Radiologically Enabled Anti-COVID-19 Targeting System (REACTS)

Student Authors: Justin Napolitano, Andrew Rifkin, Danny Lazega, Rayyan Alam, Victor Cabrera
Mentors: Jaclyn D’Avanzo, Endre Takacs, Delphine Dean

Abstract

The Radiologically Enabled Anti-Covid-19 Targeting System (REACTS) is a treatment method designed to reduce the viral load of Covid-19 within the lungs of patients. At the heart of the system is a radiosensitizer; a particle which increases the effect of radiation in a small region around it. A nebulizer is used to bring the particles to the lungs, then antiviral peptides attach the particles to the viruses. A small, safe dose of x-ray radiation is then used to deactivate the viruses and reduce the viral load within the patient’s lungs, all while keeping healthy tissue alive. This treatment method will allow patients to have a better chance of recovering from Covid-19, while also freeing up hospital resources.

Background

  • The COVID-19 pandemic is responsible for a confirmed 775,000 deaths worldwide with 21.4 million confirmed cases.^1
    • While the mortality rate worldwide is thought to be just under 3.6% at this time, studies have shown that the mortality rate for patients who are placed on a ventilator is approximately 10 times that (35.7%).^2
    • Studies suggest the average recovery time for patients is 25 days.^3
  • Despite exorbitant amounts of capital being dedicated to designing and testing vaccines for COVID-19, there are no approved vaccines as of now for SARS-CoV-2.
    • COVID-19 cases are caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
  • While patients infected with SARS-CoV-2 may be asymptomatic or experience only mild symptoms, a wide array of symptoms are not uncommon, including upper respiratory tract infections and life threatening sepsis.^4
    • Like other respiratory viral diseases, such as influenza, severe lymphopenia (the destruction of T lymphocyte cells) may also occur in patients.^5
    • A large percentage of patients who have died from the virus demonstrated intravascular coagulation, as well as thrombotic complications from inflamed lung tissues and pulmonary endothelial cells.^6
    • The COVID-19 pandemic has caused a sudden and significant increase in the amount of hospitalizations for pneumonia with multiorgan disease.

The Problem

  • After contracting COVID-19, infected patients have been observed presenting alveolar damage, lung fibrosis and other respiratory illnesses.^7
  • Large amounts of fibrotic tissue (lung tissue that is damaged/scarred) were found in the lungs of patients who have died from SARS-CoV-2, suggesting that the extent of lung fibrosis is positively correlated with the duration of SARS.^8
  • Since the beginning of the pandemic, there has been a lack of successful and efficient treatment methods for late stage patients with severe respiratory distress.
  • With overcrowded hospitals, there is potential for ventilator shortages and for hospitals to reach unmanageable case levels.
  • In order to solve the problem, a treatment method is needed that can:
    • Slow the spread of the virus within the host.
    • Decrease the viral load within the lungs of the patient.
    • Reduce the severity of continued damage.
    • Extend the treatment window for late stage patients.

Our Solution

  • The system features a radiosensitizer, which is a nanoparticle comprised of heavy atoms that increase the effect of radiation locally.
  • When radiation interacts with a radiosensitizer particle, the radiation is absorbed by the particle and the interaction produces localized increase in secondary radiation.
  • The radiation used in combination with the REACTS particle is low-dose ionizing x-ray radiation at a dose of under 10 mGy, which is comparable to a dose administered during standard x-ray imaging procedures.
  • The radiation is concentrated into an area localized directly around the particle.^9
  • For prompt and safe delivery, REACTS is administered via a nebulizer to ensure proper placement of the particles.
  • The delivery system that has been chosen is a nanomicelle, fabricated to specifically target SARS-CoV-2.
  • Once inside the lungs, the nanomicelle utilizes an antiviral peptide, causing the radiosensitizer to bind competitively to the spike proteins on the surface of the coronavirus. These antiviral peptides block the formation of the viral fusion core and will target specifically the SARS-CoV-2 viruses.^10.^11
  • The placement of the radiosensitizers near the virus cause the viruses to receive higher absorbed doses of radiation when compared to the absorbed dose received by surrounding biological particles.
  • The viral RNA is then damaged by the radiation, resulting in the deactivation of viruses within the area of effect of the radiosensitizer.
  • In prior studies, we have shown that these types of radiosensitizer particles have low toxicity.^12

Value

  • REACTS will not only increase patient survival rates, it will also increase the amount of available hospital resources, preventing hospitals from getting overwhelmed in the future.
    • By decreasing the viral load, patients will have to spend less time in the ICU, as well as less time on ventilators.
    • This will free up ventilators, save time for staff, and open up beds.
  • Patients, hospitals, and insurance companies will save money from REACTS, since total treatment time and treatment resources required will decrease.
  • Based on the estimated low production cost of REACTS, it will be readily accessible when compared to other common medical treatments.
  • By saving lives and bettering the experience of those who survive Covid-19, REACTS could prove to be one of the first truly successful Covid-19 treatments, paving the way for future innovations.
  • REACTS or derivative treatment methods could be used to treat other coronaviruses, respiratory viruses, or even other illnesses all together.
  • Our treatment method has the potential to create a sense of security in knowing that there is an effective treatment method available, which could lead to a morale boost and the overall betterment of society as a whole.

Future Work

  • Numerous experiments must be completed in order to confirm the design of the REACTS particle, as well as to determine some of the specifics regarding treatment. These experiments include, but are not limited to:
    • A series of experiments to confirm the appropriate type of radiosensitizer particle to use.
    • An experiment to confirm the targeting method used.
    • A series of experiments to confirm the delivery system used. Currently, the nanomicelle delivery system we designed appears to be the best possible option to place the radiosensitizer particles as close to the viruses as possible, while considering toxicity and consistency. To confirm that our system is appropriate, we will complete an experiment testing multiple designs of nanomicelles, along with another experiment testing different types of delivery systems.
    • An experiment to confirm the method of insertion into the body. There is a large amount of literature that suggests nebulizers are the most practical and effective devices to move REACTS particles into the lungs. Still, an experiment must be done which compares a nebulizer to other potential devices.^13
    • An array of experiments must be completed to determine the all around best total radiation dose, dosing rate, a dose of the radiosensitizer. All of these factors must be tested both independent of each other and together, while considering factors such as toxicity and virus deactivation rate.
    • An experiment to determine how long it takes after administration for REACTS particles to completely pass through the body, as well as how long after treatment it takes for standard medical radiation exposure to not have atypical adverse effects. Since radiation independent of the REACTS treatment cycle can have an unplanned impact on the body, it is crucial to know when it is safe to resume normal radiological procedures.
    • A series of experiments to determine if REACTS particles are present within other parts of the body, as well as if they have adverse effects within those parts of the body. It is possible that despite precautions taken during our design phase, REACTS particles could end up in unexpected locations if additional adjustments to the system are not made.
  • In order to properly market REACTS, research needs to be done to confirm every aspect of the value of the treatment method, as well as determine if there are any additional values not listed. Each value must also be quantified and presented in the way most appealing to a multitude of audiences.
  • All options for the future must be considered and research must be completed to determine the viability of every option. Potential avenues for the future could involve patenting REACTS or some form of it and/or the formation of a startup.
  • Additional funding must be secured to continue with the completion of the project. 
  • Given the vast amount of work we have ahead of us, we are actively seeking partnerships with numerous South Carolina based organizations.