Latent profiles of stigma and HIV pre-exposure prophylaxis among Black sexual minority men: an exploratory study

Black sexual minority men (BSMM) are a priority population for HIV prevention efforts, including pre-exposure prophylaxis (PrEP) promotion. Intersectional stigma can be associated with deterrence from PrEP utilization among BSMM;this stigma has a novel context in the COVID-19 pandemic. To examine this, we investigated latent profiles of racial, sexuality-based, and related stigmas among HIV-negative BSMM in the COVID-19 pandemic and tested their association with PrEP use. We analyzed cross-sectional data from a pilot sample of HIV-negative BSMM (n = 151) collected between July 2nd and September 3rd, 2020 in the United States, primarily located on the east coast. We conducted latent profile analysis using internalized racism and homophobia, anticipated racism and homophobia, HIV stigma, healthcare stigma, and PrEP stigma. We then tested associations between latent profiles and both PrEP use (binary) and PrEP acceptability (ordinal) using modified Poisson regression and cumulative log models, respectively. We identified three latent profiles, characterized as ‘Low Internalized Stigma, High Anticipated Stigma’ (reference profile), ‘High Internalized Stigma, Low Anticipated Stigma,’ and ‘High Internalized and Anticipated Stigma.’ The ‘High Internalized and Anticipated Stigma’ profile was associated with PrEP use (aPR 0.37, 95% CI 0.17, 0.82) and acceptability (aPR 0.32, 95% CI 0.18, 0.57) nearly three times as low as the comparing profile after adjustment for confounders. The ‘High Internalized Stigma, Low Anticipated Stigma’ was also associated with PrEP acceptability nearly three times as low as the reference (aPR 0.38, 95% CI 0.22, 0.68). We identified latent profiles characterized by internalized and anticipated stigmas among BSMM during the COVID-19 pandemic and found that the profile with the highest levels of both internalized and anticipated stigma was associated with the lowest PrEP use and acceptability. Internalized stigma may be a particularly relevant intervention target in efforts to promote PrEP uptake among BSMM. Supplementary Information The online version contains supplementary material available at 10.1007/s43545-022-00490-w.

Potential Material Basis of Yupingfeng Powder for the Prevention and Treatment of 2019 Novel Coronavirus Pneumonia: A Study Involving Molecular Docking and Molecular Dynamic Simulation Technology.

Objective: In this study, we investigated the potential material basis of Yupingfeng powder in the prevention and treatment of 2019 novel coronavirus pneumonia (NCP) by applying molecular docking and molecular dynamic simulation technology. Design: The active ingredients and predictive targets of Yupingfeng powder were sourced using the TCMSP, ETCM, and TCMIP traditional Chinese medicine databases. NCP-related targets were then acquired from the DisGeNET and GeneCards databases, and common disease-drug targets were imported into the STRING database, and Cytoscape software was used to generate a protein-protein interaction network following the use of a network topology algorithm to identify key target genes. Gene Ontology (GO) and KEGG pathway enrichment analysis was then performed using the target genes and GOEAST and DAVID online tools. The mechanism of Yupingfeng powder in the prevention and treatment of NCP was analyzed with reference to the relevant literature. AutoDock software was used for molecular docking, the preliminary analysis of binding status, and to identify the best conformation. Desmond software was used to perform molecular dynamic simulations for protein and compound complexes, perform free energy calculations and hydrogen bond analysis, and to further verify the binding mode. Results: Overall, 38 main active components and 218 predictive targets of Yupingfeng powder were identified and 298 disease targets related to NCP were retrieved from disease databases. Yupingfeng powder was found to act predominantly on the TNF, Toll-like receptor, HIF-1, NOD-like receptor, cytokine-receptor interaction, MAPK, T cell receptor, and VEGF signaling pathways. Molecular docking of the three selected key active components with the 3CL-like protease (3CL-Pro) of SARS-CoV-2 showed that they each had a strong binding force and good affinity. Conclusions: Yupingfeng powder primarily acts on multiple active ingredients and potential targets through multiple action channels and signal pathways. Molecular docking and molecular dynamic simulation technology were used to effectively predict and analyze the potential mechanism by which this Chinese medicine can combat NCP. These results provide a reference for developing new modern Chinese medicine preparations against NCP in the future.

Forecasting COVID-19 Cases Based on Social Distancing in Maryland, USA: A Time-Series Approach.

OBJECTIVE: Our objective is to forecast the number of coronavirus disease 2019 (COVID-19) cases in the state of Maryland, United States, using transfer function time series (TS) models based on a Social Distancing Index (SDI) and determine how their parameters relate to the pandemic mechanics. METHODS: A moving window of 2 mo was used to train the transfer function TS model that was then tested on the next week data. After accounting for a secular trend and weekly cycle of the SDI, a high correlation was documented between it and the daily caseload 9 days later. Similar patterns were also observed on the daily COVID-19 cases and incorporated in our models. RESULTS: In most cases, the proposed models provide a reasonable performance that was, on average, moderately better than that delivered by TS models based only on previous observations. The model coefficients associated with the SDI were statistically significant for most of the training/test sets. CONCLUSIONS: Our proposed models that incorporate SDI can forecast the number of COVID-19 cases in a region. Their parameters have real-life interpretations and, hence, can help understand the inner workings of the epidemic. The methods detailed here can help local health governments and other agencies adjust their response to the epidemic.

Assessment of two-pool multiplex long-amplicon nanopore sequencing of SARS-CoV-2.

Genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an important role in COVID-19 pandemic control and elimination efforts, especially by elucidating its global transmission network and illustrating its viral evolution. The deployment of multiplex PCR assays that target SARS-CoV-2 followed by either massively parallel or nanopore sequencing is a widely-used strategy to obtain genome sequences from primary samples. However, multiplex PCR-based sequencing carries an inherent bias of sequencing depth among different amplicons, which may cause uneven coverage. Here we developed a two-pool, long-amplicon 36-plex PCR primer panel with ~1000-bp amplicon lengths for full-genome sequencing of SARS-CoV-2. We validated the panel by assessing nasopharyngeal swab samples with a <30 quantitative reverse transcription PCR cycle threshold value and found that ≥90% of viral genomes could be covered with high sequencing depths (≥20% mean depth). In comparison, the widely-used ARTIC panel yielded 79%-88% high-depth genome regions. We estimated that ~5 Mbp nanopore sequencing data may ensure a >95% viral genome coverage with a ≥10-fold depth and may generate reliable genomes at consensus sequence levels. Nanopore sequencing yielded false-positive variations with frequencies of supporting reads <0.8, and the sequencing errors mostly occurred on the 5' or 3' ends of reads. Thus, nanopore sequencing could not elucidate intra-host viral diversity.

Detection and Differentiation of SARS-CoV-2, Influenza, and Respiratory Syncytial Viruses by CRISPR.

SARS-CoV-2, influenza, and respiratory syncytial viruses (RSVs) cause acute respiratory infections with similar symptoms. Since the treatments and outcomes of these infections are different, the early detection and accurate differentiation of the viruses are clinically important for the prevention and treatment of the diseases. We previously demonstrated that clustered regularly interspaced short palindromic repeats (CRISPR) could rapidly and precisely detect SARS-CoV-2. The objective of this study was to develop CRISPR as a test for simultaneously detecting and accurately distinguishing the viruses. The CRISPR assay with an RNA guide against each virus was performed in the reference standards of SARS-CoV-2, influenza A and B, and RSV. The CRISPR assay had a limit of detection of 1-100 copies/µL for specifically detecting SARS-CoV-2, influenza A and B, and RSV without cross-reaction with other respiratory viruses. The validation of the test in nasopharyngeal specimens showed that it had a 90-100% sensitivity and 100% specificity for the detection of SARS-CoV-2, influenza A and B, and RSV. The CRISPR assay could potentially be used for sensitive detection and specific differentiation of the respiratory viruses.

Genomic Elucidation of a COVID-19 Resurgence and Local Transmission of SARS-CoV-2 in Guangzhou, China.

While China experienced a peak and decline in coronavirus disease 2019 (COVID-19) cases at the start of 2020, regional outbreaks continuously emerged in subsequent months. Resurgences of COVID-19 have also been observed in many other countries. In Guangzhou, China, a small outbreak, involving less than 100 residents, emerged in March and April 2020, and comprehensive and near-real-time genomic surveillance of SARS-CoV-2 was conducted. When the numbers of confirmed cases among overseas travelers increased, public health measures were enhanced by shifting from self-quarantine to central quarantine and SARS-CoV-2 testing for all overseas travelers. In an analysis of 109 imported cases, we found diverse viral variants distributed in the global viral phylogeny, which were frequently shared within households but not among passengers on the same flight. In contrast to the viral diversity of imported cases, local transmission was predominately attributed to two specific variants imported from Africa, including local cases that reported no direct or indirect contact with imported cases. The introduction events of the virus were identified or deduced before the enhanced measures were taken. These results show the interventions were effective in containing the spread of SARS-CoV-2, and they rule out the possibility of cryptic transmission of viral variants from the first wave in January and February 2020. Our study provides evidence and emphasizes the importance of controls for overseas travelers in the context of the pandemic and exemplifies how viral genomic data can facilitate COVID-19 surveillance and inform public health mitigation strategies.

Public Compliance With Social Distancing Measures and SARS-CoV-2 Spread : A Quantitative Analysis of 5 States.

OBJECTIVE: We quantified the association between public compliance with social distancing measures and the spread of SARS-CoV-2 during the first wave of the epidemic (March-May 2020) in 5 states that accounted for half of the total number of COVID-19 cases in the United States. METHODS: We used data on mobility and number of COVID-19 cases to longitudinally estimate associations between public compliance, as measured by human mobility, and the daily reproduction number and daily growth rate during the first wave of the COVID-19 epidemic in California, Illinois, Massachusetts, New Jersey, and New York. RESULTS: The 5 states mandated social distancing directives during March 19-24, 2020, and public compliance with mandates started to decrease in mid-April 2020. As of May 31, 2020, the daily reproduction number decreased from 2.41-5.21 to 0.72-1.19, and the daily growth rate decreased from 0.22-0.77 to -0.04 to 0.05 in the 5 states. The level of public compliance, as measured by the social distancing index (SDI) and daily encounter-density change, was high at the early stage of implementation but decreased in the 5 states. The SDI was negatively associated with the daily reproduction number (regression coefficients range, -0.04 to -0.01) and the daily growth rate (from -0.009 to -0.01). The daily encounter-density change was positively associated with the daily reproduction number (regression coefficients range, 0.24 to 1.02) and the daily growth rate (from 0.05 to 0.26). CONCLUSIONS: Social distancing is an effective strategy to reduce the incidence of COVID-19 and illustrates the role of public compliance with social distancing measures to achieve public health benefits.

Rapid and Sensitive Detection of SARS-CoV-2 Using Clustered Regularly Interspaced Short Palindromic Repeats.

Rapid and accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for controlling the pandemic of coronavirus disease 2019. Polymerase chain reaction (PCR)-based technique is the standard test for detection of SARS-CoV-2, which, however, requires complicated sample manipulation (e.g., RNA extraction) and is time-consuming. We previously demonstrated that clustered regularly interspaced short palindromic repeats (CRISPR) could precisely detect Human papillomavirus and somatic mutations of Epidermal growth factor receptor gene and Kirsten rat sarcoma viral oncogene homolog gene in plasma. The objective of this study was to develop CRISPR as a rapid test for sensitive detection of SARS-CoV-2. We first combined reverse transcription-isothermal recombinase polymerase amplification and CRSIPR to detect SARS-CoV-2 in genomic RNA of cells infected with the virus. The CRISPR assay with guide RNA against the M gene of SARS-CoV-2 had a sensitivity of 0.1 copies per µL for detection of the virus. We then used the CRSIPR assay to directly analyze raw SARS-CoV-2 samples. The CRISPR assay could sensitively detect SARS-CoV-2 in one hour without RNA extraction. This assay can be performed at a single temperature and with minimal equipment. The results were immediately visualized either by a UV light illuminator or paper strips. The diagnostic value of the test was confirmed in nasopharyngeal swab specimens. Altogether, we have developed a rapid CRISPR test for sensitive detection of SARS-CoV-2.