“There is almost nothing surprising about COVID-19 pandemic” if we remind ourselves from the SARS outbreak that occurred in late 2002 and 2003, not long after China had resumed sovereignty over Hong Kong in 1997. Several countries are involved in multiple diagnostic, therapeutic, and preventive interventions for COVID-19. Lack of any specific therapeutic agents due to COVID-19 pandemic and substantial mortality has led to various challenges to find new treatments. The lack immunity to SARS-CoV-2 makes human population susceptible to the novel virus. COVID-19 impact is on the global level. Making decisions to mitigate COVID-19 with limited knowledge may affect directly the level of the public health response or clinical management. Patients should not be given drugs of unknown efficacy, however, for patients with life-threatening infections, off-label or compassionate use of drugs should be considered ethical (Zhang and Qian, 2020).
Several studies have been focusing on the trends in clinical trials involving “COVID-19” to fight the pandemic. Lythgoe and Middleton published an analysis involving the clinical trials for the management of the COVID-19 Pandemic last year, June 2020. The present study gives a complete overview on clinical trials involving “COVID-19”. One of the major limitation of the present analysis, based on the analysis of clinical trial databases in general, might be a reporting bias. The reason is that all studies may not have been registered on public databases, hence, limiting the representativeness of the data on this type of trials.
Although a large series of clinical trials involving COVID-19 has been registered in public databases, only a small part has been completed with results with only few studies in phase 3 and phase leaving a scope for the focus on the actual implementation of the interventions to eradicate the critical pandemic period being faced at the global scale. A substantial difference has been observed between geographical regions, where the studies have been performed. The greatest part of all trials was performed in the USA and in Europe and fewer in Asian countries. The major reasons for this may be seen in the differences in legal and/or regulatory restriction etc. The clinical trials have three phases with an increasing number of candidates. But, for COVID-19, scientists are proposing human trials to compress the timeline for developing the vaccine (Lurie et. al., 2020). However, human trials are also a challenge because even after a vaccine has crossed the final clinical trial phase, licencing and quality control takes a lot of time before the vaccine can be launched in the market and made available to the general public (Newton, 2020).
Ivermectin is FDA-approved broad-spectrum antiparasitic agent and now widely been used for SARSVOV-2 infected individuals. However, its antiviral activity against SARS-CoV-2 is currently under investigation in patients, insufficient emphasis has been placed on formulation challenges (Formiga et. al., 20121). Use of ivermectin as prophylactic against SARS-CoV-2 inhibits SARS-CoV-2 replication and likely leads to lower infection rates. Studies suggests the use of Ivermectin as potential off-label prophylactic drug in certain cases to help bridge the time until a safe and effective vaccine for SARS-CoV-2 becomes available (Hellwig and Maia, 2021). Other studies suggest that a five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness (Ahmed et. al., 2021). Use of Favipiravir as pharmacological post exposure prophylaxis for Ebola virus disease prior to COVID-19 outbreak is reported (Jacobs et. al., 2015).
Favipiravir is currently being used as an antiviral for COVID-19. Other studies have indicated a significant reduction in the time to SARS-CoV-2 viral clearance in patients treated with favipiravir compared with historical controls treated with lopinavir/ritonavir (Cai et. al., 2020). Favipiravir triphosphate acts as a competitive inhibitor of RNA-dependent RNA polymerase and has activity against influenza A and B (Furuta et. al., 2013; Wang et. al., 2020; Shiraki et. al., 2020). Use of favipiravir in the treatment protocol against SARS-CoV-2 infection is included for many countries including India. It has been shown to have promising results in clinical studies conducted in China, Russia, and Japan, and also more trials are underway in multiple countries, including USA, UK, and India (Joshi et. al., 2021). Remdesivir (RDV) is an inhibitor of RNA-dependent RNA polymerases (RdRps) a novel antiviral drug originally used for the treatment of Ebola virus disease and Marburg virus infections (Chih-Chia Lu et. al., 2020). Remdesivir has a broad-spectrum activity against many virus families e.g. Filoviridae, Paramyxoviridae, Pneumoviridae, and Orthocoronavirinae (such as pathogenic SARS-CoV and Middle East respiratory syndrome coronavirus [MERS-CoV]) (Sheahan et. al., 2017; Martinez, 2020). It was in USA where the first patient was treated successfully with remdesivir for the progression of pneumonia (Holshue et. al., 2020). Although remdesivir has entered into phase III trial for COVID-19, information regarding the pharmacokinetics of remdesivir in humans is not available (Jean et. al., 2020).
Finding effective therapies across the spectrum of clinical disease states due to variations in clinically different populations also affects the outcomes of the clinical trials processes (Jay et. al., 2020). Racial disproportionality in COVID clinical trials is due to lack of diversity in clinical trials due to long standing medical distrust on the part of minority communities is reported (Chastain et. al., 2020). Covid-19 is thus complicated and referral of patients to clinical trials is critical (David et. al., 2020). Moreover, racial disproportionality in Covid Clinical Trials is also a matter of concern as the data supporting the drug’s efficacy and safety in minority groups are limited (Chastain et. al., 2020). For example, the modest benefit to clinical improvement with remdesivir may not be generalizable to minority populations that affect the disease severity and outcomes (Chastain et. al., 2020). Covid-19 is thus complicated and since no proven therapies for Covid-19 exits till today and referral of patients to clinical trials is critical (David et. al., 2020). The case of Covid-19 is an iterative learning process and warrants the critical gaps to be filled. The policy makers must address the underrepresentation of minority groups in clinical trials for COVID-19 (Chastain et. al., 2020).