Innovative and Improved Approach to Prevent & Treat COVID-19

AutoCAD design with sensor

Inspiration

Our goal and inspiration was to improve our idea as more of a at home solution and having a more confident drug delivery when approaching COVID-19 patients.

What it does

The approach is a treatment plan for mild COVID-19 cases and serve as a therapeutic approach. We used a nebulizer with sensors so the patient can be confident the drug will get to the lungs so it can heal faster and decrease the inflammation.

How I built it

Improved Aerosolized Drug Delivery Treatment and Therapy Plan Grace Miguel, Olivia Poplawski, Tara Ravoli, Kelly DiResto, Ava Tartaglia

Proposed Improvements

The team has moved away from liposomal delivery of a corticosteroid because the steroid puts strain on the body and causes fever-like symptoms. Rather than using a steroid, the team has implemented the use of an anti-inflammatory drug called colchicine. Furthermore, the preferred method of the antiviral drug that battles COVID-19 is in the pill form because it will be dispersed in the bloodstream faster than it would in an aerosolized form. Our improvements should be used for mild COVID-19 cases and serve as a therapeutic approach. Fluid Mechanics - Does Liposome work? Liposome will get to the lung and alevoli Liposome can localize the action of inhaled drugs in the lung, improving the therapeutic outcome. Use mesh nebulizer for most efficiency[least loss of drug]- large mesh apertures are less disruptive to liposomes than jet nebulizers, especially when the vesicle size is small before entering nebulization. Inhaled drug particles should be ‘fine particle fraction’(FPF) “particles should be smaller than 5 or 6 µm, with particles smaller than 2 µm being the most suitable for deposition in the alveolar region”(Rudokas). After COVID the lungs of patients are being damaged.and it would be hard to fully get the correct amount of drug to the patient

Researched Drugs Hydroxychloroquine - Ava & Kelly Immunosuppressive drug and anti-parasite Traditionally treats/prevents malaria, as well as arthritis and lupus- its a positive that it has already been used in humans Trump claims to be taking daily doses of it “Hydroxychloroquine is being used to try and stop coronavirus from spreading inside your body. It is not yet known if hydroxychloroquine is a safe and effective treatment for COVID-19, and this use is still experimental.” Researchers have been interested in chloroquines as an anti-viral agent for some time A study in Virology Journal in 2005 found that chloroquine inhibited the closely related Sars virus in primate cells in lab conditions chloroquine could quell the spread of SARS-CoV when applied to infected human cells in culture Chloroquine disrupts the ability of the SARS-CoV virus to enter and replicate in human cells, Live Science previously reported The cell culture studies of SARS-CoV-2 revealed that the drug and its derivative hydroxychloroquine undermine the novel virus' replication in a similar way Many varying answers of result stories International Society of Antimicrobial Chemotherapy found that “hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients,” and the effect was “reinforced by azithromycin,” the antibiotic better known as a Z-pack Conducted at U.S. Veterans Health Administration medical centers found that COVID-19 patients who took hydroxychloroquine were more likely to die than those who did not A study looked at the combination of hydroxychloroquine, the antibiotic azithromycin and zinc supplements. Showed that patients who received the three-drug combination vs the two-drug combination of hydroxychloroquine and azithromycin were 44% less likely to die than the second group The FDA has authorized emergency use in adults and adolescents hospitalized with COVID-19, despite not knowing its effectiveness If we were to use this, recommended dose seems to be ~400 mg/d “Hydroxychloroquine effectiveness profile, its ability to inhibit lung viral replication for a 10-day period after only a 5- day cycle of therapy, and the large amounts of knowledge in term of safety deriving from its use for malaria prophylaxis and rheumatologic diseases permit to recommend its pre-exposure or post-exposure use for those performing procedures at high risk of viral diffusion in patients with COVID-19 pneumonia” \

Antiviral EIDD-2801 - Grace, Tara EIDD = Emory Institute for Drug Development EIDD-2801 is an oral ribonucleoside analog that inhibits the replication of multiple RNA viruses, including respiratory syncytial virus, influenza, chikungunya, Ebola, Venezuelan equine encephalitis virus, and Eastern equine encephalitis viruses. It is important that antivirals are active against a broad range of viruses so we can build a supply for a future pandemic.(Dennis C. Liotta, director of EIDD). “Our studies in the Journal of Virology show potent activity of the EIDD-2801 parent compound against multiple coronaviruses including SARS and MERS,” says Mark Denison, MD, the Stahlman Professor of Pediatrics and director of pediatric infectious diseases at Vanderbilt University School of Medicine. “It also has a strong genetic barrier to development of viral resistance, and its oral bioavailability makes it a candidate for use during an outbreak.” Must be used in early stages of contraction, would not be useful in later stages of the disease (Juliet Morrison, a virologist at UC Riverside). “Once you demonstrate its safety and efficacy, you’d like to build up a big supply of it so that when the next pandemic comes along, you have something you can potentially try with people, and if it works, you can stop that viral pandemic in its tracks.”- Dennis C. Liotta Director of EIDD EIDD-2801 works similarly to Gilead Sciences’ remdesivir, an unapproved drug that was developed for the Ebola virus and is being studied in five Phase III trials against COVID-19. Both molecules are nucleoside analogs that metabolize into an active form that blocks RNA polymerase, an essential component of viral replication. Other effects: improve pulmonary function, decrease body weight loss, and reduce amount of virus in the lungs. Positive compared to remdesivir: But remdesivir can only be given intravenously, meaning it would be difficult to deploy widely. In contrast, EIDD-2801 can be taken in pill form, says Mark Denison, a coronavirus expert and director of the infectious diseases division at Vanderbilt Medical School. Positive compared to remdesivir: He also notes that while remdesivir and EIDD-2801 both block RNA polymerase, they appear to do it in different ways, meaning they could be complementary. Negative compared to remdesivir: Unlike remdesivir, EIDD-2801 lacks human safety data. Ridgeback founder and CEO Wendy Holman says she expects the US Food and Drug Administration to give the green light for a Phase I study in COVID-19 infections within “weeks, not months.” Human trials began on April 10 in the UK- clinical trials are still underway.

Japan Drug-Olivia The antiviral drug, called favipiravir or Avigan, has been used in Japan to treat influenza, and last month, the drug was approved as an experimental treatment for COVID-19 infections, Pharmaceutical Technology reported. "There are currently no data showing that Avigan has high efficacy," said Daisuke Tamura, an associate professor at Jichi Medical University specializing in pediatric infectious disease. Chinese researchers say it was “clearly effective” It has been sent out to 42 countries Japanese Prime Minister Shinzo Abe said Monday he wants favipiravir approved for Covid-19 in May, as Japan moves to fast-track approval for remdesivir as well. In sample size of 80 it shortened the length of illness from 11 days to 4 days Also slight improvements later on in CT scan of chest https://www.sciencedirect.com/science/article/pii/S2095809920300631#f0005 Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial It was found not to be as effective as favipiravir. But study also says The Chinese government also has a reputation of manipulating research data to suit their needs.

Researched Sensors All different types of Sensors: volume, weight, flow https://www.sstsensing.com/7-main-types-of-level-sensors/ Optical level switches Better for small amounts of liquid Flow Sensors- Used to measure the flow of the drug. Calculations need to be done to show when the liquid is done and how long it flows Want to use the autoclavable(reusable) Technical documentation of sensorion mass flow meter SFM 3300 Flow Sensor should be placed on the intake channel valve. See this diagram. Good info above on sensor use in nebulizers^

Anti-Inflammatory Colchicine is a non-steroid anti-inflammatory that comes in liquid form. It is a specialized pro-resolving mediator(SPM) that represents a portion of the omega-3 fatty acid spectrum that has a powerful effect on reducing inflammation. Use in aerosolized form in nebulizer

Works Cited

“Treatments for COVID-19: Drugs Being Tested against the Coronavirus.” LiveScience, Purch, 9 Apr. 2020, www.livescience.com/coronavirus-covid-19-treatments.html.

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DeVilbiss Pulmo Aide Compressor Nebulizer Owners Patient Guide, www.americanallergy.com/pulmoaide-nebulizer/devilbiss-pulmoaide-patient-guide.htm.

“Global Coronavirus COVID-19 Clinical Trial Tracker.” covid19, www.covid19-trials.com/.

Ksiazek, et al. “Chloroquine Is a Potent Inhibitor of SARS Coronavirus Infection and Spread.” Virology Journal, BioMed Central, 1 Jan. 1970, virologyj.biomedcentral.com/articles/10.1186/1743-422X-2-69.

Lanese, Nicoletta. “Could the Anti-Malarial Drug Chloroquine Treat COVID-19?” LiveScience, Purch, 20 Mar. 2020, www.livescience.com/chloroquine-coronavirus-treatment.html.

NHS Choices, NHS, www.nhs.uk/medicines/azithromycin/.

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Halford, Bethany. “An emerging antiviral takes aim at COVID-19.” 2020, https://cen.acs.org/pharmaceuticals/drug-development/emerging-antiviral-takes-aim-COVID-19/98/web/2020/05

.“EIDD 2801.” New Drug Approvals, 28 Mar. 2020, newdrugapprovals.org/2020/03/28/eidd-2801/.

“FDA: Human Trials Can Begin for Emory COVID-19 Antiviral.” Emory University | Atlanta, GA, 7 Apr. 2020, news.emory.edu/stories/2020/04/covid_eidd2801_fda/index.html.

“EIDD-2801: Coronaviruses Inhibitor: MedChemExpress.” MedchemExpress.com, www.medchemexpress.com/eidd-2801.html. Cai, Qingxian, et al. “Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study.” Engineering, Elsevier, 18 Mar. 2020, www.sciencedirect.com/science/article/pii/S2095809920300631#f0005.

“7 Main Types of Level Sensing Methods – How Do They Differ?” SST Sensing, 4 Mar. 2020, www.sstsensing.com/7-main-types-of-level-sensors/.

“SFM3300 - Mass Flow Meter.” Sensirion AG Switzerland, www.sensirion.com/en/flow-sensors/mass-flow-meters-for-high-precise-measurement-of-gases/proximal-flow-sensors-sfm3300-autoclavable-washable-or-single-use/.

Sensirion. “Single-Use Proximal Flow Sensors.” Medical Design and Outsourcing, 15 May 2017, www.medicaldesignandoutsourcing.com/single-use-proximal-flow-sensors/.

“US8333190B2 - Nebulizer Having Flow Meter Function.” Google Patents, Google, patents.google.com/patent/US8333190B2/en.

Rudokas, Mindaugas, et al. “Liposome Delivery Systems for Inhalation: A Critical Review Highlighting Formulation Issues and Anticancer Applications.” Medical Principles and Practice : International Journal of the Kuwait University, Health Science Centre, S. Karger AG, 2016, www.ncbi.nlm.nih.gov/pmc/articles/PMC5588529/.

Cox, David. “Some Patients Who Survive COVID-19 May Suffer Lasting Lung Damage.” Science News, 6 May 2020, www.sciencenews.org/article/coronavirus-covid-19-some-patients-may-suffer-lasting-lung-damage. Puckey, Melisa. “Can Colchicine Be Used to Treat COVID-19 (Coronavirus)?” Drugs.com, www.drugs.com/medical-answers/colchicine-treat-covid-19-coronavirus-3535211/. Kunzmann, Kevin. “FDA Approves Liquid Colchicine Formulation for Gout.” HCPLive®, 26 Feb. 2019, www.mdmag.com/medical-news/fda-approves-liquid-colchicine-formulation-for-gout. Silverman, Robert G. “Specialized pro-Resolving Mediators: A New Tool for Resolving Inflammation.” Official Media Integrative Practitioner, www.integrativepractitioner.com/about/integrative-healthcare-symposium/specialized-pro-resolving-mediators-new-tool-resolving-inflammation. Ruzer, Lev S, and Naomi H Harley. “Aerosols Handbook.” Google Books, Google, books.google.com/books?id=Sn0hT9jlj9AC&pg=PA249&lpg=PA249&dq=anti-inflammatories%2Bin%2Baerosol%2Bform&source=bl&ots=9Bu0GNMd-h&sig=ACfU3U3nM7_rVQpv5T06PfipLHi5O5WtlQ&hl=en&sa=X&ved=2ahUKEwjrpZSK7MPpAhVZgXIEHQtCDakQ6AEwBnoECAoQAQ#v=onepage&q=anti-inflammatories%20in%20aerosol%20form&f=false.