# P-519. Detection & Severity of Respiratory Virus Co-Infections with SARS-CoV-2, Influenza, or RSV in U.S. Children <2 Years Old

## TL;DR

Young children in the U.S. with co-infections of SARS-CoV-2, influenza, or RSV are more likely to need hospitalization and additional medical care compared to those with single infections.

## Contribution

This study provides new evidence on the increased healthcare burden of respiratory virus co-infections in children under 2 years old.

## Key findings

- Co-infections with SARS-CoV-2 and RSV were most common and associated with higher odds of hospitalization and medical interventions.
- Children with SARS-CoV-2 co-infections had significantly higher odds of returning for outpatient care and receiving nebulizer treatment.
- Inpatient outcomes did not differ significantly by co-infection status.

## Abstract

Co-infections with multiple respiratory viruses may increase the severity of illness in young children, introducing a greater healthcare burden compared to single respiratory virus infections.

We conducted a national cohort study of Medicaid-enrolled children aged 0-24 months presenting for outpatient or inpatient care and tested by multiplex RT-PCR for SARS-CoV-2, influenza, and RSV between 1 July 2021 and 31 December 2022 using the Merative® MarketScan Multi-State Medicaid Database. ICD-10-CM and procedure codes were used to identify clinical diagnoses and the date of clinical testing. We compared the odds of outpatient encounters returning for additional outpatient care, receiving nebulizer treatment, and requiring hospitalization and the odds of inpatient encounters developing pneumonia, receiving noninvasive/invasive ventilation, or requiring critical care by co-infection status using Firth’s penalized logistic regression. Adjusted odds ratios (aOR) controlled for infant sex, age, week of diagnosis, and underlying health conditions.

Among 40,527 outpatient encounters, 13,230 (33%) were positive for a respiratory virus: 5,621 (14%) for SARS-CoV-2 only, 5,030 (12%) for RSV only, 2,230 (5.5%) for influenza only, and 349 (0.9%) for multiple viruses. Among 954 inpatient encounters, 310 (32%) were positive for a respiratory virus: 211 (22%) for RSV only, 70 (7.3%) for SARS-CoV-2 only, 15 (1.6%) for influenza only, and 14 (1.5%) for multiple viruses. The most common co-infection was SARS-CoV-2 and RSV for outpatient (n=215/349; 62%) and inpatient co-infections (n=8/14; 57%)(Figure). The odds of returning to outpatient care (aOR: 2.16; 95%CI 1.64, 2.84), receiving nebulizer treatment (aOR: 6.33; 95%CI 3.36, 11.21), and hospitalization (aOR: 3.41; 95%CI 1.59, 6.56) were higher among SARS-CoV-2 co-infections compared to SARS-CoV-2 only (Table). In-hospital outcomes did not differ by co-infection status.

Children with an outpatient-attended SARS-CoV-2 or influenza co-infection, which were mostly attributed to RSV, more frequently required hospitalization and additional medical care. Given the burden of RSV and co-infections, RSV prevention remains a priority and a possibility through maternal vaccine and monoclonal antibodies.

Annette Regan, PhD, MPH, Moderna: DSMB Membership Stacey Rowe, PhD, MPH, CSL Seqirus: Advisor/Consultant Flor M. Munoz, MD, Merck: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support Sheena G. Sullivan, PhD, Astra-Zeneca: Advisor/Consultant|CSL Behring and CSL Seqirus: Advisor/Consultant|GSK: Advisor/Consultant|Moderna: Advisor/Consultant|Novavax: Advisor/Consultant|Pfizer: Advisor/Consultant|Sanofi: Advisor/Consultant