Some therapies have been shown to work in clinical studies and other research
Authors: Jared S. Hopkins Mar. 21, 2022 4:47 pm ET The Wall Street Journal
The Food and Drug Administration authorized the first antiviral pills to treat Covid-19 from Pfizer Inc. and Merck & Co. and partner Ridgeback Biotherapeutics LP in December. The authorizations came after each drugmaker’s pill received a positive recommendation from a panel of experts advising the FDA, and weeks after the emergence of the Omicron variant.
Public-health experts say the best preventive measure to decrease the likelihood of contracting Covid-19 is to get vaccinated. The Centers for Disease Control and Prevention has recommended that everyone 12 and older get an additional shot after completing a primary series of Covid-19 vaccination.
Here’s what public-health and infectious-disease experts say about how to treat Covid-19.
I’ve contracted Covid-19; what should I do? How can I treat mild symptoms from home?
Doctors say an initial step is to monitor symptoms to determine whether infected people could be considered at low or high risk for developing severe disease. Individuals who are typically considered to be at low risk for severe disease include people who are young and healthy. They should stay at home away from others, drink plenty of fluids to stay hydrated and take over-the-counter medicines such as acetaminophen or ibuprofen to reduce fevers, according to physicians and the CDC. Physicians say people who are young, otherwise healthy and at low risk of developing severe disease should recover if they take the right steps.
People who are at high risk include those with underlying health conditions and the elderly, according to doctors. These individuals should pay close attention to any change in their health, including symptoms of fever, cough, fatigue or difficulty breathing. If high-risk individuals need medical attention, they should seek it right away.
“The management of Covid continues to depend on what your risk of progression is,” said Carlos del Rio, a professor of global health at Emory University. “Treatment has to be individualized.”
Additionally, people who are vaccinated and become infected—what is known as a breakthrough case—are unlikely to develop severe disease or need hospitalization, according to doctors and studies.
What are Covid-19 antiviral pills? When can I get one to treat myself?
Antivirals are treatments designed to impede a virus’s replication cycle, allowing people to recover from the illness, and they are most effective if they are taken by patients early in the course of disease.
Merck and partner Ridgeback say their oral antiviral, molnupiravir, reduced the risk of hospitalization and death by about 30%. Pfizer said in December a late-stage study confirmed its oral antiviral, called Paxlovid, which is taken with another antiviral called ritonavir, was 89% effective at reducing the risk of hospitalization and death in adults at high risk of severe Covid-19. A separate, preliminary analysis found that the drug may also help people at low risk of severe Covid-19. The company said lab tests showed Paxlovid works against the Omicron variant.
Both drugs are authorized by the FDA, and have been cleared for use.
The pills carry some safety risks and limitations. A component of Pfizer’s Paxlovid regimen, ritonavir, can interact with other drugs in dangerous or life-threatening ways. Drugs that interact with Paxlovid include common ones such as the cholesterol-lowering pill simvastatin, the antipsychotic lurasidone and the sedative triazolam. Patients should make sure to tell their doctor or pharmacist of any medications they take before starting an antiviral regimen from Pfizer, according to physicians. The Merck-Ridgeback drug isn’t authorized for children because of its potential effect on bone and cartilage growth. It isn’t recommended for pregnant women because of the potential for fetal harm, a safety signal seen in animal studies of the drug.
The Merck-Ridgeback drug can be prescribed by doctors to adults at high risk of severe disease shortly after they develop mild to moderate symptoms. Pfizer’s drug permits doctors to prescribe the medicine to high-risk patients age 12 and older early in the course of disease, shortly after they develop symptoms.
The companies studied their drugs in people who are at high risk of developing severe disease. They excluded certain people from their tests: Both left out pregnant women while Pfizer excluded people who take certain common medications such as heart drugs.
The pills are also being tested in people for preventive use with results expected by mid-2022.
Both treatments are taken over five days, with Pfizer’s totaling 30 pills and Merck-Ridgeback clocking in at 40 capsules.
The U.S. has purchased 20 million courses of treatment of Pfizer’s pill, although supply has been limited as the company increases manufacturing. The government purchased about 3.1 million courses of the Merck-Ridgeback pill, and Merck said all of it has been supplied.
Will antiviral pills be effective against the Omicron variant?
The antiviral manufacturers say they expect the treatments to be effective against Omicron, although they plan to conduct tests to verify. Both drugs target different parts of the virus than vaccines and other treatments, which are targeting the spike protein that plays a key role in infecting cells.
Pfizer has said so far its researchers haven’t seen any changes in the variant that suggests Paxlovid, which is given with the antiviral ritonavir, is less effective than against previous strains. The company said in January that three separate lab tests showed Paxlovid is effective against the Omicron.
Merck said last year that it was working to collect samples of Omicron to study whether molnupiravir is effective against Omicron and expected results by the end of the year. It has not announced results from any internal testing
Molnupiravir targets machinery the virus uses to replicate, rather than the spike protein, the structure that helps the virus infiltrate cells.
Merck expects molnupiravir to be effective against Omicron because testing has found the drug to be effective against other circulating variants. “Molnupiravir retains activity across all of these variants of concern, and there’s no difference in its antiviral activity,” said Daria Hazuda, vice president of infectious disease discovery at Merck. “There shouldn’t be any more or less concern about its effectiveness against Omicron versus any other variants.”
Merck and partner Ridgeback said in January that molnupiravir was active against Omicron in laboratory tests, pointing to six preclinical studies performed by researchers outside the company.
Are there any drugs approved or authorized for administration in clinics?
Monoclonal antibody treatments are available for people who develop symptoms and are considered to be at high risk of severe disease. As many as 75% of U.S. adults are eligible to take the drugs under FDA guidelines, according to experts. The drugs are lab-engineered molecules that mimic the natural antibodies produced by the immune system to fight off viruses. They are usually administered by infusion or injection at hospitals or clinics.
“It’s a lot easier to access one of these if you happen to live in a more populous area,” said Erica Johnson, chair of the Infectious Disease Board of the American Board of Internal Medicine and assistant professor of infectious diseases at Johns Hopkins University School of Medicine.
The FDA is permitting use of antibody treatments from Eli Lilly & Co., and from GlaxoSmithKline PLC and partner Vir Biotechnology. In January the agency restricted use of older antibody drugs from Lilly and Regeneron Pharmaceuticals because tests found they lost potency against the Omicron variant.
The Glaxo-Vir drug, sotrovimab, has retained effectiveness against Omicron. Regulators cleared for use in February a new drug from Lilly called bebtelovimab that retains effectiveness against Omicron, for the treatment of mild to moderate Covid-19 in nonhospitalized individuals 12 and older who are at high risk of getting severely sick.
In some parts of the U.S., the antibody treatments may be available for administration at home or through mobile clinics. Some states are also allowing low-risk patients to receive monoclonal antibodies, but it is not recommended by the National Institutes of Health. “The juice is not worth the squeeze,” Dr. del Rio said.
Evusheld, a preventive antibody cocktail from AstraZeneca PLC, which has shown strong efficacy in reducing risk of symptomatic Covid-19, was authorized by the FDA on Dec. 8. Evusheld is delivered as two shots and aims to offer an alternative to vaccines primarily for a minority of adolescents and adults age 12 and older with moderate to severely compromised immune systems. That includes those who have cancer, another illness, or take medications or undergo treatments such as chemotherapy that inhibit an immune response to Covid-19 vaccines.
The FDA in January permitted the use of Veklury, also known as remdesivir, for treatment of people who are not hospitalized with Covid-19. The antiviral was first developed for treating Ebola
For patients with mild to moderate symptoms but who are at high risk of developing severe disease and becoming hospitalized, the National Institutes of Health says the first option should be Paxlovid. If the drug is unavailable, or the patient can’t take it for some reason, sotrovimab should be administered. Veklury is the third option, followed by molnupiravir.
My loved one is hospitalized. Are there any FDA-approved treatments for hospitalized Covid-19 patients?
Most research has found that monoclonal antibodies aren’t effective once people become hospitalized and they are currently not recommended at that point.
Veklury is fully approved for treatment of people who are hospitalized with Covid-19.
Patients who may be at risk of advancing to severe disease may also be given dexamethasone, a steroid first approved in the 1950s that is successful at treating inflammation. The steroid has been found in studies of hospitalized Covid-19 patients to reduce the risk of death. It is recommended for treatment by the NIH and the Infectious Diseases Society of America.
Patients who don’t respond to dexamethasone may be given an immune-suppressing rheumatoid arthritis drug called Olumiant, which received an emergency-use authorization from the FDA after a study showed it helped hospitalized patients recover more quickly.
A similar rheumatoid arthritis drug, Actemra, made by Roche Holding AG, is also used to tamp down the potentially lethal inflammation seen in some hospitalized patients.
Doctors sometimes administer blood-thinners to hospitalized patients, which can reduce blood clots and inflammation that develop in some Covid-19 patients. Some studies have found that such treatments can also reduce the risk of patients needing mechanical ventilation and could help them leave the hospital sooner.
Which Covid-19 treatments are being tested?
Bristol-Myers Squibb Co. is testing a monoclonal antibody and expects Phase 2 results in the coming months, according to the company.
Researchers studying the antidepressant fluvoxamine recently reported in the Lancet, a peer-reviewed medical journal, that patients who took the widely available drug were significantly less likely to require hospitalization than those who didn’t. The drug is still being studied, and isn’t yet recommended by the NIH or IDSA.
Some research has suggested steroid inhalers are helpful at reducing symptoms early in the course of the disease, said David Boulware, an infectious-diseases specialist at the University of Minnesota. He said it is unlikely manufacturers would seek an emergency use authorization because they are widely available, although the NIH and IDSA hasn’t recommended them.
An oral antiviral from Japanese drugmaker Shionogi & Co. is also in clinical trials.
Is ivermectin effective in treating Covid-19?
In the latest trial, researchers testing the antiparasitic drug ivermectin against Covid-19 found that the drug didn’t reduce hospital admissions. The trial, with nearly 1,400 Covid-19 patients at risk of severe disease, is the largest to show that those who received ivermectin as a treatment didn’t fare better than those who received a placebo.
Most prior research hasn’t shown that ivermectin is an effective Covid-19 treatment, physicians say, and the drug isn’t authorized for that use. The FDA has approved ivermectin to treat some parasitic worms, as well as a topical treatment for head lice and skin conditions such as rosacea. It is also used in the U.S. to treat or prevent parasites in animals.
The drug, which was developed years ago by Merck, has been used to prevent river blindness and other diseases in Africa and other places where parasites are common. Prescriptions of the drug have shot up in recent months, and federal health regulators have warned doctors and veterinarians against the unauthorized use of ivermectin to treat Covid-19.
Can my doctor treat me with hydroxychloroquine?
Numerous studies have found that hydroxychloroquine and chloroquine, approved decades ago to treat and prevent malaria, don’t reduce the severity of Covid-19 symptoms or provide a benefit to patients. Doctors, however, are permitted to write so-called off-label prescriptions, to treat ailments that the FDA hasn’t approved, and some doctors have done so with hydroxychloroquine and chloroquine.
The drugs, which are also used to treat ailments such as lupus and rheumatoid arthritis, initially received emergency-use authorization, although the FDA later revoked it after concluding the therapies were unlikely to help fight the disease.
Early in the pandemic hospitals and doctors around the world began treating Covid-19 patients with hydroxychloroquine after several small studies suggested a benefit.
The NIH recommends against the use of hydroxychloroquine in hospitalized or nonhospitalized people, as does the IDSA, which also recommends against it as a prophylactic.
I’m vaccinated but I contracted Covid-19. Can I use any of the approved treatments?
“Vaccination remains one of the most important factors for us to consider,” said Dr. Abhijit Duggal, a staff ICU physician and director for critical care research for the medical ICU at the Cleveland Clinic. “Anything that we do after that is really trying to minimize the damage associated with the viral infection.”
He said factors that affect treatment decisions in vaccinated people included whether someone has any underlying immunity as well as any comorbidities. Doctors say that while it remains unlikely that vaccinated people will end up in the hospital, those who do will likely be eligible for similar treatments.
“Once you get hospitalized in breakthrough cases you will get all the usual therapies,” Dr. Duggal said. “Vaccination not only prevents the disease but also ameliorates the severity of disease.” He said some doctors in the U.S. have administered antibody treatments but it isn’t standard treatment and may not be appropriate since the virus infected the patient despite the presence of antibodies from the vaccines.
What if I am immunocompromised and become infected?
Most of the hospitalized patients who were previously vaccinated are immunocompromised, according to doctors. Hospitalized patients who are immunocompromised are eligible to receive convalescent plasma, a highly concentrated solution of antibodies taken from recovered Covid-19 patients. There is limited data that suggests monoclonal antibody treatments will benefit the immunocompromised, even if they are vaccinated, said Dr. Duggal.
—Joseph Walker contributed to this article.