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Sherrilyn and Ken Fisher Professor of Medicine
Division of Infectious Diseases
Johns Hopkins University School of Medicine
Dr Auwaerter: consulting fees: EMD Serono, Verily; contracted research: Humanigen; other financial or material support: Johnson & Johnson.
Patient Education and Vigilance Are Critical
The first key point that I emphasize to PCPs and specialists who have immunosuppressed patients (eg, active malignancies, rheumatology patients on significant immunosuppression) during the respiratory season is the importance of educating them to be aware that they should call their doctor as soon as possible with any influenza-like illness. There is a window of opportunity to help our patients. Still, it requires that we get that early laboratory diagnosis or make a clinical diagnosis and begin anti-influenza therapies as soon as possible. Regardless of patient risk factors, studies have strongly suggested that the earlier you start antiviral medicine, the more likely the clinical impact. I believe that educational component is essential to motivate patients to call.
We Are Likely Going to See More Influenza Activity Along With COVID-19 This Year
A second point for this respiratory season with SARS-CoV-2 in the mix would be the diagnostic considerations. As nonpharmacologic interventions for COVID-19 (such as mandated face coverings and restrictions on movement) are lifted, we can anticipate a greater amount of influenza activity than the previous year. Given the overlap in presentations between influenza and COVID-19, critical discernment will be essential. I believe an influenza diagnosis can often still be made on a clinical basis if there are high circulating rates of influenza infection in the community and either negative SARS-CoV-2 testing or low community rates of COVID-19. Unlike COVID-19, we have oral outpatient treatment options for influenza, so timely diagnosis and initiation of therapy should not be overlooked for outpatients, even during a pandemic.
Health Care Providers Have Options For Influenza Treatment
For most outpatients, influenza treatment is going to boil down to a pill-based therapy, either a 5-day treatment with oseltamivir—which has been available for over 2 decades—or the more recently approved endonuclease inhibitor baloxavir, a single-dose therapy that takes advantage of its very long half-life of up to 90 hours.
Both are effective treatments. The CAPSTONE-2 trial was a multi-national, double-blind, placebo- and oseltamivir-controlled trial that was recently published by Ison and colleagues. It was a head-to-head comparison of a single dose of baloxavir vs twice daily oseltamivir for 5 days or the corresponding placebo in a patient population that were at high risk for severe influenza, including highly immunosuppressed patients. The primary endpoint was time to improvement of influenza symptoms. This trial impressed me for several reasons. First, it is the patient population that we are most concerned about for influenza complications. Second, early treatment was emphasized with a requirement to start antivirals within 48 hours. Third, there was an interesting pattern of influenza strains that year, with almost half being influenza B. This allowed for a robust comparison of agents against both influenza A and B.
While oseltamivir was not effective against that particular strain of influenza B with similar time to improvement as placebo, baloxavir retained activity and diminished duration of illness by 1 day. Both agents were effective at reducing the course of disease for influenza A. Depending on your PCR platform, you may be able to make a timely determination of whether your patient has influenza A or B. Likewise, a knowledge of circulating influenza strains during a particular respiratory season can help to guide your choice of antiviral treatment for your patients.
Both agents are generally well tolerated. I keep in mind that oseltamivir has about a 10% incidence of nausea and occasional vomiting. In clinical trials, adverse effects associated with baloxavir have been very similar to placebo. Another piece of information that could be important, although it has not been clinically documented, is that baloxavir reduces viral shedding faster than oseltamivir which may have implications for reducing potential exposure risks in households.
Do Not Forget About Complications
The final point is that patients can still get ill even with timely treatment, and they need to be monitored if there are increased problems with shortness of breath, altered mental status, or ongoing fevers. Secondary infections, including bacterial or fungal, are important considerations in these circumstances. Immunosuppressed populations are particularly vulnerable to these potentially synergistic superinfections, with a heightened morbidity and mortality.
This brings me back to my first point that patient education and awareness are vital for early effective therapy.