As respiratory viruses and COVID-19 variants lurk seemingly everywhere, here’s how best to detect and differentiate.
It is hard to believe that in the fall of 2019, the No. 1 winter viral threat to the health of our communities was influenza. Based on its quasi-predictable genetic markers, we urgently promoted vaccination, stocked up on Clinical Laboratory Improvement Amendments–waived test kits, and prescribed antiviral medications for patients and their families to protect our communities and reduce the potential for spread. Most of us were not prepared for what was coming and how it would dwarf the severity and impact of a viral pandemic that had been the historic standard by which we measured suffering.
COVID-19’s global impact has touched every aspect of our lives and precipitated a redesign of health care as we knew it. The morbidity and mortality seen in the senior and chronically ill populations have not been seen in children, although, as of this writing, hospitalizations for children have been spiking across the United States. It is hard to estimate the incidence and severity from reported data, and the variants and availability of vaccines make it even more so. Before Omicron, 0.1% to 1.8% of children with COVID-19 needed hospitalization, whereas 0.5% to more than 10% of adults (increasing with age) were hospitalized. Less than 0.03% of infected children died; for adults, that rate was about 1% and significantly higher in those over age 65 years. The fatality rate for children is dwarfed by that caused by unintentional accidents.1
Hospitalization for influenza and COVID-19 in children has been most notable with specific underlying conditions. A retrospective analysis of 315 laboratory tests confirmed SARS-CoV-2, and 1402 laboratory tests confirmed cases of influenza A and B showed a significant increase in hospitalization for COVID-19 in children who had a neurologic diagnosis with global development delay or seizures (20% vs 8%). COVID-19 and seasonal influenza had similar rates of hospitalization, intensive care unit admission, mechanical ventilation, and duration of ventilator support.2
As we became obsessively careful with sanitizers, masks, social distancing, and quarantines, we came to recognize that COVID-19 is very different from influenza. COVID-19 is more contagious and more significant in short- and long-term morbidity yet more variable in its manifestation from asymptomatic to rapidly fatal. Symptoms can be nearly identical and only testing can differentiate, but the overlap seems to stop there, with COVID-19 adding a more diverse menu of symptoms and complications. The Table lists some similarities and differences in symptoms, complications, and the diagnosis and treatment of influenza and COVID-19.
Most pediatricians used a fever and fatigue threshold for testing for influenza, but COVID-19 testing is done for anyone, even those with no symptoms. Incidence and outcomes are all local, and following local epidemiological reports is essential for helping to differentiate what is affecting communities, but with COVID-19, vaccination rates, infection precautions such as masks, and social determinants of health can have a disproportionate impact.
We often overlook some of the complicating features that are so infrequent with influenza in kids but can be devastating. A major difference between influenza and COVID-19 is the expectation that, with influenza, once the illness has subsided, the impact of that infectious agent is over, with the secondary infection or organ damage as separate residua. COVID-19, on the other hand, has the potential to directly incite the immune system and can have lingering effects that are disabling and potentially fatal.
When discussing COVID-19 infection with families, pediatricians will often include a caution for the infrequent possibility for multisystem inflammatory syndrome in children (MIS-C), but probably the most common and actionable concern is cardiac, especially for adolescent athletes. (Of note: Since June 2020, there have also been several reported cases of MIS in adults3). We have come to recognize that myocarditis, pericarditis, and rhythm abnormalities are common to both influenza and COVID-19 yet more common, lingering, and possibly more subtle with COVID-19. The immediate focus on COVID-19 has made it more of a concern and promulgated a set of recommendations for screening patients with specific symptoms and a severity-related algorithm and staged return to sports for adolescent athletes. Although the cardiac problems can be associated with influenza or COVID-19 infection, COVID-19 has the added etiologies of MIS-C and an adverse effect of the vaccine, especially in adolescent male patients.
Both the influenza and the COVID-19 messenger RNA vaccines have seen associated with Guillain-Barre syndrome, but not at the frequency seen with actual infection. The incidence after vaccination is rare enough and the public and individual health benefit large enough to recommend vaccination against both.4
Certainly, there are so many other areas of overlap, especially as we see new formulations of vaccines that can adapt and generalize antigens that may provide better specificity and immunocompetence. However, for now we continue to deal with a hit-or-miss influenza vaccine and viral mutations that can reduce vaccine effectiveness and, unfortunately, feed the reluctant and refusers with self-justification. The elevation of COVID-19 and its identity as a pandemic magnifies the reality of both our vulnerability and our potential to effectively respond with the development of vaccines and treatments.
1. Accident statistics. Stanford Children’s Health. Accessed January 10, 2021. https://www.stanfordchildrens.org/en/topic/default?id=accident-statistics-90-P02853
2. Song X, Delaney M, Shah RK, Campos JM, Wessel DL, DeBiasi RL. Comparison of clinical features of COVID-19 vs seasonal influenza A and B in US children. JAMA Netw Open. 2020;3(9):e2020495. doi:10.1001/jamanetworkopen.2020.20495
3. Multisystem inflammatory syndrome in adults (MIS-A). Centers for Disease Control and Prevention. November 13, 2020. Accessed January 10, 2022. https://www.cdc.gov/mis/mis-a.html
4. Guillain-Barré syndrome and vaccines. Centers for Disease Control and Prevention. Updated August 25, 2021. Accessed annuary 7, 2021. https://www.cdc.gov/vaccinesafety/concerns/guillain-barre-syndrome.html
5. Pilarowski G, Lebel P, Sunshine S, et al. Performance characteristics of a rapid severe acute respiratory syndrome coronavirus 2 antigen detection assay at a public plaza testing site in San Francisco. J Infect Dis. 2021;223(7):1139-1144. doi:10.1093/infdis/jiaa802
6. Interim guidance for antigen testing for SARS-CoV-2. Centers for Disease Control and Prevention. Update September 6, 2021. Accessed Jan 10, 2022. 2021.
7. Interim guidelines for COVID-19 antibody testing. Updated September 6, 2021. Accessed January 10, 2022. https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antibody-tests-guidelines.html.