The effects of NOD-like receptors on adaptive immune responses.

It has long been appreciated that cues from the innate immune system orchestrate downstream adaptive immune responses. Although previous work has focused on the roles of Toll-like receptors in this regard, relatively little is known about how Nod-like receptors instruct adaptive immunity. Here we review the functions of different members of the Nod-like receptor family in orchestrating effector and anamnestic adaptive immune responses. In particular, we address the ways in which inflammasome and non-inflammasome members of this family affect adaptive immunity under various infectious and environmental contexts. Furthermore, we identify several key mechanistic questions that studies in this field have left unaddressed. Our aim is to provide a framework through which immunologists in the adaptive immune field may view their questions through an innate-immune lens and vice-versa.

Severe COVID-19 Infection and Pediatric Comorbidities: A Systematic Review and Meta-Analysis.

OBJECTIVE: There is limited information on the severity of COVID-19 infection in children with comorbidities. We investigated the effects of pediatric comorbidities on COVID-19 severity by means of a systematic review and meta-analysis of published literature. METHODS: PubMed, Embase, and Medline databases were searched for publications on pediatric COVID-19 infections published January 1st to October 5th, 2020. Articles describing at least one child with and without comorbidities, COVID-19 infection, and reported outcomes were included. RESULTS: 42 studies containing 275,661 children without comorbidities and 9,353 children with comorbidities were included. Severe COVID-19 was present in 5.1% of children with comorbidities, and in 0.2% without comorbidities. Random-effects analysis revealed a higher risk of severe COVID-19 among children with comorbidities than for healthy children; relative risk ratio 1.79 (95% CI 1.27 - 2.51; I2 = 94%). Children with underlying conditions also had a higher risk of COVID-19-associated mortality; relative risk ratio 2.81 (95% CI 1.31 - 6.02; I2 = 82%). Children with obesity had a relative risk ratio of 2.87 (95% CI 1.16 - 7.07; I2 = 36%). CONCLUSIONS: Children with comorbidities have a higher risk of severe COVID-19 and associated mortality than children without underlying disease. Additional studies are required to further evaluate this relationship.