If you have possible COVID-19 symptoms, get tested right away. And if you are infected with the omicron variant or BA.2 subvariant, early treatment with antiviral pills is effective. (Research currently is being done on even more recent subvariants such as BA.3, BA.4 or BA.5.)
In particular, the antiviral Paxlovid can prevent severe COVID-19 from taking hold and making you sick. Previously scarce, Paxlovid stocks are now plentiful. If Paxlovid isn’t right for you, other antiviral or monoclonal antibody drugs offer alternative options.
Your primary care provider can prescribe oral antivirals. In addition, testing and treatment venues are more accessible than ever through new nationwide programs.
Oral Antiviral Medications to Treat COVID-19
Particular oral antiviral medications have been shown to effectively treat COVID-19 infection caused by both the omicron variant and the BA.2 subvariant in high-risk patients.
In late December 2021, the Food and Drug Administration issued emergency-use authorizations, also called EUAs, for oral antiviral drugs Paxlovid and molnupiravir (Lagevrio) for the treatment of mild-to-moderate COVID-19. Also known as ‘direct-acting antivirals,’ they’re recommended for patients with COVID-19 symptoms who are not hospitalized or in need of oxygen therapy, but are at high risk of progressing to a severe case of COVID-19.
“The best data from trials come from Paxlovid and suggest that it is highly effective at reducing the risk of hospitalization and death, and that anyone who is older or who has underlying conditions should get it quickly as possible after they get diagnosed,” says Dr. Tom Frieden, president and CEO of Resolve to Save Lives, an initiative of Vital Strategies, and a former director of the Centers for Disease Control and Prevention. “It’s not likely to be very helpful after about five days, and it’s likely to be more helpful the sooner you get it.”
Frieden has followed his own advice: “When my 92-year-old mother got COVID, I made sure she got Paxlovid the same day, and she did completely fine,” he says.
“Paxlovid is very effective early on,” says Dr. Judith O’Donnell, a professor of clinical medicine at the University of Pennsylvania and director of infection prevention and control at Penn Presbyterian Medical Center in Philadelphia.
“It really shows a superb decrease in need for hospitalization or death within 30 days, if you can treat someone with Paxlovid within the first three to five days after they’ve been diagnosed with COVID-19,” O’Donnell says. “Molnupiravir has a less robust improvement response compared to Paxlovid.”
Paxlovid is nearly 90% effective in reducing the risk of hospitalization or death from COVID-19 when given early, according to a study published April 14, 2022, in the New England Journal of Medicine. On the other hand, molnupiravir is 30% effective at reducing that risk, according to data reported by the manufacturer in November 2021.
How do direct-acting antivirals stack up against long COVID? “Although we don’t know whether or not Paxlovid will reduce the risk of long COVID, I would be surprised if it did not,” says Frieden, who is also a senior fellow for global health at the Council on Foreign Relations and Prevention.
How Oral Antivirals Work: Paxlovid
What Is Paxlovid?
Paxlovid is taken orally twice daily for five days. Made by Pfizer, it combines two drugs: the antiviral drug nirmatrelvir along with ritonavir, which boosts nirmatrelvir’s action. The second Paxlovid ingredient, ritonavir, is an established drug that has previously been used to boost certain anti-HIV medications.
“Here, ritonavir is present in a very low dose, and it’s designed to enhance the concentration of the antiviral, nirmatrelvir,” explains Dr. Albert Shaw, a professor of medicine in the section of infectious diseases at Yale School of Medicine in New Haven, Connecticut. “It seems important in getting sufficient levels for clinical efficacy. It does this by inhibiting a specific kind of liver enzyme that breaks down a lot of drugs, and as a consequence, has a large number of drug interactions.”
Who Can Use Paxlovid?
Paxlovid is indicated for mild-to-moderate COVID-19 in adults or children ages 12 and older who are not hospitalized, but are at risk for severe disease progression.
Paxlovid Drug Interactions
Blood-thinning drugs, some psychiatric drugs, certain drugs for heart disease or heart arrhythmias and anti-seizure medications are included in “the really long list” of potential drug interactions for Paxlovid, Shaw says. “So, this has to be evaluated by the patient’s doctor to determine whether this would be safe or reasonable for this person to take.”
On May 24, the CDC addressed the issue of COVID-19 rebound, following reports of people experiencing bouts of mild COVID-19 symptoms or a new positive viral test shortly after their initial recovery. “A brief return of symptoms may be part of the natural history (of the virus causing COVID-19), independent of treatment with Paxlovid and regardless of vaccination status,” according to the CDC health advisory. “Limited information currently available from case reports suggests that persons treated with Paxlovid who experience COVID-19 rebound have had mild illness; there are no reports of severe disease.”
How Oral Antivirals Work: Molnupiravir
What Is Molnupiravir?
Molnupiravir is taken orally, every twelve hours, for five days. Made by Merck, the capsules contain this single antiviral agent.
Molnupiravir basically works by incorporating itself into the virus as it’s replicating, Shaw says. “Its presence induces mutations in the virus that accumulate,” he explains. “Eventually, the virus just has so many mutations that it’s not able to make a functional virus. So it’s a very clever mechanism of action — and it also seems to be effective.”
For both antiviral drugs, it’s recommended to start treatment within five days of symptom onset.
Who Can Use Molnupiravir?
Molnupiravir is indicated for adults 18 and older with mild-to-moderate COVID-19 who are not hospitalized, but are at risk for severe disease progression.
Risks of Molnupiravir
“The main issue with molnupiravir is that it’s not recommended for use during pregnancy,” Shaw says. “And it’s not recommended, at least in this emergency-use authorization, if men or women are of childbearing age. It’s certainly recommended to use effective contraception during treatment.”
Molnupiravir has not been studied in human pregnancy and may cause harm to an unborn baby, the Merck website notes. Merck safety information section adds: “You and your health care provider may decide that you should take molnupiravir during pregnancy if there are no other COVID-19 treatment options authorized by the FDA that are accessible or clinically appropriate for you.”
Women are advised to continue using contraception several days after the last dose, Shaw notes, whereas sexually active males with reproductive potential should continue using contraception for three months after the last dose. Breastfeeding is not recommended during molnupiravir treatment.
The World Health Organization updated its COVID-19 treatment guidelines in March to include a conditional recommendation on molnupiravir: WHO advises that the antiviral only be given to non-severe COVID-19 patients at higher risk of hospitalization, such as those who have not received the vaccine, older people and those who are immunocompromised or live with chronic disease.
Better Access to Oral Antivirals
Early treatment for COVID-19 can prevent serious illness from developing. Now, with good U.S. supplies of oral antivirals that health care providers can prescribe at no cost to the patient, the issue is improving access so more people take them — soon enough after testing positive to make a difference.
In March, the White House unveiled the Test to Treat initiative to provide one-stop sites where people could undergo free COVID-19 testing, immediately get results and if those are positive, receive a prescription on the spot for free antiviral pills. Now, you can find a one-stop site in your area through the online Test to Treat locator.
“Vaccines continue to be the most effective way to protect yourself and others from COVID,” emphasizes Dr. Meg Sullivan, chief medical officer for the Office of the Assistant Secretary for Preparedness and Response at the Department of Health and Human Services.
But with more COVID-19 therapeutics like oral antivirals being developed, Sullivan says, and increasing recognition of their important role in the COVID-19 response, the ASPR is striving to increase patient and health care provider awareness of who is eligible, enable counseling and appropriate prescribing for these effective drugs, and facilitate access to treatment.
As part of that larger overall effort, Sullivan says, “We wanted to answer the question of: If you don’t have a health care provider, or if you don’t have ready access to a health care provider, here are some additional sources that you could go to.” To do so, ASPR launched Test to Treat sites as an additional access point for people to receive medications in a timely way to prevent them from getting sick and going to the hospital.
Pharmacy-based clinics are primary Test to Treat access points, with CVS, Kroger and Walgreens among the main sites. In addition, Sullivan says, ASPR is working closely with federally qualified health centers, the Veterans Health Administration, the Department of Defense and states, territories and jurisdictions to increase access at local levels.
About 2,500 locations are currently identifiable on the Test to Treat locator as of mid-May, Sullivan says, with plans for that number to continue to grow. Clinicians work with patients at every site. At the pharmacy-based clinics, many of the health care providers are nurse practitioners or physician assistants. “Some are physicians and all (sites) have some kind of physician leadership,” Sullivan says.
Telehealth is another important part of the COVID-19 response, Sullivan says, including improving access to treatment. Once a patient has a positive test result, evaluation by a heath care provider can be done virtually, “and then a prescription can be written to the pharmacy of your choice,” she explains. Telehealth options may also involve shipping the medication to your home.
In mid-May, all households became eligible to order eight more free at-home coronavirus tests, in the third round of free tests to be delivered by the U.S. Postal Service. You can order your free tests via covid.gov/tests.
The message that safe, effective treatment early COVID-19 is available is being heard by the public and by health care providers. “We have seen utilization significantly increase over the past four weeks, especially as we have gotten Paxlovid out to more sites and have increased that awareness,” Sullivan says. “But we still have an ample supply in the field.”
Injected Drugs for COVID-19 Treatment
Made by Gilead Sciences and the first drug fully approved by the FDA to treat COVID-19 (not just an emergency-use authorization), remdesivir is an antiviral drug that’s administered intravenously. Remdesivir is used for adults and children ages 12 and over, who weigh at least 88 pounds.
Patients receive remdesivir infusions once daily for five to 10 days. Sometimes given off-label as an outpatient drug, remdesivir is often given along with the steroid drug dexamethasone for hospitalized patients who require supplemental oxygen.
Monoclonal Antibodies for COVID-19
These monoclonal antibody drugs are effective against BA.2 and used for early treatment or prevention:
— Evusheld (intramuscular injection).
— Bebtelovimab (intravenous).
In February, the FDA issued an EUA for a new monoclonal antibody called bebtelovimab. The intravenous therapy, manufactured by the pharmaceutical firm Eli Lilly, must be given soon after someone develops COVID-19 symptoms. The drug is authorized for non-hospitalized adults and children over 12 who test positive, and who have mild to moderate symptoms and are at risk for developing or being hospitalized, for severe COVID-19 and for whom alternative COVID-19 treatment options are not accessible or clinically appropriate.
Possible side effects include itching, rash, drug infusion reactions, nausea and vomiting.
Bebtelovimab was found effective against the omicron BA.2 variant in laboratory tests and in February, the federal government bought 600,000 doses to distribute across U.S. states and territories. In mid-May, manufacturer Eli Lilly reported that further testing has confirmed that the drug is effective against current COVID-19 variants of concern.
Evusheld is a unique drug in that it is actually used to prevent COVID-19 prior to exposure. Made by AstraZeneca, it’s a combination of two monoclonal antibody drugs: tixagevimab and cilgavimab. The FDA issued an EUA for Evusheld in December 2021.
“Evusheld is approved under EUA in use for individuals who can’t make an appropriate antibody response to the vaccine — very immunodeficient people or people who are on a lot of immunosuppressing medications because they’ve had a transplant or have an underlying disease of some kind,” O’Donnell explains. An intramuscular injection, Evusheld can be taken every six months to provide prolonged protection against COVID-19.
Hospital Treatments for COVID-19 Illness
For hospitalized patients with COVID-19, treatment has involved various drug combinations. “For severely ill patients it would be: remdesivir if appropriate, steroids (commonly dexamethasone) if appropriate and then either baricitinib or tocilizumab,” O’Donnell says.
— Baricitinib (Olumiant). This oral drug is used to treat hospitalized adult and pediatric patients who are at least two years old, and who require either supplemental oxygen, mechanical ventilation or extracorporeal membrane oxygenation, or ECMO. Baricitinib belongs to the drug class called janus kinase inhibitors and works by decreasing immune system activity in order to reduce inflammation.
— Tocilizumab (Actemra). A monoclonal antibody, tocilizumab is an intravenous drug for severely ill patients with age ranges and indications similar to those for baricitinib.
One or the other of these existing agents can be used, depending on the patient and underlying conditions as well as existing supplies, she says.
Patients hospitalized with severe COVID-19 typically have breathing problems that require treatment with oxygen. Low-flow oxygen with a nasal cannula is the least-concentrated oxygen treatment. High-flow nasal cannula therapy delivers higher concentrations of humidified and heated oxygen.
“That’s hopefully to stave off the need to put somebody on a ventilator,” O’Donnell says. However, mechanical ventilation is sometimes unavoidable.
ECMO is a complex device that replaces the function of both the heart and lungs. “ECMO is one of the treatment options that the most severely ill patients with COVID-19 are being offered,” O’Donnell says. “When they really are unable to get adequate supplies of oxygen across the stiff, infected, diseased lung, then they put patients on ECMO because that’s the only way to deliver oxygen to the rest of the body. ECMO is still the last resort before you would say you can’t do anything.”
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Update 06/01/22: This story was previously published at an earlier date and has been updated with new information.