Strategies for antiviral treatment of COVID-19 and post-COVID syndrome: a narrative review of evidence-based approaches and pharmacoeconomic considerations

Background. Post-COVID syndrome (PCS) presents with significant clinical heterogeneity and is associated with reduced quality of life, impaired status, and diminished work capacity. As no causal therapy for PCS has been approved, it is essential to distinguish the role of early antiviral treatment during acute COVID-19 (which may mitigate the risk of long-term sequelae) from the use of antiviral agents in patients with established PCS.

Objective: To review the clinical, pharmacological, technological, and pharmacoeconomic factors underlying the use of contemporary antiviral strategies for COVID-19 and PCS.

Material and methods. A narrative review was conducted in accordance with the SANRA scale criteria and the CHEERS 2022 statement for reporting economic evaluations. The literature search was conducted in PubMed/MEDLINE, ScienceDirect, SpringerLink, Google Scholar, eLibrary, and CyberLeninka. Eligible publications included randomized and observational clinical trials, systematic reviews, pharmacoeconomic evaluations, and research on antiviral agents, biological therapeutics, and emerging drug delivery technologies.

Results. Strong evidence supports early initiation of antiviral therapy in high-risk patients during acute COVID-19. Nirmatrelvir/ritonavir demonstrates the greatest clinical benefit in reducing hospitalization and mortality rates, although its effect on PCS risk remains uncertain. Remdesivir use is limited by its intravenous administration and the associated healthcare resource utilization, while molnupiravir is generally considered alternative. The economic value of monoclonal antibodies depends on the susceptibility of circulating SARS-CoV-2 variants. In the STOP-PASC trial, a 15-day course of nirmatrelvir/ritonavir showed no meaningful improvement in symptoms among patients with established PCS. Small interfering RNAs, nanoformulations, prodrugs, and intranasal delivery systems are supported primarily by preclinical or early-phase clinical data. Pharmacoeconomic assessments should distinguish between preventing PCS and treating established PCS, while accounting for disease phenotype, quality of life, work capacity, and rehabilitation needs.

Conclusion. Routine use of antiviral agents in established PCS is not supported by current evidence. Further investigation may be warranted in subgroups with indications of viral or antigenic persistence. Early antiviral therapy for acute COVID-19 in high-risk patients remains justified, although its potential to prevent PCS requires further evaluation.

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