Antiviral Pills for COVID-19: What to Know If You’re Immunocompromised or High-Risk

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Since the beginning of the pandemic, medications to treat COVID-19 have been rapidly developed or fast-tracked. One such area is antiviral pills, which can help stop the virus from replicating in outpatients (people who are not hospitalized) shortly after the onset of symptoms.

A U.S. Food and Drug Administration (FDA) panel recently recommended one antiviral pill, molnupiravir (from Merck), for authorization in a 13-10 vote. The FDA typically follows the panel’s recommendation and will make the final decision on whether or not the drug is authorized.

Pfizer has also developed an antiviral pill, which will be sold under the brand name Paxlovid, and it will be submitting full data on the treatment to the FDA shortly.

“These are going to be very important medications for immunocompromised patients,” says Monica Gandhi, MD, MPH, Professor of Medicine and Associate Division Chief of the Division of HIV, Infectious Diseases, and Global Medicine at UCSF/San Francisco General Hospital. “We’re not going to eradicate COVID-19, so having both prevention and treatment is really necessary.”

• Vaccines, of course, prevent COVID-19 infection in the first place as well as cause milder cases when breakthrough infections do occur.
• Antiviral pills reduce the risk of having a serious or life-threatening case after you’ve been infected.
• People who are vaccinated against COVID-19 can take antiviral pills if they were to get a breakthrough infection to help them fight off the virus.

Here’s everything you need to know about these treatments and what they might mean for people who are immunocompromised and high-risk for poor COVID-19 outcomes.

What Is an Antiviral Medication?

True to its name, an antiviral medication helps your body fight off specific viruses that can cause disease. These viruses may include COVID-19, Ebola, flu, genital herpes, or HIV, per the Cleveland Clinic.

Viruses are tiny agents that can only grow and multiply inside the living cells of your body. Once a virus attaches to and enters its host cell, it can make copies of itself and infect other cells. Though the mechanism of action differs by antiviral medication, these drugs typically work by either blocking receptors so viruses can’t attach and enter healthy cells or lowering the amount of active virus in the body.

Examples of FDA-approved antiviral drugs that treat flu include oseltamivir phosphate (Tamiflu®) and zanamivir (trade name Relenza®).

What’s the Difference Between the Merck and Pfizer Antiviral Pills?

While both pills are taken orally and would be picked up at a pharmacy after a doctor prescribes them to you, they do have key differences.

Merck Antiviral Pill

The Merck antiviral pill works by incorporating itself into the RNA that the coronavirus uses as its genetic material. It can do this because its structure is similar to nucleosides, the chemical building blocks that make up the virus’s RNA, per Yale Medicine. This leads to mutations in the viral RNA, which stops the virus from functioning.

“If you think of a genome [genetic information of a cell] as a paragraph in a book, molnupiravir rearranges all the words so it basically doesn’t make any sense,” says Timothy Sheahan, PhD, a virologist and Assistant Professor for the Gillings School of Global Public Health at the University of North Carolina at Chapel Hill, who has researched molnupiravir.

An early report showed that the Merck antiviral pill cut the risk of hospitalization and death by 50 percent in COVID-19 patients with mild-to-moderate disease, but a later full analysis showed a 30 percent reduction.

This is one of several things the FDA panel discussed in detail during its meeting. Some panelists questioned the effectiveness data on the drug, per STAT News. They also discussed the drug’s use during pregnancy, as concerns have been raised about whether the drug could cause birth defects.

While the panel didn’t go so far as to say the drug should never be given during pregnancy, it did recommend it only be used in rare circumstances for pregnant people (say, if monoclonal antibodies aren’t available or a new strain of COVID-19 has become resistant to other treatments) — and that the choice should be left up to the patient.

The Merck antiviral pill was already in development before the COVID-19 pandemic. In fact, it was studied in 2019 as a treatment for Venezuelan equine encephalitis virus, which has been feared as a potential bioweapon, per the New York Times.

Pfizer Antiviral Pill

Meanwhile, Pfizer’s antiviral pill, Paxlovid, has shown an 89 percent reduction in risk of COVID-19-related hospitalization or death in patients treated within three days of symptom onset, per a statement from the company.

The origins of Pfizer’s antiviral pill go back nearly 20 years to when researchers were searching for a way to fight the coronaviruses that caused SARS, per the Times. They built a molecule that could block an essential viral protein known as a protease, which cuts long molecules into smaller pieces that create new viruses.

“When the virus is making all the different proteins it needs to replicate, they’re kind of stuck together in a line, almost like cars in a train,” says Dr. Sheahan. “And the protease then separates the train cars.”

Researchers revisited the drug after the onset of the COVID-19 pandemic last year and modified it to work against the protease of SARS-CoV-2 — and also adjusted it so that it could work as a pill.

Unlike molnupiravir, Paxlovid does not introduce new mutations.

That said, our own cells make proteases, so protease-inhibitor drugs can also lock onto our own proteases rather than those made by viruses — though the short period of time the drugs need to be taken to stop COVID-19 may lower that risk, per the Times.

Both drugs are given for five days: Pfizer’s regimen involves six pills per day, while Merck’s regimen involves eight pills per day, per Reuters. The Pfizer drug must be given with a second medicine, ritonavir, which acts as a booster.

Once the medications are approved and available, doctors may prescribe a specific antiviral pill based on your medical history. Experts are still learning more about the possible side effects associated with both.

“Every drug has its own history and potential side effects, so I don’t think they’ll be used interchangeably because of the different potential complications that may be associated with each medication,” says Dr. Sheahan. “I don’t know if there’s real clarity on how that’s going to unfold for the various antivirals that are on the board for approval. A lot of information is going to come out when the Phase 3 studies are published and all the data is widely available.”

How Are Antiviral Pills Different From Other COVID-19 Treatments?

Antiviral pills provide a potentially easier way for outpatients to recover than other available treatments.

While the antiviral drug remdesivir is currently available for adults and children age 12 and older, it’s prescribed for people who are hospitalized with COVID-19 and it is given intravenously, per the Mayo Clinic.

“Remdesivir is an intravenous drug only approved for people who are very sick in the hospital with COVID-19,” says Dr. Gandhi. “And in fact, by that point, the inflammation is usually so severe that an antiviral doesn’t make a difference. We’ve already shown that very soon after you develop symptoms, your viral load decreases quite quickly.”

For that reason, a mainstay therapy in hospitals for COVID-19 is the steroid dexamethasone and other anti-inflammatories.

Meanwhile, monoclonal antibodies — lab-created proteins that help the immune system fight off viruses — are available for outpatients, but they require infusion or injection and close monitoring.

“Monoclonal antibodies are great, but they’re logistically difficult,” says Dr. Gandhi. “You need to monitor someone for about an hour after they get it or even longer and that requires a health care worker, so there are expenses beyond the cost of the drug. These antiviral pills are oral, so they’re really easy.”

Monoclonal antibodies work against the virus’s spike protein, so they may also not be effective against all new variants in the future.

As with most COVID-19 drugs, timing is important. Antiviral pills need to be taken within five days of symptom onset to work effectively.

“It’s really important to catch this as soon as possible, especially for immunocompromised patients,” says Dr. Sheahan. “As soon as you know that you’re COVID-positive, your doctor could write you a prescription. Medications do their best work if taken as early as possible after the onset of symptoms.”

Will Antiviral Pills Be Effective Against Variants?

Experts are confident that the antiviral pills will still help treat those infected with variants like Omicron because of how they work. Antiviral pills block the very enzymes that are involved in viral replication.

“They will be effective against variants because they work upstream of producing a virus that would even have a mutation along its spike protein,” says Dr. Gandhi. “The very mechanism of action is to block the virus from making new copies.”

The variants described to date have most of their mutations on the spike protein (for instance, the Omicron virus has 32 mutations along the spike protein).

“There’s no reason to believe these drugs will not work against Omicron,” says Dr. Sheahan. “The spike protein is able to change and respond to the immunity in our population, but these other proteins that antivirals target do not tolerate that kind of change — so they have remained relatively invariant over time.”

What Do Antiviral Pills Mean for Immunocompromised Patients?

Vaccines work very well for most people in preventing severe disease, but there will still be moderate breakthrough infections throughout the course of this pandemic. People who may not have a full immune response to the vaccine — say, because of taking immunosuppressant medication — and who are at risk for severe breakthrough infections need treatments like these antiviral pills available.

“Especially as new variants come out over and over again, and they are seemingly slowly chipping away at the immunity vaccines have given us, antivirals offer people with immune-related issues an extra layer of protection,” says Dr. Sheahan

Of course, antiviral pills do not replace COVID-19 vaccines, which prevent you from getting sick in the first place. Even if you’re immunocompromised and may not have a full immune response, doctors still recommend the vaccine (and boosters).

“I can’t stress enough that prevention is always better than treatment,” says Dr. Sheahan. “Even though these antiviral drugs can prevent people from going to the hospital and can shorten the duration of your disease, that’s only in people who take the medication at the right time.”

These drugs will not be much help for those who are sick for a week or need to go to the hospital.

And while Dr. Sheahan believes it’s possible that shortening the course of disease with antiviral pills could hypothetically prevent long COVID, research is needed to determine this. Preventing infection in the first place is the best way to avoid long-term symptoms and complications.

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