Persistent Gastrointestinal Symptoms in Long COVID: clinical and laboratory insights from a Two-Year Cohort

Long COVID is associated with persistent symptoms including the gastrointestinal (GI) problems. The mechanisms underlying long-term GI manifestations remain poorly understood. We conducted a prospective cohort study on 80 adults hospitalized with severe COVID-19 in Manaus, Brazil, to investigate persistent gastrointestinal (GI) symptoms two years post-infection. Data were collected at five time points over 720 days, including clinical, laboratory, and serum cytokine levels (IL-1β, IL-6, IL-8, IL-10, IL-12, TNF-α). The primary outcome was the presence of persistent GI symptoms at D720. At D720, 30 patients (37.5%) reported persistent GI symptom, with reflux (63%), abdominal pain (43%), and diarrhea (37%) being the most prevalent. This group also reported other long COVID symptoms, such as palpitations, headache, and arthralgia. Patients with persistent GI symptoms showed distinct profiles, including lower creatinine and ferritin levels, and altered platelet indices. While IL-6 levels were lower during hospitalization, they became significantly elevated at four months (D120, p = 0.005), suggesting a delayed inflammatory response. Persistent gastrointestinal symptoms are common two years after severe COVID-19 and are associated with distinct inflammatory and clinical profiles. This highlights the need for long-term GI follow-up in COVID-19 survivors and support the hypothesis that sustained immune dysregulation drives long COVID manifestations.