A Review of Treatment of Coronavirus Disease 2019 (COVID-19): Therapeutic Repurposing and Unmet Clinical Needs

Abstract

For the initial phase of pandemic of coronavirus disease 2019 (COVID-19), repurposing drugs that in vitro inhibit severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been attempted with overlooked or overestimated efficacy owing to limited clinical evidence. Most early clinical trials have the defects of study design, small sample size, non-randomized design, or different timings of treatment initiation. However, well-designed studies on asymptomatic or mild, or pediatric cases of COVID-19 are scarce and desperately needed to meet the clinical need. However, a trend could be observed based on current clinical evidence. Remdesivir and favipiravir may shorten the recovery time; lopinavir/ritonavir does not demonstrate treatment efficacy in severe patients. Triple therapy of ribavirin, lopinavir, and interferon β-1b showed early viral negative conversion, and the major effect may be related to interferon. Some small sample-size studies showed that interleukin-6 inhibitors may demonstrate clinical improvement; non-critical patients may benefit from convalescent plasma infusion in small sample-size studies; and the role of hydroxychloroquine or chloroquine in the treatment and prophylaxis of COVID-19 remains unclear. Combination therapy of traditional Chinese medicine with antiviral agents (ex. interferon, lopinavir, or arbidol) may alleviate inflammation in severe COVID-19 patients based on small sample-sized observational studies and experts’ opinion. Most of the published studies included severe or critical patients with COVID-19. Combination therapy of antiviral agents and immune-modulating drugs is reasonable especially for those critical COVID-19 patients with cytokine release syndrome. Drugs to blunt cytokine release might not benefit for patients in the early stage with mild disease or the late stage with critical illness. Traditional Chinese medicine with antiviral effects on SARS-CoV-2 and immune-modulation is widely used for COVID-19 patients in China, and is worthy of further studies. In this review, we aim to highlight the available therapeutic options for COVID-19 based on current clinical evidence and encourage clinical trials specific for children and for patients with mild disease or at the early stage of COVID-19.

PD-L1 Dysregulation in COVID-19 Patients

“…The COVID-19 pandemic has far reaching direct and indirect medical and social consequences. So far, there is still an unmet clinical need in defining patient prognosis and effective therapeutic approaches ( 17 ). Several parameters have been proposed to define COVID-19 patient prognosis.…”

A Multidisciplinary Approach to Coronavirus Disease (COVID-19)

“…Due to the prolonged pandemic process and the lack of a suitable treatment as of yet, the drug repurposing approach comes to the fore (Table 1). The fact that the side effects of the drugs used in this approach are known and clinical studies and regulation studies have been conducted provide rapid results [141][142][143][144]. Each of the drugs used in the treatment are effective at different stages of the virus's life cycle.…”

The nucleoside antiviral prodrug remdesivir in treating COVID-19 and beyond with interspecies significance

“…It is the phosphorylated metabolite that delivers potent antiviral activity through distinct but related mechanisms (Fig. 2 ): (A) interfering with the action of viral RNA-dependent RNA polymerase (RdRp); (B) evading exoribonuclease-proofreading; and (C) causing delayed/cyano-group mediated chain termination of viral genome (Chen et al 2020 ; Malin et al 2020 ; Ottoni et al 2020 ; Singh et al 2020 ; Tchesnokov et al 2019 ; Yin et al 2020 ). We have shown that human carboxylesterase-1 (CES1), a highly efficient enzyme, was involved in the hydrolytic activation of remdesivir (Shen et al 2021a , b ).…”