Adaptive immune responses and cytokine immune profiles in humans following prime and boost vaccination with the SARS-CoV-2 CoronaVac vaccine.

BACKGROUND: Adaptive immune response has been thought to play a key role in SARS-CoV-2 infection. The role of B cells, CD4+T, and CD8+T cells are different in vaccine-induced immune response, thus it is imperative to explore the functions and kinetics of adaptive immune response. We collected blood samples from unvaccinated and vaccinated individuals. To assess the mechanisms contributing to protective immunity of CoronaVac vaccines, we mapped the kinetics and durability of humoral and cellular immune responses after primary and boost vaccination with CoronaVac vaccine in different timepoints. MATERIALS AND METHODS: We separate PBMC and plasma from blood samples. The differentiation and function of RBD-spcific CD4+T and CD8+T cells were analyzed by flow cytometry and ELISA. Antibodies response was analyzed by ELISA. ELISPOT analysis was perfomed to detected the RBD-spcific memory B cells. CBA analysis was performed to detected the cytokine immune profiles. Graphpad prism 8 and Origin 2021 were used for statistical analysis. RESULTS: Vaccine-induced CD4+T cell responses to RBD were more prominent than CD8+T cell responses, and characterized by a predominant Th1 and weak Th17 helper response. CoronaVac vaccine triggered predominant IgG1 antibody response and effectively recalled specific antibodies to RBD protein after booster vaccination. Robust antigen-specific memory B cells were detected (p < 0.0001) following booster vaccination and maintained at 6 months (p < 0.0001) following primary vaccination. Vaccine-induced CD4+T cells correlated with CD8+T cells (r = 0.7147, 0.3258, p < 0.0001, p = 0.04), memory B cell responses (r = 0.7083, p < 0.0001), and IgG and IgA (r = 0.6168, 0.5519, p = 0.0006, 0.003) after vaccination. In addition, vaccine induced a broader and complex cytokine pattern in plasma at early stage. CONCLUSION: Taken together, these results highlight the potential role of B cell and T cell responses in vaccine-induced long-term immunity.

The Impact and Mechanism of the COVID-19 Pandemic on Corporate Financing: Evidence from Listed Companies in China

The unexpected emergence of COVID-19 has placed businesses throughout the globe under considerable financial hardship, and financial constraints are a significant barrier to business expansion, particularly in developing countries with insufficient credit markets. Using yearly data for Chinese listed businesses from 367 cities, we examine the impact of COVID-19 on financial restrictions and the corresponding mechanisms of action by using a difference-in-differences (DID) methodology. We discover that COVID-19 leads to a significant increase of 0.117 in the KZ index of listed firms, i.e., an increase in financing constraints, and this result is consistent with various robustness tests. We also show that COVID-19 considerably lowers a company's capacity to obtain external financing by increasing debt costs and deterring commercial credit. The pandemic significantly reduced the company's commercial credit by 0.008 and increased debt costs by 0.2%. Moreover, the data demonstrate variation across industries, business ownership, and firm scale. Our findings indicate that decreasing information asymmetries facilitate successful adaptation to and recovery from external shocks. Our analysis suggests that governments should promulgate policies that are conducive to corporate financing to help companies maintain development during the outbreak of the epidemic and ensure economic sustainability.

The impacts of COVID-19 on China insurance industry-An empirical analysis based on event study.

Introduction: At the end of 2019, the sudden outbreak of COVID-19 pneumonia has developed from a mass health event to a global epidemic disaster. Its impact extends from human health to social, economic, political, international relations and global governance. In the process of fighting against the epidemic in China, almost all economic sectors were affected, and the insurance industry with epidemic sensitive characteristics was particularly affected. Methods: In order to identify the impacts of COVID-19 on China's insurance industry, this paper uses the event study method to calculate the changes in the cumulative abnormal return rate and the cumulative excess return of Chinese listed insurance companies before and after the outbreak of COVID-19. In the empirical analysis, five different typical events are examined, including the first outbreak of COVID-19 in China, the closure of Wuhan, the dredging of Wuhan, and the listing of vaccines in China. Results: The results show that the return rate of listed companies in the insurance industry showed an "inverted N" curve with the "decreasing, rising and then decreasing." The epidemic mainly has negative effects on the insurance industry in terms of premium income and indemnity expenditure. According to the supply shock theory of the new supply economics, the epidemic has a negative impact on the insurance industry in the short term and a positive impact in the long term. Discussion: In this context, insurance enterprises should attach importance to the change of business model, strengthen the development model of public-private joint venture insurance, promote product innovation and the application of insurance technology, and the experience and practice of the insurance industry in responding to the impact of the epidemic are of great significance to the transformation of China's insurance industry.

Microbial risk score for capturing microbial characteristics, integrating multi-omics data, and predicting disease risk.

BACKGROUND: With the rapid accumulation of microbiome-wide association studies, a great amount of microbiome data are available to study the microbiome's role in human disease and advance the microbiome's potential use for disease prediction. However, the unique features of microbiome data hinder its utility for disease prediction. METHODS: Motivated from the polygenic risk score framework, we propose a microbial risk score (MRS) framework to aggregate the complicated microbial profile into a summarized risk score that can be used to measure and predict disease susceptibility. Specifically, the MRS algorithm involves two steps: (1) identifying a sub-community consisting of the signature microbial taxa associated with disease and (2) integrating the identified microbial taxa into a continuous score. The first step is carried out using the existing sophisticated microbial association tests and pruning and thresholding method in the discovery samples. The second step constructs a community-based MRS by calculating alpha diversity on the identified sub-community in the validation samples. Moreover, we propose a multi-omics data integration method by jointly modeling the proposed MRS and other risk scores constructed from other omics data in disease prediction. RESULTS: Through three comprehensive real-data analyses using the NYU Langone Health COVID-19 cohort, the gut microbiome health index (GMHI) multi-study cohort, and a large type 1 diabetes cohort separately, we exhibit and evaluate the utility of the proposed MRS framework for disease prediction and multi-omics data integration. In addition, the disease-specific MRSs for colorectal adenoma, colorectal cancer, Crohn's disease, and rheumatoid arthritis based on the relative abundances of 5, 6, 12, and 6 microbial taxa, respectively, are created and validated using the GMHI multi-study cohort. Especially, Crohn's disease MRS achieves AUCs of 0.88 (0.85-0.91) and 0.86 (0.78-0.95) in the discovery and validation cohorts, respectively. CONCLUSIONS: The proposed MRS framework sheds light on the utility of the microbiome data for disease prediction and multi-omics integration and provides a great potential in understanding the microbiome's role in disease diagnosis and prognosis. Video Abstract.

Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome.

Respiratory failure is associated with increased mortality in COVID-19 patients. There are no validated lower airway biomarkers to predict clinical outcome. We investigated whether bacterial respiratory infections were associated with poor clinical outcome of COVID-19 in a prospective, observational cohort of 589 critically ill adults, all of whom required mechanical ventilation. For a subset of 142 patients who underwent bronchoscopy, we quantified SARS-CoV-2 viral load, analysed the lower respiratory tract microbiome using metagenomics and metatranscriptomics and profiled the host immune response. Acquisition of a hospital-acquired respiratory pathogen was not associated with fatal outcome. Poor clinical outcome was associated with lower airway enrichment with an oral commensal (Mycoplasma salivarium). Increased SARS-CoV-2 abundance, low anti-SARS-CoV-2 antibody response and a distinct host transcriptome profile of the lower airways were most predictive of mortality. Our data provide evidence that secondary respiratory infections do not drive mortality in COVID-19 and clinical management strategies should prioritize reducing viral replication and maximizing host responses to SARS-CoV-2.

Danshensu alleviates pseudo-typed SARS-CoV-2 induced mouse acute lung inflammation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can induce acute inflammatory response like acute lung inflammation (ALI) or acute respiratory distress syndrome, leading to severe progression and mortality. Therapeutics for treatment of SARS-CoV-2-triggered respiratory inflammation are urgent to be discovered. Our previous study shows that Salvianolic acid C potently inhibits SARS-CoV-2 infection. In this study, we investigated the antiviral effects of a Salvia miltiorrhiza compound, Danshensu, in vitro and in vivo, including the mechanism of S protein-mediated virus attachment and entry into target cells. In authentic and pseudo-typed virus assays in vitro, Danshensu displayed a potent antiviral activity against SARS-CoV-2 with EC50 of 0.97 µM, and potently inhibited the entry of SARS-CoV-2 S protein-pseudo-typed virus (SARS-CoV-2 S) into ACE2-overexpressed HEK-293T cells (IC50 = 0.31 µM) and Vero-E6 cell (IC50 = 4.97 µM). Mice received SARS-CoV-2 S via trachea to induce ALI, while the VSV-G treated mice served as controls. The mice were administered Danshensu (25, 50, 100 mg/kg, i.v., once) or Danshensu (25, 50, 100 mg·kg-1·d-1, oral administration, for 7 days) before SARS-CoV-2 S infection. We showed that SARS-CoV-2 S infection induced severe inflammatory cell infiltration, severely damaged lung tissue structure, highly expressed levels of inflammatory cytokines, and activated TLR4 and hyperphosphorylation of the NF-κB p65; the high expression of angiotensinogen (AGT) and low expression of ACE2 at the mRNA level in the lung tissue were also observed. Both oral and intravenous pretreatment with Danshensu dose-dependently alleviated the pathological alterations in mice infected with SARS-CoV-2 S. This study not only establishes a mouse model of pseudo-typed SARS-CoV-2 (SARS-CoV-2 S) induced ALI, but also demonstrates that Danshensu is a potential treatment for COVID-19 patients to inhibit the lung inflammatory response.

From Uncoordinated Patchworks to a Coordinated System: MERS-CoV to COVID-19 in Korea

South Korea has experienced two national public health crises during this decade. The 2015 Middle East respiratory syndrome-coronavirus (MERS-CoV) response?s failure to address coordination problems or authority conflicts provided an opportunity to revise its national disease control system before the 2020 coronavirus disease 2019 (COVID-19) crisis. Our reflection on Korea?s MERS-CoV and COVID-19 responses provides a perspective on public health emergency management. It is difficult to project the scale of an emerging infectious disease in advance because of its contagious nature and ability to cross geographic boundaries. In a national epidemic or global pandemic, a centralized coordination effort at the national level is desirable, rather than fragmented local, city, or regional efforts.