Note: This is the sixty-seventh of a series of clinical briefs on the coronavirus outbreak. The information on this subject is continually evolving. The content within this activity serves as a historical reference to the information that was available at the time of this publication. We continue to add to the collection of activities on this subject as new information becomes available.

Clinical Context

The Northern Hemisphere is preparing for a potential flu season like no other, as the COVID-19 pandemic continues to take a severe toll. There is much concern about both contagious respiratory illnesses colliding and increasing death tolls. Although similar in manifestation, COVID-19 appears to be more deadly and less predictable than the flu. COVID-19 has also been shown to be more contagious (especially among susceptible populations and age groups) and is quickly and easily spread among people.

One of the many challenges of managing patients with either COVID-19 or flu (or, possibly, both) is identifying which virus is responsible for individual patient symptoms. A study by Tang and colleagues compared characteristics and outcomes of adults with acute respiratory syndrome (ARDS) due to influenza A virus subtype H1N1 (H1N1) or COVID-19. Their results were published in the July issue of Chest.^[1]

The study looked at 2 cohorts of patients who were infected with either COVID-19 or H1N1. One cohort studied 73 patients treated for ARDS secondary to COVID-19 in Wuhan, China, from December 2019 to February 2020. These were compared with the second cohort that consisted of 75 patients treated for ARDS secondary to H1N1 in Beijing, China, from March 2016 to December 2019. The median age of patients with COVID-19 was higher than that from H1N1, and more male patients were in the H1N1 cohort.

Cough and dyspnea were common in both the COVID-19 and H1N1 cohorts, but more patients in the H1N1 group reported a productive cough. In contrast, fatigue, gastrointestinal (GI) symptoms, and myalgia were more common in COVID-19 vs H1N1.

The study offered some guidance on how to possibly differentiate COVID-19 from H1N1 through clinical presentation. The severity of illness as measured by the Sequential Organ Failure Assessment (SOFA) score was greater at presentation in the H1N1 vs COVID-19 groups. Overall rates of mortality were similar in the two groups. Surprisingly, the risk for mortality adjusted for SOFA score was twice as high among patients with flu vs COVID-19.

From what researchers currently know of the virus, COVID-19 appears to be similar in adults and children, although children seem to be less likely than adults to develop severe illness. The current study by Song and colleagues compared clinical characteristics and outcomes among children with COVID-19 and flu.

Study Synopsis and Perspective

As winter approaches, distinguishing patients with COVID-19 from patients with flu will become a problem. To assist with that, Xiaoyan Song, PhD, director of the Office of Infection Control and Epidemiology at Children's National Hospital in Washington, DC, and colleagues investigated commonalities and differences between the clinical symptoms of COVID-19 and flu in children. Their results were published in the September 1 issue of JAMA Network Open.^[2]

"Distinguishing COVID-19 from flu and other respiratory viral infections remains a challenge to clinicians. Although our study showed that patients with COVID-19 were more likely than patients with flu to report fever, [GI], and other clinical symptoms at the time of diagnosis, the two groups do have many overlapping clinical symptoms," Song said. "Until future data show us otherwise, clinicians need to prepare for managing coinfections of COVID-19 with flu and/or other respiratory viral infections in the upcoming flu season."

The retrospective cohort study included 315 children diagnosed with laboratory-confirmed COVID-19 between March 25 and May 15 and 1402 children diagnosed with laboratory-confirmed seasonal influenza A or influenza B between October 1, 2019 and June 6, 2020, at Children's National Hospital. The investigation excluded asymptomatic patients who tested positive for COVID-19.

Patients with COVID-19 and patients with flu were similar with respect to the rates of hospitalization (17% vs 21%; odds ratio [OR] = 0.8 [95% CI: 0.6, 1.1]; P = .15), admission to the intensive care unit (ICU) (6% vs 7%; OR = 0.8 [95% CI: 0.5, 1.3]; P = .42), and use of mechanical ventilation (3% vs 2%; OR = 1.5 [95% CI: 0.9, 2.6]; P = .17).

The difference in the duration of ventilation for the two groups was not statistically significant. None of the patients who had COVID-19 or influenza B died, but 2 patients with influenza A did.

No patients had coinfections, which the researchers attributed to the mid-March shutdown of many schools, which they believe limited the spread of seasonal flu.

Patients who were hospitalized with COVID-19 were older (median age = 9.7 [range, 0.06-23.2] years) than patients hospitalized with either type of influenza (median age = 4.2 [range, 0.04-23.1] years). Patients older than 15 years made up 37% of patients with COVID-19 but only 6% of patients with flu.

Among patients hospitalized with COVID-19, 65% had at least one underlying medical condition compared with 42% of patients hospitalized for either influenza type (OR = 2.6 [95% CI: 1.4, 4.7]; P = .002).

The most common underlying condition was neurologic problems from global developmental delay or seizures, identified in 11 (20%) patients hospitalized with COVID-19 and in 24 (8%) patients hospitalized with flu (OR = 2.8 [95% CI: 1.3, 6.2]; P = .002). There was no significant difference between the two groups with respect to history of asthma, cardiac disease, hematologic disease, and cancer.

For both groups, fever and cough were the most frequently reported symptoms at the time of diagnosis; however, more patients hospitalized with COVID-19 reported fever (76% vs 55%; OR = 2.6 [95% CI: 1.4, 5.1]; P = .005); diarrhea or vomiting (26% vs 12%; OR = 2.5 [95% CI: 1.2, 5]; P = .01); headache (11% vs 3%; OR = 3.9 [95% CI: 1.3, 11.5]; P = .01); myalgia (22% vs 7%; OR = 3.9 [95% CI: 1.8, 8.5]; P = .001); or chest pain (11% vs 3%; OR = 3.9 [95% CI: 1.3, 11.5]; P = .01).

The researchers found no statistically significant differences between the two groups in rates of cough, congestion, sore throat, or shortness of breath.

Comparison of the symptom spectrum between COVID-19 and flu differed with respect to influenza type. More patients with COVID-19 reported fever, cough, diarrhea and vomiting, and myalgia than patients hospitalized with influenza A, but rates of fever, cough, diarrhea or vomiting, headache, or chest pain did not differ significantly in patients with COVID-19 and patients with influenza B.

Larry K. Kociolek, MD, medical director of infection prevention and control at Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, noted the lower age of patients with flu.

"Differentiating the two infections, which is difficult if not impossible based on symptoms alone, may have prognostic implications, depending on the age of the child. Because this study was performed outside peak influenza season when coinfections would be less likely to occur, we must be vigilant about the potential clinical implications of influenza and SARS-CoV-2 coinfection this fall and winter," Kociolek explained.

Clinicians will still have to use a combination of symptoms, examinations, and testing to distinguish the two diseases, said Aimee Sznewajs, MD, medical director of the pediatric hospital medicine department at Children's Minnesota, Minneapolis, Minnesota.

"We will continue to test for influenza and COVID-19 prior to hospitalizations and make decisions about whether to hospitalize based on other clinical factors, such as dehydration, oxygen requirement, and vital sign changes," she said.

Sznewajs stressed the importance of maintaining public health strategies, including "ensuring all children get the flu vaccine, encouraging mask wearing and hand hygiene, adequate testing to determine which virus is present, and other mitigation measures if the prevalence of COVID-19 is increasing in the community."

Song reiterated those points and noted that clinicians need to make the most of the options they have: "Clinicians already have many great tools on hand. It is extremely important to get the flu vaccine now, especially for kids with underlying medical conditions. Diagnostic tests are available for both COVID-19 and flu. Antiviral treatment for flu is available. Judicious use of these tools will protect the health of providers, kids, and well-being at large."

The authors noted several limitations for the study, including its retrospective design, that the data came from a single center, and that different platforms were used to detect the viruses.

Meanwhile, the Centers for Disease Control and Prevention (CDC) pointed out that children more susceptible to severe disease are babies younger than age 1 year and children with underlying conditions (ie, asthma or chronic lung disease; diabetes; genetic, neurologic, or metabolic conditions; congenital heart disease; immunosuppression; obesity; and those with medical complexity requiring external support).^[3]

The CDC recommends testing to differentiate between symptoms of flu and COVID-19. Key symptoms cited to be different between the two are the the presence of loss of taste or smell as COVID-19 symptoms.

Table. Similarities and Differences Between Flu and COVID-19

*More common in children than adults.
CDC website.^[3]

One key thing to note is that people with COVID-19 do not develop symptoms right away as compared to those with the flu. Persons with the flu are contagious for about one day before they show symptoms. In contrast, persons with COVID-19 may be contagious for a longer period of time before showing symptoms. 

Clinical Implications

• A previous study by Tang and colleagues found that patients with ARDS due to COVID-19 vs influenza were more likely to present with fatigue, GI symptoms, and myalgia but not productive cough. The overall risk for mortality was similar in comparing the two cohorts, but the risk for mortality adjusted for disease severity at presentation was twice as high among patients with influenza.
• In the current study by Song and colleagues of children and adolescents, rates of hospitalization, ICU admission, and mechanical ventilation were similar in comparing infections with COVID-19 and influenza.
• Implications for the healthcare team: The healthcare team should promote testing to discriminate COVID-19 from infection with influenza. They can also feel reassured that rates of severe illness from these infections are low among healthy children.

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