Longitudinal Analysis of Inflammatory Response to SARS-CoV-2 in the Upper Respiratory Tract Reveals an Association with Viral Load,Independent of Symptoms

Background

SARS-CoV-2 infection leads to high viral loads in the upper respiratory tract that may be determinant in virus dissemination. The extent of intranasal antiviral response in relation to symptoms is unknown. Understanding how local innate responses control virus is key in the development of therapeutic approaches.

Methods

SARS-CoV-2-infected patients were enrolled in an observational study conducted at the Geneva University Hospitals, Switzerland, investigating virological and immunological characteristics. Nasal wash and serum specimens from a subset of patients were collected to measure viral load, IgA specific for the S1 domain of the spike protein, and a cytokine panel at different time points after infection; cytokine levels were analyzed in relation to symptoms.

Results

Samples from 13 SARS-CoV-2-infected patients and six controls were analyzed. We found an increase in CXCL10 and IL-6, whose levels remained elevated for up to 3 weeks after symptom onset. SARS-CoV-2 infection also induced CCL2 and GM-CSF, suggesting local recruitment and activation of myeloid cells. Local cytokine levels correlated with viral load but not with serum cytokine levels, nor with specific symptoms, including anosmia. Some patients had S1-specific IgA in the nasal cavity while almost none had IgG.

Conclusion

The nasal epithelium is an active site of cytokine response against SARS-CoV-2 that can last more than 2 weeks; in this mild COVID-19 cohort, anosmia was not associated with increases in any locally produced cytokines.

     

Late-Onset Progressive Multifocal Leukoencephalopathy (PML) and Lymphoma in a 65-Year-Old Patient with XIAP Deficiency

Journal of Clinical Immunology -     

Mutations in SYNGAP1 Cause Intellectual Disability,Autism, and a Specific Form of Epilepsy by Inducing Haploinsufficiency

De novo mutations in SYNGAP1, which codes for a RAS/RAP GTP‐activating protein, cause nonsyndromic intellectual disability (NSID). All disease‐causing point mutations identified until now in SYNGAP1 are truncating, raising the possibility of an association between this type of mutations and NSID. Here, we report the identification of the first pathogenic missense mutations (c.1084T>C [p.W362R], c.1685C>T [p.P562L]) and three novel truncating mutations (c.283dupC [p.H95PfsX5], c.2212_2213del [p.S738X], and (c.2184del [p.N729TfsX31]) in SYNGAP1 in patients with NSID. A subset of these patients also showed ataxia, autism, and a specific form of generalized epilepsy that can be refractory to treatment. All of these mutations occurred de novo, except c.283dupC, which was inherited from a father who is a mosaic. Biolistic transfection of wild‐type SYNGAP1 in pyramidal cells from cortical organotypic cultures significantly reduced activity‐dependent phosphorylated extracellular signal‐regulated kinase (pERK) levels. In contrast, constructs expressing p.W362R, p.P562L, or the previously described p.R579X had no significant effect on pERK levels. These experiments suggest that the de novo missense mutations, p.R579X, and possibly all the other truncating mutations in SYNGAP1 result in a loss of its function. Moreover, our study confirms the involvement of SYNGAP1 in autism while providing novel insight into the epileptic manifestations associated with its disruption.     

Magnetic and spectroscopic properties of Ni–Zn–Al ferrite spinel: from the nanoscale to microscale

This article presents the annealing effect on the structural, elastic, thermodynamic, optical, magnetic, and electric properties of Ni_0.6Zn_0.4Fe_1.5Al_0.5O₄ (NZFAO) nanoparticles (NPs). The samples were successfully synthesized by the sol–gel method followed by annealing of the as-synthesized at 600, 800, 900, 1050, and 1200 °C. This approach yielded the formation of a highly crystalline structure with crystallite size ranging from 17 nm to 40 nm. X-ray diffraction (XRD), scanning electron microscopy (SEM) techniques, as well as energy disperse spectroscopy (EDS), Fourier transform infrared (FTIR) and Raman spectroscopy, were used in order to determine the structural and morphological properties of the prepared samples. Rietveld XRD refinement reveals that Ni–Zn–Al ferrite nanoparticles crystallize in inverse cubic (Fd$\bar{3}$m) spinel structure. Using FTIR spectra, the elastic and thermodynamic properties were estimated. It was observed that the particle size had a pronounced effect on elastic and thermodynamic properties. Magnetic measurements were performed up to 700 K. The prepared ferrite samples present the highest Curie temperature, which decreases with increasing particle size and which is consistent with finite-size scaling. The thickness of the surface shell of about 1 nm was estimated from size-dependent magnetization measurements using the core–shell model. Besides, spin resonance, magnetostriction, temperature coefficient of resistance (TCR), and electrical resistivity properties have been scientifically studied and appear to be different according to their size. The optical properties of synthesized NZFAO nanoparticles were investigated, and the differences caused by the particle sizes are discussed on the basis of the phonon confinement effect. This effect was also inspected by the Raman analysis. Tuning of the physical properties suggests that the Ni–Zn–Al ferrite samples may be promising for multifunctional diverse applications.

This article presents the annealing effect on the structural, elastic, thermodynamic, optical, magnetic, and electric properties of Ni_0.6Zn_0.4Fe_1.5Al_0.5O₄ (NZFAO) nanoparticles (NPs).