New York City (NYC) was an epicenter of the coronavirus disease 2019 (COVID-19) outbreak in the United States during spring 2020 (1). During March-May 2020, approximately 203,000 laboratory-confirmed COVID-19 cases were reported to the NYC Department of Health and Mental Hygiene (DOHMH). To obtain more complete data, DOHMH used supplementary information sources and relied on direct data importation and matching of patient identifiers for data on hospitalization status, the occurrence of death, race/ethnicity, and presence of underlying medical conditions. The highest rates of cases, hospitalizations, and deaths were concentrated in communities of color, high-poverty areas, and among persons aged ≥75 years or with underlying conditions. The crude fatality rate was 9.2% overall and 32.1% among hospitalized patients. Using these data to prevent additional infections among NYC residents during subsequent waves of the pandemic, particularly among those at highest risk for hospitalization and death, is critical. Mitigating COVID-19 transmission among vulnerable groups at high risk for hospitalization and death is an urgent priority. Similar to NYC, other jurisdictions might find the use of supplementary information sources valuable in their efforts to prevent COVID-19 infections. This report describes cases of laboratory-confirmed COVID-19 among NYC residents diagnosed during February 29-June 1, 2020, that were reported to DOHMH. DOHMH began COVID-19 surveillance in January 2020 when testing capacity for SARS-CoV-2 (the virus that causes COVID-19) using real-time reverse transcription-polymerase chain reaction (RT-PCR) was limited by strict testing criteria because of limited test availability only through CDC. The NYC and New York State public health laboratories began testing hospitalized patients at the end of February and early March. DOHMH encouraged patients with mild symptoms to remain at home rather than seek health care because of shortages of personal protective equipment and laboratory tests at hospitals and clinics. Commercial laboratories began testing for SARS-CoV-2 in mid-to late March. During February 29-March 15, patients with laboratory-confirmed COVID-19 were interviewed by DOHMH, and close contacts were identified for monitoring. The rapid rise in laboratory-confirmed cases (cases) quickly made interviewing all patients, as well as contact tracing, unsustainable. Subsequent case investigations
RNA splicing plays a critical role in the programming of neuronal differentiation and, consequently, normal human neurodevelopment, and its disruption may underlie neurodevelopmental and neuropsychiatric disorders. The RNA-binding protein, fox-1 homolog (RBFOX1; also termed A2BP1 or FOX1), is a neuron-specific splicing factor predicted to regulate neuronal splicing networks clinically implicated in neurodevelopmental disease, including autism spectrum disorder (ASD), but only a few targets have been experimentally identified. We used RNA sequencing to identify the RBFOX1 splicing network at a genome-wide level in primary human neural stem cells during differentiation. We observe that RBFOX1 regulates a wide range of alternative splicing events implicated in neuronal development and maturation, including transcription factors, other splicing factors and synaptic proteins. Downstream alterations in gene expression define an additional transcriptional network regulated by RBFOX1 involved in neurodevelopmental pathways remarkably parallel to those affected by splicing. Several of these differentially expressed genes are further implicated in ASD and related neurodevelopmental diseases. Weighted gene co-expression network analysis demonstrates a high degree of connectivity among these disease-related genes, highlighting RBFOX1 as a key factor coordinating the regulation of both neurodevelopmentally important alternative splicing events and clinically relevant neuronal transcriptional programs in the development of human neurons.
Background New York City (NYC) was hard-hit by the SARS-CoV-2 pandemic and is also home to a large population of people with HIV (PWH). Methods We matched lab-confirmed COVID-19 case and death data reported to the NYC Health Department as of June 2, 2020, against the NYC HIV surveillance registry. We describe and compare the characteristics and COVID-19-related outcomes of PWH diagnosed with COVID-19 with all NYC PWH and with all New Yorkers diagnosed with COVID-19. Results Through June 2, 204,583 NYC COVID-19 cases were reported. The registry match identified 2,410 PWH with diagnosed COVID-19 eligible for analysis (1.06% of all COVID-19 cases). Compared with all NYC PWH and all New Yorkers diagnosed with COVID-19, a higher proportion of PWH with COVID-19 were older, male, Black or Latino, and living in high-poverty neighborhoods. At least one underlying condition was reported for 58.9% of PWH with COVID-19. Compared with all NYC COVID-19 cases, a higher proportion of PWH with COVID-19 experienced hospitalization, intensive care unit admission and/or death; most PWH who experienced poor COVID-19-related outcomes had CD4 <500 cells/µL. Conclusions Given NYC HIV prevalence is 1.5%, PWH were not overrepresented among COVID-19 cases. However, compared with NYC COVID-19 cases overall, a greater proportion of PWH had adverse COVID-19-related outcomes, perhaps because of a higher prevalence of factors associated with poor COVID-19 outcomes. Given the pandemic’s exacerbating effects on health inequities, HIV public health and clinical communities must strengthen services and support for people living with and affected by HIV.
Sharing syndromic surveillance use cases can foster new ideas and build capacity for public health preparedness and response.
Senataxin, encoded by the SETX gene, contributes to multiple aspects of gene expression, including transcription and RNA processing. Mutations in SETX cause the recessive disorder ataxia with oculomotor apraxia type 2 (AOA2) and a dominant juvenile form of amyotrophic lateral sclerosis (ALS4). To assess the functional role of senataxin in disease, we examined differential gene expression in AOA2 patient fibroblasts, identifying a core set of genes showing altered expression by microarray and RNA-sequencing. To determine whether AOA2 and ALS4 mutations differentially affect gene expression, we overexpressed disease-specific SETX mutations in senataxin-haploinsufficient fibroblasts and observed changes in distinct sets of genes. This implicates mutation-specific alterations of senataxin function in disease pathogenesis and provides a novel example of allelic neurogenetic disorders with differing gene expression profiles. Weighted gene co-expression network analysis (WGCNA) demonstrated these senataxin-associated genes to be involved in both mutation-specific and shared functional gene networks. To assess this in vivo, we performed gene expression analysis on peripheral blood from members of 12 different AOA2 families and identified an AOA2-specific transcriptional signature. WGCNA identified two gene modules highly enriched for this transcriptional signature in the peripheral blood of all AOA2 patients studied. These modules were disease-specific and preserved in patient fibroblasts and in the cerebellum of Setx knockout mice demonstrating conservation across species and cell types, including neurons. These results identify novel genes and cellular pathways related to senataxin function in normal and disease states, and implicate alterations in gene expression as underlying the phenotypic differences between AOA2 and ALS4.
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