Treatments for COVID-19

What helps, what doesn't, and what's in the pipeline

Most people who become ill with COVID-19 will be able to recover at home. Some of the same things you do to feel better if you have the flu — getting enough rest, staying well hydrated, and taking medications to relieve fever and aches and pains — also help with COVID-19.

The antiviral drug remdesivir was FDA approved in October 2020 to treat certain hospitalized patients with COVID-19. And scientists are working hard to develop other effective treatments. Therapies that are under investigation include drugs that have been used to treat autoimmune diseases; additional antiviral drugs, and antibodies from people who have recovered from COVID-19.

What are monoclonal antibodies? Can they help treat COVID-19?

The FDA has granted emergency use authorization (EUA) to two new treatments for COVID-19. Both are monoclonal antibodies. And both have been approved to treat non-hospitalized adults and children over age 12 with mild to moderate symptoms who have recently tested positive for COVID-19, and who are at risk for developing severe COVID-19 or being hospitalized for it. This includes people over 65, people with obesity, and those with certain chronic medical conditions.

The FDA granted EUA to the first treatment, a monoclonal antibody called bamlanivimab made by Eli Lilly, based on an interim analysis of results from a well-designed but small clinical trial. The study looked at 465 non-hospitalized adults with mild to moderate COVID-19 symptoms who were at high risk of severe disease. A placebo was given to 156 of these patients. The remaining patients were given one of three different doses of bamlanivimab. Patients treated with the monoclonal antibody had a reduced risk (3% versus 10%) of being hospitalized or visiting the ER within 28 days after treatment, compared to patients given a placebo. This is a single-dose treatment that must be given intravenously and within 10 days of developing symptoms.

The FDA has also granted EUA to a combination therapy consisting of two monoclonal antibodies, casirivimab and imdevimab, made by Regeneron. The EUA was based on results from a clinical trial that enrolled 799 non-hospitalized adults with mild to moderate COVID-19 symptoms. The participants were divided into three groups, two of which received the casirivimab-imdevimab combination but at different doses. The third group received a placebo. For patients at high risk for severe disease, those treated with the monoclonal antibody treatment had a reduced risk (3% versus 9%) of being hospitalized or visiting the ER within 28 days of treatment. This treatment must also be given intravenously in a clinic or hospital.

Monoclonal antibodies are manmade versions of the antibodies that our bodies naturally make to fight invaders, such as the SARS-CoV-2 virus. Both of these FDA-approved therapies attack the coronavirus's spike protein, making it more difficult for the virus to attach to and enter human cells.

These treatments are not authorized for hospitalized COVID-19 patients or those receiving oxygen therapy. They have not shown to benefit these patients and could lead to worse outcomes in these patients.

What is convalescent plasma? Does it help people with COVID-19?

When people recover from COVID-19, their blood contains antibodies that their bodies produced to fight the coronavirus and help them get well. Antibodies are found in plasma, a component of blood.

Convalescent plasma — literally plasma from recovered patients — has been used for more than 100 years to treat a variety of illnesses from measles to polio, chickenpox, and SARS. It is widely believed to be safe.

In the current situation, antibody-containing plasma from a recovered patient is given by transfusion to a patient who is suffering from COVID-19. The donor antibodies may help the patient fight the illness, possibly shortening the length or reducing the severity of the disease.

Though convalescent plasma has been used for many years, and with varying success, not much is known about how effective it is for treating COVID-19. A recent analysis of 35,000 hospitalized patients who received convalescent plasma to treat severe COVID-19 suggests that the therapy may reduce the risk of dying. The data comes from the ongoing Expanded Access Program (EAP) led by the Mayo Clinic. The researchers found that patients with (or at risk of) severe COVID-19 who received convalescent plasma within three days of diagnosis were less likely to die than patients who received convalescent plasma later in their illness.

The problem? The study has no control group. All patients who are eligible to get convalescent plasma under the EAP receive that treatment. As a result, questions remain as to whether, or the degree to which, convalescent plasma is effective for treating COVID-19; who would benefit from this treatment; and when in the course of illness convalescent plasma is most effective. (High demand to enroll in the program may have also unintentionally driven down enrollment in randomized, controlled studies of convalescent plasma across the country.)

Despite this, the FDA has issued an emergency use authorization (EUA) for convalescent plasma, which will make it easier for hospitals to provide the treatment to their patients.

Who can donate plasma for COVID-19?

In order to donate plasma, a person must meet several criteria. They have to have tested positive for COVID-19, recovered, have no symptoms for 14 days, currently test negative for COVID-19, and have high enough antibody levels in their plasma. A donor and patient must also have compatible blood types. Once plasma is donated, it is screened for other infectious diseases, such as HIV.

Each donor produces enough plasma to treat one to three patients. Donating plasma should not weaken the donor's immune system nor make the donor more susceptible to getting reinfected with the virus.

Is there an antiviral treatment for COVID-19?

In October 2020, the FDA approved the antiviral drug remdesivir to treat COVID-19. The drug may be used to treat adults and children ages 12 and older and weighing at least 88 pounds, who have been hospitalized for COVID-19. Clinical trials suggest that in these patients, remdesivir may modestly speed up recovery time.

Other antiviral drugs are also being tested to see if they might be effective against the virus that causes COVID-19.

Why is it so difficult to develop treatments for viral illnesses?

An antiviral drug must be able to target the specific part of a virus's life cycle that is necessary for it to reproduce. In addition, an antiviral drug must be able to kill a virus without killing the human cell it occupies. And viruses are highly adaptive. Because they reproduce so rapidly, they have plenty of opportunity to mutate (change their genetic information) with each new generation, potentially developing resistance to whatever drugs or vaccines we develop.

What treatments are available to treat coronavirus?

In October 2020, the FDA approved the antiviral drug remdesivir to treat certain patients hospitalized with COVID-19.

In November 2020, the FDA granted emergency use authorization to two monoclonal antibody treatments (bamlanivimab, made by Eli Lilly; and a combination of casirivimab and imdevimab, made by Regeneron). Both treatments have been approved for non-hospitalized adults and children over age 12 with mild to moderate COVID-19 symptoms who are at risk for developing severe COVID-19 or being hospitalized for it. In these patients, the approved treatments can reduce the risk of hospitalization and emergency room visits. These therapies must be given intravenously (by IV) soon after developing symptoms.

Other treatments, still under investigation, may also be available to people who are being treated for COVID-19 in the hospital.

If you are recovering at home, these measures can help:

• While you don't need to stay in bed, you should get plenty of rest.
• Stay well hydrated.
• To reduce fever and ease aches and pains, take acetaminophen. Be sure to follow directions. If you are taking any combination cold or flu medicine, keep track of all the ingredients and the doses. For acetaminophen, the total daily dose from all products should not exceed 3,000 milligrams.

Is dexamethasone effective for treating COVID-19?

A recent report on a clinical trial showed that the corticosteroid drug dexamethasone decreased the risk of dying in very ill hospitalized COVID-19 patients. The report was released prior to publication of the study in a medical journal, which means the research results have not gone through the usual careful review.

Many doctors, including those in the United States, have been treating very ill COVID-19 patients with corticosteroids since the pandemic began. It makes biologic sense for those patients who have developed a hyper-immune response (a cytokine storm) to the viral infection. In these cases, it is the immune system's overreaction that is damaging the lungs and other organs, and too often leading to death.

Dexamethasone and other corticosteroids (prednisone, methylprednisolone) are potent anti-inflammatory drugs. They are readily available and inexpensive.

A key question if dexamethasone is effective for some COVID-19 patients: when should it be started? If you start too soon you blunt the body's natural defense system, and that could allow the virus to thrive. What might make the most biological sense is to give dexamethasone when laboratory studies suggest an immune system in overdrive after the amount of virus in the body has started to decrease.

But we will need more studies beyond this most current report to confirm the drug's effectiveness.

Is it safe to take ibuprofen to treat symptoms of COVID-19?

Some French doctors advise against using ibuprofen (Motrin, Advil, many generic versions) for COVID-19 symptoms based on reports of otherwise healthy people with confirmed COVID-19 who were taking an NSAID for symptom relief and developed a severe illness, especially pneumonia. These are only observations and not based on scientific studies.

The WHO initially recommended using acetaminophen instead of ibuprofen to help reduce fever and aches and pains related to this coronavirus infection, but now states that either acetaminophen or ibuprofen can be used. Rapid changes in recommendations create uncertainty. Since some doctors remain concerned about NSAIDs, it still seems prudent to choose acetaminophen first, with a total dose not exceeding 3,000 milligrams per day.

However, if you suspect or know you have COVID-19 and cannot take acetaminophen, or have taken the maximum dose and still need symptom relief, taking over-the-counter ibuprofen does not need to be specifically avoided.

Are chloroquine/hydroxychloroquine and azithromycin safe and effective for treating COVID-19?

Early reports from China and France suggested that patients with severe symptoms of COVID-19 improved more quickly when given chloroquine or hydroxychloroquine. Some doctors were using a combination of hydroxychloroquine and azithromycin with some positive effects.

Hydroxychloroquine and chloroquine are primarily used to treat malaria and several inflammatory diseases, including lupus and rheumatoid arthritis. Azithromycin is a commonly prescribed antibiotic for strep throat and bacterial pneumonia. Both drugs are inexpensive and readily available.

Hydroxychloroquine and chloroquine have been shown to kill the COVID-19 virus in the laboratory dish. The drugs appear to work through two mechanisms. First, they make it harder for the virus to attach itself to the cell, inhibiting the virus from entering the cell and multiplying within it. Second, if the virus does manage to get inside the cell, the drugs kill it before it can multiply.

Azithromycin is never used for viral infections. However, this antibiotic does have some anti-inflammatory action. There has been speculation, though never proven, that azithromycin may help to dampen an overactive immune response to the COVID-19 infection.

The jury is still out regarding whether these drugs, alone or in combination, can treat COVID-19 viral infection. While recent human studies suggest no benefit and possibly a higher risk of death due to lethal heart rhythm abnormalities, two studies supporting these conclusions have been retracted by the authors because of irregularities in how results were collected and analyzed.

Regarding the effectiveness of hydroxychloroquine alone to prevent coronavirus infection, the results of a clinical trial just published in the New England Journal of Medicine found that it did not prevent infection. However, how this study was conducted has been questioned by some experts.

Where does that leave us? The recommendation has not changed. Chloroquine or hydroxychloroquine with or without azithromycin should not be used to prevent or treat COVID-19 infection unless it is being prescribed in the hospital or as part of a clinical trial.

Clinical trials that were ongoing and about to be started to evaluate the effectiveness of these drugs are resuming.

Is the antiviral drug remdesivir effective for treating COVID-19?

Scientists all over the world are testing whether drugs previously developed to treat other viral infections might also be effective against the new coronavirus that causes COVID-19.

One drug that has received a lot of attention is the antiviral drug remdesivir. The drug appears to be effective in the laboratory dish, in protecting cells against infection by the COVID virus.

Human studies are also underway. One well-designed study was published in the New England Journal of Medicine in May 2020. In comparing remdesivir to a placebo in more than 1,000 people hospitalized with COVID-19, it found that patients who received remdesivir recovered more quickly than those taking a placebo (a median of 11 days for remdesivir, compared to a median of 15 days for placebo). This was a statistically significant difference. Remdesivir was less effective in sicker COVID-19 patients, including those on a ventilator or on a heart-lung machine.

However, a large study conducted as part of the WHO Solidarity trial found that treating hospitalized COVID-19 patients with remdesivir did not significantly reduce their risk of death or shorten the length of their hospitalizations. Some experts have questioned if too many of the patients received the drug too late in their disease, and therefore would not be expected to benefit.

In October 2020, the FDA approved remdesivir as a treatment for adults and children ages 12 and older and weighing at least 88 pounds, who have been hospitalized for COVID-19.

Does vitamin D protect against COVID-19?

There is some evidence to suggest that vitamin D might help protect against becoming infected with, and developing serious symptoms of, COVID-19. We know, for example, that people with low vitamin D levels may be more susceptible to upper respiratory tract infections. One meta-analysis found that people who took vitamin D supplements, particularly those who had low vitamin D levels, were less likely to develop acute respiratory tract infections than those who didn't.

Vitamin D may protect against COVID-19 in two ways. First, it may help boost our bodies' natural defense against viruses and bacteria. Second, it may help prevent an exaggerated inflammatory response, which has been shown to contribute to severe illness in some people with COVID-19.

Our bodies make vitamin D when exposed to sunshine. Five to 10 minutes of sun exposure on some or most days of the week to the arms, legs, or back without sunscreen will enable you to make enough of the vitamin. Good food sources of vitamin D include fatty fish (such as tuna, mackerel, and salmon), foods fortified with vitamin D (such as dairy products, soy milk, and cereals), cheese, and egg yolks.

The recommended dietary dose of vitamin D is 600 IU each day for adults 70 and younger and 800 IU each day for adults over 70. A daily supplement containing 1,000 to 2,000 IU of vitamin D is likely safe for most people. For adults, the risk of harmful effects increases above 4,000 IU per day.

I've heard that high-dose vitamin C is being used to treat patients with COVID-19. Does it work? And should I take vitamin C to prevent infection with the COVID-19 virus?

Some critically ill patients with COVID-19 have been treated with high doses of intravenous (IV) vitamin C in the hope that it will hasten recovery. However, there is no clear or convincing scientific evidence that it works for COVID-19 infections, and it is not a standard part of treatment for this new infection. A study is underway in China to determine if this treatment is useful for patients with severe COVID-19; results are expected in the fall.

The idea that high-dose IV vitamin C might help in overwhelming infections is not new. A 2017 study found that high-dose IV vitamin C treatment (along with thiamine and corticosteroids) appeared to prevent deaths among people with sepsis, a form of overwhelming infection causing dangerously low blood pressure and organ failure. Another study published last year assessed the effect of high-dose vitamin C infusions among patients with severe infections who had sepsis and acute respiratory distress syndrome (ARDS), in which the lungs fill with fluid. While the study's main measures of improvement did not improve within the first four days of vitamin C therapy, there was a lower death rate at 28 days among treated patients. Though neither of these studies looked at vitamin C use in patients with COVID-19, the vitamin therapy was specifically given for sepsis and ARDS, and these are the most common conditions leading to intensive care unit admission, ventilator support, or death among those with severe COVID-19 infections.

Regarding prevention, there is no evidence that taking vitamin C will help prevent infection with the coronavirus that causes COVID-19. While standard doses of vitamin C are generally harmless, high doses can cause a number of side effects, including nausea, cramps, and an increased risk of kidney stones.

What is serologic (antibody) testing for COVID-19? What can it be used for?

A serologic test is a blood test that looks for antibodies created by your immune system. There are many reasons you might make antibodies, the most important of which is to help fight infections. The serologic test for COVID-19 specifically looks for antibodies against the COVID-19 virus.

Your body takes at least five to 10 days after you have acquired the infection to develop antibodies to this virus. For this reason, serologic tests are not sensitive enough to accurately diagnose an active COVID-19 infection, even in people with symptoms.

However, serologic tests can help identify anyone who has recovered from coronavirus. This may include people who were not initially identified as having COVID-19 because they had no symptoms, had mild symptoms, chose not to get tested, had a false-negative test, or could not get tested for any reason. Serologic tests will provide a more accurate picture of how many people have been infected with, and recovered from, coronavirus, as well as the true fatality rate.

Serologic tests may also provide information about whether people become immune to coronavirus once they've recovered and, if so, how long that immunity lasts. In time, these tests may be used to determine who can safely go back out into the community.

Scientists can also study coronavirus antibodies to learn which parts of the coronavirus the immune system responds to, in turn giving them clues about which part of the virus to target in vaccines they are developing.

Serological tests are starting to become available and are being developed by many private companies worldwide. However, the accuracy of these tests needs to be validated before widespread use in the US.

Podcasts

COVID-19 therapies update: There are three potential pathways forming a bridge to a vaccine (recorded 4/13/20)

You've probably heard the anti-malarial drug hydroxychloroqine is getting a hard look as a potential therapeutic agent in the fight against COVID-19. However, as Harvard Health Publishing senior faculty editor Dr. Rob Shmerling points out, evidence remains weak. On the brighter side, he points to three potential avenues in COVID-19 research where therapies may be put to use while a vaccine remains in development.

For more information on coronavirus and COVID-19, see the Harvard Health Publishing Coronavirus Resource Center.

Image: fizkes/Getty Images

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