The word Corona whispers in every space on the globe and will set an example to the next era for whole health care sectors how to prevent this pandemic situation. This unanticipated outbreak of SARS-CoV-2 which formed a clade within the subgenus co-virus Ortho-coronavirinae subfamily. They cause many complications like pneumonia and other symptoms like fever, pharyngalgia, fatigue, diarrhea, and other non-specific symptoms. Still, we lack a better understanding of the virus, thus, effective approaches to treatment and epidemiological controls are still under construction. In this article, we present the current epidomological status of SARS-CoV-2 and current ongoing historical solidarity clinical trial review. This Solidarity clinical trial will compare four treatment options against standard care, to assess their relative effectiveness against COVID-19. The four treatments to be analyzed are Remdesivir, The combination lopinavir/Ritonavir, Hydroxychloroquine, and Optimized support care all or until discharge from hospital, whichever occurs first. We conjecture the repurposing drug treatment with a clear well designed clinical trial will produce effective relief from this global pandemic situation.
The whole globe was running normally until the emergence of COVID19 made everything to stun, everywhere it as the main flash news, and even occupied the air in every space. There cannot be even a person without knowing the name ‘Corona’. As World Health Organization (WHO) declared that, COVID-19 has become a global health concern, causing severe respiratory tract infections in humans. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus covirus. Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans1.
When SARS-CoV-2 infects a person, there will be a severe cause of pneumonia2. When SARS-CoV-2 infects a person, the lesions are not limited to the lungs. The virus causes viremia after entering the body and the main clinical manifestation is fever, pharyngalgia, fatigue, diarrhea, and other non-specific symptoms3,4. A study of early transmission dynamics of COVID-19 revealed that the mean incubation period was 5.2 days5. An unusual case was also reported in which the incubation period was as long as 19 days6. However, the scientists suggest based on the person’s immunity the exposure of symptoms may be seen and a minimum 14 days quarantine is needed.
World Health Organization (WHO) Director-General opening remarks at the media on 27 March 2020, says that “A vaccine is still at least 12 to 18 months away. In the meantime, we recognize that there is an urgent need for therapeutics to treat patients and save lives. Today we are delighted to announce that in Norway and Spain, the first patients will shortly be enrolled in the Solidarity Trial, which will compare the safety and effectiveness of four different drugs or drug combinations against COVID-19. This is a historic trial where more than 45 countries are contributing to the trial, and more have expressed interest. The more countries who join the trial, the faster we will have results7.” Now the whole world seeks for the single first vaccine or drug against Covid19 and many pharmaceutical companies heading towards the clinical trial to produce effective vaccines or drugs for Covid19.
Many treatment strategies have been going through to save many lives and they include Anti-viral drug therapy, Cellular therapy, Immunotherapy, Anti-malarial drugs, Anti-HIV drugs, Indian traditional medicines, Chinese medicines8. However, there is no specific drug or vaccine against SARS-CoV-2 communicable disease. Thus a clear understanding of the SARS-CoV-2 virus to build new strategies for exploring new vaccines or drugs with a clear framework on clinical trial design for fastest and safest drug development.
CURRENT EPIDEMIOLOGY STATUS
The outbreak of this Covid19 is now all over the world. The outbreak of COVID-19 originated from Wuhan City, Hubei province, in China. Fifty-five percent of the infected cases before 1 January 2020 were linked to the Huanan Seafood Wholesale Market. However, the first human-to-human case of SARS-CoV-2 infection reported on 1 December 2019 did not have any exposure to this market9,10. In the early stages of the global COVID-19 spread, the cases identified outside of China were mostly travelers who were infected in China and then traveled to areas outside of China11. Now, Globally about 213 countries and territories have affected by this pandemic.
Usually, Clinical trials will normally proceed through phases I–IV, which take a decade or more long and costly. Thus, the normal drug development process in a clinical trial is not appropriate to the current global pandemic condition. Therefore, there has been considerable interest in repurposing existing drugs and expediting developmental antiviral treatments, such as those for influenza, hepatitis B (HBV), hepatitis C (HCV), and filoviruses, to allow more rapid development12. At the same time, several trials were initiated to test the specific vaccines and antibodies specifically targeting SARS-CoV-213.
SOLIDATORY Clinical trial
“Solidarity” is an international clinical trial to help find an effective treatment to COVID-19, launched by the World Health Organization and partners. This trial will compare four treatment options against standard care, to assess their relative effectiveness against COVID-19. This aims whether any drug treatment slows down the progress of a disease or improves survival. Until now there is no strong sufficient evidences14.
On March 13, the United Nations Foundation, the Swiss Philanthropy Foundation, and the World Health Organization (WHO) has created the SOLIDARITY Response Fund in to raise money to support studies on COVID-19. On March 18, WHO indicated that the first trial supported by the Fund would be an adaptative study performed in ten countries, namely Argentina, Bahrain, Canada, France, Iran, Norway, South Africa, Spain, Switzerland, Thailand. India joined the trial on March 27.
On March 22, the French Institut National de la Santé Et de la Recherche Médicale (INSERM) announced a European counterpart, named Discovery, and aimed at a study of four treatments on 3100 patients in seven countries, namely France, Spain, the United Kingdom, Germany, Luxembourg, the Netherlands, and Belgium15.
The four treatments to be analyzed are:
- The combination lopinavir/ritonavir;
- The combination lopinavir/ritonavir with the addition of interferon β-1a;
- Hydroxychloroquine, eventually associated with an antibiotic (azithromycin) in add-on studies.
On 23 May 2020, the Executive Group of the Solidarity trial decided to implement a temporary pause of the hydroxychloroquine arm of the trial, because of concerns raised about the safety of the drug.
On 3 June 2020, WHO’s Director-General announced that based on the available mortality data, the members of the committee have recommended that there are no reasons for the committee to have recommended that there are no reasons to modify the trial protocol.
The Executive Group received this recommendation and endorsed the continuation of alarms of the Solidarity Trial, including hydroxychloroquine14.
Research database search
- EU Clinical Trial Registry21
- WHO International Clinical Trial Registry18
- Cochrane Controlled Register of Trial19
- Declaration of Helsinki20
In this article, we present an overview of the current state of knowledge on the SARS-CoV-2 and Study design of Solidarity of the Canadian Clinical Trial Arm. This Solidarity study uses an adaptable design that assesses a safe and effective therapeutic agent (Lopinavir/Ritonavir, Hydroxychloroquine, Remdesivir) for COVID-19 during the pandemic. Randomization and blinding are essential to establish the effectiveness of the drugs. The placebo used in this study as a mechanism for blinding participants, doctors, and other professionals in the study. Thus, a clear hypothesis and succinct methods for screening, blinding, randomization, treatment delivery, endpoints, and data analysis are the backbones of a well-designed clinical trial.
- Zhu N , Zhang D , Wang W , Li X , Yang B , Song J , et al. A novel coronavirus from patients with pneumonia in China, 2019. N Eng J Med 2020; 382:727–33.
- Song, Z., Xu, Y., Bao, L., Zhang, L., Yu, P., Qu, Y., Zhu, H., Zhao, W., Han, Y., Qin, C., 2019. From SARS to MERS, thrusting coronaviruses into the spotlight. Viruses. 11, 59. https://doi.org/10.3390/v11010059.
- Zhang W, Du RH, Li B, et al. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg Microb Infect. 2020; 9:386–389.
- Chen WL, Lan Y, Yuan XZ, et al. Detectable 2019- nCoV viral RNA in blood is a strong indicator for further clinical severity. Emerg Microb Infect. 2020; 9:469–473.
- Li Q, Guan X , Wu P , Wang X , Zhou L , Tong Y , et al. Early transmission dynamics in Wuhan, China, of novel Coronavirus-infected pneumonia. N Engl J Med 2020; 382:1199–207.
- Bai Y , Yao L , Wei T , Tian F , Jin DY , Chen L , et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA 2020.
- (https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19—27-march-2020) Accessed 9 June 2020.
- H. Li, S.-M. Liu and X.-H. Yu et al., Coronavirus disease 2019 (COVID-19): current status and future perspectives, International Journal of Antimicrobial Agents, https://doi.org/10.1016/j.ijantimicag.2020.105951.
- CDC. Coronavirus Disease 2019 (COVID-19) Situation Summary. Available online: https://www.cdc.gov/coronavirus/2019-nCoV/summary.html#risk-assessment (accessed on 3 April 2020).
- WHO. Coronavirus Disease (COVID-2019) Situation Reports-48. Available online: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200308-sitrep-48-covid-19.pdf?sfvrsn=16f7ccef_4 (accessed on 10 March 2020).
- WHO Coronavirus disease 2019 (COVID-19) Situation Report – 26 (15 Feb 2020). Available from https://www.who.int/docs/defaultsource/coronaviruse/situationreports/20200215-sitrep-26-covid-19.pdf?sfvrsn=a4cc6787_2. Accessed 02 Mar 2020.
- Li, G. and de Clercq, E. (2020) Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat. Rev. Drug Discovery, 19, 149–150.
- Yung-Fang Tu et al,. A Review of SARS-CoV-2 and the Ongoing Clinical Trials, The international journal of molecular sciences, published 10 April 2020.
- Solidarity clinical trial for COVID-19 treatments, World Health Organization, https:www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments.
- Jean Jacques Vanden Eynde et al,. COVID-19: A Brief Overview of the Discovery Clinical Trial, Pharmaceuticals journal, Published 10 April 2020.
- (https://clinicaltrials.gov/ct2/show/NCT04330690?term=Remdesivir&cond=SARS-CoV+2&age=012&draw=3&rank=12#wrapper), Canadian Arm of Solidarity Trial, Assessed 17 June 2020.
- SARS-CoV-2 Clinical trials, (https://clinicaltrials.gov), Assessed 15 June 2020.
- Clinical trials in SARS-CoV-2, (www.who.int/ictrp/en/), Assessed 15 June 2020.
- SARS-CoV-2 Clinical trials, (www.cochranelibrary.com/central/about-central), Assessed 16 June 2020.