Parametric survival analysis of long COVID among hospitalized patients in Zambia: A retrospective cohort study on the time to symptoms resolving

Abstract

Long COVID refers to the continuation or emergence of new symptoms within three months after acute SARS-CoV-2 infection, lasting for at least two months. Although several studies have described COVID-19 sequelae, gaps remain in understanding the temporal dynamics of symptoms resolution - information crucial for patients management and recovery planning. This study evaluated the resolution of COVID-19-related symptoms over time and associated factors among hospitalized patients in Zambia. We conducted a retrospective cohort study among individuals discharged after COVID-19 hospitalization and attending follow-up care in 13 specialized clinics in Zambia from August-2020 to December-2022. Severe acute COVID-19 was defined as hospitalization requiring supplemental oxygen, ICU admission, and/or treatment with steroids/remdesivir. Time-to-symptoms resolution (i.e., survival time) and changes in underlying hazard rate were our primary and secondary outcomes, respectively. We estimated incidence rates, median survival time (onset-to-resolution), and factors associated with symptom resolution using survival analysis, including hazard ratios (HRs) and changes in the underlying hazard rate over time. Among 823 participants, 616 (84.3%) had severe acute COVID-19 illness; 50.6% were female, and median age was 54 years (IQR: 43-64). Overall, 597 (72.5%) had symptoms resolution at a median 51 person-days (IQR: 34-104). Most participants (59.4%) had baseline comorbidities, and 16.6% had received ≥1 COVID-19 vaccine dose. Symptoms resolved at a rate of 12.2 per 1,000 person-days. Severe acute COVID-19 was associated with slower symptom resolution (adjusted HR: 0.68, 95% CI: 0.50-0.92), while infection during the Omicron-predominant period compared to wild-type was associated with faster resolution (aHR: 2.71; 95% CI: 1.46-5.03). The hazard rate peaked around person-day 20 and declined thereafter, indicating a non-monotonic recovery pattern. COVID-19 symptoms resolved more rapidly during the first month of post-acute infection. Patients with persistent symptoms not resolved within this period may experience prolonged recovery, underscoring the need for targeted follow-up and supportive care.