Safety and immunogenicity of heterologous boosting with orally aerosolised or intramuscular Ad5-nCoV vaccine and homologous boosting with inactivated vaccines (BBIBP-CorV or CoronaVac) in children and adolescents: a randomised, open-label, parallel-controlled, non-inferiority, single-centre study.

BACKGROUND: Heterologous booster immunisation with orally administered aerosolised Ad5-nCoV vaccine (AAd5) has been shown to be safe and highly immunogenic in adults. Here, we aimed to assess the safety and immunogenicity of heterologous booster immunisation with orally administered AAd5 in children and adolescents aged 6-17 years who had received two doses of inactivated vaccine (BBIBP-CorV or CoronaVac). METHODS: We did a randomised, open-label, parallel-controlled, non-inferiority study to assess the safety and immunogenicity of heterologous booster immunisation with AAd5 (0·1 mL) or intramuscular Ad5-nCoV vaccine (IMAd5; 0·3 mL) and homologous booster immunisation with inactivated vaccine (BBIBP-CorV or CoronaVac; 0·5 mL) in children (aged 6-12 years) and adolescents (aged 13-17 years) who had received two doses of inactivated vaccine at least 3 months earlier in Hunan, China. Children and adolescents who were previously immunised with two-dose BBIBP-CorV or CoronaVac were recruited for eligibility screening at least 3 months after the second dose. A stratified block method was used for randomisation, and participants were stratified by age and randomly assigned (3:1:1) to receive AAd5, IMAd5, or inactivated vaccine. The study staff and participants were not masked to treatment allocation. Laboratory and statistical staff were masked during the study. In this interim analysis, adverse events within 14 days and geometric mean titre (GMT) of serum neutralising antibodies on day 28 after the booster vaccination, based on the per-protocol population, were used as the primary outcomes. The analysis of non-inferiority was based on comparison using a one-sided 97·5% CI with a non-inferiority margin of 0·67. This study was registered at ClinicalTrials.gov, NCT05330871, and is ongoing. FINDINGS: Between April 17 and May 28, 2022, 436 participants were screened and 360 were enrolled: 220 received AAd5, 70 received IMAd5, and 70 received inactivated vaccine. Within 14 days after booster vaccination, vaccine-related adverse reactions were reported: 35 adverse events (in 13 [12%] of 110 children and 22 [20%] of 110 adolescents) in 220 individuals in the AAd5 group, 35 (in 18 [51%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 13 (in five [14%] of 35 children and eight [23%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. Solicited adverse reactions were also reported: 34 (13 [12%] of 110 children and 21 [10%] of 110 adolescents) in 220 individuals in the AAd5 group, 34 (17 [49%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 12 (five [14%] of 35 children and seven [20%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. The GMTs of neutralising antibodies against ancestral SARS-CoV-2 Wuhan-Hu-1 (Pango lineage B) in the AAd5 group were significantly higher than the GMTs in the inactivated vaccine group (adjusted GMT ratio 10·2 [95% CI 8·0-13·1]; p<0·0001). INTERPRETATION: Our study shows that a heterologous booster with AAd5 is safe and highly immunogenic against ancestral SARS-CoV-2 Wuhan-Hu-1 in children and adolescents. FUNDING: National Key R&D Program of China.

Association of gut microbiota with COVID-19 susceptibility and severity: A two-sample Mendelian randomization study.

Evidence supports the observational associations of gut microbiota with the risk of COVID-19; however, it is unclear whether these associations reflect a causal relationship. This study investigated the association of gut microbiota with COVID-19 susceptibility and severity. Data were obtained from a large-scale gut microbiota data set (n = 18 340) and the COVID-19 Host Genetics Initiative (n = 2 942 817). Causal effects were estimated with inverse variance weighted (IVW), MR-Egger, and weighted median, and sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots. For COVID-19 susceptibility, IVW estimates suggested that Gammaproteobacteria (odds ratio [OR] = 0.94, 95% confidence interval [CI], 0.89-0.99, p = 0.0295] and Streptococcaceae (OR = 0.95, 95% CI, 0.92-1.00, p = 0.0287) had a reduced risk, while Negativicutes (OR = 1.05, 95% CI, 1.01-1.10, p = 0.0302), Selenomonadales (OR = 1.05, 95% CI, 1.01-1.10, p = 0.0302), Bacteroides (OR = 1.06, 95% CI, 1.01-1.12, p = 0.0283), and Bacteroidaceae (OR = 1.06, 95% CI, 1.01-1.12, p = 0.0283) were associated with an increased risk (all p < 0.05, nominally significant). For COVID-19 severity, Subdoligranulum (OR = 0.80, 95% CI, 0.69-0.92, p = 0.0018), Cyanobacteria (OR = 0.85, 95% CI, 0.76-0.96, p = 0.0062), Lactobacillales (OR = 0.87, 95% CI, 0.76-0.98, p = 0.0260), Christensenellaceae (OR = 0.87, 95% CI, 0.77-0.99, p = 0.0384), Tyzzerella3 (OR = 0.89, 95% CI, 0.81-0.97, p = 0.0070), and RuminococcaceaeUCG011 (OR = 0.91, 95% CI, 0.83-0.99, p = 0.0247) exhibited negative correlations, while RikenellaceaeRC9 (OR = 1.09, 95% CI, 1.01-1.17, p = 0.0277), LachnospiraceaeUCG008 (OR = 1.12, 95% CI, 1.00-1.26, p = 0.0432), and MollicutesRF9 (OR = 1.14, 95% CI, 1.01-1.29, p = 0.0354) exhibited positive correlations (all p < 0.05, nominally significant). Sensitivity analyses validated the robustness of the above associations. These findings suggest that gut microbiota might influence the susceptibility and severity of COVID-19 in a causal way, thus providing novel insights into the gut microbiota-mediated development mechanism of COVID-19.

Occupancy-aided ventilation for airborne infection risk control: Continuously or intermittently reduced occupancies?

Ventilation is an important engineering measure to control the airborne infection risk of acute respiratory diseases, e.g., Corona Virus Disease 2019 (COVID-19). Occupancy-aided ventilation methods can effectively improve the airborne infection risk control performance with a sacrifice of decreasing working productivity because of the reduced occupancy. This study evaluates the effectiveness of two occupancy-aided ventilation methods, i.e., the continuously reduced occupancy method and the intermittently reduced occupancy method. The continuously reduced occupancy method is determined by the steady equation of the mass conservation law of the indoor contaminant, and the intermittently reduced occupancy method is determined by a genetic algorithm-based optimization. A two-scenarios-based evaluation framework is developed, i.e., one with targeted airborne infection risk control performance (indicated by the mean rebreathed fraction) and the other with targeted working productivity (indicated by the accumulated occupancy). The results show that the improvement in the airborne infection risk control performance linearly and quadratically increases with the reduction in the working productivity for the continuously reduced occupancy method and the intermittently reduced occupancy method respectively. At a given targeted airborne infection risk control performance, the intermittently reduced occupancy method outperforms the continuously reduced occupancy method by improving the working productivity by up to 92%. At a given targeted working productivity, the intermittently reduced occupancy method outperforms the continuously reduced occupancy method by improving the airborne infection risk control performance by up to 38%.

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study.

Background: Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities. Methods: We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated. Findings: 264 patients (mean age, 70.35 years; 122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27; 95% CI -2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group; ARD, -0.62; 95% CI -2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39; serious adverse events, 4.55% vs. 3.788%, P = 0.76). Interpretation: Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS-CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities. Funding: National Natural Science Foundation of China (grant number: 82172152, 81873944).

Anxiety prevalence and its association with physical activity in patients with non-communicable diseases during COVID-19 lockdown: a cross-sectional study in Shanghai, China.

BACKGROUND: Quarantine due to the COVID-19 pandemic may have created great psychological stress among vulnerable populations. We aimed to investigate the prevalence of anxiety and explore the association between physical activities (PA) and anxiety risk in people with non-communicable diseases during the period of COVID-19 lockdown. METHODS: We conducted a cross-sectional telephone survey from February 25 to April 20, 2020, the period of COVID-19 lockdown in Shanghai. Up to 8000 patients with type 2 diabetes and/or hypertension were selected using multi-stage cluster random sampling. PA level was measured based on the International Physical Activity Questionnaire using Metabolic Equivalent for Task scores, while symptoms of anxiety were assessed by the 7-item Generalized Anxiety Disorder scale. Multiple logistic regression analyses were performed to evaluate the associations of type and level of PA with the risk of anxiety. RESULTS: Of a total 4877 eligible patients, 2602 (53.4%) reported with anxiety, and 2463 (50.5%), 123 (2.5%) and 16 (0.3%) reported with mild, moderate, and severe anxiety. The prevalence of anxiety was higher in the females, the elders, non-smokers, non-drinkers, and patients with diabetes, and the associations of anxiety with sex, age, smoking, drinking and diagnosis of diabetes were significant. A significant negative association was observed for housework activities (OR 0.53, 95%CI: [0.45, 0.63], p < 0.001) and trip activities (OR 0.55, 95%CI: [0.48, 0.63], p < 0.001) with anxiety, but no significant was found for exercise activities (OR 1.06, 95%CI: [0.94, 1.20], p = 0.321). Compared with patients with a low PA level, those with a moderate (OR 0.53, 95%CI: [0.44, 0.64], p < 0.001) or a high PA level (OR 0.51, 95%CI: [0.43, 0.51], p < 0.001) had a lower prevalence of anxiety. CONCLUSION: This study demonstrates a higher prevalence of anxiety in patients with hypertension, diabetes, or both during the COVID-19 lockdown. The negative associations of housework and trip activities with anxiety highlight the potential benefit of PA among patients with non-communicable diseases.

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study

Background Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities. Methods We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated. Findings 264 patients (mean age, 70.35 years;122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27;95% CI −2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group;ARD, −0.62;95% CI −2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39;serious adverse events, 4.55% vs. 3.788%, P = 0.76). Interpretation Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS–CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities. Funding 10.13039/501100001809National Natural Science Foundation of China (grant number: 82172152, 81873944).

Airway Management in Adult Intensive Care Units: A Survey of Two Regions in China

The critical medicine residency training in China started in 2020, but no investigation on the practice of tracheal intubation in ICUs in China has been conducted. A survey was sent to the adult ICUs in public hospitals in Shenzhen (SZ) city and Xinjiang (XJ) province using a WeChat miniprogram to be completed by intensive care physicians. It included questions on training on intubation, intubation procedures, and changes in the use of personal protective equipment due to COVID-19. We analyzed 301 valid questionnaires which were from 72 hospitals. A total of 37% of respondents had completed training in RSI (SZ, 40% vs. XJ, 30%;p = 0.066), and 50% had participated in a course on the emergency front of the neck airway (SZ, 47% vs. XJ, 54%;p = 0.256). Video laryngoscopy was preferred by 75% of respondents. Manual ventilation (56%) and noninvasive positive pressure ventilation (34%) were the first-line options for preoxygenation. For patients with a high risk of aspiration, nasogastric decompression (47%) and cricoid pressure (37%) were administered. Propofol (82%) and midazolam (70%) were the most commonly used induction agents. Only 19% of respondents routinely used neuromuscular blocking agents. For patients with difficult airways, a flexible endoscope was the most commonly used device by 76% of respondents. Most participants (77%) believed that the COVID-19 pandemic had significantly increased their awareness of the need for personal protective equipment during tracheal intubation. Our survey demonstrated that the ICU doctors in these areas lack adequate training in airway management.

Corticosteroid treatment in severe patients with SARS-CoV-2 and chronic HBV co-infection: a retrospective multicenter study.

BACKGROUND: The impact of corticosteroids on patients with severe coronavirus disease 2019 (COVID-19)/chronic hepatitis B virus (HBV) co-infection is currently unknown. We aimed to investigate the association of corticosteroids on these patients. METHODS: This retrospective multicenter study screened 5447 confirmed COVID-19 patients hospitalized between Jan 1, 2020 to Apr 18, 2020 in seven centers in China, where the prevalence of chronic HBV infection is moderate to high. Severe patients who had chronic HBV and acute SARS-cov-2 infection were potentially eligible. The diagnosis of chronic HBV infection was based on positive testing for hepatitis B surface antigen (HBsAg) or HBV DNA during hospitalization and a medical history of chronic HBV infection. Severe patients (meeting one of following criteria: respiratory rate > 30 breaths/min; severe respiratory distress; or SpO2 ≤ 93% on room air; or oxygen index < 300 mmHg) with COVID-19/HBV co-infection were identified. The bias of confounding variables on corticosteroids effects was minimized using multivariable logistic regression model and inverse probability of treatment weighting (IPTW) based on propensity score. RESULTS: The prevalence of HBV co-infection in COVID-19 patients was 4.1%. There were 105 patients with severe COVID-19/HBV co-infections (median age 62 years, 57.1% male). Fifty-five patients received corticosteroid treatment and 50 patients did not. In the multivariable analysis, corticosteroid therapy (OR, 6.32, 95% CI 1.17-34.24, P = 0.033) was identified as an independent risk factor for 28-day mortality. With IPTW analysis, corticosteroid treatment was associated with delayed SARS-CoV-2 viral RNA clearance (OR, 2.95, 95% CI 1.63-5.32, P < 0.001), increased risk of 28-day and in-hospital mortality (OR, 4.90, 95% CI 1.68-14.28, P = 0.004; OR, 5.64, 95% CI 1.95-16.30, P = 0.001, respectively), and acute liver injury (OR, 4.50, 95% CI 2.57-7.85, P < 0.001). Methylprednisolone dose per day and cumulative dose in non-survivors were significantly higher than in survivors. CONCLUSIONS: In patients with severe COVID-19/HBV co-infection, corticosteroid treatment may be associated with increased risk of 28-day and in-hospital mortality.

Encyclopedia of fecal microbiota transplantation: a review of effectiveness in the treatment of 85 diseases.

ABSTRACT: Fecal microbiota transplantation (FMT) has been used as a core therapy for treating dysbiosis-related diseases by remodeling gut microbiota. The methodology and technology for improving FMT are stepping forward, mainly including washed microbiota transplantation (WMT), colonic transendoscopic enteral tubing (TET) for microbiota delivery, and purified Firmicutes spores from fecal matter. To improve the understanding of the clinical applications of FMT, we performed a systematic literature review on FMT published from 2011 to 2021. Here, we provided an overview of the reported clinical benefits of FMT, the methodology of processing FMT, the strategy of using FMT, and the regulations on FMT from a global perspective. A total of 782 studies were included for the final analysis. The present review profiled the effectiveness from all clinical FMT uses in 85 specific diseases as eight categories, including infections, gut diseases, microbiota-gut-liver axis, microbiota-gut-brain axis, metabolic diseases, oncology, hematological diseases, and other diseases. Although many further controlled trials will be needed, the dramatic increasing reports have shown the promising future of FMT for dysbiosis-related diseases in the gut or beyond the gut.

Using search trends to analyze web-based users' behavior profiles connected with COVID-19 in mainland China: infodemiology study based on hot words and Baidu Index.

Background: Mainland China, the world's most populous region, experienced a large-scale coronavirus disease 2019 (COVID-19) outbreak in 2020 and 2021, respectively. Existing infodemiology studies have primarily concentrated on the prospective surveillance of confirmed cases or symptoms which met the criterion for investigators; nevertheless, the actual impact regarding COVID-19 on the public and subsequent attitudes of different groups towards the COVID-19 epidemic were neglected. Methods: This study aimed to examine the public web-based search trends and behavior patterns related to COVID-19 outbreaks in mainland China by using hot words and Baidu Index (BI). The initial hot words (the high-frequency words on the Internet) and the epidemic data (2019/12/01-2021/11/30) were mined from infodemiology platforms. The final hot words table was established by two-rounds of hot words screening and double-level hot words classification. Temporal distribution and demographic portraits of COVID-19 were queried by search trends service supplied from BI to perform the correlation analysis. Further, we used the parameter estimation to quantitatively forecast the geographical distribution of COVID-19 in the future. Results: The final English-Chinese bilingual table was established including six domains and 32 subordinate hot words. According to the temporal distribution of domains and subordinate hot words in 2020 and 2021, the peaks of searching subordinate hot words and COVID-19 outbreak periods had significant temporal correlation and the subordinate hot words in COVID-19 Related and Territory domains were reliable for COVID-19 surveillance. Gender distribution results showed that Territory domain (the male proportion: 67.69%; standard deviation (SD): 5.88%) and Symptoms/Symptom and Public Health (the female proportion: 57.95%, 56.61%; SD: 0, 9.06%) domains were searched more by male and female groups respectively. The results of age distribution of hot words showed that people aged 20-50 (middle-aged people) had a higher online search intensity, and the group of 20-29, 30-39 years old focused more on Media and Symptoms/Symptom (proportion: 45.43%, 51.66%; SD: 15.37%, 16.59%) domains respectively. Finally, based on frequency rankings of searching hot words and confirmed cases in Mainland China, the epidemic situation of provinces and Chinese administrative divisions were divided into 5 levels of early-warning regions. Central, East and South China regions would be impacted again by the COVID-19 in the future.

Occupancy-aided ventilation for airborne infection risk control: Continuously or intermittently reduced occupancies?

Ventilation is an important engineering measure to control the airborne infection risk of acute respiratory diseases, e.g., Corona Virus Disease 2019 (COVID-19). Occupancy-aided ventilation methods can effectively improve the airborne infection risk control performance with a sacrifice of decreasing working productivity because of the reduced occupancy. This study evaluates the effectiveness of two occupancy-aided ventilation methods, i.e., the continuously reduced occupancy method and the intermittently reduced occupancy method. The continuously reduced occupancy method is determined by the steady equation of the mass conservation law of the indoor contaminant, and the intermittently reduced occupancy method is determined by a genetic algorithm-based optimization. A two-scenarios-based evaluation framework is developed, i.e., one with targeted airborne infection risk control performance (indicated by the mean rebreathed fraction) and the other with targeted working productivity (indicated by the accumulated occupancy). The results show that the improvement in the airborne infection risk control performance linearly and quadratically increases with the reduction in the working productivity for the continuously reduced occupancy method and the intermittently reduced occupancy method respectively. At a given targeted airborne infection risk control performance, the intermittently reduced occupancy method outperforms the continuously reduced occupancy method by improving the working productivity by up to 92%. At a given targeted working productivity, the intermittently reduced occupancy method outperforms the continuously reduced occupancy method by improving the airborne infection risk control performance by up to 38%.

2D Zn‐Porphyrin‐Based Co(II)‐MOF with 2‐Methylimidazole Sitting Axially on the Paddle–Wheel Units: An Efficient Electrochemiluminescence Bioassay for SARS‐CoV‐2

High electrocatalytic activity with tunable luminescence is crucial for the development of electrochemiluminescence (ECL) luminophores. In this study, a porphyrin‐based heterobimetallic 2D metal organic framework (MOF), [(ZnTCPP)Co2(MeIm)] (1), is successfully self‐assembled from the zinc(II) tetrakis(4‐carboxyphenyl)porphine (ZnTCPP) linker and cobalt(II) ions in the presence of 2‐methylimidazole (MeIm) by a facile one‐pot reaction in methanol at room temperature. On the basis of the experimental results and the theoretical calculations, the MOF 1 contains paddle–wheel [Co2(‐CO2)4] secondary building units (SBUs) axially coordinated by a MeIm ligand, which is very beneficial to the electron transfer between the Co(II) ions and oxygen. Combining the photosensitizers ZnTCPP and the electroactive [Co2(‐CO2)4] SBUs, the 2D MOF 1 possesses an excellent ECL performance, and can be used as a novel ECL probe for rapid nonamplified detection of the RdRp gene of SARS‐CoV‐2 with an extremely low limit of detection (≈30 aM). A novel porphyrin‐based heterobimetallic 2D MOF, [(ZnTCPP)Co2(MeIm)] (1) is constructed to act as an excellent electrochemiluminescence probe for rapid nonamplified detection of SARS‐CoV‐2.

Integrated system of exhaust air heat pump and advanced air distribution for energy-efficient provision of outdoor air.

A large outdoor air supply is required to control the airborne infection risk of respiratory diseases (e.g., COVID 19) but causes a high energy penalty. This study proposes a novel integrated system of the exhaust air heat pump and advanced air distribution to energy-efficiently provide outdoor air. The system energy performances are evaluated by the experimentally validated thermodynamic model of heat pump and heat removal efficiency model of advanced air distribution. Results show the exhaust air heat pump with advanced air distribution can save energy because of three mechanisms. First, the exhaust air heat pump reuses the exhaust air to reduce the condensation temperature, thereby improving the coefficient of performance. Second, advanced air distribution reduces ventilation load. Third, advanced air distribution reduces the condensation temperature and enhances the evaporation temperature, thereby improving the coefficient of performance. The exhaust air heat pump saves energy by 18%, advanced air distribution saves energy by 36%, and the integrated system of the exhaust air heat pump and advanced air distribution can save energy by 45%. As a specific application, compared with the conventional system (i.e., the outdoor air heat pump with mixing ventilation), the exhaust air heat pump with stratum ventilation saves energy by 21% - 35% under various outdoor air ratios and outdoor air temperatures. The proposed integrated system of the exhaust air heat pump and advanced air distribution contributes to the development of low-carbon and healthy buildings.

Ventilation indices for evaluation of airborne infection risk control performance of air distribution.

Air distribution is an effective engineering measure to fight against respiratory infectious diseases like COVID-19. Ventilation indices are widely used to indicate the airborne infection risk of respiratory infectious diseases due to the practical convenience. This study investigates the relationships between the ventilation indices and airborne infection risk to suggest the proper ventilation indices for the evaluation of airborne infection risk control performance of air distribution. Besides the commonly used ventilation indices of the age of air (AoA), air change effectiveness (ACE), and contaminant removal effectiveness (CRE), this study introduces two ventilation indices, i.e., the air utilization effectiveness (AUE) and contaminant dispersion index (CDI). CFD simulations of a hospital ward and a classroom served by different air distributions, including mixing ventilation, displacement ventilation, stratum ventilation and downward ventilation, are validated to calculate the ventilation indices and airborne infection risk. A three-step correlation analysis based on Spearman's rank correlation coefficient, Pearson correlation coefficient, and goodness of fit and a min-max normalization-based error analysis are developed to qualitatively and quantitatively test the validity of ventilation indices respectively. The results recommend the integrated index of AUE and CDI to indicate the overall airborne infection risk, and CDI to indicate the local airborne infection risk respectively regardless of the effects of air distribution, supply airflow rate, infectivity intensity, room configuration and occupant distribution. This study contributes to airborne transmission control of infectious respiratory diseases with air distribution.

Trafficked Malayan pangolins contain viral pathogens of humans.

Pangolins are the most trafficked wild animal in the world according to the World Wildlife Fund. The discovery of SARS-CoV-2-related coronaviruses in Malayan pangolins has piqued interest in the viromes of these wild, scaly-skinned mammals. We sequenced the viromes of 161 pangolins that were smuggled into China and assembled 28 vertebrate-associated viruses, 21 of which have not been previously reported in vertebrates. We named 16 members of Hunnivirus, Pestivirus and Copiparvovirus pangolin-associated viruses. We report that the L-protein has been lost from all hunniviruses identified in pangolins. Sequences of four human-associated viruses were detected in pangolin viromes, including respiratory syncytial virus, Orthopneumovirus, Rotavirus A and Mammalian orthoreovirus. The genomic sequences of five mammal-associated and three tick-associated viruses were also present. Notably, a coronavirus related to HKU4-CoV, which was originally found in bats, was identified. The presence of these viruses in smuggled pangolins identifies these mammals as a potential source of emergent pathogenic viruses.

Distinguishing COVID-19 From Influenza Pneumonia in the Early Stage Through CT Imaging and Clinical Features.

Background: Both coronavirus disease 2019 (COVID-19) and influenza pneumonia are highly contagious and present with similar symptoms. We aimed to identify differences in CT imaging and clinical features between COVID-19 and influenza pneumonia in the early stage and to identify the most valuable features in the differential diagnosis. Methods: Seventy-three patients with COVID-19 confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and 48 patients with influenza pneumonia confirmed by direct/indirect immunofluorescence antibody staining or RT-PCR were retrospectively reviewed. Clinical data including course of disease, age, sex, body temperature, clinical symptoms, total white blood cell (WBC) count, lymphocyte count, lymphocyte ratio, neutrophil count, neutrophil ratio, and C-reactive protein, as well as 22 qualitative and 25 numerical imaging features from non-contrast-enhanced chest CT images were obtained and compared between the COVID-19 and influenza pneumonia groups. Correlation tests between feature metrics and diagnosis outcomes were assessed. The diagnostic performance of each feature in differentiating COVID-19 from influenza pneumonia was also evaluated. Results: Seventy-three COVID-19 patients including 41 male and 32 female with mean age of 41.9 ± 14.1 and 48 influenza pneumonia patients including 30 male and 18 female with mean age of 40.4 ± 27.3 were reviewed. Temperature, WBC count, crazy paving pattern, pure GGO in peripheral area, pure GGO, lesion sizes (1-3 cm), emphysema, and pleural traction were significantly independent associated with COVID-19. The AUC of clinical-based model on the combination of temperature and WBC count is 0.880 (95% CI: 0.819-0.940). The AUC of radiological-based model on the combination of crazy paving pattern, pure GGO in peripheral area, pure GGO, lesion sizes (1-3 cm), emphysema, and pleural traction is 0.957 (95% CI: 0.924-0.989). The AUC of combined model based on the combination of clinical and radiological is 0.991 (95% CI: 0.980-0.999). Conclusion: COVID-19 can be distinguished from influenza pneumonia based on CT imaging and clinical features, with the highest AUC of 0.991, of which crazy-paving pattern and WBC count play most important role in the differential diagnosis.

Contaminant removal and contaminant dispersion of air distribution for overall and local airborne infection risk controls.

Proper air distribution is crucial for airborne infection risk control of infectious respiratory diseases like COVID-19. Existing studies evaluate and compare the performances of different air distributions for airborne infection risk control, but the mechanisms of air distribution for airborne infection risk control remain unclear. This study investigates the mechanisms of air distribution for both overall and local airborne infection risk controls. The experimentally validated CFD models simulate the contaminant concentration fields in a hospital ward based on which the airborne infection risks of COVID-19 are evaluated with the dilution-based expansion of the Wells-Riley model. Different air distributions, i.e., stratum ventilation, displacement ventilation, and mixing ventilation, with various supply airflow rates are tested. The results show that the variations of the overall and local airborne infection risks under different air distributions and different supply airflow rates are complicated and non-linear. The contaminant removal and the contaminant dispersion are proposed as the mechanisms for the overall and local airborne infection risk controls, respectively, regardless of airflow distributions and supply airflow rates. A large contaminant removal ability benefits the overall airborne infection risk control, with the coefficient of determination of 0.96 between the contaminant removal index and the reciprocal of the overall airborne infection risk. A large contaminant dispersion ability benefits the local airborne infection risk control, with the coefficient of determination of 0.99 between the contaminant dispersion index and the local airborne infection risk.

COVID-19 associated EBV reactivation and effects of ganciclovir treatment.

BACKGROUND: Systemic reactivation of Epstein-Barr virus (EBV) may occur in novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the clinical consequences of EBV reactivation remain uncertain. METHODS: In this retrospective study, we screened 1314 patients with confirmed COVID-19 who died or were discharged between January 1, 2020 and March 12, 2020, in Wuhan Infectious Disease Hospital, Wuhan, China. Patients who had complete data for EBV serology and cytomegalovirus (CMV) serology were eligible. Serum levels of viral capsid antigen (VCA)-immunoglobulin G (IgG), Epstein-Barr nuclear antigen-IgG, VCA-IgM, early antigen (EA)-IgG, CMV-IgG, and CMV-IgM were compared between survivors and nonsurvivors. Dynamic changes of laboratory tests and outcomes were compared in patients with and without ganciclovir treatment. We used 1:1 matching based on age, gender, and illness severity to balance baseline characteristics. RESULTS: EBV reactivation was present in 55 of 217 patients. EBV reactivation was associated with age (57.91 [13.19] vs. 50.28 [12.66] years, p < .001), female gender (31 [56%] vs. 60 [37%], p = .02). Patients with EBV reactivation have statistically nonsignificant higher mortality rate (12 [22%] vs. 18 [11%], p = .08). EA-IgG levels were significantly higher in nonsurvivors than in survivors (median difference: -0.00005, 95% confidence interval, CI [-3.10, 0.00], p = .05). As compared to patients with COVID-19 who did not receive ganciclovir therapy, ganciclovir-treated patients had improved survival rate (0.98, 95% CI [0.95, 1.00] vs. 0.88, 95% CI [0.81, 0.95], p = .01). Hemoglobin (p < .001) and prealbumin (p = .02) levels were significantly higher in ganciclovir-treated patients. CONCLUSION: A high proportion of COVID-19 patients had EBV reactivation that may be associated with an increased risk of death. Whether treatment with ganciclovir may decrease the mortality of COVID-19 patients complicated with EBV reactivation warrants to be addressed in a placebo-controlled randomized trial in the future.

Study of the Inactivated COVID-19 Vaccine Contamination in Vaccination Sites — Zigong City, Sichuan Province, China, January, 2021

Vaccines are a crucial weapon in combating the global coronavirus disease 2019 (COVID-19) pandemic. At present, China is in a critical period of COVID-19 vaccination, and most of the approved vaccines are developed by inactivated vaccine technology, which contains the complete nucleic acid sequence of the virus (1-2). The inactivated COVID-19 vaccine may contaminate people and environments during the vaccination process, thus triggering a false alarm of the COVID-19 surveillance system. In this study, we selected some vaccination sites to assess the intensity and distribution of vaccine contamination.;;Before field study, we used Reverse Transcription-Polymerase Chain Reaction (RT-PCR) method with kits that produced by Da An Gene and ZJ Bio-Tech to estimate the signal strength of inactivated COVID-19 vaccine (SinovacBiotech). The average Cycle threshold (Ct) value of ORF1Ab /N gene of the vaccine solution was 15.30±0.77, while the Ct value of the kit’s positive control was 28.01±2.38.

Ruxolitinib attenuates secondary injury after traumatic spinal cord injury.

Excessive inflammation post-traumatic spinal cord injury (SCI) induces microglial activation, which leads to prolonged neurological dysfunction. However, the mechanism underlying microglial activation-induced neuroinflammation remains poorly understood. Ruxolitinib (RUX), a selective inhibitor of JAK1/2, was recently reported to inhibit inflammatory storms caused by SARS-CoV-2 in the lung. However, its role in disrupting inflammation post-SCI has not been confirmed. In this study, microglia were treated with RUX for 24 hours and then activated with interferon-γ for 6 hours. The results showed that interferon-γ-induced phosphorylation of JAK and STAT in microglia was inhibited, and the mRNA expression levels of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-1ß, interleukin-6, and cell proliferation marker Ki67 were reduced. In further in vivo experiments, a mouse model of spinal cord injury was treated intragastrically with RUX for 3 successive days, and the findings suggest that RUX can inhibit microglial proliferation by inhibiting the interferon-γ/JAK/STAT pathway. Moreover, microglia treated with RUX centripetally migrated toward injured foci, remaining limited and compacted within the glial scar, which resulted in axon preservation and less demyelination. Moreover, the protein expression levels of tumor necrosis factor-α, interleukin-1ß, and interleukin-6 were reduced. The neuromotor function of SCI mice also recovered. These findings suggest that RUX can inhibit neuroinflammation through inhibiting the interferon-γ/JAK/STAT pathway, thereby reducing secondary injury after SCI and producing neuroprotective effects.