Safety and immunogenicity of SW-BIC-213, a modified COVID-19 Lipo-Polyplex mRNA vaccine, in Laotian healthy adults aged 18 years and above: a Phase 1/2 trial (preprint)

Background The mRNA vaccine against SARS-CoV-2 has demonstrated remarkable efficacy in protecting against coronavirus disease 2019 (COVID-19), including providing high protection against severe disease during the emergence of variant waves. In this study, we aimed to investigate the safety and immunogenicity of a 2-dose regimen of the LPP-based mRNA vaccine, SW-BIC-213, in Laos. Methods For this phase 1/2 clinical trial, we recruited healthy adults aged 18-60 years (phase 1) or [≥]18 years (phase 2) from Mahosot Hospital (Vientiane) and Champhone District Hospital (Savannakhet). Participants with SARS-CoV-2 infection, previous COVID-19 vaccination, known allergies to any vaccine component, or pregnancy were excluded. In the phase 1 trial, 41 eligible participants were sequentially assigned to either the 25 g dose group (25 g) or the 45 g dose group (45 g) in accordance with their enrollment order, with 21 participants in 45 g dose group and 20 participants in 25 g dose group. In the phase 2 trial, 480 participants were randomly allocated (2:2:1 ratio) to either the 25 g dose group, 45 g dose group, or placebo group. The primary endpoints for the phase 1 trial were the incidence of local/systemic solicited adverse reactions/events (0-6 days after each vaccination dose), unsolicited adverse events (0-21 days and 0-28 days after the first and second dose of immunization, respectively), and serious adverse events from the first dose of vaccination to 28 days after completing the full course of immunization. In the phase 2 trial, the primary endpoints were the seroconversion rate and geometric mean titer (GMT) of SARS-CoV-2 S-protein specific IgG antibodies and neutralizing antibodies 14 days after the second dose in participants. As for neutralizing antibodies, we detected pseudo-virus neutralizing antibody against wild type (WT), Delta, BA.1 and BA.2. We also detected live viral neutralizing antibody against WT strain 14 days after the second dose. Furthermore, the safety endpoints were also measured during the trial. This seamless phase 1/2 trial was registered with ClinicalTrials.gov under the identifier NCT05144139. Results Between December 3, 2021, and March 31, 2022, a total of 41 participants were recruited in the phase 1 trial, while the phase 2 trial enrolled 480 participants from January 20 to July 6, 2022. In the phase 1 trial, a total of 32 subjects (80.0%) reported 103 cases of adverse reactions. All adverse reactions were limited to Grade 1-2. In the phase 2 trial, a total of 479 subjects, 372 subjects (77.7%) reported 929 cases of adverse reactions. All adverse reactions in severity of Grade 3 were manifested as fever (3.4%, 2.1% and 2.9% in 45 g dose, 25 g dose and placebo group respectively, only observed in adults), except which all other reactions were limited to Grade 1-2. All adverse reactions noted during the study were tolerable, predominantly transient, and resolved spontaneously. No serious adverse events (SAEs) related to vaccination were observed. In Phase 2 study, SW-BIC-213 could elicit a high level of seroconversion rate of pseudo-virus neutralizing antibody against WT (100.0% in 25 g dose group, 99.3% in 45 g dose group), Delta (99.2% in 25 g dose group, 98.0% in 45 g dose group), Omicron BA.1 (84.1% in 25 g dose group, 84.7% in 45 g dose group) and Omicron BA.2 (96.0% in 25 g dose group, 88.8% in 45 g dose group) at 14 days after the second dose. The pseudo-virus neutralizing antibody titer against WT, Delta, BA.1 and BA.2 was all significant higher (P<0.0001) in both 45 g dose group (1175.02, 620.62, 72.39 and 172.80) and 25 g dose group (885.80, 579.40, 47.24 and 101.96) compared with the placebo group (9.67, 10.66, 13.99 and 29.53) at 14 days after the second dose. As for live viral neutralizing antibodies against WT strain, the seroconversion rate could reach more than 94% at 14 days after second dose. The neutralizing antibody titer against WT strain was significantly higher (P<0.0001) in both 45 g dose group (315.00) and 25 g dose group (323.18) compared with the placebo group (8.51) at 14 days after second dose. Conclusion: COVID-19 mRNA vaccine SW-BIC-213 manifests a favorable safety profile and is highly immunogenic in eligible subjects aged [≥]18 years.

Parallel use of human stem cell lung and heart models provide insights for SARS-CoV-2 treatment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily infects the respiratory tract, but pulmonary and cardiac complications occur in severe coronavirus disease 2019 (COVID-19). To elucidate molecular mechanisms in the lung and heart, we conducted paired experiments in human stem cell-derived lung alveolar type II (AT2) epithelial cell and cardiac cultures infected with SARS-CoV-2. With CRISPR-Cas9-mediated knockout of ACE2, we demonstrated that angiotensin-converting enzyme 2 (ACE2) was essential for SARS-CoV-2 infection of both cell types but that further processing in lung cells required TMPRSS2, while cardiac cells required the endosomal pathway. Host responses were significantly different; transcriptome profiling and phosphoproteomics responses depended strongly on the cell type. We identified several antiviral compounds with distinct antiviral and toxicity profiles in lung AT2 and cardiac cells, highlighting the importance of using several relevant cell types for evaluation of antiviral drugs. Our data provide new insights into rational drug combinations for effective treatment of a virus that affects multiple organ systems.

Multi-scale sequential feature selection for disease classification using Raman spectroscopy data.

Raman spectroscopy (RS) optical technology promises non-destructive and fast application in medical disease diagnosis in a single step. However, achieving clinically relevant performance levels remains challenging due to the inability to search for significant Raman signals at different scales. Here we propose a multi-scale sequential feature selection method that can capture global sequential features and local peak features for disease classification using RS data. Specifically, we utilize the Long short-term memory network (LSTM) module to extract global sequential features in the Raman spectra, as it can capture long-term dependencies present in the Raman spectral sequences. Meanwhile, the attention mechanism is employed to select local peak features that were ignored before and are the key to distinguishing different diseases. Experimental results on three public and in-house datasets demonstrate the superiority of our model compared with state-of-the-art methods for RS classification. In particular, our model achieves an accuracy of 97.9 ± 0.2% on the COVID-19 dataset, 76.3 ± 0.4% on the H-IV dataset, and 96.8 ± 1.9% on the H-V dataset.

Oral Fungal Alterations in Patients with COVID-19 and Recovered Patients.

The oral bacteriome, gut bacteriome, and gut mycobiome are associated with coronavirus disease 2019 (COVID-19). However, the oral fungal microbiota in COVID-19 remains unclear. This article aims to characterize the oral mycobiome in COVID-19 and recovered patients. Tongue coating specimens of 71 COVID-19 patients, 36 suspected cases (SCs), 22 recovered COVID-19 patients, 36 SCs who recovered, and 132 controls from Henan are collected and analyzed using internal transcribed spacer sequencing. The richness of oral fungi is increased in COVID-19 versus controls, and beta diversity analysis reveals separate fungal communities for COVID-19 and control. The ratio of Ascomycota and Basidiomycota is higher in COVID-19, and the opportunistic pathogens, including the genera Candida, Saccharomyces, and Simplicillium, are increased in COVID-19. The classifier based on two fungal biomarkers is constructed and can distinguish COVID-19 patients from controls in the training, testing, and independent cohorts. Importantly, the classifier successfully diagnoses SCs with positive specific severe acute respiratory syndrome coronavirus 2 immunoglobulin G antibodies as COVID-19 patients. The correlation between distinct fungi and bacteria in COVID-19 and control groups is depicted. These data suggest that the oral mycobiome may play a role in COVID-19.

Prevalence and risk factors of post-traumatic stress disorder symptoms among Chinese health care workers following the COVID-19 pandemic

In December 2019, coronavirus disease 2019 (COVID-19) appeared in Wuhan (Hubei, China) and subsequently swept the globe. In addition to the risk of infection, there is a strong possibility that post-traumatic stress disorder (PTSD) may be a secondary effect of the pandemic. Health care workers (HCWs) participating in the pandemic are highly exposed to and may bear the brunt out of stressful or traumatic events. In this cross-sectional study, we assessed the morbidity and risk factors of PTSD symptoms among Chinese HCWs. A total of 457 HCWs were recruited from March 15, 2020, to Mach 22, 2020, including HCWs in Wuhan and Hubei Province (excluding Wuhan), the areas first and most seriously impacted by COVID-19. The morbidity of PTSD symptoms was assessed by the Event Scale–Revised (IES-R). The risk factors for PTSD symptoms were explored by means of logistic regression analysis. Over 40% of the respondents experienced PTSD symptoms more than one month after the COVID-19 outbreak, and this proportion increased to 57.7% in Wuhan HCWs, especially females and HCWs on the frontline. Thus, rapid mental health assessment and effective psychological interventions need to be developed for frontline HCWs to prevent long-term PTSD-related disabilities. Moreover, Negative coping style and neuroticism personality may be regarded as high risk factors for PTSD symptoms. Improving individual coping strategies to enhance resilience should be the focus of further preventive intervention strategies.

Prevalence and risk factors of post-traumatic stress disorder symptoms among Chinese health care workers following the COVID-19 pandemic.

In December 2019, coronavirus disease 2019 (COVID-19) appeared in Wuhan (Hubei, China) and subsequently swept the globe. In addition to the risk of infection, there is a strong possibility that post-traumatic stress disorder (PTSD) may be a secondary effect of the pandemic. Health care workers (HCWs) participating in the pandemic are highly exposed to and may bear the brunt out of stressful or traumatic events. In this cross-sectional study, we assessed the morbidity and risk factors of PTSD symptoms among Chinese HCWs. A total of 457 HCWs were recruited from March 15, 2020, to Mach 22, 2020, including HCWs in Wuhan and Hubei Province (excluding Wuhan), the areas first and most seriously impacted by COVID-19. The morbidity of PTSD symptoms was assessed by the Event Scale-Revised (IES-R). The risk factors for PTSD symptoms were explored by means of logistic regression analysis. Over 40% of the respondents experienced PTSD symptoms more than one month after the COVID-19 outbreak, and this proportion increased to 57.7% in Wuhan HCWs, especially females and HCWs on the frontline. Thus, rapid mental health assessment and effective psychological interventions need to be developed for frontline HCWs to prevent long-term PTSD-related disabilities. Moreover, Negative coping style and neuroticism personality may be regarded as high risk factors for PTSD symptoms. Improving individual coping strategies to enhance resilience should be the focus of further preventive intervention strategies.

Pulmonary fibrosis in patients with COVID-19: A retrospective study.

Background: Coronavirus disease 2019 (COVID-19) pandemic has caused substantial threats to people's physical health and lives, claiming the lives of over 6 million people worldwide. Although the mortality rate of COVID-19 is very low, many survivors may have different degrees and various sequelae. Previous studies have shown that pulmonary fibrosis (PF) were common on discharged COVID-19 patients, and PF itself is a poor prognostic factor. Methods: 227 COVID-19 hospitalized patients' clinical and laboratory data from the first 15 days following admission were collected in this retrospective study. Groups were based on with or without PF of COVID-19. Categorical variables were compared with the chi-square test or Fisher's exact test. Continuous variables were tested by Wilcoxon rank-sum test for the non-normal distribution. Spearman correlations were used to assess the correlations between PF with clinic parameters of multiple time points. Univariate and multivariate logistic regression were used to analyze for risk factors of COVID-19 patients with pulmonary fibrosis. Results: Sixty cases of COVID-19 patients were diagnosed with PF. Compared with 167 non-PF patients, those with PF were older and had higher proportions of fever, shortness of breath, hemoptysis, abdominal pain, hypertension, cardiovascular, diabetes, high flow nasal cannula (HFNC), severe disease, and virus shedding duration. Furthermore, the correlation analysis between PF and clinic parameters showed that PF were positively related to the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and negatively correlated with hemoglobin (HGB) and albumin (ALB) at all time points in the first 15 days after admission. Moreover, We found that PF were significantly correlated with coagulation indexes prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and fibrinolysis index D-Dimer at some phases. In addition, Univariate logistic regression analyses showed that age, fever, shortness of breath, hemoptysis, hypertension, cardiovascular, diabetes, HFNC, severe disease were the risk factors of COVID-19 patients with PF. However, multivariate logistic regression showed that age was the risk factor of COVID-19 patients with PF. Conclusion: Combining various factors, advanced age is an independent risk factor of COVID-19 patients with PF. PF was significantly related with clinic parameter of inflammation/coagulopathy/fibrinolysis.

Peak-easing strategies for urban subway operations in the context of COVID-19 epidemic.

Subways play an important role in public transportation to and from work. In the traditional working system, the commuting time is often arranged at fixed time nodes, which directly leads to the gathering of "morning peak" and "evening peak" in the subway. Under the COVID-19 pandemic, this congestion is exacerbating the spread of the novel coronavirus. Several countries have resorted to the strategy of stopping production to curb the risk of the spread of the epidemic seriously affecting citizens' living needs and hindering economic operation. Therefore, orderly resumption of work and production without increasing the risk of the spread of the epidemic has become an urgent problem to be solved. To this end, we propose a mixed integer programming model that takes into account both the number of travelers and the efficiency of epidemic prevention and control. Under the condition that the working hours remain the same, it can adjust the working days and commuting time flexibly to realize orderly off-peak travel of the workers who return to work. Through independent design of travel time and reasonable control of the number of passengers, the model relaxes the limitation of the number of subway commuters and reduces the probability of cross-travel between different companies. We also take the data of Beijing subway operation and apply it to the solution of our model as an example. The example analysis results show that our model can realize the optimal travel scheme design of returning to work at the same time node and avoiding the risk of cross infection among enterprises under different epidemic prevention and control levels.

Global incidence pattern and factors associated with common cutaneous reactions related to COVID-19 vaccination of 2.55 million participants in real-world settings: A systematic review and meta-analysis.

Background: Understanding the incidence pattern of cutaneous reactions is crucial for promoting COVID-19 vaccination. We aimed to report the global incidence pattern of, and factors associated with common cutaneous reactions related to COVID-19 vaccination in real-world settings. Methods: We searched five databases (PubMed, Web of Science, Embase, CNKI, and Wanfang) from inception to May 13, 2022, for studies reporting the incidence of common cutaneous reactions related to COVID-19 vaccines in real-world settings. The outcomes were the systematic skin reactions (rash and urticaria) and the local injection site reactions (pain, swelling, redness, and erythema). We conducted random-effects meta-analyses and explored associated factors using multi-step statistical analyses. Results: We included 35 studies and assessed 2 549 968 participants from 23 countries. The pooled incidence of overall systemic skin reactions was 3.8% (95% confidence interval (CI) = 2.4%-5.5%) with short duration (about one week). Specifically, the pooled incidence rates of rash and urticaria were 3.0% (95% CI = 2.1%-3.9%) and 1.1% (95% CI = 0.7%-1.5%), respectively. For overall local injection site reactions, the pooled incidence was 72.4% (95% CI = 65.7%-78.7%) with short duration (1 to 4.5 days). Except for local pain (72.2%, 95% CI = 65.3%-78.5%), other localized reactions had low incidence, including swelling (13.3%, 95% CI = 9.5%-17.7%), redness (11.5%, 95% CI = 5.7%-19.0%), and erythema (5.8%, 95% CI = 0.7%-15.4%). Geographically, different distribution patterns were observed for these reactions. Regarding associated factors, mRNA vaccines showed lower incidence of urticaria (P < 0.001). Asia population showed higher incidence of urticaria (P < 0.001). We observed lower incidence rates of overall local injection site reactions and pain among inactivated vaccines (P < 0.001). We found no significant difference among reactions between the first and the second dose of vaccines. Conclusions: We examined the global incidence pattern of common cutaneous reactions related to COVID-19 vaccination and found low incidence and short duration of systemic skin reactions and local injection site reactions (except for pain); discrepancies in these reactions were observed across different vaccine types. The cutaneous side effects related to COVID-19 vaccination do not seem to cause concern. Registration: PROSPERO: CRD42021258012.

The Association Between Alveolar-Arterial Oxygen Tension Difference and the Severity of COVID-19 in Patients.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) emerged as a global pandemic and resulted in a significantly high death toll. Therefore, there is an urgent need to find a potential biomarker related to the disease severity that can facilitate early-stage intervention. METHODS: In the present study, we collected 242 laboratory-confirmed COVID-19-infected patients. The patients were grouped according to the alveolar to arterial oxygen tension difference (PA-aO2) value of COVID-19 infection after admission. RESULTS: Among the 242 laboratory-confirmed COVID-19- infected patients, 155 (64.05%) had an abnormal PA-aO2 value on admission. Compared with the normal PA-aO2 group, the median age of the abnormal PA-aO2 group was significantly older (p = 0.032). Symptoms such as fever, cough, and shortness of breath were more obvious in the abnormal PA-aO2 group. The proportion of severe events in the abnormal PA-aO2 group was higher than the normal PA-aO2 group (10.34% vs. 23.23%, p = 0.013). The abnormal PA-aO2 group had a higher possibility of developing severe events compared with the normal PA-aO2 group (HR 2.622, 95% CI 1.197-5.744, p = 0.016). After adjusting for age and common comorbidities (hypertension and cardiovascular disease), the abnormal PA-aO2 group still exhibited significantly elevated risks of developing severe events than the normal PA-aO2 group (HR 2.986, 95% CI 1.220-7.309, p = 0.017). Additionally, the abnormal PA-aO2 group had more serious inflammation/coagulopathy/fibrinolysis parameters than the normal PA-aO2 group. CONCLUSION: Abnormal PA-aO2 value was found to be common in COVID-19 patients, was strongly related to severe event development, and could be a potential biomarker for the prognosis of COVID-19 patients.

Clinical characteristics and risk factors for a prolonged length of stay of patients with asymptomatic and mild COVID-19 during the wave of Omicron from Shanghai, China.

BACKGROUND: This study aims to investigate the clinical characteristics and the length of hospital stay (LOS), as well as risk factors for prolonged LOS in a cohort of asymptomatic and mild COVID-19 patients infected with the Omicron variant. METHODS: A total of 1166 COVID-19 patients discharged from the inpatient ward of the largest makeshift hospital (May 8-10, 2022) in Shanghai, China, were included. The demographics, medical history, and the lowest and admission cycle threshold (Ct) values of the RT-PCR tests for SARS-CoV-2 genes of the open reading frame 1ab (Ct-ORF) and the nucleocapsid protein (Ct-N) during hospitalization were recorded. Patients with LOS > 7 days, or LOS ≤ 7 days were included in the Prolonged group or the Control group, separately. The clinical characteristics and LOS of the participants in the two groups were described and compared. Multivariate Logistic and linear regression analyses were applied to explore the risk factors for prolonged LOS. The diagnostic efficacy of the lowest and admission Ct values for the Prolonged group was tested via the receiver operating characteristic (ROC) curve analysis. RESULTS: The median LOS was 6 days in the total study population. The age was older (45.52 ± 14.78 vs. 42.54 ± 15.30, P = 0.001), while both the lowest and admission Ct-ORF (27.68 ± 3.88 vs. 37.00 ± 4.62, P < 0.001; 30.48 ± 5.03 vs. 37.79 ± 3.81, P < 0.001) and Ct-N (25.79 ± 3.60 vs. 36.06 ± 5.39, P < 0.001; 28.71 ± 4.95 vs. 36.95 ± 4.59, P < 0.001) values were significantly lower in the Prolonged group. There were more mild cases in the Prolonged group (23.8% vs. 11.5%, P < 0.001). The symptom spectrum differed between the two groups. In multivariate analyses, age, disease category, and the lowest Ct-N values were shown to be associated with prolonged LOS. Besides, both the lowest and admission Ct-ORF (AUC = 0.911 and 0.873) and Ct-N (AUC = 0.912 and 0.874) showed robust diagnostic efficacy for prolonged LOS. CONCLUSIONS: Our study firstly reports the clinical characteristics and risk factors for prolonged LOS during the wave of the Omicron epidemic in Shanghai, China. These findings provide evidence for the early identification of asymptomatic and mild COVID-19 patients at a high risk of prolonged hospitalization who may require early intervention, and long-term monitoring and management.

The ‘Dual Circulation' development model of China: Background and insights

Purpose>Global supply chains experienced unprecedented changes in 2020 and the relationship between domestic and global markets needed adjustments considering the long-term impacts of the changes that are unfolding around these markets. China has become the first country to announce a formal strategy – "Dual Circulation” Strategy (DCS) – to guide its self-reliant economic development in the post-COVID era. However, what exactly is the DCS and what drove China to publicize this strategy is not yet clear. This study aims to answer these questions.Design/methodology/approach>Based on an extensive review of literature and media reports, a background has been constructed that justifies the DCS as a long-overdue historic necessity.Findings>A novel definition of "Dual Circulation” is introduced. A novel construct to visualize the domestic circulation in light of international and domestic markets and international circulation has been presented. The study argues that maintaining optimum levels of consumption and saving rates is crucial to the DCS's success.Originality/value>The study pioneers the first scientific definition of the "Dual Circulation” that will pave way for future debate on the topic. Also, it is the first time an academic study on the DCS has been executed.

Pulmonary fibrosis in patients with COVID-19: A retrospective study

Background Coronavirus disease 2019 (COVID-19) pandemic has caused substantial threats to people's physical health and lives, claiming the lives of over 6 million people worldwide. Although the mortality rate of COVID-19 is very low, many survivors may have different degrees and various sequelae. Previous studies have shown that pulmonary fibrosis (PF) were common on discharged COVID-19 patients, and PF itself is a poor prognostic factor. Methods 227 COVID-19 hospitalized patients' clinical and laboratory data from the first 15 days following admission were collected in this retrospective study. Groups were based on with or without PF of COVID-19. Categorical variables were compared with the chi-square test or Fisher's exact test. Continuous variables were tested by Wilcoxon rank-sum test for the non-normal distribution. Spearman correlations were used to assess the correlations between PF with clinic parameters of multiple time points. Univariate and multivariate logistic regression were used to analyze for risk factors of COVID-19 patients with pulmonary fibrosis. Results Sixty cases of COVID-19 patients were diagnosed with PF. Compared with 167 non-PF patients, those with PF were older and had higher proportions of fever, shortness of breath, hemoptysis, abdominal pain, hypertension, cardiovascular, diabetes, high flow nasal cannula (HFNC), severe disease, and virus shedding duration. Furthermore, the correlation analysis between PF and clinic parameters showed that PF were positively related to the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and negatively correlated with hemoglobin (HGB) and albumin (ALB) at all time points in the first 15 days after admission. Moreover, We found that PF were significantly correlated with coagulation indexes prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and fibrinolysis index D-Dimer at some phases. In addition, Univariate logistic regression analyses showed that age, fever, shortness of breath, hemoptysis, hypertension, cardiovascular, diabetes, HFNC, severe disease were the risk factors of COVID-19 patients with PF. However, multivariate logistic regression showed that age was the risk factor of COVID-19 patients with PF. Conclusion Combining various factors, advanced age is an independent risk factor of COVID-19 patients with PF. PF was significantly related with clinic parameter of inflammation/coagulopathy/fibrinolysis.

An ACE2-Based Decoy Inhibitor Effectively Neutralizes SARS-CoV-2 Omicron BA.5 Variant.

The recently circulating SARS-CoV-2 Omicron BA.5 is rampaging the world with elevated transmissibility compared to the original SARS-CoV-2 strain. Immune escape of BA.5 was observed after treatment with many monoclonal antibodies, calling for broad-spectrum, immune-escape-evading therapeutics. In retrospect, we previously reported Kansetin as an ACE2 mimetic and a protein antagonist against SARS-CoV-2, which proved potent neutralization bioactivity on the Reference, Alpha, Beta, Delta, and Omicron strains of SARS-CoV-2. Since BA.5 is expected to rely on the interaction of the Spike complex with human ACE2 for cell entry, we reasonably assumed the lasting efficacy of the ACE2-mimicking Kansetin for neutralizing the new SARS-CoV-2 variant. The investigation was accordingly performed on in vitro Kansetin-Spike binding affinity by SPR and cell infection inhibition ability with pseudovirus and live virus assays. As a result, Kansetin showed dissociation constant KD and half inhibition concentration IC50 at the nanomolar to picomolar level, featuring a competent inhibition effect against the BA.5 sublineage. Conclusively, Kansetin is expected to be a promising therapeutic option against BA.5 and future SARS-CoV-2 sublineages.

Effectiveness of Inactivated COVID-19 Vaccines against COVID-19 Caused by the SARS-CoV-2 Delta and Omicron Variants: A Retrospective Cohort Study.

BACKGROUND: Real-world evidence on the effectiveness of inactivated vaccines against the Delta and Omicron (BA.2.38) variants remains scarce. METHODS: A retrospective cohort study was conducted to estimate the adjusted vaccine effectiveness (aVE) of one, two, and three doses of inactivated vaccines in attenuating pneumonia, severe COVID-19, and the duration of viral shedding in Delta and Omicron cases using modified Poisson and linear regression as appropriate. RESULTS: A total of 561 COVID-19 cases were included (59.2% Delta and 40.8% Omicron). In total, 56.4% (184) of Delta and 12.0% (27) of Omicron cases had COVID-19 pneumonia. In the two-dose vaccinated population, 1.4% of Delta and 89.1% of Omicron cases were vaccinated for more than 6 months. In Delta cases, the two-dose aVE was 52% (95% confidence interval, 39-63%) against pneumonia and 61% (15%, 82%) against severe disease. Two-dose vaccination reduced the duration of viral shedding in Delta cases, but not in booster-vaccinated Omicron cases. In Omicron cases, three-dose aVE was 68% (18%, 88%) effective against pneumonia, while two-dose vaccination was insufficient for Omicron. E-values were calculated, and the E-values confirmed the robustness of our findings. CONCLUSIONS: In Delta cases, two-dose vaccination within 6 months reduced pneumonia, disease severity, and the duration of viral shedding. Booster vaccination provided a high level of protection against pneumonia with Omicron and should be prioritized.

Investigating the Impacting Factors on the Public's Attitudes towards Autonomous Vehicles Using Sentiment Analysis from Social Media Data

The attitudes of the public play a critical role in the acceptance, purchase, utilization, and research and development of autonomous vehicles (AVs). Currently, the attitudes of the public toward AVs have been mostly estimated through traditional survey data, which bears a low quantity of samples with high labor costs. It is probably also one of the reasons why the critical factors on the attitudes of the public toward AVs have not been studied from a comprehensive perspective yet. To address the issue, this study aims to propose a method by using large-scale social media data to investigate key factors that affect the attitudes of the public toward AVs. A total of 954,151 Twitter data related to AVs and 53 candidate independent variables from seven categories were extracted using the web scraping method. Then, sentiment analysis was used to measure the public attitudes towards AVs by calculating sentiment scores. Random forests algorithm was employed to preliminarily select candidate independent variables according to their importance and a linear mixed model was utilized to explore the impacting factors, considering the unobserved heterogeneities caused by the subjectivity level of tweets. The results showed that the attitudes of the public toward AVs were slightly optimistic. Factors, such as 'drunk';, 'blind spot';, and 'mobility';, had the largest impacts on public attitudes. In addition, people were more likely to express positive feelings when talking about words, such as 'lidar';and 'Tesla';, related to high technologies. Conversely, factors, such as 'COVID-19';, 'pedestrian';, 'sleepy';, and 'highway';, were found to have significantly negative effects on the attitudes of the public. The findings of this study are beneficial for the development of AV technologies, the guidelines for AV-related policy formulation, and the understanding and acceptance of the public toward AVs.

Parallel use of pluripotent human stem cell lung and heart models provide new insights for treatment of SARS-CoV-2 (preprint)

SARS-CoV-2 primarily infects the respiratory tract, but pulmonary and cardiac complications occur in severe COVID-19. To elucidate molecular mechanisms in the lung and heart, we conducted paired experiments in human stem cell-derived lung alveolar type II (AT2) epithelial cell and cardiac cultures infected with SARS-CoV-2. With CRISPR-Cas9 mediated knock-out of ACE2, we demonstrated that angiotensin converting enzyme 2 (ACE2) was essential for SARS-CoV-2 infection of both cell types but further processing in lung cells required TMPRSS2 while cardiac cells required the endosomal pathway. Host responses were significantly different; transcriptome profiling and phosphoproteomics responses depended strongly on the cell type. We identified several antiviral compounds with distinct antiviral and toxicity profiles in lung AT2 and cardiac cells, highlighting the importance of using several relevant cell types for evaluation of antiviral drugs. Our data provide new insights into rational drug combinations for effective treatment of a virus that affects multiple organ systems.

Healthcare worker trauma and related mental health outcomes during the COVID-19 outbreak in New York City.

Healthcare workers (HCWs) faced a range of stressors during the coronavirus (COVID-19) pandemic, contributing to psychological stress. We use a psychological trauma framework to characterize the mental health burden for clinical and non-clinical healthcare worker occupations during the COVID-19 pandemic. The objective was to measure and characterize risk factors for trauma and anxiety-related mental health problems among HCWs at a public hospital in the epicenter of the COVID-19 pandemic in New York City (NYC). This study reports findings from a cross-sectional survey of NYC HCWs shortly after the initial 2020 infection surge. Over 800 hospital employees completed the survey that assessed professional quality of life indicators (compassion satisfaction [CS], burnout [BO], secondary traumatic stress [STS]), Coronavirus Anxiety (CS), Obsession with Coronavirus (OC), and PTSD symptoms. The survey also assessed pandemic-related work and life circumstances such as "do you have a family member or friend who tested positive for COVID". Relatively small percentages of HCWs endorsed probable Coronavirus Anxiety (6%), PTSD (13%), and Coronavirus Obsession (21%). We observed higher proportions of Burnout (29%), Moderate or High Secondary Traumatic Stress (45%), and High Compassion Satisfaction (52%). Adjusted regression models showed important implications for prior behavioral/emotional health concerns among HCWs, providing care for a patient that died from COVID-19, and other characteristics. This study supports prior studies documenting the mental health consequences for the healthcare workforce during the COVID-19 pandemic. This study builds on that base by including non-clinical staff in the sample and assessing pandemic life-stressors such as caring for sick family members.

Twin peaks of in-hospital mortality among patients with STEMI across five phases of COVID-19 outbreak in China: a nation-wide study.

Lockdown and re-opening may become cyclical due to the recurrent waves of the COVID-19 epidemic. Few studies have examined temporal trends and determinants of in-hospital mortality among patients with ST-segment elevation myocardial infarction (STEMI), a life-threatening condition that requires emergency medical care. Using nation-wide data before, during and after the Wuhan lockdown, we aimed to depict temporal patterns and major determinants of STEMI in-hospital mortality in China across five time periods of the COVID-19 epidemic. We analyzed the data of 283,661 STEMI patients who were admitted to 4,487 chest-pain-centers across China, from January 1, 2019 to May 31, 2020. Compared with the period before the lockdown, STEMI in-hospital mortality increased by 25% (OR 1.25, 95%CI 1.16-1.34) during Early Lockdown, by 12% (OR 1.12, 95%CI 1.03-1.22) during Later Lockdown, by 35% (OR 1.35, 95%CI 1.21-1.50) during Early Lift, and returned to pre-COVID risk (OR 1.04, 95%CI 0.95-1.14) during Later Lift. For each time-period, we observed a clear mortality gradient by timing and types of revascularization procedure. In conclusion, the COVID-19 epidemic had a significant adverse impact on STEMI in-hospital mortality, with bimodal peaks during early lockdown and early lift periods and clear mortality gradients by timing and types of revascularization procedure, independent of the time periods.