In the battle against COVID-19, antiviral drugs have emerged as a clinical tool in preventing the progression from mild-to-moderate disease to severe illness, particularly when administered within 5 days of symptom onset. This insight highlights the crucial connection of education, preparedness, and health care in mitigating severe COVID-19-associated outcomes, including death.

Despite recommendations for antiviral use among high-risk adults to prevent severe COVID-19, its uptake remains low at ≤35% in the general adult population. A review of 110 high-risk Veterans Health Administration (VA) patients—all vaccinated and with mild-to-moderate COVID-19— revealed reasons for underuse: 20% declined the offered treatment. In contrast, 80% were not offered any treatment.

“We focused on eligible patients who truly didn’t get antiviral treatment, rather than on estimating the amount of use overall,” said coinvestigator Paul A. Monach, MD, PhD, chief of rheumatology, VA Boston Healthcare System. “The electronic search indicated that only 28% of patients received antivirals, but we found during chart review that additional patients did receive antivirals, just not in a way easily found by searching VA pharmacy records. The actual amount of use is about 50%, although that calculation isn’t in the final version of the paper, so it shouldn’t be considered peer-reviewed.”

“Limited information is available on reasons for failure to prescribe antivirals to eligible patients with COVID-19,” the study investigators wrote. “Algorithms to determine these reasons using electronic medical records (EMR) review would have to be based entirely on text data; therefore, measures to develop them would likely be prone to bias.”

For those not offered treatment, reasons included symptom duration exceeding 5 days (22.7%), potential drug interactions (5.7%), or lack of symptoms (22.7%). And nearly half (48.9%) gave no reason beyond mild symptoms. Notably, 55.8% of these patients only received follow-up calls without any treatment discussion, underscoring the need for targeted interventions to address antiviral underuse.

Improving Antiviral Uptake

“On the provider side, a few patients fewer than we expected were not offered treatment because of drug interactions with Paxlovid,” said Monach. “However, other antivirals are available, and the safety of discontinuing another drug for 5 days to take Paxlovid probably varies a lot and is safe for most drugs. Finally, about 40% of patients who didn’t receive an antiviral weren’t offered one and didn’t have a contraindication that we could find in the chart. Therefore, some providers need an education that high-risk patients with mild symptoms are exactly the target population – although it was clear from the review that most providers in emergency departments and primary care know that.”

Monarch explains how there should be primary care follow-up calls after patients have gone home, especially regarding test results because this could be a key area for improvement. Initially, these calls emphasized isolation and visiting the emergency room if symptoms worsened, advice that was apt during 2020-21. However, with the availability of antivirals, this approach is now considered outdated and misdirected. It is recommended that healthcare institutions update their guidance for staff responsible for these calls to include current treatment options, ensuring that the advice given is relevant and comprehensive.

Among the reasons for not providing treatment, delays in seeking care and potential drug interactions were noted, alongside a notable percentage of patients who were not given any explanation for the lack of treatment offered, particularly if their symptoms were considered mild. Furthermore, many of these patients did not have antiviral treatment discussed with them, pointing to a gap in patient management, and the need for improved strategies to ensure that eligible patients are informed and offered potentially life-saving antiviral treatments.

“Although the original studies were done in unvaccinated patients, it is clear from our previous work and others’ work that some patients remain at high risk for severe COVID-19 despite vaccination and boosting,” explains Monach. “Studies in high-risk patients indicate the benefit of antivirals for them as well, it’s just not clear whether the risk is reduced by 50% or more than that.”

Monarch says patients with comorbidities should be considered for antivirals. “There’s general agreement that patients who are immune-suppressed or have serious lung, heart, or kidney disease should be offered treatment. There’s also general agreement that at some point age confers high risk even in a patient without other risk factors.”

Overall, antiviral drugs are undervalued clinically in the ongoing battle of COVID-19 in preventing severe disease outcomes. While clinicians continue managing the complexity of COVID-19, they need to consider to ensure that every patient eligible for antiviral therapy is informed, offered, and supported through their treatment journey.

Reference

Monach PA, Anand ST, Fillmore NR, La J, Branch-Elliman W. Underuse of Antiviral Drugs to Prevent Progression to Severe COVID-19 — Veterans Health Administration, March–September 2022. MMWR Morb Mortal Wkly Rep. Published January 25, 2024. Accessed January 31, 2024. DOI: http://dx.doi.org/10.15585/mmwr.mm7303a2