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, or PASC, is an emerging public health concern. Longitudinal data from South Asia remain limited and the burden of persistent symptoms in Pakistan is not well characterized. This study examined the long term clinical course of PASC and its relationship with fecal viral shedding and serotonin levels over a 12 month follow up period. We conducted a prospective longitudinal study of individuals with PASC. Participants underwent serial assessments of clinical symptoms, stool SARS CoV 2 RNA detection, and serum serotonin measurements. A symptom score was developed using 22 symptoms reported by more than 30 percent of participants. Participants were predominantly female with 60 percent female participation and a mean age of 42.1 years. Overall, 66 percent were overweight or obese and 23 percent reported multiple SARS CoV 2 reinfections. Symptom burden decreased significantly at 9 months and 12 months compared with baseline. Despite overall improvement, several symptoms persisted. Myalgia remained common, increasing slightly from 60 percent at baseline to 63 percent at 12 months. Musculoskeletal symptoms remained stable at approximately 60 percent. Neurocognitive symptoms declined from 40 percent to 31.3 percent, whereas psychological symptoms increased slightly from 40 percent to 45.8 percent. Fecal viral shedding was detected in 50 percent of participants and demonstrated intermittent or persistent patterns. Significant associations between fecal shedding and symptoms emerged at 6 months, particularly breathlessness, fatigue, weakness, and joint pain. Serotonin levels were comparable to those reported during acute COVID 19 infection. PASC symptoms including myalgia, joint pain, weakness, and fatigue persisted for up to one year after infection. The association between ongoing fecal viral shedding and persistent symptoms suggests that viral persistence and sustained physiological disturbances may contribute to Long COVID pathogenesis in a subset of individuals.