Testing for COVID-19, influenza virus, and respiratory syncytial virus (RSV)—along with prompt antiviral treatment of patients at high risk for poor outcomes—is increasingly important because clinical presentations of each have considerable overlap, cases have presented outside of the typical season, and the rate of coinfection has increased considerably.
The guidance comes from a recent Peer Exchange panel hosted by parnter publication Contagion® and moderated by Tina Tan, MD. Panelists also discussed patient populations at increased risk for poor outcomes and potential strategies for mitigating disparities in the availability of testing and treatment due to structural barriers and supply chain issues.
According to the panelists, the populations at high risk for poor outcomes from respiratory viruses include individuals over age 65 years, pediatric patients (particularly infants younger than 6 months), immunocompromised individuals (eg, those living with HIV or cancer, or who are taking biologic drugs), and persons with comorbidities such as diabetes or chronic obstructive pulmonary disease. However, poor outcomes could occur with any patient, said Wendy Wright, DNP, ANP-BC, FNP-BC. Tan noted that she has seen severe RSV disease in patients not typically thought to be at high risk.
Measures to prevent infections (eg, influenza vaccination) in low-risk individuals who are in close contact with high-risk individuals (eg, older siblings of infants younger than 6 months) are an important part of avoiding severe illness, said Kevin Michael Reiter, MD, PA. He added that symptomatic influenza virus infections can trigger congestive heart failure, atrial fibrillation, and coronary disease in older individuals and noted that the influenza vaccine is protective against myocardial infarctions in patients with coronary disease.
“Folks with chronic conditions, chronic liver disease, chronic kidney disease…need to be the most protected because they are, by far, the most vulnerable,” he said. “That starts with protecting the younger, healthy folk.”
Others more vulnerable to respiratory infections include members of Black, Hispanic, and American Indian populations, who tend to have relatively low rates of vaccination against COVID-19 and influenza virus and to be employed in “essential working positions” with high person-to-person contact, said Jacinda Abdul-Mutakabbir, PharmD. Tan added that the COVID-19 pandemic highlighted disparities in these populations, and that health care providers should focus on improving access to vaccines, health care, and treatments for these patients.
Reiter noted that the considerable overlap in clinical presentations for COVID-19, influenza virus, and RSV underscores the importance of viral testing. Before the pandemic, he and his urgent care colleagues assumed a diagnosis of influenza virus if a patient presented with high-grade fever, body aches, fatigue, headache, sore throat, cough, and nasal congestion; however, many strains of COVID-19 present with similar symptoms. Reiter added that many respiratory viruses now are presenting earlier in the year because of the lack of low-level exposure and resulting buildup of immunity due to the isolation at the height of the pandemic.
“We had a saying in our urgent care: If it walked like a duck and talked like a duck, it was probably a duck in the peak of flu season,” he said. “That’s not true anymore because COVID-19 came to town, and with the varying strains of COVID-19 that we’ve seen over the years, the presentations are so different.”
Priya Nori, MD, added that coinfection is also a possibility, and testing for RSV and influenza virus may be indicated for patients who test positive for COVID-19 at home but do not improve or respond to treatment as expected. “I would love to see in the next, let’s say, 18 months or so that there is an approved or at least authorized home test that can pick up all 3 of these viruses,” she said. “That would be a game changer in terms of access, speediness of treatment, and off-loading the health care system.”
Although clinicians often use the common presentations for each of the respiratory viruses to guide diagnosis, Wright noted that using the clinical presentation alone is not reliable, as more than 60 symptoms have been associated with COVID-19.
“All bets are off at this point,” she said. “I’d like to tell you that if they lose their smell and their taste, it’s definitely COVID-19, but with the Omicron strain we’re not seeing that as much. I had someone today who has a low-grade fever and diarrhea, and she’s positive for COVID-19.”
Wright also pointed out that clinicians often overlook RSV in adult patients, and that RSV and influenza virus are appearing outside of their typical seasons. She added that early testing and intervention are important but may be difficult with overextended urgent care centers and emergency departments.
Tan also noted that clinical presentations in children are often different than those in adults. For example, young children may only have fever and gastrointestinal symptoms as the initial presentation of influenza and not the sudden onset of fever, chills, cough, and sore throat often seen in adults. Additionally, older children often have a different RSV presentation than very young infants, who may only have labored breathing and apnea.
The frequency of respiratory coinfections has increased in recent years, although it is unclear whether coinfection leads to more severe illness or complications, said Nori. However, she added that access to antiviral drugs, particularly those for influenza virus, may be limited because of manufacturing delays and back orders, and clinicians should preferentially offer these drugs to patients at highest risk for poor outcomes (eg, those who are extremely young or old or who have serious comorbidities).
Reiter added that although the severity of the 2022-2023 influenza virus season was predictable based on activity in other parts of the world (eg, Australia), the United States was inadequately prepared as far as availability of diagnostic tests and antiviral therapies. He added that the predisposition for respiratory coinfections may have been caused by the early initiation of the influenza virus and RSV seasons.
Baloxavir marboxil, a single-dose influenza antiviral drug approved by the FDA for children aged 5 to 11 years and all individuals 12 years or older, may be able to prevent hospital admission if administered in the emergency department or outpatient setting, followed by a phone-based discharge follow-up procedure, said Nori. However, she noted that other options tend to be better for the inpatient setting and that concerns exist about lower viral susceptibility with this drug. Tan added that although it is approved for select children aged 5 to 11 years, the user must be able to swallow a capsule because the suspension form is not available this year.
Tan said patients hospitalized for or experiencing progressive disease with influenza virus and COVID-19 coinfection should receive antivirals targeting both viruses. “There’s no way to predict which one of these viruses is causing the bulk of what you’re seeing,” she said. “But we know that if [patients are] sick enough to be hospitalized, you do need to treat them for both.”
Nori added that for a patient at high risk of death, the theoretical risk for long-term effects from combining antiviral drugs is less than the risk for poor outcomes from the concomitant illnesses. She said that COVID-19 antiviral therapies such as nirmatrelvir/ritonavir (Paxlovid) and molnupiravir are underutilized by providers, particularly in Black and Hispanic communities with elevated risk for illness.
Reiter concluded that, if available, baloxavir with a COVID-19 antiviral drug could be an ideal strategy because it involves fewer pills and less frequent dosing, which helps with adherence. “It’s a great theoretic strategy, and hopefully we can make that a reality as we battle this coinfection and triple threat we’re dealing with.”