With COVID-19 cases surging in Europe and the possibility of a new late-year wave in the U.S., it is becoming clear that vaccination alone will not result in the desired effect of zero or near-zero COVID-19. In retrospect, it was probably overly optimistic a year ago to believe that at reasonably high vaccination rates, COVID-19 infections would largely be controlled.
Vaccination still remains the mainstay, but unlike the case of smallpox, it will not eliminate the virus for at least three reasons. First, there are the unvaccinated who, out of hesitation or lack of access, are present in virtually every country. Second, there are those with waning immunity post-vaccination, which is the basis for booster jabs. Finally, there are the inevitable breakthrough infections, which are currently neither predictable nor preventable. Unless some unforeseen event occurs, our goal, at least for the near future, should be to forestall the major complications of COVID-19.
With this in mind, two oral antiviral medicines that can prevent the coronavirus from reproducing in the body may soon be released for outpatient treatment of early COVID-19. This would constitute a real breakthrough. With the independent peer review and FDA approval pending, things could change, but right now here is the “what, who, where, when and why” that you should know about these drugs.
What: The first drug, Merck’s molnupiravir, has already been granted conditional authorization in the United Kingdom. Merck’s studies have shown the drug reduced hospitalizations and deaths by 50%. The Food and Drug Administration has been studying the drug since October and will hold hearings to review its findings on Nov. 30.
The second drug, paxlovid, is from Pfizer, and the company’s data indicates that it reduced the risk of hospitalization and death from severe COVID-19 in adults by 89%. These results are being independently reviewed.
Who: The drugs would be recommended as oral therapy for outpatients with COVID-19, who are either more severely ill or who have existing health conditions that put them at greater risk of hospitalization or death. There may yet be other uses for the drugs including treatment in outpatients with milder disease or as prophylactic therapy for people with known exposure to the coronavirus, but who are not yet infected.
The side effects of these drugs are now being evaluated, and restrictions and precautions in certain patient groups (e.g., pregnant women) may be an important consideration when they are released.
Where: The key to these drugs is that they are outpatient therapy. Currently, the only option for outpatients with early COVID-19 at risk of serious outcome is the injection of one of the current monoclonal antibody preparations, which must be given in a health care setting, limiting their use.
The estimate right now is that the cost of a five-day course of the new medications could be in the range of $700, expensive to be sure, but less costly than administration of monoclonal antibodies and certainly less expensive than hospital care for COVID-19. It has not been determined yet whether private insurance or the government will cover the cost. Merck has already licensed molnupiravir at a cheaper price for developing countries.
When: The trials of the two new medications focused on outpatients with COVID-19 receiving treatment within five days of the onset of symptoms. This makes the availability of testing essential.
Precise testing to confirm infection may take as much as 48 hours, so patients would have to receive a test within the first three to four days of symptoms. In theory, once patients suspect they have been infected, they can take a rapid 15-minute antigen test, which if positive, would lead to referral for the more precise test. If that was positive, therapy could begin. (Symptomatic patients without access to rapid testing or those with a negative antigen test would have to visit a health care provider for a precise test at the onset of symptoms.) The Centers for Disease Control and Prevention and local health departments should provide practical guidelines to ensure timely testing and treatment.
Why: The first-order benefits of these new oral medications are primarily for individuals — reduced rates of hospitalization and death. But the advantages could extend beyond individual patients to preventing hospital overload, health care worker burnout and the adverse effects the pandemic has had on health care, inpatient and outpatient, for non-COVID-19 conditions. If, as the data suggests, these drugs minimize the ability of COVID-19 patients to infect other people, this will reduce cases in the community and bring more people back to work and school.
Prevention is always preferable to cure, and these new treatments should be viewed as an important adjunct to, not a replacement for, vaccination and essential public health control measures.
Nevertheless, the option of early outpatient treatment with a course of highly effective oral medications could completely change the trajectory of the current COVID-19 resurgence, just as it did for the AIDS pandemic.
Nearly 150 years ago, Louis Pasteur, one of the legendary figures in the history of medicine and among the first to both administer vaccines and identify disease-causing microbes, said, “It is a terrifying thought that life is at the mercy of the multiplication of these minute bodies. It is a consoling hope that science will not always remain powerless before such enemies.”
Dr. Cory Franklin is a retired intensive care physician. Dr. Robert Weinstein is an infectious disease specialist at Rush University Medical Center.)
