Oral Simnotrelvir for Adult Patients with Mild-to-Moderate Covid-19.

BACKGROUND: Simnotrelvir is an oral 3-chymotrypsin-like protease inhibitor that has been found to have in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential efficacy in a phase 1B trial. METHODS: In this phase 2-3, double-blind, randomized, placebo-controlled trial, we assigned patients who had mild-to-moderate coronavirus disease 2019 (Covid-19) and onset of symptoms within the past 3 days in a 1:1 ratio to receive 750 mg of simnotrelvir plus 100 mg of ritonavir or placebo twice daily for 5 days. The primary efficacy end point was the time to sustained resolution of symptoms, defined as the absence of 11 Covid-19-related symptoms for 2 consecutive days. Safety and changes in viral load were also assessed. RESULTS: A total of 1208 patients were enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir and 605 to receive placebo. Among patients in the modified intention-to-treat population who received the first dose of trial drug or placebo within 72 hours after symptom onset, the time to sustained resolution of Covid-19 symptoms was significantly shorter in the simnotrelvir group than in the placebo group (180.1 hours [95% confidence interval {CI}, 162.1 to 201.6] vs. 216.0 hours [95% CI, 203.4 to 228.1]; median difference, -35.8 hours [95% CI, -60.1 to -12.4]; P = 0.006 by Peto-Prentice test). On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group than in the placebo group (mean difference [±SE], -1.51±0.14 log10 copies per milliliter; 95% CI, -1.79 to -1.24). The incidence of adverse events during treatment was higher in the simnotrelvir group than in the placebo group (29.0% vs. 21.6%). Most adverse events were mild or moderate. CONCLUSIONS: Early administration of simnotrelvir plus ritonavir shortened the time to the resolution of symptoms among adult patients with Covid-19, without evident safety concerns. (Funded by Jiangsu Simcere Pharmaceutical; ClinicalTrials.gov number, NCT05506176.).

A context-dependent perspective to understand the relation between parent-child physiological synchrony and child socioemotional adjustment.

Physiological synchrony is an important biological process during which parent-child interaction plays a significant role in shaping child socioemotional adjustment. The present study held a context-dependent perspective to examine the conditional association between parent-child physiological synchrony and child socioemotional adjustment (i.e., relationship quality with parents and child emotion regulation) under different (i.e., from highly unsupportive to highly supportive) emotional contexts. One hundred and fifty school-age Chinese children (Mage = 8.64 years, 63 girls) and their primary caregivers participated in this study. After attaching electrocardiogram (ECG) electrodes, parent-child dyads were instructed to complete a 4-minute conflict discussion task. Parent-child physiological synchrony was calculated based on the within-dyad association between parents' and children's respiratory sinus arrhythmia (RSA) levels across eight 30-second epochs. Parental emotional support, child relationship quality with parents, and child emotion regulation during the discussion task were coded by trained research assistants. Supporting our hypotheses, parental emotional support moderated the relations of parent-child RSA synchrony with both child relationship quality with parents and child emotion regulation. Furthermore, the Johnson-Neyman technique of moderation indicated that the associations between parent and child RSA synchrony and child socioemotional adjustment indicators shifted from negative to positive as the parental emotional support became increasingly high. Our findings suggest that parent-child physiological synchrony may not be inherently adaptive or maladaptive, highlighting the importance of understanding the function of parent-child physiological synchrony under specific contexts. RESEARCH HIGHLIGHTS: Physiological synchrony may not be inherently adaptive or maladaptive, and the meanings of parent-child physiological synchrony might be contingent on contextual factors. Parental emotional support moderated the relations between parent-child respiratory sinus arrhythmia (RSA) synchrony and child socioemotional adjustment indicators (i.e., child relationship quality with parents and child emotion regulation). More positive/less negative parent-child RSA synchrony was associated with better child socioemotional adjustment under a supportive emotional context, whereas with poorer child socioemotional adjustment under an unsupportive emotional context. These findings highlight the significance of considering the emotional context in physiological synchrony studies.

Interleukin-31 expression and relation to disease severity in human asthma.

Interleukin 31 (IL-31) is a novel T helper type 2 effector cytokine that plays an important role in the pathogenesis of allergic diseases. However, its role in human asthma remains unclear. The aim of this study was to measure IL-31 levels in the serum, bronchoalveolar lavage fluid (BALF) and bronchial tissue of asthmatics and healthy subjects, and identify its possible correlation to disease severity. We quantified IL-31 levels in the serum of patients with asthma (n = 44), as well as in controls (n = 22). Of these subjects, 9 asthmatics and five controls underwent bronchoscopy with endobronchial biopsy and BALF collection. Our data showed that serum and BALF IL-31 levels were significantly elevated in patients with asthma compared with controls. Expressions of IL-31 and IL-31 receptor (IL-31RA and OSMR) were more prominent in the bronchial tissue in severe compared to mild asthma and controls. Serum IL-31 levels correlated positively with Th2 related cytokines (IL-5, IL-13, and TSLP), asthma severity or total serum immunoglobulin E (IgE), and inversely with asthma control and the forced expiratory volume in 1 second (FEV1). The current data may provide insight into the underlying pathogenesis of asthma, in which IL-31 has an important pathogenic role.