Efficacy and Safety of the RBD-Dimer-Based Covid-19 Vaccine ZF2001 in Adults.

BACKGROUND: The ZF2001 vaccine, which contains a dimeric form of the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 and aluminum hydroxide as an adjuvant, was shown to be safe, with an acceptable side-effect profile, and immunogenic in adults in phase 1 and 2 clinical trials. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to investigate the efficacy and confirm the safety of ZF2001. The trial was performed at 31 clinical centers across Uzbekistan, Indonesia, Pakistan, and Ecuador; an additional center in China was included in the safety analysis only. Adult participants (≥18 years of age) were randomly assigned in a 1:1 ratio to receive a total of three 25-µg doses (30 days apart) of ZF2001 or placebo. The primary end point was the occurrence of symptomatic coronavirus disease 2019 (Covid-19), as confirmed on polymerase-chain-reaction assay, at least 7 days after receipt of the third dose. A key secondary efficacy end point was the occurrence of severe-to-critical Covid-19 (including Covid-19-related death) at least 7 days after receipt of the third dose. RESULTS: Between December 12, 2020, and December 15, 2021, a total of 28,873 participants received at least one dose of ZF2001 or placebo and were included in the safety analysis; 25,193 participants who had completed the three-dose regimen, for whom there were approximately 6 months of follow-up data, were included in the updated primary efficacy analysis that was conducted at the second data cutoff date of December 15, 2021. In the updated analysis, primary end-point cases were reported in 158 of 12,625 participants in the ZF2001 group and in 580 of 12,568 participants in the placebo group, for a vaccine efficacy of 75.7% (95% confidence interval [CI], 71.0 to 79.8). Severe-to-critical Covid-19 occurred in 6 participants in the ZF2001 group and in 43 in the placebo group, for a vaccine efficacy of 87.6% (95% CI, 70.6 to 95.7); Covid-19-related death occurred in 2 and 12 participants, respectively, for a vaccine efficacy of 86.5% (95% CI, 38.9 to 98.5). The incidence of adverse events and serious adverse events was balanced in the two groups, and there were no vaccine-related deaths. Most adverse reactions (98.5%) were of grade 1 or 2. CONCLUSIONS: In a large cohort of adults, the ZF2001 vaccine was shown to be safe and effective against symptomatic and severe-to-critical Covid-19 for at least 6 months after full vaccination. (Funded by the National Science and Technology Major Project and others; ClinicalTrials.gov number, NCT04646590.).

The association between plasminogen activator inhibitor type-1 and clinical outcome in paediatric sepsis.

: Acute phase protein plasminogen activator inhibitor type-1 (PAI-1) is a key element in fibrinolysis inhibition in sepsis-induced disseminated intravascular coagulation (DIC). Elevated PAI-1 level is related to worse outcome in sepsis. The aim of this study was to investigate the relationship between plasma PAI-1 level and clinical outcome in children with sepsis. A total of 35 children with sepsis were enrolled into this prospective study. Plasma PAI-1 was measured on day-1 and day-4. Systemic coagulation profile was measured on day-4. Individuals were followed up until 28 days. The mean PAI-1 from day-1 to day-4 in overt DIC children was not statistically significant. Contrarily, among nonovert DIC individuals, there was a significant difference (P ≤ 0.001) in PAI-1 levels on day-1 compared with day-4 were 95.25 ±â€Š46.57 vs. 60.36 ±â€Š37.31 ng/ml, respectively. Among survivors, mean PAI-1 level on day-1 was statistically higher than PAI-1 level on day-4 (82.47 ±â€Š44.43 vs. 58.39 ±â€Š32.98 ng/ml), P = 0.021. There was no significant difference between PAI-1 levels on day-1 compared with day-4 in nonsurvivors. PAI-1 was correlated to DIC score with r = 0.606 (P ≤ 0.001). PAI-1 levels significantly decreased on day-4 compared with day-1 among nonovert DIC individuals, and not in overt DIC individuals. Changes in PAI-1 levels in nonsurvivors did not differ. PAI-1 level was positively correlated with DIC score.

Zika Virus Seropositivity in 1-4-Year-Old Children, Indonesia, 2014.

We assessed Zika virus seroprevalence among healthy 1-4-year-old children using a serum sample collection assembled in 2014 representing 30 urban sites across Indonesia. Of 662 samples, 9.1% were Zika virus seropositive, suggesting widespread recent Zika virus transmission and immunity. Larger studies are needed to better determine endemicity in Indonesia.