Dr. Robert Pastore, PhD, CNS

Coronavirus
COVID-19

An Overview of Treatment Research for COVID-19

2020-05-087 min read

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Please let me be clear that COVID-19 treatment is a fast-moving target and what I am about to write will definitely change in the near future. As for now (May 8th, 2020) there is no FDA or CDC recommended approved treatment for COVID-19. Patients are receiving lifesaving therapy and many doctors are using all they have at their disposal to save lives. I applaud them daily.

Having said that, please note there are multiple research endeavors transpiring at the same time right now. At the time of this writing there are many trials completed, planned, recruiting, or underway. I have a spreadsheet of 1,159 as of this writing. Here is just some of the current research.

1. Repurposing Small Molecule Drugs

There is the aggressive analysis for repurposing small molecule drugs to treat COVID-19. That means scientists are using drugs that have already been approved for other conditions and are currently being studied for a new use, to combat COVID-19 in different ways:

  • Remdesivir is believed to inhibit the action of RNA polymerase and has been in a COVID-19 trial, with more planned. The delivery is intravenous.

    What we understand at this point in time is that the RNA-Dependent RNA Polymerase (RdRp also called nsp12) is the central replication and transcription component of the novel coronavirus responsible for COVID-19, which is why drugs that are inhibitors or binders of RdRp are are part of clinical trials. Both inhibition and binding of RdRp may truncate transcription and replication of the novel coronavirus. Early studies may indicate Remdesivir potentially having both characteristics.

    Based on short term favorable outcomes in shortening the duration of COVID-19 in study participants, the drug has been issued an Emergency Use Authorization (EUA) in the U.S. However, this is far from the full story. We still do not have enough information about the safety and efficacy of using remdeisvir to treat people with COVID-19. Please note receiving EUA is not the same as receiving FDA approval. The FDA needed to evaluate the current state of limited evidence and way the risk versus benefits and made the EUA decision.
  • EDP1815 is a monoclonal microbial drug that acts as an anti-inflammatory agent. The drug is taken orally. Rutgers University is leading the Phase 1b clinical trial right now on COVID-19 patients. In preclinical models, the novel monoclonal microbial drug EDP1815 has been found to exert a positive influence on cytokines that have been implicated in the cytokine storm of certain COVID-19 patients. Addressing such hyperinflammation while attacking the replication pathways of this novel coronavirus may expedite recovery.
  • Galidesivir is a viral RNA-polymerase binder. It is in trial right now. The delivery is oral and intravenous.
  • Camostat is a transmembrane protease serine 2 inhibitor. It is in trial right now. It is an oral medication. Viral host cell entry requires serine proteases that activate what are called viral spike glycoproteins. Transmembrane protease serine 2 known as TMPRSS2 is a potential target in COVID-19 treatment. Drugs that act as transmembrane protease serine 2 inhibitors, like Camostat (but there is also Trasylol and Flumadine) have potential to stop the novel coronavirus from cell entry and subsequent spread.
  • Favipiravir is a selective viral RNA-polymerase inhibitor. It is in trial and the route is oral.
  • Darunavir and Cobicistat are two HIV drugs that have been studied in a clinical environment. These are oral medications. At this time there is lack of evidence to support their use for COVID-19.
  • Fingolimod, which is a sphingosine 1-phosphate receptor modulator, is an oral medication in phase 2 clinical trial right now, with an estimated primary completion date of July 1, 2020. It is in a class of drugs used as immunomodulators. These medications are used in conditions such as multiple sclerosis. This drug is being used in an attempt to truncate the immune response to acute respiratory distress syndrome caused by the cytokine storm associated with COVID-19.
  • Plaquenil, better known as hydroxychloroquine, was part of a clinical trial because it is possible that it may inhibit the terminal glycosylation of ACE2 of this virus. A study just published in the New England Journal of Medicine did not conclude any benefit of using this drug for COVID-19 patients. In fact, over 800 patients that took the medication were more ill than those that did not. However, this is the first observational study in the US and the recommendation is further study. Currently, the FDA is cautioning against the use of this medication for COVID-19 outside of a hospital environment due to the high risk of heart rhythm abnormalities (such as Long QT or QT prolongation).

There are at least 7 more drugs and remember these are the repurposed medications. That doesn’t include the new drugs that are currently in development. The repurposed medications would receive a fast approval due to the fact that they have a track record and a dataset of safety vs. risks for other conditions.

2. Other Therapies

Additionally, there is research ongoing to address some of the symptom complexes of COVID-19 that would allow other medications to work more rapidly or with higher efficacy. Interestingly, NYU is conducting a trial on hyperbaric oxygen therapy (HBOT) on COVID-19 patients and is currently recruiting patients as of April 2nd, 2020.

There is interesting data on addressing the cytokine storm by blocking specific receptors. One such receptor is the cell surface receptor GPR55. This receptor can signal an immune response that results in a cytokine expression. I’m working with researchers on these efforts.

The CDC recently provided recommendations for investigational COVID-19 convalescent plasma. It is important to note that convalescent plasma has not yet been approved for use by FDA as a treatment, but it is encouraged as part of the research to find a treatment. The reasoning for studying convalescent plasma is sound scientifically because it has successfully been used in SARS, MERS and the 2009 N1H1. It is considered classic adaptive immunotherapy. The plasma is donated from patients who have completely recovered from COVID-19 with a high titer of neutralizing antibodies and delivered intravenously into those battling the infection. In a very small study of 10 patients, seven recovered after receiving the donor plasma. Larger studies are needed and are underway.

3. Vaccines

The following paragraph may be antiquated by the time of publication but at the time of this writing there are at least 23 pharmaceutical companies and universities involved in the race for a vaccine for the novel coronavirus. For example, there is a vaccine trial underway at the University of Oxford with the first two subjects receiving the test vaccine as an injection in late April. The goal is to reach over 1000 participants with half receiving the potential vaccine and the other half a placebo. It will take months for the data to come to fruition.

While waiting for an approved treatment and or vaccine, the current method of care in an emergency room / hospital environment is supportive care and managing any comorbidities/illnesses, along with the discretionary use of the aforementioned EUA status drug Remdesivir and other treatments as warranted.

For more information on the coronavirus and COVID-19, you can listen to my podcast here and read my previous article on COVID-19 & Cytokine Storms here.