Persistent SARS-CoV-2 Nucleocapsid Protein Presence in the Intestinal Epithelium of a Pediatric Patient 3 Months After Acute Infection.

In addition to the severe impact of acute respiratory disease during the SARS-CoV-2 pandemic, the issue of "Long COVID" illness has impacted large numbers of patients following the initial infection. Wide ranges of Long Covid incidence have been reported, ranging from 30 to 87%. Long COVID has a variety of clinical manifestations, including gastrointestinal symptoms. Here, we report a case of persistent abdominal pain, 3 months following a SARS-CoV-2 diagnosis, associated with chronic colonic inflammation and the presence of mucosal SARS-CoV-2 virions.

Epidemiologic Assessment of Pediatric Inflammatory Bowel Disease Presentation in NYC During COVID-19.

Inflammatory bowel disease (IBD) pathogenesis is thought to be induced by a mix of genetic susceptibility, microbial populations, and immune triggers such as infections. Severe acute respiratory syndrome coronavirus 2 (SARS-nCoV2) may have increased capacity to generate autoimmune disease as evidenced by known spikes in diseases such as type 1 diabetes mellitus. Public health interventions like masking and closures additionally created remarkable drops in typical viral infections, with remarkable shifts in influenza-like illness reporting in 2020. This study aims to evaluate the impact of SARS-nCoV2 and associated interventions on pediatric IBD presentation in New York City using records of new diagnoses at a consortium of 4 institutions between 2016 and June 2022. We fit time series model (autoregressive integrated moving average model) to monthly and quarterly number of cases of each disease for January 2016-March 2020 and forecast the period between April 2020 and June 2022. We note no decrease in ulcerative colitis (UC) or Crohn disease (CD) in the aftermath of historic low levels of overall viral illness, and statistically significant increases in CD diagnoses and elevation in UC diagnoses creating a trend suggesting overall increase in IBD diagnoses exceeding the baseline rate of increase. These data suggest a possible linkage between SARS-nCoV2 infection rates and subsequent pediatric IBD presentation.

Distinct SARS-CoV-2 RNA fragments activate Toll-like receptors 7 and 8 and induce cytokine release from human macrophages and microglia.

Introduction: The pandemic coronavirus disease 19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is marked by thromboembolic events and an inflammatory response throughout the body, including the brain. Methods: Employing the machine learning approach BrainDead we systematically screened for SARS-CoV-2 genome-derived single-stranded (ss) RNA fragments with high potential to activate the viral RNA-sensing innate immune receptors Toll-like receptor (TLR)7 and/or TLR8. Analyzing HEK TLR7/8 reporter cells we tested such RNA fragments with respect to their potential to induce activation of human TLR7 and TLR8 and to activate human macrophages, as well as iPSC-derived human microglia, the resident immune cells in the brain. Results: We experimentally validated several sequence-specific RNA fragment candidates out of the SARS-CoV-2 RNA fragments predicted in silico as activators of human TLR7 and TLR8. Moreover, these SARS-CoV-2 ssRNAs induced cytokine release from human macrophages and iPSC-derived human microglia in a sequence- and species-specific fashion. Discussion: Our findings determine TLR7 and TLR8 as key sensors of SARS-CoV-2-derived ssRNAs and may deepen our understanding of the mechanisms how this virus triggers, but also modulates an inflammatory response through innate immune signaling.

Distinct SARS-CoV-2 RNA fragments activate Toll-like receptors 7 and 8 and induce cytokine release from human macrophages and microglia

Introduction The pandemic coronavirus disease 19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is marked by thromboembolic events and an inflammatory response throughout the body, including the brain Methods Employing the machine learning approach BrainDead we systematically screened for SARS-CoV-2 genome-derived single-stranded (ss) RNA fragments with high potential to activate the viral RNA-sensing innate immune receptors Toll-like receptor (TLR)7 and/or TLR8. Analyzing HEK TLR7/8 reporter cells we tested such RNA fragments with respect to their potential to induce activation of human TLR7 and TLR8 and to activate human macrophages, as well as iPSC-derived human microglia, the resident immune cells in the brain. Results We experimentally validated several sequence-specific RNA fragment candidates out of the SARS-CoV-2 RNA fragments predicted in silico as activators of human TLR7 and TLR8. Moreover, these SARS-CoV-2 ssRNAs induced cytokine release from human macrophages and iPSC-derived human microglia in a sequence- and species-specific fashion. Discussion Our findings determine TLR7 and TLR8 as key sensors of SARS-CoV-2-derived ssRNAs and may deepen our understanding of the mechanisms how this virus triggers, but also modulates an inflammatory response through innate immune signaling.