Association between the side effect induced by COVID-19 vaccines and the immune regulatory gene polymorphism.

People often worry about the side effects after vaccination, reducing the willingness to vaccinate. Thus, we tried to find out the risk of single nucleotide polymorphism (SNP) vaccines to improve the willingness and confidence in vaccination. Allergic and inflammatory reactions are the common vaccine side effects caused by immune system overreaction. In addition, a previous study showed significantly higher frequency of febrile reactions to measles vaccines in American Indians than in Caucasian children, indicating that the side effects varied in accordance with genetic polymorphisms in individuals. Thus, SNPs of immune regulatory genes, cytotoxic T-lymphocyte-associated protein 4 (CTLA4), CD28, tumor necrosis factor ligand superfamily member 4 (TNFSF4) and programmed cell death protein 1 (PDCD1) were included in this study to analyze their association with vaccine side effects. Moreover, 61 healthy participants were asked on the number of doses they received, the brand of the vaccine, and the side effects they suffered. We found that several SNPs were associated with side effects after the first or second dose of mRNA or adenoviral vector vaccines. Furthermore, these SNPs were associated with several autoimmune diseases and cancer types; thus, they played an important role in immune regulation. Moreover, rs3181096 and rs3181098 of CD28, rs733618 and rs3087243 of CTLA, and rs1234314 of TNFSF4 were associated with mild vaccine side effects induced by mRNA and adenoviral vector vaccines, which would play a potential role in vaccine-induced immune responses and may further lead to fatal side effects. These results could serve as a basis for investigating the mechanism of vaccine side effects. Furthermore, it was hoped that these results would address public concerns about the side effects of the COVID-19 vaccination. In clinical application, a rapid screening test can be performed to assess the risk of vaccine side effects before vaccination and provide immediate treatment.

Statin Therapy and the Risk of Viral Infection: A Retrospective Population-Based Cohort Study.

Statins exert cholesterol-independent beneficial effects, including immunomodulatory effects. In this study, we attempted to investigate the association between statin therapy and the risk of viral infection. We conducted a retrospective cohort study using data from Taiwan's National Health Insurance Research Database. We identified patients with hyperlipidemia and divided them into two cohorts: statin users and statin nonusers. A 1:1 propensity score matching was conducted between the two cohorts, and a Cox proportional hazards model was used to evaluate the risk of viral infection. Overall, a total of 20,202 patients were included in each cohort. The median follow-up durations were 4.41 and 6.90 years for statin nonusers and users, respectively. The risk of viral infection was 0.40-fold (95% confidence interval = 0.38-0.41) in statin users than in statin nonusers after adjustment for potential confounders. Statin treatment was associated with a significantly lower risk of viral infection in all age groups older than 18 years in both men and women. Moreover, the risk of viral infection substantially reduced as the duration of statin treatment increased. Our findings suggest that statin therapy is associated with a significantly lower risk of viral infection in patients with hyperlipidemia.

Spike-based adenovirus vectored COVID-19 vaccine does not aggravate heart damage after ischemic injury in mice.

An unprecedented number of COVID-19 vaccination campaign are under way worldwide. The spike protein of SARS-CoV-2, which majorly binds to the host receptor angiotensin converting enzyme 2 (ACE2) for cell entry, is used by most of the vaccine as antigen. ACE2 is highly expressed in the heart and has been reported to be protective in multiple organs. Interaction of spike with ACE2 is known to reduce ACE2 expression and affect ACE2-mediated signal transduction. However, whether a spike-encoding vaccine will aggravate myocardial damage after a heart attack via affecting ACE2 remains unclear. Here, we demonstrate that cardiac ACE2 is up-regulated and protective after myocardial ischemia/reperfusion (I/R). Infecting human cardiac cells or engineered heart tissues with a spike-based adenovirus type-5 vectored COVID-19 vaccine (AdSpike) does not affect their survival and function, whether subjected to hypoxia-reoxygenation injury or not. Furthermore, AdSpike vaccination does not aggravate heart damage in wild-type or humanized ACE2 mice after I/R injury, even at a dose that is ten-fold higher as used in human. This study represents the first systematic evaluation of the safety of a leading COVID-19 vaccine under a disease context and may provide important information to ensure maximal protection from COVID-19 in patients with or at risk of heart diseases.

Epidemiological Characteristics of COVID-19 Outbreak in Yangzhou, China, 2021.

Objective: Epidemiological characteristics of COVID-19 outbreak in Yangzhou city caused by the highly contagious Delta variant strain of SARS-CoV-2 virus were investigated in this retrospective descriptive study to provide prevention and control guidelines for outbreaks in the future. Methods: All the epidemiological data used in this study were collected manually from the official website of the Yangzhou Municipal Health Committee from 28 July to 26 August 2021, and then were analyzed systematically and statistically in this study. Results: A total of 570 COVID-19 cases were reported during the short-term outbreak in Yangzhou City. The ages of infected individuals ranged from 1 to 90 years with the average age at 49.47 ± 22.69 years. As for gender distributions, the ratio of male- to-female patients was 1:1.36 (242:328). Geographic analysis showed that 377 patients (66.1%) were in Hanjiang District while 188 patients (33.0%) were in Guangling District. Clinical diagnosis showed that 175 people (30.7%) had mild symptoms, 385 people were in moderate conditions (67.5%), and 10 people were in severe situations (1.8%). Significant age differences were found among the three groups (P < 0.001). However, no significant difference was identified in terms of gender ratio (P > 0.05). Based on the transmission chain formed by 6 generations of infected persons with a clear transmission relationship, the age showed a gradually decreasing trend, while the median time of diagnosis in 2 adjacent generations was 3 days. In addition, the estimated basic reproduction number R 0 of the Delta variant was 3.3651 by the classical Susceptible, Infectious, and/or Recovered (SIR) model. Conclusion: The Delta variant of SARS-CoV-2 was highly infectious and has obvious clustering characteristics during the Yangzhou outbreak in China.

Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study

ObjectiveTo delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.DesignRetrospective case series.SettingTongji Hospital in Wuhan, China.ParticipantsAmong a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020.Main outcome measuresClinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.ResultsThe median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83;73%) than in recovered patients (88;55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113;100%), type I respiratory failure (18/35;51%), sepsis (113;100%), acute cardiac injury (72/94;77%), heart failure (41/83;49%), alkalosis (14/35;40%), hyperkalaemia (42;37%), acute kidney injury (28;25%), and hypoxic encephalopathy (23;20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.ConclusionSevere acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

Prevention, treatment and potential mechanism of herbal medicine for Corona viruses: A review.

The pandemic of coronavirus disease 2019 (COVID-19) caused by the SARS-coronavirus 2(SARS-CoV-2) virus has become the greatest global public health crisis in recent years,and the COVID-19 epidemic is still continuing. However, due to the lack of effectivetherapeutic drugs, the treatment of corona viruses is facing huge challenges. In thiscontext, countries with a tradition of using herbal medicine such as China have beenwidely using herbal medicine for prevention and nonspecific treatment of corona virusesand achieved good responses. In this review, we will introduce the application of herbalmedicine in the treatment of corona virus patients in China and other countries, andreview the progress of related molecular mechanisms and antiviral activity ingredients ofherbal medicine, in order to provide a reference for herbal medicine in the treatment ofcorona viruses. We found that herbal medicines are used in the prevention and fightagainst COVID-19 in countries on all continents. In China, herbal medicine has beenreported to relieve some of the clinical symptoms of mild patients and shorten the length of hospital stay. However, as most herbal medicines for the clinical treatment of COVID-19still lack rigorous clinical trials, the clinical and economic value of herbal medicines in theprevention and treatment of COVID-19 has not been fully evaluated. Future work basedon large-scale randomized, double-blind clinical trials to evaluate herbal medicines andtheir active ingredients in the treatment of new COVID-19 will be very meaningful.

Comparative miRNA Transcriptomics of Mouse and Macaque Reveals MYOC is An Inhibitor for C. neoformans Invasion into Brain (preprint)

Cryptococcal meningoencephalitis is an emerging infection shifted from primarily ART-naive to being ART-experienced HIV/AIDS patients, COVID-19 patients and also in immune competent individuals, mainly caused by the human opportunistic pathogen Cryptococcus neoformans , yet mechanisms of the brain or CNS dissemination remain to elucidate, which is the deadest process for the disease. Meanwhile, illustrations of clinically relevant responses in cryptococcosis were limited, as the low availabilities of clinical samples. In this study, macaque and mouse infection models were employed and miRNA-mRNA transcriptomes were performed and combined, which revealed cytoskeleton, a major feather in HIV/AIDS patients, was a centric pathway regulated in both two infection models. Notably, assays of clinical immune cells confirmed an enhanced “Trojan Horse” in HIV/AIDS patients, which can be shut down by cytoskeleton inhibitors. Furthermore, we identified a novel enhancer for macrophage “Trojan Horse”, myocilin, and an enhanced fungal burden was achieved in brains of MYOC transgenic mice. Taking together, this study reveals fundamental roles of cytoskeleton and MYOC in blocking fungal CNS dissemination, which not only helps to understand the high prevalence of cryptococcal meningitis in HIV/AIDS, but also facilitates the development of novel drugs for therapies of meningoencephalitis caused by C. neoformans and other pathogenic microorganisms.

Pig farmers' willingness to recover their production under COVID-19 pandemic shock in China - empirical evidence from a farm survey. (Special Focus: Impacts of COVID-19 on agriculture and rural poverty in China.)

Pig farmers' willingness to recover production under the COVID-19 pandemic shock is significant to recover live pigs' supply in China in 2020. Increasing farmers' willingness to recover pig production contributes to enhance pig supply, stabilize the pig and pork market, and to improve pig farmers' income. This research studies the determinants of pig farmers' willingness to recover production under COVID-19 pandemic shock by applying survey data of 201 farmers in Huai'an City and Lin'an City and a logit regression model. The estimation results show that a farmer's risk perception, the duration time of a farmer's feed supply under COVID-19 pandemic shock, whether or not being a cooperative member, and a farmer's knowledge on government's policy designed to encourage pig production, a farmer's education level and production experience are the key determinants to a farmer's willingness to recover pig production. Thus, it's important for policymakers to solve the problems for farmers to get access to feed during the pandemic, to encourage the development of cooperatives, as well as to issue and advocate policies to encourage pig production. The study contributes to the scant literature by providing fresh empirical evidences on determinants of farmers' willingness to recover pig production. It has significance to farmers and governments to enhance farmers' willingness to recover production, which contributes to secure pig supply in China after the COVID-19 pandemic.

A Synergetic R-Shiny Portal for Modeling and Tracking of COVID-19 Data.

The purpose of this paper is to introduce a useful online interactive dashboard (https://mahdisalehi.shinyapps.io/Covid19Dashboard/) that visualize and follow confirmed cases of COVID-19 in real-time. The dashboard was made publicly available on 6 April 2020 to illustrate the counts of confirmed cases, deaths, and recoveries of COVID-19 at the level of country or continent. This dashboard is intended as a user-friendly dashboard for researchers as well as the general public to track the COVID-19 pandemic, and is generated from trusted data sources and built in open-source R software (Shiny in particular); ensuring a high sense of transparency and reproducibility. The R Shiny framework serves as a platform for visualization and analysis of the data, as well as an advance to capitalize on existing data curation to support and enable open science. Coded analysis here includes logistic and Gompertz growth models, as two mathematical tools for predicting the future of the COVID-19 pandemic, as well as the Moran's index metric, which gives a spatial perspective via heat maps that may assist in the identification of latent responses and behavioral patterns. This analysis provides real-time statistical application aiming to make sense to academic- and public consumers of the large amount of data that is being accumulated due to the COVID-19 pandemic.

The effect of emergency surgery on acute abdomen patients with COVID-19 pneumonia: a retrospective observational study.

During the COVID-19 outbreak, some patients with COVID-19 pneumonia also suffered from acute abdomen requiring surgical treatment; however, there is no consensus for the treatment of such patients. In this study, we retrospectively reviewed 34 patients with acute abdomen who underwent emergency surgery during the COVID-19 outbreak. Among the 34 patients with acute abdomen, a total of six cases were found with COVID-19 pneumonia (clinical classification for COVID-19 pneumonia: all were the common type). On the premise of similar demographics between both groups, patients with COVID-19 pneumonia had worse indicators of liver and coagulation function. Compared with acute abdomen patients without COVID-19, patients with COVID-19 pneumonia had a longer hospital stay, but there were no significant differences in postsurgical complications (P = 0.58) or clinical outcomes (P = 0.56). In addition, an obvious resolution of lung inflammation after surgery was observed in five COVID-19 patients (83.3%). No new COVID-19 cases occurred during the patients' hospital stays. Therefore, for the common type of COVID-19 pneumonia, emergency surgery could not only improve the outcomes of COVID-19 pneumonia patients with acute abdomen, but also benefit the resolution of pulmonary inflammation.

Identification of Complex Pneumonia during the Outbreak of COVID-19: Bacterial Pneumonia Combined with Acute Eosinophilic Pneumonia in Patients with Maintenance Hemodialysis.

It is of crucial importance to diagnose patients in a timely and clear manner during the outbreak of COVID-19. Different causes of pneumonia makes it difficult to differentiate COVID-19 from others. Hemodialysis patients are a special group of people in this outbreak. We present a successfully treated case of a patient with maintenance hemodialysis from acute eosinophilic pneumonia for using meropenem when treating bacterial pneumonia, avoiding possible panic and waste of quarantine materials in dialysis centers.

COVID-19 severity is associated with immunopathology and multi-organ damage (preprint)

COVID-19 is characterised by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand how host responses contribute to COVID-19 pathophysiology, we used a multi-omics approach to identify molecular markers in peripheral blood and plasma samples that distinguish COVID-19 patients experiencing a range of disease severities. A large number of expressed genes, proteins, metabolites and extracellular RNAs (exRNAs) were identified that exhibited strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients, indicative of multi-organ damage. The continuous activation of IFN-I signalling and neutrophils, as well as a high level of inflammatory cytokines, were observed in severe disease patients. In contrast, COVID-19 in mild patients was characterised by robust T cell responses. Finally, we show that some of expressed genes, proteins and exRNAs can be used as biomarkers to predict the clinical outcomes of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19 and will help guide future studies in this area.