vomiting and diarrhoea.² Normally people recover from acute COVID after 7-10 days, but it can take 3-6 weeks in more critical/severe cases.³

However, for some individuals, symptoms of COVID persisted for weeks and months after their initial infection, even though if tested, they would not be positive for the virus.⁴ In some cases, these symptoms were continuously present from the initial infection, whereas for others, the symptoms would be relapsing and remitting in nature.⁵ To differentiate those with long-term COVID symptoms from those who are taking longer than expected to recover from the disease, a distinction was made: if symptoms lasted longer than 3 weeks, but less than 12 weeks, this is referred to as post-acute COVID; but if symptoms extended beyond 12 weeks, this is known as ‘Chronic’ or ‘Long COVID’.⁶

However, this diagnosis criteria is harder to apply to individuals who were initially asymptomatic but developed recurring symptoms later down the line.¹ Equally, it is difficult to take into account those who may have initially received a false negative COVID test result, and then developed symptoms later on.7 This has led to a proposal to categorise suspected Long COVID cases on the basis of an individual’s initial exposure to the virus, where confirmed cases must have an initial positive test result or positive antibody test result, which demonstrates infection with the virus. If either of these results is missing, individuals are classed as a Probable Long Covid case if they have had contact with a confirmed or suspected case, within the previous 2 weeks prior to symptom onset, and if there is no positive test result and no known exposure to an infected individual, the individual is classed as a Possible Long Covid case.⁸

With this in mind, a diagnosis of Long COVID by a clinician is not always feasible. This has led to many individuals self-reporting their symptoms, which includes around 2 million people just in England and Scotland, with many of them experiencing symptoms for longer than 2 years.9 These self-reported symptoms can vary greatly and, in the following section, this range will be explored in greater detail.

What are the symptoms of Long COVID?

Research has indicated that there are two main groups of Long COVID symptoms: fatigue, headache and upper respiratory complaints (such as shortness of breath, persistent cough, sore throat and loss of smell), and multi-system complaints which include ongoing fever, diarrhoea, joint pain, rash, hair loss, myalgia and weakness, impaired balance and insomnia.¹⁰ A report found that 26.5% of those with Long COVID experienced painful symptoms.¹¹ While another study showed that 50% of those infected with COVID in a cohort suffered from fatigue.¹² This parallels experiences of those who were infected with Severe Acute Respiratory Syndrome (SARS), another type of coronavirus, as many of them suffered from persistent fatigue following the 2003 outbreak.¹³

Additionally, many have reported experiencing cognitive and neurological impairment since their COVID infection with symptoms ranging from headache, memory loss, tremors, cognitive blunting (brain fog), anxiety, depression, PTSD, dysfunction in the peripheral nerves and stroke.¹⁴ This may be partially explained by some individuals suffering from encephalitis (inflammation of the brain) and/or nerve damage from their initial COVID infection.¹⁵

Cardiac issues may also arise depending on the severity of the initial infection, with reported cardiac events such as: aortic aneurysm, coronary artery aneurysm, accelerated atherosclerosis (buildup of plaque in the arteries), pulmonary embolism, venous and arterial thromboembolic disease.¹⁶

How can Long COVID be managed?

Given the recent emergence of Long COVID and the various ways it can manifest in individuals, there is no universal treatment for the condition. Instead, a holistic assessment of each individual based on their symptoms and needs is performed, with the National Institute for Health and Care Excellence (NICE) in the UK recommending an investigation into potential Long COVID symptoms as early as 4 weeks after the initial infection, so that the condition can be spotted at an earlier stage, and the patients can be treated accordingly.¹⁷

While a symptom-based approach is recommended, a comprehensive assessment and full medical history should be undertaken with each patient, which includes conducting tests including a full blood count, thyroid function test, C-reactive protein test, renal function test, liver function test, vitamin D, vitamin B12, haemoglobin A1c (HbA1c), magnesium, folate and ferritin levels.¹⁷ Furthermore, the International Consensus Conference in Critical Care recommends screening tests for the prediction and identification of mental and physical impairment.¹⁸

If patients are also presenting with cardiopulmonary symptoms, pulmonary function tests, chest imaging, electrocardiography and corticosteroid treatment should be considered.¹⁸

Due to prior research indicating that high levels of mast cells are often found in those with Long COVID, which leads to allergy-like inflammation, antihistamines have been found to be effective in relieving some associated symptoms.¹⁹ Another treatment that has shown to be effective in some individuals is dietary supplements such as vitamins and minerals, due to their antioxidative and anti-inflammatory benefits.²⁰

What is the latest research on the condition?

Recent research into Long COVID has illuminated some of the biomechanic underpinning of the condition, which could pave the way for new treatment. A study into the blood plasma proteins of 657 people hospitalised for COVID was conducted in the UK, which compared the phenotypes of those who experienced Long COVID-related symptoms following their hospitalisation, to those who made a full recovery.²¹ This comparison has revealed there were a number of markers associated with different symptom groups that were significantly higher in those with Long COVID, than in those who made a full recovery. This suggests that Long COVID results in tissue damage to the initiation of specific inflammatory pathways, and that these pathways have the potential to be the target of future treatment.

Summary

Long COVID refers to the set of symptoms experienced by individuals who have been infected from COVID and recovered from their initial illness but later became unwell due to a recurrence of symptoms. The official time period for symptoms arising to be classed as Long COVID is beyond 12 weeks. There are two main sets of Long COVID symptoms which are fatigue, headache and upper respiratory complaints, and multisystem complaints. The former group consists of symptoms including persistent cough, loss of smell, shortness of breath and a sore throat, whereas the latter group refers to symptoms such as diarrhoea, ongoing fever, joint pain, myalgia and weakness, impaired balance, insomnia, hair loss and rash. Additionally, many report cognitive and neurological-related symptoms including memory loss, cognitive blunting (memory loss), peripheral nerve dysfunction, headache, tremor, anxiety, depression, PTSD and stroke. Long COVID is also thought to increase the risk of serious cardiac event incidence.

Current treatment for Long COVID is performed on a holistic basis given the heterogeneity present in the types of symptoms observed. Because of this, a full medical history and comprehensive medical assessments should be performed on each patient to best determine their course of treatment. NICE recommends monitoring patients following the 4th week of COVID symptoms presenting, so if any potential issues occur, they can be dealt with at an earlier stage. Following this, the requisite interventions and treatments should be performed given the symptoms and needs of the patient, but when considering more general treatment options for Long COVID sufferers, antihistamines and vitamin supplements have been shown to be effective in relieving symptoms due to their anti-inflammatory nature.

Recent research has suggested that there are specific inflammatory pathways which are responsible for tissue damage in Long COVID patients that are activated at an increased rate compared to people who have had acute COVID, but not any further symptoms past their initial infection. This suggests that these pathways could be targeted in the future to treat the condition.