Q&A: How to treat outpatients with COVID-19
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Key takeaways:
- Several available antiviral medications could potentially reduce serious disease in high-risk patients.
- Treatment depends upon individual factors that need to be understood by patients and providers.
Mutations have allowed SARS-CoV-2 to evade previously effective treatments and preventives that have become a crucial tool for reducing severe COVID-19 and have made treating outpatients with COVID-19 more complicated.
Healio spoke with William A. Werbel, MD, PhD, assistant professor of medicine at the Johns Hopkins University School of Medicine and associate director of epidemiology and quantitative sciences at the Johns Hopkins Transplant Research Center, about treating outpatients with COVID-19 and what the best options are for vulnerable populations.
Healio: What are the main issues that need to be considered before treating a patient?
Werbel: The first key steps in considering the immediacy and route of treatment for a patient are, first, the severity of their current syndrome, ie, how sick they are, do they need to be hospitalized or otherwise urgently treated due to severe shortness of breath or other symptoms? And second, what is their overall risk profile for developing severe disease.
The latter calculus relates to many factors about an individual, most importantly their age (>70 years, for example, is highest risk). Medical conditions also matter, such as having obesity, kidney or lung diseases, or diabetes. Other important factors to consider are a person’s “immune status,” which is composed of the number of prior times they have been previously “exposed” to SARS-CoV-2 (ideally via vaccination and recent, updated boosting), but also with consideration to having been previously infected. Generally, the more prior exposures, the less likely someone is to have severe disease with a subsequent exposure. This needs to be further interpreted in the context of the strength of their immune system, ie, whether a person’s ability to respond to vaccination as well as generally fight off viruses is compromised by medications such as chemotherapy or having undergone organ transplantation.
Once a person is identified as being severely ill and/or infected and at higher risk for developing severe illness, then a patient and their provider can select among available antiviral drugs and pair the more appropriate medication to the patient. Ultimately, decision-making depends upon individual factors such as a person’s kidney and liver function, what medications they are taking, their age, whether they are or might be pregnant and how long it has been since they first noted symptoms. Importantly, emergency use authorizations limit use of antivirals for outpatients to within the first 5 to 7 days of symptoms, depending on the drug.
Healio: What’s best for older adults? How about for pregnant women and kids?
Werbel: There have been very few head-to-head treatments directly comparing antiviral medications for specific populations. Rather, there is a body of accumulated evidence to support the potential beneficial effect of certain medications and, as above, information regarding the potential side effects of certain medications and ability to choose one that is likely safer for a particular individual. In general, the two antiviral medications with the best effectiveness data, particularly in higher risk populations, are the oral pill Paxlovid (nirmatrelvir/ritonavir, Pfizer) and the IV medication Veklury (remdesivir, Gilead). There is less, and more conflicting data, for use of Lagevrio (molnupiravir, Merck).
The main consideration for Paxlovid is the potential for drug-drug interactions with many common medications; this may be more challenging for adults who take many medications, some of which would need to be lowered or stopped if taking this antiviral. There are also recommended dose adjustments for people with kidney disease, and the drug is not recommended for people with severe kidney or liver disease. There are less available data for use of this drug in pregnant persons, and it is not recommended for children aged younger than 12 years.
Remdesivir is available only as an IV formulation, which is a major limitation, but it has good safety data in children and pregnant persons; thus, if accessible, this drug would generally be preferred for those groups. There are many fewer drug-drug interactions, although there has been some signal for mild liver enzyme elevations. The package label recommends against use in people with kidney disease, but many practitioners have safely used this drug in this setting.
Molnupiravir is not authorized for use in children aged younger than18 years and advised against use in pregnant persons because of the potential for mutagenicity. There is also package labeling recommending that men use contraceptives for 3 months following use. This drug, however, does not have major drug-drug interactions and does not need adjustment for liver or kidney disease, so this makes it otherwise easier to prescribe.
Healio: Is there a resource that physicians can check before prescribing something?
Werbel: There are several excellent resources for physicians regarding antiviral prescribing.
The University of Liverpool has a useful website to assess drug interactions.
The Infectious Diseases Society of America also has a list of some key drug-drug interactions for nirmatrelvir/ritonavir, with some recommended dose adjustments.
The CDC has a side-by-side comparison of medications and an ability to check local availability.
HHS/ASPR has resources for therapeutic decision-making.
Healio: What is your main message regarding outpatient COVID-19 treatment options in the current SARS-CoV-2 climate?
Werbel: My main message is that there are several available antiviral medications that have the potential to reduce serious disease in high-risk individuals; this is one key reason why COVID-19 in 2023 is very different from COVID-19 in 2020. It is important that patients and their providers understand their own risk for developing severe COVID-19 based on their age, medical conditions, number of prior vaccinations and immune system. If a person is considered higher risk, they should seek early treatment if they become infected or ill. The available medications have pros and cons, so it makes sense to plan ahead and understand which medication might be the best fit based on their profile — this is a good discussion to have with one’s doctor.
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