Thursday, March 26, 2020

COVID-19: Hopeful News, Treatments are Under Development

COVID-19: Hopeful News, Treatments are Under Development

All over the world researchers are looking for treatments for COVID-19, and some drugs are showing promising results. These results, however, are preliminary and proper clinical trials (normally conducted in 4 phases), with randomization and controls need to be carried out. The World Health Organization (WHO) has started a large global clinical trial (named SOLIDARITY) testing the four leading drugs (all previously passing clinical trials and approved for the treatment of other illnesses). To participate in the SOLIDARITY clinical trials, COVID-19 patients need to fulfill the inclusion criteria, assessed by the physician ( such as being COVID-19 positive and presenting respiratory symptoms), and sign the informed consent form.

1- Remdesivir. This compound inhibits the activity of the viral RNA polymeranse, a protein that the virus needs in order to replicate. The pharma company Gilead Sciences, initially developed the drug to inhibit the Ebola virus, but it failed to show any significant improvement in Ebola patients. In 2017, early drug development studies showed that remdesivir inhibited the RNA-polymerase of MERS and SARS viruses (2 coronaviruses) both in-vitro (tested on proteins and/or cells grown in the lab ) and in animal studies. Recently it was tested in two American patients with severe COVID-19 symptoms, and both patients recovered rapidly.

2- Chloroquine and hydroxychloroquine
These compounds work by decreasing the acidity in separated compartments inside cells that are used by some viruses as a point of entry into the cells. Clinical trials using these drugs on other viruses, however, have shown negative results. Interestingly though, these compounds efficiently inhibited SARS-CoV-2 infection in vitro. One letter published by Chinese researchers claimed that patients treated with these compounds showed improvement in their recovery outcome. Unfortunately, the study results have not yet been published. In another study, hydroxychloroquine, a more tolerable form of chloroquine, didn't perform better than placebo at clearing the coronavirus among Chinese patients with mild cases, or at helping them reach lower temperature sooner. Other researchers from China and France tested these drugs in COVID-19 patients and reported a significantly reduced viral load in nasal swabs. The USA Society of Critical Care Medicine, however, has declared that “there is insufficient evidence to issue a recommendation on the use of chloroquine or hydroxychloroquine in critically ill adults with COVID-19.”
Researchers are also raising flags about the dose and general use of Hydroxychloroquine as it has shown to cause adverse effects.

3- Ritonavir and lopinavir. Initially, this combo drug treatment was developed by Abbott Laboratories to treat HIV infections. These compounds inhibit a viral protein that is vital for the correct processing of other viral proteins. The first study using these drugs in “very ill” COVID-19 patients in China did not show positive results.

4- Ritonavir/lopinavir and interferon-beta combined. In this study, each antiviral (Ritonavir or lopinavir) is used in combination with interferon. Interferon is an antiviral used to treat patients suffering flu and other viral infections. Interferon is a regulatory protein that modulates inflammation in humans. It is well established that some interferons activate an antiviral gene program in epithelial cells with minimal perturbation to the specific immune response. Furthermore, it has been tested for the prevention of Winter colds and flu alone and in combination with other anti-virals. Interferon has also been used to treat poultry against flu.

Other potential therapies include:
Regeneron and Sanofi-marketed antibody, Kevzara, a drug used to treat arthritis, is now being tested in patients with severe COVID-19 infection. Fujifilm-marketed Avigan (favipiravir), a drug used to treat flu-infected patients, is being studied for the treatment of COVID-19. Studies in China and Japan have shown moderately positive results, depending on the severity of the patients’ condition. Patients who were given the medicine in Shenzhen turned negative for the virus after approximately four days following having become positive, compared with a median of 11 days for those who were not treated with the drug. They also showed improvements in lung condition in about 91% of the patients who were treated with favipiravir, compared to 62% on those without the drug.

Researchers, for example at Mount Sinai Hospital in New York and at the Pasteur Institute in Paris, are testing in vitro (on human cells grown in the lab that are infected with COVID-19) hundreds of compounds and drug combinations trying to identify potential therapies.
Another promising therapy, coming from Mount Sinai Hospital in NYC, is the use (or re-use) or antibodies from patients who recovered from COVID-19. The body-rich plasma from COVID-19 patients to help critically ill patients was already used successfully in China, as they reported that some patients improved within 24 hours, with reduced inflammation and viral loads, and better oxygen levels in the blood.

Some interesting ideas are also to be tested, for example Dr. Dan Batlle has a paper in Clin Sci. discussing the potential therapeutic utility of overwhelming the body with more soluble ACE2 protein (the receptor in the membrane of human cells that interacts with COVID-19 surface proteins) in an attempt to diminish viral infection into membrane-bound ACE2. COVID-19 surface proteins need to interact (bind) to the ACE2 proteins (located in the surface of human cells) in order to enter the cells. This hypothesis is based on the idea that the free ACE2 protein (not in the surface of human cells) will bind and therefore block the membrane/surface proteins on the COVID-19 that are necessary for the viral infection. In this case the viral proteins won’t be able to bind to the ACE2 protein on the surface of human cells, and therefore they won’t infect the cells.

Importantly: you should NOT take any of these treatments without a prescription from your doctor, as they can cause adverse effects and even death.
For now, the best way to take care of your health and avoid contracting COVID-19 is to wash your hands thoroughly and regularly, keep your hands away from your face, stay in self-isolation or and maintain social distancing, have good hygiene (aka wash your hands).

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