Impact of Viral Lower Respiratory Tract Infection (LRTI) in Early Childhood (0-2 Years) on Lung Growth and Development and Lifelong Trajectories of Pulmonary Health: A National Institutes of Health (NIH) Workshop Summary

Abstract

Viral lower respiratory tract infections (LRTI) are ubiquitous in early life. They are disproportionately severe in infants and toddlers (0-2 years), leading to more than 100,000 hospitalizations in the United States per year. The recent relative resilience to severe Coronavirus disease (COVID-19) observed in young children is surprising. These observations, taken together, underscore current knowledge gaps in the pathogenesis of viral lower respiratory tract diseases in young children and respiratory developmental immunology. Further, early-life respiratory viral infections could have a lasting impact on lung development with potential life-long pulmonary sequelae. Modern molecular methods, including high-resolution spatial and single-cell technologies, in concert with longitudinal observational studies beginning in the prenatal period and continuing into early childhood, promise to elucidate developmental pulmonary and immunophenotypes following early-life viral infections and their impact on trajectories of future respiratory health. In November 2019, under the auspices of a multi-disciplinary Workshop convened by the National Heart Lung Blood Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, experts came together to highlight the challenges of respiratory viral infections, particularly in early childhood, and emphasize the knowledge gaps in immune, virological, developmental, and clinical factors that contribute to disease severity and long-term pulmonary morbidity from viral LRTI in children. We hope that the scientific community will view these challenges in clinical care on pulmonary health trajectories and disease burden not as a window of susceptibility but as a window of opportunity.

Keywords: mother‐infant dyads; pulmonary immune ontogeny; viral LRTI.

Figure 1

Immune response to respiratory viruses. Complex crosstalk between epithelial cells and stromal cells and resident and recruited immune cell populations in either (A) airways or (B) Alveolus. This figure provides specific examples and is not exhaustive. AT1, alveolar epithelial type 1 cells; AT2, alveolar epithelial type 2 cells; DC, dendritic cell; MAIT cell, mucosal‐associated invariant T cell; T_RM cell, tissue‐resident memory T cell. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

Neonatal window of opportunity: Ontogeny of pulmonary immune development, increase in lung volume and colonization by the gut microbiome. Insults during the developmental window, for example, premature birth, poor maternal health, antibiotic use during the neonatal period, mechanical ventilation, environmental exposures, and viral infections interrupt the programmed increase in pulmonary immune cells, maturation of lung function, contributing to durable, consequences for child health and morbidity. [Color figure can be viewed at wileyonlinelibrary.com]