The COVID-19 pandemic is one of the greatest threats to human health in the 21st century with more than 257 million cases and over 5.17 million deaths reported worldwide (as of November 23, 2021. Various agents were initially proclaimed to be effective against SARS-CoV-2, the etiological agent of COVID-19. Hydroxychloroquine, lopinavir/ritonavir, and ribavirin are all examples of therapeutic agents, whose efficacy against COVID-19 was later disproved. Meanwhile, concentrated efforts of researchers and clinicians worldwide have led to the identification of novel therapeutic options to control the disease including PAXLOVID™ (PF-07321332). Although COVID-19 cases are currently treated using a comprehensive approach of anticoagulants, oxygen, and antibiotics, the novel Pfizer agent PAXLOVID™ (PF-07321332), an investigational COVID-19 oral antiviral candidate, significantly reduced hospitalization time and death rates, based on an interim analysis of the phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) randomized, double-blind study of non-hospitalized adult patients with COVID-19, who are at high risk of progressing to severe illness. The scheduled interim analysis demonstrated an 89 % reduction in risk of COVID-19-related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset (primary endpoint). However, there still exists a great need for the development of additional treatments, as the recommended therapeutic options are insufficient in many cases. Thus far, mRNA and vector vaccines appear to be the most effective modalities to control the pandemic. In the current review, we provide an update on the progress that has been made since April 2020 in clinical trials concerning the effectiveness of therapies available to combat COVID-19. We focus on currently recommended therapeutic agents, including steroids, various monoclonal antibodies, remdesivir, baricitinib, anticoagulants and PAXLOVID™ summarizing the latest original studies and meta-analyses. Moreover, we aim to discuss other currently and previously studied agents targeting COVID-19 that either show no or only limited therapeutic activity. The results of recent studies report that hydroxychloroquine and convalescent plasma demonstrate no efficacy against SARS-CoV-2 infection. Lastly, we summarize the studies on various drugs with incoherent or insufficient data concerning their effectiveness, such as amantadine, ivermectin, or niclosamide.

COVID-19 大流行是 21 世纪对人类健康最大的威胁之一，全球报告病例数超过 2.57 亿，死亡人数超过 517 万人（截至 2021 年 11 月 23 日）。最初宣称多种药物可有效对抗 SARS- SARS-CoV-2是COVID-19的病原体。羟氯喹、洛匹那韦/利托那韦和利巴韦林都是治疗药物的例子，它们对COVID-19的疗效后来被证明是错误的。同时，全世界研究人员和临床医生的集中努力导致了确定控制疾病的新治疗方案，包括 PAXLOVID™ (PF-07321332)。尽管目前使用抗凝剂、氧气和抗生素的综合方法治疗 COVID-19 病例，但辉瑞新型药物 PAXLOVID™ (PF-07321332)，一种正在研究的 COVID-19 口服抗病毒候选药物，根据 2/3 期 EPIC-HR（高危患者中 COVID-19 蛋白酶抑制评估）的中期分析，显着降低了住院时间和死亡率。对未住院的成年 COVID-19 患者进行盲法研究，这些患者进展为重症的风险很高。预定的中期分析表明，与安慰剂相比，在症状出现三天内接受治疗的患者（主要终点），与 COVID-19 相关的住院或全因死亡风险降低了 89%。然而，仍然非常需要开发额外的治疗方法，因为推荐的治疗方案在许多情况下是不够的。迄今为止，mRNA 和载体疫苗似乎是控制大流行的最有效方式。在当前的综述中，我们提供了自 2020 年 4 月以来有关抗击 COVID-19 疗法有效性的临床试验进展的最新信息。我们重点关注当前推荐的治疗药物，包括类固醇、各种单克隆抗体、瑞德西韦、巴瑞替尼、抗凝剂和 PAXLOVID™，总结了最新的原始研究和荟萃分析。此外，我们的目的是讨论目前和之前研究的其他针对 COVID-19 的药物，这些药物要么没有显示出治疗活性，要么显示出有限的治疗活性。最近的研究结果表明，羟氯喹和恢复期血浆对 SARS-CoV-2 感染没有功效。最后，我们总结了各种药物的研究，这些药物的有效性数据不连贯或不充分，例如金刚烷胺、伊维菌素或氯硝柳胺。