Beckhalberg9794

Evaluation of nasopharyngeal microbiome profiles in children, adolescents, and young adults with a SARS-CoV-2-infected close contact identified specific bacterial species that vary in abundance with age and are associated with SARS-CoV-2 susceptibility and the presence of SARS-CoV-2-associated respiratory symptoms.The persistence of the COVID-19 pandemic demands a dramatic increase in testing efficiency. Testing pooled samples for SARS-CoV-2 could meet this need; however, the sensitivity of RT-qPCR, the gold standard, significantly decreases with an increasing number of samples pooled. Here, we introduce DIVER, a method that quantifies intact virus and is robust to sample dilution. DIVER first tags viral particles with exogeneous oligonucleotides, then captures the tagged particles on ACE2-functionalized beads, and finally quantifies the oligonucleotide tags using qPCR. Using spike-presenting liposomes and Spike-pseudotyped lentivirus as SARS-CoV-2 models, we show that DIVER can detect 1×10 5 liposomes and 100 pfu lentivirus and can successfully identify positive samples in pooling experiments. Overall, DIVER is well-positioned for efficient sample pooling and expanded community surveillance.

Individuals with chronic disease may be at higher risk of dying from COVID-19, yet no association has been established between chronic illness and COVID-19 risk perception, engagement with nonpharmaceutical interventions (NPIs), or vaccine acceptance.

We surveyed US residents who self-reported a chronic respiratory or autoimmune disease in February 2021. Respondents reported beliefs about the risk of COVID-19 to personal and public health, adoption and support of NPIs, willingness to be vaccinated against COVID-19, and reasons for vaccination willingness. We evaluated the association between disease status and COVID-19 behaviors or attitudes, adjusting for demographic and political factors.

Compared to healthy controls, chronic disease was associated with increased belief that COVID-19 was a personal (Respiratory = 0.12, 95% confidence interval (CI) = 0.10 - 0.15; Autoimmune = 0.11, CI = 0.08 - 0.14) and public threat (Respiratory = 0.04, CI = 0.02 - 0.06; Autoimmune = 0.03, CI = 0.01 - 0.06), and support for NPIs. Chronic respiratory disease was associated with willingness to be vaccinated (0.6, CI = 0.05 - 0.09). Personal protection was associated with vaccination (Respiratory = 1.08, CI = 1.03 - 1.13; Autoimmune = 1.06, CI = 1.01 - 1.11). Autoimmune disease was associated with fear of a bad vaccine reaction (1.22, CI = 1.06 - 1.41) among those unwilling to be vaccinated.

In the US, chronic disease status is significantly related to risk perceptions of COVID, support of personal and community risk mitigation measures, and willingness to be vaccinated.

In the US, chronic disease status is significantly related to risk perceptions of COVID, support of personal and community risk mitigation measures, and willingness to be vaccinated.A locus containing OAS1/2/3 has been identified as a risk locus for severe COVID-19 among Europeans ancestry individuals, with a protective haplotype of ∼75 kilobases derived from Neanderthals. Here, we show that among several potentially causal variants at this locus, a splice variant of OAS1 occurs in people of African ancestry independently of the Neanderthal haplotype and confers protection against COVID-19 of a magnitude similar to that seen in individuals without African ancestry.

To directly measure SARS-CoV-2 infection in diverse schools with either remote or onsite learning.

4 schools participated. Schools A and B served low-income Hispanic learners, school C special needs, and all three provided predominantly remote instruction. School D served middle and upper-middle income, White learners, with predominantly onsite instruction. 320 learners [10.5±2.1(SD); 7-17 y.o.]; 86% had phlebotomy. Testing occurred early in the fall (2020), at lower levels of COVID-19, and 6-8 weeks later during the fall-winter surge (tenfold increase in COVID-19 cases).

Nasal RT-qPCR for SARS-CoV-2 and 21 respiratory pathogens was performed. Phlebotomy was obtained for circulating immunity. Face covering and physical distancing fidelity was measured by direct observation. 17 learners were SARS-CoV-2 positive during the surge. School A (97% remote) had the highest infection rate (9/70, 12.9%, p<0.01) and IgG positivity rate (13/70, 18.6%). School D had the lowest infection and IgG positive rate (1/8nfection. Infectivity and immunobiology of SARS-CoV-2 in children attending schools not understood.

School-associated infections reflected regional rates rather than remote or onsite learning. Successful mitigation was implemented across a diverse range of schools. Reduced immune mediator concentrations coupled with robust humoral and cellular immunity may explain the milder symptoms in school-aged children.

School-associated infections reflected regional rates rather than remote or onsite learning. Successful mitigation was implemented across a diverse range of schools. Reduced immune mediator concentrations coupled with robust humoral and cellular immunity may explain the milder symptoms in school-aged children.The COVID-19 pandemic has been accompanied by the largest mobilization of therapeutic convalescent plasma (CCP) in over a century. Initial identification of high titer units was based on dose-response data using the Ortho VITROS IgG assay. The proliferation of SARS-CoV-2 serological assays and non-uniform application has led to uncertainty about their interrelationships. The purpose of this study was to establish correlations and analogous cutoffs between commercially available serological tests (Ortho, Abbott, Roche), a spike ELISA, and a virus neutralization assay using convalescent plasma from a cohort of 79 donors from April 2020. Relationships relative to FDA-approved cutoffs under the CCP EUA were identified by linear regression and receiver operator characteristic curves. mTOR inhibitor Relative to the Ortho VITROS assay, the r 2 of the Abbott, Roche, the anti-Spike ELISA and the neutralizing assay were 0.58, 0.5, 0.82, and 0.44, respectively. The best correlative index for establishing high-titer units was 3.82 S/C for the Abbott, 10.89 COI for the Roche, 11,202 for the anti-Spike ELISA, and 1200 by the neutralization assay. The overall agreement using derived cutoffs compared to the CCP EUA Ortho VITROS cutoff of 9.5 was 92.4% for Abbott, 84.8% for Roche, 87.3% for the anti-S ELISA and 78.5% for the neutralization assay. Assays based on antibodies against the nucleoprotein (Roche, Abbott) and neutralizing antibody tests were positively associated with the Ortho assay, although their ability to distinguish FDA high-titer specimens was imperfect. The resulting relationships help reconcile results from the large body of serological data generated during the COVID-19 pandemic.

Little is known about the dynamics of SARS-CoV-2 antigen burden in respiratory samples in different patient populations at different stages of infection. Current rapid antigen tests cannot quantitate and track antigen dynamics with high sensitivity and specificity in respiratory samples.

We developed and validated an ultra-sensitive SARS-CoV-2 antigen assay with smartphone readout using the Microbubbling Digital Assay previously developed by our group, which is a platform that enables highly sensitive detection and quantitation of protein biomarkers. A computer vision-based algorithm was developed for microbubble smartphone image recognition and quantitation. A machine learning-based classifier was developed to classify the smartphone images based on detected microbubbles. Using this assay, we tracked antigen dynamics in serial swab samples from COVID patients hospitalized in ICU and immunocompromised COVID patients.

The limit of detection (LOD) of the Microbubbling SARS-CoV-2 Antigen Assay was 0.5 pg/m. With smartphone compatibility and automated image processing, the assay is well-positioned to be adapted for point-of-care diagnosis and to explore the clinical implications of antigen dynamics in future studies.Coronaviruses have caused three major epidemics since 2003, including the ongoing SARS-CoV-2 pandemic. In each case, coronavirus emergence in our species has been associated with zoonotic transmissions from animal reservoirs 1,2 , underscoring how prone such pathogens are to spill over and adapt to new species. Among the four recognized genera of the family Coronaviridae - Alphacoronavirus, Betacoronavirus, Deltacoronavirus, Gammacoronavirus , - human infections reported to date have been limited to alpha- and betacoronaviruses 3 . We identify, for the first time, porcine deltacoronavirus (PDCoV) strains in plasma samples of three Haitian children with acute undifferentiated febrile illness. Genomic and evolutionary analyses reveal that human infections were the result of at least two independent zoonoses of distinct viral lineages that acquired the same mutational signature in the nsp15 and the spike glycoprotein genes by convergent evolution. In particular, structural analysis predicts that one of the changes in the Spike S1 subunit, which contains the receptor-binding domain, may affect protein's flexibility and binding to the host cell receptor. Our findings not only underscore the ability of deltacoronaviruses to adapt and potentially lead to human-to-human transmission, but also raise questions about the role of such transmissions in development of pre-existing immunity to other coronaviruses, such as SARS-CoV-2.Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has incited a global health crisis. Currently, there are no orally available medications for prophylaxis for those exposed to SARS-CoV-2 and limited therapeutic options for those who develop COVID-19. We evaluated the antiviral activity of sulforaphane (SFN), a naturally occurring, orally available, well-tolerated, nutritional supplement present in high concentrations in cruciferous vegetables with limited side effects. SFN inhibited in vitro replication of four strains of SARS-CoV-2 as well as that of the seasonal coronavirus HCoV-OC43. Further, SFN and remdesivir interacted synergistically to inhibit coronavirus infection in vitro. Prophylactic administration of SFN to K18-hACE2 mice prior to intranasal SARS-CoV-2 infection significantly decreased the viral load in the lungs and upper respiratory tract and reduced lung injury and pulmonary pathology compared to untreated infected mice. SFN treatment diminished immune cell activation in the lungs, including significantly lower recruitment of myeloid cells and a reduction in T cell activation and cytokine production. Our results suggest that SFN is a promising treatment for prevention of coronavirus infection or treatment of early disease.The COVID-19 pandemic has highlighted the need for new antiviral targets, as many of the currently approved drugs have proven ineffective against mitigating SARS-CoV-2 infections. The host transmembrane serine protease TMPRSS2 is a highly promising antiviral target, as it plays a direct role in priming the spike protein before viral entry occurs. Further, unlike other targets such as ACE2, TMPRSS2 has no known biological role. Here we utilize virtual screening to curate large libraries into a focused collection of potential inhibitors. Optimization of a recombinant expression and purification protocol for the TMPRSS2 peptidase domain facilitates subsequent biochemical screening and characterization of selected compounds from the curated collection in a kinetic assay. In doing so, we demonstrate that serine protease inhibitors camostat, nafamostat, and gabexate inhibit through a covalent mechanism. We further identify new non-covalent compounds as TMPRSS2 protease inhibitors, demonstrating the utility of a combined virtual and experimental screening campaign in rapid drug discovery efforts.