The Impact of COVID-19 Pandemic on the Clinical Practice Patterns in Atrial Fibrillation: A Multicenter Clinician Survey in China.

The COVID-19 pandemic has severely impacted healthcare systems worldwide. This study investigated cardiologists' opinions on how the COVID-19 pandemic impacted clinical practice patterns in atrial fibrillation (AF). A multicenter clinician survey, including demographic and clinical questions, was administered to 300 cardiologists from 22 provinces in China, in April 2022. The survey solicited information about their treatment recommendations for AF and their perceptions of how the COVID-19 pandemic has impacted their clinical practice patterns for AF. The survey was completed by 213 cardiologists (71.0%) and included employees in tertiary hospitals (82.6%) and specialists with over 10 years of clinical cardiology practice (53.5%). Most respondents stated that there were reductions in the number of inpatients and outpatients with AF in their hospital during the pandemic. A majority of participants stated that the pandemic had impacted the treatment strategies for all types of AF, although to different extents. Compared with that during the assumed non-pandemic period in the hypothetical clinical questions, the selection of invasive interventional therapies (catheter ablation, percutaneous left atrial appendage occlusion) was significantly decreased (all p < 0.05) during the pandemic. There was no significant difference in the selection of non-invasive therapeutic strategies (the management of cardiovascular risk factors and concomitant diseases, pharmacotherapy for stroke prevention, heart rate control, and rhythm control) between the pandemic and non-pandemic periods (all p > 0.05). The COVID-19 pandemic has had a profound impact on the clinical practice patterns of AF. The selection of catheter ablation and percutaneous left atrial appendage occlusion was significantly reduced, whereas pharmacotherapy was often stated as the preferred option by participating cardiologists.

Awake prone positioning for patients with COVID-19 pneumonia in intensive care unit: A systematic review and meta-analysis.

Background: Awake prone positioning (APP) has been widely used in non-intubated COVID-19 patients during the pandemic. However, high-quality evidence to support its use in severe COVID-19 patients in an intensive care unit (ICU) is inadequate. Therefore, we aimed to assess the efficacy and safety of APP for intubation requirements and other important outcomes in this patient population. Methods: We searched for potentially relevant articles in PubMed, Embase, and the Cochrane database from inception to May 25, 2022. Studies focusing on COVID-19 adults in ICU who received APP compared to controls were included. The primary outcome was the intubation requirement. Secondary outcomes were mortality, ICU stay, and adverse events. Study quality was independently assessed, and we also conducted subgroup analysis, sensitivity analysis, and publication bias to explore the potential influence factors. Results: Ten randomized controlled trials with 1,686 patients were eligible. The quality of the included studies was low to moderate. Overall, the intubation rate was 35.2% in the included patients. The mean daily APP duration ranged from <6 to 9 h, with poor adherence to APP protocols. When pooling, APP significantly reduced intubation requirement (risk ratio [RR] 0.84; 95%CI, 0.74-0.95; I 2 = 0%, P = 0.007). Subgroup analyses confirmed the reduced intubation rates in patients who were older (≥60 years), obese, came from a high mortality risk population (>20%), received HFNC/NIV, had lower SpO2/FiO2 (<150 mmHg), or undergone longer duration of APP (≥8 h). However, APP showed no beneficial effect on mortality (RR 0.92 [95% CI 0.77-1.10; I 2 = 0%, P = 0.37] and length of ICU stay (mean difference = -0.58 days; 95% CI, -2.49 to 1.32; I 2 = 63%; P = 0.55). Conclusion: APP significantly reduced intubation requirements in ICU patients with COVID-19 pneumonia without affecting the outcomes of mortality and ICU stay. Further studies with better APP protocol adherence will be needed to define the subgroup of patients most likely to benefit from this strategy.

Correction: Reasons for COVID-19 Vaccine Hesitancy Among Chinese People Living With HIV/AIDS: Structural Equation Modeling Analysis.

[This corrects the article DOI: 10.2196/33995.].

Emerging role of the cGAS-STING signaling pathway in autoimmune diseases: Biologic function, mechanisms and clinical prospection.

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, as vital component of innate immune system, acts a vital role in distinguishing invasive pathogens and cytosolic DNA. Cytosolic DNA sensor cGAS first binds to cytosolic DNA and catalyzes synthesis of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), which is known as the second messenger. Next, cGAMP activates the adaptor protein STING, triggering a molecular chain reaction to stimulate cytokines including interferons (IFNs). Recently, many researches have revealed that the regulatory role of cGAS-STING signaling pathway in autoimmune diseases (AIDs) such as Rheumatoid arthritis (RA), Aicardi Goutières syndrome (AGS) and systemic lupus erythematosus (SLE). Moreover, accumulated evidence have showed inhibition of the cGAS-STING signaling pathway could remarkably suppress the joint swelling and inflammatory cell infiltration in RA mice. Therefore, in this review, we describe the molecular properties, biologic function and mechanisms of the cGAS-STING signaling pathway in AIDs. In addition, potential clinical applications especially selective small molecule inhibitors targeting the cGAS-STING signaling pathway are also discussed.

A panel regression analysis for the COVID-19 epidemic in the United States.

This study explored the roles of epidemic-spread-related behaviors, vaccination status and weather factors during the COVID-19 epidemic in 50 U.S. states since March 2020. Data from March 1, 2020 to February 5, 2022 were incorporated into panel model. The states were clustered by the k-means method. In addition to discussing the whole time period, we also took multiple events nodes into account and analyzed the data in different time periods respectively by panel linear regression method. In addition, influence of cluster grouping and different incubation periods were been discussed. Non-segmented analysis showed the rate of people staying at home and the vaccination dose per capita were significantly negatively correlated with the daily incidence rate, while the number of long-distance trips was positively correlated. Weather indicators also had a negative effect to a certain extent. Most segmental results support the above view. The vaccination dose per capita was unsurprisingly proved to be the most significant factor especially for epidemic dominated by Omicron strains. 7-day was a more robust incubation period with the best model fit while weather had different effects on the epidemic spread in different time period. The implementation of prevention behaviors and the promotion of vaccination may have a successful control effect on COVID-19, including variants' epidemic such as Omicron. The spread of COVID-19 also might be associated with weather, albeit to a lesser extent.

Reasons for COVID-19 Vaccine Hesitancy Among Chinese People Living With HIV/AIDS: Structural Equation Modeling Analysis.

BACKGROUND: Many countries and organizations recommended people living with HIV/AIDS (PLWHA) receive the COVID-19 vaccine. However, vaccine hesitancy still exists and becomes a barrier for promoting COVID-19 vaccination among PLWHA. OBJECTIVE: This study aims to investigate factors that contributed to COVID-19 vaccine hesitancy among PLWHA. METHODS: The study used a multicenter cross-sectional design and an online survey mode. We recruited PLWHA aged 18-65 years from 5 metropolitan cities in China between January 2021 and February 2021. Participants completed an online survey through Golden Data, a widely used encrypted web-based survey platform. Multiple linear regression models were used to assess the background characteristics in relation to COVID-19 vaccine hesitancy, and structural equation modeling was performed to assess the relationships among perceived benefits, perceived risks, self-efficacy, subjective norms, and COVID-19 vaccine hesitancy. RESULTS: Among 1735 participants, 41.61% (722/1735) reported COVID-19 vaccine hesitancy. Older age, no other vaccinations in the past 3 years, and having chronic disease history were positively associated with COVID-19 vaccine hesitancy. Structural equation modeling revealed a direct relationship of perceived benefits, perceived risks, and subjective norms with self-efficacy and vaccine hesitancy and an indirect relationship of perceived benefits, perceived risks, and subjective norms with vaccine hesitancy. Moreover, self-efficacy toward COVID-19 vaccination was low. PLWHA had concerns of HIV disclosure during COVID-19 vaccination. Family member support could have an impact on COVID-19 vaccination decision-making. CONCLUSIONS: COVID-19 vaccine hesitancy was high among PLWHA in China. To reduce COVID-19 vaccine hesitancy, programs and strategies should be adopted to eliminate the concerns for COVID-19 vaccination, disseminate accurate information on the safety and efficacy of the COVID-19 vaccine, encourage family member support for COVID-19 vaccination, and improve PLWHA's trust of medical professionals.

Comprehensive Analysis of the COVID-19: Based on the Social-Related Indexes From NUMBEO.

Background: The COVID-19 has been spreading globally since 2019 and causes serious damage to the whole society. A macro perspective study to explore the changes of some social-related indexes of different countries is meaningful. Methods: We collected nine social-related indexes and the score of COVID-safety-assessment. Data analysis is carried out using three time series models. In particular, a prediction-correction procedure was employed to explore the impact of the pandemic on the indexes of developed and developing countries. Results: It shows that COVID-19 epidemic has an impact on the life of residents in various aspects, specifically in quality of life, purchasing power, and safety. Cluster analysis and bivariate statistical analysis further indicate that indexes affected by the pandemic in developed and developing countries are different. Conclusion: This pandemic has altered the lives of residents in many ways. Our further research shows that the impacts of social-related indexes in developed and developing countries are different, which is bounded up with their epidemic severity and control measures. On the other hand, the climate is crucial for the control of COVID-19. Consequently, exploring the changes of social-related indexes is significative, and it is conducive to provide targeted governance strategies for various countries. Our article will contribute to countries with different levels of development pay more attention to social changes and take timely and effective measures to adjust social changes while trying to control this pandemic.

Epidemiological study on severe acute respiratory syndrome coronavirus 2 virus transmission network in northeast China.

ABSTRACT: In this study, corona virus disease 2019 (COVID-19) transmission networks were built to analyze the epidemic situation of COVID-19 in Liaoning and Jilin provinces in early 2020. We explore the characteristics of the spread of COVID-19, and put forward effective recommendations for epidemic prevention and control. We collected demographic characteristics, exposure history, and course of action of COVID-19 cases. We described the demographic and case characteristics of these cases to show the basic characteristics of COVID-19 cases in both provinces. Combined with the spatial analysis of confirmed cases, the distribution law of the number of confirmed cases in different regions was analyzed. We exhibit the relationship among COVID-19 cases with a transmission network. The transmission characteristics of COVID-19 were analyzed through the transmission network. Mainly cases in Liaoning and Jilin provinces were imported cases from other provinces and the vast majority of these cases were related to Hubei province. The number of confirmed cases in different regions was positively correlated with their GDP and population. The main clinical symptoms of the cases were fever. Judge from the transmission network relationship between the 2 provinces, the transmission chain in Liaoning province contains fewer cases than that in Jilin province. The main transmission routes of the local cases in the 2 provinces were the family members, and the infection of the imported cases were mainly occurred in public places. It was estimated that the unidentified asymptomatic infected cases in the 2 provinces account for approximately 7.3% of the total number of infected cases. The length of the transmission chain suggests that the spread of COVID-19 can be effectively controlled with effective prevention measures.

The Therapeutic Effect of Traditional Chinese Medicine on Inflammatory Diseases Caused by Virus, Especially on Those Caused by COVID-19.

Inflammasomes are large multimolecular complexes best recognized because of their ability to control activation of caspase-1, which in turn regulates the maturation of interleukin-18 (IL-18) and interleukin-1 ß (IL-1ß). IL-1ß was originally identified as a pro-inflammatory cytokine, capable of inducing local and systemic inflammation as well as a fever response reaction in response to infection or injury. Excessive production of IL-1ß is related to inflammatory and autoimmune diseases. Both coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) are characterized by excessive inflammatory response. For SARS, there is no correlation between viral load and worsening symptoms. However, there is no specific medicine which is available to treat the disease. As an important part of medical practice, TCM showed an obvious therapeutic effect in SARS-CoV-infected patients. In this article, we summarize the current applications of TCM in the treatment of COVID-19 patients. Herein, we also offer an insight into the underlying mechanisms of the therapeutic effects of TCM, as well as introduce new naturally occurring compounds with anti-coronavirus activity, in order to provide a new and potential drug development strategy for the treatment of COVID-19.

Protective Efficacy of Inactivated Vaccine against SARS-CoV-2 Infection in Mice and Non-Human Primates.

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused more than 96 million infections and over 2 million deaths worldwide so far. However, there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease causative agent. Vaccine is the most effective approach to eradicate a pathogen. The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations. Here we evaluated the safety, immunogenicity, and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates. Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates, and subsequently provided partial (in low dose) or full (in high dose) protection of challenge in the tested animals. In addition, passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice. These results warranted positive outcomes in future clinical trials in humans.

Kinetic changes in virology, specific antibody response and imaging during the clinical course of COVID-19: a descriptive study.

BACKGROUND: To explore the kinetic changes in virology, specific antibody response and imaging during the clinical course of COVID-19. METHODS: This observational study enrolled 20 patients with COVID-19, who were hospitalized between January 20-April 6, 2020, in the two COVID-19 designated hospitals of Zhoushan, Zhejiang and Rushan, Shandong, China, The laboratory findings, imaging, serum response to viral infection, and viral RNA level in the throat and stool samples were assessed from onset to recovery phase in patients with COVID-19. RESULTS: SARS-COV-2 RNA was positive as early as day four. It remained positive until day 55 post-onset in the sputum-throat swabs and became negative in most cases (55%) within 14 days after onset. Lymphocytopenia occurred in 40% (8/20) of patients during the peak infection period and returned to normal at week five. The most severe inflammation in the lungs appeared in week 2 or 3 after onset, and this was completely absorbed between week 6 and 8 in 85.7% of patients. All patients had detectable antibodies to the receptor binding domain (RBD), and 95% of these patients had IgG to viral N proteins. The antibody titer peaked at week four. Anti-S IgM was positive in 7 of 20 patients after week three. CONCLUSIONS: All COVID-19 patients in this study were self-limiting and recovered well though it may take as long as 6-8 weeks. Our findings on the kinetic changes in imaging, serum response to viral infection and viral RNA level may help understand pathogenesis and define clinical course of COVID-19.

Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in Rhesus macaques.

The 2019 novel coronavirus (SARS-CoV-2) outbreak is a major challenge for public health. SARS-CoV-2 infection in human has a broad clinical spectrum ranging from mild to severe cases, with a mortality rate of ~6.4% worldwide (based on World Health Organization daily situation report). However, the dynamics of viral infection, replication and shedding are poorly understood. Here, we show that Rhesus macaques are susceptible to the infection by SARS-CoV-2. After intratracheal inoculation, the first peak of viral RNA was observed in oropharyngeal swabs one day post infection (1 d.p.i.), mainly from the input of the inoculation, while the second peak occurred at 5 d.p.i., which reflected on-site replication in the respiratory tract. Histopathological observation shows that SARS-CoV-2 infection can cause interstitial pneumonia in animals, characterized by hyperemia and edema, and infiltration of monocytes and lymphocytes in alveoli. We also identified SARS-CoV-2 RNA in respiratory tract tissues, including trachea, bronchus and lung; and viruses were also re-isolated from oropharyngeal swabs, bronchus and lung, respectively. Furthermore, we demonstrated that neutralizing antibodies generated from the primary infection could protect the Rhesus macaques from a second-round challenge by SARS-CoV-2. The non-human primate model that we established here provides a valuable platform to study SARS-CoV-2 pathogenesis and to evaluate candidate vaccines and therapeutics.

A novel biparatopic antibody-ACE2 fusion that blocks SARS-CoV-2 infection: implications for therapy (preprint)

In the absence of a proven effective vaccine preventing infection by SARS-CoV-2, or a proven drug to treat COVID-19, the positive results of passive immune therapy using convalescent serum provides a strong lead. We have developed a new class of tetravalent, biparatopic therapy, 89C8-ACE2. It combines the specificity of a monoclonal antibody (89C8) that recognizes the relatively conserved N-terminal domain (NTD) of the viral S glycoprotein, and the ectodomain of ACE2, which binds to the receptor-binding domain (RBD) of S. This molecule shows exceptional performance in vitro, inhibiting the interaction of recombinant S1 to ACE2 and transduction of ACE2-overexpressing cells by S-pseudotyped lentivirus with IC50s substantially below 100 pM, and with potency approximately 100-fold greater than ACE2-Fc itself. Moreover, 89C8-ACE2 was able to neutralize authentic virus infection in a standard assay at low nanomolar concentrations, making this class of molecule a promising lead for therapeutic applications.