Waltersepstein7062

With over three million deaths worldwide attributed to the respiratory disease COVID-19 caused by the novel coronavirus SARS-CoV-2, it is essential that continued efforts be made to track the evolution and spread of the virus globally. We previously presented a rapid and cost-effective method to sequence the entire SARS-CoV-2 genome with 95% coverage and 99.9% accuracy. This method is advantageous for identifying and tracking variants in the SARS-CoV-2 genome when compared to traditional short read sequencing methods which can be time consuming and costly. Herein we present the addition of genotyping probes to our DNA chip which target known SARS-CoV-2 variants. The incorporation of the genotyping probe sets along with the advent of a moving average filter have improved our sequencing coverage and accuracy of the SARS-CoV-2 genome.Infection with SARS-CoV-2 has caused a pandemic of unprecedented dimensions. SARS-CoV-2 infects airway and lung cells causing viral pneumonia. The importance of type I interferon (IFN) production for the control of SARS-CoV-2 infection is highlighted by the increased severity of COVID-19 in patients with inborn errors of type I IFN response or auto-antibodies against IFN-α. Plasmacytoid dendritic cells (pDCs) are a unique immune cell population specialized in recognizing and controlling viral infections through the production of high concentrations of type I IFN. In this study, we isolated pDCs from healthy donors and showed that pDCs are able to recognize SARS-CoV-2 and rapidly produce large amounts of type I IFN. Sensing of SARS-CoV-2 by pDCs was independent of viral replication since pDCs were also able to recognize UV-inactivated SARS-CoV-2 and produce type I IFN. Transcriptional profiling of SARS-CoV-2 and UV-SARS-CoV-2 stimulated pDCs also showed a rapid type I and III IFN response as well as induction n. In this study we show that plasmacytoid dendritic cells are able to recognize SARS-CoV-2 and produce type I IFN, and that pDCs are able to help control viral infection in SARS-CoV-2 infected airway epithelial cells.

Type I interferons (IFNs) are a major part of the innate immune defense against viral infections. The importance of type I interferon (IFN) production for the control of SARS-CoV-2 infection is highlighted by the increased severity of COVID-19 in patients with defects in the type I IFN response. Interestingly, many cells are not able to produce type I IFN after being infected with SARS-CoV-2 and cannot control viral infection. In this study we show that plasmacytoid dendritic cells are able to recognize SARS-CoV-2 and produce type I IFN, and that pDCs are able to help control viral infection in SARS-CoV-2 infected airway epithelial cells.While mRNA vaccines are proving highly efficacious against SARS-CoV-2, it is important to determine how booster doses and prior infection influence the immune defense they elicit, and whether they protect against variants. Focusing on the T cell response, we conducted a longitudinal study of infection-naïve and COVID-19 convalescent donors before vaccination and after their first and second vaccine doses, using a high-parameter CyTOF analysis to phenotype their SARS-CoV-2-specific T cells. Vaccine-elicited spike-specific T cells responded similarly to stimulation by spike epitopes from the ancestral, B.1.1.7 and B.1.351 variant strains, both in terms of cell numbers and phenotypes. In infection-naïve individuals, the second dose boosted the quantity but not quality of the T cell response, while in convalescents the second dose helped neither. Spike-specific T cells from convalescent vaccinees differed strikingly from those of infection-naïve vaccinees, with phenotypic features suggesting superior long-term pe cells preferentially express the longevity-associated marker CD127 and respiratory tract homing receptors.

Neidleman et al. conducted CyTOF on antigen-specific T cells in longitudinal samples from infection-naïve and COVID-19 convalescent mRNA vaccinees. Vaccine-elicited T cells respond identically to variants, and change in quantity but not quality after first dose. Convalescents' T cells preferentially express the longevity-associated marker CD127 and respiratory tract homing receptors.Some patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) develop severe pneumonia and the acute respiratory distress syndrome (ARDS) [1]. Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from other types of pneumonia [2]. We collected bronchoalveolar lavage fluid samples from 86 patients with SARS-CoV-2-induced respiratory failure and 252 patients with known or suspected pneumonia from other pathogens and subjected them to flow cytometry and bulk transcriptomic profiling. We performed single cell RNA-Seq in 5 bronchoalveolar lavage fluid samples collected from patients with severe COVID-19 within 48 hours of intubation. In the majority of patients with SARS-CoV-2 infection at the onset of mechanical ventilation, the alveolar space is persistently enriched in alveolar macrophages and T cells without neutrophilia. Bulk and single cell transcriptomic profiling suggest SARS-CoV-2 infects alveolar macrophages that respond by recruiting T cells. These T cells release interferon-gamma to induce inflammatory cytokine release from alveolar macrophages and further promote T cell recruitment. Our results suggest SARS-CoV-2 causes a slowly unfolding, spatially-limited alveolitis in which alveolar macrophages harboring SARS-CoV-2 transcripts and T cells form a positive feedback loop that drives progressive alveolar inflammation. This manuscript is accompanied by an online resource https//www.nupulmonary.org/covid-19/.

SARS-CoV-2-infected alveolar macrophages form positive feedback loops with T cells in patients with severe COVID-19.

SARS-CoV-2-infected alveolar macrophages form positive feedback loops with T cells in patients with severe COVID-19.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of Coronavirus disease 2019 (COVID-19) which is an infectious disease that spread throughout the world and was declared as a pandemic by the World Health Organization (WHO). In this study, we performed a genome-wide analysis on the codon usage bias (CUB) of 13 SARS-CoV-2 isolates from different geo-locations (countries) in an attempt to characterize it, unravel the main force shaping its pattern, and understand its adaptation to Homo sapiens . Overall results revealed that, SARS-CoV-2 codon usage is slightly biased similarly to other RNA viruses. HDAC inhibitor Nucleotide and dinucleotide compositions displayed a bias toward A/U content in all codon positions and CpU-ended codons preference, respectively. Eight common putative preferred codons were identified, and all of them were A/U-ended (U-ended 7, A-ended 1). In addition, natural selection was found to be the main force structuring the codon usage pattern of SARS-CoV-2. However, mutation pressure and other factors such as compositional constraints and hydrophobicity had an undeniable contribution.