Kat Eschner
Some of the most promising COVID-19 treatments have relied on giving the patient’s own immune system a boost using antibodies from other people.
Once someone is exposed to a pathogen, their immune system tries to develop antibodies against it, but the process of developing one’s own antibodies can take some time. Adding antibodies from another source to the bloodstream can buy that time. Doctors have been using plasma, the liquid part of blood, and the part that contains antibody proteins against COVID-19 for this purpose. This so-called convalescent plasma is drawn from people who have already had the disease (hence the name).
Convalescent plasma contains more than just COVID-19 antibodies, which means it’s not the strongest treatment. A small but well done clinical trial performed in Argentina and published in The New England Journal of Medicine in early January found that if the treatment is given within days of start of illness, the treatment does prevent older adults from getting severe COVID-19.
In the meantime, researchers have been working to supercharge the immune system using lab-made COVID-19 antibodies, called monoclonal antibodies, that can shore up a patient’s immune system ahead of its own antibodies. Two companies, Eli Lilly and Regeneron, have been granted an Emergency Use Authorization (EUA) by the Food and Drug Administration for their monoclonal antibodies.
But monoclonal antibodies aren’t a cure. Their use is only recommended for people who are newly infected with SARS-CoV-2 to help keep the disease from taking root. In a Nature Biotechnology commentary from October, a panel of experts note these treatments are hard to develop and are generally used mostly for diseases that we don’t have vaccines for, like HIV. In the case of COVID-19, they note, monoclonal antibodies may prove most useful to help people who don’t respond to a vaccine—for example, older adults with weakened immune systems—since they may still be susceptible after the rest of the population is immunized.
A recent study published in January 2021 in Science gave nursing home residents a single infusion of Eli Lily’s monoclonal antibodies at four times the typical dose and found that the antibodies reduced the risk of becoming ill with COVID-19 over a period of two months by 57 percent. The trial involved 1000 nursing home residents and half the participants received a placebo. Its unclear how this could fit in, given the continued expansion of vaccines in nursing homes as a way to prevent COVID-19.
Antivirals
Antivirals work by targeting virus’ ability to infect other cells. In early December, the World Health Organization released results from a large-scale trial of three antivirals: remdesivir, hydroxychloroquine, and lopinavir. Its results led the international organization to conclude that the drugs had “little or no effect on hospitalized patients with COVID-19.”
Remdesivir, the most widely used drug of this class in treating COVID-19, works by blocking an enzyme that SARS-CoV-2 uses to replicate itself. Remdesivir was initially designed to combat Ebola, and although it didn’t prove effective for that disease, the Ebola studies demonstrated that the drug was at least not harmful to humans.
Back in October of 2020, the FDA officially approved remdesivir to treat COVID-19, making it the first drug to be green-lit to treat the disease (after being given emergency-use authorization in May). Despite this regulatory success, studies have not shown equal achievement. Even the most robust studies showed no evidence that remdesivir prevents deaths from the novel disease.
Further, another tricky thing about antivirals in general is that they often have serious side effects, since the mechanism of action they’re blocking isn’t always unique to a virus. It might be something your cells need to do as well. Take, for example, hydroxychloroquine and chloroquine, potent antimalarials that have been shown to be ineffective against COVID-19. These drugs work by impairing a part of the cell called the lysosome, which basically breaks down and gets rid of cellular garbage. In the single-celled parasite that causes malaria, messing up its lysosome kills it. But these drugs also screw with the lysosomes inside your cells too, which accounts for the serious side-effects they have. They’re only recommended for use in cases where the benefits of the treatment outweigh the harmful side-effects.
A few other antiviral are also being investigated including favipiravir, which is still being studied for use against COVID-19. It’s been approved for use by some countries, including India. But we’re still learning more about its effectiveness and the FDA has not yet approved it.
Steroids
Steroids like dexamethasone have been used to treat the worst effects of COVID-19 by reducing the body’s own immune response. They’re effective in preventing the potentially life-threatening inflammation that results from severe infection and that can cause Acute Respiratory Distress Syndrome (ARDS), which is a main cause of COVID-19 fatalities.
But just like antivirals, sometimes the side effects from steroids can actually make things worse. Since steroids suppress the immune system, they can also make it harder for your body to fight off a COVID-19 infection. The trick is in knowing when they can be more helpful than harmful, and which dose is best. Here again, research is ongoing, but trials earlier in the year demonstrated that steroids definitely can help in treating the most severely affected COVID-19 patients.
Other drugs that influence the immune response, though not steroids, have also been looked into for preventing the overwhelming inflammation that often accompanies an infection with the novel coronavirus. One, Baricitinib, which is approved by the FDA to treat rheumatoid arthritis, has been investigated when used in conjuction with remdesivir, though the results were modest at best. Those who benefited most were on high-flow oxygen, not ventilation. For that group Baricitinib and remdesivir, taken together, shorten recovery time from 18 days to 10 days.
A whole host of other treatments have been tried for COVID-19, but none of them have been shown to be effective. Even as our methods have advanced, the best route is still to try and avoid getting sick if at all possible. Wear a mask, maintain social distance, wash your hands, and stay at home as much as possible. A vaccine is coming—we just need to keep each other safe until then.
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