The COVID-19 pandemic has swept across the globe, affecting millions of individuals with varying degrees of severity. While many individuals recover from the acute phase of the infection, a significant proportion continue to experience persistent and debilitating symptoms long after the initial SARS-CoV-2 infection. This condition, known as Long COVID (LC) or sometimes referred to as Post-COVID Condition (PCC) or post-acute sequelae of COVID-19 (PASC), has emerged as a complex multisystemic condition and challenging public health issue.

Contrary to initial perceptions, pediatric Long COVID is a significant health concern, with studies suggesting its prevalence ranges from 10% to 25% following infection. Research in the pediatric population has largely been limited to observational studies based on self-reported symptoms or large electronic healthcare datasets. The long-term outcomes and predictors of LC in children remain poorly described, highlighting an urgent need for further mechanistic research to characterize this complex condition. While acute COVID-19 symptoms are often milder in children relative to adults, some go on to develop a range of chronic physical, immunological, psychological, and neurological symptoms persisting for weeks to years after initial infection. The most commonly reported symptoms are similar to those seen in adults and include debilitating fatigue, respiratory distress, headaches, gastrointestinal symptoms, and neurocognitive impairment. Other frequently reported symptoms include muscle pain, sleep disturbances, olfactory and gustatory disturbances, exercise intolerance, and heart palpitations/cardiovascular symptoms. These symptoms can be new, or they may persist or fluctuate from the initial illness. Additionally, many children with LC experience psychological symptoms such as anxiety, depression, and mood disturbances, which are thought to be exacerbated by experiencing prolonged illness and subsequent lifestyle disruptions.

Currently, effective treatments for LC remain elusive, leaving patients to contend with persistent symptoms that significantly impair their quality of life. For children and adolescents, these issues can profoundly impact their daily activities, academic performance, and social interactions/friendships. Symptoms like debilitating fatigue, cognitive impairment, and mood disturbances are especially disruptive by interfering with memory, energy levels, and overall development, often leading to school absenteeism, social withdrawal, and psychological distress. Therefore, it is imperative to explore novel therapeutic approaches that may alleviate the suffering of this patient population.

Purpose: The primary objective is to quantify the increase in plasma taurine concentrations in adolescents following three months of taurine supplementation and evaluate the efficacy and safety of taurine supplementation in treating and managing prolonged symptoms related to LC.

Hypothesis: Increasing taurine levels in the body through treatment with taurine supplements will have a beneficial effect on Long COVID symptoms particularly neurocognitive-associated symptoms and fatigue.

Justification: Previous studies have suggested a correlation between low plasma taurine levels and symptoms associated with Long COVID. The decreasing trajectory of taurine levels observed in long COVID could partly explain the fatigue, as taurine plays multiple roles in skeletal muscle function, the central nervous system, and energy metabolism. Furthermore, in various clinical and preclinical studies, including antioxidant, anti-aging, cytoprotective, and cardioprotective effects, taurine has demonstrated various therapeutic activities. Taurine also has a role in neuromodulation and the treatment of other central nervous system disorders, including depression. These findings suggest that taurine may be important in addressing the persistent symptoms and adverse outcomes in LC patients.

Given the robust association between taurine levels and symptoms and adverse outcomes of LC and the safety profile, there is a strong biological and clinical rationale for investigating taurine supplementation. There is a lack of effective treatments for LC in adolescents, and exploring taurine supplementation as a novel therapeutic approach is justified and holds the potential to significantly improve the lives of affected individuals with an excellent safety profile.

Objectives: The overall trial objectives are to to quantify the increase in plasma taurine concentrations in adolescents following three months of taurine supplementation and evaluate the efficacy and safety of taurine supplementation in treating and managing prolonged symptoms related to LC.

Inclusion Criteria:

1. Subjects must be between 10 and 17 years of age at the time of study enrollment
2. Positive COVID-19 test by nasopharyngeal swab RT-PCR test, antibody or antigen tests at least 3 months prior to trial; OR Presumed COVID-19 assessed by the site investigator (no positive COVID-19 test) with acute illness after October 15, 2019, and at least 3 months prior to trial enrollment.
3. If participants have treatable symptoms, they should have had a stable regimen of treatment prior to entering the study (i.e. started treatment for at least 4 weeks).
4. Lingering COVID-19 symptoms beyond 3 months from onset of acute COVID and symptoms have lasted at least 2 months. The onset of COVID is considered the earliest of two dates: the date of positive testing or the date of first symptoms.
5. Lingering symptoms from COVID-19 present at the time of trial enrollment.
6. Individuals of childbearing potential (as assessed by the overseeing Investigator) who are sexually active must agree to practice true abstinence or use at least one highly effective method of contraception while on study treatment. Highly effective methods of contraception must be discussed and approved by the overseeing Investigator.
7. Medication(s) only available through a prescription for the purposes of treating fatigue or cognitive function have been discontinued for four weeks prior to randomization.
8. Participants must be able to assent to their participation in the study and be both willing and able to comply with study requirements.
9. Parents/caregivers/guardians must be able to provide informed consent for participation.
10. Participants must agree to avoid taking supplemental taurine (e.g. from over-the-counter preparations, energy drinks, etc.)

Exclusion Criteria:

1. Patients who had mechanical ventilation or extracorporeal membrane oxygen (ECMO) for COVID-19.
2. Current end-organ failure, organ transplantation, or current hospitalization in an acute care hospital.
3. Contraindications to the study intervention.
4. Currently already on the study intervention (Participants would be eligible if they stopped taking Taurine for a minimum of 4 weeks prior to enrollment).
5. Co-enrolment in another interventional trial (co-enrolment in an observational study is permitted).
6. Currently pregnant or breastfeeding.
7. The participant is currently enrolled in another research trial to treat neurocognitive symptoms in LC.