Summary

Background

     Important insights into the early pathogenesis of Alzheimer’s disease can be provided by studies of autosomal dominant Alzheimer’s disease and Down syndrome. However, it is unclear whether the timing and spatial distribution of amyloid accumulation differs between people with autosomal dominant Alzheimer’s disease and those with Down syndrome. We aimed to directly compare amyloid changes between these two groups of people.

Methods

     In this cross-sectional study, we included participants (aged ≥25 years) with Down syndrome and sibling controls who had MRI and amyloid PET scans in the first data release (January, 2020) of the Alzheimer’s Biomarker Consortium-Down Syndrome (ABC-DS) study. We also included carriers of autosomal dominant Alzheimer’s disease genetic mutations and non-carrier familial controls who were within a similar age range to ABC-DS participants (25–73 years) and had MRI and amyloid PET scans at the time of a data freeze (December, 2020) of the Dominantly Inherited Alzheimer Network (DIAN) study. Controls from the two studies were combined into a single group. All DIAN study participants had genetic testing to determine PSEN1, PSEN2, or APP mutation status. APOE genotype was determined from blood samples. CSF samples were collected in a subset of ABC-DS and DIAN participants and the ratio of amyloid β42 (Aβ42) to Aβ40 (Aβ42/40) was measured to evaluate its Spearman’s correlation with amyloid PET. Global PET amyloid burden was compared with regards to cognitive status, APOE ɛ4 status, sex, age, and estimated years to symptom onset. We further analysed amyloid PET deposition by autosomal dominant mutation type. We also assessed regional patterns of amyloid accumulation by estimated number of years to symptom onset. Within a subset of participants the relationship between amyloid PET and CSF Aβ42/40 was evaluated.

Findings

     192 individuals with Down syndrome and 33 sibling controls from the ABC-DS study and 265 carriers of autosomal dominant Alzheimer’s disease mutations and 169 non-carrier familial controls from the DIAN study were included in our analyses. PET amyloid centiloid and CSF Aβ42/40 were negatively correlated in carriers of autosomal dominant Alzheimer’s disease mutations (n=216; r=–0·565; p<0·0001) and in people with Down syndrome (n=32; r=–0·801; p<0·0001). There was no difference in global PET amyloid burden between asymptomatic people with Down syndrome (mean 18·80 centiloids [SD 28·33]) versus asymptomatic mutation carriers (24·61 centiloids [30·27]; p=0·11) and between symptomatic people with Down syndrome (77·25 centiloids [41·76]) versus symptomatic mutation carriers (69·15 centiloids [51·10]; p=0·34). APOE ɛ4 status and sex had no effect on global amyloid PET deposition. Amyloid deposition was elevated significantly earlier in mutation carriers than in participants with Down syndrome (estimated years to symptom onset –23·0 vs –17·5; p=0·0002). PSEN1 mutations primarily drove this difference. Early amyloid accumulation occurred in striatal and cortical regions for both mutation carriers (n=265) and people with Down syndrome (n=128). Although mutation carriers had widespread amyloid accumulation in all cortical regions, the medial occipital regions were spared in people with Down syndrome.

Interpretation

     Despite minor differences, amyloid PET changes were similar between people with autosomal dominant Alzheimer’s disease versus Down syndrome and strongly supported early amyloid dysregulation in individuals with Down syndrome. Individuals with Down syndrome aged at least 35 years might benefit from early intervention and warrant future inclusion in clinical trials, particularly given the relatively high incidence of Down syndrome.

Funding

     The National Institute on Aging, Riney and Brennan Funds, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the German Center for Neurodegenerative Diseases, and the Japan Agency for Medical Research and Development.

Introduction

     Down syndrome, caused by full or partial triplication of chromosome 21, is one of the most common genetic disorders, with approximately one in 700 children born with Down syndrome in the USA each year.1 Due to this triplication, individuals with Down syndrome have an extra copy of the APP gene and overproduce amyloid β (Aβ). Consequently, almost all adults with Down syndrome develop amyloid plaques and tau neurofibrillary tangles, which are the hallmarks of Alzheimer’s disease.2 Given this fact and the substantial increase in life expectancy in people with Down syndrome, there is a growing population of adults with Down syndrome developing Alzheimer’s disease.1,3

     Previous studies have used cognition, fluid biomarker, and imaging measures to understand the presentation and progression of Alzheimer’s disease in individuals with Down syndrome.3–6 The cognitive symptoms of Alzheimer’s disease develop at approximately 50–55 yearsof-age in people with Down syndrome, with CSF markers changing years before the onset of these symptoms.3–5 PET imaging studies have also identified amyloid accumulation in cortical and subcortical brain regions years before the presentation of clinical symptoms.6 However, questions remain regarding the nature of amyloid deposition in individuals with Down syndrome versus individuals with other forms of Alzheimer’s disease, particularly autosomal dominant Alzheimer’s disease.

Results

     192 individuals with Down syndrome and 33 sibling controls from the ABC-DS study and 265 carriers of autosomal dominant Alzheimer’s disease mutations and 169 non-carrier familial controls from the DIAN study were included in our analyses. Controls from the two studies were combined into a single group. For the autosomal dominant mutation types present in people included in our study, see appendix (pp 8–9). Participant characteristics for each group are shown in the table. Groups did not differ by age or APOE ε4-positivity status. There were fewer women in the Down syndrome group (44%) compared with the control (61%) and mutation carrier (53%) groups. Compared with carriers of autosomal dominant Alzheimer’s disease mutations, a smaller proportion of individuals with Down syndrome identified as non-White (p=0∙031), although most people in our analysis identified as White. A higher proportion of mutation carriers (38%) than people with Down syndrome (15%) were categorised as symptomatic (p<0∙0001). Of the 101 symptomatic mutation carriers, 57 (56%) had very mild dementia (CDR 0∙5), 27 (27%) had mild dementia (CDR 1), and 17 (17%) had moderate or severe dementia (CDR 2–3). Of the 28 symptomatic participants with Down syndrome, 16 (57%) had mild cognitive impairment and 12 (43%) had dementia due to Alzheimer’s disease.

Abstract

Objective

     To characterize distinct comorbidities, outcomes, and treatment patterns in children with Down syndrome and pulmonary hypertension in a large, multicenter pediatric pulmonary hypertension registry.

Study design

     We analyzed data from the Pediatric Pulmonary Hypertension Network (PPHNet) Registry, comparing demographic and clinical characteristics of children with Down syndrome and children without Down syndrome. We examined factors associated with pulmonary hypertension resolution and a composite outcome of pulmonary hypertension severity in the cohort with Down syndrome.

Results

     Of 1475 pediatric patients with pulmonary hypertension, 158 (11%) had Down syndrome. The median age at diagnosis of pulmonary hypertension in patients with Down syndrome was 0.49 year (IQR, 0.21-1.77 years), similar to that in patients without Down syndrome. There was no difference in rates of cardiac catheterization and prescribed pulmonary hypertension medications in children with Down syndrome and those without Down syndrome. Comorbidities in Down syndrome included congenital heart disease (95%; repaired in 68%), sleep apnea (56%), prematurity (49%), recurrent respiratory exacerbations (35%), gastroesophageal reflux (38%), and aspiration (31%). Pulmonary hypertension resolved in 43% after 3 years, associated with a diagnosis of pulmonary hypertension at age <6 months (54% vs 29%; P = .002) and a pretricuspid shunt (65% vs 38%; P = .02). Five-year transplantation-free survival was 88% (95% CI, 80%-97%). Tracheostomy (hazard ratio [HR], 3.29; 95% CI, 1.61-6.69) and reflux medication use (HR, 2.08; 95% CI, 1.11-3.90) were independently associated with a composite outcome of severe pulmonary hypertension.

Conclusions

     Despite high rates of cardiac and respiratory comorbidities that influence the severity of pulmonary hypertension, children with Down syndrome–associated pulmonary hypertension generally have a survival rate similar to that of children with non–Down syndrome–associated pulmonary hypertension. Resolution of pulmonary hypertension is common but reduced in children with complicated respiratory comorbidities.

Methods

     The PPHNet registry includes comprehensive clinical data from 8 centers in the US and Canada that enrolled patients between October 2014 and February 2018 and includes follow-up data submitted through May 18, 2020.20 The PPHNet registry was supported in part by a National Heart, Lung, and Blood Institute–funded U01 program (U01 HL12118; Data Fusion: A Sustainable, Open Source Registry Advancing Pediatric Pulmonary Vascular Disease Research; S.A. and K.M., principal investigators). The study protocol was approved by the Institutional Review Board of each participating center. Parents and/or guardians provided signed informed consent, and participants gave assent when appropriate, according to institutional guidelines.

Results

     Of the 1475 children enrolled in the PPHNet Registry, 158 (10.7%) were identified as subjects with Down syndrome.20 There was a slight preponderance of males in the Down syndrome group (53.8%). The proportion of patients with pulmonary hypertension with Down syndrome differed by study site, ranging from 6% to 22%. Compared with the non-Down syndrome cohort, patients with Down syndrome were less likely to be White and more likely to be Asian (P < .001). There were 12 deaths and no lung transplants in the Down syndrome cohort, which was followed for a median of 2.9 years. There was no difference in the proportion of patients with death/transplant for the Down syndrome and non-Down syndrome cohorts (Table I).

     The distribution of the primary WSPH classification of pulmonary hypertension differed between the Down syndrome and non-Down syndrome cohorts (P < .001). The Down syndrome cohort was more commonly group 1 (pulmonary arterial hypertension) compared with the non-Down syndrome cohort (69.6% vs 37.3%), and group 3 pulmonary hypertension (related to lung disease) was more common in the nonDown syndrome group (52.2% vs 20.9%) (Table I). Of the 110 patients with Down syndrome categorized as having group 1 pulmonary hypertension (pulmonary arterial hypertension), 109 were further classified: 103 (94.5%) with pulmonary arterial hypertension associated with CHD, 5 (4.6%) with idiopathic pulmonary arterial hypertension, and 1 (0.9%) with pulmonary arterial hypertension induced by drugs and toxins. Relatively few patients were classified as group 10 (pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis), group 100 (PPHN), and group 2 pulmonary hypertension (related to left heart disease), and prevalence was similar in children with Down syndrome and those without Down syndrome. No patients were classified as having chronic thromboembolic pulmonary hypertension (group 4). Group 5 (multifactorial) pulmonary hypertension was uncommon across the registry (Table I).

 Highlights

Abstract

Keywords

1. Introduction

2. Materials and methods

3. Results

4. Discussion

5. Conclusion

Financial support and sponsorship

Declaration of Competing interest

Appendix A. Lifestyle related behaviour questionnaire

Appendix B. Scoring instructions for the questionnaire to assess impact of COVID 19 on individual’s lifestyle-related behaviour

References

Abstract

Background and aims
The lasting impact of COVID 19 pandemic and associated restrictions are bound to be significant on lifestyle-related behaviour including diet, physical activity and sleep which is one of the important components in the management of diabetes mellitus and metabolic syndrome. This study was conducted to develop and validate a questionnaire to assess changes in individual’s lifestyle-related behaviour during COVID 19 pandemic.

Materials and methods
The questionnaire was developed through a standardised methodology including literature review, focus group discussion, expert evaluation, pre-testing and validation. The face validity and content validity of the questionnaire were analysed. A cross-sectional survey was carried out on 103 participants to validate the questionnaire that used a 5-point Likert scale for the response option. Exploratory factor analysis was performed to establish construct validity. Cronbach’s alpha was calculated to test the internal consistency of the whole questionnaire.

Results
A questionnaire with 20 items to assess the lifestyle-related behaviour of people was developed. The questionnaire shows a satisfactory validity and a good internal consistency with the Cronbach’s alpha value of 0.72.

Conclusion
The developed tool is valid and reliable to assess the changes in lifestyle-related behaviour of individuals during COVID 19 pandemic.

1. Introduction
COVID pandemic has led to life-changing challenges among people across the globe. Terms like “social distancing” and “selfisolation” have become a reality. As people are trying to get accustomed with this, the confinement has drastically impacted citizens’ lives bringing about a sudden and radical change in their daily routine and lifestyle [1].
Social isolation for extended periods can lead to boredom and stress which may further subject individuals to develop a greater tendency of overeating especially “comfort foods” which are usually high in calories [2,3]. Moreover, prolonged confinement at home may induce an increased screen time and reduced outdoor time thus, augmenting sedentarism [4]. Apart from this, being homebound and facing disruptions in daily routines may affect the sleeping patterns as well as the quality of sleep [5].

The full impact of the Coronavirus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 virus, on the field of hematopoietic cell transplantation (HCT) is unknown. This perspective paper reviews the following: current COVID-19 epidemiology, diagnosis and potential therapies; care considerations unique to HCT patients; and the concept of a learning network to assimilate emerging guidelines and best practices and to optimize patient outcomes through facilitating shared learning and experience across transplant centers.

Introduction

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel single strand (ss) RNA beta-coronavirus, has caused the current Coronavirus Disease 2019 (COVID-19) pandemic. As of April 13, 2020, the World Health Organization (WHO) reported 1,773,084 laboratory confirmed cases and 111,652 deaths globally. 1 What ultimate impact COVID-19 will have on the field of hematopoietic cell transplantation (HCT) is currently unknown. This perspectives paper anticipates the significant influence of COVID-19 on HCT patients given their immune compromise, presence of other medical co-morbidities, and concerns for higher infection-related severity and mortality and also reviews the substantial impact of COVID-19 on the HCT-related healthcare system. To address these challenges, novel care approaches and ways to assimilate and share information in the background of rapid change are critically needed. Therefore, the concept of learning networks as interactive platforms for effectively assimilating and distributing evolving information to transplant centers is introduced.

Background: The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries; cases have also been reported worldwide. This novel coronavirus disease (COVID-19) is associated with a respiratory illness that may lead to severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which to date are not completely understood. Aims: To provide a review of the differences in pathogenesis, epidemiology and clinical features of COVID-19, SARS and MERS. Sources: The most recent literature in the English language regarding COVID-19 has been reviewed, and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics. Content: COVID-19 seems not to be very different from SARS regarding its clinical features. However, it has a fatality rate of 2.3%, lower than that of SARS (9.5%) and much lower than that of MERS (34.4%). The possibility cannot be excluded that because of the less severe clinical picture of COVID-19 it can spread in the community more easily than MERS and SARS. The actual basic reproductive number (R0) of COVID-19 (2.0e2.5) is still controversial. It is probably slightly higher than the R0 of SARS (1.7e1.9) and higher than that of MERS (<1). A gastrointestinal route of transmission for SARS-CoV-2, which has been assumed for SARS-CoV and MERS-CoV, cannot be ruled out and needs further investigation. Implications: There is still much more to know about COVID-19, especially as concerns mortality and its capacity to spread on a pandemic level. Nonetheless, all of the lessons we learned in the past from the SARS and MERS epidemics are the best cultural weapons with which to face this new global threat.

Introduction

The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which emerged at the end of December 2019 in Wuhan, China. It is currently spreading with epidemic features in China and other Asian countries, and cases have been reported in Europe, Australia and North America. Currently (as of 8th March 2020) 105 586 confirmed cases have been reported in 101 countries, with a total of 3584 deaths [1]. Coronavirus disease (COVID-19) is the clinical syndrome associated with SARS-CoV-2 infection; it is characterized by a respiratory syndrome with a variable degree of severity, ranging from a mild upper respiratory tract illness to severe interstitial pneumonia and acute respiratory distress syndrome (ARDS) [2e4]. Although SARS-CoV-2 belongs to the same Betacoronavirus genus as the coronaviruses responsible for the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) (SARS-CoV and MERS-CoV, respectively), this novel virus seems to be associated with milder infections.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; previously provisionally named 2019 novel coronavirus or 2019-nCoV) disease (COVID-19) in China at the end of 2019 has caused a large global outbreak and is a major public health issue. As of 11 February 2020, data from the World Health Organization (WHO) have shown that more than 43 000 confirmed cases have been identified in 28 countries/regions, with >99% of cases being detected in China. On 30 January 2020, the WHO declared COVID-19 as the sixth public health emergency of international concern. SARS-CoV-2 is closely related to two bat-derived severe acute respiratory syndrome-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. It is spread by human-to-human transmission via droplets or direct contact, and infection has been estimated to have mean incubation period of 6.4 days and a basic reproduction number of 2.24–3.58. Among patients with pneumonia caused by SARS-CoV-2 (novel coronavirus pneumonia or Wuhan pneumonia), fever was the most common symptom, followed by cough. Bilateral lung involvement with ground-glass opacity was the most common finding from computed tomography images of the chest. The one case of SARS-CoV-2 pneumonia in the USA is responding well to remdesivir, which is now undergoing a clinical trial in China. Currently, controlling infection to prevent the spread of SARS-CoV-2 is the primary intervention being used. However, public health authorities should keep monitoring the situation closely, as the more we can learn about this novel virus and its associated outbreak, the better we can respond.

Introduction

Since the emergence of the 2019 novel coronavirus (2019- nCoV) infection in Wuhan, China, in December 2019 [1], it has rapidly spread across China and many other countries [2–8]. So far, 2019-nCoV has affected more than 43 000 patients in 28 countries/regions and has became a major global health concern (https: //www.who.int/docs/default-source/coronaviruse/situation-reports/ 20200211-sitrep-22-ncov.pdf?sfvrsn=6f80d1b9_4). On 11 February 2020, the World Health Organization (WHO) announced a new name for the epidemic disease caused by 2019-nCoV: coronavirus disease (COVID-19). Regarding the virus itself, the International Committee on Taxonomy of Viruses has renamed the previously provisionally named 2019-nCoV as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) [3]. Although early studies reported a link between a single local fish and wild animal market and most cases of infection, indicating possible animal-to-human transmission, studies have increasingly demonstrated human-to-human transmission of SARS-CoV-2 through droplets or direct contact [2,8–10]. Moreover, according to one study, presumed hospital-related transmission of SARS-CoV-2 was suspected in 41% of patients [8]. Based on the evidence of a rapidly increasing incidence of infections [11] and the possibility of transmission by asymptomatic carriers [12], SARS-CoV-2 can be transmitted effectively among humans and exhibits high potential for a pandemic [5,10,13].

The aim of this systematic review was to report pregnancy and perinatal outcomes of coronavirus spectrum infections, and particularly coronavirus 2019 (COVID-19) disease because of severe acute respiratory syndromeecoronavirus-2 infection during pregnancy. DATA SOURCES: Medline, Embase, Cinahl, and Clinicaltrials.gov databases were searched electronically utilizing combinations of word variants for coronavirus or severe acute respiratory syndrome or SARS or Middle East respiratory syndrome or MERS or COVID-19 and pregnancy. The search and selection criteria were restricted to English language. STUDY ELIGIBILITY CRITERIA: Inclusion criteria were hospitalized pregnant women with a confirmed coronavirus relatedeillness, defined as severe acute respiratory syndrome, Middle East respiratory syndrome, or COVID-19. STUDY APPRAISAL AND SYNTHESIS METHODS: We used meta-analyses of proportions to combine data and reported pooled proportions. The pregnancy outcomes observed included miscarriage, preterm birth, preeclampsia, preterm prelabor rupture of membranes, fetal growth restriction, and mode of delivery. The perinatal outcomes observed were fetal distress, Apgar score <7 at 5 minutes, neonatal asphyxia, admission to a neonatal intensive care unit, perinatal death, and evidence of vertical transmission. RESULTS: Nineteen studies including 79 hospitalized women were eligible for this systematic review: 41 pregnancies (51.9%) affected by COVID-19, 12 (15.2%) by Middle East respiratory syndrome, and 26 (32.9%) by severe acute respiratory syndrome. An overt diagnosis of pneumonia was made in 91.8%, and the most common symptoms were fever (82.6%), cough (57.1%), and dyspnea (27.0%). For all coronavirus infections, the rate of miscarriage was 39.1% (95% confidence interval, 20.2e59.8); the rate of preterm birth <37 weeks was 24.3% (95% confidence interval, 12.5e38.6); premature prelabor rupture of membranes occurred in 20.7% (95% confidence interval, 9.5e34.9), preeclampsia in 16.2% (95% confidence interval, 4.2e34.1), and fetal growth restriction in 11.7% (95% confidence interval, 3.2e24.4); 84% were delivered by cesarean; the rate of perinatal death was 11.1% (95% confidence interval, 84.8e19.6), and 57.2% of newborns (95% confidence interval, 3.6e99.8) were admitted to the neonatal intensive care unit. When focusing on COVID-19, the most common adverse pregnancy outcome was preterm birth <37 weeks, occurring in 41.1% of cases (95% confidence interval, 25.6e57.6), while the rate of perinatal death was 7.0% (95% confidence interval, 1.4e16.3). None of the 41 newborns assessed showed clinical signs of vertical transmission. CONCLUSION: In hospitalized mothers infected with coronavirus infections, including COVID-19, >90% of whom also had pneumonia, preterm birth is the most common adverse pregnancy outcome. COVID-19 infection was associated with a relatively higher rate of preterm birth, preeclampsia, cesarean, and perinatal death.

Coronaviruses are a large group of viruses known to cause illnesses that vary between the common cold and more severe diseases to include severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). A novel coronavirus was identified in December 2019 in Wuhan city, Hubei province, China. This virus represents a new strain that has not been previously identified in humans. The virus is now known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting disease is called coronavirus disease 2019 (COVID-19). The World Health Organization (WHO) declared the novel coronavirus outbreak a global pandemic in March 2020. Despite rigorous global containment and quarantine efforts, the incidence of COVID19 continues to rise, with more than 1,948,617 laboratory-confirmed cases and over 121,846 deaths worldwide. Currently, no specific medication is recommended to treat COVID-19 patients. However, governments and pharmaceutical companies are struggling to quickly find an effective drug to defeat the coronavirus. In the current review, we summarize the existing state of knowledge about COVID-19, available medications, and treatment options. Favilavir is an antiviral drug that is approved in Japan for common influenza treatment and is now approved to treat symptoms of COVID-19 in China. Moreover, Chloroquine and hydroxychloroquine, drugs used to treat malaria and arthritis, respectively, were recommended by the National Health Commission of the People’s Republic of China for treatment of COVID-19. Presently, chloroquine and hydroxychloroquine are under investigation by the US Food and Drug Administration (FDA) as a treatment for COVID-19. The first COVID-19 vaccine is not expected to be ready for clinical trials before the end of the year.

Introduction

In the second week of December 2019, unknown viral infection was identified in a small local fish and wild animal market in Wuhan city, Hubei province in China (Lu et al., 2020). Since this time, the virus has rapidly spread across mainland China, and now has reached other countries (Li et al., 2020a; Chen et al., 2020a). In the early stages of this virus spread, several cases of pneumonia of unknown etiology were reported. Patients have been diagnosed with severe acute respiratory infection symptoms and others with rapidly developing acute respiratory distress syndrome, acute respiratory failure and other serious complications leading to death (Nijuan et al., 2013). The Chinese Center for Disease Control and Prevention (CCDC) identified this infection as a novel coronavirus infection on Jan 7, 2020 and on Feb 11, 2020, the WHO announced a new name for the epidemic disease as 2019-new coronavirus disease (2019-nCoV and now known as COVID19) (Organization, W.H., 2020). Additionally, the International Committee on Taxonomy of Viruses named 2019-nCoV as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has become a major global health concern and the WHO declared the coronavirus outbreak a global pandemic on March 2020 (Whitworth, 2020). As of April 14, 2020, COVID-19 has affected more than 1,948,617 patients in 210 countries and territories around the world and two international conveyances and left around 121,846 deaths worldwide.

Hong Kong has been recently attacked by the coronavirus disease-2019 (COVID-19). In late January 2020, it’s shown a steadily increasing trend of confirmed cases. There is a 257 in total infected cases confirmed including 4 deaths until 20th of March 2020. To prevent further outbreak of COVID-19, this article discusses the current understanding of COVID-19 and compares with the outbreak of SARS-CoV-2 in 2003 of Hong Kong from the causes, transmission, symptoms, diagnosis, treatments and preventions to study for an applicable measurement to control COVID-19.

Introduction

An outbreak of pneumonia with unknown etiology emerged in Wuhan of Hubei Province, China on December in 2019. Chinese scientists confirmed that a new coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of pneumonia outbreak. Now, this severe acute respiratory syndrome has been termed as coronavirus disease 2019 (COVID-19) by the World Health of Organization (WHO) [1]. Coronavirus is a group of viruses categorized into alphacoronavirus and betacoronavirus often causing cold and other mild upper respiratory tract infections in the human body. Alphacoronavirus consists of HCoV-229E and HCoV-NL63; Betacoronavirus consists of HCoVOC43 and HCoV-HKU1. Nevertheless, the rare form would be lethal such as SARS, MERS and COVID-19 [2]. SRAS-CoV, MERS-CoV and SARS-CoV-2 are betacoronavirus [3]. However, SARSr-CoVs belong to the subgenus Sarbecovirus (previously lineage B) of genus Betacoronavirus and occupy a unique phylogenetic position. It’s the most lethal [4]. On the 20th of March 2020, 178 countries or territories reported that there are 234073 in the total confirmed case with 9840 deaths globally; 81300 confirmed cases and 3253 deaths reported in China [5]; 257 confirmed case with 4 deaths in Hong Kong [6]. In response to the outbreak, we summarize the current knowledge of COVID-19 and compare it with the previous experiences of the SARS outbreak in Hong Kong to study for an effective measurement to control the COVID-19 epidemic.

Coronavirus disease 2019 SARS-CoV-2 (COVID-19) is a zoonotic virus causing a variety of severe respiratory diseases. SARS-CoV-2 is closest to SARS-CoV and MERS-CoV in structure. The high prevalence of COVID-19 is a result of a lack of symptoms at onset. Our study aimed to present an overview of the virus in terms of structure, epidemiology, symptoms, treatment and prevention. Whole genome sequences and some viral proteins were investigated to determine gaps and changes in alternation of nucleotides and amino acid sequences. We evaluate 11 complete genome sequences of different coronaviruses using BAST and MAFFT software. We also selected seven types of structural proteins. We conclude that COVID-19 might produce new mutations, specifically in glycoproteins, so caution and complete preparation by health authorities is required.

Introduction

Novel coronavirus disease 19 (COVID-19) first emerged on 31 December 2019 in Wuhan city, China. COVID-19 is classified as the seventh member of the subfamily Orthocoronavirinae under the family Coronaviridae. Most members of this family are zoonotic viruses transmitted to humans through contact with infected animals. Although bats and snakes are the natural reservoir of most coronaviruses, there is no evidence so far that COVID-19 originated in or was transmitted from a seafood market [1]. Comparison of the lipid rafts of coronaviruses has indicated that the new strain COVID-19 has 80% identity with severe acute respiratory syndrome coronavirus (SARS-CoV). Lipid molecules such as caveolins, clathrins and dynamin have a fundamental role in the internalization of viruses. These molecules are involved in the entry of viruses into host cells, and targeting host lipids is being studied as an antiviral strategy and could have various applications [2]. COVID-19 seems to need to bind to the angiotensin-converting enzyme-2 receptor on the membrane host cell to enable it to infect the host cell upon coupled with a reliance of serine protease TMPRSS2. This intracellular protein seems to be a determinant of the virus ability to infect the cell [3].

Coronavirus disease 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus strain disease, has recently emerged in China and rapidly spread worldwide. This novel strain is highly transmittable and severe disease has been reported in up to 16% of hospitalized cases. More than 600,000 cases have been confirmed and the number of deaths is constantly increasing. COVID-19 hospitalized patients, especially those suffering from severe respiratory or systemic manifestations, fall under the spectrum of the acutely ill medical population, which is at increased venous thromboembolism risk. Thrombotic complications seem to emerge as an important issue in patients infected with COVID-19. Preliminary reports on COVID-19 patients’ clinical and laboratory findings include thrombocytopenia, elevated D-dimer, prolonged prothrombin time, and disseminated intravascular coagulation. As the pandemic is spreading and the whole picture is yet unknown, we highlight the importance of coagulation disorders in COVID-19 infected patients and review relevant data of previous coronavirus epidemics caused by the severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and the Middle East Respiratory Syndrome coronavirus (MERS-CoV).

COVID-19 and coagulation disorders

A novel coronavirus strain disease, Coronavirus disease 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), has recently emerged in Wuhan, China and rapidly spread throughout China and subsequently worldwide [1,2]. Currently, more than 600,000 cases have been diagnosed and over 25,000 infected people have died [3]. Patients usually present with fever (> 80%), cough (> 60%), and myalgia or fatigue (> 40%) [1,4]. Males are more commonly affected (∼60% of cases) with a median age of approximately 50 years [1,4,5]. The complete spectrum of presentations and complications associated with COVID-19 is not fully elucidated. Clinical manifestations range from asymptomatic or very mild to severe illness, sepsis and death. While the current state of evidence suggests that most COVID-19 illness is mild, the study by Guan et al. suggests severe illness occurs in 16% of cases [4,6]. As the pandemic is still in progression, with an incomplete picture and potential treatments in preliminary stages only, we sought to review the available literature relevant to coagulation disorders in patients infected by the severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and the Middle East Respiratory Syndrome coronavirus (MERS-CoV) to raise awareness about these potential complications in patients with COVID-19. Thrombotic complications seem to emerge as an important issue in patients with COVID-19. Preliminary reports on COVID-19 pandemic outcomes have shown that infected patients commonly develop thrombocytopenia (36.2%) and may have elevated D-dimer (46.4%) [4], while these rates are even higher in patients with severe COVID-19 disease (57.7% and 59.6%, respectively) [4]. Emerging data support that patients infected by this novel coronavirus are at risk of developing disseminated intravascular coagulation (DIC) [4,7,8].

The novel coronavirus infection that initially found at the end of 2019 has attracted great attention. So far, the number of infectious cases has increased globally to more than 100 thousand and the outbreak has been defined as a pandemic situation, but there are still no “specific drug” available. Relevant reports have pointed out the novel coronavirus has 80% homology with SARS. In the difficulty where new synthesized drug cannot be applied immediately to patients, “conventional drug in new use” becomes a feasible solution. The first medication experience of the recovered patients in the US has led remdesivir to be the “specific drug”. China has also taken immediate action to put remdesivir into clinical trials with the purpose of applying it into clinical therapeutics for Corona Virus Disease 2019 (COVID-19). We started from the structure, immunogenicity, and pathogenesis of coronavirus infections of the novel coronavirus. Further, we analyzed the pharmacological actions and previous trials of remdesivir to identify the feasibility of conducting experiments on COVID-19.

Introduction

The novel coronavirus 2019 (2019-nCoV), officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a newlyemerged human infectious coronavirus. Since December 2019, it has spread rapidly in China in a short period of time. As of March 17, 2020, there have been 81116 confirmed cases and 3231 deaths. It has also outbreak in other countries, such as Korea, Japan, Italy, Singapore, and Iran, with a total of 85296 cases confirmed. Due to it is a newlyemerged virus, researchers have taken quick actions to isolate the virus and perform gene sequencing, making identifying treatments possible. Even so, it takes time to develop new drugs and vaccines, as well as to explore biotherapeutics, thus it is unlikely to be applied to patients with urgent need. Therefore, “conventional drug in new use” becomes a viable solution. The SARS-CoV-2 is 80% homologous with the acute respiratory syndrome-associated coronavirus (SARS-CoV), which also broke out in China in 2002, and some enzymes are even more than 90% homologous [1]. Consequently, we are expecting to find drugs for the treatment of COVID-19 from the experience of SARS-CoV and Middle East Respiratory Syndrome (MERS-CoV). Some drugs, such as ribavirin, interferon, lopinavir, and corticosteroids, have been used in patients with SARS or MERS [2], within the selection range of “conventional drug in new use”. Through clinical treatment of the COVID-19, it has been found that neuraminidase inhibitors (oseltamivir, peramivir, zanamivir), ganciclovir, acyclovir, ribavirin are ineffectual and not recommended for clinical application [3].

1- The controversy over the classification of Asperger’s syndrome

2- In children and adolescents

3- In adult population

4- Conclusion

5- Search strategy and selection criteria

References

Abstract

Asperger’s syndrome is a neurodevelopmental disorder which is part of the large family of autism spectrum disorders. People with Asperger’s syndrome have difficulties in social interactions, verbal and non-verbal communication, and may display behavioural oddities, with stereotypies and limited interests. They show no language delay and their cognitive development is not marked by an overall delay but by specific impairments in certain areas such as the executive functions. The clinical presentations are very heterogeneous, varying according to age and psychiatric comorbidities. Screening, diagnosis and specialized treatment are not made any easier by the diversity of the clinical manifestations. Asperger’s syndrome is often diagnosed belatedly, at 11 years of age on average and even in adulthood in some cases. This late diagnosis has a significant impact on the risks of depression and a poor quality of life. However, in adulthood or in adolescence, certain situations, personality traits and cognitive profiles or certain comorbidities should suggest the hypothesis of an Asperger-type autism spectrum disorder. We propose here a review of the clinical situations at different ages of life that could help with the screening and the referral of patients to specialized clinicians for diagnosis and appropriate treatment.

The controversy over the classification of Asperger’s syndrome

The nosography of psychiatric disorders is relatively complex, and the successive classifications have not helped to clarify the issue, particularly in child and adolescent psychiatry. However, this evolution reflects new scientific discoveries that have led to the better understanding of certain neurodevelopmental disorders, thereby causing changes to diagnostic criteria. Asperger’s syndrome, which was first described by the Russian psychiatrist Grounia Efimovna Soukhareva [1] and by the German psychiatrist Asperger (1943) [2], who gave his name to it after the work done by Lorna Wing (1981) [3] appeared in the chapter “Pervasive Development Disorders” in DSM-IV alongside autistic disorder [4]. At the time of DSM-IV-TR [5], the large family of pervasive developmental disorders (PDD) included 5 subtypes: • autistic disorders (including Kanner’s childhood autism); • childhood disintegrative disorder; • Rett syndrome; • unspecified developmental disorders (PPD-NOS); • Asperger’s syndrome.