Effects of SARS-CoV-2 Omicron BA.1 Spike Mutations on T-Cell Epitopes in Mice.

T-cell immunity plays an important role in the control of SARS-CoV-2 and has a great cross-protective effect on the variants. The Omicron BA.1 variant contains more than 30 mutations in the spike and severely evades humoral immunity. To understand how Omicron BA.1 spike mutations affect cellular immunity, the T-cell epitopes of SARS-CoV-2 wild-type and Omicron BA.1 spike in BALB/c (H-2d) and C57BL/6 mice (H-2b) were mapped through IFNγ ELISpot and intracellular cytokine staining assays. The epitopes were identified and verified in splenocytes from mice vaccinated with the adenovirus type 5 vector encoding the homologous spike, and the positive peptides involved in spike mutations were tested against wide-type and Omicron BA.1 vaccines. A total of eleven T-cell epitopes of wild-type and Omicron BA.1 spike were identified in BALB/c mice, and nine were identified in C57BL/6 mice, only two of which were CD4+ T-cell epitopes and most of which were CD8+ T-cell epitopes. The A67V and Del 69-70 mutations in Omicron BA.1 spike abolished one epitope in wild-type spike, and the T478K, E484A, Q493R, G496S and H655Y mutations resulted in three new epitopes in Omicron BA.1 spike, while the Y505H mutation did not affect the epitope. These data describe the difference of T-cell epitopes in SARS-CoV-2 wild-type and Omicron BA.1 spike in H-2b and H-2d mice, providing a better understanding of the effects of Omicron BA.1 spike mutations on cellular immunity.

A Non-Contact Detection Method for Multi-Person Vital Signs Based on IR-UWB Radar.

With the vigorous development of ubiquitous sensing technology, an increasing number of scholars pay attention to non-contact vital signs (e.g., Respiration Rate (RR) and Heart Rate (HR)) detection for physical health. Since Impulse Radio Ultra-Wide Band (IR-UWB) technology has good characteristics, such as non-invasive, high penetration, accurate ranging, low power, and low cost, it makes the technology more suitable for non-contact vital signs detection. Therefore, a non-contact multi-human vital signs detection method based on IR-UWB radar is proposed in this paper. By using this technique, the realm of multi-target detection is opened up to even more targets for subjects than the more conventional single target. We used an optimized algorithm CIR-SS based on the channel impulse response (CIR) smoothing spline method to solve the problem that existing algorithms cannot effectively separate and extract respiratory and heartbeat signals. Also in our study, the effectiveness of the algorithm was analyzed using the Bland-Altman consistency analysis statistical method with the algorithm's respiratory and heart rate estimation errors of 5.14% and 4.87%, respectively, indicating a high accuracy and precision. The experimental results showed that our proposed method provides a highly accurate, easy-to-implement, and highly robust solution in the field of non-contact multi-person vital signs detection.

Batch-to-batch consistency trial of an adenovirus type-5 vector-based COVID-19 vaccine in adults aged 18 years and above.

BACKGROUND: The demonstration of batch-to-batch consistency is indispensable for quality control of vaccines. METHODS: We conducted a randomized, double-blind, parallel-controlled trial to evaluate the immunogenicity consistency of a single shot of Ad5-nCoV in healthy adults who had not previously received any COVID-19 vaccine. All eligible participants were randomly assigned equally to receive one of the three consecutive batches of Ad5-nCoV (5 × 1010 viral particles/vial, 0.5 mL). The primary endpoint was geometric mean titers (GMTs) of serum SARS-CoV-2 receptor-binding domain (RBD)-specific IgG on day 28 post-vaccination. RESULTS: One thousand fifty participants were enrolled, with 350 (33%) participants per group. On day 28 post-vaccination, GMTs in three groups were 78.3 binding antibody units (BAU)/mL (95% CI 70.3-87.3), 82.9 BAU/mL (73.9-92.9), and 78.8 BAU/mL (70.2-88.4), respectively. The two-sided 95% CIs for the GMT ratios between each pair of batches were all between 0.67 and 1.5. The highest incidence of solicited adverse reactions within 7 days post-vaccination was reported by batch 3 recipients (23.1% versus 15.1% in batch 1 recipients and 14.6% in bath 2 recipients; p = 0.0039). None of the serious adverse events were related to vaccination. CONCLUSIONS: Immunogenicity consistency between consecutive batches of Ad5-nCoV was well established in adults. CLINICAL TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT05313646).

Comparative characterization of antibody responses induced by Ad5-vectored spike proteins of emerging SARS-CoV-2 VOCs.

Highly divergent SARS-CoV-2 variants have continuously emerged and spread around the world, and updated vaccines and innovative vaccination strategies are urgently needed to address the global SARS-COV2 pandemic. Here, we established a series of Ad5-vectored SARS-CoV-2 variant vaccines encoding multiple spike proteins derived from the Alpha, Beta, Gamma, Epsilon, Kappa, Delta and Omicron lineages and analyzed the antibody immune responses induced by single-dose and prime-boost vaccination strategies against emerging SARS-CoV-2 variants of concern (VOCs). Single-dose vaccination with SARS-CoV-2 variant vaccines tended to elicit the optimal self-matched neutralizing effects, and Ad5-B.1.351 produced more broad-spectrum cross-neutralizing antibodies against diverse variants. In contrast, prime-boost vaccination further strengthened and broadened the neutralizing antibody responses against highly divergent SARS-CoV-2 variants. The heterologous administration of Ad5-B.1.617.2 and Ad5-B.1.429 to Ad5-WT-primed mice resulted in superior antibody responses against most VOCs. In particular, the Omicron spike could only stimulate self-matched neutralizing antibodies with infrequent cross-reactivities to other variants used in single-dose vaccination strategies; moreover, with prime-boost regimens, this vaccine elicited an optimal specific neutralizing antibody response to Omicron, and prompted cross-antibody responses against other VOCs that were very similar to those obtained with Ad5-WT booster. Overall, this study delineated the unique characteristics of antibody responses to the SARS-CoV-2 VOC spikes with the single-dose or prime-boost vaccination strategies and provided insight into the vaccine development of next SARS-CoV-2 VOCs.

The Impact of Hotel Customer Engagement and Service Evaluation on Customer Behavior Intention: The Mediating Effect of Brand Trust.

Because of the COVID-19, the tourism industry has been greatly affected, especially the occupancy rate of hotel companies. This study analyzes the effects of customer engagement and service evaluation on brand trust and customer behavioral intention based on 437 valid questionnaires from Chinese economy hotel companies using SPSS and AMOS. The components of customer engagement are subdivided into five dimensions: identification, enthusiasm, attention, absorption and interaction, and the impact of these five dimensions on brand trust in the COVID- 19 is investigated. Finally, it verifies the influence of trust on customers' word-of-mouth (WOM) intention and customers' reuse intention. The results of this study not only enrich the research on customer engagement and service evaluation in marketing circles but also give some advice to hotel companies in the COVID-19 customer engagement and service evaluation that can enhance the trust of enterprises and promote the behavior intention of customers, which has certain practical reference value.

Broadly neutralizing antibodies against Omicron-included SARS-CoV-2 variants induced by vaccination.

The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection- and vaccination-induced antibodies, highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies (bnAbs). Here, we developed a panel of bnAbs against Omicron and other variants of concern (VOCs) elicited by vaccination of adenovirus-vectored COVID-19 vaccine (Ad5-nCoV). We also investigated the human longitudinal antibody responses following vaccination and demonstrated how the bnAbs evolved over time. A monoclonal antibody (mAb), named ZWD12, exhibited potent and broad neutralization against SARS-CoV-2 variants Alpha, Beta, Gamma, Kappa, Delta, and Omicron by blocking the spike protein binding to the angiotensin-converting enzyme 2 (ACE2) and provided complete protection in the challenged prophylactic and therapeutic K18-hACE2 transgenic mouse model. We defined the ZWD12 epitope by determining its structure in complex with the spike (S) protein via cryo-electron microscopy. This study affords the potential to develop broadly therapeutic mAb drugs and suggests that the RBD epitope bound by ZWD12 is a rational target for the design of a broad spectrum of vaccines.

Safety, tolerability, and immunogenicity of an aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in adults: preliminary report of an open-label and randomised phase 1 clinical trial.

BACKGROUND: SARS-CoV-2 has caused millions of deaths, and, since Aug 11, 2020, 20 intramuscular COVID-19 vaccines have been approved for use. We aimed to evaluate the safety and immunogenicity of an aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in adults without COVID-19 from China. METHOD: This was a randomised, single-centre, open-label, phase 1 trial done in Zhongnan Hospital (Wuhan, China), to evaluate the safety and immunogenicity of the Ad5-nCoV vaccine by aerosol inhalation in adults (≥18 years) seronegative for SARS-CoV-2. Breastfeeding or pregnant women and people with major chronic illnesses or history of allergies were excluded. Participants were enrolled and randomly assigned (1:1:1:1:1) into five groups to be vaccinated via intramuscular injection, aerosol inhalation, or both. Randomisation was stratified by sex and age (18-55 years or ≥56 years) using computer-generated randomisation sequences (block sizes of five). Only laboratory staff were masked to group assignment. The participants in the two aerosol groups received an initial high dose (2 × 1010 viral particles; HDmu group) or low dose (1 × 1010 viral particles; LDmu group) of Ad5-nCoV vaccine on day 0, followed by a booster on day 28. The mixed vaccination group received an initial intramuscular (5 × 1010 viral particles) vaccine on day 0, followed by an aerosolised booster (2 × 1010 viral particles) vaccine on day 28 (MIX group). The intramuscular groups received one dose (5 × 1010 viral particles; 1Dim group) or two doses (10 × 1010 viral particles; 2Dim group) of Ad5-nCoV on day 0. The primary safety outcome was adverse events 7 days after each vaccination, and the primary immunogenicity outcome was anti-SARS-CoV-2 spike receptor IgG antibody and SARS-CoV-2 neutralising antibody geometric mean titres at day 28 after last vaccination. This trial is registered with ClinicalTrials.gov, number NCT04552366. FINDINGS: Between Sept 28, 2020, and Sept 30, 2020, 230 individuals were screened for inclusion, of whom 130 (56%) participants were enrolled into the trial and randomly assigned into one of the five groups (26 participants per group). Within 7 days after vaccination, adverse events occurred in 18 (69%) in the HDmu group, 19 (73%) in the LDmu group, 19 (73%) in the MIX group, 19 (73%) in the 1Dim group, and 15 (58%) in the 2Dim group. The most common adverse events reported 7 days after the first or booster vaccine were fever (62 [48%] of 130 participants), fatigue (40 [31%] participants), and headache (46 [35%] participants). More adverse events were reported in participants who received intramuscular vaccination, including participants in the MIX group (49 [63%] of 78 participants), than those who received aerosol vaccine (13 [25%] of 52 participants) after the first vaccine vaccination. No serious adverse events were noted within 56 days after the first vaccine. At days 28 after last vaccination, geometric mean titres of SARS-CoV-2 neutralising antibody was 107 (95% CI 47-245) in the HDmu group, 105 (47-232) in the LDmu group, 396 (207-758) in the MIX group, 95 (61-147) in the 1Dim group, and 180 (113-288) in the 2Dim group. The geometric mean concentrations of receptor binding domain-binding IgG was 261 EU/mL (95% CI 121-563) in the HDmu group, 289 EU/mL (138-606) in the LDmu group, 2013 EU/mL (1180-3435) in the MIX group, 915 EU/mL (588-1423) in the 1Dim group, and 1190 EU/mL (776-1824) in the 2Dim group. INTERPRETATION: Aerosolised Ad5-nCoV is well tolerated, and two doses of aerosolised Ad5-nCoV elicited neutralising antibody responses, similar to one dose of intramuscular injection. An aerosolised booster vaccination at 28 days after first intramuscular injection induced strong IgG and neutralising antibody responses. The efficacy and cost-effectiveness of aerosol vaccination should be evaluated in future studies. FUNDING: National Key Research and Development Programme of China and National Science and Technology Major Project. TRANSLATION: For the Chinese translation of the Summary see Supplementary Material.

Baduanjin exercise can alleviate anxiety and depression of patients with COVID-19 in Square cabin hospital: A cross-sectional survey.

ABSTRACT: To investigate the anxiety and depression of patients with the coronavirus disease 2019 (COVID-19) who participated in Baduanjin exercise.From February 20, 2020 to March 7, 2020, the Hospital Anxiety and Depression scale (HAD) were used to investigate the anxiety and depression levels of patients with COVID-19 who participated in Baduanjin exercise. Ninety one questionnaires were received, including 40 males and 51 females. Stepwise regression analysis was used to analyze the effects of related factors on anxiety and depression levels.In Square cabin hospital, 91% of patients participated in Baduanjin exercise had no obvious anxiety and 82% had no obvious depression. The scores of anxiety and depression of female patients were significantly higher than that of male patients. Bachelor degree or above with low scores for anxiety and depression. The frequency of Baduanjin exercise was negatively correlated with anxiety and depression score.The development of Baduanjin exercise has a certain positive influence on the COVID-19 patients in the Square cabin hospital, which is conducive to alleviate anxiety and depression symptoms of the patients.

Lacking Communication Would Increase General Symptom Index Scores of Medical Team Members During COVID-19 Pandemic in China: A Retrospective Cohort Study.

There are few studies on the psychological status of medical staff during the COVID-19 outbreak. Our study addresses whether lack of communication affects the psychological status of medical team members supporting Wuhan during the COVID-19 pandemic in China. We used general symptom index (GSI) scores of the Symptom Checklist-90 (SCL-90) to evaluate participants' psychological status. We adopted a stratified sampling method and selected the fourth team, with a total of 137 members, as participants. In total 76.6% and 69.7% of female and male participants, respectively, had bachelor's degrees; 41.6% and 21.2% of female and male participants, respectively, were unmarried. Regarding communication, 14.29% and 6.06% of female and male participants, respectively, reported a lack of communication with the team (LCWT). Additionally, 13.0% and 6.1% of female and male participants, respectively, experienced fear of being infected (FoBI). LCWT and FoBI were positively correlated with GSI score (estimated change = 0.2, 95% CI [0.1-0.3]). When adjusted for gender, age, and FoBI, LCWT was positively correlated with GSI score (P < .05). Increasing communication among medical team members can reduce GSI scores.

A single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV-2 challenge.

The unprecedented coronavirus disease 2019 (COVID-19) epidemic has created a worldwide public health emergency, and there is an urgent need to develop an effective vaccine to control this severe infectious disease. Here, we find that a single vaccination with a replication-defective human type 5 adenovirus encoding the SARS-CoV-2 spike protein (Ad5-nCoV) protect mice completely against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts. Additionally, a single vaccination with Ad5-nCoV protects ferrets from wild-type SARS-CoV-2 infection in the upper respiratory tract. This study suggests that the mucosal vaccination may provide a desirable protective efficacy and this delivery mode is worth further investigation in human clinical trials.

A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2.

Developing therapeutics against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein but also across the full Spike (S) protein. We isolated and characterized monoclonal antibodies (mAbs) from 10 convalescent COVID-19 patients. Three mAbs showed neutralizing activities against authentic SARS-CoV-2. One mAb, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2 but does not bind the RBD. We defined the epitope of 4A8 as the N-terminal domain (NTD) of the S protein by determining with cryo-eletron microscopy its structure in complex with the S protein to an overall resolution of 3.1 angstroms and local resolution of 3.3 angstroms for the 4A8-NTD interface. This points to the NTD as a promising target for therapeutic mAbs against COVID-19.

Correlation analysis of risk factors and GSI score of a medical team assisting Wuhan city during the epidemic of COVID-19 in China -A cohort study (preprint)

Importance: There are few studies on the psychological status of medical staff during the COVID-19 outbreak. This study is the first in the world about the psychological status of the medical team during the COVID-19 outbreak. Objective: To study the correlation between risk factors and general symptom index (GSI) score of medical team members who support Wuhan against COVID-19. Design: Cohort study. Setting: Population-based. Participants: Anhui Province sent a total of eight medical teams,including 1382 members,to support Hubei Province. We adopted a stratified sampling method and selected the fourth team sent by Anhui Provincial Hospital, with a total of 137 members as our subjects. Exposures: Four main exposures were collected, including basic information, preparations before going to Wuhan, life issues and working issues after going to Wuhan. Main Outcomes and Measures: The GSI score of SCL-90 scale was used to reflect the frequency and intensity of psychological symptoms. We made the hypothesis of this study before data collection. Results: 110(80.29%) members completed the questionnaire, of which, 77(70.00%) female and 33(30.00%) male. When adjusted age, gender and covariates, DC, LCWT had a positive correlations with GSI score(beta was 10.17, 95%CI was 3.30 to 17.04 for DC, P=0.00<0.05;beta was 11.55, 95%CI was 0.40 to 22.71 for LCWT, P =0.04<0.05;respectively), RBT had a negative positive correlation with GSI score (beta was -28.09, 95%CI was -45.79 to -10.40, P=0.00<0.05), AoBI did not had a correlation with GSI score (beta was 11.55, 95%CI was 0.40 to 22.71, P=0.16>0.05). When adjusted covariates, DC had a positive and RBT had a negative correlation with GSI score of female (beta was 13.20, 95%CI was 4.55 to 21.85, P=0.00<0.05; beta was -57.85, 95%CI was -94.52 to -21.18, P=0.00<0.05; respectively), but for male was not (P=0.59>0.05, P=0.08>0.05, respectively), LCWT and AoBI didn't had correlation with GSI score between genders (P>0.05). Conclusions and Relevance: Improving DC, RBT and decreasing LCWT can reduce the GSI score. AoBI didn't affect the psychological status; male members have a more stable mood than female. Whether other countries medical team has the same result still needs further research.