BackgroundThe herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01B Adjuvant System, was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials. We present immunogenicity results from those trials.MethodsParticipants (ZOE-50: ≥50; ZOE-70: ≥70 years of age) received 2 doses of HZ/su or placebo, 2 months apart. Serum anti-gE antibodies and CD4 T cells expressing ≥2 of 4 activation markers assessed (CD42+) after stimulation with gE-peptides were measured in subcohorts for humoral (n = 3293) and cell-mediated (n = 466) immunogenicity.ResultsAfter vaccination, 97.8% of HZ/su and 2.0% of placebo recipients showed a humoral response. Geometric mean anti-gE antibody concentrations increased 39.1-fold and 8.3-fold over baseline in HZ/su recipients at 1 and 36 months post-dose 2, respectively. A gE-specific CD42+ T-cell response was shown in 93.3% of HZ/su and 0% of placebo recipients. Median CD42+ T-cell frequencies increased 24.6-fold (1 month) and 7.9-fold (36 months) over baseline in HZ/su recipients and remained ≥5.6-fold above baseline in all age groups at 36 months. The proportion of CD4 T cells expressing all 4 activation markers increased over time in all age groups.ConclusionsMost HZ/su recipients developed robust immune responses persisting for 3 years following vaccination.Clinical Trials RegistrationNCT01165177; NCT01165229.

BackgroundThis study investigated the clinical value of interleukin-6 (IL-6), pentraxin 3 (PTX3), and procalcitonin (PCT) in patients with sepsis and septic shock diagnosed according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).MethodsSerum levels of IL-6, PTX3, and PCT were measured in 142 enrolled subjects (51 with sepsis, 46 with septic shock, and 45 as controls). Follow-up IL-6 and PTX3 levels were measured in patients with initial septic shock within 24 h of hospital discharge. Optimal cut-off values were determined for sepsis and septic shock, and prognostic values were evaluated.ResultsSerum IL-6 levels could discriminate sepsis (area under the curve [AUC], 0.83–0.94, P <  0.001; cut-off value, 52.60 pg/mL, 80.4% sensitivity, 88.9% specificity) from controls and could distinguish septic shock (AUC, 0.71–0.89; cut-off value, 348.92 pg/mL, 76.1% sensitivity, 78.4% specificity) from sepsis. Twenty-eight-day mortality was significantly higher in the group with high IL-6 (≥ 348.92 pg/mL) than in the group with low IL-6 (< 348.92 pg/mL) (P = 0.008). IL-6 was an independent risk factor for 28-day mortality among overall patients (hazard ratio, 1.0004; 95% confidence interval, 1.0003–1.0005; p = 0.024). In septic shock patients, both the initial and follow-up PTX3 levels were consistently significantly higher in patients who died than in those who recovered (initial p = 0.004; follow-up P <  0.001).ConclusionsThe diagnostic and prognostic value of IL-6 was superior to those of PTX3 and PCT for sepsis and septic shock.

Asymptomatic infection and atypical manifestations of COVID-19: Comparison of viral shedding duration Dear Editor, Coronavirus disease 2019 (COVID-19) bears several challenging problems, including insidious symptom onset, subclinical manifestations and highly transmissible property during early stage of infection. 1 In the recent study by Huang et al., SARS-CoV-2infection presented strong infectivity during the incubation period with rapid transmission. 2 Some patients with COVID-19 are asymptomatic, while others complain of atypical symptoms including loss of smell and taste sense. 3 However, there is insufficient data on the prevalence of asymptomatic infection and atypical manifestations of COVID-19. In this study, we aimed to evaluate the prevalence of asymptomatic infection, anosmia (smell loss) and ageusia (taste loss) among patients with mild COVID-19 in a residential treatment center (RTC). We also compared the duration of SARS-CoV-2 viral shedding between groups with different clinical manifestations. An observational cohort study was conducted for 199 patients with COVID-19 in a RTC at Gyeongju, Gyeongsangbuk province, Republic of Korea (ROK). The RTC was introduced to care patients with mild COVID-19 for the efficient distribution of limited medical resources during large epidemic in early March 2020. Data on demographic findings, symptoms, and duration of viral shedding were collected. The patients were interviewed about initial symptoms and their duration in detail. Real-time PCR (RT-PCR) to detect SARS-CoV-2 was performed every 2-7 days. Duration of viral shedding was considered as time from diagnosis date to the day before first negative conversion of two consecutive negative results of RT-PCR. RT-PCR was conducted using Allplex 2019-nCoV assay (Seegene, Seoul, South Korea). Statistical analyses were performed using SPSS 20.0 program. Mann-Whitney U test was performed to compare the duration of viral shedding between groups with different clinical manifestations. P-value < 0.05 was considered statistically significant. This study was approved by the Institutional Review Board of Korea University Guro Hospital (approval number: 2020GR0135). Among 199 patients with COVID-19, male was 34.7% and mean age of the patients was 38.0 years (Table 1). Most patients (187, 94.0%) were healthy without chronic medical conditions. Among 199 patients, 26.6% were asymptomatic. In the early study, asymptomatic cases accounted for 10.7% (3/28) of COVID-19 cases in the ROK. 1 Asymptomatic proportion of COVID-19 was estimated as 17.9% (95% credible interval, 15.5-20.2%) on the Diamond Princess cruise ship, Japan. 4 Among clinical manifestations, cough (41.2%) was most common, followed by rhinorrhea and nasal stuffiness (30.2%). Of note, 26.1% (52/199) of patients presented anosmia, and 22.6% (45/199) complained of ageusia. Thirty-eight (19.1%) patients complained of both anosmia and ageusia. Duration of anosmia and

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cases have been reported, with 230 deaths in Korea. COVID-19 patients may be asymptomatic or show various clinical manifestations, including acute symptoms such as fever, fatigue, sore throat; pneumonia presenting as acute respiratory distress syndrome; and multiple organ failure. As COVID-19 has such varied clinical manifestations and case fatality rates, no standard antiviral therapy regimen has been established other than supportive therapy. In the present guideline, we aim to introduce potentially helpful antiviral and other drug therapies based on in vivo and in vitro research and clinical experiences from many countries.

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According to recent studies, patients with COVID-19 have different feature characteristics on chest X-ray (CXR) than those with other lung diseases. This study aimed at evaluating the layer depths and degree of fine-tuning on transfer learning with a deep convolutional neural network (CNN)-based COVID-19 screening in CXR to identify efficient transfer learning strategies. The CXR images used in this study were collected from publicly available repositories, and the collected images were classified into three classes: COVID-19, pneumonia, and normal. To evaluate the effect of layer depths of the same CNN architecture, CNNs called VGG-16 and VGG-19 were used as backbone networks. Then, each backbone network was trained with different degrees of fine-tuning and comparatively evaluated. The experimental results showed the highest AUC value to be 0.950 concerning COVID-19 classification in the experimental group of a fine-tuned with only 2/5 blocks of the VGG16 backbone network. In conclusion, in the classification of medical images with a limited number of data, a deeper layer depth may not guarantee better results. In addition, even if the same pre-trained CNN architecture is used, an appropriate degree of fine-tuning can help to build an efficient deep learning model.