Cytokine storm in COVID-19: from viral infection to immune responses,diagnosis and therapy

The COVID-19 outbreak is emerging as a significant public health challenge. Excessive production of proinflammatory cytokines, also known as cytokine storm, is a severe clinical syndrome known to develop as a complication of infectious or inflammatory diseases. Clinical evidence suggests that the occurrence of cytokine storm in severe acute respiratory syndrome secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is closely associated with the rapid deterioration and high mortality of severe cases. In this review, we aim to summarize the mechanism of SARS-CoV-2 infection and the subsequent immunological events related to excessive cytokine production and inflammatory responses associated with ACE2-AngII signaling. An overview of the diagnosis and an update on current therapeutic regimens and vaccinations is also provided.     

A mini-review on the effects of COVID-19 on younger individuals

Coronavirus disease 2019 (COVID-19) pandemic has uprooted our lives like never before since its onset in the late December 2019. The world has seen mounting infections and deaths over the past few months despite the unprecedented measures countries are implementing, such as lockdowns, social distancing, mask-wearing, and banning gatherings in large groups. Interestingly, young individuals seem less likely to be impacted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19. While the rate of transmission, symptom presentation, and fatality is lower in children than people from other age groups, they have been disproportionately affected by strict lockdown measures needed to curb viral spread. In this review, we describe the association between patient age and COVID-19, epidemiology of SARS-CoV-2 infection in children, psychological effects associated with lockdowns and school closures, and possible mechanisms underlying lower transmission rate of COVID-19 in children.     

Serological tests for COVID-19: Potential opportunities

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel betacoronavirus, caused a pandemic leading to a standstill of nearly all global activities. There are some controversies on the production of specific immunoglobulin M (IgM) and IgG antibodies after the infection with SARS-CoV-2. This paper seeks to elaborate on the potential application of IgM and IgG antibodies and the viral antigens for the diagnosis and the course of the disease as well as the recurrence of positive nucleic acid tests after discharge.     

The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic

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mRNA vaccines for COVID-19: what,why and how

The Coronavirus disease-19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2), has impacted human lives in the most profound ways with millions of infections and deaths. Scientists and pharmaceutical companies have been in race to produce vaccines against SARS-CoV-2. Vaccine generation usually demands years of developing and testing for efficacy and safety. However, it only took less than one year to generate two mRNA vaccines from their development to deployment. The rapid production time, cost-effectiveness, versatility in vaccine design, and clinically proven ability to induce cellular and humoral immune response have crowned mRNA vaccines with spotlights as most promising vaccine candidates in the fight against the pandemic. In this review, we discuss the general principles of mRNA vaccine design and working mechanisms of the vaccines, and provide an up-to-date summary of pre-clinical and clinical trials on seven anti-COVID-19 mRNA candidate vaccines, with the focus on the two mRNA vaccines already licensed for vaccination. In addition, we highlight the key strategies in designing mRNA vaccines to maximize the expression of immunogens and avoid intrinsic innate immune response. We also provide some perspective for future vaccine development against COVID-19 and other pathogens.     

新型冠状病毒感染相关嗅觉障碍的流行现状、机制和康复

新型冠状病毒感染（coronavirus disease 2019,COVID-19）,下简称“新冠”,是由严重急性呼吸系统综合征冠状病毒2（severe acute respiratory syndrome coronavirus 2,SARS-CoV-2）引发的全球流行传染病。鉴于嗅觉障碍是其主要神经症状,明确相关流行现状、机制和康复对促进公共健康非常重要。文献报道的新冠相关嗅觉障碍的发生率存在差异,与评估工具、人群以及变异毒株3个因素有关。其中,不同毒株之间嗅觉障碍发生率的差异可能源于刺突糖蛋白和侵入方式的变异。在外周嗅觉系统,SARS-CoV-2主要引发嗅裂炎症、支持细胞死亡和宿主免疫反应,而关于SARS-CoV-2入侵中枢的途径和机制仍存争议。部分“长新冠”患者存在持续的嗅觉障碍,SARS-CoV-2诱发慢性炎症反应和对嗅上皮再生的破坏是其潜在的病理基础。根据嗅觉媒介假说,SARS-CoV-2可能借由嗅觉系统影响中枢功能并最终诱发神经退行性变。嗅觉训练、药物等方法可帮助新冠相关嗅觉障碍的康复。     

Total anti-SARS-CoV-2 antibodies measured 6 months after Pfizer-BioNTech COVID-19 vaccination in healthcare workers

BackgroundThis study aimed at monitoring the kinetics of serum total anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) antibodies in a cohort of healthcare workers after voluntary vaccination with Pfizer-BioNTech coronavirus disease 2019 (COVID-19) mRNA-based vaccine.MethodsThe study population consisted of 787 healthcare workers (mean age 44±12 years; 66% females), who received two 30 mg doses of Pfizer-BioNTech COVID-19 vaccine, 3 weeks apart. Venous blood was drawn before the first vaccine dose, immediately before the second vaccine dose, and then at 1, 3 and 6 months after the second vaccine dose. Serological testing employed the total antiSARS-CoV-2 antibodies measurement with Roche Elecsys Anti-SARS-CoV-2 S chemiluminescent immunoassay.ResultsThe median serum levels of total anti-SARS-CoV-2 antibodies reached the peak (1762 kU/L) 1 month after the second vaccine dose, but tended to progressively decline at the 3-month (1086 kU/L) and 6-month (802 kU/L) follow-up points. Overall, the values after 3and 6months were 37% and 57% lower than the corresponding concentrations measured at the peak. No healthcare worker had total anti-SARS-CoV-2 antibodies below the method-dependent cut-off after 6 months. The decline compared to the peak was more accentuated in baseline seropositive persons than in those who were baseline seronegative (74% vs. 52%) cohort. The 6-month post-vaccination anti-SARS-CoV-2 antibodies in subjects aged <65 years remained over 2-fold higher than in those aged ≥65 years (813 vs. 343 kU/L) and also remained consistently higher in women than in men.ConclusionsGradual decline of total anti-SARS-CoV-2 antibodies occurred 6 months after Pfizer-BioNTech COVID-19 vaccination, though values remained higher than the method-dependent cut-off, with no case of sero-negativization.     

Humoral and Cellular Immune Responses of COVID-19 vaccines against SARS-Cov-2 Omicron variant: a systemic review

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has undergone multiple mutations since its emergence, and its latest variant, Omicron (B.1.1.529), is the most contagious variant of concern (VOC) which poses a major and imminent threat to public health. Since firstly reported by World Health Organization (WHO) in November 2021, Omicron variant has been spreading rapidly and has become the dominant variant in many countries worldwide. Omicron is the most mutated variant so far, containing 60 mutations in its genome, including 37 mutations in the S-protein. Since all current COVID-19 vaccines in use were developed based on ancestral SARS-CoV-2 strains, whether they are protective against Omicron is a critical question which has been the center of study currently. In this article, we systemically reviewed the studies regarding the effectiveness of 2- or 3-dose vaccines delivered in either homologous or heterologous manner. The humoral and cellular immune responses elicited by various vaccine regimens to protect against Omicron variant are discussed. Current understanding of the molecular basis underlying immune escape of Omicron was also analyzed. These studies indicate that two doses of vaccination are insufficient to elicit neutralizing antibody responses against Omicron variant. Nevertheless, Omicron-specific humoral immune responses can be enhanced by booster dose of almost all type vaccines in certain degree, and heterologous vaccination strategy may represent a better choice than homogenous regimens. Intriguingly, results of studies indicate that all current vaccines are still able to elicit robust T cell response against Omicron. Future focus should be the development of Omicron variant vaccine, which may induce potent humoral as well as cellular immune responses simultaneously against all known variants of the SARS-CoV-2 virus.     

A Dynamic Immune Response Shapes COVID-19 Progression

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Humoral Immunity against SARS-CoV-2 and the Impact on COVID-19 Pathogenesis

It has been more than a year since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged. Many studies have provided insights into the various aspects of the immune response in coronavirus disease 2019 (COVID-19). Especially for antibody treatment and vaccine development, humoral immunity to SARS-CoV-2 has been studied extensively, though there is still much that is unknown and controversial. Here, we introduce key discoveries on the humoral immune responses in COVID-19, including the immune dynamics of antibody responses and correlations with disease severity, neutralizing antibodies and their cross-reactivity, how long the antibody and memory B-cell responses last, aberrant autoreactive antibodies generated in COVID-19 patients, and the efficacy of currently available therapeutic antibodies and vaccines against circulating SARS-CoV-2 variants, and highlight gaps in the current knowledge.     

COVID-19 one year later: a retrospect of CRISPR-Cas system in combating COVID-19

Coronavirus disease 2019 (COVID-19), an infectious disease caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a persistent global threat. The transmission of SARS-CoV-2 is wide and swift. Rapid detection of the viral RNA and effective therapy are imperative to prevent the worldwide spread of the new infectious disease. Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR)- CRISPR-associated protein (Cas) system is an RNA-directed adaptive immune system, and it has been transformed into a gene editing tool. Applications of CRISPR-Cas system involves in many fields, such as human gene therapy, drug discovery and disease diagnosis. Under the background of COVID-19 pandemic, CRISPR-Cas system shows hidden capacity to fight the emergency in many aspects. This review will focus on the role of gene editing in COVID-19 diagnosis and treatment. We will describe the potential use of CRISPR-Cas-based system in combating COVID-19, from diagnosis to treatment. Furthermore, the limitation and perspectives of this novel technology are also evaluated.     

COVID-19检测技术的优点和局限性

由严重急性呼吸系统综合症冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)感染引起的2019年冠状病毒肺炎(COVID-19),其持续大流行已对世界公共卫生安全造成严重的危害。发展病毒检测技术并运用于卫生管理包括人员排查、患者鉴别与治疗、减缓病毒传播等方面已发挥了重要作用。本文简要概述了SARS-CoV-2生物学特征,对全球发展使用的SARS-CoV-2病毒主要检测技术和新兴发展检测技术进行了比较详尽的介绍,并对病毒检测技术进行了展望,以期为临床医疗诊断、公共卫生防护、疾病预防和控制等提供理论和技术帮助。     

The Rapid Assessment and Early Warning Models for COVID-19

Human beings have experienced a serious public health event as the new pneumonia (COVID-19), caused by the severe acute respiratory syndrome coronavirus ha     

COVID-ONE-hi: The One-stop Database for COVID-19-specific Humoral Immunity and Clinical Parameters

Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (named COVID-ONE-hi). COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients. In addition, 96 clinical parameters for the 2360 serum samples and basic information for the 783 patients are integrated into the database. Furthermore, COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the “START” button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-hi is freely available at www.COVID-ONE.cn.     

COVID-19-related coagulopathy: A review of pathophysiology and pharmaceutical management

December 2019 will never be forgotten in the history of medicine when an outbreak of pneumonia of unknown etiology in Wuhan, China sooner or later prompted the World Health Organization to issue a public health warning emergency. This is not the first nor will it be the last time that a member of β-coronaviruses (CoVs) is waging a full-scale war against human health. Notwithstanding the fact that pneumonia is the primary symptom of the novel coronavirus (2019nCoV; designated as SARS-CoV-2), the emergence of severe disease mainly due to the injury of nonpulmonary organs at the shadow of coagulopathy leaves no choice, in some cases, rather than a dreadful death. Multiple casual factors such as inflammation, endothelial dysfunction, platelet and complement activation, renin-angiotensin-aldosterone system derangement, and hypoxemia play a major role in the pathogenesis of coagulopathy in coronavirus disease 2019 (COVID-19) patients. Due to the undeniable role of coagulation dysfunction in the initiation of several complications, assessment of coagulation parameters and the platelet count would be beneficial in early diagnosis and also timely prediction of disease severity. Although low-molecular-weight heparin is considered as the first-line of treatment in COVID-19-associated coagulopathy, several possible therapeutic options have also been proposed for better management of the disease. In conclusion, this review would help us to gain insight into the pathogenesis, clinical manifestation, and laboratory findings associated with COVID-19 coagulopathy and would summarize management strategies to alleviate coagulopathy-related complications.