The World Health Organization has initiated a trial to test four treatments that may be effective against the global pandemic of COVID-19.
The COVID-19 pandemic has swept around the globe, shutting down cities and bringing countries to a standstill as governments scramble to control its spread. Though many researchers are racing to develop a vaccine against SARS-CoV-2, the virus that causes COVID-19, the earliest one is expected to be available in 12 to 18 months. In the meantime, researchers and clinicians are hard at work to find a treatment for the infected.
Given the urgency of treating the pandemic, scientists are hoping that an existing drug will prove effective against the disease. Repurposing an existing drug would save the time needed to develop a new compound and would avoid the need for potentially lengthy safety testing and approval. The only requirement would be to demonstrate that the drug is an effective treatment for COVID-19 – a significant hurdle in its own right.
Four proposed treatments
The World Health Organization has identified four treatments that show promise, and on March 20, it launched a global trial to evaluate them. This trial, named SOLIDARITY, is designed to be simple to join so that hospitals can participate without taking on much additional burden. The treatments are chloroquine or hydroxychloroquine, the antiviral drug remdesivir, the HIV drug combination lopinavir and ritonavir, and the HIV drugs together with interferon beta. SOLIDARITY is designed to adjust to changing circumstances by adding or dropping treatments as more data becomes available.
Hydroxychloroquine was brought to public attention after a 34-patient trial in France concluded that the drug reduced the viral load in COVID-19 patients, particularly when combined with azithromycin, another drug used in antiviral treatment . The method by which this drug impedes SARS-CoV-2 transmission is not known, and the complete biological effects of chloroquine and related drugs are not fully understood .
The second treatment, remdesivir, was originally developed to combat the Ebola virus by interfering with RNA polymerase. It proved ineffective against Ebola last year, but trials in 2017 showed that it could inhibit the coronaviruses behind SARS and MERS , offering hope that it may prove effective against SARS-CoV-2.
Ritonavir and lopinavir are a combination treatment that targets proteases, enzymes that process proteins during viral assembly. Lopinavir attacks the protease, while riponavir protects lopinavir from the proteases in our cells, extending its lifespan. The combination was effective against the MERS virus in a test in marmosets , but trials in SARS and MERS patients have been inconclusive. Interferon beta regulates inflammation, and this marmoset test also showed it to be effective against MERS, leading researchers to hope that the three drugs might prove more effective together.
Researchers are scrambling to fill gaps in our knowledge about SARS-CoV-2 itself, so we can understand how it causes illness and why the disease progresses as it does. This information could be vital in designing therapies and interventions. For example, knowing the structure of the SARS-CoV-2 spike protein, which the virus uses to attach to receptors on our cells, enabled scientists at New York’s Icahn School of Medicine at Mount Sinai to develop an antibody test that could be used to identify people who have had COVID-19 and recovered. The existing test, which relies on a technique known as PCR to detect viral RNA, can only detect active infections.
(The Icahn School of Medicine is also where we wish to hold Ending Age-Related Diseases 2020 in August, if it is safe to do so at that time.)
Why just the elderly?
One outstanding question is why the COVID-19 fatality rate is much higher among elderly patients. Part of the explanation may be that older people are more likely to have pre-existing conditions which increase their vulnerability. The declining performance of our immune system as we age may also be a factor, but COVID-19 fatality rates suggest that something else is going on.
Virologist Vineet Menachery of the University of Texas Medical Branch explained that respiratory infections usually have a U-shaped mortality curve, with the elderly at risk because of their immune system is weaker and young children at risk because their immune system is underdeveloped. COVID-19 isn’t following this pattern. Older patients are at greater risk, but the disease seems to be sparing young children, who mainly experience mild symptoms, if any, and rarely become critically ill.
SARS-CoV-2 isn’t the first coronavirus to cause this mortality pattern. SARS and MERS, both caused by coronaviruses, also left young children largely unscathed. This pattern has led Menachery and infectious disease specialists to believe that the increased mortality in older patients isn’t simply because their immune system is weaker. Menachery thinks that it may result from dysregulation of the immune system causing it to overreact to the virus, perhaps by causing excessive inflammation.
Understanding how the immune system changes as we age is an important element of longevity research, and the current crisis demonstrates how it could have immediate implications. Many people are afflicted by the biological burdens of aging. Learning more about how those burdens develop will enable us to manage, mitigate, and perhaps even eliminate them.
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