Strategies for Detection, Prevention, and a search for Cure
A number of misinformation or half-truths have been in circulation regarding the SARS-COV2 infection and its resultant disease- COVID 19 in the past few days. To bust all the unnecessary information in circulation,here are some relevant (and current) information about drugs and vaccines that are under trial and are being tested and how some have been found effective (or ineffective) in certain demographics. All information comes with legitimate sources.
Current status of the spread: SARS-COV2 or COVID-19 viral infection, its exponential rate of spread and community transmission has reached to alarming levels all over the world, making it a pandemic disease.
The contagion has made its imprint globally affecting more than 300,000 or more populace (confirmedsource: https://coronavirus.jhu.edu/) leading to over 13500 or more deaths. The recovery rate is still at a lower percentage, butt currently the active confirmed cases across the globe is of real concern.
The exponential spread of this virus (Source: https://medium.com/@tomaspueyo/coronavirus-act-today-or-people-will-die-f4d3d9cd99ca) has led to several opinions of various infectious disease experts, however, the data shared have always fall short of the actual curve indicating the number of infected people.
Three pronged approach against COVID-19 is taken up by the Pharmaceutical/Biotechs:
- Detection
- Prevention
- Cure
Sars-Cov was discovered in China before being spread globally, infecting 8,098 people and killing 774. This was later found to be zoonotic in origin and thought to have started amongst a bat reservoir before later infecting wild civet cats and raccoon dogs that were being sold at live wild animal markets destined for human consumption. In 2012, Mers-Cov was discovered in Saudi Arabia before also spreading globally resulting in 2506 confirmed cases and killing 862 people worldwide. Again, this started as a zoonotic virus, shown to move from camels to humans and again thought to have initially emerged from bats.
The efforts undertaken in each of these three directions is detailed below:
- Detection: Fast and timely detection is key to containing and managing the spread of the disease. The best advancement in this sector is the new detection test available, which gives results in less than an hour thereby helping the patients et speedy detection and thereby fast paced treatment.
- CDC’s own 2019-nCoV Real Time RT-PCR diagnostics test kit is available. Turnaround time: ~1 day (source: https://www.cdc.gov/coronavirus/2019-ncov/about/testing.html)
- CDC is also working on a Serology Test which should be able to detect asymptomatic people. This is important in order to understand the true spread of the disease.
- There are a number of diagnostics companies and labs who have come up with the methods to devise their own detection kits and have now been given emergency approval by FDA.
The latest one is from Cepheid, this test takes around 45 minutes to complete. (source: https://www.cnn.com/2020/03/21/politics/fda-coronavirus-test/index.html), the full list is available here: https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations)
- Prevention:For viral spread prevention, certainly maximum efforts are concentrated around development of vaccines, other than regular Dos and Don’ts. Vaccines are only useful for people who are at risk have not contracted the disease yet. The currently expected timeline of vaccine development may take around a year. Concerted efforts from various organisations is leading to human testing protocols for faster outcomes. Leading them is The Coalition for Epidemic Preparedness Innovations (CEPI) (https://cepi.net/covid-19/).
To produce and market the first vaccine at the earliest, CEPI is working in consortium with a number of pharmaceutical and Biotech companies. It’s important to understand that a vaccine being ready to be tested in humans is not the same as the vaccine being available for public dispensation. The latter takes time as it requires the product to go through several rounds of human trials and testing to verify its efficacy.
HERE IS A LIST OF COMPANIES WHO ARE WORKING TOWARDS A VACCINE: (NOT EXHAUSTIVE)
| Company | Country | Compound | Stage of development |
| Moderna | USA | Mrna-1273 | Phase I (human testing) |
| CanSino Biologics | China | Unknown | Approval to begin Phase I |
| Arcturus Therapeutics | USA | Unknown | Preclinical |
| BioNTech/Pfizer | Germany | mRNA based | Phase I to begin in April |
| CureVac | Germany | mRNA based | Preclinical to begin in April |
| GSK/Clover biopharm | USA/China | Unknown | TBD |
| Inovio Pharma/Beijing Advaccine Biotech | USA/China | INO-4800 | Preclinical |
| Johnson and Johnson | USA | Unknown | Early preclinical |
| Sanofi/BARDA | France | DNA based | Lab testing in 6 months |
| University of Queensland/CEPI | Australia | Unknown | Preclinical |
| Medicago/Laval University | Canada | Unknown | IND Approval pending |
| Altimmune | USA | Intranasal | Preclinical |
| Migal Research Institute | Israel | IBV modified | Still in Lab |
| Tonix Pharma/ Southern research | USA | TNX-1800 | Still in Lab |
| Clover Biopharma | China | S-Trimer | Still in Lab |
| Novavax/CEPI | USA/Sweden | major surface S-protein binder | Preclinical |
Source: https://www.clinicaltrialsarena.com/analysis/coronavirus-mers-cov-drugs/, https://www.statnews.com/2020/03/19/an-updated-guide-to-the-coronavirus-drugs-and-vaccines-in-development/, http://dootiroy/blogpost/
- Cure:This is the most important section to which most of the populace is looking up to find answers. The search is still on.
WHO says 80% of people who get COVID-19 show mild symptoms or are asymptomatic (source: https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf). About 1 out of 6 people becomes seriously ill and develops breathingdifficulty. In almost all the serious cases, people develop a special type of (source: https://www.theguardian.com/world/2020/mar/21/coronavirus-what-happens-to-lungs-covid-19).
Another article provides a clearer clarifies as to what exactly happens to our body when onecontractsCOVID-19: https://www.forbes.com/sites/brucelee/2020/03/21/how-does-the-covid-19-coronavirus-kill-what-happens-when-you-get-infected/#1c2b7e5d6146
Below is a list of compounds or potential drugs being tested for benefits. Most of the compounds are repurposed drugs already approved by FDA to treat other viral infections or they effect similar pathways as the SAR2-CoV2 virus.
There is currently one compound (Avigan) which has shown efficacy in a clinical trial mostly for mild to moderate patients. This treatment is currently only approved in China for use.
This list is not exhaustive and only contains the most common compounds which are in human trial conduct. There are 38 trials currently in Phase 2/3 (advanced clinical testing).
| Company | Country | Compound | Stage of development | Evidence |
| Fujifilm Toyama Chemical | Japan | Favipiravir(Avigan) | Approved in China | A trial of 340 patients in Wuhan and Shenzhen. (https://www.theguardian.com/world/2020/mar/18/japanese-flu-drug-clearly-effective-in-treating-coronavirus-says-china) |
| Generic | USA | Chloroquine | Phase I in China, US, UK, Spain.University of Minnesota (1500 patients) | Repurposed, used to treat malaria and arthritis. |
| Gilead Sciences Inc. | USA | Remdesivir | Phase 3 | https://clinicaltrials.gov/ct2/show/record/NCT04292730?cond=Coronavirus&draw=3&rank=87A number of trials are looking at efficacy of this compound. |
| Regeneron | USA | Sarilumab | Phase 2/3 | https://clinicaltrials.gov/ct2/show/NCT04315298?cond=Coronavirus&draw=3&rank=115 |
| University of Minnesota (Generic) | USA | Losartan | Phase 2 | https://clinicaltrials.gov/ct2/show/NCT04312009?term=Losartan&type=Intr&cond=Coronavirus&draw=2&rank=1 |
| Wuhan Jinyintan Hospital,Jiangxi Qingfeng Pharmaceutical Co. Ltd. | China | Lopinavir/ritonavir | Phase 2/3 | This combination is a drug called Kaletra/Aluvia by AbbVie. A number of trials are evaluating this treatment. However, a study (199 patients) published in New England Journal of Medicine found no clinical benefit for hospitalized Chinese patients. (https://www.nejm.org/doi/full/10.1056/NEJMoa2001282).Rest of the trials can be found here:(https://clinicaltrials.gov/ct2/results?cond=Coronavirus&term=Lopinavir%2F+ritonavir&cntry=&state=&city=&dist=&Search=Search&type=Intr) |
| Sanofi, Shanghai Public Health Clinical Center, University of Minnesota | USA, China | Hydroxychloroquine(and combination of Azithromycin) | Phase 2, 3 | The compound is being tested as a treatment for pneumonia/pulmonary infections which is one of most common complications for severely ill patients. A small, open label, study in France with 42 patients (36 to be honest, rest were lost to follow up), found that 13/20 patients with Hydroxychloroquine no longer had the virus after 5 days’ post treatment. Out of the 13 responders, 6 subjects also were treated with Azithromycin. The response rate was significantly better for the combination therapy. (https://www.sciencedirect.com/science/article/pii/S0924857920300996?via%3Dihub)https://clinicaltrials.gov/ct2/results?cond=Coronavirus&term=Hydroxychloroquine&cntry=&state=&city=&dist=&Search=Search&type=Intr |
| Massachusetts General Hospital | Nitric Oxide Gas | Phase 2 | FDA opened up testing of this compound recently and already there are 5 trials planned. https://www.fiercebiotech.com/medtech/fda-expands-access-to-bellerophon-s-nitric-oxide-gas-for-covid-19-lung-symptoms https://clinicaltrials.gov/ct2/results?cond=Coronavirus&term=Nitric+Oxide+Gas&cntry=&state=&city=&dist=&Search=Search&type=Intr |
Note: In the tables above, preclinical means the product is being tested in animals. Phase I: Healthy volunteers, Phase II/III: Diseased patients.
Source: https://www.clinicaltrialsarena.com/analysis/coronavirus-mers-cov-drugs/, https://www.statnews.com/2020/03/19/an-updated-guide-to-the-coronavirus-drugs-and-vaccines-in-development/
There are currently total 116 ongoing/about to begin/completed clinical trials for a detection/cure/vaccine of COVID-19, out of them 81 are interventional.
The exhaustive list can be foundhere: https://clinicaltrials.gov/ct2/results?cond=Coronavirus&term=&cntry=&state=&city=&dist=
To Summarize:
This list is reflective of the scale of humanity’s fight against this pandemic contagion and the concerted efforts undertaken globally to find a fast and remedial solution. This fight is a proof that- will get out of this nightmare stronger and armed better for future.
Till a cure/vaccine is found, our best bet is to practice extreme safety measures: social distancing, minimize exposure and washing& sanitizing hands regularly.
(source: https://www.cdc.gov/coronavirus/2019-ncov/prepare/prevention.html).
ARITA ACHARJEE
