Chronic Neurological Disorders and Predisposition to Severe COVID-19 in Pediatric Patients in the United States.

BACKGROUND: We investigated the association between chronic pediatric neurological conditions and the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This matched retrospective case-control study includes patients (n = 71,656) with chronic complex neurological disorders under 18 years of age, with laboratory-confirmed diagnosis of COVID-19 or a diagnostic code indicating infection or exposure to SARS-CoV-2, from 103 health systems in the United States. The primary outcome was the severity of coronavirus disease 2019 (COVID-19), which was classified as severe (invasive oxygen therapy or death), moderate (noninvasive oxygen therapy), or mild/asymptomatic (no oxygen therapy). A cumulative link mixed effects model was used for this study. RESULTS: In this study, a cumulative link mixed effects model (random intercepts for health systems and patients) showed that the following classes of chronic neurological disorders were associated with higher odds of severe COVID-19: muscular dystrophies and myopathies (OR = 3.22; 95% confidence interval [CI]: 2.73 to 3.84), chronic central nervous system disorders (OR = 2.82; 95% CI: 2.67 to 2.97), cerebral palsy (OR = 1.97; 95% CI: 1.85 to 2.10), congenital neurological disorders (OR = 1.86; 95% CI: 1.75 to 1.96), epilepsy (OR = 1.35; 95% CI: 1.26 to 1.44), and intellectual developmental disorders (OR = 1.09; 95% CI: 1.003 to 1.19). Movement disorders were associated with lower odds of severe COVID-19 (OR = 0.90; 95% CI: 0.81 to 0.99). CONCLUSIONS: Pediatric patients with chronic neurological disorders are at higher odds of severe COVID-19. Movement disorders were associated with lower odds of severe COVID-19.

Neuropeptidergic Signaling in the American Lobster Homarus americanus: New Insights from High-Throughput Nucleotide Sequencing.

Peptides are the largest and most diverse class of molecules used for neurochemical communication, playing key roles in the control of essentially all aspects of physiology and behavior. The American lobster, Homarus americanus, is a crustacean of commercial and biomedical importance; lobster growth and reproduction are under neuropeptidergic control, and portions of the lobster nervous system serve as models for understanding the general principles underlying rhythmic motor behavior (including peptidergic neuromodulation). While a number of neuropeptides have been identified from H. americanus, and the effects of some have been investigated at the cellular/systems levels, little is currently known about the molecular components of neuropeptidergic signaling in the lobster. Here, a H. americanus neural transcriptome was generated and mined for sequences encoding putative peptide precursors and receptors; 35 precursor- and 41 receptor-encoding transcripts were identified. We predicted 194 distinct neuropeptides from the deduced precursor proteins, including members of the adipokinetic hormone-corazonin-like peptide, allatostatin A, allatostatin C, bursicon, CCHamide, corazonin, crustacean cardioactive peptide, crustacean hyperglycemic hormone (CHH), CHH precursor-related peptide, diuretic hormone 31, diuretic hormone 44, eclosion hormone, FLRFamide, GSEFLamide, insulin-like peptide, intocin, leucokinin, myosuppressin, neuroparsin, neuropeptide F, orcokinin, pigment dispersing hormone, proctolin, pyrokinin, SIFamide, sulfakinin and tachykinin-related peptide families. While some of the predicted peptides are known H. americanus isoforms, most are novel identifications, more than doubling the extant lobster neuropeptidome. The deduced receptor proteins are the first descriptions of H. americanus neuropeptide receptors, and include ones for most of the peptide groups mentioned earlier, as well as those for ecdysis-triggering hormone, red pigment concentrating hormone and short neuropeptide F. Multiple receptors were identified for most peptide families. These data represent the most complete description of the molecular underpinnings of peptidergic signaling in H. americanus, and will serve as a foundation for future gene-based studies of neuropeptidergic control in the lobster.

Prediction of the neuropeptidomes of members of the Astacidea (Crustacea, Decapoda) using publicly accessible transcriptome shotgun assembly (TSA) sequence data.

The decapod infraorder Astacidea is comprised of clawed lobsters and freshwater crayfish. Due to their economic importance and their use as models for investigating neurochemical signaling, much work has focused on elucidating their neurochemistry, particularly their peptidergic systems. Interestingly, no astacidean has been the subject of large-scale peptidomic analysis via in silico transcriptome mining, this despite growing transcriptomic resources for members of this taxon. Here, the publicly accessible astacidean transcriptome shotgun assembly data were mined for putative peptide-encoding transcripts; these sequences were used to predict the structures of mature neuropeptides. One hundred seventy-six distinct peptides were predicted for Procambarus clarkii, including isoforms of adipokinetic hormone-corazonin-like peptide (ACP), allatostatin A (AST-A), allatostatin B, allatostatin C (AST-C) bursicon α, bursicon ß, CCHamide, crustacean hyperglycemic hormone (CHH)/ion transport peptide (ITP), diuretic hormone 31 (DH31), eclosion hormone (EH), FMRFamide-like peptide, GSEFLamide, intocin, leucokinin, neuroparsin, neuropeptide F, pigment dispersing hormone, pyrokinin, RYamide, short neuropeptide F (sNPF), SIFamide, sulfakinin and tachykinin-related peptide (TRP). Forty-six distinct peptides, including isoforms of AST-A, AST-C, bursicon α, CCHamide, CHH/ITP, DH31, EH, intocin, myosuppressin, neuroparsin, red pigment concentrating hormone, sNPF and TRP, were predicted for Pontastacus leptodactylus, with a bursicon ß and a neuroparsin predicted for Cherax quadricarinatus. The identification of ACP is the first from a decapod, while the predictions of CCHamide, EH, GSEFLamide, intocin, neuroparsin and RYamide are firsts for the Astacidea. Collectively, these data greatly expand the catalog of known astacidean neuropeptides and provide a foundation for functional studies of peptidergic signaling in members of this decapod infraorder.

Identification of the first neuropeptides from the enigmatic hexapod order Protura.

The Hexapoda consists of two classes, the Entognatha and the Insecta, with the former group considered basal to the latter. The Protura is a basal order within the Entognatha, the members of which are minute soil dwellers first identified in the early 20th century. Recently, a transcriptome shotgun assembly (TSA) was generated for the proturan Acerentomon sp., providing the first significant molecular resource for this enigmatic hexapod order. As part of an ongoing effort to predict peptidomes for little studied members of the Arthropoda, we have mined this TSA dataset for transcripts encoding putative neuropeptide precursors and predicted the structures of mature peptides from the deduced proteins. Forty-seven peptide-encoding transcripts were mined from the Acerentomon TSA dataset, with 202 distinct peptides predicted from them. The peptides identified included isoforms of adipokinetic hormone, adipokinetic hormone-corazonin-like peptide, allatostatin A, allatostatin B, allatostatin C, allatotropin, bursicon α, bursicon ß, CCHamide, corazonin, crustacean cardioactive peptide, crustacean hyperglycemic hormone/ion transport peptide, diuretic hormone 31, diuretic hormone 44, ecdysis-triggering hormone, eclosion hormone, FMRFamide-like peptide, GSEFLamide, insulin-like peptide, intocin, leucokinin, myosuppressin, neuropeptide F, orcokinin, proctolin, pyrokinin, RYamide, short neuropeptide F, SIFamide, sulfakinin and tachykinin-related peptide; these are the first neuropeptides described from any proturan. Comparison of the Acerentomon precursors and mature peptides with those from other arthropods revealed features characteristic of both the insects and the crustaceans, which is consistent with the hypothesized phylogenetic position of the Protura within the Pancrustacea, i.e. at or near the point of divergence of the hexapods from the crustaceans.

Neuropeptide discovery in the Araneae (Arthropoda, Chelicerata, Arachnida): elucidation of true spider peptidomes using that of the Western black widow as a reference.

The public deposition of large transcriptome shotgun assembly (TSA) datasets for the Araneae (true spiders) provides a resource for determining the structures of the native neuropeptides present in members of this chelicerate order. Here, the Araneae TSA data were mined for putative peptide-encoding transcripts using the recently deduced neuropeptide precursors from the Western black widow Latrodectus hesperus as query templates. Neuropeptide-encoding transcripts from five spiders, Latrodectus tredecimguttatus, Stegodyphus mimosarum, Stegodyphus lineatus, Stegodyphus tentoriicola and Acanthoscurria geniculata, were identified, including ones encoding members of the allatostatin A, allatostatin B, allatostatin C, allatotropin, CAPA/periviscerokinin/pyrokinin, crustacean cardioactive peptide, crustacean hyperglycemic hormone/ion transport peptide, diuretic hormone 31, diuretic hormone 44, eclosion hormone, FMRFamide-like peptide (FLP), GSEFLamide, insulin-like peptide, orcokinin, proctolin, short neuropeptide F, SIFamide, sulfakinin and tachykinin-related peptide (TRP) families. A total of 156 distinct peptides were predicted from the precursor proteins deduced from the S. mimosarum transcripts, with 65, 26, 21 and 12 peptides predicted from those deduced from the A. geniculata, L. tredecimguttatus, S. lineatus and S. tentoriicola sequences, respectively. Among the peptides identified were variant isoforms of FLP, orcokinin and TRP, peptides whose structures are similar to ones previously identified from L. hesperus. The prediction of these atypical peptides from multiple spiders suggests that they may be broadly conserved within the Araneae rather than being species-specific variants. Taken collectively, the data described here greatly expand the number of known Araneae neuropeptides, providing a foundation for future functional studies of peptidergic signaling in this important Chelicerate order.