A new review article titled “Pharmacological Approaches to the Management of Long COVID” by Kaushik Bharati has been published in Trends in Pharmacology and Toxicology. The article provides a timely and comprehensive synthesis of current pharmacological strategies being explored to manage Long COVID, a complex and increasingly recognized post-viral condition affecting millions worldwide.
Long COVID, also referred to as post-COVID-19 condition, is characterized by persistent and often fluctuating symptoms such as fatigue, dyspnea, cognitive impairment (“brain fog”), autonomic dysfunction, and psychological disturbances that continue for weeks or months after acute SARS-CoV-2 infection. Epidemiological evidence summarized in the review suggests that approximately 10–30% of infected individuals develop Long COVID, including patients who initially experienced mild disease. The condition poses a substantial burden on healthcare systems due to reduced quality of life, impaired work capacity, and long-term care needs.
The review emphasizes that the heterogeneity of Long COVID symptoms reflects multiple underlying pathophysiological mechanisms, including chronic inflammation, immune dysregulation, endothelial dysfunction, microvascular injury, viral persistence, and autonomic nervous system imbalance. This mechanistic diversity has complicated the development of universally effective therapies and necessitates individualized treatment approaches.
Current pharmacological management strategies remain largely symptomatic and rely on drug repurposing. Antiviral agents such as nirmatrelvir/ritonavir (Paxlovid), remdesivir, and molnupiravir are discussed for their potential role in reducing viral persistence, although evidence for benefit in established Long COVID remains limited. Immunomodulatory and anti-inflammatory agents, including baricitinib, low-dose naltrexone, and novel NLRP3 inflammasome inhibitors, are highlighted as promising candidates targeting sustained immune activation and neuroinflammation. The article also reviews experimental therapies such as monoclonal antibodies and autoantibody-neutralizing agents aimed at addressing autoimmune components of Long COVID.
In addition, the review covers supportive pharmacological options tailored to specific symptom clusters. These include antihistamines for mast cell activation–related symptoms, agents targeting gut permeability and endothelial dysfunction, and cardiac or autonomic drugs such as ivabradine and beta-blockers for postural orthostatic tachycardia syndrome (POTS). Importantly, the author underscores that pharmacological treatment should be integrated with multidisciplinary supportive care, rehabilitation, and long-term follow-up.
A key strength of the article lies in its forward-looking perspective. It highlights the limitations of existing evidence, noting that most clinical trials are early-phase or exploratory, and stresses the urgent need for large, well-designed, stratified trials. The review advocates a precision-medicine framework in which therapies are matched to patient phenotypes and dominant biological mechanisms, rather than a one-size-fits-all approach.
Overall, this publication serves as a valuable resource for clinicians, researchers, and policymakers seeking to understand the evolving therapeutic landscape of Long COVID. By consolidating current knowledge and identifying emerging drug candidates, it contributes meaningfully to ongoing efforts to develop effective, safe, and personalized interventions for this global public health challenge.