Pathogenicity of SARS-CoV-2 Omicron Subvariants JN.1, KP.2, and EG.5.1 in K18-hACE2 Transgenic Mice

Decision letter: SARS-CoV-2 shedding dynamics across the respiratory tract, sex, and disease severity for adult and pediatric COVID-19

The comparative absorption and excretion of chemical vapors by the upper, lower, and intact respiratory tract of rats

BackgroundThe Centers for Disease Control and Prevention (CDC) recommends upper respiratory tract (URT) polymerase chain reaction (PCR) testing as the initial diagnostic test for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Lower respiratory tract (LRT) testing for patients requiring mechanical ventilation is also recommended. The goal of this study was to evaluate concordance between paired URT and LRT specimens in children undergoing pre-admission/procedure screening or diagnostic testing. We hypothesized that < 10% of paired tests would have discordant results.MethodsSingle center cross-sectional study including children with artificial airways who had paired URT and LRT SARS-CoV-2 PCR testing between 4/1/2020 and 6/8/2020. URT specimens included nasopharyngeal (NP) swabs and aspirates. LRT specimens included tracheal aspirates and bronchoalveolar lavages. URT and LRT specimens were classified as paired if the two specimens were collected within 24 hours. Artificial airways included tracheostomies and endotracheal tubes. Tests were classified as diagnostic versus screening based on the indication selected in the order.Results102 paired specimens were obtained during the study period. Fifty-nine were performed for screening and 43 were performed for diagnosis of suspected SARS-CoV-2. Overall, 94 specimens (92%) were concordant, including 89 negative from both sources and 5 positive from both sources. Eight specimens (8%) were discordant, all of which were positive from the URT and negative from the LRT (Figure 1). Among patients undergoing screening, 3 of 4 positive tests were discordant and among symptomatic patients, 5 of 9 positive tests were discordant. There were no instances of a positive LRT specimen with a negative URT specimen.Figure 1. Performance of upper and lower respiratory tract SARS-CoV-2 PCR testing in children with artificial airwaysConclusionOverall, most paired samples from the URT and LRT yielded concordant results with no pairs positive from the LRT and negative from the URT. These data support the CDC recommendation that URT specimens are the preferred initial SARS-CoV-2 test, while LRT specimens should be collected only from mechanically ventilated with suspected SARS-CoV-2.DisclosuresAll Authors: No reported disclosures

Nasal nitric oxide.

81 The concordance between the microbiome of the upper and lower respiratory tract is investigated in infants with cystic fibrosis

Nasal vaccination induces protective immunity without immunopathology.

Analysis of Eimeria acervulina-induced changes in the intestinal T lymphocyte subpopulations in two chicken strains showing different levels of susceptibility to coccidiosis

Autoimmunity may be due to augmentation of immune responses by human CD8 cells which bind the lectin Vicia villosa (VV). We have investigated T cells in rheumatoid arthritis (RA) by double immunofluorescence flow cytometry, in order to assess VV-binding CD8 and CD4 cells from the peripheral blood and synovial fluid. A significant increase in CD8+VV adherent (P less than 0.0001) and CD4+VV adherent cells (P less than 0.001) was found in synovial fluid, as compared with peripheral blood from patients with RA. A significant increase in VV-binding CD8+ or CD4+ cells was, however, not found in the blood of patients with RA, as compared with controls. We suggest that the lack of VV-binding T cells separated from blood, in contrast to those from synovial fluid, may be due to an inhibiting agent expressing N-acetyl D-galactosamine. Indeed, IgA1 is rich in N-acetyl D-galactosamine, it inhibits VV binding to T cells and is significantly bound to CD8 cells (P less than 0.001). The IgA1 was then characterized and in about half the patients J chains and secretory component was found, suggesting that the IgA1 is of the polymeric and secretory variety. IgA bound to the T cells engaged the Fc alpha receptors and a significant decrease in the Fc alpha receptors was found in CD8 cells (P less than 0.0001) and CD4 cells (P less than 0.01). Desorption studies were then carried out on CD8 and CD4 cells which showed that a loss of cell-bound IgA1 was associated with an increase in VV binding. Conversely, adsorption of IgA to T cells was associated with a loss in VV binding. The results suggest that the failure of VV binding to CD8+ and CD4+ cells from peripheral blood of patients with RA can be ascribed to cell-bound IgA1. Cytophilic IgA1 may inhibit the function of CD8+VV binding cells, thereby preventing augmentation of the systemic immune response, consistent with the lack of extra-articular disease in these patients with RA.

In vitro fitness of SARS-CoV-2 variants as assessed by competition experiments followed by ddRT-PCR and whole genome sequencing.

Variation of p53 mutational spectra between carcinoma of the upper and lower respiratory tract

The purpose of this study is to evaluate the significance of IFN-gamma and IL-4 production in controlling mycoplasma infection and the pathogenesis of disease in the upper and lower respiratory tract. By using IFN-gamma knockout and IL-4 knockout BALB/c mice, we were able to study the contribution of these cytokines in the development of pathogenesis and/or protection in response to mycoplasma respiratory infection, in both the upper and lower respiratory tracts. The loss of either IFN-gamma or IL-4 does not affect disease pathogenesis or mycoplasma organism numbers in the upper respiratory tract. However, in the absence of IL-4, the nasal passages developed a compensatory immune response, characterized by higher numbers of macrophages and CD8(+) T cells, which may be masking detrimental effects due to IL-4 deficiency. This is in contrast to the lower respiratory tract, where the loss of IFN-gamma, but not IL-4, leads to higher mycoplasma numbers and increased disease severity. The loss of IFN-gamma impacted the innate immune system's ability to effectively clear mycoplasma, as the number of organisms was higher by day 3 postinfection. This higher organism burden most likely impacted disease pathogenesis; however, the development of Th2 cell-mediated adaptive immune response most likely contributed to lesion severity at later time points during infection. Our studies demonstrate that the upper and lower respiratory tracts are separate and distinct in their cytokine requirements for generating immunity against mycoplasma infection.

Comparative analysis of SARS-CoV-2 quasispecies in the upper and lower respiratory tract shows an ongoing evolution in the spike cleavage site

Exchange of gene segments through reassortment is a major feature of influenza A virus evolution and frequently contributes to the emergence of novel epidemic, pandemic, and zoonotic strains. It has long been evident that viral diversification through reassortment is constrained by genetic incompatibility between divergent parental viruses. In contrast, the role of virus-extrinsic factors in determining the likelihood of reassortment has remained unclear. To evaluate the impact of such factors in the absence of confounding effects of segment mismatch, we previously reported an approach in which reassortment between wild-type (wt) and genetically tagged variant (var) viruses of the same strain is measured. Here, using wt/var systems in the A/Netherlands/602/2009 (pH1N1) and A/Panama/2007/99 (H3N2) strain backgrounds, we tested whether inoculation of parental viruses into distinct sites within the respiratory tract limits their reassortment. Using a ferret (Mustella putorius furo) model, either matched parental viruses were coinoculated intranasally or one virus was instilled intranasally whereas the second was instilled intratracheally. Dual intranasal inoculation resulted in robust reassortment for wt/var viruses of both strain backgrounds. In contrast, when infections were initiated simultaneously at distinct sites, strong compartmentalization of viral replication was observed and minimal reassortment was detected. The observed lack of viral spread between upper and lower respiratory tract tissues may be attributable to localized exclusion of superinfection within the host, mediated by innate immune responses. Our findings indicate that dual infections in nature are more likely to result in reassortment if viruses are seeded into similar anatomical locations and have matched tissue tropisms.IMPORTANCE Genetic exchange between influenza A viruses (IAVs) through reassortment can facilitate the emergence of antigenically drifted seasonal strains and plays a prominent role in the development of pandemics. Typical human influenza infections are concentrated in the upper respiratory tract; however, lower respiratory tract (LRT) infection is an important feature of severe cases, which are more common in the very young, the elderly, and individuals with underlying conditions. In addition to host factors, viral characteristics and mode of transmission can also increase the likelihood of LRT infection: certain zoonotic IAVs are thought to favor the LRT, and transmission via small droplets allows direct seeding into lower respiratory tract tissues. To gauge the likelihood of reassortment in coinfected hosts, we assessed the extent to which initiation of infection at distinct respiratory tract sites impacts reassortment frequency. Our results reveal that spatially distinct inoculations result in anatomical compartmentalization of infection, which in turn strongly limits reassortment.

Co-infection of epithelial cells established from the upper and lower bovine respiratory tract with bovine respiratory syncytial virus and bacteria

In order to better understand how the immune system interacts with environmental triggers to produce organ-specific disease, we here address the hypothesis that B and plasma cells are free to migrate through the mucosal surfaces of the upper and lower respiratory tracts, and that their total antibody repertoire is modified in a common respiratory tract disease, in this case atopic asthma. Using Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) we have catalogued the antibody repertoires of B cell clones retrieved near contemporaneously from multiple sites in the upper and lower respiratory tract mucosa of adult volunteers with atopic asthma and non-atopic controls and traced their migration. We show that the lower and upper respiratory tracts are immunologically connected, with trafficking of B cells directionally biased from the upper to the lower respiratory tract and points of selection when migrating from the nasal mucosa and into the bronchial mucosa. The repertoires are characterized by both IgD-only B cells and others undergoing class switch recombination, with restriction of the antibody repertoire distinct in asthmatics compared with controls. We conclude that B cells and plasma cells migrate freely throughout the respiratory tract and exhibit distinct antibody repertoires in health and disease.