key: cord-0948077-nedsqmr0 authors: Khan, Zakir; Karataş, Yusuf; Rahman, Hazir title: Anti COVID-19 Drugs: Need for More Clinical Evidence and Global Action date: 2020-04-29 journal: Adv Ther DOI: 10.1007/s12325-020-01351-9 sha: 9b23256b2e7750890fe88f0e3b8be2a480a90b87 doc_id: 948077 cord_uid: nedsqmr0 The World Health Organization (WHO) called the outbreak of coronavirus infectious disease-2019 (COVID-19) a “Public Health Emergency of International Concern” (PHEIC). According to the WHO, Centers for Disease Control and Prevention (CDC), and the US Food and Drug Administration (FDA), currently there are no medicines or vaccines that have been claimed to be useful in the prevention or treatment of COVID-19. Several existing antiviral drugs, previously developed or used as treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), human immunodeficiency virus (HIV), and malaria, are being investigated as COVID-19 treatments and some of them are being used in clinical trials. According to the CDC and Chinese treatment guidelines for COVID-19, chloroquine, hydroxychloroquine, lopinavir/ritonavir, and one of the investigational agents (remdesivir) are recommended in critically ill older patients. The use of other potential drugs reported in different studies may be considered if treatment with first-line drugs is ineffective. There are currently no complete data available from large randomized clinical trials (RCTs) to provide clinical guidance on the use, dosing, or duration to validate the effective role, safety profile, and adverse effects of all of the trial drugs for prophylaxis or treatment of COVID-19. Until now, it is still unclear which drug can successfully fight against the disease. Therefore, for the better safety of patients with COVID-19, further clinical trials and large randomized controlled studies are needed to validate the effective role, safety profile, and adverse effects of all the potential drugs. Such a measure requires action at the global level. According to the WHO, Centers for Disease Control and Prevention (CDC), and the US Food and Drug Administration (FDA), there is currently no proven effective drug or vaccine for the treatment or prevention of COVID-19. However, several existing drugs are being investigated as COVID-19 treatments and some of them are being used in clinical trials. According to the CDC, two licensed drugs (chloroquine and hydroxychloroquine) and investigational agent (remdesivir) are currently in use in the USA. On the other hand, the China International Exchange and Promotive Association for Medical and Health Care (CPAM) has released COVID-19 guidelines and recommended the use of lopinavir/ritonavir tablets or chloroquine in critically ill older patients. Hydroxychloroquine is also recommended when chloroquine is unavailable. The use of other potential drugs reported in different studies may be considered if treatment with first-line drugs is ineffective. Currently no complete data are available from large randomized clinical trials (RCTs) to provide clinical guidance on the use, dosing, or duration to validate the effective role, safety profile, and adverse effects of all of the trial drugs for prophylaxis or treatment of COVID-19. Until now, it is still unclear which drug can successfully fight against the disease. Further clinical trials, large randomized controlled studies, and global action are needed for effective and safe Anti COVID-19 therapy. The city of Wuhan, China became the center of an outbreak of an unknown cause of pneumonia in December 2019 and raised intense global attention. Chinese scientists isolated a novel coronavirus from infected patients in Wuhan by January 7, 2020. This strain of coronavirus became formally known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and also referred to as 2019-nCoV. The infection caused by this virus is known as coronavirus infectious disease-2019 (COVID-19) [1] . Cases of COVID-19 are no longer restricted to Wuhan, with the growing number of cases and expanding geographic distribution raising serious questions about the outbreak's future trajectory [2, 3] . The World Health Organization (WHO) called the outbreak of COVID-19 a ''Public Health Emergency of International Concern'' (PHEIC) on January 30, 2020 [4] . COVID-19 cases had been recorded around the world, including Western Pacific, European, Southeast Asia, Eastern Mediterranean, Americas, and African regions. More than 220 countries registered cases of COVID-19 with 1,773,084 confirmed cases and 111,652 deaths worldwide, according to the WHO report on April 13, 2020 [5] . As a result of the serious global health threat, international health authorities' efforts have concentrated on rapid detection and isolation of patients with COVID-19, as well as the search for treatments capable of mitigating the disease's most serious consequences. In the absence of a known effective treatment and because of the public health emergency, the world is endangered by the risk of a SARS-CoV-2 pandemic. According to the WHO [6] , Centers for Disease Control and Prevention (CDC) [7] , and the US Food and Drug Administration (FDA) [8] , there is currently no proven effective drug or vaccine for the treatment or prevention of SARS-CoV-2 infection. Now the world is desperately searching for ways to stop the spread of the novel coronavirus and find effective therapies. Drug repositioning (drug repurposing) is the investigation of existing drugs for new therapeutic purposes. It is a line of scientific research aimed at developing safe and effective treatments for COVID-19 [9] . Therefore, different clinical trials have been conducted to identify possible treatment options for COVID-19. Several existing antiviral drugs, previously developed or used as treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), human immunodeficiency virus (HIV), and malaria, are being investigated as treatments for COVID-19 and some have moved into clinical trials conducted around the globe [10] . According to the CDC, two licensed drugs (chloroquine and hydroxychloroquine) and one investigational agent (remdesivir) are currently in use in the USA [11] . However, remdesivir is not approved by the FDA for a COVID-19 indication [12] . On the other hand, the China International Exchange and Promotive Association for Medical and Health Care (CPAM) has released COVID-19 guidelines and recommended the use of lopinavir/ritonavir tablets (400 mg/100 mg orally twice daily) or chloroquine (500 mg orally two times daily) in critically ill older patients. Hydroxychloroquine (orally 400 mg once daily) is also recommended when chloroquine is unavailable [13] . The use of other drugs such as hydroxychloroquine plus azithromycin [14, 15] , ribavirin [16, 17] , interferon [18, 19] , oseltamivir [20] , favipiravir [21] , sofosbuvir [22] , ivermectin [23] , ozone therapy [24] , and tocilizumab [25] has not been recommended as first-line therapies; however, use of such drugs may be considered if treatment with first-line drugs (chloroquine, hydroxychloroquine, and lopinavir/ritonavir) is ineffective [13] . These products have shown some effectiveness in laboratory and animal experiments but it is not possible to make an evidence-based recommendation on their use in COVID-19 treatment unless a large human trial is conducted. The name ''SOLIDARITY trial'' was given to such an effort by the WHO [26] . Currently, limited data from randomized clinical trials (RCTs) are available to inform clinical guidance on the use, dosing, or duration of the aforementioned drugs for prophylaxis or treatment of SARS-CoV-2 infection [8, 14] . Moreover, the recommended anti COVID-19 medications are likely to have adverse effects, such as the risk of macular retinopathy [27] and cardiomyopathy due to chloroquine [28] , and cardiotoxicity (prolonged QT syndrome) due to extended use of hydroxychloroquine alone or in combination with azithromycin in hepatic, renal, and immunocompromised patients [11, 29] . Additionally, hydroxychloroquine in combination with azithromycin has been reported to reduce the detection of SARS-CoV-2 RNA in upper respiratory tract specimens compared to a non-randomized control group but did not assess clinical benefit [15] , and in a recent randomized, controlled, open-clinical trial in China, lopinavir/ritonavir did not show promise for the treatment of hospitalized patients with COVID-19 and pneumonia [30] . Therefore, for the better safety of patients with COVID-19, further clinical trials and large randomized controlled studies are needed to validate the effective role, safety profile, and adverse effects of all the test drugs [26, 31] . However, any approvals for the use of a new drug, of course, require further clinical testing, followed by the approval of widespread use by the relevant regulatory body for medical treatment in each country. To accomplish this, there is an urgent need for global collaboration, access conditions for public funds, and upfront agreements and affordability arrangements with those involved in the development of new medical technologies. Products for the prevention and treatment of COVID-19 should be global public goods. Such a measure requires action at the global level. Funding. No funding or sponsorship was received for this study or publication of this article. Authorship. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Disclosures. Zakir Khan, Yusuf Karataş, and Hazir Rahman declare no conflict of interest. Compliance with Ethics Guidelines. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors. Data Availability. Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. Open Access. This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/bync/4.0/. World Health Organization (WHO). 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