Respiratory Viral Co-infection in SARS-CoV-2-Infected Children During the Early and Late Pandemic Periods

Abstract

Background: Knowledge regarding the impact of respiratory pathogen co-infection in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children seeking emergency department care is limited, specifically as it relates to the association between SARS-CoV-2 viral co-infection and disease severity and factors associated with co-infection.

Methods: This secondary analysis included data from 2 prospective cohort studies conducted between March 2020 and February 2022 that included children <18 years of age tested for SARS-CoV-2 infection along with additional respiratory viruses in a participating emergency department. Outcomes included the detection rate of other respiratory viruses and the occurrence of severe outcomes (ie, intensive interventions, severe organ impairment and death).

Results: We included 2520 participants, of whom 388 (15.4%) were SARS-CoV-2-positive. Detection of additional respiratory viruses occurred in 18.3% (71/388) of SARS-CoV-2-positive children, with rhinovirus/enterovirus being most frequently detected (42/388; 10.8%). In multivariable analyses (adjusted odds ratio and 95% confidence interval), among SARS-CoV-2-positive children, detection of another respiratory virus was not associated with severe outcomes [1.74 (0.80-3.79)], but detection of rhinovirus/enterovirus [vs. isolated SARS-CoV-2 detection 3.56 (1.49-8.51)] and having any preexisting chronic medical condition [2.15 (1.06-4.36)] were associated with severe outcomes. Among SARS-CoV-2-positive children, characteristics independently associated with an increased odds of any other viral co-infection included: age and delta variant infection.

Conclusions: Approximately 1 in 5 children infected with SARS-CoV-2 had co-infection with another respiratory virus, and co-infection with rhinovirus/enterovirus was associated with severe outcomes. When public health restrictions were relaxed, co-infections increased.

FIGURE 1.

Study participants and outcomes*.*A severe outcome was defined based on the occurrence of any of the following events at or within 14 days of the index ED visit: cardiac or cardiovascular (eg, cardiac arrest, cardiac ischemia, congestive heart failure, endocarditis, myocarditis, pericarditis and stroke), infectious (eg, disseminated intravascular coagulation, mastoiditis, sepsis with bacteremia, septic shock and toxic shock syndrome), neurologic (eg, encephalitis and meningitis), respiratory (eg, acute respiratory distress syndrome, empyema, necrotizing or cryptogenic organizing pneumonia, pleural effusion or pneumothorax or pneumomediastinum requiring drainage and respiratory failure) and death. Performance of any of the following interventions was also deemed to represent a severe outcome: chest drainage, extracorporeal membrane oxygenation, high flow oxygen by nasal cannula, inotropic support, positive pressure ventilation and renal replacement therapy. The diagnosis of multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease were reported as assigned by the clinical care teams and were considered severe if accompanied by one of the aforementioned diagnoses or interventions.

FIGURE 2.

Detection rates of non-SARS-CoV-2 respiratory viruses in SARS-CoV-2 positive and negative groups. P values were obtained from χ² and Fisher exact test as appropriate for the between SARS-CoV-2-positive and negative groups comparison of the detection rates. The error bars represented 95% CI of the detection rates.