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COVID-19 Treatments: What We Know So Far

BY KATHY KATELLA May 26, 2023

These medicines can protect people at high risk for severe illness from COVID-19.

[Originally published: March 10, 2022. Updated: May 26, 2023]

Note: Information in this article was accurate at the time of original publication. Because information about COVID-19 changes rapidly, we encourage you to visit the websites of the Centers for Disease Control & Prevention (CDC), World Health Organization (WHO), and your state and local government for the latest information.

Most people with COVID-19 will experience a mild illness, and they’ll be able to take care of themselves at home. But some—especially those with underlying health conditions—could benefit from one of several COVID-19 treatments. Some of these are available in pill form and others are given intravenously or by injection—and all of them must be prescribed by a health care provider.

It’s important to remember that while new treatments are effective at reducing the severity of symptoms and helping prevent hospitalization and death in people who become infected with COVID-19, they are not a substitute for vaccination, which remains the single most effective strategy to prevent serious disease.

Below is Yale Medicine’s guide to COVID-19 treatments.

Paxlovid

What is it? Paxlovid is Pfizer’s brand name for an antiviral oral medication (in pill form) that combines two generic drugs, nirmatrelvir and ritonavir. It is fully approved for adults by the Food and Drug Administration (FDA), and has an emergency use authorization (EUA) for adolescents and teenagers, ages 12 and older (and weighing at least 88 pounds). It is meant for people who have a current mild-to-moderate COVID-19 infection and who are at high risk for severe disease. The National Institutes of Health (NIH) prioritizes its use over other treatments for eligible patients.

When it was authorized: December 2021 for adolescents and teenagers ages 12 and older. It was fully approved in May 2023 for adults.

Who can get it: People ages 12 and older who weigh at least 88 pounds, have a positive COVID-19 test result, have mild-to-moderate COVID-19, and are at high risk for developing severe COVID-19.

How you take it: For most people, the dose is three pills twice daily for five days, and it must be started within five days of developing COVID-19 symptoms.

Side effects: The most common side effects of taking Paxlovid include impaired sense of taste (for example, a metallic taste in the mouth) and diarrhea, according to the FDA. Side effects usually are mild, and may include altered or impaired sense of taste, diarrhea, increased blood pressure, or muscle aches. Because Paxlovid is still being studied, it’s possible that all of the risks aren’t yet known.

How it works: Paxlovid is an antiviral medication, a type of drug that stops viruses from replicating inside the body’s cells. Two of the pills in the three-pill dose are nirmatrelvir, which prevents the SARS-CoV-2 virus from replicating. The other medication is ritonavir, which gives the first drug’s levels a boost by essentially shutting down its metabolism in the liver, so that nirmatrelvir levels remain high and can work longer to fight the infection.

How well it works: The FDA’s approval of Paxlovid for adults in 2023 was based on scientific evidence submitted by Pfizer, including efficacy data from a study showing an 86% reduction in risk of COVID-19-related hospitalization or death from any cause in patients. Based on virology data, Paxlovid retains activity against currently circulating Omicron variants, according the latest FDA statement.

In November 2022, the CDC reported on a real-world study that showed adults who took Paxlovid within five days of a COVID-19 diagnosis had a 51% lower hospitalization rate within the next 30 days than those who were not given the drug. The study included people who had been vaccinated or had a previous infection, which the CDC said implied the drug should be offered to people who are eligible regardless of their vaccination status.

What else you should know: Paxlovid interacts with many medications, including common ones that are sold over the counter like St. John’s Wort, blood thinners, cholesterol medicines, and many more. In some cases, this can cause complications that are serious enough to justify not taking it. So, it’s important for health care providers to have an up-to-date medication list, including over-the-counter medications and supplements; they may consider other treatments for some patients. Pharmacists may also provide Paxlovid [with certain limitations], if they’ve opted to do so, provided you can share your electronic or printed medical records, including a list of medications you are already taking, and blood test results from the last 12 months.)

There is no experience treating pregnant women or breastfeeding mothers with Paxlovid. Women who are pregnant should discuss their options with their health care provider. It is also recommended that patients use effective barrier contraception or do not have sexual activity while taking Paxlovid.

Paxlovid is also not recommended for patients with severe liver or kidney disease and those with HIV who are not on treatment.

There have been reports of a “rebound” of COVID-19 symptoms in some people who have completed the five-day course of Paxlovid; in those cases, symptoms have recurred four or five days after completing the treatment. However, when it approved Paxlovid in May, the FDA said there was not a clear association between Paxlovid treatment and a COVID-19 rebound based on available data, and rebound rates in clinical trials were similar among participants who took Paxlovid and those who took a placebo.

CDC guidance for clinicians says a brief return of symptoms may be part of the natural history of SARS-CoV-2 infection in some people, independent of treatment with Paxlovid, adding that there is no evidence additional treatment is needed.

More information: FDA Paxlovid fact sheet for patients, parents, and caregivers.

Remdesivir

What is it? The antiviral treatment remdesivir, sold under the brand name Veklury, was the first COVID-19 therapy to get full FDA approval, and, so far, it's still the only one. Although originally used in COVID-19 patients only after they were hospitalized, new data suggests it can be helpful in outpatients who become infected and who are at high risk for severe disease. It is meant for people who have a current COVID-19 infection.

When it was authorized: Full approval was granted in October 2020. (It was first authorized in May 2020 for critically ill patients who were being treated with oxygen for COVID-19.) The authorization was later expanded to include other groups, and it was authorized to treat non-hospitalized patients in January 2022.

Who can get it: Fully approved for children and adults who are at high risk for severe disease. Infants and children must be at least 28 days old, weigh over 6.5 pounds or more, and be either hospitalized or at high risk for severe illness.

How you take it: Via injection or IV and administered only in a health care setting by a health care professional. For outpatients, the treatment is a three-day course of infusions that must be initiated within seven days of symptom onset.

Side effects: Nausea is the most common side effect. Hypersensitivity, including infusion-related and anaphylactic reactions, has been observed following treatment. There is insufficient data on the safety of using remdesivir in pregnant women or women who are breastfeeding; patients should speak with their health care provider.

How it works: Administered intravenously to patients who are in the hospital or in an ambulatory setting, the drug inserts itself into new viral genes to block replication of the virus, shortening the time it takes seriously ill patients to recover. A number of experts believe that the drug may work best early in the course of an infection.

How well it works: 87% reduction in risk of hospitalization in non-hospitalized patients given a three-day course, according to a study published in The New England Journal of Medicine in December 2021.

What else you should know: For hospitalized patients, research in early 2020 showed that the therapy reduced length of stay (the number of days in the hospital) from 15 days to 12. However, questions have been raised about remdesivir’s trial results for hospitalized patients. In late 2021, the World Health Organization (WHO) recommended against remdesivir after releasing data that showed disappointing results. Still, many U.S. hospitals continue to provide this medication. 

This is one of two NIH-preferred therapies (after Paxlovid) for COVID-19.

More information: Gilead remdesivir fact sheet for patients.

Molnupiravir

What is it? Molnupiravir, also known by the brand name Lagevrio, was developed by Merck and Ridgeback Biotherapeutics. It was heralded as a potential game-changer when the companies announced their initial clinical trial results in 2021. But when the data was finalized, it showed the drug to have lower efficacy than originally reported. Its FDA authorization came after a close vote that took into account the lowered efficacy and safety profile. The Centers for Disease Control & Prevention (CDC) now recommends that this drug should be used when the above-mentioned treatments aren’t available.

When it was authorized: December 2021.

Who can get it: People ages 18 and up who are at high risk for hospitalization and death from COVID-19.

How you take it: Four capsules every 12 hours (for example, at 8 a.m. and 8 p.m.) for five days. It must be taken as soon as possible, within five days of symptom onset.

How it works: When the drug enters the bloodstream, it blocks the ability of the SARS-CoV-2 virus to replicate.

How well it works: 30% efficacy against hospitalization and death. Merck initially reported the efficacy as 50%, but later adjusted that figure. Some laboratory studies from Merck have shown that molnupiravir is effective against the Omicron variant.

Side effects: Diarrhea, nausea, and dizziness are the most common side effects. You should stop taking the pills right away if you have an allergic reaction. Because molnupiravir is still being studied, it’s possible that all of the risks aren’t yet known.

What else you should know: Molnupiravir is not recommended during pregnancy, since it has not been studied in pregnant women and has shown potential harm in in vitro studies—therefore, the true risk for harm to an unborn baby is unknown.

Individuals who are able to become pregnant should use reliable birth control during treatment and for four days after their last dose. It is also not known if molnupiravir could affect sperm, so individuals who are taking molnupiravir and who are sexually active with partners who are able to become pregnant should use reliable birth control during treatment and for three months after the last dose. (Studies to understand the risk to sperm beyond three months are ongoing.)

The NIH considers this to be an alternative treatment, which should be used only when neither of the NIH-preferred therapies (Paxlovid and remdesivir) are available, feasible to use, or clinically appropriate. 

More information: FDA molnupiravir fact sheet for patients and caregivers.

Evusheld (not currently authorized)

What is it? Evusheld is a monoclonal antibody that was granted FDA authorization in December 2021; however, it was halted in January 2023 until further notice. The FDA is limiting use of the treatment to times when the strains Evusheld is able to protect against make up less than or equal to 90% of infections. Recent data has shown that Evusheld is unlikely to be effective against newer SARS-CoV-2 strains (including XXB.1.5) that, combined, make up more than 90% of infections.

Evusheld combines two drugs, tixagevimab and cilgavimab, and it has been used differently than the medications listed above. It was not designed to treat COVID-19; rather, its purpose was to keep immunocompromised people and those who did not respond to vaccination from getting sick. Developed by AstraZeneca, it was the first long-acting antibody to receive an EUA for pre-exposure prevention of COVID-19.

The U.S. government is recommending that providers retain any Evusheld products they have in stock in case it is able to neutralize future variants.

Bebtelovimab (not currently authorized)

What is it? Bebtelovimab is a monoclonal antibody treatment that had its FDA authorization paused in November 2022. The treatment showed efficacy against early strains of Omicron, but it proved to be ineffective against Omicron sublineages BQ.1 and BQ.1.1. It was an important treatment for certain immunocompromised COVID-19 patients who weren’t able to take Paxlovid or faced challenges with other treatments. The government recommended that providers retain the product in the event that SARS-CoV-2 variants susceptible to bebtelovimab become more prevalent in the future in the United States.

Note: If you are experiencing symptoms of COVID-19 and think you are eligible for a treatment, you can visit the government Test-to-Treat Locator. You can use the site to search for places near you where you can fill a COVID-19 prescription or identify sites that provide testing, medical care, and COVID-19 medications.

This article was medically reviewed by Jaimie Meyer, MD, MS, a Yale Medicine infectious diseases specialist, and Dayna McManus, PharmD, a senior clinical pharmacy specialist in infectious diseases for Yale New Haven Hospital.

Information provided in Yale Medicine articles is for general informational purposes only. No content in the articles should ever be used as a substitute for medical advice from your doctor or other qualified clinician. Always seek the individual advice of your health care provider with any questions you have regarding a medical condition.