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In a recent article published in the American Academy of Pediatrics, researchers assessed the clinical impact and epidemiology of viral co-detections in children in the United States of America (USA) during the coronavirus disease 2019 (COVID-19) pandemic.
The ongoing COVID-19 pandemic and interventions targeted to mitigate it widely affected the circulation of many common respiratory viruses. Though many respiratory viruses co-circulated with SARS-CoV-2, hence, co-detected, studies have barely investigated their clinical relevance and epidemiology in pediatric cases. Co-detection implies these children did not necessarily have an active infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and another respiratory virus, as with co-infection cases.
About the study
In the present study, researchers acquired data on all children under <18 years of age through the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET) for the period between March 2020 and November 2021. This population-based surveillance system covers data on COVID-19-related hospitalizations for inhabitants of 14 USA states and 99 counties.
The study analysis had around 4372 children between March 2020 and February 2022 who sought hospitalization for presumed COVID-19 or some respiratory illness. Two reviewers analyzed whether their complaints were not likely COVID-19-related. Next, they described the proportion and frequency of children, including weighted and unweighted, who underwent testing for non-SARS-CoV-2 viral diagnoses. The other respiratory viruses included respiratory syncytial virus (RSV), enterovirus, parainfluenza, and influenza A and B. In addition, there were human metapneumovirus, adenovirus, and endemic human coronaviruses (e.g., OC43).
The researchers compared proportions (including adjusted odds ratios (aORs) with 95% confidence intervals [CI]) among children with co-detections stratified based on age, causal pathogen, and time, using χ2 tests. A multivariable logistic regression model described the relationship between severe respiratory illness and viral co-detections. Severe illness implied these hospitalized children underwent treatment in an intensive care unit (ICU) and needed bilevel positive airway pressure (BiPAP) or continuous (CPAP) or invasive mechanical ventilation (IMV). The researchers specifically assessed rhinovirus or enterovirus co-detections because of their uncertain clinical relevance.
The researchers noted that respiratory virus co-detections likely increased the severity of respiratory illness among children <5 years old who had completed additional viral testing. They were approximately at double the odds of severe respiratory illness than those testing negative. In addition, children under two years of age with RSV co-detection also had double the odds of developing severe respiratory illness.
The study analysis uncovered that though infections from RSV, influenza, and other viruses whose advent rise with fall and winter occurred among children hospitalized with COVID-19 even during the pre-Delta period, they could not be identified. Conversely, co-detections for rhinos and enteroviruses continued throughout the pandemic. Notably, the frequency of RSV co-detections increased in the Delta predominance era. All these data points to the decreased circulation of the influenza virus during the first two years of the COVID-19 pandemic. It also showed that the circulation of rhinoviruses or enteroviruses did not reduce during that time.
Another observation was that non-Hispanic white children underwent non-SARS-CoV-2 testing more often. Also, children with co-detections were more likely to have severe respiratory illness. Accordingly, they were on systemic steroids more than the children who suffered from COVID-19. Doctors prescribe systemic steroids to hospitalized children with COVID-19 who require more respiratory support. However, steroids are often not recommended for respiratory illnesses due to RSV-associated bronchiolitis. Most likely, the increased use of steroids in children was correlated with differential clinical presentation in cases with co-detections.
Nevertheless, rhino or enteroviruses co-detections in hospitalized children <5 years of age approximately doubled the odds of severe illness. Rhinovirus detections often occur in asymptomatic children or those with mild symptoms. However, it can cause severe respiratory illness, especially in children <5 years of age, due to asthma exacerbations, pneumonia, and bronchiolitis. Likewise, RSV co-detections double the odds of severe respiratory illness in hospitalized children <2 years of age.
It is not unknown who is the primary driver of illness in children hospitalized with RSV and SARS-CoV-2 co-detections. However, cocirculation of these viruses must have burdened pediatric hospitals during high incidence times due to severe respiratory illnesses-related admissions.
The present study demonstrated increased co-detections with non-SARS-CoV-2 respiratory viruses among children hospitalized with respiratory illnesses in the USA, starting from the summer of 2021. The frequency of co-detections varied, increasing markedly during the Delta- and Omicron dominance era between June 2021 and February 2022. These co-detections most likely contributed to the increased severity of illness among young children. Thus, their identification could help inform public health practices, including the prediction of clinical courses, infection control recommendations, and the time of escalation of care.
Most importantly, the study highlighted the need for continued surveillance of the transmission of SARS-CoV-2 and other respiratory viruses because such re-emergences burdened pediatric hospitals. A better understanding of the prevalence of multiple viruses could also help better align diagnostic and therapeutic resources and vaccine development.
- Nickolas T. Agathis, Kadam Patel, Jennifer Milucky, Christopher A. Taylor, Michael Whitaker, Huong Pham, Onika Anglin, Shua J. Chai, Nisha B. Alden, James Meek, Evan J. Anderson, Andy Weigel, Sue Kim, Ruth Lynfield, Chad Smelser, Alison Muse, Kevin Popham, Laurie M. Billing, Melissa Sutton, H. Keipp Talbot, Andrea George, Meredith McMorrow, Fiona P. Havers. (2023). CDC COVID-NET Surveillance Team. Codetections of Other Respiratory Viruses Among Children Hospitalized With COVID-19. Pediatrics. doi: https://doi.org/10.1542/peds.2022-059037 https://publications.aap.org/pediatrics/article/doi/10.1542/peds.2022-059037/190475/Codetections-of-Other-Respiratory-Viruses-Among?autologincheck=redirected