Clinical Phenotypes of Post-Acute Sequelae of SARS-CoV-2 (PASC) Infection: A Longitudinal Cohort Study from Karachi, Pakistan

Post-Acute Sequelae of SARS-CoV-2 infection (PASC), commonly referred to as Long COVID, is increasingly recognized as a significant public health concern. However, longitudinal studies examining its clinical course remain limited in South Asia, and the true burden of persistent symptoms in Pakistan is not well established. This study aimed to characterize the long-term clinical manifestations of PASC and investigate the relationship between symptom persistence, faecal viral shedding, and serotonin levels over a one-year follow-up period.

We conducted a prospective longitudinal study involving individuals diagnosed with PASC (n=60). Participants underwent serial assessments for clinical symptoms, stool SARS-CoV-2 RNA detection, and serotonin measurements in platelets rich plasma at multiple time points over 12 months. A symptom score was developed using 22 symptoms reported by more than 30% of participants.

Among the study population, 60% were female, with a mean age of 42.1 ± 12.1 years. Two-thirds (66%) were overweight or obese, and 28.3% reported multiple SARS-CoV-2 reinfections. Longitudinal analysis demonstrated a significant reduction in overall symptom burden at 9 months (β = −2.68, 95% CI: −3.81 to −1.55; p < 0.001) and 12 months (β = −3.00, 95% CI: −4.13 to −1.87; p < 0.001) compared with baseline. Despite this overall improvement, several symptoms persisted throughout follow-up. The prevalence of myalgia remained largely unchanged (60% at baseline vs. 63% at 12 months), while musculoskeletal symptoms persisted at similar levels (59% vs. 60%). Neurocognitive symptoms declined from 40% to 31.3%, whereas psychological symptoms increased slightly from 40% to 45.8% over the study period.

Faecal viral shedding was detected in 56.7% of participants and demonstrated both intermittent and persistent patterns. Although no association was observed between faecal shedding and symptoms at baseline, significant associations emerged at six months, particularly for breathlessness, fatigue, weakness (77.8%), and joint pain (88.9%). Serotonin levels remained broadly comparable to those reported during acute COVID-19 infection.

These findings highlight the prolonged nature of PASC, with persistent symptoms such as myalgia, joint pain, weakness, and fatigue continuing for at least one year after infection. The persistence of symptoms, together with evidence of ongoing faecal viral shedding, suggests that viral persistence and sustained physiological disturbances may contribute to the long-term pathogenesis of Long COVID in a subset of affected individuals.