Practical Insights for NPs and PAs: FAQs on Assessment and Treatment of Acute Outpatient COVID-19

Key Takeaways

• COVID-19 rebound can occur with or without antiviral treatment, and there are no recommendations to repeat or extend a treatment course in this scenario.
• It is unnecessary and impractical to measure post–COVID-19 vaccination antibody titers in individual patients.
• Corticosteroids have no role in the outpatient treatment of acute COVID-19.

In this commentary, Jason E. Farley, PhD, MPH, ANP-BC, FAAN, FAANP, AACRN, addresses the most important questions asked by nurse practitioners and physician associates/physician assistants in a series of recent webinars reviewing practical case studies in outpatient COVID-19 management.

What percentage of patients experience COVID-19 rebound after treatment with nirmatrelvir plus ritonavir? Do you recommend extending the treatment course in those situations?
In clinical trials of nirmatrelvir plus ritonavir, the incidence of COVID-19 rebound following the 5‑day treatment course was approximately 2%. Patients treated with other antiviral agents (eg, molnupiravir) and even untreated patients also can experience COVID-19 rebound—it is not unique to treatment with a specific antiviral agent.

Recently published data suggested that culturable virus could be found in untreated patients infected with SARS-CoV-2 past the 10-day isolation window; they continued to have positive tests after 10 days. That said, there is no current recommendation to either extend the isolation period or to extend treatment duration when or if COVID-19 rebound occurs.

How do you manage a fully vaccinated patient who has had several previous COVID-19 infections—the most recent being 4 months ago, treated with an antiviral—and is now reinfected?
There are limited data on repeated treatment courses in patients who have more than 1 COVID‑19 infection. I would want to find out the answers to several questions before deciding how to proceed, including:

• How did the patient respond to antiviral treatment the last time they were treated?
• Did the patient have a negative repeat rapid antigen test within the treatment period, or could this be prolonged viral shedding (eg, in a patient with immunocompromise)?

These questions may help to decide whether to treat with the same antiviral as before or treat with a different antiviral or monoclonal antibody (if effective against the currently circulating variant and accessible to the patient).

Given the patient’s history of multiple infections, I would consider an investigation into whether there is an underlying immunodeficiency that may have led to an inadequate vaccination response and could be responsible for the sequential COVID-19 infections.

Are there laboratory tests to determine post–COVID-19 vaccination antibody status in patients with immunocompromise?
There are tests to measure antibody levels. There is also a correlation between antispike immunoglobulin G (IgG) titers post vaccination and incidence of symptomatic COVID-19 infection at the population level that is used to evaluate vaccine effectiveness. Unfortunately, IgG is not useful for clinical decision making for an individual as a standardized antibody titer has not been established for the prevention of infection and/or disease progression.

Checking antibody titers in an individual patient may give people a misleading view of the benefits of COVID-19 vaccination. Vaccines work at both the cellular and humoral level. Cellular immunity involving T-cells and natural killer cells is a critical component of mobilizing the entire cellular response. The measurements of cellular immunity are heterogenous (ie, difficult to standardize) and expensive.

There is no practical utility in drawing an IgG titer in an individual patient, as it does not give us information to inform how they should or should not change their behavior in terms of COVID-19 prevention.

Is there a role for corticosteroids in patients with acute COVID-19?
Dexamethasone remains a treatment option within the National Institutes of Health (NIH) list of treatment options for hospitalized patients with acute COVID-19 who require oxygen therapy.

If you look at the clinical pathology and the time course of symptom burden, the point of using a corticosteroid is to get that anti-inflammatory response on board once it is clear that the antiviral response has not been successful. The point of using an anti-inflammatory such as dexamethasone is to try to prevent the cytokine storm and processes that lead to consequences such as pleural effusion and acute respiratory distress syndrome.

In the outpatient setting, the NIH recommends against use of corticosteroids due to lack of benefit. 

Your Thoughts?
What question related to outpatient management of acute COVID-19 comes up most often in your clinical practice? Join the conversation by posting a comment below.