* There was a statistically significant difference between treated patients and controls at days 3-4-5 and 6 (negative PCR)
*At day 6, 70% of HCQ-treated patients were virologically cured comparing with 12.5% in the control group (p= 0.001)
HCQ vs HCQ-Azithromycin combination
* There was a statistically significant difference between treated patients and controls at days 3-4-5 and 6 (negative PCR)
* At day 6, 100% of patients treated with HCQ and azithromycin combination were virologically cured comparing with 57.1% in patients treated with HCQ only, and 12.5% in the control group (p < 0.001)
Conclusion:
*HCQ is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin
|-
| style="padding: 5px 5px; background: #DCDCDC;" |Marqués de Valdecilla University Hospital, Cantabria, Spain<ref name="pmid32493494">{{cite journal| author=Cuadrado-Lavín A, Olmos JM, Cifrian JM, Gimenez T, Gandarillas MA, García-Saiz M | display-authors=etal| title=Controlled, double-blind, randomized trial to assess the efficacy and safety of hydroxychloroquine chemoprophylaxis in SARS CoV2 infection in healthcare personnel in the hospital setting: A structured summary of a study protocol for a randomised controlled trial. | journal=Trials | year= 2020 | volume= 21 | issue= 1 | pages= 472 | pmid=32493494 | doi=10.1186/s13063-020-04400-4 | pmc=7268173 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32493494 }}</ref>
| style="padding: 5px 5px; background: #DCDCDC;" |Eight hospitals in Spain<ref name="pmid32493475">{{cite journal| author=García IG, Rodriguez-Rubio M, Mariblanca AR, de Soto LM, García LD, Villatoro JM | display-authors=etal| title=A randomized multicenter clinical trial to evaluate the efficacy of melatonin in the prophylaxis of SARS-CoV-2 infection in high-risk contacts (MeCOVID Trial): A structured summary of a study protocol for a randomised controlled trial. | journal=Trials | year= 2020 | volume= 21 | issue= 1 | pages= 466 | pmid=32493475 | doi=10.1186/s13063-020-04436-6 | pmc=7267766 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32493475 }}</ref>
The investigational therapies for COVID-19 is an area of vast research due to its global health impact. Many world-renowned research scientists and pharmaceutical companies have joined hands to address the health impact of COVID-19 on the human race. Investigational therapies include both preventative and treatment based strategies.
Future or Investigational Therapies
The following pharmacological therapies are currently under investigation as potentials to treat COVID-19:
Dexamethasone
Chloroquine/Hydroxycholoroquine
Arbidol
Remdesivir
Favipiravir
Ongoing Clinical Trials
Dexamethasone:
Randomized clinical trial
Phase 2 and phase 3
12000 patients
Patients with severe acute respiratory syndrome (ventilated or hypoxic)
The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]).
Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported.
NIH halts clinical trial of hydroxychloroquine
Solidarity clinical trial
WHO and partners have launched an in an international clinical trial to help find an effective treatment for COVID-19. It will compare four treatment options against standard of care, to assess their relative effectiveness against COVID-19.
On 17 June 2020, WHO announced that the hydroxychloroquine (HCQ) arm of the Solidarity Trial to find an effective COVID-19 treatment was being stopped.
FDA approved Phase II and III clinical trial
Clinical Study To Evaluate The Performance And Safety Of Favipiravir in COVID-19 NCT04336904
Ruxolitinib in Covid-19 Patients With Defined Hyperinflammation (RuxCoFlam) NCT04338958
Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734™) in Participants With Moderate Coronavirus Disease (COVID-19) Compared to Standard of Care Treatment NCT04292730
Tocilizumab in the Treatment of Coronavirus Induced Disease (COVID-19) (CORON-ACT) NCT04335071
A Study of Quintuple Therapy to Treat COVID-19 Infection (HAZDpaC Hydroxychloroquine, azithromycin, vitamin C, Vitamin D, zinc) [Phase II] NCT04334512
An Adaptive Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID-19
A Multi-center, Randomized, Parallel-Controlled Clinical Trial of the Application of A Hydrogen-Oxygen Generator With Nebulizer in the Improvement of Symptoms in Patients Infected With COVID-19
A Randomized, Double-blind, Placebo-controlled, Multi-site, Phase III Study to Evaluate the Safety and Efficacy of CD24Fc in COVID-19 Treatment
Use of cSVF For Residual Lung Damage COPD/Fibrotic Lung Disease After Symptomatic COVID-19 Infection For Residual Pulmonary Injury or Post-Adult Respiratory Distress Syndrome Following Viral Infection
A Pragmatic Adaptive Open Label, Randomized Phase II/III Multicenter Study of IFX-1 in Patients With Severe COVID-19 Pneumonia
Chloroquine Phosphate Against Infection by the Novel Coronavirus SARS-CoV-2: The HOPE Open-Label, Non Randomized Clinical Trial
A Phase 2, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Leronlimab for Mild to Moderate Coronavirus Disease 2019 (COVID-19)
A Phase 1b, Randomized, Double-blinded, Placebo-controlled Study of Hydroxychloroquine in Outpatient Adults With COVID-19
Vaccine
AstraZeneca is a potential coronavirus vaccine that is likely to provide protection against contracting Covid-19 for about a year
Immune Targets
The B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins are currently under investigation as immune targets for development of vaccine.
Phylogenetic similarity between SARS-CoV and COVID-19 at the level of structural proteins S, E, M, and N is providing guidance for development of a possible vaccine.
Current Clinical Trials
The following countries are currently working on the development of a vaccine for COVID-19 (SARS-CoV2)
USA
Beth Israel Deaconess Medical Center (BIDMC), Boston and Johnson & Johnson (J&J) are currently collaborating to advance COVID-19 vaccine. A Phase I trial is expected to launch during the last quarter of 2020. AdVac and PER.C6 technologies are being used for rapid production.
National Institute for Allergy and Infectious Diseases (NIAID) has announced that a phase 1 trial has begun for COVID-19 immunization in Washington state.
The trial includes 45 young, healthy volunteers with different doses of immunization shots co-developed by NIH and Moderna Inc.
Israel
Researchers at Israel’s Institute for Biological Research are expected to announce in the coming days that they have completed development of a vaccine for COVID-19
China
China was the first country to release the genetic sequence of the virus on open scientific databases so that research institutes and commercial companies could try to develop treatments and vaccines without needing to obtain samples.
China has announced the first animal tests.
Australia
Following successful in vitro experiments, animal testing has begun in University of Queensland in Australia
Prior Work
The following table depicts major vaccine products that have been developed against SARS-CoV and MERS-CoV:[2][3]
Vaccine Base
Antigen
Clinical Testing
Pros
Cons
DNA
Spike protein S1
Phase I, II
(NCT03721718)
Reduced production time
Easy design and manipulation
Stimulates B and T cells responses
Requires efficient intradermal gene gun delivery to antigen-presenting cells
Weaker immune response compared to live vaccine
Viral Vector
Spike protein S1; Chimpanzee adenovirus vector, Modified Vaccinia Ankara
Phase I
(NCT03399578,
NCT03615911)
Competent immune response
Varied immune response based of mode of delivery
Th2 bias
Conjugated subunit
Spike protein S1
Receptor binding domain
Nucleocapsid
Membrane protein
Envelope protein
Delta Inulin Adjuvant and/or fusion with Fc
Stimulates humoral and cellular responses
Increased safety
Ease of production
Reduced cost-effectiveness may hinder production
Adjuvants required
Virion
Spike protein S1
Receptor binding domain
Membrane protein
Envelope protein
Prepared in baculovirus
Multi-unit
Preservation of whole virus
Requires optimum nucleocapsid assembly
Inactivated
Whole virus
Formaldehyde or gamma irradiation inactivation
Preservation of whole virus
Reduced production time
Competent neutralizing antibody production
Enhanced Protection while ameliorating lung eosinophilic immunopathology
Hypersensitivity reaction
Th2-bias
Live attenuated
Mutant MERS-CoV and SARS-CoV or recombination with other live attenuated virus
Sensitivity to mutagenesis
Excellent B and T cell response
Completed Studies
Medication
Location
Randomized
Controlled
Objective
Severity
Endpoint
Mechanism of action
The Recovery Trial
Dexamethazone
Oxford university
Yes
To test a range of potential treatments for COVID-19, including low-dose dexamethasone
Critically ill-ventilated patients who require oxygen
Reduces mortality by between a sixth and a third.
Reduced mortality from 40% to 25% in ventilated patients
Reduced mortality from 25% to 20% in patients requiring oxygen
It turns down the inflammatory response (overreaction) caused by Cytokine storm
Ongoing Studies
References
↑Boulware DR, Pullen MF, Bangdiwala AS, Pastick KA, Lofgren SM, Okafor EC, Skipper CP, Nascene AA, Nicol MR, Abassi M, Engen NW, Cheng MP, LaBar D, Lother SA, MacKenzie LJ, Drobot G, Marten N, Zarychanski R, Kelly LE, Schwartz IS, McDonald EG, Rajasingham R, Lee TC, Hullsiek KH (June 2020). "A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19". N. Engl. J. Med. doi:10.1056/NEJMoa2016638. PMID32492293Check |pmid= value (help).