What is the global prevalence of long COVID?

Coronavirus disease 2019 (COVID-19) is a highly communicable disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in great challenges to global healthcare systems. The acute phase of the infection is associated with symptoms such as dyspnea, dry cough, fever, anosmia, and fatigue. Less common symptoms associated with COVID-19 include issues with the brain, kidneys, and heart. The vast majority of individuals survive a SARS-CoV-2 infection, with an estimated fatality rate of 2%. However, some survivors of COVID-19 are at risk of developing Post-Acute Sequelae of COVID-19 (PASC).

Estimating the prevalence of PASC is likely to be influenced by acute phase severity, time since infection, geographic region, age, and sex. Recent research has found that females are at an increased risk of PASC. At this moment, there are no reviews investigating the relationship between age and increased risk of PASC. However, there is evidence to suggest the majority of PASC exhibiting individuals are older. It appears that the increase of prolonged COVID-19 symptoms increases for ten-year increments past the age of 40.

In this study, researchers from the University of Michigan highlight that PASC should be well-defined and understood to allow for data to be produced to inform clinical decision-making and guidance and allow for better treatments for those affected. This study aims to provide a comprehensive synthesis of information on the prevalence and symptoms of PASC.

A preprint version of this study, which is yet to undergo peer review, is available on the medRxiv* server.

The study

Due to a unified definition of PASC remaining under investigation, the authors focussed on understanding the prevalence of specific symptoms following a SARS-CoV-2 infection. This study assessed 23 symptoms that were reported in 30 studies. Out of all the reported symptoms, the five most common were fatigue, insomnia, dyspnea, joint pain, and memory issues.

Reported PASC risk factors were screened for in all of the studies reviewed in this article. The only risk factors estimated in multiple studies were sex and pre-existing asthma, so they were meta-analyzed by the authors. Individuals with pre-existing asthma and females had higher odds of having PASC with pooled estimated odds ratios (OR) of 2.15 and 1.57, respectively. The meta-analyzed ORs were based on less than five studies, so they should be interpreted with caution.

From the studies that the authors did not meta-analyze, several showed that when individuals experienced a more severe acute phase of COVID-19, they were at a higher risk of developing PASC. In addition, older age was associated with the development of PASC in two of the studies not meta-analyzed. Other risk factors for PASC include several symptoms that occur during the acute phase of COVID-19, such as muscle pain, fatigue, headache, dyspnea, myalgia, and pre-existing conditions such as hypothyroidism, obesity, and comorbidity were also found to be positively associated with PASC.

Due to not reporting a composite binary endpoint as prevalence, the authors excluded six studies from their meta-analysis. Three of the excluded studies used incidence density or incidence rate to measure PASC. A study from the UK found joint pain and breathlessness to be the most common symptoms two months post-COVID-19. In contrast, another reported increased rates of major cardiovascular events and respiratory disease.

The other excluded studies focussed on psychiatric and neurological illness as a determinant of PASC. One paper focussed on cognitive and psychiatric consequences of COVID-19, reporting increased incidence of generalized anxiety disorder, depression, and mixed anxiety-depression. Another paper also concentrated on psychiatric disorders, reporting the probability of patients suffering from a psychiatric illness 90-days after COVID-19 diagnosis being 5.8%. An additional paper showed the most common complaints four to six months after hospital discharge were psychiatric problems, worsened depression, and worsened dyspnea.

Implications

The results from this study provide an insight into the observed estimates of risk factors, prevalence, and symptoms of PASC, with an evaluation of variations between several factors, including age and sex. It could be suggested that continued focus should be aimed at identifying patients at risk of developing PASC and quantifying the duration of PASC to help in the clinical advancements for better treatment options for the long-lasting adverse health effects of COVID-19.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Colin Lightfoot

Colin graduated from the University of Chester with a B.Sc. in Biomedical Science in 2020. Since completing his undergraduate degree, he worked for NHS England as an Associate Practitioner, responsible for testing inpatients for COVID-19 on admission.