The local and systemic response to SARS-CoV-2 infection in children and adults

While a substantial proportion of adults infected with SARS-CoV-2 progress to develop severe disease, children rarely manifest respiratory complications. Therefore, understanding differences in the local and systemic response to SARS-CoV-2 infection between children and adults may provide important clues about the pathogenesis of SARS-CoV-2 infection. To address this, we first generated a healthy reference multi-omics single cell data set from children (n=30) in whom we have profiled triple matched samples: nasal and tracheal brushings and PBMCs, where we track the developmental changes for 42 airway and 31 blood cell populations from infancy, through childhood to adolescence. This has revealed the presence of naive B and T lymphocytes in neonates and infants with a unique gene expression signature bearing hallmarks of innate immunity. We then contrast the healthy reference with equivalent data from severe paediatric and adult COVID-19 patients (total n=27), from the same three types of samples: upper and lower airways and blood. We found striking differences: children with COVID-19 as opposed to adults had a higher proportion of innate lymphoid and non-clonally expanded naive T cells in peripheral blood, and a limited interferon-response signature. In the airway epithelium, we found the highest viral load in goblet and ciliated cells and describe a novel inflammatory epithelial cell population. These cells represent a transitional regenerative state between secretory and ciliated cells; they were found in healthy children and were enriched in paediatric and adult COVID-19 patients. Epithelial cells display an antiviral and neutrophil-recruiting gene signature that is weaker in severe paediatric versus adult COVID-19. Our matched blood and airway samples allowed us to study the spatial dynamics of infection. Lastly, we provide a user-friendly interface for this data1 as a highly granular reference for the study of immune responses in airways and blood in children

Local and systemic responses to SARS-CoV-2 infection in children and adults

It is not fully understood why COVID-19 is typically milder in children1–3. To examine differences in response to SARS-CoV-2 infection in children and adults, we analysed paediatric and adult COVID-19 patients and healthy controls (total n=93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In healthy paediatric airways, we observed cells already in an interferon-activated state, that upon SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon-responses restrict viral replication and disease progression. The systemic response in children was characterised by increases in naive lymphocytes and a depletion of natural killer cells, while in adults cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signaling in early infection, and identify novel epithelial cell states that associate with COVID-19 and age. Our matching nasal and blood data showed a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were massively reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children

Single-cell multi-omics analysis of the immune response in COVID-19

Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy

EHD-LIGHT SCATTERING AND ABSORPTION IN AN INHOMOGENEOUS STRESSED GERMANIUM

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Time-resolved photoluminescence from hot two-dimensional carriers in GaAsGaAlAs MQWS

Picosecond time-resolved measurements of luminescence from hot carriers confined in GaAsGaAlAs multiple quantum wells show that energy loss rates are substantially slower than those predicted for 2D carriers. We review our recent experiments and present results for photoexcitation of (1) GaAs layers only, (2) both GaAs and GaAlAs layers. We compare the energy loss rates in samples with different well widths. Finally, we present measurements of hot 2D carrier relaxation in the presence of high magnetic fields; at low fields the energy loss rate is reduced, but for B > 9 T we observe a rapid increase. © 1986

Picosecond photoluminescence measurements of Landau level lifetimes and time dependent Landau level linebroadening in modulation-doped GaAs-GaAlAs multiple quantum wells

We report the first picosecond time-resolved photoluminescence measurementsof hot-carrier relaxation in a modulation-doped GaAs-GaAlAs MQW in the presence of strong magnetic fields. We have measured the lifetimes of carriers in excited Landau levels and have determined the time-dependent carrier temperature. We find that the cooling rate is slower in applied field tthan at B=0; also there is a significant increase in the cooling rate for B {greater-than or approximate} 10T. We report also the observation of highly time-dependent linewidths of the Landau levels. © 1985

Time-resolved photoluminescence of two-dimensional hot carriers in GaAs-AlGaAs heterostructures

We have studied the picosecond time dependence of luminescence from a two-dimensional electron system following absorption of an ultrashort light pulse. From our measurements we determine the temporal evolution of the carrier temperature, finding that the cooling of hot carriers is suppressed by a factor 60 below that predicted on a three-dimensional nondegenerate-electron model. Additionally, we determine the electron-hole radiative life-time and invoke a hole trap to explain shortened luminescence lifetimes at low carrier densities. © 1984 The American Physical Society

HOT ELECTRON RELAXATION AND TRAPPING IN MODULATION-DOPED GaAs/GaA1As MULTIPLE QUANTUM WELL HETEROSTRUCTURES.

There is much current interest in determining the energy relaxation processes of hot carriers confined in quantum well heterostructures. We present measurements of time-resolved photoluminescence from hot carriers and from carrier recombination at shallow traps. The experimental technique is basically the same as described previously except that the laser (h upsilon //L equals 1. 76 eV) excites carriers only in the GaAs layers