The perfect storm: In­fluenza and RSV during the season of COVID-19

Most of North America is now well into what we consider our cold and flu season, when influenza and respiratory syncytial virus (RSV) peak. Every season brings something new, and the 2020-2021 season has been no different. We have all heard a great deal about coronavirus disease 2019 (COVID-19) throughout 2020, and it is the one big variable to this flu season. In practicing general pediatrics for over 30 years, I have seen influenza hit as early as November and still hang around as late as April. RSV seems to come a little later, around January to February, and when the two overlap, pediatricians’ offices are swamped, and hospital beds are full. This year, what does having COVID-19 in circulation mean to pediatricians at the time of year that’s considered the sick season?

Influenza, RSV, and COVID-19 symptoms

Influenza typically presents with a sudden onset of fever and chills with cough and headache. Myalgias, malaise, sore throat, and rhinitis are also common, as well as abdominal pain with vomiting and diarrhea. The presentation will vary, with some patients appearing with severe upper respiratory symptoms and others with few respiratory symptoms yet high fever and fatigue. Influenza is an important cause of otitis media and can cause acute myositis with calf tenderness. In infants, influenza can present as a sepsis-like illness or croup, bronchiolitis, and pneumonia. Most children will recover in 3 to 7 days, but even previously healthy children can develop severe symptoms and complications such as febrile seizures or encephalopathy. Death from influenza-associated myocarditis has been reported.¹

Respiratory syncytial virus causes acute respiratory infections in individuals of all ages but is one of the most common early childhood diseases. Most infants infected with RSV will have upper respiratory symptoms, and 20% to 30% will develop lower respiratory symptoms such as bronchiolitis and pneumonia with the first infection. Infection with RSV will begin with rhinitis and cough and can progress to increased respiratory effort with tachypnea, wheezing, crackles, and retractions. Fever may be high or low grade, and apnea may occur in those infected during the first few weeks of life. From 1% to 3% of all children infected with RSV in the first 12 months of life will be hospitalized with lower respiratory infections, but most are less than 6 months of age. At increased risk of severe disease are infants with prematurity, chronic lung disease of prematurity, and certain types of congenital heart disease. Yet mortality is rare when supportive care is available. Almost all children are infected by RSV at least once by the age of 24 months, and reinfection is common.²

Influenza is spread person to person, primarily through large-particle respiratory droplet transmission requiring close contact between individuals, but is thought to also spread via transmission from contaminated surfaces by hand transfer of influenza virus to mucosal surfaces. It may have the airborne transmission of small-particle aerosols in the vicinity of an infectious person. Similarly, RSV is also spread via direct or close contact with contaminated secretions either by large-particle respiratory droplets or persisting on surfaces for several hours, allowing hand to mucosal surface spread.^1,2 Now that COVID-19 in the mix, health care providers (HCP) see how difficult it will be to determine which patients are infected because there are so many similarities. Health care providers need to remember that coinfection can exist, further complicating diagnoses.

What's new with influenza vaccines

Distinguishing between influenza and RSV can also be difficult, with many symptoms overlapping, but often, with a good history and a full physical, a proper diagnosis is possible. Some distinctions include loss of taste and smell, which may lead pediatricians to think it might be COVID-19 in older patients. As children are harder hit with influenza, the droopy red eyes and high fever with cough should lead pediatricians toward an influenza diagnosis in younger patients. Although RSV can present with high fever, it will cause more wheezing in infants and toddlers.

The incubation period for influenza is 1 to 4 days compared with 2 to 8 days with RSV; 4-6 days being the most common. Now we add COVID-19 to that picture, with a 2- to 14-day incubation period, and it becomes a numbers game and a discussion about who to test. Influenza testing should be done when it will influence clinical management. The decision to test is related to the level of suspicion, local influenza activity, and the sensitivity and specificity of available tests. Nasopharyngeal swabs have the highest yield, but midturbinate nasal swabs are acceptable, and ideally, specimens should be obtained in the first 4 days of illness because the quantity of virus shed decreases rapidly beyond that point as the illness progresses. Rapid RSV testing is also available with nasopharyngeal specimens, and the sensitivity in small children is 80% to 90% with most, but less reliable in older children. False-positive results are likely to occur during periods of low viral circulation for both RSV and influenza testing.^1,2

Multiplex assays are available using reverse transcriptase-polymerase chain reaction (RT-PCR) and may be preferred because of increased sensitivity. These tests should be interpreted with caution as more than one virus can be detected: Some viruses can persist in the airway for weeks after the acute infection has resolved (eg, RSV, rhinovirus, and adenovirus).² We may even add COVID-19 to this list, as some patients have tested positive for weeks after their symptoms have resolved.

Managing RSV

No available treatment shortens the course of RSV bronchiolitis or hastens the resolution of symptoms, but supportive care with hydration and careful monitoring of respiratory status is the primary management to alleviate symptoms in the patient. Hospitalization for supplemental oxygen and, if necessary, mechanical ventilation may be required. Neither ßadrenergic agents nor the use of racemic epinephrine is recommended for use in first-time wheezing associated with RSV. Bronchodilators do not improve oxygen saturation or time to resolution of illness. For those at high risk, palivizumab is a monoclonal antibody administered by intramuscular injection and recommended by the American Academy of Pediatrics for monthly administration during the RSV season.⁴ There are no changes to these recommendations this year.

Influenza may be treated with antiviral medications, including neuraminidase inhibitors (eg, oral oseltamivir, inhaled zanamivir, or intravenous peramivir), endonuclease inhibitors (eg, oral baloxavir marboxil), and adamantanes (eg, amantadine and rimantadine). Oseltamivir is the drug of choice and has been approved for use down to 2 weeks of age. Widespread resistance to adamantanes with H3N2 and H1N1 strains since 2005 has led to neuraminidase inhibitors as the only recommended antiviral drug for influenza. Treatment should be initiated early in the illness as the greatest effect on outcome is achieved if given within 48 hours of the onset of symptoms.1 In one randomized controlled trial, baloxavir marboxil had greater efficacy than oseltamivir in adolescents and adults with influenza B virus infection.³

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Conclusions

Pediatricians know the when, the how, and the treatment for influenza and RSV, but when COVID-19 is added to the winter mix, the puzzle becomes complicated. Health care providers are already seeing a less severe influenza and RSV season due to the COVID-19 precautions, with individuals wearing masks and continued physical distancing. Some have witnessed a significant drop in the number of febrile illnesses with secondary otitis or sinusitis presenting in office. When daycare centers and schools refuse sick children and clean more efficiently, the spread of any infectious disease will slow. Pediatricians may not remember a fall season with so few group A streptococcal infections. The caveat to this is what it will mean if and when children get coinfections of COVID-19 and influenza or RSV. This is the question of the day as influenza and RSV appear in the community.

What HCPs can do in the meantime is test as many patients as they can to determine the infecting organism and the most appropriate treatment. Antivirals won’t help with RSV and have limited use with COVID-19 infections. Because HCPs know that the 2018-2019 influenza vaccine reduced pediatric influenza A-associated hospitalizations and emergency department visits by 40% to 60%,⁵ this season’s approach has been to immunize as many children with the influenza vaccine and test as many as possible for influenza and COVID-19. There are many single testing options available and a few multiplex assays using RT-PCR, mostly in hospital labs. However, as the flu season marches on, I anticipate more assays to be available for use in the office as well.

References

1. Kimberlin DW, ed. Red Book 2018, 31st edition, American Academy of Pediatrics; 2018.

2. Respiratory syncytial virus. In: Kimberlin DW, ed. Red Book 2018, 31st edition, American Academy of Pediatrics; 2018:682-692.

3. Influenza antiviral medications: summary for clinician. Centers for Disease Control and Prevention. Updated November 30, 2020. Accessed December 7, 2020. https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm

4. Respiratory syncytial virus infection (RSV): for healthcare professionals. Centers for Disease Control and Prevention. June 26, 2018. Accessed December 7, 2020. https://www.cdc.gov/rsv/clinical/index.html

5. Vaccine effectiveness against pediatric influenza hospitalizations and emergency visits. American Academy of Pediatrics. Accessed December 7, 2020. https://pediatrics.aappublications.org/content/146/5/e20201368

6. American Academy of Pediatrics. Recommendations for prevention and control of influenza in children, 2020-2021. Accessed December 7, 2020. https://pediatrics.aappublications.org/content/146/4/e2020024588