In patients with post-acute sequelae of COVID-19 (PASC), depression has been associated with symptom severity, the duration since infection and ongoing functional impairment. However, the interconnections between these factors remain inadequately understood.

This study aimed to explore the roles of depressive symptoms in moderating and mediating the relationships between post-COVID-19 conditions and functional capacity.

The PERCEIVE study recruited 1794 participants from Victoria and Tasmania through online advertisements based on possible PASC for a cross-sectional study. Of these, 461 participated in the longitudinal study. Post-COVID-19 duration and symptoms were recorded, and depressive symptoms and functional capacity were self-reported using the 9-item Patient Health Questionnaire and the Duke Activity Status Index (DASI), respectively. The association of depression with functional capacity was explored using ordinary least squares (OLS) regression, with companion OLS models, Sobel-Goodman tests and 1000 bootstrap iterations to assess mediation. Longitudinal data were analysed to assess changes in functional capacity and depressive symptoms over time, with mediation analysis using mixed models to explore depression as a mediator.

Participants had a mean DASI score of 35 (SD 21). Fatigue (18%), shortness of breath (11%) and chest pain (6%) were common symptoms, with severe depression linked to fatigue (93%) and shortness of breath (66%). The severity of post-COVID-19 symptoms was associated with severe depression (β=6.31, 95% CI 5.42 to 7.21) and reduced functional capacity (β=–6.40, 95% CI –9.20 to –3.61), with depression mediating 36% of the association between post-COVID-19 symptom severity and functional capacity. PASC was associated with higher depression scores (β=2.06, 95% CI 1.15 to 2.97) and lower functional capacity (β=–3.99, 95% CI –6.21 to –1.77), with depression mediating 51% of the association between PASC and reduced functional capacity. The longitudinal analysis suggested that depression is associated with the relationship between PASC and changes in functional capacity over time (unstandardised estimate=–5.16, p

Depression plays a key role in exacerbating post-COVID-19 functional impairment. This observation underscores the need for targeted physical and mental health interventions to enhance long-term recovery for those with severe conditions.

Black ethnic cohorts, when compared with white cohorts, have disproportionately higher rates of essential hypertension and related complications. Ethnic differences in the renin-angiotensin-aldosterone system have been identified in black ethnic cohorts displaying a low-renin, salt-sensitive phenotype in comparison to white individuals. Studies have highlighted lower levels of aldosterone in black cohorts compared with white cohorts. However, when renin is considered, in the form of the aldosterone-renin ratio (ARR), the ARR is higher in black cohorts. The Framingham study highlighted that people in the upper quartile for baseline aldosterone were more likely to have a higher blood pressure and develop hypertension at 4 year follow-up. Therefore, the inappropriately suppressed aldosterone may be contributing to the ethnic differences in hypertension prevalence and prognosis.

Four databases will be searched (MEDLINE, Embase, Scopus and Cochrane Library) to identify eligible studies from database creation to August 2025. Two investigators will independently review the search results and document reasons for full-text exclusions. The main outcomes are to assess if there are ethnic differences in baseline aldosterone, baseline plasma renin activity (PRA) and ARR. We will also look at ethnic differences in regulatory mechanisms of aldosterone, such as serum potassium and 24 hour urinary electrolytes, that may explain the potential differences in aldosterone and ARR in black and white ethnic cohorts. Studies looking at normotensive and hypertensive individuals will be included. Studies in paediatric populations (

As this review will involve analysis of previously published data, ethical approval is not required. The results will be submitted to a peer-reviewed journal.

CRD420251025642.