Short-Term Effects of Air Pollution on the Risk of Influenza in Jinan, China during 2020-2021: A Time-Series Analysis

Background: Air pollution leads to many adverse diseases, especially respiratory diseases and cardiac symptoms. However, it has not been studied the association between air pollution and influenza cases in Jinan City, especially during the outbreak of COVID-19;Methods: The data were obtained from China's Disease Information System, and influenza cases during 2020-2021 in Jinan City were collected from it. We used the generalized additive Poisson model to measure the association between air pollutants and the daily influenza cases after adjusting for possible influence variables;Results: There were 4767 influenza cases. PM2.5 and PM10 on lag 0, lag 3, and lag 4 were significantly associated with an increased risk of influenza;gaseous pollutants (NO2 and SO2) led to higher risk than particulate matter pollutants (PM2.5 and PM10). There were no significant differences for sex subgroup analyses. Except for O3, the incidence risk of males and females was highest on lag 3 and lag 4. For the study of different age groups, influenza cases aged over 59 years had a slightly larger relative risk when exposed to all air pollutants (except O3) than the younger group;Conclusions: The overall number of influenza cases decreased in 2020-2021. PM2.5, SO2, CO, and NO2 were significantly associated with the risk of influenza during 2020-2021. Countermeasures should be developed according to the characteristics of influenza risk to prevent and control it.

PM2.5-Related Health Risk during Chinese Spring Festival in Taizhou, Zhejiang: The Health Impacts of COVID-19 Lockdown

Exposure to high concentrations of fine particles (PM2.5) with toxic metals can have significant health effects, especially during the Chinese spring festival (CSF), due to the large amount of fireworks' emissions. Few studies have focused on the potential health impact of PM2.5 pollution in small cities in China during the 2020 CSF, which coincided with the COVID-19 outbreak that posed a huge challenge to the environment and obvious health issues to countries around the world. We examined the characteristics of PM2.5, including carbonaceous matter and elements, for three intervals during the 2020 CSF in Taizhou, identified the sources and evaluated the health risks, and compared them with those of 2018. The results showed that PM2.5 increased by 13.20% during the 2020 CSF compared to those in the 2018 CSF, while carbonaceous matter (CM) and elements decreased by 39.41% and 53.84%, respectively. The synergistic effects of emissions, chemistry, and transport may lead to increased PM2.5 pollution, while the lockdown measures contributed to the decrease in CM and elements during the 2020 CSF. Fe, Mn, and Cu were the most abundant elements in PM2.5 in both years, and As and Cr(VI) should be of concern as their concentrations in both years exceeded the NAAQS guideline values. Industry, combustion, and mineral/road dust sources were identified by PCA in both years, with a 5.87% reduction in the contribution from industry in 2020 compared to 2018. The noncarcinogenic risk posed by As, Co, Mn, and Ti in 2018 and As and Mn in 2020 was significant. The carcinogenic risk posed by As, Cr(VI), and Pb exceeded the accepted precautionary limit (1 ×10-6) in both years. Mn was the dominant contributor to the total noncarcinogenic risks, while Cr(VI) showed the largest excessive cancer risks posed by metals in PM2.5, implying its associated source, industry, was the greatest risk to people in Taizhou after exposure to PM2.5. Despite the increase in PM2.5 mass concentration, the health impacts were reduced by the lockdown policy implemented in Taizhou during the 2020 CSF compared to 2018. Our study highlights the urgent need to consider the mitigation of emissions in Taizhou and regional joint management efforts based on health protection objectives despite the rough source apportionment by PCA.

A novel RBD-protein/peptide vaccine elicits broadly neutralizing antibodies and protects mice and macaques against SARS-CoV-2.

The development of safe and effective vaccines to respond to COVID-19 pandemic/endemic remains a priority. We developed a novel subunit protein-peptide COVID-19 vaccine candidate (UB-612) composed of: (i) receptor binding domain of SARS-CoV-2 spike protein fused to a modified single-chain human IgG1 Fc; (ii) five synthetic peptides incorporating conserved helper and cytotoxic T lymphocyte (Th/CTL) epitopes derived from SARS-CoV-2 structural proteins (three from S2 subunit, one from membrane and one from nucleocapsid), and one universal Th peptide; (iii) aluminum phosphate as adjuvant. The immunogenicity and protective immunity induced by UB-612 vaccine were evaluated in four animal models: Sprague-Dawley rats, AAV-hACE2 transduced BALB/c mice, rhesus and cynomolgus macaques. UB-612 vaccine induced high levels of neutralizing antibody and T-cell responses, in all animals. The immune sera from vaccinated animals neutralized the SARS-CoV-2 original wild-type strains and multiple variants of concern, including Delta and Omicron. The vaccination significantly reduced viral loads, lung pathology scores, and disease progression after intranasal and intratracheal challenge with SARS-CoV-2 in mice, rhesus and cynomolgus macaques. UB-612 has been tested in primary regimens in Phase 1 and Phase 2 clinical studies and is currently being evaluated in a global pivotal Phase 3 clinical study as a single dose heterologous booster.

A feasibility study of Covid-19 detection using breath analysis by high-pressure photon ionization time-of-flight mass spectrometry.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a tremendous threat to global health. polymerase chain reaction (PCR) and antigen testing have played a prominent role in the detection of SARS-CoV-2-infected individuals and disease control. An efficient, reliable detection tool is still urgently needed to halt the global COVID-19 pandemic. Recently, the food and drug administration (FDA) emergency approved volatile organic component (VOC) as an alternative test for COVID-19 detection. In this case-control study, we prospectively and consecutively recruited 95 confirmed COVID-19 patients and 106 healthy controls in the designated hospital for treatment of COVID-19 patients in Shenzhen, China. Exhaled breath samples were collected and stored in customized bags and then detected by high-pressure photon ionization time-of-flight mass spectrometry for VOCs. Machine learning algorithms were employed for COVID-19 detection model construction. Participants were randomly assigned in a 5:2:3 ratio to the training, validation, and blinded test sets. The sensitivity (SEN), specificity (SPE), and other general metrics were employed for the VOCs based COVID-19 detection model performance evaluation. The VOCs based COVID-19 detection model achieved good performance, with a SEN of 92.2% (95% CI: 83.8%, 95.6%), a SPE of 86.1% (95% CI: 74.8%, 97.4%) on blinded test set. Five potential VOC ions related to COVID-19 infection were discovered, which are significantly different between COVID-19 infected patients and controls. This study evaluated a simple, fast, non-invasive VOCs-based COVID-19 detection method and demonstrated that it has good sensitivity and specificity in distinguishing COVID-19 infected patients from controls. It has great potential for fast and accurate COVID-19 detection.

How should designated COVID-19 hospitals in megacities implement a precise management strategy in response to Omicron?

As a new variant of COVID-19 with varied mutations, Omicron is more transmissible, more rapidly contagious, and has a greater risk of reinfection. Given those facts, a precise manage strategy needs to be formulated and implemented in designated megacities. Here, the precise COVID-19 prevention and control strategy for a designated hospital in Shenzhen, China is summarized, including implementation of a two-wing "On duty/On standby" approach based on busy and calm periods, an identification, classification, and grading system for the occupational exposure risks of medical staff, classification of patient transmission risks, separate admission, and an innovative treatment (nasal irrigation). The strategy has enabled the efficient and orderly integration of resources, it has resulted in zero infections among medical staff even during the peak hours of the pandemic at the hospital (1,930 patients admitted to both wings in a single day), and it has significantly reduced the initial period of no virus detection when patients infected with Omicron received saline nasal irrigation (P < 0.001). This strategy has provided evidence of precise prevention and control in a hospital, infection control, and efficient patient treatment in an era when Omicron is widespread.

Effectiveness and Safety of Baidu Jieduan Granules for COVID-19: A Retrospective Observational Multicenter Study.

OBJECTIVE: To evaluate the effectiveness and safety of Baidu Jieduan Granules (BDJDG) to treat common type coronavirus disease 2019 (COVID-19). METHODS: This multicenter, retrospective, and observational clinical trial included 230 common COVID-19 patients in Leishenshan, Huangshi, and Laohekou Hospitals in Wuhan from January 21 to March 26, 2020. The included patients were further divided into two subgroups according to the use of supplemental oxygen, mild and moderate groups. During the first 14 d of hospitalization, all patients were administered BDJDG combined with conventional Western medicine, and observed for continuous 28 d. Primary outcomes were disease progression rate and discharge rate. Secondary outcomes included negative conversion time of nucleic acid, hospitalization duration, clinical symptom subsidence time, and symptom regression rate. RESULTS: A total of 230 common COVID-19 patients were analyzed (138 in moderate group and 92 in mild group). By day 28, the disease progression rate was 4.3% and the discharge rate was 95.7%. All mild cases recovered and were discharged from hospital. The median negative conversion time of nucleic acid of all 230 COVID-19 patients was 12 d [inter-quartile range (IQR) 3.5-17], the median hospitalization duration was 15 d (IQR 12-20). The median time to fever, cough, and fatigue recovery was 4 d (IQR 2-6), 8 d (IQR 5-12), and 8 d (IQR 5-11). The recovery rate of fever, cough, and fatigue was 94.6%, 90.5%, and 93.5%. The median time to clinical improvement was 12 d (IQR 10-17). Compared with the baseline, total leukocyte counts, neutrophil counts, lymphocyte counts, and platelet counts were increased significantly on days 7 and 14 (P<0.01). C-reactive protein markedly increased on day 3 and significantly decreased on days 7 and 14 (P<0.01). No serious adverse events occurred during treatment. CONCLUSION: BDJDG may be effective and safe for treatment of common type COVID-19. (Registration No. ChiCTR2000030836).

Combing pre-workshop, web-based learning and hands-on workshop as a flipped classroom clinical skill training model during the COVID-19 pandemic.

OBJECTIVE: Due to the COVID-19 pandemic, there is a dramatic drop in in-person residency training due to the implementation of isolation and triage measurements. Here, we propose a new flipped classroom clinical skill training model utilizing a combination of pre-workshop, web-based learning and hands-on workshop that shortens in-person contact time to maintain residency training during the pandemic. Effectiveness of this training model was evaluated with a pre-test and post-test skills competency assessment, two-way feedback, and a five-point Likert scale structured survey questionnaire. MATERIALS AND METHODS: The workshop was conducted in a flipped classroom fashion by the obstetrics and gynecology (OBGYN) department of a single tertiary teaching medical center covering topics from five OBGYN subspecialities. Every topic consisted of a pre-workshop, web-based, mini lecture (PWML) followed by a hands-on workshop (HW). All first to fourth year OBGYN residents were invited to attend the workshop. All the trainees were required to complete the PWML prior to the day of HW. The workshop consisted of rotational station for each topic and was conducted within one afternoon. A 0-100-point scale pre-test and post-test skills competency evaluation were performed for each station and was assessed by the attending doctor or fellow doctor of each subspeciality. Two-way feedback was done after the post-test evaluation. A five-point Likert scale structured survey instrument consisting of participant's perceptions of the workshop design, relevance to clinical practice, and quality of instructors and materials was created during the curriculum development process and sent to each participant one month after the workshop. RESULTS: A total of 19 residents including five first-year, six second-year, three third-year, and five fourth-year residents completed the entire pre-workshop lecture, workshop, pre-test, and post-test. For all residents, the average post-test score of 5 stations was 95 and was significantly higher than the pre-test score of 60 (p < 0.001). For both junior residents and senior residents, the average post-test scores of 5 stations were also significantly higher than pre-test scores (p < 0.001). Survey generated one month after the workshop showed a high overall satisfaction with the workshop instructors on their professional knowledge, communication skills, and interactions between the instructors and trainees. The average satisfaction scores for manipulation of vaginal breech delivery (VBD), semen analysis (SA), cervical conization (CC), obstetrics anal sphincter injury (OASIS), and laparoscopic suture techniques (LST) were 4.84, 4.96, 4.92, 4.88, and 4.92, respectively The average score for practical application of the training materials, class design and teaching method, overall satisfaction of the session, and time scheduling was 4.84, 4.96, 4.96, and 4.48, respectively. The entire HW was completed within 180 min and was carried out within half a day. CONCLUSION: With the implementation of isolation and triage measures in the COVID-19 pandemic, there is a dramatic drop in in-person exposure to all aspects of the residency training, in particular, non-emergent surgeries. Utilization of PWML saved 1/3 of in-person time and the entire workshop was completed within 180 min that could be carried out within half a day. The decrease of person-to-person contact time during the COVID-19 pandemic is necessary while still providing curriculum-based residency training in spite of decreased hands-on experience.

An innovative two-wing model for balancing the demands of inpatients with COVID-19 and general medical service in a designated hospital for COVID-19 in Shenzhen, China.

Since COVID-19 was first reported in 2019, the pandemic has posed a great threat to human health. Due to its multiple transmission pathways and virus mutation, this epidemic may be protracted further, and it has already placed a heavy burden on healthcare systems. A strategy needs to be devised to address both needs for COVID-19 treatment and demands for general medical service. A two-wing model of hospital operation, which provides a safe treatment environment for patients, an On duty/On Standby work approach for medical staff, and a reliable surveillance system for hospital operation, is an effective management template to help achieve a balance between multiple demands for medical service in this new era of a long-term war against COVID-19.

Cell-derived membrane biomimetic nanocarriers for targeted therapy of pulmonary disease.

Pulmonary diseases are currently one of the major threats of human health, especially considering the recent COVID-19 pandemic. However, the current treatments are facing the challenges like insufficient local drug concentrations, the fast lung clearance and risks to induce unexpected inflammation. Cell-derived membrane biomimetic nanocarriers are recently emerged delivery strategy, showing advantages of long circulation time, excellent biocompatibility and immune escape ability. In this review, applications of using cell-derived membrane biomimetic nanocarriers from diverse cell sources for the targeted therapy of pulmonary disease were summarized. In addition, improvements of the cell-derived membrane biomimetic nanocarriers for augmented therapeutic ability against different kinds of pulmonary diseases were introduced. This review is expected to provide a general guideline for the potential applications of cell-derived membrane biomimetic nanocarriers to treat pulmonary diseases.

Do Commodities React More to Time-Varying Rare Disaster Risk? A Comparison of Commodity and Financial Assets

Using a rare disaster risk database from almost the last one hundred years, we examine the differences in the reaction of asset prices to rare disaster risk between commodity and financial assets. We first employ time-varying parameter VAR (TVP-VAR) models to investigate the role of rare disaster risk in the price dynamics of major asset markets. The results indicate that disaster risk generally has a more intense and persistent impact on crude oil and stock markets when compared to gold and bond markets. However, the role of rare disaster risk differs substantially between commodity and financial assets, as well as between the short and long term. Moreover, when using a nonparametric causality-in-quantiles method to detect causal relationships, we provide evidence of the nonlinear causality effect of rare disaster risks on asset volatilities, and not their returns, except for crude oil. In addition, we demonstrate that augmenting a diversified portfolio of stock or bonds with gold can significantly increase its risk-adjusted performance. The findings have important implications for investors as well as policymakers.

Potent Anti-Delta Effect By a Booster Third-Dose of UB-612, a Precision-Designed SARS-CoV-2 Multitope Protein-Peptide Vaccine (preprint)

SARS-CoV-2 breakthrough infection occurs due to waning immunity time-to-vaccine, to which the globally-dominant, highly-contagious Delta variant is behind the scene. In the primary 2-dose and booster series of clinical Phase-1 trial, UB-612 vaccine, which contains S1-RBD and synthetic Th/CTL peptide pool for activation of humoral and T-cell immunity, induces substantial, prolonged viral-neutralizing antibodies that goes parallel with a long-lasting T-cell immunity; and a booster (3rd ) dose can prompt recall of memory immunity to induce profound, striking antibodies with the highest level of 50% viral-neutralizing GMT titers against live Delta variant reported for any vaccine. The unique design of S1-RBD only plus multitope T-cell peptides may have underpinned UB-612’s potent anti-Delta effect, while the other full S protein-based vaccines are affected additionally by mutations in the N-terminal domain sequence which contains additional neutralizing epitopes. UB-612, safe and well-tolerated, could be effective for boosting other vaccine platforms that have shown modest homologous boosting. [Funded by United Biomedical Inc., Asia; ClinicalTrials.gov ID: NCT04967742 and NCT04545749]

Iron oxide nanoparticles augment the intercellular mitochondrial transfer-mediated therapy.

The transfer of mitochondria between cells has recently been revealed as a spontaneous way to protect the injured cells. However, the utilization of this natural transfer process for disease treatment is so far limited by its unsatisfactory transfer efficiency and selectivity. Here, we demonstrate that iron oxide nanoparticles (IONPs) can augment the intercellular mitochondrial transfer from human mesenchymal stem cells (hMSCs) selectively to diseased cells, owing to the enhanced formation of connexin 43­containing gap junctional channels triggered by ionized IONPs. In a mouse model of pulmonary fibrosis, the IONP-engineered hMSCs achieve a remarkable mitigation of fibrotic progression because of the promoted intercellular mitochondrial transfer, with no serious safety issues identified. The present study reports a potential method of using IONPs to enable hMSCs for efficient and safe transfer of mitochondria to diseased cells to restore mitochondrial bioenergetics.

Effective Preventive Strategies to Prevent Secondary Transmission of COVID-19 in Hemodialysis Unit: The First Month of Community Outbreak in Taiwan.

BACKGROUND: Dialyzed patients are vulnerable to coronavirus infection disease 2019 (COVID-19). The incidence and outcome of COVID-19 in hemodialysis (HD) patients in Taiwan remain unclear. A series of preventive measures were executed to combat COVID-19 transmission among HD patients. METHODS: We carried out a series of forward-looking and practical preventive strategies of COVID-19 control in our HD center. Incidences of COVID-19 of our HD unit were compared with those of national and local estimates from a community outbreak from 15 May to 30 June 2021. Prognostic factors associated with mortality were analyzed. RESULTS: The national incidence of COVID-19 was 0.062%; being highest in Taipei City (0.173%), followed by New Taipei City (0.161%) and Keelung (0.083%). The overall incidence in Keelung HD patients was 0.666%. One patient of our HD center contracted COVID-19 from the household; however, we have contained secondary transmission in our HD center by implementing strict preventive measures. The mortality rate of HD patients in Keelung was 66.6%. The median Ct value of HD patients was 17.53 (11.75-27.90) upon diagnosis. The deceased patients had a higher cardiac/thoracic ratio than alive (0.61 vs. 0.55, p = 0.036). CONCLUSIONS: Taking aggressive and proactive infection preventive measures impedes the secondary transmission of COVID-19 in HD facilities. COVID-19-associated mortality was high in HD patients, being the high cardiac-thoracic ratio, an important prognostic factor for clinical outcome of infected HD patients.

Epidemiological analysis of 67 local COVID-19 clusters in Sichuan Province, China.

BACKGROUND: This study was intended to investigate the epidemiological characteristics of COVID-19 clusters and the severity distribution of clinical symptoms of involved cases in Sichuan Province, so as to provide information support for the development and adjustment of strategies for the prevention and control of local clusters. METHODS: The epidemiological characteristics of 67 local clusters of COVID-19 cases in Sichuan Province reported as of March 17, 2020 were described and analyzed. Information about all COVID-19 clusters and involved cases was acquired from the China Information System for Disease Control and Prevention and analyzed with the epidemiological investigation results taken into account. RESULTS: The clusters were temporally and regionally concentrated. Clusters caused by imported cases from other provinces accounted for 73.13%; familial clusters accounted for 68.66%; the average attack rate was 8.54%, and the average secondary attack rate was 6.11%; the median incubation period was 8.5 d; a total of 28 cases met the criteria for incubation period determination, and in the 28 cases, the incubation period was > 14 d in 21.43% (6/28). a total of 226 confirmed cases were reported in the 67 clusters. Ten cases were exposed before the confirmed cases they contacted with developed clinical symptoms, and the possibility of exposure to other infection sources was ruled out; two clusters were caused by asymptomatic carriers; confirmed cases mainly presented with fever, respiratory and systemic symptoms; a gradual decline in the severity of clinical symptoms was noted with the increase of the case generation. CONCLUSIONS: Population movement and gathering restrictions and strict close contact management measures will significantly contribute to the identification and control of cases. Transmission during the incubation period and asymptomatic infections have been noted. Studies on the pathogenicity and transmissibility in these populations and on COVID-19 antibody levels and protective effects in healthy people and cases are required.

Estimating the instant case fatality rate of COVID-19 in China.

OBJECTIVE: The outbreak of coronavirus disease 2019 (COVID-19) in China has been basically controlled. However, the global epidemic of COVID-19 is worsening. We established a method to estimate the instant case fatality rate (CFR) and cure rate of COVID-19 in China. METHODS: A total of 82 735 confirmed cases released officially by the Chinese authorities from December 8, 2019 to April 18, 2020 were collected. The estimated diagnosis dates of deaths and cured cases were calculated based on the median cure time or median death time of individual cases. Following this, the instant CFR was calculated according to the number of deaths and cured cases on the same estimated diagnosis date. RESULTS: In China, the instant CFR of COVID-19 was 3.8-14.6% from January 1 to January 17; it then declined gradually and stabilized at 5.7% in April. The average CFR in China was 6.1±2.9%, while the CFR was 1.0±0.4% in China except Hubei Province. The cure rate of COVID-19 was 93.9±2.9% in China, and stabilized at 94.3%, while it was 99.0±0.4% in China except Hubei Province. CONCLUSIONS: The instant CFR of COVID-19 in China overall was much higher than that in China except Hubei Province. The CFR of COVID-19 in China was underestimated.