Considering Paxlovid’s Role in the Emergency Department Setting
Harry Kuperstein
A New Therapy
The FDA authorization of Pfizer’s Paxlovid (nirmatrelvir/ritonavir) antiviral therapy for mild-to-moderate symptomatic COVID-19 represents the introduction of the newest and potentially the most potent pharmaceutical intervention to mitigate COVID-19 disease severity. Other pharmaceutical interventions utilized throughout the COVID-19 pandemic have failed to prevent a deluge of hospital admissions, many of which led to prolonged hospital stays, severely limiting both ICU and general medicine floor capacities. Monoclonal antibodies (mAbs) remain a promising therapy that could prevent hospital admission outright or reduce the length of stay, but many of these options do not appear to withstand viral evolution with the proliferation of the Omicron variant. In addition, the remaining Omicron-responsive mAbs remain extremely constrained by supply and the challenges with delivering IV infusions. Now recently authorized, the NIH recommends Paxlovid as the preferred treatment for high-risk, non-hospitalized patients over the still Omicron-responsive mAbs based on the EPIC-HR trial.
Creating a Plan
Simultaneously, reported COVID-19 cases have taken a sharp downturn while the distribution of Paxlovid continues to ramp up. As of now (March 2022), Paxlovid is available at every approved DC pharmacy, as well as in other states, though in limited quantities. By the end of June 2022, Pfizer estimates that 10 million doses will have been delivered throughout the United States, with 10 million additional doses available by the end of 2022, enough for 6% of the U.S. population. Given that the Paxlovid supply will soon be far greater, healthcare systems must act during this relative lull in COVID-19 cases to consider how Paxlovid will be most efficiently distributed should the level of cases rise.
Any institutional plan to administer Paxlovid on a mass scale must incorporate early diagnosis and prioritization of high-risk groups. The EPIC-HR trial investigated the efficacy of Paxlovid within 5 days of symptom onset. The trial also showed the most benefit in groups such as those who were SARS-CoV-2 seronegative and 65 years or older. Central to the effective use of this new antiviral therapy will be the promotion of COVID-19 testing as a social norm as public health restrictions and mask mandates are rolled back. Local public health messaging must emphasize that a “return to normal” is driven mostly by the availability of pharmaceutical interventions (vaccines, antivirals, and mAbs) in addition to low baseline rates and high rates of vaccination. This emphasis ensures that the public continues to test and seek treatment expeditiously in the event of a positive result.
Test Early, Prescribe Early
While a robust primary care system may be best suited to test for COVID-19 and determine Paxlovid eligibility and benefit, emergency departments will inevitably see undiagnosed cases of mild to moderate COVID-19 in high-risk individuals, particularly during future surges where immediate access to outpatient healthcare may be strained. As such, emergency departments may be stewards in the proliferation of this new therapy requiring standardization of their criteria for high-risk individuals and broadening of these criteria if the supply of Paxlovid allows. Patients not meeting criteria for severe COVID-19 illness could be tested, prescribed Paxlovid to be taken outpatient, and discharged within a few hours without taking up emergency department beds.
Paxlovid remains a promising therapy due to its potential to alter the disease course of COVID-19, the unlikelihood of viral evolution if used judiciously, and its lack of controversy as compared to other pharmaceutical options (i.e., vaccines). It should be noted Paxlovid arrives at a time when SARS-CoV-2 has evolved to be seemingly less virulent, and the general population has immunity through vaccination or prior infection. In January, the Omicron wave is suspected of having infected 40% of the U.S. population. As a result, patients who are high-risk may not follow the same disease time course as clinicians have seen to date.
Impact of Paxlovid
Paxlovid may mitigate COVID-19’s burden on hospital admissions in high-risk populations, clearing up space in overwhelmed and overburdened emergency departments. A reduction in testing could be problematic to the use of Paxlovid during times of low caseloads. If used appropriately in conjunction with a priority on early and accessible testing, Paxlovid may represent a life-saving tool to complement vaccine-derived immunity in high-risk groups. This has beneficial implications for the ability of emergency departments to function, beyond the obvious benefit to mortality caused by COVID-19.
