A recent study published in the eClinicalMedicine Journal evaluated the risk of post-acute sequelae of coronavirus disease 2019 (COVID-19) in the United Kingdom (UK) and Hong Kong (HK).
Study: Long-term post-acute sequelae of COVID-19 infection: a retrospective, multi-database cohort study in Hong Kong and the UK. Image Credit: RalfLiebhold/Shutterstock.com
Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is defined as a host of symptoms and signs involving several organ systems that linger after an initial episode of COVID-19.
Long COVID has emerged as a significant public health concern, with systematic reviews suggesting that up to 80% of survivors suffer from at least one symptom after acute COVID-19. Notwithstanding the efforts, evidence from existing studies is inconsistent due to heterogeneous estimates.
About the study
In the present study, researchers characterized the risk of long-term sequelae in COVID-19 survivors in HK and the UK. The researchers obtained patients’ electronic medical records from the UK Biobank (UKB) and HK Hospital Authority (HKHA).
Patients aged 18 or older with a laboratory-confirmed COVID-19 diagnosis were eligible for inclusion. COVID-19 patients were identified between April 2020 and May 2022 from the HKHA and between March 2020 and May 2021 from the UKB.
Individuals without a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test served as controls. Controls were matched to COVID-19 cases by sex and birth year.
All subjects were followed up until the occurrence of outcome(s) or death, whichever was first. The index date was the date 21 days after the first COVID-19 diagnosis. Additionally, the team collected anonymized longitudinal healthcare data since 2016.
Outcomes included the incidence of major cardiovascular events (defined as a composite outcome of coronary heart disease, stroke, and heart failure), myocardial infarction (MI), deep vein thrombosis (DVT), coronary artery disease, Bell’s palsy, acute respiratory distress syndrome (ARDS), post-traumatic stress disorder (PTSD), encephalitis, anxiety, and mortality, among others. Individuals were excluded if previously diagnosed with any of these outcomes.
The authors applied inverse probability treatment weighting via propensity scores accounting for confounders. Logistic regression models were used to estimate propensity scores. The incidence rates of outcomes were calculated.
Cox proportional hazard regressions were used to compute hazard ratios and 95% confidence intervals of outcomes.
In sensitivity analyses, the researchers re-defined the index date as 30- or 90-days post-diagnosis; they adjusted for all-cause mortality and excluded subjects with multiple COVID-19 diagnoses.
In sub-group analyses, subjects were stratified by age, sex, COVID-19 vaccination status before the index date, Charlson comorbidity index (CCI), and disease severity.
The researchers identified 535,186 COVID-19 patients from the HKHA and 16,400 patients from the UK. Around 47% of patients were males. The mean age of HKHA and UKB subjects was 54.1 and 68.1, respectively.
HKHA and UKB subjects were followed up for a median of 146 and 243 days, respectively. Around 0.8% of COVID-19 patients in the HKHA and none from the UKB were re-diagnosed at least 30 days later.
COVID-19 cases, compared to controls, showed an elevated risk of atrial fibrillation, DVT, heart failure, ARDS, chronic pulmonary disease, anxiety disorder, PTSD, seizure, acute kidney disease, end-stage renal disease, interstitial lung disease, pancreatitis, cardiovascular mortality, coronary artery disease, and all-cause mortality. The incidence of major cardiovascular events was higher in the UKB and HKHA.
COVID-19 cases in HK showed a higher incidence of liver injury, whereas UK cases had higher incidences of Bell’s Palsy, MI, and stroke. Results from sensitivity analyses were consistent with the primary analyses.
Sub-group analyses indicated that severe COVID-19 patients, females, recipients of less than two vaccine doses, older patients (65 or above), and patients with a CCI of 4 or higher were at a higher risk of PASC than others.
The researchers reported elevated incidence of PASC affecting the cardiovascular, psychiatric, nephrological, respiratory, and hepatic systems among patients in the UK and HK.
Females, older patients, those with a severe illness or multimorbidity, and those receiving less than two vaccine doses were at greater risk of developing PASC.
COVID-19 cases in HK were predominantly due to the SARS-CoV-2 Omicron variant. The risk of all-cause death was lower in the HK cohort than in the UK cohort. Nonetheless, both cohorts had a similar risk of PASC.
The study’s limitations include detection or indication bias and under-detection of asymptomatic COVID-19 cases, among others.
Further, several unmeasured confounding factors might have introduced bias. Besides, the risk of mild symptoms and the potential benefit of the fourth vaccine dose against PASC were unaddressed due to sample size limitations.
Together, the study reported consistent increases in the incidence of diverse sequelae and all-cause mortality after acute COVID-19 in the UK and HK.