Background MVC-COV1901, a recombinant protein vaccine containing pre-fusion-stabilised spike protein S-2P adjuvanted with CpG 1018 and aluminium hydroxide, has been shown to be well tolerated with a good safety profile in healthy adults aged 20–49 years in a phase 1 trial, and provided a good cellular and humoral immune responses. We present the interim safety, tolerability, and immunogenicity results of a phase 2 clinical trial of the MVC-COV1901 vaccine in Taiwan. Methods This is a large-scale, double-blind, randomised, placebo-controlled phase 2 trial done at ten medical centres and one regional hospital in Taiwan. Individuals aged 20 years or older who were generally healthy or had stable pre-existing medical conditions were eligible for enrolment. Exclusion criteria included (but were not limited to) travel overseas within 14 days of screening, intention to travel overseas within 6 months of the screening visit, and the absence of prespecified medical conditions, including immunosuppressive illness, a history of autoimmune disease, malignancy with risk to recur, a bleeding disorder, uncontrolled HIV infection, uncontrolled hepatitis B and C virus infections, SARS-CoV-1 or SARS-CoV-2 infections, an allergy to any vaccine, or a serious medical condition that could interfere with the study. Study participants were randomly assigned (6:1) to receive two doses of either MVC-COV1901 or placebo, administered via intramuscular injection on day 1 and day 29. MVC-COV1901 contained 15 μg of S-2P protein adjuvanted with 750 μg CpG 1018 and 375 μg aluminium hydroxide in a 0·5 mL aqueous solution, and the placebo contained the same volume of saline. Randomisation was done centrally by use of an interactive web response system, stratified by age (≥20 to <65 years and ≥65 years). Participants and investigators were masked to group assignment. The primary outcomes were to evaluate the safety, tolerability, and immunogenicity of MVC-COV1901 from day 1 (the day of the first dose) to day 57 (28 days after the second dose). Safety was assessed in all participants who received at least one dose. Immunogenicity was assessed by measuring geometric mean titres (GMTs) and seroconversion rates of neutralising antibody and antigen-specific IgG in the per-protocol population. This study is registered with ClinicalTrials.gov , NCT04695652 . Findings Of 4173 individuals screened between Dec 30, 2020, and April 2, 2021, 3854 were enrolled and randomly assigned: 3304 to the MVC-COV1901 group and 550 to the placebo group. A total of 3844 participants (3295 in the MVC-COV1901 group and 549 in the placebo group) were included in the safety analysis set, and 1053 participants (903 and 150) had received both doses and were included in the per-protocol immunogenicity analysis set. From the start of this phase 2 trial to the time of interim analysis, no vaccine-related serious adverse events were recorded. The most com...

Human enterovirus D68 (EV-D68) was first reported in the United States in 1962; thereafter, a few cases were reported from 1970 to 2005, but 2 outbreaks occurred in the Philippines (2008) and the United States (2014). However, little is known regarding the molecular evolution of this globally reemerging virus due to a lack of whole-genome sequences and analyses. Here, all publically available sequences including 147 full and 1248 partial genomes from GenBank were collected and compared at the clade and subclade level; 11 whole genomes isolated in Taiwan (TW) in 2014 were also added to the database. Phylogenetic trees were constructed to identify a new subclade, B3, and represent clade circulations among strains. Nucleotide sequence identities of the VP1 gene were 94% to 95% based on a comparison of subclade B3 to B1 and B2 and 87% to 91% when comparing A, C, and D. The patterns of clade circulation need to be clarified to improve global monitoring of EV-D68, even though this virus showed lower diversity among clades compared with the common enterovirus EV-71. Notably, severe cases isolated from Taiwan and China in 2014 were found in subclade B3. One severe case from Taiwan occurred in a female patient with underlying angioimmunoblastic T-cell lymphoma, from whom a bronchoalveolar lavage specimen was obtained. Although host factors play a key role in disease severity, we cannot exclude the possibility that EV-D68 may trigger clinical symptoms or death. To further investigate the genetic diversity of EV-D68, we reported 34 amino acid (aa) polymorphisms identified by comparing subclade B3 to B1 and B2. Clade D strains had a 1-aa deletion and a 2-aa insertion in the VP1 gene, and 1 of our TW/2014 strains had a shorter deletion in the 5′ untranslated region than a previously reported deletion. In summary, a new subclade, genetic indels, and polymorphisms in global strains were discovered elucidating evolutionary and epidemiological trends of EV-D68, and 11 genomes were added to the database. Virus variants may contribute to disease severity and clinical manifestations, and further studies are needed to investigate the associations between genetic diversity and clinical outcomes.

BackgroundAnnoying snore is the principle symptom and problem in obstructive sleep apnea syndrome (OSAS). However, investigation has been hampered by the complex snoring sound analyses.ObjectiveThis study was aimed to investigate the energy types of the full-night snoring sounds in patients with OSAS.Patients and MethodTwenty male OSAS patients underwent snoring sound recording throughout 6 hours of in-lab overnight polysomnogragphy. Snoring sounds were processed and analyzed by a new sound analytic program, named as Snore Map®. We transformed the 6-hour snoring sound power spectra into the energy spectrum and classified it as snore map type 1 (monosyllabic low-frequency snore), type 2 (duplex low-&mid-frequency snore), type 3 (duplex low- & high-frequency snore), and type 4 (triplex low-, mid-, & high-frequency snore). The interrator and test-retest reliabilities of snore map typing were assessed. The snore map types and their associations among demographic data, subjective snoring questionnaires, and polysomnographic parameters were explored.ResultsThe interrator reliability of snore map typing were almost perfect (κ = 0.87) and the test-retest reliability was high (r = 0.71). The snore map type was proportional to the body mass index (r = 0.63, P = 0.003) and neck circumference (r = 0.52, P = 0.018). Snore map types were unrelated to subjective snoring questionnaire scores (All P>0.05). After adjustment for body mass index and neck circumference, snore map type 3–4 was significantly associated with severity of OSAS (r = 0.52, P = 0.026).ConclusionsSnore map typing of a full-night energy spectrum is feasible and reliable. The presence of a higher snore map type is a warning sign of severe OSAS and indicated priority OSAS management. Future studies are warranted to evaluate whether snore map type can be used to discriminate OSAS from primary snoring and whether it is affected by OSAS management.