Quantification of how mechanical ventilation influences the airborne infection risk of COVID-19 and HVAC energy consumption in office buildings.

This paper presents an EnergyPlus-based parametric analysis to investigate the infection risk of Coronavirus Disease 2019 (COVID-19) under different mechanical ventilation scenarios for a typical medium-sized office building in various climate zones. A Wells-Riley (WR) based Gammaitoni-Nucci (GN) model was employed to quantitatively calculate the airborne infection risk. The selected parameters for the parametric analysis include the climate zone, outdoor air fraction, fraction of infectors, quanta generation rate, and exposure time. The loss and deposition of particles are not considered. The results suggest that the COVID-19 infection risk varies significantly with climate and season under different outdoor air fraction scenarios since the building heating and cooling load fundamentally impacts the supply airflow rate and thus directly influences the amount of mechanical ventilation, which determines the dilution ratio of contaminants. This risk assessment identified the climate zones that benefit the most and the least from increasing the outdoor air fraction. The climate zones such as 1A (Honolulu, HI), 2B (Tucson, AZ), 3A (Atlanta, GA), and 7 (International Falls, MN) are the most energy-efficient locations when it comes to increasing the outdoor air fraction to reduce the COVID-19 infection risk. In contrast, the climate zones such as 6A (Rochester, MN) and 6B (Great Falls, MT) are the least energy-efficient ones. This paper facilitates understanding a widely recommended COVID-19 risk mitigation strategy (i.e., increase the outdoor airflow rate) from the perspective of energy consumption. Electronic Supplementary Material: Supplementary material is available for this article at 10.1007/s12273-022-0937-5 and is accessible for authorized users.

Potent Therapeutic Strategies for COVID-19 with Single-Domain Antibody Immunoliposomes Neutralizing SARS-CoV-2 and Lip/cGAMP Enhancing Protective Immunity.

The worldwide spread of COVID-19 continues to impact our lives and has led to unprecedented damage to global health and the economy. This highlights the need for an efficient approach to rapidly develop therapeutics and prophylactics against SARS-CoV-2. We modified a single-domain antibody, SARS-CoV-2 VHH, to the surface of the liposomes. These immunoliposomes demonstrated a good neutralizing ability, but could also carry therapeutic compounds. Furthermore, we used the 2019-nCoV RBD-SD1 protein as an antigen with Lip/cGAMP as the adjuvant to immunize mice. Lip/cGAMP enhanced the immunity well. It was demonstrated that the combination of RBD-SD1 and Lip/cGAMP was an effective preventive vaccine. This work presented potent therapeutic anti-SARS-CoV-2 drugs and an effective vaccine to prevent the spread of COVID-19.

Effect of polymorphism in Rhinolophus affinis ACE2 on entry of SARS-CoV-2 related bat coronaviruses.

Bat coronavirus RaTG13 shares about 96.2% nucleotide sequence identity with that of SARS-CoV-2 and uses human and Rhinolophus affinis (Ra) angiotensin-converting enzyme 2 (ACE2) as entry receptors. Whether there are bat species other than R. affinis susceptible to RaTG13 infection remains elusive. Here, we show that, among 18 different bat ACE2s tested, only RaACE2 is highly susceptible to transduction by RaTG13 S pseudovirions, indicating that the bat species harboring RaTG13 might be very limited. RaACE2 has seven polymorphic variants, RA-01 to RA-07, and they show different susceptibilities to RaTG13 S pseudovirions transduction. Sequence and mutagenesis analyses reveal that residues 34, 38, and 83 in RaACE2 might play critical roles in interaction with the RaTG13 S protein. Of note, RaACE2 polymorphisms have minimal effect on S proteins of SARS-CoV-2 and several SARS-CoV-2 related CoVs (SC2r-CoVs) including BANAL-20-52 and BANAL-20-236 in terms of binding, membrane fusion, and pseudovirus entry. Further mutagenesis analyses identify residues 501 and 505 in S proteins critical for the recognition of different RaACE2 variants and pangolin ACE2 (pACE2), indicating that RaTG13 might have not been well adapted to R. affinis bats. While single D501N and H505Y changes in RaTG13 S protein significantly enhance the infectivity and minimize the difference in susceptibility among different RaACE2 variants, an N501D substitution in SARS-CoV-2 S protein displays marked disparity in transduction efficiencies among RaACE2 variants with a significant reduction in infectivity on several RaACE2 variants. Finally, a T372A substitution in RaTG13 S protein not only significantly increases infectivity on all RaACE2 variants, but also markedly enhances entry on several bat ACE2s including R. sinicus YN, R. pearsonii, and R. ferrumeiqunum. However, the T372A mutant is about 4-fold more sensitive to neutralizing sera from mice immunized with BANAL-20-52 S, suggesting that the better immune evasion ability of T372 over A372 might contribute to the natural selective advantage of T372 over A372 among bat CoVs. Together, our study aids a better understanding of coronavirus entry, vaccine design, and evolution.

Quantification of how mechanical ventilation influences the airborne infection risk of COVID-19 and HVAC energy consumption in office buildings

This paper presents an EnergyPlus-based parametric analysis to investigate the infection risk of Coronavirus Disease 2019 (COVID-19) under different mechanical ventilation scenarios for a typical medium-sized office building in various climate zones. A Wells-Riley (WR) based Gammaitoni-Nucci (GN) model was employed to quantitatively calculate the airborne infection risk. The selected parameters for the parametric analysis include the climate zone, outdoor air fraction, fraction of infectors, quanta generation rate, and exposure time. The loss and deposition of particles are not considered. The results suggest that the COVID-19 infection risk varies significantly with climate and season under different outdoor air fraction scenarios since the building heating and cooling load fundamentally impacts the supply airflow rate and thus directly influences the amount of mechanical ventilation, which determines the dilution ratio of contaminants. This risk assessment identified the climate zones that benefit the most and the least from increasing the outdoor air fraction. The climate zones such as 1A (Honolulu, HI), 2B (Tucson, AZ), 3A (Atlanta, GA), and 7 (International Falls, MN) are the most energy-efficient locations when it comes to increasing the outdoor air fraction to reduce the COVID-19 infection risk. In contrast, the climate zones such as 6A (Rochester, MN) and 6B (Great Falls, MT) are the least energy-efficient ones. This paper facilitates understanding a widely recommended COVID-19 risk mitigation strategy (i.e., increase the outdoor airflow rate) from the perspective of energy consumption. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s12273-022-0937-5 and is accessible for authorized users.

Individualized positive end-expiratory pressure setting in patients with severe acute respiratory distress syndrome supported with veno-venous extracorporeal membrane oxygenation.

BACKGROUND: Patients with acute respiratory distress syndrome supported with veno-venous extracorporeal membrane oxygenation benefit from higher positive end-expiratory pressure combined with conventional ventilation during the early extracorporeal membrane oxygenation period. The role of incremental positive end-expiratory pressure titration in patients with severe acute respiratory distress syndrome supported with veno-venous extracorporeal membrane oxygenation remains unclear. This study aimed to determine the preferred method for setting positive end-expiratory pressure in patients with severe acute respiratory distress syndrome on veno-venous extracorporeal membrane oxygenation support. METHODS: We retrospectively reviewed all subjects supported with veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome from 2009 to 2019 in the intensive care units in Tianjin Third Central Hospital. Subjects were divided into two groups according to the positive end-expiratory pressure titration method used: P-V curve (quasi-static pressure-volume curve-guided positive end-expiratory pressure setting) group or Crs (respiratory system compliance-guided positive end-expiratory pressure setting) group. RESULTS: Forty-three subjects were included in the clinical outcome analysis: 20 in the P-V curve group and 23 in the Crs group. Initial positive end-expiratory pressure levels during veno-venous extracorporeal membrane oxygenation were similar in both groups. Incidence rates of barotrauma and hemodynamic events were significantly lower in the Crs group (all p < 0.05). Mechanical ventilation duration, intensive care unit length of stay, and hospital length of stay were significantly shorter in the Crs group than the P-V curve group (all p < 0.05). Subjects in the Crs group showed non-significant improvements in the duration of extracorporeal membrane oxygenation support and 28-day mortality (p > 0.05). CONCLUSION: Respiratory system compliance-guided positive end-expiratory pressure setting may lead to more optimal clinical outcomes for patients with severe acute respiratory distress syndrome supported by veno-venous extracorporeal membrane oxygenation. Moreover, the operation is simple, safe, and convenient in clinical practice.

Parameter estimation of the incubation period of COVID-19 based on the doubly interval-censored data model.

With the spread of the novel coronavirus disease 2019 (COVID-19) around the world, the estimation of the incubation period of COVID-19 has become a hot issue. Based on the doubly interval-censored data model, we assume that the incubation period follows lognormal and Gamma distribution, and estimate the parameters of the incubation period of COVID-19 by adopting the maximum likelihood estimation, expectation maximization algorithm and a newly proposed algorithm (expectation mostly conditional maximization algorithm, referred as ECIMM). The main innovation of this paper lies in two aspects: Firstly, we regard the sample data of the incubation period as the doubly interval-censored data without unnecessary data simplification to improve the accuracy and credibility of the results; secondly, our new ECIMM algorithm enjoys better convergence and universality compared with others. With the framework of this paper, we conclude that 14-day quarantine period can largely interrupt the transmission of COVID-19, however, people who need specially monitoring should be isolated for about 20 days for the sake of safety. The results provide some suggestions for the prevention and control of COVID-19. The newly proposed ECIMM algorithm can also be used to deal with the doubly interval-censored data model appearing in various fields.

Coevolving Dynamics between Epidemic and Information Spreading considering the Dependence between Vigilance and Awareness Prevalence

It has been demonstrated that the propagation of information and awareness regarding a disease can assist in containing the outbreak of epidemics. Previous models for this coevolving usually introduced the dependence between these two processes by setting a lower but time-independent infection rate for individuals with awareness. However, a realistic scenario can be more complicated, as individual vigilance and the adopted protective measures may depend on the extent of the discussion on the disease, whereas individuals may be irrational or lack relevant knowledge, leading to improper measures being taken. These can introduce a time-varying dependence between epidemic dynamics and awareness prevalence and may weaken the effect of spreading awareness in containing a pandemic. To better understand this effect, we introduce a nonlinear dependence of the epidemic infection rate on awareness prevalence, focusing on the effect of different forms of dependence on the coevolving dynamics. We demonstrate that a positive correlation between vigilance and awareness prevalence can enhance the effect of information spreading in suppressing epidemics. However, this enhancement can be weakened if some individuals are irrational. Our results demonstrate the importance of rational behavior in the strategy of containing epidemics by propagation of disease information.

Stability and optimal control strategies for a novel epidemic model of COVID-19.

In this paper, a novel two-stage epidemic model with a dynamic control strategy is proposed to describe the spread of Corona Virus Disease 2019 (COVID-19) in China. Combined with local epidemic control policies, an epidemic model with a traceability process is established. We aim to investigate the appropriate control strategies to minimize the control cost and ensure the normal operation of society under the premise of containing the epidemic. This work mainly includes: (i) propose the concept about the first and the second waves of COVID-19, as well as study the case data and regularity of four cities; (ii) derive the existence and stability of the equilibrium, the parameter sensitivity of the model, and the existence of the optimal control strategy; (iii) carry out the numerical simulation associated with the theoretical results and construct a dynamic control strategy and verify its feasibility.

[CT Characteristics of Consolidation Type of Pulmonary Cryptococcosis in Immunocompetent Patients].

Objective To analyze the CT characteristics of consolidation type of pulmonary cryptococcosis in immunocompetent patients,and thus improve the diagnosis of this disease. Methods A total of 20 cases with consolidation-type pulmonary cryptococcosis confirmed by pathological examinations were studied.Each patient underwent breath-hold multislice spiral CT,and 10 patients underwent contrast enhanced CT.The data including lesion number,lesion distribution,lesion density,performance of enhanced CT scan,accompanying signs,and prognosis were analyzed. Results The occurrence rates of single and multiple lesions were 80.0%(n=16)and 20.0%(n=4),respectively.In all the 16 multiple-lesion patients,the occurrence rate of unilateral lobar distribution was 56.0%(n=9).The 76 measurable lesions mainly presented subpleural distribution(71.1%,n=54)and lower pulmonary distribution(75.0%,n=57).A total of 39 lesions were detected in the 10 patients received contrast enhanced CT,in which 31 lesions(79.5%)showed homogeneous enhancement,34 lesions(87.2%)showed moderate enhancement,and all the lesions manifested angiogram sign.Consolidation lesions were accompanied by many CT signs,of which air bronchogram sign had the occurrence rate of 63.2%(n=48),including types Ⅲ(n =37)and Ⅳ(n=11).Other signs included halo signs(43/76,56.6%),vacuoles or cavities(9/76,11.8%),pleural thickening(14/20,70.0%),and pleural effusion(2/20,10.0%).After treatment,the lesions of 7 patients were basically absorbed and eventually existed in the form of fibrosis. Conclusions The lesions in the immunocompetent patients with consolidation type of pulmonary cryptococcosis usually occur in the lower lobe and close to the pleura,mainly presenting unilateral distribution.The CT angiogram signs,proximal air bronchogram signs,and halo signs are the main features of this disease,which contribute to the diagnosis.

Modular composite building in urgent emergency engineering projects: A case study of accelerated design and construction of Wuhan Thunder God Mountain/Leishenshan hospital to COVID-19 pandemic.

Wuhan Leishenshan/Leishenshan ("Leishenshan" for short) hospital is a makeshift emergency hospital for treating patients diagnosed with the novel coronavirus-infected pneumonia (NCIP). Engineering construction uses modular composite building finished products to the greatest extent, which reduces the workload of field operations and saves a lot of time. The building information model (BIM) technology assists in design and construction work to meet rapid construction requirements. Besides, based on the unmanned aerial vehicles (UAVs) data analysis and application platform, digitization and intelligence in engineering construction are improved. Simultaneously, on-site construction and overall hoisting were carried out to achieve maximum efficiency. This article aims to take the construction of Leishenshan Hospital as an example to illustrate how to adopt BIM technology and other high-tech technology such as big data, artificial intelligence, drones, and 5G for the fast construction of the fabricated steel structure systems in emergency engineering projects.

Early Treatment Effect of Chinese Herbal Medicine Formula Huashibaidu Granule on Mild COVID-19 Patients in Fangcang Hospital: An Unblinded, Cluster-Randomized Clinical Trial (preprint)

BACKGROUND: Previous study suggested that Chinese Herbal Medicine (CHM) Formula Huashibaidu granule might shorten disease course of Corona Virus Disease 2019 (COVID-19) patients. Our research aims to investigate the early treatment effect of Huashibaidu granule in mild COVID-19 patients under well clinical management.METHODS: An unblended cluster-randomized clinical trial was conducted at the Dongxihu FangCang hospital. 2 cabins were randomly allocated to CHM or control group, with 204 randomly sampled mild COVID-19 patients in each cabin. All participants received a 7-day conventional treatment, and CHM group cabin used additional Huashibaidu granule 10g twice daily. Participants were followed up until they met clinical endpoint. The primary outcome was patient become worsening before clinical endpoint occurred. The secondary outcomes was discharge with cure before clinical endpoint occurred and relief of composite symptoms after 7 days treatment.FINDINGS: All 408 participants were followed up to meet clinical endpoint and included in statistical analysis. The baseline characteristics were comparable between 2 groups. The number of worsening patients in the CHM group was 5 (2.5%), and that in the control group was 16 (7.8%). There was a significant difference between groups (P=0.014). 8 foreseeable mild adverse events occurred without statistical difference between groups.INTERPRETATION: 7-day early treatment with Huashibaidu granule reduced worsening conversion of mild COVID-19 patients. Our study supports Huashibaidu Granule as an active option for early treatment of mild COVID-19 in similar medical locations with well management.TRIAL REGISTRATION: The Chinese Clinical Trial Registry: ChiCTR2000029763.FUNDING: This study was supported by “National Key R&D Program of China” (No.2020YFC0841500).DECLARATION OF INTERESTS: The authors guaranteed that there existed no competing interest in this paper.ETHICS APPROVAL STATEMENT: Ethics Review Committee of Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences Approval of Ethical Review Acceptance Number: S2020-001; Approval Number: P20001/PJ01.

[Dynamic measurement of volume of atelectasis area in the evaluation of the prognosis of patients with moderate-to-severe acute respiratory distress syndrome].

OBJECTIVE: To assess the impact of not inflated lung tissue (NILT) volume on the prognosis of patients with moderate-to-severe acute respiratory distress syndrome (ARDS). METHODS: The clinical data of 131 patients with moderate-to-severe ARDS admitted to the intensive care unit (ICU) of Tianjin Third Central Hospital from March 2016 to June 2019 were collected. The basic data of patients, including gender, age, body mass index (BMI), causes of ARDS, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score and oxygenation index (PaO2/FiO2), were collected. The CT imaging data of patients on the 1st and 7th day in the ICU were collected. According to the CT value, they were divided into hyperventilated areas (-1 000 to -900 HU), normal ventilation areas (-899 to -500 HU), poorly ventilated areas (-499 to -100 HU), and atelectasis area (-99 to 100 HU). The total lung volume and the percentage of NILT to the total lung volume (NILT%) were calculate. At the same time, duration of mechanical ventilation, length of ICU stay, total length of hospital stay were collected. According to the 28-day follow-up, they were divided into survival group and death group. Multivariate Logistic regression analysis was used to determine the risk factors for 28-day death in ARDS patients. The receiver operating characteristic (ROC) curve was drawn, the area under ROC curve (AUC) and 95% confidence interval (95%CI) were calculated to determine the accuracy of NILT% in predicting the 28-day prognosis of ARDS patients, and the NILT% threshold was used for subgroup analysis of patients. RESULTS: Among the 131 patients with moderate-to-severe ARDS, patients were excluded for more than 48 hours after ARDS diagnosis, repeated admission to ICU due to ARDS, the ICU duration less than 7 days, death within 72 hours of admission, chronic interstitial lung disease or congestive heart failure, no chest CT examination within 7 days of admission to ICU, and no specimen collection within 2 hours of admission to ICU. Finally, a total of 53 patients were enrolled in the analysis. Of the 53 patients, 31 patients survived and 22 patients died. The 28-day mortality was 41.5%. Compared with the survival group, patients in the death group were older (years old: 65.32±11.29 vs. 55.77±14.23), and had a higher SOFA score (11.68±3.82 vs. 8.39±2.23) with significant differences (both P < 0.05), while there were no significant differences in gender, BMI, ARDS cause, APACHE II score and PaO2/FiO2 between the two groups. There was no significant difference in CT value, total lung volume and NILT% between the two groups at 1st day after admission to ICU; NILT% on day 7 after admission to ICU in the death group was significantly higher than that in the survival group [(28.95±8.40)% vs. (20.35±5.91)%, P < 0.01], but there was no significant difference in CT value and total lung volume between the two groups. Multivariate Logistic regression analysis showed that the 28-day prognosis of ARDS was related to age, SOFA score and NILT% independently [age: odds ratio (OR) = 0.892, 95%CI was 0.808-0.984, P = 0.023; SOFA score: OR = 0.574, 95%CI was 0.387-0.852, P = 0.006; NILT%: OR = 0.841, 95%CI was 0.730-0.968, P = 0.016]. ROC curve analysis showed that 7-day NILT% could predict the 28-day prognosis of patients with moderate-to-severe ARDS, and AUC was 0.810 (95%CI was 0.678-0.952, P < 0.01). The NILT% threshold was 15.50%, sensitivity was 95.5%, specificity was 80.6%, positive predictive value was 85.7%, and negative predictive value was 74.6%. According to the 7-day NILT% threshold, a subgroup analysis of patients was performed, and 7-day NILT% > 15.50% was defined as a high-risk clinical prognosis, and ≤ 15.50% was a low-risk. Compared with low-risk patients (n = 7), the duration of mechanical ventilation, the length of ICU stay and total length of hospital stay in high-risk patients (n = 46) were significantly prolonged [duration of mechanical ventilation (days): 9.37±6.14 vs. 4.43±1.72, length of ICU stay (days): 12.11±5.85 vs. 7.57±1.13, total length of hospital stay (days): 18.39±5.87 vs. 11.29±2.22, all P < 0.05]. CONCLUSIONS: The 7-day NILT% > 15.50% of patients with moderate-to-severe ARDS after ICU admission is related to poor prognosis.

Spread mechanism and control strategy of social network rumors under the influence of COVID-19.

Since the outbreak of coronavirus disease in 2019 (COVID-19), the disease has rapidly spread to the world, and the cumulative number of cases is now more than 2.3 million. We aim to study the spread mechanism of rumors on social network platform during the spread of COVID-19 and consider education as a control measure of the spread of rumors. Firstly, a novel epidemic-like model is established to characterize the spread of rumor, which depends on the nonautonomous partial differential equation. Furthermore, the registration time of network users is abstracted as 'age,' and the spreading principle of rumors is described from two dimensions of age and time. Specifically, the susceptible users are divided into higher-educators class and lower-educators class, in which the higher-educators class will be immune to rumors with a higher probability and the lower-educators class is more likely to accept and spread the rumors. Secondly, the existence and uniqueness of the solution is discussed and the stability of steady-state solution of the model is obtained. Additionally, an interesting conclusion is that the education level of the crowd is an essential factor affecting the final scale of the spread of rumors. Finally, some control strategies are presented to effectively restrain the rumor propagation, and numerical simulations are carried out to verify the main theoretical results.