Event rates and incidence of post-COVID-19 condition in hospitalised SARS-CoV-2 positive children and young people and controls across different pandemic waves: exposure-stratified prospective cohort study in Moscow (StopCOVID).

BACKGROUND: Long-term health outcomes in children and young people (CYP) after COVID-19 infection are not well understood and studies with control groups exposed to other infections are lacking. This study aimed to investigate the incidence of post-COVID-19 condition (PCC) and incomplete recovery in CYP after hospital discharge and compare outcomes between different SARS-CoV-2 variants and non-SARS-CoV-2 infections. METHODS: A prospective exposure-stratified cohort study of individuals under 18 years old in Moscow, Russia. Exposed cohorts were paediatric patients admitted with laboratory-confirmed COVID-19 infection between April 2 and December 11, 2020 (Wuhan variant cohort) and between January 12 and February 19, 2022 (Omicron variant cohort). CYP admitted with respiratory and intestinal infections, but negative lateral flow rapid diagnostic test and PCR-test results for SARS-CoV-2, between January 12 and February 19, 2022, served as unexposed reference cohort. Comparison between the 'exposed cohorts' and 'reference cohort' was conducted using 1:1 matching by age and sex. Follow-up data were collected via telephone interviews with parents, utilising the long COVID paediatric protocol and survey developed by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). The WHO case definition was used to categorise PCC. RESULTS: Of 2595 CYP with confirmed COVID-19, 1707 (65.7%) participated in follow-up interviews, with 1183/1707 (69%) included in the final 'matched' analysis. The median follow-up time post-discharge was 6.7 months. The incidence of PCC was significantly higher in the Wuhan variant cohort (89.7 cases per 1000 person-months, 95% CI 64.3-120.3) compared to post-infection sequalae in the reference cohort (12.2 cases per 1000 person-months, 95% CI 4.9-21.9), whereas the difference with the Omicron variant cohort and reference cohort was not significant. The Wuhan cohort had higher incidence rates of dermatological, fatigue, gastrointestinal, sensory, and sleep manifestations, as well as behavioural and emotional problems than the reference cohort. The only significant difference between Omicron variant cohort and reference cohort was decreased school attendance. When comparing the Wuhan and Omicron variant cohorts, higher incidence of PCC and event rates of fatigue, decreased physical activity, and deterioration of relationships was observed. The rate of incomplete recovery was also significantly higher in the Wuhan variant cohort than in both the reference and the Omicron variant cohorts. CONCLUSIONS: Wuhan variant exhibited a propensity for inducing a broad spectrum of physical symptoms and emotional behavioural changes, suggesting a pronounced impact on long-term health outcomes. Conversely, the Omicron variant resulted in fewer post-infection effects no different from common seasonal viral illnesses. This may mean that the Omicron variant and subsequent variants might not lead to the same level of long-term health consequences as earlier variants.

Alkyl Substituent in Heterocyclic Substrate, Carbon Skeleton Length of O-Nucleophilic Agent and Conditions Influence the Product Composition from Competitive Reactions of SNipso Substitution by Aliphatic Oligoethers.

Using 1H NMR spectroscopy, we studied the relative mobility of the NO2 group in 1-alkyl-5-nitro-1,2,4-triazoles in the reaction of nucleophilic heterocyclic substitution by aliphatic oligoethers. The main pathways of the SNipso substitution process and the composition of resultant products from competitive reactions were examined, and the key factors influencing the relative mobility of the nitro group, such as the nitrotriazole substrate constitution, the carbon skeleton length of the O-nucleophilic agent and the process conditions, were discussed. Several independent competitive reactions directed towards the substitution of the nitro group at position C(5) in the alkyltriazole substrate by different types of nucleophiles such as alkoxide-, hydroxide- and triazolonate anions were observed to take place under conditions used. The major reaction yielded oligoethers containing terminal alkyltriazole heterocycles. Secondary reactions occurred to form the corresponding triazolone and N-C triazolyl triazolone structures in the reaction system. Additionally, in excess of the alkaline agent, alkaline hydrolysis was observed to proceed at the final stages of the process involving the O-nucleophile having a longer oligoether backbone in the series studied, leading to the formation of new O-nucleophilic sites. The obtained findings can provide a foundation for devising a method for the modification of a wide range of commercially available aliphatic oligo- or polyethers to prepare functional macromolecules whose terminals carry bioactive 1,2,4-triazole heterocycles located at a desired distance from each other.

New 5-Aminotetrazole-Based Energetic Polymers: Synthesis, Structure and Properties.

An N-glycidyl-5-aminotetrazole homopolymer was synthesized herein by nucleophilic substitution of 5-aminotetrazole heterocycles for chlorine atoms in poly-(epichlorohydrin)-butanediol. Copolymers of N-glycidyl-5-aminotetrazole and glycidyl azide with a varied ratio of energetic elements were synthesized by simultaneously reacting the 5-aminotetrazole sodium salt and the azide ion with the starting polymeric matrix. The 5-aminotetrazole-based homopolymer was nitrated to furnish a polymer whose macromolecule is enriched additionally with energy-rich terminal ONO2 groups and nitrate anions. The structures of the synthesized polymers were characterized by 1H and 13C NMR and IR spectroscopies, elemental analysis and gel-permeation chromatography. The densities were experimentally measured, and thermal stability data were acquired by differential scanning calorimetry. The insertion of aminotetrazole heterocycles into the polymeric chain and their modification via nitration provides an acceptable thermal stability and a considerable enhancement in density and nitrogen content compared to azide homopolymer GAP. By the 1.3-dipolar cycloaddition reaction, we demonstrated the conceptual possibility of preparing spatially branched, energy-rich polymeric binders bearing 5-aminotetrazole and 1,2,3-triazole heterocycles starting from the plasticized azide copolymers. The presence of the aforesaid advantages makes the reported polymers attractive candidates for use as a scaffold of energetic binders.

Prevalence and risk factors of post-COVID-19 condition in adults and children at 6 and 12 months after hospital discharge: a prospective, cohort study in Moscow (StopCOVID).

BACKGROUND: Previous studies assessing the prevalence of COVID-19 sequelae in adults and children were performed in the absence of an agreed definition. We investigated prevalence of post-COVID-19 condition (PCC) (WHO definition), at 6- and 12-months follow-up, amongst previously hospitalised adults and children and assessed risk factors. METHODS: Prospective cohort study of children and adults with confirmed COVID-19 in Moscow, hospitalised between April and August, 2020. Two follow-up telephone interviews, using the International Severe Acute Respiratory and Emerging Infection Consortium survey, were performed at 6 and 12 months after discharge. RESULTS: One thousand thirteen of 2509 (40%) of adults and 360 of 849 (42%) of children discharged participated in both the 6- and 12-month follow-ups. PCC prevalence was 50% (95% CI 47-53) in adults and 20% (95% CI 16-24) in children at 6 months, with decline to 34% (95% CI 31-37) and 11% (95% CI 8-14), respectively, at 12 months. In adults, female sex was associated with PCC at 6- and 12-month follow-up (OR 2.04, 95% CI 1.57 to 2.65) and (OR 2.04, 1.54 to 2.69), respectively. Pre-existing hypertension (OR 1.42, 1.04 to 1.94) was associated with post-COVID-19 condition at 12 months. In children, neurological comorbidities were associated with PCC both at 6 months (OR 4.38, 1.36 to 15.67) and 12 months (OR 8.96, 2.55 to 34.82) while allergic respiratory diseases were associated at 12 months (OR 2.66, 1.04 to 6.47). CONCLUSIONS: Although prevalence of PCC declined one year after discharge, one in three adults and one in ten children experienced ongoing sequelae. In adults, females and persons with pre-existing hypertension, and in children, persons with neurological comorbidities or allergic respiratory diseases are at higher risk of PCC.

Energetic Materials Based on N-substituted 4(5)-nitro-1,2,3-triazoles.

The regularities and synthetic potentialities of the alkylation of 4(5)-nitro-1,2,3-triazole in basic media were explored, and new energetic ionic and nitrotriazole-based coordination compounds were synthesized in this study. The reaction had a general nature and ended with the formation of N1-, N2-, and N3-alkylation products, regardless of the conditions and reagent nature (alkyl- or aryl halides, alkyl nitrates, dialkyl sulfates). This reaction offers broad opportunities for expanding the variability of substituents on the nitrotriazole ring in the series of primary and secondary aliphatic, alicyclic, and aromatic substituents, which is undoubtedly crucial for solving the problems related to both high-energy materials development and medicinal chemistry when searching for new efficient bioactive compounds. An efficient methodology for the separation of regioisomeric N-alkyl(aryl)nitrotriazoles has been devised and relies on the difference in their basicity and reactivity during quaternization and complexation reactions. Based on the inaccessible N3-substitution products that exhibit a combination of properties of practical importance, a series of energy-rich ionic systems and coordination compounds were synthesized that are gaining ever-increasing interest for the chemistry of energy-efficient materials, coordination chemistry, and chemistry of ionic liquids.

Assessment of the combined effects of chromium and benzene on the rat neuroendocrine and immune systems.

This study assessed the hypothalamic-pituitary-adrenocortical (HPA) axis and lymphoid organs (thymus, spleen, and bone marrow) of Wistar rats treated with a mixture of chromium and benzene. Animals were assessed at three time-points (45, 90 and 135 days) following oral mixture exposure. The hypothalamus-pituitary system was examined in light and electron microscopy. Lymphoid organs underwent a morphological assessment and the immunophenotype of splenocytes was characterized immunohistochemically using monoclonal antibodies. Splenocytes cytokine production of was determined by ELISA after Con-A stimulation. Combined exposure to chromium and benzene in average doses of 20 mg Cr (VI)/kg body weight/day and 0.6 ml benzene/kg body weight/day impaired the responsiveness of the central compartment of the HPA axis, as evidenced by functional activation of the secretory activity of the hypothalamus and pituitary gland, which was not followed by a sufficient extrusion of nonapeptides at the neurohypophysis and hypothalamic median eminence. Chromium and benzene exposure reduced the thymus mass, thymocytes count, and caused a number of structural and functional changes indicative of transient thymus involution. In the spleen, exposure to both chemicals resulted in lymphoreticular hyperplasia and plasma cell-macrophage transformation (also observed in lymph nodes). Apoptosis of thymocytes and lymphocytes was also observed in T-zones of the spleen. Notably, the effects were similar to those observed earlier for the single agents, under the same experimental conditions, without evidence of additivity.