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Introduction: Melatonin has been suggested an adjunctive therapy in neonatal encephalopathy (NE). Melatonin reduces oxidative stress and neutrophil activation; however, the immunological effects in NE have not been studied. Methods: Infants with NE and neonatal controls were prospectively recruited. Whole blood was sampled in the first week of life. Following endotoxin and or melatonin treatment, diurnal variation was measured by RT PCR for circadian rhythm genes (brain and Muscle Arnt-Like protein [BMAL1], circadian locomotor output cycles kaput [CLOCK], Nuclear Receptor Subfamily 1 Group D Member 2 [REV Erβ], and cryptochrome circadian clock [CRY]). Neutrophil and monocyte cell surface markers of activation CD11b, reactive oxygen intermediates (ROIs), and Toll-like receptor (TLR)-4 were also examined by flow cytometry in matching samples. Results: Serum and RNA samples from forty infants were included (controls n = 20; NE n = 20) over the first week of life. Melatonin reduced neutrophil CD11b and TLR-4 expression in response to LPS in infants with NE compared to controls. There were no differences in ROIs. BMAL1 and CLOCK baseline gene expression levels were similar. BMAL1 was significantly decreased with LPS stimulation in NE. There was no significant diurnal variation in melatonin, neutrophil, and monocyte function or circadian genes. Conclusions: Melatonin alters immune function ex vivo in infants with NE. Infants with NE have altered immune circadian responses following LPS stimulation, which have potential for modulation. [ABSTRACT FROM AUTHOR]

Unusually for a viral infection, the immunological phenotype of severe COVID-19 is characterised by a depleted lymphocyte and elevated neutrophil count, with the neutrophil-to-lymphocyte ratio correlating with disease severity. Neutrophils are the most abundant immune cell in the bloodstream and comprise different subpopulations with pleiotropic actions that are vital for host immunity. Unique neutrophil subpopulations vary in their capacity to mount antimicrobial responses, including NETosis (the generation of neutrophil extracellular traps), degranulation and de novo production of cytokines and chemokines. These processes play a role in antiviral immunity, but may also contribute to the local and systemic tissue damage seen in acute SARS-CoV-2 infection. Neutrophils also contribute to complications of COVID-19 such as thrombosis, acute respiratory distress syndrome and multisystem inflammatory disease in children. In this Progress review, we discuss the anti-viral and pathological roles of neutrophils in SARS-CoV-2 infection, and potential therapeutic strategies for COVID-19 that target neutrophil-mediated inflammatory responses. [ABSTRACT FROM AUTHOR]