Pathophysiology of SARS-CoV-2 Infection in the Upper Respiratory Tract and Its Relation to Breath Volatile Organic Compounds.

Among the many products of metabolic processes are volatile organic compounds (VOCs). In the airways, these volatile metabolites are emitted through breathing and thus are easily sampled for analysis. Recent work has connected the functions and structure of the human microbiome with health and disease. Alteration in microbial function in this context can result in differences in metabolite composition, including that of VOCs, presenting the possibility of a new noninvasive method for clinical diagnosis. Screening methods that assess VOCs arising from changes in the airway microbiome could be highly useful in diagnosing viral upper respiratory tract infections (URTIs), e.g., COVID-19, which are highly contagious and have an enormous public health impact worldwide. A rapid noninvasive screening test for URTIs would pose major advantages in containing the disease. As early evidence shows that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters the human microbiome (both in the gut and the respiratory tract), we propose that detection of a VOC signature of an altered nasal microbiome could be fruitful as a rapid noninvasive measure of URTI in general and of SARS-CoV-2 in particular.

ICAMs Are Not Obligatory for Functional Immune Synapses between Naive CD4 T Cells and Lymph Node DCs.

Protective immune responses depend on the formation of immune synapses between T cells and antigen-presenting cells (APCs). The two main LFA-1 ligands, ICAM-1 and ICAM-2, are co-expressed on many cell types, including APCs and blood vessels. Although these molecules were suggested to be key players in immune synapses studied in vitro, their contribution to helper T cell priming in vivo is unclear. Here, we used transgenic mice and intravital imaging to examine the role of dendritic cell (DC) ICAM-1 and ICAM-2 in naive CD4 T cell priming and differentiation in skin-draining lymph nodes. Surprisingly, ICAM deficiency on endogenous CD40-stimulated lymph node DCs did not impair their ability to arrest and prime CD4 lymphocyte activation and differentiation into Th1 and Tfh effectors. Thus, functional T cell receptor (TCR)-specific helper T cell synapses with antigen-presenting DCs and subsequent proliferation and early differentiation into T effectors do not require LFA-1-mediated T cell adhesiveness to DC ICAMs.