Application of extracorporeal therapies in critically ill COVID-19 patients

The coronavirus disease 2019 (COVID-19) pandemic is a major public health event caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has spread widely all over the world. A high proportion of patients become severely or critically ill, and suffer high mortality due to respiratory failure and multiple organ dysfunction. Therefore, providing timely and effective treatment for critically ill patients is essential to reduce overall mortality. Convalescent plasma therapy and pharmacological treatments, such as aerosol inhalation of interferon-α (IFN-α), corticosteroids, and tocilizumab, have all been applied in clinical practice; however, their effects remain controversial. Recent studies have shown that extracorporeal therapies might have a potential role in treating critically ill COVID-19 patients. In this review, we examine the application of continuous renal replacement therapy (CRRT), therapeutic plasma exchange (TPE), hemoadsorption (HA), extracorporeal membrane oxygenation (ECMO), and extracorporeal carbon dioxide removal (ECCO₂R) in critically ill COVID-19 patients to provide support for the further diagnosis and treatment of COVID-19.

     

Structural and physiological changes of the human body upon SARS-CoV-2 infection

Since December 2019, the novel coronavirus(severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)) has spread to many countries around the world, developing into a global pandemic with increasing numbers of deaths reported worldwide. To data, although some vaccines have been developed, there are no ideal drugs to treat novel coronavirus pneumonia(coronavirus disease 2019(COVID-19)). By examining the structure of the coronavirus and briefly describing its possible pathogenesis based on recent autopsy reports conducted by various teams worldwide, this review analyzes the possible structural and functional changes of the human body upon infection with SARS-CoV-2. We observed that the most prominent pathological changes in COVID-19 patients are diffuse alveolar damage(DAD) of the lungs and microthrombus formation,resulting in an imbalance of the ventilation/perfusion ratio and respiratory failure. Although direct evidence of viral infection can also be found in other organs and tissues, the viral load is relatively small. The conclusion that the injuries of the extrapulmonary organs are directly caused by the virus needs further investigation.     

Molecular hydrogen is a promising therapeutic agent for pulmonary disease

Molecular hydrogen exerts biological effects on nearly all organs. It has anti-oxidative, anti-inflammatory, and anti-aging effects and contributes to the regulation of autophagy and cell death. As the primary organ for gas exchange, the lungs are constantly exposed to various harmful environmental irritants. Short- or long-term exposure to these harmful substances often results in lung injury, causing respiratory and lung diseases. Acute and chronic respiratory diseases have high rates of morbidity and mortality and have become a major public health concern worldwide. For example, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. An increasing number of studies have revealed that hydrogen may protect the lungs from diverse diseases, including acute lung injury, chronic obstructive pulmonary disease, asthma, lung cancer, pulmonary arterial hypertension, and pulmonary fibrosis. In this review, we highlight the multiple functions of hydrogen and the mechanisms underlying its protective effects in various lung diseases, with a focus on its roles in disease pathogenesis and clinical significance.     

Seasonal coronaviruses and SARS-CoV-2: effects of preexisting immunity during the COVID-19 pandemic

Although the coronavirus disease 2019 (COVID-19) epidemic is still ongoing, vaccination rates are rising slowly and related treatments and drugs are being developed. At the same time, there is increasing evidence of preexisting immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans, mainly consisting of preexisting antibodies and immune cells (including T cells and B cells). The presence of these antibodies is mainly due to the seasonal prevalence of four common coronavirus types, especially OC43 and HKU1. The accumulated relevant evidence has suggested that the target of antibodies is mainly the S2 subunit of S protein, followed by evolutionary conservative regions such as the nucleocapsid (N) protein. Additionally, preexisting memory T and B cells are also present in the population. Preexisting antibodies can help the body protect against SARS-CoV-2 infection, reduce the severity of COVID-19, and rapidly increase the immune response post-infection. These multiple effects can directly affect disease progression and even the likelihood of death in certain individuals. Besides the positive effects, preexisting immunity may also have negative consequences, such as antibody-dependent enhancement (ADE) and original antigenic sin (OAS), the prevalence of which needs to be further established. In the future, more research should be focused on evaluating the role of preexisting immunity in COVID-19 outcomes, adopting appropriate policies and strategies for fighting the pandemic, and vaccine development that considers preexisting immunity.     

Science knowledge and trust in medicine affect individuals’ behavior in pandemic crises

In pandemic crises such as the COVID-19 pandemic, individuals’ behavior has a strong impact on epidemiological processes. Compliance with prevention guidelines, such as social distancing, is critical to avoid further spreading an infectious disease or to slow down its spread. However, some individuals also or instead engage in panic behavior, such as hoarding. We investigate how education prepares individuals to respond adequately by modelling the path from seeking information about COVID-19 to eventual behavior. Based on a sample of N = 1182 adult Americans, gathered at the pandemic’s onset (March 2020), we conclude that science knowledge helps individuals convert information into coronavirus knowledge. This knowledge then helps individuals avoid panic behavior. Individuals lacking coronavirus knowledge and science knowledge still comply with prevention guidelines when they have a general trust in medicine. Individuals lacking knowledge still follow prevention guidelines when they trust in medicine. Facilitating science knowledge and trust in science through education and targeted public health messaging are likely to be of fundamental importance for bringing crises such as the COVID-19 pandemic under control.

     

Factors associated with a SARS-CoV-2 recurrence after hospital discharge among patients with COVID-19: systematic review and meta-analysis

Background: The proportion of recurrences after discharge among patients with coronavirus disease 2019 (COVID-19) was reported to be between 9.1% and 31.0%. Little is known about this issue, however, so we performed a meta-analysis to summarize the demographical, clinical, and laboratorial characteristics of non-recurrence and recurrence groups. Methods: Comprehensive searches were conducted using eight electronic databases. Data regarding the demographic, clinical, and laboratorial characteristics of both recurrence and non-recurrence groups were extracted, and quantitative and qualitative analyses were conducted. Results: Ten studies involving 2071 COVID-19 cases were included in this analysis. The proportion of recurrence cases involving patients with COVID-19 was 17.65% (between 12.38% and 25.16%) while older patients were more likely to experience recurrence (weighted mean difference (WMD)=1.67, range between 0.08 and 3.26). The time from discharge to recurrence was 13.38 d (between 12.08 and 14.69 d). Patients were categorized as having moderate severity (odds ratio (OR)=2.69, range between 1.30 and 5.58), while those with clinical symptoms including cough (OR=5.52, range between 3.18 and 9.60), sputum production (OR=5.10, range between 2.60 and 9.97), headache (OR=3.57, range between 1.36 and 9.35), and dizziness (OR=3.17, range between 1.12 and 8.96) were more likely to be associated with recurrence. Patients presenting with bilateral pulmonary infiltration and decreased leucocyte, platelet, and CD4⁺ T counts were at risk of COVID-19 recurrence (OR=1.71, range between 1.07 and 2.75; WMD=−1.06, range between −1.55 and −0.57, WMD=−40.39, range between −80.20 and −0.48, and WMD=−55.26, range between −105.92 and −4.60, respectively). Conclusions: The main factors associated with the recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after hospital discharge were older age, moderate severity, bilateral pulmonary infiltration, laboratory findings including decreased leucocytes, platelets, and CD4⁺ T counts, and clinical symptoms including cough, sputum production, headache, and dizziness. These factors can be considered warning indicators for the recurrence of SARS-CoV-2 and might help the development of specific management strategies.     

Clinical characteristics and plasma antibody titer of patients with COVID-19 in Zhejiang,China

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first affected humans in China on December 31, 2019 (Shi et al., 2020). Coronaviruses generally cause mild, self-limiting upper respiratory tract infections in humans, such as the common cold, pneumonia, and gastroenteritis (To et al., 2013; Berry et al., 2015; Chan et al., 2015). According to the Report of the World Health Organization (WHO)-China Joint Mission on COVID-19 (WHO, 2020), the case fatality rate of COVID-19 increases with age, while the rate among males is higher than that among females (4.7% and 2.8%, respectively). Since an effective vaccine and specific anti-viral drugs are still under development, passive immunization using the convalescent plasma (CP) of recovered COVID-19 donors may offer a suitable therapeutic strategy for severely ill patients in the meantime. So far, several studies have shown therapeutic efficacy of CP transfusion in treating COVID-19 cases. A pilot study first reported that transfusion of CP with neutralizing antibody titers above 1:640 was well tolerated and could potentially improve clinical outcomes through neutralizing viremia in severe COVID-19 cases (Chen et al., 2020). Immunoglobulin G (IgG) and IgM are the most abundant and important antibodies in protecting the human body from viral attack (Arabi et al., 2015; Marano et al., 2016). Our study aimed to understand the aspects of plasma antibody titer levels in convalescent patients, as well as assessing the clinical characteristics of normal, severely ill, and critically ill patients, and thus provide a basis for guiding CP therapy. We also hoped to find indicators which could serve as a reference in predicting the progression of the disease.     

Comparison of COVID-19 and influenza characteristics

The emergence of coronavirus disease 2019(COVID-19) not only poses a serious threat to the health of people worldwide but also affects the global economy. The outbreak of COVID-19 began in December 2019, at the same time as the influenza season. However, as the treatments and prognoses of COVID-19 and influenza are different, it is important to accurately differentiate these two different respiratory tract infections on the basis of their respective early-stage characteristics. We reviewed official documents and news released by the National Health Commission of the People's Republic of China, the Chinese Center for Disease Control and Prevention(China CDC), the United States CDC, and the World Health Organization(WHO), and we also searched the PubMed, Web of Science, Excerpta Medica database(Embase), China National Knowledge Infrastructure(CNKI), Wanfang, preprinted bioRxiv and medRxiv databases for documents and guidelines from earliest available date up until October 3 rd, 2020. We obtained the latest information about COVID-19 and influenza and summarized and compared their biological characteristics, epidemiology, clinical manifestations, pathological mechanisms, treatments, and prognostic factors. We show that although COVID-19 and influenza are different in many ways, there are numerous similarities;thus, in addition to using nucleic acid-based polymerase chain reaction(PCR) and antibody-based approaches, clinicians and epidemiologists should distinguish between the two using their respective characteristics in early stages. We should utilize experiences from other epidemics to provide additional guidance for the treatment and prevention of COVID-19.     

Development and validation of an individualized nomogram for early prediction of the duration of SARS-CoV-2 shedding in COVID-19 patients with non-severe disease

With the number of cases of coronavirus disease-2019(COVID-19) increasing rapidly, the World Health Organization(WHO) has recommended that patients with mild or moderate symptoms could be released from quarantine without nucleic acid retesting, and self-isolate in the community. This may pose a potential virus transmission risk. We aimed to develop a nomogram to predict the duration of viral shedding for individual COVID-19 patients. This retrospective multicentric study enrolled 135 patients as a training cohort and 102 patients as a validation cohort. Significant factors associated with the duration of viral shedding were identified by multivariate Cox modeling in the training cohort and combined to develop a nomogram to predict the probability of viral shedding at 9, 13, 17, and 21 d after admission. The nomogram was validated in the validation cohort and evaluated by concordance index(C-index), area under the curve(AUC), and calibration curve. A higher absolute lymphocyte count(P=0.001) and lymphocyte-to-monocyte ratio(P=0.013) were correlated with a shorter duration of viral shedding, while a longer activated partial thromboplastin time(P=0.007) prolonged the viral shedding duration. The C-indices of the nomogram were 0.732(95% confidence interval(CI): 0.685-0.777) in the training cohort and 0.703(95% CI: 0.642-0.764) in the validation cohort. The AUC showed a good discriminative ability(training cohort: 0.879, 0.762, 0.738, and 0.715 for 9, 13, 17, and 21 d; validation cohort: 0.855, 0.758, 0.728, and 0.706 for 9, 13, 17, and 21 d), and calibration curves were consistent between outcomes and predictions in both cohorts. A predictive nomogram for viral shedding duration based on three easily accessible factors was developed to help estimate appropriate self-isolation time for patients with mild or moderate symptoms, and to control virus transmission.     

Analysis of an improved workflow of endoscope reprocessing for bedside endoscopic diagnosis and treatment on COVID-19 patients

Journal of Zhejiang University-SCIENCE B - Severe cases infected with the coronavirus disease 2019 (COVID-19), named by the World Health Organization (WHO) on Feb. 11, 2020, tend to present a...     

Tracking public opinion about online education over COVID-19 in China

Educational technology research and development - Due to the novel coronavirus disease (COVID-19) outbreak in China, a large number of Chinese students resorted to online learning resources. The...     

ADP-ribosylhydrolases: from DNA damage repair to COVID-19

Adenosine diphosphate(ADP)-ribosylation is a unique post-translational modification that regulates many biological processes,such as DNA damage repair.During DNA repair,ADP-ribosylation needs to be reversed by ADP-ribosylhydrolases.A group of ADP-ribosylhydrolases have a catalytic domain,namely the macrodomain,which is conserved in evolution from prokaryotes to humans.Not all macrodomains remove ADP-ribosylation.One set of macrodomains loses enzymatic activity and only binds to ADP-ribose(ADPR).Here,we summarize the biological functions of these macrodomains in DNA damage repair and compare the structure of enzymatically active and inactive macrodomains.Moreover,small molecular inhibitors have been developed that target macrodomains to suppress DNA damage repair and tumor growth.Macrodomain proteins are also expressed in pathogens,such as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).However,these domains may not be directly involved in DNA damage repair in the hosts or pathogens.Instead,they play key roles in pathogen replication.Thus,by targeting macrodomains it may be possible to treat pathogen-induced diseases,such as coronavirus disease 2019(COVID-19).     

Influence of Public Engagement with Science on Scientific Information Literacy During the COVID‑19 Pandemic

Science & Education - During the COVID-19 pandemic, we are fighting not only the novel coronavirus, but also the “infodemic” induced by the pandemic. Therefore, it is urgent to...     

Preschoolers’ Approaches to Learning and Family-school Connections During COVID-19: An Empirical Study Based on a Wuhan Sample

The concept, approaches to learning (ATL), is an important dimension of children’s school readiness, which reflects children’s enthusiasm and engagement in learning settings. Due to coronavirus disease 2019 (COVID-19), when preschools were shut down for months and children’s social interactions were greatly limited, preschoolers’ ATL might be negatively affected. However, strengthened family-school connections might have the potential to reduce the adverse effects of the pandemic. Based on a sample of 340 preschoolers from 30 classes of 6 preschools in Wuhan, China, we explored the association between family-preschool connections and preschoolers’ ATL scores. The findings showed that the preschoolers’ ATL were statistically and positively associated with parental attendance at the online parent-teacher meetings initiated by the preschools (standardized coefficient?=?0.15). Policy implications regarding the enhancement of family-preschool connections are discussed.

     

Stress,Anxiety, and Depression Among Undergraduate Students during the COVID-19 Pandemic and their Use of Mental Health Services

Innovative Higher Education - The coronavirus 2019 (COVID-19) has brought significant changes to college students, but there is a lack of empirical studies regarding how the pandemic has affected...     

普通型2019冠状病毒病的临床特征和HRCT表现

目的探讨普通型2019冠状病毒病(COVID-19)患者的临床表现与高分辨率CT(HRCT)的影像特征。方法回顾性分析我院收治的25例COVID-19确诊患者的临床资料及胸部CT检查,进一步分析其临床特征、实验室指标及HRCT影像学特征。结果我院收治的25例COVID-19患者均为普通型,发热(19/25,76%),干咳(18/25,72%);所有患者白细胞计数均正常,淋巴细胞计数不同程度减少(15/25,60%),血沉增快(12/25,48%),C反应蛋白升高(10/25,40%),出现降钙素原降低(2/25,8%);平均住院日为19.8±3.9天,从出现临床症状到CT检查阳性平均时间为4.9±2.7天。首次胸部HRCT病灶分布为单侧9例(36%,左肺4/25,16%;右肺5/25,20%),双侧16例(64%);20例(80%)病灶分布位于周边,5例(20%)位于周边为主及中心同时受累。HRCT表现中单纯磨玻璃影(GGO)为25例(100%),GGO伴局灶性实变为5例(20%),4例(16%)伴片状实变影。在第二次HRCT检查中,大部分患者病灶增多、范围变广,局部病灶融合,并见支气管充气征。结论普通型COVID-19患者临床表现相对较轻,HRCT是其诊断和评估的重要手段。     

抗击COVID-19疫情一线护士压力知觉现状调查及分析

目的了解参加抗击新型冠状病毒肺炎疫情临床一线护士的压力知觉现状,并分析其影响因素,为制定缓解疫情抗击一线护士压力感知相关措施提供理论依据。方法采用中文版压力知觉量表(CPSS)、领悟社会支持量表(PSSS)对盐城市区参加支援湖北COVID-19疫情抗击的95名一线护士进行问卷调查,并对现状进行分析。结果95名参与COVID-19疫情抗击的临床一线护士CPSS总分为(38.11±6.88)分,PSSS总分为(38.11±6.88)分,压力感知与社会支持呈负相关(r=-0.462)。多元回归分析显示,性别、是否独生子女、社会支持水平是影响疫情抗击一线护士压力感知的主要因素。结论COVID-19疫情抗击一线护士压力知觉得分总体较高,压力较大,医疗机构管理者应采取适当的激励制度等积极有效措施,缓解其压力,改善其身心健康。     

CRISPR/Cas: a Nobel Prize award-winning precise genome editing technology for gene therapy and crop improvement

Since it was first recognized in bacteria and archaea as a mechanism for innate viral immunity in the early 2010 s,clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein(Cas) has rapidly been developed into a robust, multifunctional genome editing tool with many uses. Following the discovery of the initial CRISPR/Cas-based system, the technology has been advanced to facilitate a multitude of different functions. These include development as a base editor, prime editor, epigenetic editor, and CRISPR interference(CRISPRi) and CRISPR activator(CRISPRa) gene regulators. It can also be used for chromatin and RNA targeting and imaging. Its applications have proved revolutionary across numerous biological fields, especially in biomedical and agricultural improvement. As a diagnostic tool, CRISPR has been developed to aid the detection and screening of both human and plant diseases, and has even been applied during the current coronavirus disease 2019(COVID-19) pandemic. CRISPR/Cas is also being trialed as a new form of gene therapy for treating various human diseases, including cancers, and has aided drug development. In terms of agricultural breeding, precise targeting of biological pathways via CRISPR/Cas has been key to regulating molecular biosynthesis and allowing modification of proteins, starch, oil, and other functional components for crop improvement. Adding to this, CRISPR/Cas has been shown capable of significantly enhancing both plant tolerance to environmental stresses and overall crop yield via the targeting of various agronomically important gene regulators. Looking to the future, increasing the efficiency and precision of CRISPR/Cas delivery systems and limiting off-target activity are two major challenges for wider application of the technology. This review provides an in-depth overview of current CRISPR development, including the advantages and disadvantages of the technology,recent applications, and future considerations.