What You Need to Know About COVID-19 Treatments

The COVID-19 treatment options available in the form of a pill are the antiviral medications Paxlovid™ and molnupiravir. They were developed by the pharmaceutical companies Pfizer and Merck to prevent people who are at high risk from becoming severely ill after infection with the SARS-CoV-2 virus, the virus that causes COVID-19. The FDA issued emergency use authorizations in late 2021 for both medications. The pills are available by prescription from some Milwaukee-area pharmacies. Another antiviral treatment, remdesivir, sold under the brand name Veklury^®, is also effective. Remdesivir was developed by the drugmaker Gilead. It is a 3-day IV treatment. Antiviral pills and IV therapy are available to eligible people who are not hospitalized with COVID-19.

How Do the COVID-19 Pills Work?

Paxlovid and molnupiravir are antivirals that work by stopping the viral replication process. This reduces a person’s viral load and lessens the severity of their symptoms. However, the way the drugs function is slightly different.

Paxlovid is a protease inhibitor that blocks a part of the virus’ life cycle. Protease inhibitors bind to the enzyme the virus uses to replicate and prevent the production of new viral particles. Molnupiravir is a nucleoside analogue, which means it stops the viruses’ genetic material from being accurately replicated, rendering new viral particles noninfectious. 

Both pills require a five-day course of treatment. Most people who are prescribed Paxlovid take three tablets at the same time, twice a day (there is a dose reduction for people with moderate kidney disease). People prescribed molnupiravir take four capsules twice a day.

How Effective Are the COVID-19 Pills?

Clinical trials of Paxlovid and molnupiravir were so successful, they were stopped early. Results showed the pills were much more effective than placebos. Pfizer’s clinical trial found Paxlovid reduced a person’s risk of hospitalization by 89% when given within three days of symptom onset. Merck’s clinical trial showed molnupiravir cut the rate of hospitalization or death by 30% when the drug was given within five days of symptoms onset. 

It is important to note that both of these clinical trials were conducted in a small number of patients, and both drugs remain investigational in nature. They are authorized for emergency use but are not FDA-approved, and the full extent of risks and benefits may not yet be determined.

How Does Remdesivir Work?

Remdesivir is an antiviral medication administered by an intravenous (IV) method that works against the COVID-19 virus by directly stopping the viral replication process. It interferes with one of the key enzymes the virus needs to replicate and stops the infection from progressing. Remdesivir was one of the original treatments for COVID-19 when it was approved for use by the FDA in 2020. At the time, it was only for use in patients who were hospitalized with the virus. In January 2022, in response to the surge of the omicron variant, the FDA expanded remdesivir’s use for outpatients with mild-to-moderate COVID-19.

How Effective is Remdesivir Against COVID-19?

The clinical trial that led to the expanded the use of remdesivir for outpatient treatment showed that a 3-day course of the medication started within 7 days of COVID-19 symptom onset reduced a person’s risk of hospitalization or death by 87%.

Outpatient treatment with remdesivir requires an intravenous infusion given over at least 30 minutes daily for three days in an infusion treatment center.

Who Is Eligible for the COVID-19 Treatments?

Not everyone who tests positive for COVID-19 will be able to get a prescription for Paxlovid, molnupiravir or remdesivir. Per the FDA, Paxlovid and molnupiravir are only authorized for use in people who have tested positive for COVID-19, are experiencing mild-to-moderate disease and are at a high risk for progression to severe disease. Paxlovid is authorized for people ages 12 and older. Molnupiravir is authorized for people ages 18 and older. Neither pill is intended or authorized for people who require hospitalization for severe COVID-19. They are also not intended for the prevention of COVID-19 in someone who was exposed to the virus. Remdesivir is authorized for anyone who tests positive for COVID-19, has mild-to-moderate symptoms and is at high risk of severe illness. With the expanded use of remdesivir in 2022, you no longer have to be hospitalized to be eligible for treatment.

If you tested positive for COVID-19 in the last five days and have questions about your eligibility or risk factors, talk to your doctor. 

These medications are widely available. If your positive test was done at a Froedtert & MCW lab location, your doctor is part of the Froedtert & MCW health network and you are eligible for this treatment, a nurse will reach out to you through MyChart. Patients who do not use MyChart will receive a phone call. If your positive test result was from an at-home test or external lab, you should contact your Froedtert & MCW primary care provider or schedule an E-Visit to be referred for treatment. 

How Are COVID-19 Antiviral Medications Different Than Monoclonal Antibody Therapy?

The difference between monoclonal antibody therapy and antiviral medications such as Paxlovid, molnupiravir and remdesivir is the mechanism by which the treatments prevent infection from progressing. Monoclonal antibody therapy is a treatment given by infusion that supplies the body with man-made antibodies to fight COVID-19. In January 2023, the FDA suspended the use of monoclonal antibody therapies because they were no longer effective against the dominant strains of the COVID-19 virus.

The antiviral medications work inside the cells to inhibit viral replication, while the monoclonal antibodies targeted the virus’ spike protein or other surface proteins by binding to the virus particles to block them from entering the body’s cells. Treatment should be given as soon as possible after a positive COVID-19 test. Antiviral medications can only be prescribed within five days of symptom onset.

Which COVID-19 Treatment Is Right for Me?

Based on your health history and current medications, your health care team will determine which COVID-19 treatment is best for you. This will also depend on availability, as the Wisconsin Department of Health and Human Services oversees the distribution of supplies and determines how much of each drug is sent to Wisconsin hospitals. 

“Between remdesivir therapy and the two different COVID-19 pills, we have been able to reach out to nearly 95% of eligible patients and offer one of these therapies,” said Mark Lodes, MD, a Froedtert & MCW internal medicine and pediatric physician. Dr. Lodes is also vice president and chief medical officer for Froedtert & MCW Population Health and Medical Education.

Led by Dr. Lodes, the Froedtert & MCW Population Health and Medical Education team developed a centralized process to make it easier for patients to receive the right COVID-19 treatment and for providers to prescribe it. When a provider submits a referral, the database matches each patient with the best treatment, based on their risk factors, and in some cases, lab results, which are ordered the same day.

“If you did a home test and got a positive result, all you need to do is share that result with your doctor’s office,” Dr. Lodes said. “If you tested with us and got a positive result, we automatically receive the alert. In both cases, this kicks off our internal evaluation process of eligible patients. If you are eligible for one of the oral COVID-19 antiviral medications or remdesivir, we’ll reach out to you with the appropriate treatment option.”

Many health networks have moved toward a similar centralized system because it simplifies and speeds up the dispensing process, while maximizing the ability to treat as many people as possible.

What Are the Side Effects of the COVID-19 Treatments?

Pfizer’s Paxlovid is a combination of two drugs, nirmatrelvir and ritonavir. Ritonavir is widely known for its use in HIV medications. It is not active against COVID-19, but it acts as a boosting agent to increase the levels of nirmatrelvir in the body to fight the virus that causes COVID-19. Many widely used medications for chronic conditions, like blood thinners or antidepressants, have known drug interactions with ritonavir.

“Some of these drug interactions are manageable by adjusting doses of the other medications, when possible,” said Deanna Olexia, RPh, antimicrobial stewardship coordinator for the Froedtert & MCW health network. “But when this isn’t an option or when interactions could be significant, we direct patients toward an alternative therapy.”

Paxlovid isn’t recommended for people with severe kidney or liver disease. The most common side effect is an altered sense of taste that usually goes away after treatment is completed.

Molnupiravir doesn’t have any known drug interactions, and no significant side effects have been reported. However, based on available research, it is not recommended for use during pregnancy. Women of child-bearing age undergoing treatment are asked to use contraception for the duration of the treatment and through four days after the last dose. Men who are sexually active should use contraception during treatment and for three months after the last dose. 

Remdesivir is an IV infusion, so there is a chance for allergic/infusion reactions to remdesivir or components of the medications during infusion. Remdesivir is not recommended for people with severe kidney disease or liver disease.

Your health care team will keep track of all of this for you and make sure you are matched with the best treatment for you.

Rebound COVID-19

Rebound COVID-19 is when a person who has been treated for COVID-19 tests negative, then shortly after, gets symptoms again. Rebound symptoms typically occur within two to eight days of completing a treatment course. Rebound COVID-19 has also been reported in untreated patients and is likely a natural disease process. It is uncommon, happening in 1%-2% of patients. It is not the same as reinfection with the virus or resistance to treatment.

People with rebound COVID-19 should not be retreated for the virus. They should manage symptoms with over-the-counter medications, as advised by their doctor, return to isolation and wear a face mask. If symptoms progress or become more severe, they should consult with their doctor.

Do I Need to Take the COVID-19 Pills or Remdesivir if I’m Not Feeling Sick?

The COVID-19 pills and remdesivir are prescribed early in the disease process, within five to seven days of a positive COVID-19 test. People are only eligible if they have symptoms, but during this timeframe, it is possible you will not feel severely ill or you may have milder symptoms. While the decision to move forward with treatment is yours, it is important to understand why your provider recommended the treatment for you.

“If you were prescribed a COVID-19 pill or remdesivir , you are part of a group of people that is at risk for worsening disease,” Olexia said. “Consider the impact this would have on you or your family and take into account the information we have about the medication so far. These medications appear to be quite effective and safe, and they may prevent you from becoming more sick or needing to be hospitalized.”

If you’re prescribed antiviral therapy, you are still asked to isolate while you are undergoing treatment, following current CDC guidelines.

Are Vaccinations Against COVID-19 Still Necessary With COVID-19 Treatments?

The COVID-19 vaccines lower your risk of becoming infected and of spreading the virus. The antiviral pills and remdesivir are not substitutes for vaccination because they do not prevent COVID-19, They are treatments. 

“Public health mitigation measures like vaccines, face masks and social distancing are still the best ways to prevent you from getting admitted to the hospital for COVID-19,” Dr. Lodes said. “If you are infected, these new medications are a potential lifesaving therapy.”

To learn more about COVID-19 care and testing options, visit froedtert.com/coronavirus.