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1.
Clin Infect Dis ; 73(11): e3949-e3955, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1561940

ABSTRACT

BACKGROUND: We evaluated an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine for immunogenicity and safety in adults aged 18-59 years. METHODS: In this randomized, double-blinded, controlled trial, healthy adults received a medium dose (MD) or a high dose (HD) of the vaccine at an interval of either 14 days or 28 days. Neutralizing antibody (NAb) and anti-S and anti-N antibodies were detected at different times, and adverse reactions were monitored for 28 days after full immunization. RESULTS: A total of 742 adults were enrolled in the immunogenicity and safety analysis. Among subjects in the 0, 14 procedure, the seroconversion rates of NAb in MD and HD groups were 89% and 96% with geometric mean titers (GMTs) of 23 and 30, respectively, at day 14 and 92% and 96% with GMTs of 19 and 21, respectively, at day 28 after immunization. Anti-S antibodies had GMTs of 1883 and 2370 in the MD group and 2295 and 2432 in the HD group. Anti-N antibodies had GMTs of 387 and 434 in the MD group and 342 and 380 in the HD group. Among subjects in the 0, 28 procedure, seroconversion rates for NAb at both doses were both 95% with GMTs of 19 at day 28 after immunization. Anti-S antibodies had GMTs of 937 and 929 for the MD and HD groups, and anti-N antibodies had GMTs of 570 and 494 for the MD and HD groups, respectively. No serious adverse events were observed during the study period. CONCLUSIONS: Adults vaccinated with inactivated SARS-CoV-2 vaccine had NAb as well as anti-S/N antibody and had a low rate of adverse reactions. CLINICAL TRIALS REGISTRATION: NCT04412538.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Double-Blind Method , Humans , Immunogenicity, Vaccine
2.
mBio ; 12(5): e0137221, 2021 10 26.
Article in English | MEDLINE | ID: covidwho-1462899

ABSTRACT

Interleukin6 (IL-6) is a key driver of hyperinflammation in COVID-19, and its level strongly correlates with disease progression. To investigate whether variability in COVID-19 severity partially results from differential IL-6 expression, functional single-nucleotide polymorphisms (SNPs) of IL-6 were determined in Chinese COVID-19 patients with mild or severe illness. An Asian-common IL-6 haplotype defined by promoter SNP rs1800796 and intronic SNPs rs1524107 and rs2066992 correlated with COVID-19 severity. Homozygote carriers of C-T-T variant haplotype were at lower risk of developing severe symptoms (odds ratio, 0.256; 95% confidence interval, 0.088 to 0.739; P = 0.007). This protective haplotype was associated with lower levels of IL-6 and its antisense long noncoding RNA IL-6-AS1 by cis-expression quantitative trait loci analysis. The differences in expression resulted from the disturbance of stimulus-dependent bidirectional transcription of the IL-6/IL-6-AS1 locus by the polymorphisms. The protective rs2066992-T allele disrupted a conserved CTCF-binding locus at the enhancer elements of IL-6-AS1, which transcribed antisense to IL-6 and induces IL-6 expression in inflammatory responses. As a result, carriers of the protective allele had significantly reduced IL-6-AS1 expression and attenuated IL-6 induction in response to acute inflammatory stimuli and viral infection. Intriguingly, this low-producing variant that is endemic to present-day Asia was found in early humans who had inhabited mainland Asia since ∼40,000 years ago but not in other ancient humans, such as Neanderthals and Denisovans. The present study suggests that an individual's IL-6 genotype underlies COVID-19 outcome and may be used to guide IL-6 blockade therapy in Asian patients. IMPORTANCE Overproduction of cytokine interleukin-6 (IL-6) is a hallmark of severe COVID-19 and is believed to play a critical role in exacerbating the excessive inflammatory response. Polymorphisms in IL-6 account for the variability of IL-6 expression and disparities in infectious diseases, but its contribution to the clinical presentation of COVID-19 has not been reported. Here, we investigated IL-6 polymorphisms in severe and mild cases of COVID-19 in a Chinese population. The variant haplotype C-T-T, represented by rs1800796, rs1524107, and rs2066992 at the IL-6 locus, was reduced in patients with severe illness; in contrast, carriers of the wild-type haplotype G-C-G had higher risk of severe illness. Mechanistically, the protective variant haplotype lost CTCF binding at the IL-6 intron and responded poorly to inflammatory stimuli, which may protect the carriers from hyperinflammation in response to acute SARS-CoV-2 infection. These results point out the possibility that IL-6 genotypes underlie the differential viral virulence during the outbreak of COVID-19. The risk loci we identified may serve as a genetic marker to screen high-risk COVID-19 patients.


Subject(s)
COVID-19/metabolism , COVID-19/prevention & control , Interleukin-6/metabolism , A549 Cells , Genotype , Haplotypes/genetics , HeLa Cells , Humans , Interleukin-6/genetics , Polymorphism, Single Nucleotide/genetics , Real-Time Polymerase Chain Reaction , Software
3.
Disease Surveillance ; 36(3):201-203, 2021.
Article in Chinese | CAB Abstracts | ID: covidwho-1302606

ABSTRACT

Objective: To assess the risk of public health emergencies, both the indigenous ones and the imported ones, which might occur in the mainland of China in March 2021.

4.
Chinese Journal of Zoonoses ; 36(5):372-376, 2020.
Article in Chinese | CAB Abstracts | ID: covidwho-647937

ABSTRACT

The epidemiology characteristics of 2019 novel coronavirus diseases (COVID-19) cases in Hainan were collected and analyzed for providing next stage control and prevention strategy in next stage. Spatial and temporal distribution, population characteristic, cluster, the interval between onset, visiting clinic, admitted were analyzed. Local cases and severe cases were also included in the analysis. Result showed that a total of 168 confirmed cases, including 36 severe cases and 5 fatal cases were reported. Cases were mainly distributed in Haikou, Sanya etc tourism cities and counties. The first case occurred in Jan 13th and the epidemic peak occurred in Jan 24th. Since Feb 6th, onset of illness has declined. The male-to-female ratio was 0.9:1. The median age was 51 years. Cases older than 50 years accounted for 54.8%. Retirees accounted for 36.9%, which was highest in all cases. Since Feb, the proportion of local cases rose dramatically. The period from onset to visiting clinic (OTV), from first visiting clinic to diagnosis (VTF), from onset to diagnosis (OTD) and from onset to be admitted (OTA) was longer in local cases than imported cases. Median age and the percentage of underlying diseases of severe/extreme cases were higher than mild/ordinary cases. OTV of severe/extreme cases was longer than mild/ordinary cases, while for VTF, the former was shorter than latter. The epidemic was divided into three stages. Most of cases in the first stage were imported cases, while in the second stage most of cases were local cases. There were few cases in the third stages. We should strengthen personal protection and health monitoring for people in service industry, isolate the close contacts, and carry out publicity and education to raise the awareness of medical treatment for people, especially for old people. Clinical doctors should monitor the state of the patients older than 60 years and with underlying diseases. We should step up epidemic monitoring prevention and control measure for people return from holiday and immigrant to consolidate the effects of prevention and control work.

5.
Preprint in English | medRxiv | ID: ppmedrxiv-20041061

ABSTRACT

BACKGROUNDThere is little information about the coronavirus disease 2019 (Covid-19) during pregnancy. This study aimed to determine the clinical features and the maternal and neonatal outcomes of pregnant women with Covid-19. METHODSIn this retrospective analysis from five hospitals, we included pregnant women with Covid-19 from January 1 to February 20, 2020. The primary composite endpoints were admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Secondary endpoints included the clinical severity of Covid-19, neonatal mortality, admission to neonatal intensive care unit (NICU), and the incidence of acute respiratory distress syndrome (ARDS) of pregnant women and newborns. RESULTSThirty-three pregnant women with Covid-19 and 28 newborns were identified. One (3%) pregnant woman needed the use of mechanical ventilation. No pregnant women admitted to the ICU. There were no moralities among pregnant women or newborns. The percentages of pregnant women with mild, moderate, and severe symptoms were 13 (39.4%),19(57.6%), and 1(3%). One (3.6%) newborn developed ARDS and was admitted to the NICU. The rate of perinatal transmission of SARS-CoV-2 was 3.6%. CONCLUSIONSThis report suggests that pregnant women are not at increased risk for severe illness or mortality with Covid-19 compared with the general population. The SARS-CoV-2 infection during pregnancy might not be associated with as adverse obstetrical and neonatal outcomes that are seen with the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) infection during pregnancy. (Funded by the National Key Research and Development Program.)

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