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Researchers Work on New Ways to Prevent and Treat COVID-19

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We now have several very effective COVID-19 vaccines, but that doesn’t mean the research into preventing and treating the disease caused by the SARS-CoV-2 virus has slowed down. Researchers continue to find new and innovative ways to treat COVID-19 and its symptoms, from the use of an over-the-counter dietary supplement to a wide range of new vaccine candidates.

Research to Prevent, Treat COVID-19Melatonin and COVID-19

Melatonin is a natural hormone best known for its use in promoting healthy sleep and regulating the body’s internal clock. Now, researchers are looking at whether melatonin has an effect on COVID-19—both the virus itself and the vaccines created to prevent it.

According to a study by the Cleveland Clinic, using melatonin reduces the chance of catching COVID-19 by 28%. For Black participants, melatonin use cut the risk by 52%. While the finding indicates that melatonin usage could help prevent and treat COVID-19, the study authors called for more randomized controlled clinical trials to test the theory.

Whether or not it offers protection against the disease, researchers say melatonin can help in another important way—by making COVID-19 vaccines more effective. Not only does quality sleep boost the immune system, which helps the vaccine achieve maximum effectiveness, melatonin also enhances the immune response to vaccines by increasing key immune cells, and can even ease vaccination side effects.

A New Use for an OCD Drug

Fluvoxamine is a serotonin reuptake inhibitor (SSRI) drug used to treat obsessive-compulsive disorder (OCD), and now researchers are looking into whether it can be used to treat COVID-19 as well.

Researchers made the connection because fluvoxamine is a cytokine inhibitor and had already been used to treat sepsis in mice by lowering inflammatory cytokine production. Cytokine storm, or cytokine release syndrome, is a life-threatening systemic inflammatory syndrome triggered by an infection, and is one of the hallmarks of severe cases of COVID-19.

The cytokines that flood the body during cytokine storm can kill tissue and lead to organ failure, so a cytokine inhibitor, while it would not prevent COVID-19 infection, could lessen the severity of inflammation-related symptoms.

Researchers conducted a clinical trial with COVID-19 patients to test the effectiveness of fluvoxamine in preventing cytokine overproduction and found that none of the participants who received fluvoxamine had to be hospitalized, while 8.7% of the placebo group had to be hospitalized within 14 days due to worsening symptoms. A subsequent trial had similar results: 12.5% of those who did not receive fluvoxamine experienced worsening symptoms, while none of those who received fluvoxamine saw an increase in symptom severity. There are now several clinical trials under way to assess fluvoxamine's effect on COVID-19.

Improving Lung Function in Mice with the Flu

A new treatment that reduces the severity of acute respiratory distress syndrome caused by the flu in mice could help humans with COVID-19 avoid going on a respirator, and may also be an effective treatment for lung damage caused by SARS-CoV-2 and other viruses and conditions that affect the lungs.

The research, conducted in mice at The Ohio State University, found that flu-affected lungs show a shortage of surfactant, a substance that allows lungs to expand and contract, which is linked to acute respiratory distress syndrome. When researchers introduced liponucleotide molecules to the mice, which are essential for making surfactant, the mice experienced normalized blood oxygen levels and reduced inflammation in the lungs.

While the treatment does not protect against or kill the coronavirus, it could offer protection against lung damage in people who have been infected, and help those experiencing severe COVID-19 symptoms to recover faster and avoid the ICU.

An At-Home Pill to Treat Coronavirus

Pfizer was the first company to market with an approved COVID-19 vaccine, and now it may also be the first to deliver an effective treatment in pill form.

In March, Pfizer announced it had begun phase 1 trials of a new pill that could be prescribed and taken at home as a preventive measure or at the first signs of illness from COVID-19. While the pill does not protect against the virus in the same way as a vaccine, it blocks the SARS-CoV2 virus from replicating, therefore preventing patients from becoming severely ill.

The pill, currently called PF-07321332, should enter phase 2/3 trials early in the second quarter and could be generally available by the end of the year.

The Next Generation of COVID Vaccines

COVID-19 vaccines from Pfizer, Moderna, Johnson & Johnson and AstraZeneca are already in use worldwide, but several companies are still working to develop new COVID-19 vaccines.

Novavax: Maryland-based biotechnology company Novavax has been part of the effort to develop a COVID-19 vaccine since the early days, and received $1.6 billion in funding from the U.S. government’s Operation Warp Speed. Its vaccine candidate, called NVX‑CoV2373, a recombinant nanoparticle vaccine that also includes Novavax’s patented adjuvant, showed 89%-90% effectiveness in clinical trials in the U.K. and South Africa, including against variant strains emerging in those countries. Novavax plans to apply for U.S. authorization for the vaccine. If approved, it could deliver up to 100 million doses to the U.S. by the end of the year.

Scripps: Scientists at Scripps Research in San Diego are working on an experimental COVID-19 vaccine that delivers the “spike” from the virus on tiny spherical proteins that mimic the shape of the real virus to trick the body’s immune system into increasing its protective measures. In tests with mice, the new vaccine appeared to provide a good level of protection against three known COVID-19 variants: B.1.1.7, B.1.351 and P.1. The team hopes to enter clinical trials soon.

University of Virginia/Virginia Tech: Scientists at UVA and Virginia Tech are working on an experimental COVID-19 vaccine using a new platform designed to enable researchers to rapidly produce vaccines at very low cost (about $1 per dose). The vaccine, which uses synthesized DNA inserted into a plasmid to train the immune system how to mount a protective immune response against the virus, would be easy to store and transport and could be mass-produced in existing vaccine-manufacturing facilities worldwide. The vaccine, which has shown promising results in animal testing, could not only provide protection against existing strains of COVID-19, it could also work against new variants of COVID-19 and other coronaviruses, potentially even the common cold.

Intravacc: Based in the Netherlands, Intravacc has announced positive preclinical results for its nose spray SARS-CoV-2 vaccine, called Outer Membrane Vesicle (OMV) based recombinant Spike protein (rSp). Testing with mice and hamsters showed that the nose spray vaccine candidate generated virus neutralizing antibodies in 30%-90% of the mice and 100% of the hamsters. The company plans to move forward with human trials.

Inovio Pharmaceuticals: Inovio’s COVID-19 vaccine candidate, called INO-4800, is a synthetic DNA-based vaccine using technology the company had previously used to develop an experimental vaccine for Middle East respiratory syndrome (MERS), another disease caused by a coronavirus. In preclinical tests, INO-4800 prompted mice and guinea pigs to develop COVID-19 antibodies. One unusual benefit of the Inovio vaccine candidate is that is does not need to be kept an extremely low temperatures for transport and storage—it is stable at room temperature for more than a year and has a five-year projected shelf life when refrigerated. The vaccine candidate is currently in phase 2/3 testing.

Additional vaccine candidates are in development by Zydus Cadila in India, Cuba’s Center for Genetic Engineering and Biotechnology, German company CureVac in cooperation with GlaxoSmithKline and Bayer, Canada-based Medicago, and Melbourne, Australia-based Murdoch Children’s Research Institute, which is testing a live-attenuated tuberculosis vaccine to see if it also protects against COVID-19.

The world has been dealing with COVID-19 for more than a year and the virus shows no signs of disappearing. Fortunately, the research community is working hard to find new treatment and prevention methods that could help turn the pandemic around.

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