Global Trends in Clinical Trials-SARSCOV-2

It was on March 11, 2020, the World Health Organization (WHO) declared the SARS-CoV-2 (COVID-19) outbreak as a pandemic. According to WHO reports, there have been 156,496,592 conrmed cases of COVID-19, including 3,264,143 deaths, globally, as of 8 May 2021. COVID-19 is contributing to an unconscionable loss of life. Several clinical studies involving COVID-19 are currently in human trials. This study is based on a comprehensive analysis of all clinical trials involving COVID-19 as on May 8, 2021. In total, 5619 studies were identied at “ClinicalTrials.gov” and further classied as observational or interventional study types. The results showed a total of 3156 interventional studies and 2429 observational studies. Phase wise distribution of interventional clinical trials indicate that maximum clinical trials are in phase 2 stage. Observational studies has 6 completed studies with results and interventional trial has 23 completed studies with results. Overall, the study reveals the perspective view of the global clinical translational trends involving COVID-19.


Introduction
WHO has de ned Coronavirus disease 2019 (COVID-19) as a pneumonia of unknown cause detected in Wuhan, China. It was declared was declared a Public Health Emergency of International Concern on 30th January 2020 by WHO. Coronaviruses has been described as an enveloped, pleomorphic or spherical particles of 150 to 160 nm in size (Wu et. al., 2020). CoVs contains an envelope of positive single stranded RNA that can be divided into four genera, i.e., alpha, beta, gamma, and delta, of which alpha-and beta-CoVs are known to infect humans (Wilde et.al. 2018). The difference between coronavirus (CoVs) and COVID-19 encodes an additional glycoprotein that has acetyl esterase and hemagglutination (HE) properties as compared with that of coronavirus (Wu et. al., 2020). COVID-19 infects human by binding its S protein to the human cellular receptors angiotensinconverting enzyme 2 (ACE2) (Dong et. al., 2020). Formation of virion-containing vesicles made of glycoproteins and nucleocapsid proteins that fuses with the plasma membrane helps to release the virus into the host cell (Sevajol et. al., 2014). This binding is weaker for SARS-CoV, than that SARS-CoV-2 that causes less severe infection in patients than SARS-CoV (Dong et. al., 2020).
SARS-CoV continues to rapidly spread throughout the world and its transmission and infection incidence varies greatly among different countries. It is unfortunate that the COVID-19 pandemic may lead to constantly increase burdens of morbidity and mortality and simultaneously disrupting societies and economies at the global level (Lazarus et.al. 2021). In the rst week of May 2021, Brazil's total death toll from COVID-19 passed 400,000 and in India, the pandemic is taking around 3,500 lives every day (Editorial Nature, 2021). This has prompted a global response to tackle the situation in several ways-scienti cally, economically or politically. Several country are involved in multiple diagnostic, therapeutic, and preventive interventions for COVID-19 are being trialed. Emergency efforts are underway to nd optimum medical products to ght COVID-19 pandemic.
COVID-19 pandemic threatens a global surge in substandard and falsi ed medical products either directly or indirectly related to COVID-19. The aim of the study was to perform a comprehensive analysis of all clinical trials involving COVID-19 as on May 8, 2021.

Systematic search of databases
The aim of the study was to perform a comprehensive analysis of all clinical trials involving COVID-19 as on May 8, 2021. First a search was performed in the database "ClinicalTrials.gov" using the search terms "COVID-19" OR "SARSCOV-2". In total 5619 studies were identi ed at "ClinicalTrials.gov". The studies were generally classi ed as observational or interventional study types.

Results
Geographical distribution of clinical trials (total number) involving COVID-19 varied at the global level and a total of 5619 studies were found for COVID-19. Of these, 3156 studies were found for interventional and 2429 for observational studies (Fig. 1B & C). Observational studies has 6 completed studies with results and interventional trial has 23 completed studies with results. Phase wise distribution of interventional clinical trials indicate that maximum clinical trials are in phase 2 stage (Fig. 3A). The duration of the completion of the studies varied with maximum duration for study completion is up to 12 years (Fig. 3B).

Completed clinical trials
Observational studies has 6 completed studies with results and 23 interventional trial has 23 completed studies with results (See  Table 1.  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 nal 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, insu cient emphasis has been  (Sheahan et. al., 2017;Martinez, 2020). It was in USA where the rst 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 e cacy and safety in minority groups are limited (Chastain et. al., 2020). For example, the modest bene t 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 lled. The policy makers must address the underrepresentation of minority groups in clinical trials for COVID-19 (Chastain et. al., 2020