How to Distinguish Among COVID, Flu, and RSV in a High-Risk Patient

Charles P. Vega, MD


December 15, 2022

Dr Vega's Take

Those of us who have been hoping for a nice, quiet season for upper respiratory infections (URIs) have once again been rudely disappointed by an increase in rates of URIs during fall 2022. But this year has been different from the cold and flu seasons of 2020 and 2021. Instead of SARS-CoV-2 dominating all cases of URIs, respiratory syncytial virus (RSV) and influenza have made a dramatic comeback.

This year's influenza season arrived early, with a prevalence similar to what we expected to see in January of previous flu seasons. By November 5, 2022, the US Centers for Disease Control and Prevention (CDC) estimates that there were at least 2.8 million illnesses related to influenza in the United States. In all, 23,000 of these patients were hospitalized and 1300 patients had died because of influenza.

The spike in cases of influenza is bad enough, but rates of RSV are also unseasonably high. The rate of RSV-related hospitalization by October 2022 had exceeded the rate of these hospitalizations during the previous two winter seasons. Children have bore the brunt of this RSV outbreak, but there is strong concern regarding how this outbreak will affect vulnerable adults like Agnes.

The situation might be more tolerable if rates of SARS-CoV-2 infection were declining, but this is not the case (take a mandatory 30-second break now to stare into space and wonder what we could have done to deserve all this; personal note: I came up with 31 reasons in just 18 seconds!). National rates of COVID-19 have been rising slightly over the past 2 months, and the rate of hospitalizations for COVID-19 has been stable. Each week, more than 2000 people are still killed by SARS-CoV-2 infection in the United States.

Agnes presents with what appear to be nonspecific symptoms: cough, myalgia, and fever. Can we discriminate among important viral infections on the basis of patient symptoms? An analysis of 200 patients with COVID-19 and influenza found many similar clinical characteristics when comparing the two infections. Patients with COVID-19 were more likely to have fever and altered mental status, whereas patients with influenza were more likely to report myalgias and nausea or vomiting. Sore throat was also more common in the influenza cohort, but bear in mind that this study focused on patients in 2021. Currently, circulating variants of SARS-CoV-2 are more likely to promote sore throat compared with previous variants of SARS-CoV-2.

Can't Diagnose by Symptoms Alone

Symptoms of influenza, SARS-CoV-2, and RSV are too similar to reliably differentiate when all three viruses are in wide circulation, and this is particularly true among children. At the same time, the prevalence of these viruses will vary from week to week. Before ordering tests or treatments for a URI, healthcare professionals should determine the prevalence of RSV, SARS-CoV-2, and influenza in their local communities and base clinician decisions on those data. Epidemiology data have a significant impact on the accuracy of clinical testing and care for viral URIs.

Molecular testing for viral URIs is important when such testing affects the potential management of patients. For this patient, a positive test for influenza and/or SARS-CoV-2 should prompt immediate and urgent treatment with an anti-influenza drug, such as oseltamivir or baloxavir, or an anti–COVID-19 drug, such as nirmatrelvir-ritonavir, because this patient is at high risk for complications from both influenza and COVID-19. There is no specific treatment for the vast majority of adults with RSV, but the amount of time Agnes needs to stay in isolation will be dictated by those PCR results.

A rapid multiplex PCR test that includes testing for RSV, SARS-CoV-2, and influenza will be ideal for this patient. After a 15- to 30-minute wait for results, we can discharge the patient with the right prescriptions. The sensitivity of the PCR tests is better than that of antigen testing, making clinicians more confident in either a positive or negative result.

Time is of the essence when starting treatment for COVID-19 or influenza. These antiviral agents are most effective when initiated as soon as possible after the onset of symptoms. Agnes needs to understand this, and it is worthwhile for the treating healthcare professional to ensure a plan for her to initiate medication that same day.

What Do You Think?

This clinical scenario plays out thousands of times daily in healthcare settings around the country. What is your experience in managing URI in the fraught times we live in? I look forward to reading your comments and sharing your feedback next month!

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