Persistent symptoms and long-term health impacts more common after COVID-19, with age and preexisting conditions driving higher risks.

Study: Antecedent and persistent symptoms in COVID-19 and other respiratory illnesses: insights from prospectively collected data in the BRACE trial. Image Credit: ktsdesign / Shutterstock

A recent study published in the Journal of Infection explored antecedent and persistent symptoms in coronavirus disease 2019 (COVID-19) and non-COVID-19 respiratory illnesses.

By mid-2020, there was evidence of symptom persistence beyond the acute COVID-19 phase. The World Health Organization (WHO) defines post-acute COVID-19 syndrome (PACS) as symptoms appearing three months after an initial COVID-19 diagnosis and lingering for ≥ two months with no alternative diagnosis. PACS symptoms include fatigue, dyspnea, cough, cognitive dysfunction, and changes in smell and taste, which vary in intensity and fluctuate or recur over time.

Conversely, the United Kingdom (UK) National Institute for Health and Care Excellence (NICE) defines post-COVID-19 syndrome as symptoms lingering beyond 12 weeks with fluctuating symptom clusters that affect any body system without a fixed pattern or length. NICE and WHO definitions vary, particularly in terms of how the duration and behavior of persistent symptoms are quantified.

About the study

In the present study, researchers compared symptoms between COVID-19 and non-COVID-19 respiratory illnesses and investigated PACS-related risk factors. They used data from an international, multicenter, phase 3, randomized controlled (BRACE) trial. Participants were healthcare workers recruited in Brazil, Australia, the UK, the Netherlands, and Spain and followed up for one year.

Data on symptoms were collected every week. Symptoms included cough, fever, dyspnea, runny nose, sore throat, headache, loss of smell or taste, diarrhea, vomiting, muscle ache, and fatigue. If symptoms were reported, participants were followed up daily until resolution. Blood samples were collected quarterly and tested for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid.

Further, quarterly surveys were administered to ensure the accuracy and completeness of daily data acquisition. An illness episode was defined as starting on the first day of symptom report and ending on the day when symptoms were no longer reported. Participants who did not report illness episodes lasting ≥ three days and Australian subjects were excluded.

A COVID-19 case had an illness episode for more than three days with any of the specified symptoms, during which they also tested SARS-CoV-2-positive on a nucleic acid or antigen test and had no subsequent infection. Non-COVID-19 respiratory controls had at least one of the respiratory symptoms and were negative for SARS-CoV-2 and serology.

The associations between illness type and severity, duration, and preexisting symptoms were investigated. Among COVID-19 cases, associations between demographic and comorbidity factors and PACS were examined.

Daily symptom data were classified into three periods to assess the relationship of symptoms before (period 1) and during illness (period 2) with post-illness (period 3) symptoms.

Findings

Of 2,442 eligible participants, 593 had a COVID-19 episode, and 1,112 had other non-COVID-19 respiratory episodes. Baseline characteristics were similar between COVID-19 cases and non-COVID-19 controls.

The odds of a severe illness were higher among COVID-19 cases than controls. Symptom durations meeting NICE and WHO PACS definitions occurred in more COVID-19 cases than controls.

No significant differences in symptoms were reported before illness episodes between cases and controls. Age was associated with PACS using WHO and NICE definitions.

According to WHO and NICE definitions, preexisting symptoms and chronic respiratory disease were associated with PACS.

The most common post-acute symptoms included runny nose, headache, and cough. Subjects with PACS had a median of seven symptoms in period 2 and four in period 3.

The cumulative number of days with respiratory or other symptoms was greater for COVID-19 cases across all periods, especially for loss of smell/taste and fatigue in periods 2 and 3.

Most symptoms were reported in cases during the initial weeks of period 2. The duration and extent of symptoms were comparable between controls and cases. More cases had symptom onset in period 1. Fatigue, headache, muscle aches, and loss of smell/taste contributed the most to the symptom burden in some cases.

Conclusions

The study compared symptom severity, patterns, and durations between COVID-19 and non-COVID-19 respiratory episodes. COVID-19 cases had seven times greater odds of severe illness than non-COVID-19 controls. Age, preexisting symptoms, and chronic respiratory disease elevated the risk of PACS.

Overall, the findings offer a robust estimate of PACS incidence using current definitions, underscoring that persistent symptoms are more common following COVID-19 than after non-COVID-19 respiratory illnesses.