In a recent study published in the journal Nature Communications, a group of researchers compared the proportion of emergency department patients who developed Post-Coronavirus disease 2019 (COVID-19) Condition (PCC) symptoms between those who tested positive and those who tested negative for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection.

Study: Post-COVID-19 condition symptoms among emergency department patients tested for SARS-CoV-2 infection. Image Credit: p.ill.i / Shutterstock

Background 

The COVID-19 pandemic has caused over 775 million infections globally, with millions experiencing persistent symptoms, commonly known as long COVID. The World Health Organization (WHO) defines PCC as symptoms lasting at least two months, typically starting three months after confirmed or probable SARS-CoV-2 infection. Based on estimates, over 77 million people could be living with PCC. Further research is needed to refine diagnostic criteria for PCC, as its symptoms overlap with other conditions, leading to potential overdiagnosis and hindering accurate treatment.

About the study

The Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) conducted a PCC sub-study across 33 sites in five provinces. Ethical approval was granted with a waiver of informed consent, and participants provided verbal consent for follow-up phone interviews. Adults tested for SARS-CoV-2 in emergency departments between October 2020 and February 2022 were eligible, with exclusions for those deceased, hospitalized, unreachable, or unable to communicate. Positive SARS-CoV-2 cases were defined by confirmed infection, while negative controls had no positive tests or symptoms during follow-up.

PCC was defined per the WHO’s criteria: patients reporting new symptoms within three months of their emergency visit, lasting at least two months. Symptoms included cough, dyspnea (difficulty or shortness of breath), anosmia (loss of the sense of smell), and cognitive impairments. Symptoms had to persist beyond the initial three months for PCC at six or twelve months.

Research assistants collected data through chart reviews and phone follow-ups, documenting demographic, clinical, and vaccination information. The primary outcome was the proportion of patients reporting PCC-consistent symptoms at three months, with secondary outcomes assessing specific symptoms at six and twelve months. Statistical analyses, including logistic regression, were performed to evaluate associations between SARS-CoV-2 status and PCC symptoms, adjusting for key covariates.

Study results 

Of 29,838 individuals assessed for eligibility, 6,723 met the inclusion criteria, with 58.5% (3,933) testing positive for SARS-CoV-2. The sample was nearly evenly split by gender, with 50.6% identified as female. The mean age was 54.4 years. Among test-positive patients, 38.9% reported at least one PCC symptom at three months, compared to 20.7% of test-negative patients. PCC symptoms were more frequently reported by female participants (45.5%) compared to males (32.8%).

At six months, 38.2% of test-positive patients and 19.5% of test-negative patients reported PCC symptoms, decreasing to 33.1% and 17.3%, respectively, by twelve months. Compared to the three-month mark, 5.8% fewer test-positive and 3.4% fewer test-negative patients had ongoing symptoms at twelve months. Patients with PCC at three months differed from those without it in age, sex, race, education, comorbidities, Intensive Care Unit (ICU) admissions, and perceived fitness. There were no differences in vaccination status or timing.

Test-positive patients reported PCC symptoms at twice the rate of test-negative patients, particularly for anosmia, dysgeusia (distorted or altered sense of taste), and persistent cough. Patients infected during the Omicron period reported more memory, concentration, and dizziness issues than those infected pre-Omicron. The strongest predictor of PCC at three months was testing positive for SARS-CoV-2 during the index visit (adjusted OR = 4.42). Other significant predictors included ICU admission, female sex, dysgeusia/anosmia, fatigue, dexamethasone treatment, and ambulance arrival. Lower education levels were associated with a reduced risk of PCC, while vaccination status had no effect. 

Patients with three or more PCC symptoms were significantly more common among test-positive individuals (21.4%) compared to test-negative ones (6.1%). Olfactory symptoms were rare among test-negative patients, especially during the Omicron period, where none reported anosmia. Despite frailty not being a risk factor for PCC, those who reported “managing well” compared to being “fit and well” had an increased risk of developing PCC. Overall, vaccination did not alter the likelihood of developing PCC.

Conclusions

To summarize, many emergency department patients reported ongoing PCC symptoms at three, six, and twelve months, regardless of SARS-CoV-2 infection status. Test-positive patients were more likely to experience PCC, with key risk factors including female sex, dexamethasone use, ICU admission, and baseline fatigue or olfactory symptoms. No comorbidities increased PCC risk, and vaccination did not reduce the likelihood of developing PCC. Interestingly, test-negative patients also reported persistent symptoms, suggesting the current WHO PCC definition may lead to overdiagnosis.