Long Covid — mechanisms, risk factors, and management

The review in the British Medical Journal entitled "Long Covid - mechanisms, risk factors and management" summarises studies of the long term effects of covid-19 in hospitalized and non-hospitalized patients and describes the persistent symptoms they endure. Risk factors for acute covid-19 and Long Covid and possible therapeutic options are also discussed.


Coronavirus disease 2019 (covid-19) has spread across the world. As of 4 July 2021, more than 183 million confirmed cases of covid-19 have been recorded worldwide, and more than 3.97 million deaths have been reported by the World Health Organization . The clinical spectrum of covid-19 ranges from asymptomatic infection to fatal disease. The virus responsible for causing covid-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enters cells via the angiotensin-converting enzyme 2 (ACE2) receptor.

Once internalized, the virus undergoes replication and maturation, provoking an inflammatory response that involves the activation and infiltration of immune cells by various cytokines in some patients. The ACE2 receptor is present in numerous cell types throughout the human body, including in the oral and nasal mucosa, lungs, heart, gastrointestinal tract, liver, kidneys, spleen, brain, and arterial and venous endothelial cells, highlighting how SARS-CoV-2 can cause damage to multiple organs.

The impact of covid-19 thus far has been unparalleled, and long term symptoms could have a further devastating effect. Recent evidence shows that a range of symptoms can remain after the clearance of the acute infection in many people who have had covid-19, and this condition is known as Long Covid. The National Institute for Health and Care Excellence (NICE) defines Long Covid as the symptoms that continue or develop after acute covid-19 infection and which cannot be explained by an alternative diagnosis. This term includes ongoing symptomatic covid-19, from four to 12 weeks post-infection, and post-covid-19 syndrome, beyond 12 weeks post-infection. Conversely, The National Institutes of Health (NIH) uses the US Centers for Disease Control and Prevention (CDC) definition of long covid, which describes the condition as sequelae that extend beyond four weeks after initial infection. People with Long Covid exhibit involvement and impairment in the structure and function of multiple organs. Numerous symptoms of Long Covid have been reported and attributed to various organs, an overview of which can be seen in Figure 1.

Figure 1.

Long term symptoms following covid-19 have been observed across the spectrum of disease severity. This review examines the long term impact of symptoms reported following covid-19 infection and discusses the current epidemiological understanding of Long Covid, the risk factors that may predispose a person to develop the condition, and the treatment and management guidelines aimed at treating it.

Long Covid definition Long Covid gained widespread attention following an account published on 5 May 2020 in BMJOpinion where an infectious disease professor shared his experience of seven weeks on a “rollercoaster of ill health” following covid-19. The patient-made term long covid was then made popular following the rise in the use of #LongCovid on Twitter. This, plus the growing number of peer reviewed articles published since, has highlighted a post-covid-19 syndrome that can last for many weeks after the acute infection. Long Covid is now a recognized term in scientific literature. The NICE guidelines on managing the long term effects of covid-19 and the CDC10 define long covid patients or covid long haulers as individuals with ongoing symptoms of covid-19 that persist beyond four weeks from initial infection.


Studies around the world have reported various incidence rates for long covid with different follow-up examination times after the acute infection, including 76% of people at 6 months, 32.6% at 60 days, 87% at 60 days, and 96% at 90 days. These findings are not fully corroborative, but they show that a substantial proportion of people who have had covid-19 may develop Long Covid. The UK Office for National Statistics (ONS) has released data on the prevalence of long covid symptoms. They estimated that the five week prevalence of any symptom among survey respondents who tested positive for covid-19 between 22 April and 14 December 2020 was 22.1%, while the 12 week prevalence was 9.9%. These figures are worrying for patients, service providers, and governments, with many patients likely to develop long covid and require long term support and treatment. Further studies are required to consolidate our epidemiological understanding of Long Covid.

Risk factors Risk factors for severe covid-19 and hospital admission, and risk factors for death as a result of covid-19 include older age, male sex, non-white ethnicity, being disabled, and pre-existing comorbidities including obesity, cardiovascular disease, respiratory disease, and hypertension. Linked to risk of covid-19 severity and possibly the risk of Long Covid, the role of immune suppression is still being debated. Immune suppression may have protective effects against long term effects of covid-19 infection; however, these findings are conflicted. The risk factors for developing Long Covid are less appreciated. To explore the characteristics associated with symptoms of Long Covid, 274 non-hospitalized patients who had covid-19 were interviewed between 14 and 21 days following their positive test. Risk factors for not returning to “usual health” included age (P=0.01), with the ≥50 years age group having the greatest odds ratio, and number of pre-existing medical conditions (P=0.003), with a greater number of conditions associated with a greater odds ratio of not returning to “usual health.”

Of the pre-existing conditions, having

  • hypertension (odds ratio (OR)=1.3, P=0.018)

  • obesity (OR=2.31, P=0.002)

  • a psychiatric condition (OR=2.32, P=0.007)

  • an immunosuppressive condition (OR=2.33, P=0.047)

corresponded with the greatest odds of not returning to “usual health.” A cross sectional study identified an association between the severity of acute covid-19 infection and post-recovery manifestations in people who have had covid-19, showing that a more severe acute phase may transform into the development of more severe symptoms of Long Covid.

A cohort study, meanwhile, corroborated this finding, with patients with more than five symptoms during the initial covid-19 infection and those that required hospital admission more likely to experience long covid symptoms.

Although certain factors may increase the risk of both severe covid-19 and Long Covid, some factors associated with covid-19 do not also increase risk for Long Covid. Male sex and older age are associated with an increased risk of severe covid-19, however, the ONS reported that the prevalence of any long covid symptoms is

  • higher in women compared with men (23.6% versus 20.7%)

  • age group estimated to be most greatly affected by long covid symptoms is 35-49 years (26.8%), followed by 50-69 years (26.1%), and the ≥70 years group (18%).

  • male sex, age, and pre-existing conditions including obesity, diabetes, and cardiovascular disease have shown no association with the risk of developing Long Covid.

  • pre-existence of asthma has been found to be significantly associated with Long Covid.

Tomorrow I will cover symptoms, why they might occur and treatment/management of Long Covid as discussed in this article. If you can't wait see the reference below for the full clinical review!


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