Obesity,a major risk factor for immunity and severe outcomes of COVID-19

An influenza-like virus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for COVID-19 disease and spread worldwide within a short time. COVID-19 has now become a significant concern for public health. Obesity is highly prevalent worldwide and is considered a risk factor for impairing the adaptive immune system. Although diabetes, hypertension, cardiovascular disease (CVD), and renal failure are considered the risk factors for COVID-19, obesity is not yet well-considered. The present study approaches establishing a systemic association between the prevalence of obesity and its impact on immunity concerning the severe outcomes of COVID-19 utilizing existing knowledge. Overall study outcomes documented the worldwide prevalence of obesity, its effects on immunity, and a possible underlying mechanism covering obesity-related risk pathways for the severe outcomes of COVID-19. Overall understanding from the present study is that being an immune system impairing factor, the role of obesity in the severe outcomes of COVID-19 is worthy.     

COVID-19, leprosy,and neutrophils

Coronavirus Disease 2019 (COVID-19), a disease caused by the betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has only recently emerged, while Mycobacterium leprae, the etiological agent of leprosy, has endured for more than 2,000 years. As soon as the initial reports of COVID-19 became public, several entities, including the Brazilian Leprosy Society, warned about the possible impact of COVID-19 on leprosy patients. It has been verified that COVID-19 carriers can be either asymptomatic or present varying degrees of severe respiratory failure in association with cytokine storm and death, among other diseases. Severe COVID-19 patients show increased numbers of neutrophils and serum neutrophil extracellular trap (NET) markers, in addition to alterations in the neutrophil-to-lymphocyte ratio (NLR). The absence of antiviral drugs and the speed of COVID-19 transmission have had a major impact on public health systems worldwide, leading to the almost total collapse of many national and local healthcare services. Leprosy, an infectious neurological and dermatological illness, is widely considered to be the most frequent cause of physical disabilities globally. The chronic clinical course of the disease may be interrupted by acute inflammatory episodes, named leprosy reactions. These serious immunological complications, characterized by cytokine storms, are responsible for amplifying peripheral nerve damage. From 30% to 40% of all multibacillary leprosy (MB) patients experience erythema nodosum leprosum (ENL), a neutrophilic immune-mediated condition. ENL patients often present these same COVID-19-like symptoms, including high levels of serum NET markers, altered NLR, and neutrophilia. Moreover, the consequences of a M. leprae–SARS-CoV-2 coinfection have yet to be fully investigated. The goal of the present viewpoint is to describe some of the similarities that may be found between COVID-19 and leprosy disease in the context of neutrophilic biology.     

Immune response pattern across the asymptomatic,symptomatic and convalescent periods of COVID-19

We present an integrated analysis of urine and serum proteomics and clinical measurements in asymptomatic, mild/moderate, severe and convalescent cases of COVID-19. We identify the pattern of immune response during COVID-19 infection. The immune response is activated in asymptomatic infection, but is dysregulated in mild and severe COVID-19 patients. Our data suggest that the turning point depends on the function of myeloid cells and neutrophils. In addition, immune defects persist into the recovery stage, until 12 months after diagnosis. Moreover, disorders of cholesterol metabolism span the entire progression of the disease, starting from asymptomatic infection and lasting to recovery. Our data suggest that prolonged dysregulation of the immune response and cholesterol metabolism might be the pivotal causative agent of other potential sequelae. Our study provides a comprehensive understanding of COVID-19 immunopathogenesis, which is instructive for the development of early intervention strategies to ameliorate complex disease sequelae.     

基于地理信息系统的重庆地区COVID-19疫情空间分布格局演化

探讨重庆地区COVID-19疫情时空分布特征及扩散模式,以期未来为本地应对公共卫生应急事件积累经验。本文收集重庆市卫生健康委员会公布的官方数据,采用ArcGIS 10.2软件进行空间计量分析,并实现区域分布可视化,描述性统计和社会因素相关分析采用SPSS 20.0和Graphpad Prism 7.0软件进行统计和作图。结果5个时间节点,重庆地区COVID-19累计报告发病率的Moran’s I值均为正值(均P<0.05);局部Getis-ord Gi*指数分析探测到渝东北高渝东南低的态势越发明显;标准差椭圆展布呈现东北-西南的空间格局,随时间的变化经历了扩散-极化-扩散-稳定的过程;重心走势呈现向西南(渝西片区)移动距离逐渐减弱态势,市内出行(r=0.449,P=0.007)和交通网络(rs=0.321,P=0.049)对COVID-19的流行具有正相关性。重庆地区COVID-19疫情存在空间聚集性,高发聚集区域集中在渝东北片区,GIS较好地揭示了疫情聚集性变化过程和传播的时空趋势,市内出行和交通网络2个社会因素对重庆地区疫情影响较大。     

A Comprehensive Review of Animal Models for Coronaviruses: SARS-CoV-2, SARS-CoV,and MERS-CoV

The recent outbreak of coronavirus disease(COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has already affected a large population of the world. SARS-CoV-2 belongs to the same family of severe acute respiratory syndrome coronavirus(SARS-CoV) and Middle East respiratory syndrome coronavirus(MERSCoV). COVID-19 has a complex pathology involving severe acute respiratory infection, hyper-immune response, and coagulopathy. At present, there is no therapeutic drug or vaccine approved for the disease. There is an urgent need for an ideal animal model that can reflect clinical symptoms and underlying etiopathogenesis similar to COVID-19 patients which can be further used for evaluation of underlying mechanisms, potential vaccines, and therapeutic strategies. The current review provides a paramount insight into the available animal models of SARS-CoV-2, SARS-CoV, and MERS-CoV for the management of the diseases.     

miRNAs; a novel strategy for the treatment of COVID-19

Coronavirus disease 2019 (COVID-19) is the seventh member of the bat severe acute respiratory syndrome family. COVID-19 can fuse their envelopes with the host cell membranes and deliver their genetic material. COVID-19 attacks the respiratory system and stimulates the host inflammatory responses, enhances the recruitment of immune cells, and promotes angiotensin-converting enzyme 2 activities. Patients with confirmed COVID-19 may have experienced fever, dry cough, headache, dyspnea, acute kidney injury, acute respiratory distress syndrome, and acute heart injury. Several strategies such as oxygen therapy, ventilation, antibiotic or antiviral therapy, and renal replacement therapy are commonly used to decrease COVID-19-associated mortality. However, these approaches may not be good treatment options. Therefore, the search for an alternative-novel therapy is urgently important to prevent the disease progression. Recently, microRNAs (miRNAs) have emerged as a promising strategy for COVID-19. The design of oligonucleotide against the genetic material of COVID-19 might suppress virus RNA translation. Several previous studies have shown that host miRNAs play an antiviral role and improve the treatment of patients with COVID-19. miRNAs by binding to the 3′-untranslated region (UTR) or 5′-UTR of viral RNA play an important role in COVID-19-host interplay and viral replication. miRNAs interact with multiple pathways and reduce inflammatory biomarkers, thrombi formation, and tissue damage to accelerate the patient outcome. The information in this review provides a summary of the current clinical application of miRNAs for the treatments of patients with COVID-19.     

新型冠状病毒肺炎与牙周炎的潜在关联

新型冠状病毒肺炎(COVID-19)是目前全球面临的最紧迫的公共卫生问题之一。牙周炎是一种高发病率的慢性疾病,同时也是多种全身性疾病的诱因。最新研究表明COVID-19与心血管疾病、高血压、糖尿病、肥胖和慢性肾病等其他慢性疾病存在相关性。旨在基于严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的感染与牙周炎发生的主要致病机制探讨两者之间是否存在潜在关联。总结发现牙周炎与COVID-19发病率的上升没有直接关联,但是牙周炎能间接影响COVID-19预后。对两者关系的进一步了解,不仅可以预防牙周炎,还可以降低COVID-19不良预后的发生。本文为COVID-19合并牙周炎患者的治疗提供新型研究思路及理论参考。     

Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative

Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10^-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.     

Hyper-inflammatory responses in COVID-19 and anti-inflammatory therapeutic approaches

The coronavirus disease 2019 (COVID-19) is an ongoing global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe COVID-19 exhibit hyper-inflammatory responses characterized by excessive activation of myeloid cells, including monocytes, macrophages, and neutrophils, and a plethora of pro-inflammatory cytokines and chemokines. Accumulating evidence also indicates that hyper-inflammation is a driving factor for severe progression of the disease, which has prompted the development of anti-inflammatory therapies for the treatment of patients with COVID-19. Corticosteroids, IL-6R inhibitors, and JAK inhibitors have demonstrated promising results in treating patients with severe disease. In addition, diverse forms of exosomes that exert anti-inflammatory functions have been tested experimentally for the treatment of COVID-19. Here, we briefly describe the immunological mechanisms of the hyper-inflammatory responses in patients with severe COVID-19. We also summarize current anti-inflammatory therapies for the treatment of severe COVID-19 and novel exosome-based therapeutics that are in experimental stages.     

COVID-19: Pathogenesis,cytokine storm and therapeutic potential of interferons

The outbreak of the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) responsible for coronavirus disease 2019 (COVID-19) has developed into an unprecedented global pandemic. Clinical investigations in patients with COVID-19 has shown a strong upregulation of cytokine and interferon production in SARS-CoV2- induced pneumonia, with an associated cytokine storm syndrome. Thus, the identification of existing approved therapies with proven safety profiles to treat hyperinflammation is a critical unmet need in order to reduce COVI-19 associated mortality. To date, no specific therapeutic drugs or vaccines are available to treat COVID-19 patients. This review evaluates several options that have been proposed to control SARS-CoV2 hyperinflammation and cytokine storm, eincluding antiviral drugs, vaccines, small-molecules, monoclonal antibodies, oligonucleotides, peptides, and interferons (IFNs).     

A comprehensive perspective of traditional Arabic or Islamic medicinal plants as an adjuvant therapy against COVID-19

COVID-19 is a pulmonary disease caused by SARS-CoV-2. More than 200 million individuals are infected by this globally. Pyrexia, coughing, shortness of breath, headaches, diarrhoea, sore throats, and body aches are among the typical symptoms of COVID-19. The virus enters into the host body by interacting with the ACE2 receptor. Despite many SARS-CoV-2 vaccines manufactured by distinct strategies but any evidence-based particular medication to combat COVID-19 is not available yet. However, further research is required to determine the safety and effectiveness profile of the present therapeutic approaches. In this study, we provide a summary of Traditional Arabic or Islamic medicinal (TAIM) plants' historical use and their present role as adjuvant therapy for COVID-19. Herein, six medicinal plants Aloe barbadensis Miller, Olea europaea, Trigonella foenum-graecum, Nigella sativa, Cassia angustifolia, and Ficus carica have been studied based upon their pharmacological activities against viral infections. These plants include phytochemicals that have antiviral, immunomodulatory, antiasthmatic, antipyretic, and antitussive properties. These bioactive substances could be employed to control symptoms and enhance the development of a possible COVID-19 medicinal synthesis. To determine whether or if these TAIMs may be used as adjuvant therapy and are appropriate, a detailed evaluation is advised.     

Repercussions of the COVID-19 pandemic on athletes: a cross-sectional study

The COVID-19 pandemic has presented significant challenges and implications for the sports community. Thus, this study aimed to describe the prevalence of COVID-19 in Brazilian athletes and identify the epidemiological, clinical, athletic, life and health factors associated with the disease in these individuals. A cross-sectional study was performed involving 414 athletes from 22 different sports using an online questionnaire from August to November 2020. The association between the athletes’ characteristics and COVID-19 was evaluated using a logistic regression model. The prevalence of COVID-19 was 8.5%, although only 40% of athletes reported having been tested. Being under 27 years of age (3-fold), having children (~5-fold), having a teammate test positive for COVID-19 (2.5-fold), and smoking (14-fold) were associated with a possible higher risk of disease. Almost 20% of athletes self-reported musculoskeletal injuries during the period of the pandemic that was studied. Athletes with a university education (P = 0.02), a profession other than sports (P < 0.001), those from a low-income family (P = 0.01), and public health system users (P = 0.04) were significantly less frequently tested for COVID-19, whereas international competitors, athletes who received a wage, and athletes who had a teammate who tested positive for COVID-19 were 2-, 3-, and 15-fold more likely to be tested for COVID-19, respectively. Approximately 26% of the athletes who tested negative or were untested reported more than three characteristic COVID-19 symptoms, and 11% of athletes who tested positive for COVID-19 were asymptomatic. The identification of modifiable (have children, smoking, and teammates positively tested) and non-modifiable (age under 27 years) factors related to COVID-19 in athletes can contribute to implementing surveillance programmes to decrease the incidence of COVID-19 in athletes and its negative impacts in sports.     

Epidemiological,Clinical and Serological Characteristics of Children with Coronavirus Disease 2019 in Wuhan: A Single-centered,Retrospective Study

In December 2019, SARS-CoV-2 was first detected in the samples obtained from three adult patients who suffered from an unknown viral pneumonia in Wuhan (Li et al. 2020). This unknown viral pneumonia is further named as coronavirus disease 2019 (COVID-19) by the World Health Organization. To date, the number of new COVID-19 cases has continued to skyrocket and the impact of SARS-CoV-2 on humans is far greater than any pathogen of this century in both breadth and depth. Previous studies have shown that adults with COVID-19 have symptoms of fever, dry cough, dyspnea, fatigue and lymphocytopenia. Moreover, COVID-19 is more likely to cause death in the elderly, especially those with chronic comorbidities (Huang et al. 2020). In Wuhan, more than 50, 000 COVID-19 cases have been confirmed, including over 780 pediatric patients, and only one child death case (Lu et al. 2020). Although the number of children cases was far fewer than that of adults, COVID-19 might endanger children's health and the information on children remains limited, especially in serological study. In the retrospective study, the investigators analyzed the epidemiological, clinical and serological characteristics of children with COVID-19 in Wuhan in the early stages of the outbreak, which might provide theoretical and practical help in controlling COVID-19 and similar emerging infectious diseases in the future.     

COVID-19 Pandemic: Insights into Interactions between SARS-CoV-2 Infection and MAFLD

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become an ongoing global health pandemic. Since 2019, the pandemic continues to cast a long shadow on all aspects of our lives, bringing huge health and economic burdens to all societies. With our in-depth understanding of COVID-19, from the initial respiratory tract to the later gastrointestinal tract and cardiovascular systems, the multiorgan involvement of this infectious disease has been discovered. Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly named nonalcoholic fatty liver disease (NAFLD), is a major health issue closely related to metabolic dysfunctions, affecting a quarter of the world''s adult population. The association of COVID-19 with MAFLD has received increasing attention, as MAFLD is a potential risk factor for SARS-CoV-2 infection and severe COVID-19 symptoms. In this review, we provide an update on the interactions between COVID-19 and MAFLD and its underlying mechanisms.     

Molecular Perspectives of SARS-CoV-2: Pathology,Immune Evasion,and Therapeutic Interventions

The outbreak of coronavirus disease 2019 (COVID-19) has not only affected human health but also diverted the focus of research and derailed the world economy over the past year. Recently, vaccination against COVID-19 has begun, but further studies on effective therapeutic agents are still needed. The severity of COVID-19 is attributable to several factors such as the dysfunctional host immune response manifested by uncontrolled viral replication, type I interferon suppression, and release of impaired cytokines by the infected resident and recruited cells. Due to the evolving pathophysiology and direct involvement of the host immune system in COVID-19, the use of immune-modulating drugs is still challenging. For the use of immune-modulating drugs in severe COVID-19, it is important to balance the fight between the aggravated immune system and suppression of immune defense against the virus that causes secondary infection. In addition, the interplaying events that occur during virus–host interactions, such as activation of the host immune system, immune evasion mechanism of the virus, and manifestation of different stages of COVID-19, are disjunctive and require thorough streamlining. This review provides an update on the immunotherapeutic interventions implemented to combat COVID-19 along with the understanding of molecular aspects of the immune evasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may provide opportunities to develop more effective and promising therapeutics.     

An analytical study of the factors that influence COVID-19 spread

The outbreak of the coronavirus disease 2019 (COVID-19) continues to constitute an international public health emergency. Seasonality is a long-recognized attribute of many viral infections of humans. Nevertheless, the relationship between environmental factors and the spread of infection, particularly for person-to-person communicable diseases, remains poorly understood. This study explores the relationship between environmental factors and the incidence of COVID-19 in 188 countries with reported COVID-19 cases as of April 13, 2020. Here we show that COVID-19 growth rates peaked in temperate zones in the Northern Hemisphere during the outbreak period, while they were lower in tropical zones. The relationships between COVID-19 and environmental factors were resistant to the potentially confounding effects of air pollution, sea level, and population. To prove the effect of those factors, study, and analysis of the prevalence of COVID-19 in Italy, Spain, and China was undertaken. A fuzzy logic system was designed to predict the effects of that variables on the rate of viral spread of COVID-19.     

Functional consequences of SARS-CoV-2 infection in pregnant women,fetoplacental unit,and neonate

The SARS-CoV-2 infection causes COVID-19 disease, characterized by acute respiratory distress syndrome, bilateral pneumonia, and organ failure. The consequences of maternal SARS-CoV-2 infection for the pregnant woman, fetus, and neonate are controversial. Thus, it is required to determine whether there is viral and non-viral vertical transmission in COVID-19. The disease caused by SARS-CoV-2 leads to functional alterations in asymptomatic and symptomatic pregnant women, the fetoplacental unit and the neonate. Several diseases of pregnancy, including COVID-19, affect the fetoplacental function, which causes in utero programming for young and adult diseases. A generalized inflammatory state and a higher risk of infection are seen in pregnant women with COVID-19. Obesity, diabetes mellitus, and hypertension may increase the vulnerability of pregnant women to infection by SARS-CoV-2. Alpha, Delta, and Omicron variants of SARS-CoV-2 show specific mutations that seem to increase the capacity of the virus to infect the pregnant woman, likely due to increasing its interaction via the virus S protein and angiotensin-converting enzyme 2 receptors. This review shows the literature addressing to what extent COVID-19 in pregnancy affects the pregnant woman, fetoplacental unit, and neonate. Prospective studies that are key in managing SARS-CoV-2 infection in pregnancy are discussed.     

S100A8/A9 in COVID-19 pathogenesis: Impact on clinical outcomes

Coronavirus disease 2019 (COVID-19) has a broad range of clinical manifestations, highlighting the need for specific diagnostic tools to predict disease severity and improve patient prognosis. Recently, calprotectin (S100A8/A9) has been proposed as a potential biomarker for COVID-19, as elevated serum S100A8/A9 levels are associated with critical COVID-19 cases and can distinguish between mild and severe disease states. S100A8/A9 is an alarmin that mediates host proinflammatory responses during infection and it has been postulated that S100A8/A9 modulates the cytokine storm; the hallmark of fatal COVID-19 cases. However, it has yet to be determined if S100A8/A9 is a bona-fide biomarker for COVID-19. S100A8/A9 is widely implicated in a variety of inflammatory conditions, such as cystic fibrosis (CF) and chronic obstructive pulmonary disorder (COPD), as well as pulmonary infectious diseases, including tuberculosis and influenza. Therefore, understanding how S100A8/A9 levels correlate with immune responses during inflammatory diseases is necessary to evaluate its candidacy as a potential COVID-19 biomarker. This review will outline the protective and detrimental roles of S100A8/A9 during infection, summarize the recent findings detailing the contributions of S100A8/A9 to COVID-19 pathogenesis, and highlight its potential as diagnostic biomarker and a therapeutic target for pulmonary infectious diseases, including COVID-19.