The number of similar epitopes determines the longevity of immunological memory (preprint)

The half-life of specific antibodies against various antigens varies tremendously from a few months to over 10,000 years. The reasons are largely unknown. Through epitope analysis of representative viruses, we found that the longevity of immunological memory may be correlated with the number of epitopes with similar sequences (EWSS) within each virus. Accordingly, a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with 4.5-times higher antibody titers and over 100 months of half-life was developed in a rabbit model. The decay pattern of antibodies against each epitope or the entire SARS-CoV-2 spike protein was roughly correlated with the number of EWSS in immunizationtreatments, –that is, for every additional EWSS, the half-life of the antibody would be doubled. After immunization, proportions of antigen-specific memory B cells (MBC) first increased and then decreased. In the descending phase, the antibody titers were positively correlated with the numbers of MBC. This study also discusses improvement measures for vaccines against other viruses.

Evaluation of the clinical effectiveness of telephone consultation compared to face-to-face consultation in terms of glycaemic control among patients with suboptimally controlled type 2 diabetes: a retrospective cohort study.

OBJECTIVE: With the COVID-19 pandemic, telemedicine has been increasingly deployed in lieu of face-to-face consultations for management of diabetes in primary care. There was a need to evaluate clinical effectiveness of telephone consultations for diabetes management and this study aimed to show whether one-off telephone consultation was inferior or not to face-to-face consultation in terms of glycaemic control among patients with suboptimally controlled type 2 diabetes. DESIGN: Retrospective cohort study. Data of all patients with type 2 diabetes who had a chronic disease consultation during the period 9 April 2020-18 September 2020, and met the study's inclusion and exclusion criteria was obtained from the electronic medical records. SETTING: A primary care clinic in the north-eastern region of Singapore. The clinic's patient population was representative of Singapore's population in terms of gender and age. PARTICIPANTS: 644 patients with type 2 diabetes and glycated haemoglobin (HbA1c) 7.0% and above, aged 21-80 years old. INTERVENTIONS: Participants either underwent telephone or face-to-face consultation for diabetes management. OUTCOME MEASURE: Mean HbA1c change (∆HbA1c) between preintervention and postintervention. RESULTS: Over 4 months, the mean ∆HbA1c was -0.16 percentage points (p.p.) (95% CI -0.26 to -0.07) and -0.11 p.p. (95% CI -0.20 to -0.02) for face-to-face and telephone consultation groups, respectively. The difference in mean ∆HbA1c between the two groups was +0.05 p.p. (95% CI -∞ to 0.16), with the upper limit of the one-sided 95% CI less than the prespecified non-inferiority margin of 0.5 p.p. (p<0.05). In those with HbA1c≥9%, the difference in mean ∆HbA1c was +0.31 p.p. (95% CI -∞ to 0.79), which exceeded the non-inferiority margin. CONCLUSION: For patients with suboptimally controlled type 2 diabetes, one-time telephone consultation was non-inferior to face-to-face consultation in terms of glycaemic control in the short term. However, more studies are required to investigate the long-term effects of telephone consultations and for those with HbA1c≥9%.

Robust crisis communication in turbulent times: Conceptualization and empirical evidence from the United States

Drawing on recent research on robust governance, we conceptualize robust crisis communication as a dynamic process centered on evolving public communication demands. We propose a three‐dimensional measurement for empirically examining the robustness of government crisis communication in the context of the COVID‐19 pandemic. We collected 43,642 Twitter messages posted by 50 state governors in the United States from January 1 to June 30, 2020. We applied machine learning algorithms to code the voluminous Twitter data based on messaging topics, sentiments, and interactions. This study found an overall low level of robustness in the governors' crisis communication. Governors most frequently posted reputation management tweets, followed by tweets about the government's handling of the pandemic. This research presents empirical evidence for the heavy influence of politics on governors' crisis communication strategies and highlights the need to understand and build robust crisis communication.摘要本文借鉴稳健性治理的最新相关研究，提出稳健性危机沟通的概念，将其界定为聚焦于满足危机中持续变化的公众沟通需求的动态沟通过程与模式。基于此概念，本文以新型冠状病毒肺炎疫情中的危机沟通为例，构建三维测量方法，用以检验政府危机沟通在内容主题、情感表达和对话互动三方面的稳健程度。本文收集美国50个州长在2020年1月1日至2020年6月30日期间发布的43,642条推特信息，并应用机器学习对所有信息的主题、情感和互动特征进行编码分析。本文发现美国州长危机沟通的稳健性程度总体偏低。美国州长最经常发布与声誉管理相关的推文，其次是政府的疫情防控措施。文章进一步阐释与例证政治因素对州长危机沟通策略的深刻影响，并强调政府部门理解与践行稳健性风险沟通的必要性与重要性。

Economic risk framing increases intention to vaccinate among Republican COVID-19 vaccine refusers.

OBJECTIVE: To determine if framing communications about COVID-19 vaccines in economic terms can increase Republicans' likelihood to get vaccinated. METHODS: We examined Twitter posts between January 2020 and September 2021 by Democratic and Republican politicians to determine how they framed the COVID-19 pandemic. Based on these posts, we carried out a survey study between September and November 2021 to examine whether motivations for COVID-19 vaccine uptake matched message frames that were widely used by these politicians. Finally, we conducted a randomized controlled experiment to examine how these frames (economic vs. health) affected intentions to vaccinate by vaccine refusers in both parties. RESULTS: Republican politicians were more likely to frame the pandemic in economic terms, whereas Democrats predominantly used health frames. Accordingly, vaccinated Republicans' choices were more likely to be motivated by economic consideration (ß = 0.25, p = 0.02) and personal financial rationales (ß = 0.24, p = 0.03). Among vaccine refusers, Republicans exposed to messages using economic rationales to encourage vaccination reported higher vaccination intentions compared to those exposed to messages using public health rationales (F1,119 = 4.16, p = 0.04). CONCLUSION: Messages highlighting economic and personal financial risks could increase intentions to vaccinate for vaccine-hesitant Republicans. PUBLIC HEALTH IMPLICATIONS: Agencies should invest in developing messages that are congruent with frames that are already widely used by co-partisans. Social media may be helpful in eliciting these frames.

Miller-Fisher syndrome and Guillain-Barre syndrome overlap syndrome following inactivated COVID-19 vaccine: Case report and scope review.

Miller-Fisher syndrome (MFS) is a rare variant of Guillain-Barré syndrome (GBS) manifesting as the triad of ataxia, areflexia, and ophthalmoplegia. With the extensive 2019 coronavirus disease (COVID-19) immunization program, cases of GBS or MFS following vaccination are increasingly being reported. A 64-y-old Chinese man presented with new-onset paresthesia of the extremities, bilateral abduction limitation, right facial palsy, areflexia of bilateral lower limbs, and left-dominant limb ataxia 12 d after the second dose of inactivated vaccine against COVID-19. Cerebrospinal fluid analysis indicated albumin-cytological dissociation and was positive for anti-GQ1b IgG and anti-GT1b IgG. Nerve conduction studies of limbs showed evidence of axonal neuropathy with reduced sensory amplitudes. Based on the clinical presentations, temporal progression of symptoms, and laboratory findings, the diagnosis of MFS-GBS overlap syndrome was made. The patient was treated with intravenous immunoglobulin and acupuncture and made a complete recovery 54 d after the onset of his initial neurological signs. To the best of our knowledge, we report the first case of MFS-GBS overlap syndrome following the inactivated COVID-19 vaccination. However, a coincidental relationship with this inactivated vaccine cannot be excluded. Although the benefits of COVID-19 vaccination largely outweigh its risk and the prognosis of MFS is generally favorable, a close surveillance of neurological complications post-COVID-19 vaccination is always necessary, considering its potentially disabling and lethal effects on vaccinated populations.

Oridonin Inhibits SARS‐CoV‐2 by Targeting Its 3C‐Like Protease

Oridonin Inhibits SARS‐CoV‐2 Oridonin, a natural product extracted from Rabdosia rubescens, possesses a wide range of pharmacological properties, including anti‐inflammatory, anti‐cancer, anti‐microbial, neuroprotection, immunoregulation, etc. In article number 2100124, Baisen Zhong, Litao Sun, and co‐workers demonstrate that Oridonin targets the SARS‐CoV‐2 3CL protease by covalently binding to cysteine145 in its active pocket to exert an anti‐SARS‐CoV‐2 effect, which provides a novel candidate for the treatment of COVID‐19. © 2022 WILEY‐VCH GmbH

Identification of serum metabolites enhancing inflammatory responses in COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by a strong production of inflammatory cytokines such as TNF and IL-6, which underlie the severity of the disease. However, the molecular mechanisms responsible for such a strong immune response remains unclear. Here, utilizing targeted tandem mass spectrometry to analyze serum metabolome and lipidome in COVID-19 patients at different temporal stages, we identified that 611 metabolites (of 1,039) were significantly altered in COVID-19 patients. Among them, two metabolites, agmatine and putrescine, were prominently elevated in the serum of patients; and 2-quinolinecarboxylate was changed in a biphasic manner, elevated during early COVID-19 infection but levelled off. When tested in mouse embryonic fibroblasts (MEFs) and macrophages, these 3 metabolites were found to activate the NF-κB pathway that plays a pivotal role in governing cytokine production. Importantly, these metabolites were each able to cause strong increase of TNF and IL-6 levels when administered to wildtype mice, but not in the mice lacking NF-κB. Intriguingly, these metabolites have little effects on the activation of interferon regulatory factors (IRFs) for the production of type I interferons (IFNs) for antiviral defenses. These data suggest that circulating metabolites resulting from COVID-19 infection may act as effectors to elicit the peculiar systemic inflammatory responses, exhibiting severely strong proinflammatory cytokine production with limited induction of the interferons. Our study may provide a rationale for development of drugs to alleviate inflammation in COVID-19 patients.

Oridonin Inhibits SARS-CoV-2 by Targeting Its 3C-Like Protease.

The current COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an enormous threat to public health. The SARS-CoV-2 3C-like protease (3CLpro), which is critical for viral replication and transcription, has been recognized as an ideal drug target. Herein, it is identified that three herbal compounds, Salvianolic acid A (SAA), (-)-Epigallocatechin gallate (EGCG), and Oridonin, directly inhibit the activity of SARS-CoV-2 3CLpro. Further, blocking SARS-CoV-2 infectivity by Oridonin is confirmed in cell-based experiments. By solving the crystal structure of 3CLpro in complex with Oridonin and comparing it to that of other ligands with 3CLpro, it is identified that Oridonin binds at the 3CLpro catalytic site by forming a C-S covalent bond, which is confirmed by mass spectrometry and kinetic study, blocking substrate binding through a nonpeptidomimetic covalent binding mode. Thus, Oridonin is a novel candidate to develop a new antiviral treatment for COVID-19.

The Landscape of Aminoacyl-tRNA Synthetases Involved in Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes in translation by linking amino acids onto their cognate tRNAs during protein synthesis. During evolution, aaRSs develop numerous non-canonical functions that expand the roles of aaRSs in eukaryotic organisms. Although aaRSs have been implicated in viral infection, the function of aaRSs during infections with coronaviruses (CoVs) remains unclear. Here, we analyzed the data from transcriptomic and proteomic database on human cytoplasmic (cyto) and mitochondrial (mt) aaRSs across infections with three highly pathogenic human CoVs, with a particular focus on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We found an overall downregulation of aaRSs at mRNA levels, while the protein levels of some mt-aaRSs and the phosphorylation of certain aaRSs were increased in response to SARS-CoV-2 infection. Strikingly, interaction network between SARS-CoV-2 and human aaRSs displayed a strong involvement of mt-aaRSs. Further co-immunoprecipitation (co-IP) experiments confirmed the physical interaction between SARS-CoV-2 M protein and TARS2. In addition, we identified the intermediate nodes and potential pathways involved in SARS-CoV-2 infection. This study provides an unbiased, overarching perspective on the correlation between aaRSs and SARS-CoV-2. More importantly, this work identifies TARS2, HARS2, and EARS2 as potential key factors involved in COVID-19.

The Landscape of Aminoacyl-tRNA Synthetases Involved in Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes in translation by linking amino acids onto their cognate tRNAs during protein synthesis. During evolution, aaRSs develop numerous non-canonical functions that expand the roles of aaRSs in eukaryotic organisms. Although aaRSs have been implicated in viral infection, the function of aaRSs during infections with coronaviruses (CoVs) remains unclear. Here, we analyzed the data from transcriptomic and proteomic database on human cytoplasmic (cyto) and mitochondrial (mt) aaRSs across infections with three highly pathogenic human CoVs, with a particular focus on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We found an overall downregulation of aaRSs at mRNA levels, while the protein levels of some mt-aaRSs and the phosphorylation of certain aaRSs were increased in response to SARS-CoV-2 infection. Strikingly, interaction network between SARS-CoV-2 and human aaRSs displayed a strong involvement of mt-aaRSs. Further co-immunoprecipitation (co-IP) experiments confirmed the physical interaction between SARS-CoV-2 M protein and TARS2. In addition, we identified the intermediate nodes and potential pathways involved in SARS-CoV-2 infection. This study provides an unbiased, overarching perspective on the correlation between aaRSs and SARS-CoV-2. More importantly, this work identifies TARS2, HARS2, and EARS2 as potential key factors involved in COVID-19.

Identification of Key Pathways and Genes in SARS-CoV-2 Infecting Human Intestines by Bioinformatics Analysis.

COVID-19 is a serious infectious disease that has recently swept the world, and research on its causative virus, SARS-CoV-2, remains insufficient. Therefore, this study uses bioinformatics analysis techniques to explore the human digestive tract diseases that may be caused by SARS-CoV-2 infection. The gene expression profile data set, numbered GSE149312, is from the Gene Expression Omnibus (GEO) database and is divided into a 24-h group and a 60-h group. R software is used to analyze and screen out differentially expressed genes (DEGs) and then gene ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses are performed. In KEGG, the pathway of non-alcoholic fatty liver disease exists in both the 24-h group and 60-h group. STRING is used to establish a protein-protein interaction (PPI) network, and Cytoscape is then used to visualize the PPI and define the top 12 genes of the node as the hub genes. Through verification, nine statistically significant hub genes are identified: AKT1, TIMP1, NOTCH, CCNA2, RRM2, TTK, BUB1B, KIF20A, and PLK1. In conclusion, the results of this study can provide a certain direction and basis for follow-up studies of SARS-CoV-2 infection of the human digestive tract and provide new insights for the prevention and treatment of diseases caused by SARS-CoV-2.

2D MOF-Based Photoelectrochemical Aptasensor for SARS-CoV-2 Spike Glycoprotein Detection.

A reliable and sensitive detection approach for SARS-CoV 2 is essential for timely infection diagnosis and transmission prevention. Here, a two-dimensional (2D) metal-organic framework (MOF)-based photoelectrochemical (PEC) aptasensor with high sensitivity and stability for SARS-CoV 2 spike glycoprotein (S protein) detection was developed. The PEC aptasensor was constructed by a plasmon-enhanced photoactive material (namely, Au NPs/Yb-TCPP) with a specific DNA aptamer against S protein. The Au NPs/Yb-TCPP fabricated by in situ growth of Au NPs on the surface of 2D Yb-TCPP nanosheets showed a high electron-hole (e-h) separation efficiency due to the enhancement effect of plasmon, resulting in excellent photoelectric performance. The modified DNA aptamer on the surface of Au NPs/Yb-TCPP can bind with S protein with high selectivity, thus decreasing the photocurrent of the system due to the high steric hindrance and low conductivity of the S protein. The established PEC aptasensor demonstrated a highly sensitive detection for S protein with a linear response range of 0.5-8 µg/mL with a detection limit of 72 ng/mL. This work presented a promising way for the detection of SARS-CoV 2, which may conduce to the impetus of clinic diagnostics.

Quantification of Cytokine Storms During Virus Infections.

Highly pathogenic virus infections usually trigger cytokine storms, which may have adverse effects on vital organs and result in high mortalities. The two cytokines interleukin (IL)-4 and interferon (IFN)-γ play key roles in the generation and regulation of cytokine storms. However, it is still unclear whether the cytokine with the largest induction amplitude is the same under different virus infections. It is unknown which is the most critical and whether there are any mathematical formulas that can fit the changing rules of cytokines. Three coronaviruses (SARS-CoV, MERS-CoV, and SARS-CoV-2), three influenza viruses (2009H1N1, H5N1 and H7N9), Ebola virus, human immunodeficiency virus, dengue virus, Zika virus, West Nile virus, hepatitis B virus, hepatitis C virus, and enterovirus 71 were included in this analysis. We retrieved the cytokine fold change (FC), viral load, and clearance rate data from these highly pathogenic virus infections in humans and analyzed the correlations among them. Our analysis showed that interferon-inducible protein (IP)-10, IL-6, IL-8 and IL-17 are the most common cytokines with the largest induction amplitudes. Equations were obtained: the maximum induced cytokine (max) FC = IFN-γ FC × (IFN-γ FC/IL-4 FC) (if IFN-γ FC/IL-4 FC > 1); max FC = IL-4 FC (if IFN-γ FC/IL-4 FC < 1). For IFN-γ-inducible infections, 1.30 × log2 (IFN-γ FC) = log10 (viral load) - 2.48 - 2.83 × (clearance rate). The clinical relevance of cytokines and their antagonists is also discussed.

Clinical Characteristics and Factors Associated with Disease Progression of Mild to Moderate COVID-19 Patients in a Makeshift (Fangcang) Hospital: A Retrospective Cohort Study.

OBJECTIVE: Information regarding the epidemiology and clinical features of mild to moderate patients caused by COVID-19 in Fangcang Hospital is scarce. Through a retrospective cohort study, the clinical characteristics of COVID-19 patients in Dongxihu Fangcang shelter hospitals were analyzed, and the factors that affected the disease progression of COVID-19 patients were explored. METHODS: The clinical characteristics of 714 patients with COVID-19 were retrospectively analyzed at Dongxihu Fangcang Hospital between February 7 and March 8, 2020. We described the clinical characteristics and distribution of discharge or transfer times for each patient. According to the disease progression of COVID-19 patients, we divided all patients into Non-Deteriorated group and Deteriorated group. Furthermore, binary logistic regression was used for a single outcome and multiple response variables. RESULTS: We treated 789 patients with mild and moderate COVID-19, of which 714 were included in this study, which included 326 (45.66%) deteriorated patients and 388 (54.34%) non-deteriorated patients. The mean age of the study population was 48.16±12.44 years. Of all patients, 319 (44.7%) were men and 395 (55.3%) were women. The average length of the patient's stay was 16.08±5.13 days. The most common clinical feature on admission was fever (593 of 714, 83.05%). It is worth noting that 80 (11.20%) of the 714 patients were asymptomatic from exposure to admission. Multivariate logistic regression analysis showed that gender, age, diabetes, respiratory system disease, fever, dyspnea, and nasal congestion were risk factors associated with deterioration in cases with COVID-19 patients, and asymptomatic (OR: 0.058; 95% CI: 0.022-0.155; P<0.001) was the protective factor for deterioration of COVID-19 patients. CONCLUSION: Accompanied by chronic diseases, old age, fever, nasal congestion, and dyspnea were factors that influenced the aggravation of COVID-19 patients, and more attention and treatment should be given to these patients.

The Role of Alveolar Edema in COVID-19.

The coronavirus disease 2019 (COVID-19) has spread over the world for more than one year. COVID-19 often develops life-threatening hypoxemia. Endothelial injury caused by the viral infection leads to intravascular coagulation and ventilation-perfusion mismatch. However, besides above pathogenic mechanisms, the role of alveolar edema in the disease progression has not been discussed comprehensively. Since the exudation of pulmonary edema fluid was extremely serious in COVID-19 patients, we bring out a hypothesis that severity of alveolar edema may determine the size of poorly-ventilated area and the blood oxygen content. Treatments to pulmonary edema (conservative fluid management, exogenous surfactant replacements and ethanol-oxygen vapor therapy hypothetically) may be greatly helpful for reducing the occurrences of severe cases. Given that late mechanical ventilation may cause mucus (edema fluid) to be blown deep into the small airways, oxygen therapy should be given at the early stages. The optimal time and blood oxygen saturation (SpO2) threshold for oxygen therapy are also discussed.