Recharge the cells to overcome the debilitating symptoms in long-COVID

Long coronavirus disease (COVID) is defined as prolonged symptoms following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), not explained by any alternative diagnosis.[1] It is estimated that at 12–16 weeks after COVID-19 infection, up to 5% of patients suffer from long-COVID symptoms.[2] Fatigue, low exercise tolerance, deconditioning, chest discomfort, and breathlessness are the most common long-COVID symptoms.[3] These symptoms often worsen with routine physical activity, thereby interfering with daily activities.

The pathophysiology of long-COVID is not fully understood, and it is often multifactorial. Chronic low-grade ongoing tissue inflammation, multi-organ microvascular inflammatory disease leading to thrombosis and endothelial dysfunction, autoimmune response to the virus, and COVID-19-induced neurologic damage, particularly affecting the autonomic nervous system, are some of the basic mechanisms behind the pathogenesis of long-COVID symptoms.[4]

Long-COVID affects patients in different ways with different degrees of severity. Any organ system can be affected. Often, these patients present with multiple symptoms. COVID-19 disease often leads to worsening of preexisting systemic illnesses. Besides, some patients may develop some new onset of illness not related to COVID-19. Psychological and physical stress following COVID-19 also can lead to nonspecific multiple somatic symptoms which may mimic long-COVID. Hence, before labeling symptoms as long-COVID, proper history, physical examination, and appropriate systemic evaluation should be done in each patient.[4] Evaluation should be guided by symptoms, and serious underlying illness should be ruled out.

Management of long-COVID is directed toward specific remediable measures, if any, and treatment of comorbidities. Many patients do not have specific remediable causes for their symptoms. There is no standard protocol for treating the debilitating symptoms of long-COVID. Management strategy should aim at improving the physical health and mental well-being of these patients.[5] The optimal content, delivery method, and duration of these programs are currently unknown. Modified pulmonary rehabilitation program is useful to ameliorate the symptoms to some extent.[5] Appropriate symptomatic medications may help to reduce the different symptom clusters.[6] COVID vaccines may help to reduce long-COVID symptoms in unvaccinated or partially vaccinated patients.

Many patients can be managed effectively in primary care. Patients with severe symptoms, debilitating symptoms, persisting symptoms after a severe acute illness, atypical symptoms, and those with profound functional disability require specialist care.[6] Ideally, these patients should be managed by a long-COVID care clinic, which should have the services of respiratory medicine, cardiology, neurology, rehabilitation medicine, physiotherapists, and psychologists with facilities for detailed evaluation.

Despite all these measures, some patients continue to suffer from debilitating symptoms. Fatigue, low exercise tolerance, deconditioning, chest discomfort, and breathlessness are the most common debilitating symptoms. There has been ongoing research to ameliorate these debilitating symptoms. Various interventions including nutritional supplementation have been tried with varying results in these patients.

Dietary supplementation with vitamins, minerals, antioxidants, probiotics, and supplements which boost energy have been used with varying results in these patients.[5] Mitochondrial dysfunction is thought to be one of the causes for these debilitating symptoms. Creatine supplement may help to upregulate the mitochondrial function and recharge the cells, thereby improving the symptoms in long-COVID.[7]

In this issue of the journal, Slankaumenac et al.[8] have reported that creatine supplementation combined with breathing exercises reduces lung discomfort and improves tissue creatine status in a small group of patients with long-COVID. This was a double-blind, parallel-group design study, in which the study group had a better outcome compared to the other group. Hence, they have postulated that creatine supplementation may be beneficial in patients with long-COVID. Since the study consisted of only a small number of participants, more research is needed to elucidate whether the findings of this study can be put into clinical practice.

It should be noted that preliminary renal and liver function tests should be done before administering creatine supplement as safety has not been established in patients with impaired liver and renal function.[9] Creatine is better avoided in patients with uncontrolled diabetes and psychiatric disorders. Creatine supplement has been used since many years to improve exercise tolerance and muscle strength, especially by athletes. There have been no reports of serious systemic adverse effects when creatine supplement is used within the recommended dosage in healthy adults. Overdose of creatine can lead to gastrointestinal discomfort, vomiting, diarrhea, fatigue, and muscle cramps.

Patients with debilitating symptoms due to long-COVID need a multidisciplinary approach and multi-pronged treatment strategies to ameliorate their symptoms. Dietary supplements can be useful as an adjunctive treatment in these patients.