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When a patient presents with acute respiratory symptoms this fall, clinicians should consider three options: influenza, COVID-19, or co-infection, CDC experts said.

And given the likelihood that influenza and SARS-CoV-2 will be co-circulating in the community, clinicians should pay special attention to local surveillance data about each virus.

On a , CDC officials reminded clinicians that not only do influenza and COVID-19 have overlapping signs and symptoms, but co-infection with both has been documented in both case reports and case series.

"The only difference is loss of smell and loss of taste ... [which] has not been reported with influenza virus infection," said Timothy Uyeki, MD, of the CDC. "The fact that co-infection can occur has implications."

He elaborated on the largest case series of patients with influenza and SARS-CoV-2 co-infection: a series of 93 adult patients hospitalized with COVID-19 in Wuhan, China, where 49.5% had serologically diagnosed influenza infection.

But he added that there are several unknowns, including the frequency of co-infection, what it means about the severity of either illness, and what the risk factors are for co-infection.

Co-infection, or even distinguishing SARS-CoV-2 from influenza, is particularly important because of the implications of treatment. For example, Uyeki noted that dexamethasone is recommended for severe COVID-19 infection in hospitalized patients, but corticosteroids actually prolong viral replication in influenza.

Testing then becomes key in distinguishing the viruses, and Uyeki said that, as noted by Department of Health and Human Services officials, there are several kinds of "multiplex" assays that received FDA emergency use authorization (EUA), including some that received EUAs "this week," he added.

These are multiplex nucleic acid detection assays that can detect both influenza A and B viruses and SARS-CoV-2 simultaneously in respiratory specimens. Turnaround times for results within the lab vary quite a bit, from 20 minutes to 8 hours.

"Most are for high-complexity labs, some are for moderate complexity, and there's one CLIA [Clinical Laboratory Improvement Amendments]-waived [assay]," Uyeki said. He predicted that more assays will receive EUAs, and said that clinicians should refer to the FDA's website for the latest information.

He also stressed the importance of telemedicine, which gained new prominence during the COVID-19 pandemic, adding that providers might consider implementing "phone triage" lines for patients at higher risk of influenza complications if they have symptoms of acute respiratory illness.

Uyeki urged clinicians to encourage their high-risk patients to call their provider "as soon as possible" if they have these symptoms "with or without a fever," especially if they may benefit from early antiviral treatment for influenza.

He added that interestingly, patients at high risk for influenza complications, and who may benefit from early antiviral treatment, mirror those at higher risk for SARS-CoV-2:

• Adults ages 65 and older

• Pregnant/postpartum women

• American Indians/Alaska Natives

• People with underlying medical conditions -- such as pulmonary, cardiac, and neurologic problems -- and who are immunosuppressed or have a body mass index over 40

• Residents of nursing homes/chronic care facilities

In addition, children ages 18 and younger receiving long-term aspirin therapy, as well as children under age 2, may also be considered for early antiviral treatment, Uyeki said.

Angela Campbell, MD, of the CDC, reviewed 2019-2020 influenza data. While influenza activity dropped off sharply with the COVID-19 pandemic in the U.S., cumulative hospitalization rates among pediatric and young adult patients were the highest in the last 10 seasons, and 188 pediatric influenza deaths tied with 2017-2018 as the highest number recorded, she said.

She also warned that while community mitigation measures helped stem the tide of influenza and COVID-19 in the spring, "influenza viruses are currently circulating in locations where less mitigation is exercised."

Campbell also dismissed the idea that these measures are the best way to prevent influenza, saying "vaccination is still the best way to prevent [flu]."

"Every flu season is unpredictable, and in this unprecedented year, I'm not going to predict the future," she said.

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