Preprints on COVID-19 and SARS-CoV-2
Reminder: Please bear in mind that these are early stage research which have not gone through a rigorous peer review process, and should not be regarded as conclusive clinical guidance or be reported in news media as established fact.
REVIEW | doi:10.20944/preprints202009.0757.v1
Online: 30 September 2020 (15:08:34 CEST)
Human civilizations are under enormous threats due to the outbreak of novel coronavirus (COVID-19) originated from Wuhan, China. The asymptomatic carriers are the potential spreads of this novel virus. Since, guaranteed antiviral treatments have not been available in the market so far, it is really challenging to fight against this contagious disease. To save the living mankind, it is urgent to know more about how the virus transmits itself from one to another quite rapidly and how we can predict future infections. Scientists and Researchers are working hard in investigating to understand its high infection rate and transmission process. One possible way to know is to use our existing COVID-19 infection data and prepare a useful model to predict the future trend. Mathematical modelling is very useful to understand the basic principle of COVID-19 transmission and provide necessary guidelines for future prediction. Here, we have reviewed 9 distinct commonly used models based on Mathematical implementations for COVID-19 transmission and dig into the deep head to head comparison of each model. Finally, we have discussed interesting key behaviour of each model, relevant upcoming important issues, challenges and future directions.
ARTICLE | doi:10.20944/preprints202008.0620.v2
Subject: Social Sciences, Accounting Keywords: Urban green space; COVID-19; urban parks; open space; New York City; urban infrastructure; equity
Online: 30 September 2020 (10:00:40 CEST)
Urban green spaces provide a range of environmental and health benefits, which may become even more critical during times of crisis such as the current COVID-19 pandemic. However, with a radical shift in mobility, additional concerns over safety, and access temporarily restricted during the implementation of social distancing policies, the experience and use of urban green spaces may be reduced. This is particularly concerning for densely populated cities like New York, considered the first U.S. epicenter or vanguard of the outbreak. To better understand the impact of COVID-19 on the perception and use of urban green spaces, we conducted a social survey during the early months of the Covid-19 pandemic in New York City (May 13 - June 15, 2020). The results of the survey show respondents continued to use urban green spaces during the pandemic and consider them to be more important for mental and physical health than before the pandemic began. However, the study revealed a pattern of concerns residents have about green space accessibility and safety, and found key differences between the concerns and needs of different populations, suggesting a crucial role for inclusive decision-making, support for additional management strategies, and urban ecosystem governance that reflect the differential values, needs and concerns of communities across the City. As urban centers face looming budget cuts and reduced capacity, this study provides some empirical evidence to illustrate the value of urban green spaces as critical urban infrastructure, and may have implications for funding, policy, and management, of urban green spaces in NYC, with potential applications to other cities, particularly during times of crisis.
Subject: Medicine & Pharmacology, Allergology Keywords: clozapine; schizophrenia; early-onset; pregnancy; bipolar affective disorder; agranulocytosis; COVID-19; pharmacogenetic
Online: 30 September 2020 (08:06:26 CEST)
Background: Clozapine use is precarious due to its side effects - neurological, cardiovascular, and hematological; however, it is the gold standard in the therapy of resistant schizophrenia (TRS) in adults and harshly underused. Objective: Our purpose is to systematically examine the most recent data regarding clozapine in order to update the knowledge in pharmacological mechanisms, therapy benefits versus side effects to optimize its use in the context of a narrow and scarce of resources pathology, with particularities in the COVID-19 pandemic. (2) Data sources: We performed an accurate search in the primary sources of Databases (PubMed, BMC Public Health, Global Health, Cross Ref, Scopus, Web of Science, and Google Scholar) with specific keywords: “clozapine” and “schizophrenia,” “risks” agranulocytosis” “TRS” “bipolar affective disorder” “pregnancy” “early-onset schizophrenia” “resistance”. Study eligibility criteria: we extracted information regarding drug treatment, side effects profile, and efficacy for each trial; (3) Results: Of all the searched data we selected RCT’s, C.T.’s, reviews, systematic reviews, and meta-analyses; Data were converted and analyzed in a random-effects model. We included 45 studies, centered on six main topics in the search area: (a) treatment-resistant schizophrenia, (b) use in bipolar disorder, (c) side effects during the clozapine therapy - agranulocytosis, metabolic side effects, pharmacogenetic severity markers, dysmetabolic side effects, pulmonary embolism, seizure risk – (d) safety of clozapine in pregnancy, (e) clozapine resistance and ECT augmentation, (f) clozapine therapy and COVID-19 infection. Limitations: _______(4) Conclusions and implications of key findings: (a) The genetic vulnerability postulates predictors of severity so clozapine doses should be personalises for each patient based on pharmacogenetic testing; patients with a lower genetic risk may benefit from a more relaxed hematological monitoring schedule; (b) Pulmonary embolism associated with clozapine has a mortality rate of 36.36%, prophylactic measures for venous thromboembolism for six months after initiating therapy is mandatory; (c) Convulsive episodes are not an indication for stopping the treatment, side effect (s.e.) incidence increases with the dose, the plasma concentration of clozapine (1300 ng/ml) it is a better s. e. predictor than the dosage; (d) clozapine refractory improves up to 69% early-onset schizophrenia, assesed by the Brief Psychiatric Rating Scale (BPRS) (e) more pharmacogenetic studies of the Romanian schizophrenic patients are needed in relation with the clozapine therapy in order to define more precise safety margins; (f) COVID-19 infection may enhance clozapine toxicity generating an increased risk of pneumonia therapy must be continued with proper monitoring of the white blood count and with the decrease of the clozapine dose by half until three days after the subside of the fever; psychiatrists and healthcare providers must act togheder. As in the past four decades, research has failed to generate effective novel psycho-pharmaceuticals, there is an urgent need to enhance the access to clozapine for people with TRS at the worldwide level. The progress of pharmacogenetic researches, endocrinology, genetic testing - offer the psychiatrists nowadays the chance to use this drug at its highest potential in a personalized manner for every patient - minimizing the adverse side-effects.
COMMUNICATION | doi:10.20944/preprints202009.0702.v1
Subject: Life Sciences, Biochemistry Keywords: SARS-CoV-2; influenza vaccine; systematic review; infection; severity; risk
Online: 29 September 2020 (09:14:03 CEST)
We reviewed the association between seasonal influenza vaccination and the risk of SARS-CoV-2 infection or complicated illness or poor outcome (e.g. severe disease, need for hospitalization or ventilatory support, or death) among COVID-19 patients. None of the studies that were reviewed (n=12) found a significant increase in the risk of infection or in the illness severity or lethality, while some reported significantly inverse associations. Our findings support measures aimed at raising influenza vaccination coverage in the coming months.
COMMUNICATION | doi:10.20944/preprints202009.0701.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Challenges; coinfection; COVID-19; dengue fever; co-epidemic; health care facility
Online: 29 September 2020 (09:12:06 CEST)
The current global COVID-19 pandemic is compounding on populations susceptible to tropical illnesses like dengue in different developing countries like Bangladesh. The growing concern is that Bangladesh is a dengue-endemic zone and the peak transmission occurs in the monsoon season (June to October). In the most recent monsoon, a total of 354 dengue cases have been confirmed until 27th July 2020, data-driven from only 41 hospitals alone. A fifty-three-year-old male patient was found to be co-infected with COVID-19 and dengue fever. Concerns arise as hospitals are increasingly denying to admit the patients. Moreover, reports of the false-positive results in dengue screening tests recorded in different countries further exacerbate the issue. These conditions could postpone the early diagnosis of COVID-19 cases and aggravate the situation. In addition, the overwhelming wave of the dengue cases would be a challenge for the vulnerable health care system of the country which is already under strain due to the COVID-19 pandemic. Failure to establish and implement proper policies might lead to the dengue outbreak with the burdens of the concurrent COVID pandemic, resulting in the collapse of the health and social system, as well as the economic growth of the country.
ARTICLE | doi:10.20944/preprints202009.0690.v1
Subject: Medicine & Pharmacology, Allergology Keywords: COVID-19 Pandemic; Finland; health care personnel; psychological distress; post-traumatic stress disorder
Online: 28 September 2020 (15:37:39 CEST)
On March 2020 strict measures took place in Finland to limit the COVID -19 pandemic. A majority of the Finnish COVID -19 –patients have been located in the southern Finland and consequently cared for in the HUS Helsinki University Hospital. During the ongoing pandemic, HUS personnel’s psychological symptoms are followed via an electronic survey, which also delivers information on psychosocial support services. The baseline survey in June 2020 was sent to 25494 HUS employees out of whom 4804 (19%) answered; altogether 62.4% of the respondents were nursing staff and 8.9% medical doctors. While the follow-up continues for a year and a half, this report shares the sociodemographic characteristics of the respondents and the first results of psychological symptoms from the baseline survey. Out of those who were directly involved in pandemic patients` care, 43.4% reported potentially traumatic COVID-19 pandemic-related experiences vs. 21.8% among the other (p < 0.001). While over a half of the personnel was symptomless, a group of respondents reported pandemic work –related traumatic events and concurrent depressive, insomnia and anxiety symptoms. This highlights the need to ensure appropriate psychosocial support services to all traumatized personnel and PTEs were present especially among nursing staff.
ARTICLE | doi:10.20944/preprints202005.0040.v2
Online: 28 September 2020 (03:19:50 CEST)
To address the expression pattern of the SARS-CoV-2 receptor ACE2 and the viral priming protease, TMPRSS2, in the respiratory tract, this study investigated RNA sequencing transcriptome profiling of samples of airway and oral mucosa. As shown, ACE2 has medium levels of expression in both small airway epithelium and masticatory mucosa, and high levels of expression in nasal epithelium. The expression of ACE2 is low in mucosal associated invariant T (MAIT) cells, and can’t be detected in alveolar macrophages. TMPRSS2 is highly expressed in small airway epithelium and nasal epithelium, and has lower expression in masticatory mucosa. Our results provide the molecular basis that the nasal mucosa is the most susceptible locus in the respiratory tract for SARS-CoV-2 infection and consequently for subsequent droplet transmission and should be the focus for protection against SARS-CoV-2 infection.
ARTICLE | doi:10.20944/preprints202009.0658.v1
Subject: Medicine & Pharmacology, Allergology Keywords: COVID-19; health literacy; information sharing; family well-being; preventive measures
Online: 27 September 2020 (03:05:51 CEST)
Objective: We tested a model of individual health literacy, information sharing with family members, personal preventive behaviours and family well-being during COVID-19 pandemic in Hong Kong. Methods: We analysed data of 1501 randomly selected Chinese adults from a cross-sectional survey in Hong Kong from 9 to 23 April 2020. Individual health literacy, COVID-19 information sharing with family members, preventive behaviours against COVID-19 and family well-being were measured. Structural equation modelling analysis tested the proposed model. Findings: COVID-19 information sharing with family members partially mediated the association between individual health literacy and personal preventive behaviours. The direct effect of .24 was shown and indirect effect through COVID-19 information sharing with family members was small with .03 (Z = 3.66, p < .001). Family well-being was associated with personal preventive behaviours against COVID-19. The model was adjusted for sex, age, and socioeconomic status factors and had good ﬁt with RMSEA = .04, CFI = .98, TLI = .96, and SRMR = .02. Conclusion: COVID-19 information sharing with family members was a partial mediator between individual health literacy and personal preventive behaviours against COVID-19. Strategies for enhancing health literacy and preventive measures against COVID-19 are needed to promote family well-being in the pandemic.
ARTICLE | doi:10.20944/preprints202009.0657.v1
Subject: Medicine & Pharmacology, Allergology Keywords: HIV; workplace intervention; SMS; HIV testing; construction; mobile phone; Covid-19; health promotion; text messaging
Online: 27 September 2020 (03:02:41 CEST)
Background: HIV poses a threat to global health. With effective treatment options available, education and testing strategies are essential in preventing transmission. Text messaging is an effective tool for health promotion and can be used to target higher risk populations. This study reports on the design, delivery and testing of a mobile text messaging SMS intervention for HIV prevention and awareness, aimed at adults in the construction industry and delivered during the COVID-19 pandemic. Method: Participants were recruited at [email protected] workplace health promotion events (21 sites, n=464 employees), including health checks with HIV testing. Message development was based on a participatory design and included a focus group (n=9) and message fidelity testing (n=291) with assessment of intervention uptake, reach, acceptability, and engagement. Barriers to HIV testing were identified and mapped to the COM-B behavioural model. 23 one-way push SMS messages (19 included short web links) were generated and fidelity tested, then sent via automated SMS to two employee cohorts over a 10-week period during the COVID-19 pandemic. Engagement metrics measured were; opt-outs, SMS delivered/read, number of clicks per web link, and four two-way pull messages exploring repeat HIV testing, learning new information, perceived usefulness and behaviour change. Results: 291 people participated (68.3% of eligible attendees). A total of 7,726 messages were sent between March and June 2020, with 91.6% successfully delivered (100% read). 12.4% of participants opted out over 10 weeks. Of delivered messages, links were clicked an average of 14.4%, max 24.1% for HIV related links. The number of clicks on web links declined over time (r= -6.24, p=0.01). Response rate for two-way pull messages was 13.7% of participants. Since the workplace HIV test offer at recruitment, 21.6% reported having taken a further HIV test. Qualitative replies indicated behavioural influence of messaging on exercise, lifestyle behaviours and intention to HIV test. Conclusion: SMS messaging for HIV prevention and awareness is acceptable to adults in the construction industry, has high uptake, low attrition and good engagement with message content, when delivered during a global pandemic. Data collection methods may need refinement for audience and effect of COVID-19 on results is yet to be understood.
ARTICLE | doi:10.20944/preprints202009.0647.v1
Subject: Mathematics & Computer Science, Algebra & Number Theory Keywords: Lung condition; COVID-19; Machine learning; Custom Vision; Core ML; Auto ML; AI; Pneumonia; Smartphone application; Real-time diagnosis
Online: 26 September 2020 (16:14:39 CEST)
AI is leveraging all aspects of life. Medical services are not untouched. Especially in the field of medical image processing and diagnosis. Big IT and Biotechnology companies are investing millions of dollars in medical and AI research. The recent outbreak of SARS COV-2 gave us a unique opportunity to study for a non interventional and sustainable AI solution. Lung disease remains a major healthcare challenge with high morbidity and mortality worldwide. The predominant lung disease was lung cancer. Until recently, the world has witnessed the global pandemic of COVID19, the Novel coronavirus outbreak. We have experienced how viral infection of lung and heart claimed thousands of lives worldwide. With the unprecedented advancement of Artificial Intelligence in recent years, Machine learning can be used to easily detect and classify medical imagery. It is much faster and most of the time more accurate than human radiologists. Once implemented, it is more cost-effective and time-saving. In our study, we evaluated the efficacy of Microsoft Cognitive Service to detect and classify COVID19 induced pneumonia from other Viral/Bacterial pneumonia based on X-Ray and CT images. We wanted to assess the implication and accuracy of the Automated ML-based Rapid Application Development (RAD) environment in the field of Medical Image diagnosis. This study will better equip us to respond with an ML-based diagnostic Decision Support System(DSS) for a Pandemic situation like COVID19. After optimization, the trained network achieved 96.8% Average Precision which was implemented as a Web Application for consumption. However, the same trained network did not perform like Web Application when ported to Smartphone for Real-time inference, which was our main interest of study. The authors believe, there is scope for further study on this issue. One of the main goals of this study was to develop and evaluate the performance of AI-powered Smartphone-based Real-time Applications. Facilitating primary diagnostic services in less equipped and understaffed rural healthcare centers of the world with unreliable internet service.
ARTICLE | doi:10.20944/preprints202009.0633.v1
Subject: Social Sciences, Accounting Keywords: COVID-19; pandemic; tourism; tourist behavior; tourism sustainability
Online: 26 September 2020 (13:19:47 CEST)
This research aims to understand the vision and the reaction of the population towards tourism and holidays during this period of the COVID-19 pandemic. It investigates also the tourist needs of the Algerian population after the closure of international borders. Methods: The data were collected using mixed quantitative and qualitative methods through a questionnaire applied to 203 people in different regions of Algeria (a North African country) from 1st June to 13 July 2020. Results: The needs of Algerian tourists are characterized by a great need for leisure to relieve psychological stress caused by COVID-19 (M = 25.33) among the study sample (p <0.05). The results also show an average need to rationalize the costs of tourist services (M = 5.26) according to the respondents (p <0.01). This is in addition to the great need (M = 7.75) among respondents (p <0.05) of the awareness that the tourism sector can contribute to the economic recovery in Algeria after the confinement period. About 75.86% of respondents demand the cleanliness of tourist sites, while 69.95% recommend improving safety because of the size of tourist sites in the Algerian territory and also measures related to social distancing. The results show that 53.69% of respondents preferred the month of August to go on vacation, 29.06% chose the month of September, and 17.25% would prefer the months of October, November and December since they expect a reduction in the risks of the COVID-19 pandemic. Conclusions: The COVID-19 pandemic has affected the tourism needs of the Algerian population, which has become increasingly aware of the consequences of the pandemic in relation to their health and on the country's economy. These results can help the authorities of the tourism sector to better understand and identify the tourism needs of this population in the current period and after the COVID-19 pandemic.
Online: 26 September 2020 (13:08:55 CEST)
The issues mothers face in the academy have been discussed for decades. Routinely, new studies report significant differences between women and men at comparable career stages with respect to salary, service demands, publications, grant submissions, and overall funding rates. The COVID-19 pandemic is further exposing these inequalities as women scientists who are parenting while also engaging in a combination of academic related duties are falling further behind. COVID-19 is shaking the very foundations of our society and laying bare the many inequalities that defined our pre-COVID world. We can solve these inequities by investing strategically in creative solutions, thereby making the most of women’s contributions to scientific endeavors. Here we describe strategies that would make the academy more equitable for working mothers now and into the future. Importantly, while the data are clear that mothers are being disproportionally impacted by COVID-19, many groups could benefit from these same ideas. Now is the time to act. Rather than rebuilding what we once knew, let us be the architects of a new world.
ARTICLE | doi:10.20944/preprints202009.0631.v1
Subject: Life Sciences, Biochemistry Keywords: COVID-19; SARS-CoV-2; In silico; Immunoinformatics; Vaccine designing
Online: 26 September 2020 (13:01:26 CEST)
As the number of infections and deaths caused by the recent COVID-19 pandemic is increasing dramatically day-by-day, scientists are rushing towards developing possible counter-measures to fight the deadly virus, SARS-CoV-2. Although many efforts have already been put forward for designing and developing potential vaccines, however, most of them are proved to possess negative consequences. Therefore, in this study, the methods of immunoinformatics were exploited to design novel epitope-based subunit vaccine against the SARS-CoV-2, targeting four essential proteins of the virus i.e., spike glycoprotein, nucleocapsid phosphoprotein, membrane glycoprotein, and envelope protein. The highly antigenic, non-allergenic, non-toxic, non-human homolog and 100% conserved (across other isolates from different regions of the world) epitopes were used for constructing the vaccine. In total, fourteen CTL epitopes and eighteen HTL epitopes were used to construct the vaccine. Thereafter, several in silico validations i.e., the molecular docking, molecular dynamics simulation (including the RMSF and RMSD studies), and immune simulation studies were also performed which predicted that the designed vaccine should be quite safe, effective, and stable within the biological environment. Finally, in silico cloning and codon adaptation studies were also conducted to design an effective mass production strategy of the vaccine. However, more in vivo and in vitro studies are required on the predicted vaccine to finally validate its safety and efficacy.
ARTICLE | doi:10.20944/preprints202009.0630.v1
Online: 26 September 2020 (12:47:42 CEST)
In this COVID-19 pandemic, the use and dependency on Internet has grown exponentially. The number of people doing online activities such as e-learning, remote working, online shopping and others have increased. This has also led to increased vulnerability to cyber crimes. Cyber security attacks have become a serious problem. The common types of cyber security attacks are phishing, malware, ransomware, social engineering, identity theft and denial-of-service. The attackers target the victims in order to get their credential information or financial benefits. Those people who are doing online activities are vulnerable to cyber threats. This is because the network is not safe. The attackers are able to code according to the weaknesses of the Internet. Once the attackers hack into the devices, they have the root access and can do whatever they want to do with the device. In this research paper, the concept of cyber security attack and detailed research about real attacks are discussed. This is followed by detailed review about the recent cyber security attacks with a critical analysis. Moreover, the research paper will be proposing the latest research contribution of cyber security during COVID-19 and the implementation scenario which will give the examples about how the companies maintain privacy as well as the limitations. Then, the paper will be discussing the reasons that people are vulnerable to cyber security and the unique solution to the problems stated. Finally, this paper will conclude with an in-depth analysis and future direction for cyber security research.
ARTICLE | doi:10.20944/preprints202009.0628.v1
Subject: Medicine & Pharmacology, Allergology Keywords: SARS-CoV-2; corona virus; COVID-19; non-parametric model
Online: 26 September 2020 (12:31:57 CEST)
Based on comprehensible non-parametric methods, estimates of crucial parameters that characterise the COVID-19 pandemic with a focus on the German epidemic are presented. Where appropriate, the estimates for Germany are compared with the results for six other countries (FR, IT, US, UK, ES, CH) to get an idea of the breadth of applicability and a relational understanding. Thereby, only prevalence data of daily reported new counts of diagnosed cases and fatalities provided by the ECDC are used. Where appropriate, the results are compared with conclusions drawn from using the dataset provided by the RKI. Drawing on uncertain a priori knowledge is avoided. Specifically, we present estimates for the duration from diagnosis to death being 13 days for Germany and about 2 days for Italy as the extremes. Furthermore, based on the knowledge of this time lag between diagnoses and deaths, properly delayed asymptotic as well as instantaneous fatality-case ratios are calculated having superiority compared to the commonly published case-fatality rate. The median of the time series of the instantaneous fatality-case ratio with proper delay of 13-days between cases and deaths for Germany turns out to be 0.024. Asymptotic values are presented for other countries with France ranking highest with a fatality-case ratio of almost 0.2 at its peak. The basic reproduction number, R_0, for Germany is estimated to be between 2.4 and 3.4. The uncertainty stems from uncertain knowledge of the generation time. A delay autocorrelation shows resonances at about 4 days and 7 days, where the latter resonance is at least partially attributable to the sampling process with weekly periodicity. The calculation of the basic reproduction number is based on an evaluation of cumulative numbers of cases yielding time-dependent doubling times as an intermediate step. This allows to infer to the reproduction number during the early phase of onset of the epidemic. In a second approach, the instantaneous basic reproduction number is derived from the incident (counts of new) cases and allows, in contrast to the first version, to infer to the temporal behaviour of the reproduction number during the later epidemic course. To conclude, by avoiding complicated parametric models we provide insights into basic features of the COVID-19 epidemic in an utmost transparent and comprehensible way.
ARTICLE | doi:10.20944/preprints202009.0619.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: COVID-19 Mexico; stress in healthcare professionals; COVID-19 stress scale
Online: 26 September 2020 (08:07:00 CEST)
The world is currently, subjected to the worst health crisis documented in modern history; an epidemic led by the novel coronavirus disease 2019 (COVID-19). At the epicenter of this crisis, healthcare professionals continue working to safeguard our well-being. To the regular high levels of stress, COVID new heights even more to healthcare professionals so depending on the area, specialty, and type of work. Here we investigated what are the tendencies, or areas most affected. Through an adaptation of the original COVID-stress scale, we developed a remote, fast test designed for healthcare professionals of the Northeastern part of Mexico, an important part of the country with economic and cultural ties to the US. Our results showed 4 key correlations as highly dependent: Work area – Xenophobia (p < 0.045), Work with COVID patients - Traumatic stress (p < 0.001) and Total number of COVID patients per day – Traumatic stress (p < 0.027), and Total number of COVID patients - Compulsive checking and reassurance. Overall concluding that normal levels of stress have increased (mild – moderate). Additionally, we further determine that the fear of being an asymptomatic patient (potential to spread without knowing) continues being a concern.
ARTICLE | doi:10.20944/preprints202009.0602.v1
Subject: Medicine & Pharmacology, Allergology Keywords: COVID-19; Genomes; microRNA; SARS-CoV-2; Variant discovery
Online: 25 September 2020 (10:14:46 CEST)
Background SARS-CoV-2 has generated a life-treating pandemic and is the main challenge of this century. Some untranslated regions (UTRs) in SARS-CoV-2 genome, specifically leader sequence and transcription regulatory sequence (TRS) in 5’UTR, can be considered as Achilles' heel of virus. Leader sequence are found at the 5' ends of all encoded transcripts that highlights its importance. TRS can explain the host range and pathogenicity of coronavirus. However, our knowledge on the evolution and the role of UTRs in SARS-CoV-2 pathogenicity is very limited. This study is a pioneering attempt to unravel the evolution of key regions in 5' UTR of SARS-CoV-2 and discover the inhibitory microRNAs against 5' UTR of virus. Methods Evolution of TRS and leader sequence was compared between human pathogenic (SARS-CoV-2, SARS, and MERS) and non-pathogenic (bovine) coronaviruses. Profiling of microRNAs that can inactive the key UTR regions of coronaviruses, UTR-inhibitory microRNAs, was carried out. Findings We found a distinguished pattern of evolution in leader sequence and TRS of SARS-CoV-2, compared to the other coronaviruses. Mining all available microRNA families against leader sequences of coronaviruses resulted in discovery of 39 microRNAs with an acceptable thermodynamic binding energy against SARS-COV-2, SARS, MERS, Bat Coronavirus, or Bovine Coronavirus. Multivariate analysis demonstrated a distinguished pattern of binding of leader sequence of SARS-CoV-2 against microRNAs, with a lower binding stability. hsa-MIR-5004-3p was the only human microRNA that can target leader sequence of SARS and SARS-CoV-2. However, its binding stability remarkably decreased in SARS-COV-2 (-19.4 kcal/mol), compared to SARS-COV-2 (-25.9 kcal/mol). We found an insertion-type mutation in leader sequence of SARS-COV-2 that results in lower binding stability and escaping of viral leader sequence from hsa-MIR-5004-3p. Altogether, we suggest lack of innate human inhibitory microRNAs to bind to leader sequence and TRS of SARS-CoV-2 contributes to its high replication in infected human cells. On the other hand, mining of two hundred million deposited human genomic variants led us to discovery of 49 missense and splice-disrupt mutations in genomic structure of hsa-MIR-5004-3p. These mutations can negatively affect hsa-MIR-5004-3p function in preventing SARS-CoV-2 replication. Interpretation This study unravels the evolution of key regions in 5’UTR of SARS-CoV-2. Inducing microRNAs to bind to the leader sequence and TRS regions by drugs or food supplements can reduce virus replication. Enhancing the microRNA defence machinery against TRS and leader of virus has a potential to prevent SARS-CoV-2 infection at the first place. The mentioned strategy is rapidly achievable against COVID-19. Missense variation in genomic sequence of 5’UTR inhibitory microRNAs, such as hsa-MIR-5004-3p, can be considered as risk factor of COVID-19.
Subject: Keywords: undergraduate, research, COVID-19, CUREs, interest, communication, identity
Online: 24 September 2020 (18:14:34 CEST)
Course-based Undergraduate Research Experiences (CUREs) provide active and authentic scientific involvement to tens of thousands of students each year. Through this process, CUREs offer the benefits of increased learning outcomes, improved equity, and increased retention in STEM. During the COVID-19 pandemic, however, research and teaching labs have limited capacity. Some universities are closed for in-person learning altogether, and others are likely to face emergency shut-downs throughout the year. In this setting, the inability to conduct experiments limits a core aspect of CUREs. Without experimentation as a basis for student engagement, interest, and broader relevance, true course-based research this year becomes a major challenge. We suggest that this limitation provides a moment to enhance CUREs with research-enriching learning activities that are obtainable while away from the bench. In this essay we outline a variety of these student-centered activities and review their benefits in terms of student interest, learning, and equity. While useful during emergency teaching transitions during COVID-19, we make the case that these new evidence-based practices for CUREs will also be helpful for the enrichment of research-based learning beyond the current crisis.
ARTICLE | doi:10.20944/preprints202009.0577.v1
Subject: Engineering, Other Keywords: personal protective equipment (PPE); COVID-19; manufacturing; prototyping; 3D-printing; biocompatibility; sterilization; face shields; regulatory sciences; local resilience
Online: 24 September 2020 (10:45:53 CEST)
The disruption of conventional manufacturing, supply, and distribution channels for medical supplies during the COVID-19 pandemic has caused widespread shortages and catalyzed local efforts to use nontraditional, rapid manufacturing to meet urgent healthcare needs. Here we present a crisis-responsive design framework designed to assist with product development under pandemic conditions. The framework utilizes extensive stakeholder engagement, comprehensive and dynamic needs assessment, local manufacturing, and product testing for the accelerated development of healthcare products. We contrast this framework with traditional medical device manufacturing and discuss relevant regulatory policies. We highlight the applicability of the crisis-responsive framework to a successful local program that designed and supplied face shields for a large US academic hospital. Finally, we make recommendations aimed at improving future resilience to healthcare emergencies. These include continued development of open source designs suitable for rapid manufacturing and changes in regulatory policy that strike a balance between rigidity and uncontrolled innovation.
Subject: Life Sciences, Molecular Biology Keywords: COVID-19; SARS-CoV-2; RT-PCR; control strategy; Morocco
Online: 24 September 2020 (10:45:21 CEST)
Since March 2nd, 2020, date of the first SARS-COV-2 detected case in Morocco; multiples activities were adopted as COVID-19 control strategies. If the first period of COVID-19 noticed a few numbers of cases and deaths, the second half from July until today is marked with an exponential increase of the number of cases and a spread in almost all provinces with more intensive care needs and more deaths. The fatality rate of this disease is mainly compared with the highest developed countries in Europe and America. Instead of comparing the strategy and the deaths, with similar Arabic, African or Asiatic Middle-Income countries like Tunisia, Jordan, Cote d’Ivoire, Uzbekistan; that socio-demographic situation, behaviours, population density, and individual vulnerabilities create less confounding factors to make fair comparisons. Thus, this report has the aim to present how the COVID-19 pandemic was dealt in Morocco during this 200 days, by highlighting some discrepancies with corrective advice to get better future control results against COVID-19 and afford a possible comparison with other countries.The policy analysis approach was followed as a method to defines the pitfalls themes and to compare with the updated available international information about was it work and what is not needed to do. In conclusion, molecular biology represented by q-RT-PCR is the immediate action to do to enhance the diagnostic and the overall control strategy by knowing how to interpret its results following the time progress of cycle quantification values.
REVIEW | doi:10.20944/preprints202009.0565.v1
Subject: Life Sciences, Virology Keywords: Coronavirus; SARS-CoV-2; COVID-19; Immunobiochemical aspects; pathogenesis; diagnosis; management
Online: 24 September 2020 (04:39:38 CEST)
Background: A new coronavirus (SARS-CoV-2) that emerged from Wuhan, Hubei Province, China, has spread throughout the world and is declared a pandemic by the World Health Organization (WHO). A lot remains to be understood of SARS-CoV-2 and the disease (COVID-19). SARS-CoV-2 has until recently been identified as responsible for both asymptomatic and serious life-threatening infections. The unavailability of specific therapeutic agents is a major hurdle in the treatment and management of COVID-19 patients. The present review attempts to evaluate the immunobiochemical aspects of the pathogenesis, diagnosis, and management of SARS-CoV-2 infection. Main Body: This review is a comprehensive evaluation of the data collected through various sources, including Google Scholar, PubMed, and Scopus. The articles were searched and selected using key words such as “Coronavirus disease (COVID-19)”, “Diagnosis of COVID-19”, Pathogenesis of Covid-19”, “management of COVID-19”, “Immunology of COVID-19”, and “Complications of COVID-19”. The study noted that the novel Coronavirus infection could result in an exaggerated immune response, causing a cytokine storm and damaging several organs of the body. The infected patients develop several complications, including immunological, hematological, and biochemical alterations. Consequently, COVID-19 patients may develop cardiovascular, liver, renal, and neurological complications, among others. Conclusion: An increased understanding of the immunobiochemical aspects of the disease may contribute to better management of SARS-CoV-2-infected persons, as evidenced from the available literature. A holistic approach to the management of COVID-19 patients taking into consideration the effect of COVID-19 infection on various organs of the body assumes increased significance in patient management.
REVIEW | doi:10.20944/preprints202009.0561.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: covid19; immunostimulant; immunomodulator; vitamin D; vitamin C; zinc
Online: 24 September 2020 (03:40:34 CEST)
Background & Aims: The covid19 is a world changing challenge. Furthermore, this disease challenges our capacities to change our point of view in the domain of infectiology, immunology and global public health. Many trials try some drug such as antiviral (lopinavir, remdesivir) interferon, and the chloroquine. Unfortunately, all approach is not really convincing at this time. We are proposing another approach on this issue. In infectiology there are two protagonists : the host and its immune system versus pathogens and its virulence. Our approach focuses on an intervention on the host’s immune system and how stimulate and modulate its reactions. Methods: We searched on PubMed and Google Scholar databases for French and English-language studies, without a limit of date of publications, for randomized clinical trials, meta-analyses, reviews, systematic reviews, observational studies, case report. We performed a review on the field of immunology enhancements by nutrients use. Results: We identified groups of vitamins (D and C), oligo-elements (magnesium, zinc, selenium) and nutrition advice which enhance immune system response. Indeed, these supplements have some proved properties in modulating and stimulating the immune system. For example, a recent study demonstrates that vitamin D deficiency is linked with the severity of covid19. Majority of the population has a deficiency in these elements. According to this, we propose a therapeutic protocol using these elements to reach an efficient therapy against covid19 by enhancing host’s immune system. Conclusion: Due to this serious pandemic, any solutions must not be disregarded. The nutrition way is an entire part of the solution.
BRIEF REPORT | doi:10.20944/preprints202009.0555.v1
Online: 23 September 2020 (17:44:21 CEST)
Background: Coronavirus disease (COVID-19) has caused more than 745,000 deaths worldwide. Vitamin D has been identified as a potential strategy to prevent or treat this disease. The purpose of the study was to measure vitamin D at hospital admission of COVID-19; Methods: We included critically ill patients with the polymerase chain reaction positive test for COVID-19, from March to April, 2020. Statistical significance was defined as P < .05. All tests were 2-tailed; Results: A total of 35 patients (median age, 60 years; 26 [74.3%] male) were included. Vitamin D levels were categorized as deficient for 14 participants (40%). Vitamin D deficiency was associated with vitamin A (P= 0.003) and Zinc (P= 0.019) deficiency and lower levels of albumin (P= 0.026) and prealbumin (P= 0.009). Overall, none of the studied variables were associated with vitamin D status: mortality, intensive care unit (ICU) or hospital stay, necessity of vasoactive agents, intubation, prone position, C reactive protein (CRP), Dimer-D, Interleukin 6 levels (IL-6), ferritin levels, or bacterial superinfection; Conclusions: In this single-center, retrospective cohort study, deficient vitamin D status was found in 40% in COVID-19 critically ill patients. However, deficient vitamin D status was not associated with inflammation or outcome.
ARTICLE | doi:10.20944/preprints202008.0204.v2
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; SARS-Cov-2; epidemic surveillance; emerging infectious disease; epidemic threshold
Online: 23 September 2020 (11:10:15 CEST)
Background: Understanding SARS-CoV-2 dynamics and transmission is a serious issue. Its propagation needs to be modeled and controlled. The Alsace region in the East of France has been among the first French COVID-19 clusters in 2020. Methods: We confront evidence from three independent and retrospective sources: a population-based survey through internet, an analysis of the medical records from hospital emergency care services, and a review of medical biology laboratory data. We also check the role played in virus propagation by a large religious meeting that gathered over 2,000 participants from all over France mid-February in Mulhouse. Results: Our results suggest that SARS-CoV-2 was circulating several weeks before the first officially recognized case in Alsace on February 26th 2020 and the sanitary alert on March 3rd. The religious gathering seems to have played a role for secondary dissemination of the epidemic in France, but not in creating the local outbreak. Conclusions: Our results illustrate how the integration of data coming from multiple sources could help trigger an early alarm in the context of an emerging disease. Good information data systems, able to produce earlier alerts, could have avoided a general lockdown in France.
REVIEW | doi:10.20944/preprints202009.0535.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; Pandemic; Global health; Health inequalities
Online: 23 September 2020 (04:13:51 CEST)
The COVID-19 crisis has brought unprecedented strain on healthcare systems around the world. It has perhaps taught us some key lessons that are worth considering and addressing to help build more sustainable health systems as well as improve our ability to combat future epidemics.
REVIEW | doi:10.20944/preprints202009.0526.v1
Subject: Life Sciences, Virology Keywords: COVID-19 testing; molecular diagnostics; immunological testing; RT-qPCR; ELISA; pool PCR; lateral flow assay; rapid assay
Online: 23 September 2020 (03:33:12 CEST)
Accurate diagnosis at an early stage of infection is essential for the successful management of any contagious disease. The COVID-19, caused by the SARS-CoV-2 virus is a pandemic that has affected 214 countries affecting more than 30.8 million people causing 0.957 million deaths as of third week of September, 2020. The primary diagnosis of the infection is done either by the molecular technique of RT-qPCR by detecting portions of the RNA of the viral genome or through immunodiagnostic tests by detecting the viral proteins or the antibodies produced by the host. As the demand for the test increased rapidly many naive manufacturers entered the market with novel kits and more and more laboratories also entered the diagnostic arena making the test result more error-prone. There are serious debates globally and regionally on the sensitivity and specificity of these tests and about the overall accuracy and reliability of the tests for decision making on control strategies. The significance of the test is also complexed by the presence of asymptomatic carriers, re-occurrence of infection in cured patients as well as by the varied incubation periods of the infection and shifting of the viral location in the host tissues. In this paper, we review the techniques available for SARS-CoV-2 diagnosis and probable factors that can reduce the sensitivity and specificity of the different test methods currently in vogue. We also provide a check-list of factors to be taken care to avoid fallacious practices to reduce false positive and false negative results by the clinical laboratories
ARTICLE | doi:10.20944/preprints202009.0524.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: COVID-19; chest X-ray images; deep convolutional neural network; COV-MCNet; deep learning
Online: 23 September 2020 (03:31:30 CEST)
The COVID-19 pandemic situation has created even more difficulties in the quick identification and screening of the COVID-19 patients for the medical specialists. Therefore, a significant study is necessary for detecting COVID-19 cases using an automated diagnosis method, which can aid in controlling the spreading of the virus. In this paper, the study suggests a Deep Convolutional Neural Network-based multi-classification approach (COV-MCNet) using eight different pre-trained architectures such as VGG16, VGG19, ResNet50V2, DenseNet201, InceptionV3, MobileNet, InceptionResNetV2, Xception which are trained and tested on the X-ray images of COVID-19, Normal, Viral Pneumonia, and Bacterial Pneumonia. The results from 3-class (Normal vs. COVID-19 vs. Viral Pneumonia) showed that only the ResNet50V2 model provides the highest classification performance (accuracy: 95.83%, precision: 96.12%, recall: 96.11%, F1-score: 96.11%, specificity: 97.84%) compared to rest of the models. The results from 4-class (Normal vs. COVID-19 vs. Viral Pneumonia vs. Bacterial Pneumonia) demonstrated that the pre-trained model DenseNet201 provides the highest classification performance (accuracy: 92.54%, precision: 93.05%, recall: 92.81%, F1-score: 92.83%, specificity: 97.47%). Notably, the ResNet50V2 (3-class) and DenseNet201 (4-class) models in the proposed COV-MCNet framework showed higher accuracy compared to the rest six models. This indicates that the designed system can produce promising results to detect the COVID-19 cases on the availability of more data. The proposed multi-classification network (COV-MCNet) significantly speeds up the existing radiology-based method, which will be helpful to the medical community and clinical specialists for early diagnosis of the COVID-19 cases during this pandemic.
REVIEW | doi:10.20944/preprints202009.0198.v2
Subject: Life Sciences, Virology Keywords: coronavirus; aquatic organisms; fish; marine mammals; frogs; birds
Online: 22 September 2020 (11:45:01 CEST)
Coronaviruses are pathogens recognized for having an animal origin, commonly associated with terrestrial environments. However, although in a few cases, there are reports of their presence in aquatic organisms like fish, frogs, waterfowls and marine mammals. None of these cases has led to human health effects when contact with these infected organisms has taken place, whether they are alive or dead. Aquatic birds seem to be the main group carrying and circulating these types of viruses among healthy bird populations. Although the route of infection for CoVID-19 by water or aquatic organisms has not yet been observed in the wild, the relevance of its study is highlighted because there are cases of other viral infections known to have been transferred to humans by aquatic biota. It is encouraging to know that aquatic species, such as fish, marine mammals, and amphibians, shows very few cases of coronaviruses and that some other aquatic animals may also be a possible source of cure or treatment against then, as some evidence with algae and marine sponges suggest.
Subject: Keywords: malnutrition; COVID-19; protein; immune system; SARS-CoV-2; cell proliferation; starvation
Online: 22 September 2020 (08:32:14 CEST)
Many of the wide-ranging symptoms of COVID-19 have not been associated previously with a respiratory illness. A similarity between these atypical symptoms and the symptoms of malnutrition was observed. To investigate, a comparison of COVID-19 symptomatology with recognised states of malnutrition showed a significant relationship that was further explored in a review of the literature. This hypothesis links the atypical symptoms to the effects of increasing protein malnutrition. The rapid appearance of malnutrition symptoms at the beginning of the COVID-19 infection is concurrent with the rapid cell proliferation of the immune system. Although previous work has, in general, assumed that the body is capable of providing for the needs of the immune system during infection, heightened immune activity from the commencement of COVID-19 could require an early increase in energy yielding sources. Should insufficient availability of protein resources occur, this could quickly lead to malnutrition. Any continuing insufficiency, during the active phase of the virus, might result in widespread depletions in the tissues and the consequential malfunctioning of many organs. A new appraisal of the immune system requirements needed to counteract the impact of the novel virus, COVID-19, could show the potential benefit for earlier protein intervention in the disease process. This hypothesis could also have relevance for other life situations where a rapid cell proliferation might occur.
REVIEW | doi:10.20944/preprints202009.0500.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; impact on society during COVID-19; behavioral impact of COVID-19; government policies against COVID-19; measures adopted by the government; COVID-19 Statistics; Infection rate and Data analysis
Online: 21 September 2020 (11:09:11 CEST)
Background: COVID-19 pandemic has pulled us all a few steps back, were we never shake hands or hug each other when we meet our friends and family after a gap, but instead we greet them by saying Namaste and joining our hands together. As we all know, COVID-19 spreads through air and the only way to shield ourselves is by maintaining a safe distance from one another. Methodology: In order to conduct a meta-analysis on the number of COVID-19 cases in Kerala and India, the data was retrieved from various sites hosted by the government bodies. The data for analysis was collected from May 2020 to July 2020. The average number of days required to reach every 5000 fresh cases were also calculated using this data. COVID-19 has affected all the economy holistically regardless of financial, behavioral, or societal aspects. Conclusion: Lifting of the lockdown in a step by step process keeping in mind the necessities for the nation was a thoughtful act, but the people who mistook this opportunity and did not remain in quarantine after coming from abroad was recognized as the reasons behind the sudden and uncontrolled rise in the number of COVID-19 cases in Kerala, India. The government authorities had no other option but to lift the restrictions to reduce the economic burdens that had already affected the daily wage worker and farmers prompting them to give up their lives.
ARTICLE | doi:10.20944/preprints202009.0498.v1
Subject: Engineering, Energy & Fuel Technology Keywords: Cattle farming; COVID-19 pandemic; economic point of view; food safety; HOMER; hybrid system; smallholder; thin-film coating
Online: 21 September 2020 (07:32:51 CEST)
This paper reports on the optimization of thin-film coating assisted self-sustainable off-grid hybrid power generation systems for cattle farming in rural areas of Bangladesh. Bangladesh is a lower middle-income country with declining rates of poverty among its 160 million people due to persistent economic growth in conjunction with balanced agricultural improvements. Most of the rural households adopt a mixed farming system by cultivating crops and simultaneously rearing livestock. Among the animals raised, cattle are considered as the most valuable asset for the small/medium-scale farmers in terms of their meat and milk production. Currently, along with the major health issue, the COVID-19 pandemic is hindering the world’s economic growth and has thrust millions into unemployment; Bangladesh is also in this loop. However, natural disasters such as COVID-19 pandemic and floods, largely constrain rural smallholder cattle farmers from climbing out of their poverty. In particular, small and medium-scale cattle farmers face many issues that obstruct them from taking advantage of market opportunities and imposing a greater burden on their families and incomes. An appropriate measure can give a way to make those cattle farmers’ businesses both profitable and sustainable. Optimization of thin-film coating assisted self-sustainable off-grid hybrid power generation system for cattle farming is a new and forward-looking approach for sustainable development of the livestock sector. In this study, we design and optimize a thin-film coating assisted hybrid (photovoltaic-battery-generator) power system by using the Hybrid Optimization of Multiple Energy Resources (HOMER, Version 3.14.0) simulation tool. An analysis of the results has suggested that the off-grid hybrid system is more feasible for small and medium-scale cattle farming systems with long-term sustainability to overcome the significant challenges faced by smallholder cattle farmers in Bangladesh.
Subject: Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; coronavirus; signaling pathway; molecular alteration
Online: 21 September 2020 (04:17:24 CEST)
Emerging viruses description have grown at an unprecedented rate since the beginning of the 21st century. The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its related illness, Coronavirus Disease 2019 (COVID-19) has been reported as the third highly pathogenic coronavirus introducing itself into human population in the current era after the SARS-CoV and Middle East Respiratory Syndrome (MERS-CoV). Molecular and cellular studies considering the pathogenesis of this novel coronavirus are still in the early stages of research, however, regarding the similarity of SARS-CoV-2 and other coronaviruses, it could be hypothesized that the NF-κB, Cytokine regulation, ERK, and TNF-α signaling pathways are the more likely causes of inflammation upon onset of COVID-19. There are several drugs prescribed and used to alleviate the activity of these inflammatory cellular signaling pathways which might be beneficial for developing novel therapeutic modalities against COVID-19. In this review, we briefly summarized the alteration of cellular signaling pathways affected by coronavirus infection, particularly SARS-CoV and MERS-CoV and tabulated the current therapeutic agents approved for previous human diseases.
ARTICLE | doi:10.20944/preprints202009.0487.v1
Online: 21 September 2020 (03:35:15 CEST)
The age-related mortality and morbidity risk of COVID-19 has been considered speculative without enough scientific evidence. This study aimed to collect more evidence on the association between patient age and risk of severe disease state and/or mortality from SARS-CoV-2 infection. Genomic dataset along with metadata (3608 samples) retrieved from GISAID from different geographical regions were grouped into 10 age groups (0-10, 11-20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90, 91-100 years) as well as high-risk or low-risk according to patient clinical status. Genomic sequences were aligned and analyzed using MAFFT and FASTTREE to build a phylogenetic tree in order to identify age-risk associations based on phylogenetic clustering. Case fatality rates (CFR), as well as the Odds ratio (OR) for high-risk outcomes, were calculated for different age groups. Results revealed that individuals aged between 25-50 years have the best immune response to the infection. On the other hand, disease fatality was higher in patients aging above 50 years. We created an application to calculate the OR of being at high risk given a certain age threshold from GISAID datasets. OR values increased between ages 1-10 years (1.271) and 11-20 years (1.313) but reduced at age range 21-30 years (1.290) and increased again for 61-70 years (2.465). CFR calculated for each of the age groups had peak values at 90-100 years (26.8%) and the lowest at 0-10 years (0%). The CFR for ages above 50 years was about twice greater (11.6%-26.8%) than that for ages below (0-6.6%). The phylogenetic analysis revealed that the majority of samples obtained from India showed low-risk among different age groups and were defined as clade GH. Another cluster from Singapore visualization showed unfavorable patient outcome across several age groups and were classified under clade O. To conclude, this study analyses showed a variety of age-risk associations. As scientists from different countries upload more genomes to globally shared databases, more evidence will reinforce mortality risk associations in COVID-19 patients.
ARTICLE | doi:10.20944/preprints202009.0486.v1
Subject: Life Sciences, Immunology Keywords: COVID-19; comorbidity; SARS-CoV-2; leukemia; NAFLD; psoriasis; cancer; type II diabetes
Online: 21 September 2020 (03:32:58 CEST)
Background: Comorbidities have been frequently reported in COVID-19 patients, which often lead to more severe outcomes. The underlying molecular mechanisms behind these clinical observations have not yet been explained. Herein, we investigated the disease-specific gene expression signatures that may induce susceptibility to SARS-CoV-2 infection. Methods: We studied 30 frequently occurring acute, chronic, or infectious diseases of recent times that have shown comorbidity in one or another respiratory disease(s) caused by pathogenic human infecting coronaviruses, especially SARS-CoV-2. We retrieved array-based gene expression data for each disease and control from relevant datasets. Subsequently, all the datasets were quantile normalized, and log-2 transformed data was used for analysis. Results The expression of ACE2 receptor and host proteases, namely FURIN and TMPRSS2 that are essential for cellular entry of SARS-CoV-2, was upregulated in all six studied subtypes of leukemia (hereafter, referred as leukemia). The expression of ACE2 was also increased in psoriasis, lung cancer, Non-alcoholic fatty liver disease (NAFLD), breast cancer, and pulmonary arterial hypertension patients. The expression of FURIN was higher in psoriasis, NAFLD, lung cancer, and in type II diabetic liver, whereas it was lowered in breast cancer. Similarly, the expression of TMPRSS2 was increased during lung cancer and type II diabetes; it was decreased during psoriasis, NAFLD, lung cancer, breast cancer, and cervical cancer.Furthermore, a heightened expression of genes that are involved in immune response was observed in leukemia patients, as shown by the higher expression of IFNA2, IFNA8, IFNA10, IFNA14, IFNA16, IFNA21, IFNB1, CXCL10, and IL6. The expression of JAK1, STAT1, IL6, and CXCL10 was higher in NAFLD. Besides, JAK1 and STAT1 were upregulated in type II diabetic muscles. In addition, most of the upregulated genes in COVID-19 patients showed a similar trend in leukemia, NAFLD, and psoriasis. Furthermore, SARS-CoV-2, SARS-CoV and MERS CoV, were found to commonly alter two genes, namely, CARBONIC ANHYDRASE 11 and CLUSTERIN.Conclusions: The genes that may confer susceptibility to SARS-CoV-2 infection are mostly upregulated in leukemia patients; hence, leukemia patients are relatively more susceptible to develop COVID-19, followed by other chronic disorders, such as, NAFLD, type II diabetes, psoriasis, and hypertension. This study identifies key genes that are altered in the studied diseases types, which may aid in the infection of SARS-CoV-2 and underlie COVID-19 associated comorbidities.
ARTICLE | doi:10.20944/preprints202009.0459.v1
Online: 19 September 2020 (11:34:12 CEST)
The COVID-19 global pandemic has created dire consequences with an alarming rate of morbidity and mortality. There are not yet vaccine or efficacious treatment options to combat the causative SARS-CoV-2 infection. This paper describes the identification of potentially repurposable drugs for COVID-19 treatment by conducting pathway enrichment analysis on publicly available Gene Expression Omnibus datasets. We first determined SARS-CoV-2 infection-induced alterations of host gene expressions and pathways. We then identified drugs or compounds that target and counter virus-triggered cellular perturbations, suggesting their potential repurposing for COVID-19 treatment. The key findings are that SARS-CoV-2 infection in host cells induces mitochondrial dysfunction, inhibits oxidative phosphorylation, and activates several immune response and pro-inflammatory pathways. Triptolide, the major bioactive component of a traditional Chinese medicine herb, may rescue mitochondrial dysfunction by activating oxidative phosphorylation. Further in vitro and in vivo studies are necessary to verify these results prior to clinical application.
ARTICLE | doi:10.20944/preprints202009.0450.v1
Subject: Life Sciences, Molecular Biology Keywords: COVID-19; rRT-PCR; dilution; viral diagnosis; RNA extraction
Online: 19 September 2020 (08:27:13 CEST)
Although rRT-PCR is the gold standard method for SARS-CoV-2 detection, some factors, such as amplification inhibitors presence, lead to false-negative results. Here we describe differences between rRT-PCR results for SARS-CoV-2 infection in normal and diluted samples, simulating the need for dilution due to amplification inhibitors presence. Viral RNA extraction of nasopharyngeal swabs samples from 20 patients previously detected as 'Negative' and 21 patients detected as 'Positive' for SARS-CoV-2 was realized with the EasyExtract DNA-RNA (Interprise®) for extraction. rRT-PCR was realized with OneStep/COVID-19 (IBMP) kit with normal and diluted (80µl of H₂O RNAse free) samples, totaling 82 tests. The results indicate that there is an average variation (ɑ < 0.05) delaying Ct between the amplification results of internal control (IC), N Gene (NG), and ORF-1ab (OF) of 1.811Ct, 3.840Ct, and 3.842Ct, respectively. The extraction kit does not completely purify the inhibitor compounds, therefore non-amplification by inhibitors may occur. In this study, we obtained a 19.04% false-negative diagnosis after sample dilution, and this process reduces the efficiency of rRT-PCR to 29.8% for detecting SARS-CoV-2. Knowing the rRT-PCR standards of diluted samples can help in the identification of false-negative cases, and consequently avoid a wrong diagnosis.
ARTICLE | doi:10.20944/preprints202009.0446.v1
Subject: Medicine & Pharmacology, Other Keywords: Novel coronavirus diseases 2019; vaccination; target population; China
Online: 19 September 2020 (05:02:54 CEST)
All countries are facing decisions about which groups to prioritise for COVID-19 vaccination after the first vaccine product has been licensed, at which time supply shortages are inevitable. Here we define the key target populations and their size in China for a phased introduction of COVID-19 vaccination with evolving goals, accounting for the risk of illness and transmission. Essential workers (47.2 million) like healthcare workers could be prioritized for vaccination to maintain essential services. Subsequently, older adults, individuals with underlying health conditions and pregnant women (616.0 million) could be targeted to reduce severe COVID-19 outcomes. Then it could be further extended to target adults without underlying health conditions and children (738.7 million) to reduce symptomatic infections and/or to stop virus transmission. The proposed framework could assist Chinese policy-makers in the design of a vaccination program, and could be generalized to inform other national and regional COVID-19 vaccination strategies.
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: SARS-CoV-2; COVID-19; CNS; infant; Choroid plexus
Online: 19 September 2020 (04:49:18 CEST)
Coronavirus disease 2019 (COVID-19) was initially characterized as a respiratory illness. Neurological manifestations were reported mostly in severely affected patients. Routes for brain infection and the presence of virus particles in situ have not been well described, raising controversy about how the virus causes neurological symptoms. Here, we report the autopsy findings of a 1-year old infant with COVID-19. In addition to pneumonitis, meningitis and multiple organ damage related to thrombosis, a previous encephalopathy may have contributed to additional cerebral damage. SARS-CoV-2 infected the choroid plexus, ventricles, and cerebral cortex. This is the first evidence of SARS-CoV-2 detection in an infant post-mortem brain.
REVIEW | doi:10.20944/preprints202009.0439.v1
Subject: Medicine & Pharmacology, Dentistry Keywords: KAP; Dental professionals; COVID-19; Pandemic; risk of infection, SARS-CoV-2
Online: 18 September 2020 (12:15:24 CEST)
Background: Dental professions are at high risk of contracting novel corona virus (COVID-19) infections during the dental procedure due to the droplets and aerosols generated during various dental procedures on infected patients. To prevent and avoid the cross-infection of the infection to dental professionals or the patients attending the dental clinic, good knowledge of the infection and its prevention mechanisms is mandatory among the professionals. Until to date, there is no pooled estimate on the knowledge,attitude and practice (KAP) of dental professionals to COVID-19 in the globe. Hence, this study aimed to determine the pooled estimate of KAP of dental professionals in this pandemic disease. Methods: Article search was done electronically using Medline, Scopus, Web of Science, EMBASE, SciELO and Google Scholar from June 1, 2020 to August 20, 2020. All studies that assessed the KAP of dental professionals to COVID-19 were searched and included in this review after passing the inclusion criteria. The pooled analysis of their knowledge (sign and symptom, mode of transmission and prevention mechanisms), attitude (their concern, intention to treat suspected patients) and practice (face mask usage, hand washing and alcohol based hand rub usage, handshaking practice, deferred procedures and checkup of patients temperature) was computed using RevMan 5.3 and random effect model was used. The presence of publication bias was assessed using the funnel plot. Results: Twelve articles with a total of 5,362 study participants were included in this study. The pooled estimate revealed that 59.91% of the dental professionals had good knowledge of the signs and symptoms of COVID-19. Two-third of dental professionals know the prevention mechanisms of the infection, and 70.13% had enough knowledge of the transmission modalities of the infection. The professional attitude revealed that only 36.43% of the participants had intention to treat a patient with cough or suspected COVID-19 (36.43%, 95%CI: 8.57, 64.29). Moreover, 47.85% of the dentists were concerned about their life, and the fate of their profession due to this pandemic disease (47.85%, 95%CI: 26.74, 68.97). The pooled analysis showed only 50.86% (95%CI: 18.64, 83.09) of the study participants worn face mask and 52.63% (95%CI: 10.54, 94.71) had avoided handshaking practice during this pandemic period. Non-emergency dental procedures were canceled by 83.98%. Conclusion: The dental professional KAP is not optimal. Thus, dental professionals should be aware of the recently updated knowledge about COVID-19 and practice according to the standards of treatment guidelines, and the recommended infection control measures in dental settings. Moreover, as saliva and droplets are the major sources of infection, dentists should follow essential protocols to regulate droplet and aerosol contamination in the dental practice
ARTICLE | doi:10.20944/preprints202009.0436.v1
Subject: Biology, Ecology Keywords: 2019-nCoV; COVID-19; excess mortality; all-cause deaths; case fatality ratio; CFR; early transmission; SARS
Online: 18 September 2020 (11:31:51 CEST)
late in December 2019 2019-nCoV was identified as the pathogen responsible for an outbreak of severe respiratory distress in Wuhan, China. The virus was detected in multiple countries during January, but it is believed widespread community transmission began late in February or early March. Since March the virus has caused over 100k confirmed deaths in the US, with some states more severely impacted, notably NY and NJ. Here I examine excess mortality at the national and state level from January through July 2020. I find that the increase in excess mortality began in late February, suggesting the pathogen was circulating undetected earlier than assumed. The timing and intensity of the increase in excess mortality varied across states, with two patterns emerging: an early, sharp increase reaching a peak during April-May, best exemplified by NY and NJ, and a shallower, sustained increase, reaching a peak in late July, observed mostly in the southern regions of the US.
ARTICLE | doi:10.20944/preprints202009.0435.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: PIMS; MIS-C; SARS-CoV-2; COVID-19; Kawasaki disease; survey
Online: 18 September 2020 (11:29:49 CEST)
Pediatric inflammatory multisystem syndrome (PIMS) is a new entity in children, likely associated with previous coronavirus disease 19 (COVID-19). Most of reports about PIMS come from countries particularly hit by the COVID-19 pandemic. Our aim was to investigate the nature of inflammatory syndromes in Poland (a country with low COVID-19 prevalence) and to perceive the emergence of PIMS in our country. On May 25th, we have launched a nationwide survey of inflammatory syndromes in children for retrospective (since 4th March 2020) and prospective data collection. Up to 28th July, 39 reported children met inclusion criteria. We stratified them according to age (<5 and ≥ 5 years old) and COVID-19 status. The majority of children had clinical and laboratory features of Kawasaki disease, probably non-associated with COVID-19. However, children ≥5 years of age had PIMS characteristics, and 9 children had COVID-19 confirmation. This is the first to our knowledge report of PIMS register from the country with low COVID-19 prevalence, and it proves that PIMS may emerge in any area involved in the COVID-19 pandemic. In a context of limited COVID-19 testing availability, other risk factors of PIMS, e.g. older age should be considered in the differential diagnosis of inflammatory syndromes in children.
REVIEW | doi:10.20944/preprints202009.0361.v2
Subject: Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; foodborne viruses; enteric viruses; fecal-oral transmission; fresh produce, berries, fruits, hepatitis A virus, Norovirus, ready-to-eat foods.
Online: 18 September 2020 (10:35:33 CEST)
Background:Although highly strict social distancing and viral spread protection guidelines are in force, the reported numbers of COVID-19 cases across the world are still increasing. This indicates that we are still unable to completely understand the transmission routes of SARS-CoV-2. One of the possible routes that can play a significant role is the fecal-oral transmission since SARS-CoV-2 can replicate in the intestines as demonstrated by isolation of infectious virus from fecal samples of COVID-19 cases. Scope and approach:In this review, we compare the characteristics of SARS-CoV-2 with the distinctive characteristics of enteric foodborne viruses. We also discuss and respond to the arguments given in some reports that downplay the importance of foodborne transmission route of SARS-CoV-2. Key findings and conclusions:Enteric viruses such as human noroviruses (HuNoVs) and hepatitis A virus (HAV) are known to transmit through foods such as fresh produce and berries, leading to frequent multistate foodborne disease outbreaks all over the world. SARS-CoV-2 was found to share four distinctive characteristics of foodborne viruses that allow them to transmit through foods. This similarity in characteristics, recent report of detecting SARS-CoV-2 particles from frozen food packages in China, and recent suspected foodborne COVID-19 case in New Zealand, indicate that foodborne transmission of SARS-CoV-2 is more evident than previously thought possible. To support or deny this route of transmission, urgent research needs to be undertaken to answer two primary questions and many secondary ones as described in this review.
REVIEW | doi:10.20944/preprints202009.0425.v1
Online: 18 September 2020 (09:58:49 CEST)
The Coronavirus disease 2019 (COVID-19) pandemic is clearly taking a firmer grip on South Africa and more podiatrists will face the potential transmission of SARS-CoV-2. Government response was swift with the implementation of a travel ban, strict national lockdown as well as social distancing and hygiene protocols in line with international health regulations. Co-morbidities such as tuberculosis and HIV/AIDS, endemic to South Africa, are considered a dangerous combination with COVID-19, making many South Africans vulnerable to contracting the COVID-19. Patients with diabetes as well as the aged are vulnerable, both in terms of potential combined complications and challenges in continuity in foot care. The demands of the pandemic may outstrip the ability of the health systems to cope. Should this time arrive, all healthcare practitioners, including podiatrists, would have to step in and take on a role beyond their scope of practice in order to ensure that the healthcare system does not get overwhelmed. It is important for podiatrists to keep abreast with the developments around the COVID-19, in order that they may institute appropriate clinical practice which will ensure maximum protection for themselves, staff and patients as well as providing quality foot health care.
REVIEW | doi:10.20944/preprints202009.0420.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: COVID-19; SARS-CoV-2; ACE2 receptor; spike glycoprotein; S glycoprotein immunogenic sequences; ACE2 polymorphism
Online: 18 September 2020 (04:56:02 CEST)
Pneumonia cases of unknown etiology in Wuhan, China, were reported to the WHO on 31st of December 2019. Later the pathogen was reported to be a novel coronavirus designated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that causes Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 is a novel pathogenic beta coronavirus that infects humans causing severe respiratory illness. However, multifarious factors can contribute to the susceptibility to COVID-19 related morbidity and mortality such as age, gender and underlying comorbidities. Importantly, SARS-CoV and SARS-CoV-2 entry into the host cells is mediated via ACE2 receptor. However, ACE2 receptor binding affinity to SARS-CoV-2 is 4 folds higher than that to SARS-CoV. Identification of different aspects such as binding affinity, differential antigenic profiles of spike glycoproteins, and ACE2 polymorphisms might influence the investigation of potential therapeutic strategies targeting SARS-CoV-2/ACE2 binding interface. Here we aim to elaborate on SARS-CoV-2 S1/ACE2 ligand that facilitates viral internalization as well as to highlight the differences between SARS-CoVs binding affinity to ACE2. We also discuss the possible immunogenic sequences of spike glycoprotein and the effect of ACE2 polymorphism on viral binding/infectivity and host susceptibility to disease. Furthermore, targeting of ACE2 will be discussed to understand its role in therapeutics.
ARTICLE | doi:10.20944/preprints202009.0404.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: Social Distancing; COVID-19; Human Detection and Tracking; Distance Estimation, Deep Convolutional Neural Networks; Crowd Monitoring, Inverse Perspective Mapping
Online: 17 September 2020 (11:57:01 CEST)
Social distancing is a recommended solution by the World Health Organisation (WHO) to minimise the spread of COVID-19 in public places. The majority of governments and national health authorities have set the 2-meter physical distancing as a mandatory safety measure in shopping centres, schools and other covered areas. In this research, we develop a Deep Neural Network-based Model for automated people detection, tracking, and inter-people distances estimation in the crowd, using common CCTV security cameras. The proposed DNN model along with an inverse perspective mapping technique leads to a very accurate people detection and social distancing monitoring in challenging conditions, including people occlusion, partial visibility, and lighting variations. We also provide an online infection risk assessment scheme by statistical analysis of the Spatio-temporal data from the moving trajectories and the rate of social distancing violations. We identify high-risk zones with the highest possibility of virus spread and infection. This may help authorities to redesign the layout of a public place or to take precaution actions to mitigate high-risk zones. The efficiency of the proposed methodology is evaluated on the Oxford Town Centre dataset, with superior performance in terms of accuracy and speed compared to three state-of-the-art methods.
ARTICLE | doi:10.20944/preprints202009.0403.v1
Online: 17 September 2020 (11:48:17 CEST)
This study has been taken during COVID-19. It describes the working scenario of all class of peoples and their mental anxieties are analysed based on their psychological behaviour patterns.
REVIEW | doi:10.20944/preprints202009.0395.v1
Subject: Life Sciences, Virology Keywords: Spike protein, V483A, substitution mutation, virus-host cell interaction, high transmission, infectivity.
Online: 17 September 2020 (10:43:02 CEST)
Exploring the biological significance of mutations in SARS-CoV-2 coronavirus, causing the COVID–19 pandemic, has recently become an area of paramount interest for many researchers, who are pouring their tremendous efforts, in cracking the COVID–19 pandemic code. One of many such mutations that have occurred in the viral genome is V483A mutation, which is a part of the receptor-binding motif (RBM), present in the S1 domain of the spike protein. V483A mutant virus is becoming popular in North America with 36 cases so far, due to its frequent occurrences in recent days. In this review, we have assembled all information, currently available on V483A mutation, and have made a critical analysis based on the perspectives of many researchers all around the world. Comparison is made between the wild type and the V483A mutants to analyze certain factors like the type of interaction between the virus and host cell interface, binding affinity, stability, partition energy, hydrophobicity, occurrence rate, and transmissibility. Insilico dynamic analysis shows minimal alteration in the receptor-binding domain (RBD) of V483A mutant protein in free-state and no significant change of mutant tertiary structure of RBM upon binding to the ACE2 receptor. Comprehensive details about infectivity and evasion of the immune system by the virus are discussed. This information can in turn be of monumental importance in the field of vaccine and drug development because the mutants are becoming resistant to the vaccines and monoclonal antibodies.
ARTICLE | doi:10.20944/preprints202009.0390.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: Recombinant protein; Protease; DPP4; Covid-19
Online: 17 September 2020 (08:44:17 CEST)
Proteases catalyse irreversible posttranslational modifications that often alter a biological function of the substrate. The protease dipeptidyl peptidase 4 (DPP4) is a pharmacological target in type 2 diabetes therapy primarily because it inactivates glucagon-like protein-1. DPP4 also has roles in steatosis, insulin resistance, cancers and inflammatory and fibrotic diseases. In addition, DPP4 binds to the spike protein of MERS virus, causing it to be the human cell surface receptor for that virus. DPP4 has been identified as a potential binding target of SARS-CoV-2 spike protein, so this question requires experimental investigation. Understanding protein structure and function requires reliable protocols for production and purification. We developed such strategies for baculovirus generated soluble recombinant human DPP4 (residues 29-766) produced in insect cells. Purification used differential ammonium sulfate precipitation, hydrophobic interaction chromatography, dye affinity chromatography in series with immobilised metal affinity chromatography, and ion exchange chromatography. The binding affinities of DPP4 to the SARS-CoV-2 full-length spike protein and its receptor binding domain (RBD) were measured using surface plasmon resonance. This optimised DPP4 purification procedure yielded 1 to 1.8 mg of pure fully active soluble DPP4 protein per litre of insect cell culture with specific activity >30 U/mg, indicative of high purity. No specific binding between DPP4 and CoV-2 spike protein was detected. In summary, a procedure for high purity high yield soluble human DPP4 was achieved and used to show that, unlike MERS, SARS-CoV-2 does not bind human DPP4.
ARTICLE | doi:10.20944/preprints202009.0375.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: co-infection; SARS-CoV-2; pike glycoprotein; stop mutations
Online: 17 September 2020 (05:33:59 CEST)
There is a rising global concern for the ongoing outbreak of SARS-CoV-2 due to its high transmission rate and unavailability of treatment. Through the binding of its spike glycoprotein with angiotensin type 2 (ACE2), SARS-CoV-2 can efficiently get in the cells of patients and start its pandemic cycle. Herein, the biological diversity of SARS-CoV-2 infection was assessed in Babylon province of Iraq by investigating the possible genetic variations of the spike glycoprotein. A specific coding region of 795 bp within the viral spike (S) gene was amplified from 19 patients who suffered from obvious symptoms of SARS-CoV-2 infection. Sequencing results identified fifteen novel nucleic acid variations with a variety of distributions within the investigated samples. The electropherograms of all the identified variations showed obvious co-infections with at least two different viral strains per sample. Within these co-infections, the majority of samples exhibited three nonsense single nucleotide polymorphism (SNP)s, p.301Cdel, p.380Ydel, and p.436del, which yielded three truncated SARS-CoV-2 spike glycoproteins of 301, 380, and 436 amino acids length, respectively. The network and phylogenetic analyses indicated that for all viral infections were derived from multi-ancestral origins. Results inferred from the specific clade-based tree entailed that some viral strains were derived from European G-clade sequences. In conclusion, our data demonstrated the absence of any single strain infection among all investigated viral samples in the studied area, which may entail a higher risk of SARS-CoV-2 in this country. Through the identified high frequency of truncated spike proteins, we suggest that defective SARS-CoV-2 may depend on helper strains having intact spikes in its infection. Alternatively, another putative ACE2-independent route of viral infection way also suggested. To the best of our knowledge, this is the first report to describe the co-infection of multiple strains of SARS-CoV-2 in patients with COVID-19.
ARTICLE | doi:10.20944/preprints202009.0367.v1
Subject: Mathematics & Computer Science, Numerical Analysis & Optimization Keywords: lattice model; computer simulation; COVID-19
Online: 17 September 2020 (03:04:02 CEST)
Susceptible, infective, recovered, and hospitalized/isolated individuals are placed on the cells of a nxn square lattice, where each cell is occupied by a single individual or is vacant. At discrete time units (typically one day each) all susceptibles and infectives execute a random movement and when a coincidence of the two types occurs the susceptible is converted to infective status according to some probability. Infectives are labelled by the number of days since originally infected. At each time increment the age label of the infectives is increased by one unit. When the label reaches a number like 15 or 20 days the susceptibles recover with some probability or become isolated/hospitalized. Upon reaching some age the latter types either recover or die. Probabilities for the movements and conversions from one status to another are implemented by random numbergeneration. Simulations were carried out to investigate the effect of several probability and age parameters, the size of population (proportional to nxn) and density (related to fraction of occupied cells), and the size of the movements. Mid-term gradual conversion of susceptibles to isolated was explored as intervention policy.
ARTICLE | doi:10.20944/preprints202009.0358.v1
Subject: Medicine & Pharmacology, Dentistry Keywords: Covid-19; HVE; Aerosol; Dentistry; Particle; Suction; External; PM1; PM2.5; PM10; Drilling
Online: 16 September 2020 (11:12:31 CEST)
(1) Introduction: External high volume extraction devices may offer a way to reduce any aerosol particulate generated. The aim of this study was to measure the particle count during dental aerosol procedures and compare the results to when a High Volume Extraction device is used; (2) Methods: A comparative clinical study measuring the amount of PM1, PM2.5 and PM10 aerosol particulate with and without the use of an external High Volume Extraction device was undertaken. In total, 10 restorative procedures were monitored with an an industrial Trotec PC220 particle counter. The air sampler was placed at the average working distance of the clinicians involved in the study - 420mm.; (3) Results: In the present study aerosol particulate was recorded at statistically significantly increased levels during dental procedures without an external high volume extraction device versus with the device. The null hypothesis was rejected, in that significant differences were found between the results of the amount of aerosol particle count with and without a High Volume Extraction device.; (4) Conclusion: If the results of the present study are repeated in an in vivo setting, an external high volume suction device may potentially lower the risk of transmission of viral particulate.
ARTICLE | doi:10.20944/preprints202009.0345.v1
Subject: Biology, Agricultural Sciences & Agronomy Keywords: food safety; SARS-CoV-2; coronavirus; ACEII; agricultural security; national security
Online: 16 September 2020 (03:57:36 CEST)
Coronavirus is now a significant human pathogen with the emergence of SARS-CoV-2. Until now there has been no data to support a threat to agricultural industries. Using a comparative genomic protein analysis, this study examined the angiotensin-converting enzyme II (ACEII) gene of 17 animal species with an emphasis on agriculture. To determine viral vulnerability the 20 known SARS-CoV-2 receptor-binding domain (RBD)/ACEII receptor interaction sites were compared to determine their potential susceptibility to the SARS-CoV-2 virus. With the known bat host’s (XP_032963186) number of binding sites as a threshold, we note that ALL animal species examined in this study contained significant numbers (≥10) of SARS-CoV-2 binding sites and could be at risk for SARS-CoV-2 infection. The data from this study suggest SARS-CoV-2 imposes a grave threat to the safety and security of the agricultural industry. Urgent studies are needed to determine if infected animals can transmit SARS-CoV-2 before and/or after processing.
REVIEW | doi:10.20944/preprints202009.0334.v2
Online: 16 September 2020 (03:01:07 CEST)
COVID-19, previously known as “2019 novel coronavirus”, is a newly discovered virus which causes severe acute respiratory syndrome, similar to corona virus 2 (SARS-CoV-2), which has spread widely through human to human contact and was declared a pandemic by the WHO in March 2020. To cope with this pandemic many countries have adopted nationwide lockdowns which restrict nonessential activities and encourage their populations to avoid public transport, work from hone wherever possible, and to maintain social distancing at all times. While the severity of these shutdowns has varied with country, large geographic regions of the world (including China, India, Iran, Italy, Spain, and the USA) have all been severely affected, not just in the loss of human life, but also in terms of the financial impacts the lockdowns will have on their countries future prosperityIt was previously reported that a number of environmental factors, including humidity and temperature, played an important role in development and spread of the SARS-Corona Virus infection with the virus retaining viability for over 5 days at temperatures between 22–25oC and relative humidity (RH) of 40–50%. Whereas, elevated temperatures and higher RH (38oC, and >95% RH) decreased virus viability (Kroumpouzos et al., 2020). The spread of COVID-19 started in low temperature areas of China, with major outbreaks subsequently occurring in Iran, Japan, Northern Italy and South Korea. These new virus epicenters all had similar temperature and latitude, along the 30-50◦N” zone. Subsequently, the virus was spread to regions of elevated temperature, such as India, the Middle East and Thailand, due to international travel (Kroumpouzos et al., 2020).The aim of this study was to consider the environmental impact of COVID-19, including water pollution. The paper is divided into four sections. In the first section the current literature related to COVID-19 is reviewed. In the second section a recent update on COVID-19 globally is presented, followed by a descriptive impact on the environment in the third section and finally in the fourth section the COVID-19 related worldwide environmental impact is discussed. Since COVID-19 is a currently an active pandemic with no end in sight, while constructive conclusions can only be made on the limited data currently, which may be prone to high errors. However, these conclusions may provide some preliminary suggestions for assisting in assessing spreading patterns of COVID-19 across the globe, and may be of long-term significances with respect to assessing the environmental impact of lockdown policies due to COVID-19 worldwide.
ARTICLE | doi:10.20944/preprints202009.0338.v1
Subject: Life Sciences, Virology Keywords: COVID-19; vaccine hesitancy; vaccine attitudes; vaccine development; SARS-CoV-2
Online: 15 September 2020 (10:32:28 CEST)
The COVID-19 pandemic continues to ravage the world, with the United States being highly affected. A vaccine provides the best hope for a permanent solution to controlling the pandemic. However, to be effective, a vaccine must be accepted and used by a large majority of the population. Structural equation modelling was used to analyze the relationships of several factors with attitudes toward potential COVID-19 vaccination. The survey was administered to 316 respondents across the United States by a survey corporation. Prior vaccine usage and attitudes predicted attitudes towards COVID-19 vaccination. Assessment of the severity of COVID-19 for the United States was also predictive. Approximately 68% of all respondents were supportive of being vaccinated for COVID-19, but side effects, efficacy, and length of testing remained concerns. Longer testing, increased efficacy and development in the United States were significantly associated with increased vaccine acceptance. Messages promoting COVID-19 vaccination should seek to alleviate the concerns of those who are already vaccine-hesitant. Messaging directed at the benefits of vaccination for the United States as a country would address the second predictive factor. Enough time should be taken to allay concerns about both short and long-term side effects before a vaccine is released.
REVIEW | doi:10.20944/preprints202009.0337.v1
Subject: Medicine & Pharmacology, Other Keywords: hand sanitizers; hand rubs; alcohol based; disinfection; hand hygiene; coronavirus; COVID-19
Online: 15 September 2020 (09:07:09 CEST)
The global use of alcohol based hand sanitizers (ABHS) as a means of controlling the transmission of infectious disease increased dramatically in 2020 as governments and public health agencies across the world advocated hand hygiene as a preventative measure during the COVID-19 pandemic. Although the performance of these products is most commonly defined as a function of their alcohol concentration, they are multifaceted products in which an interplay of several factors is important in determining efficacy. The hand sanitizer tetrahedron, is a novel concept that considers both ABHS formulation factors and product performance factors from a multi-dimensional perspective. The four faces of the tetrahedron represent input/formulation factors: 1) the type and amount of alcohol, 2) inactive ingredients, 3) the type of formulation/delivery system and 4) manufacturing practices. The four corners of the tetrahedron represent output/product performance factors: 1) efficacy, 2) sensory characteristics, 3) usage, usability and compliance and 4) product safety/adverse effects. All factors are of importance to ensuring the effectiveness and utility of these products.
ARTICLE | doi:10.20944/preprints202009.0327.v1
Online: 15 September 2020 (04:24:17 CEST)
In regions lacking genomic data, analysis of sequences from the early stages of an outbreak can provide important insights into the diversity of pathogens present. Following the detection of the first imported case of COVID-19 in the Northern sector of Ghana on 13th March 2020, we have now molecularly characterized and phylogenetically analysed sequences including three (3) complete genomes of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) isolated from nine (9) patients observed in Ghana. Eight (8) of these patients reported with a recent history of foreign travel and one (1) with no history of foreign travel. We performed high throughput sequencing for 9 samples following the determination of high concentration of viral RNA. In addition, we estimated the potential impact that long distance transportation of samples to testing centres may have on sequencing outcomes. Here, two samples that were closest in terms of viral RNA concentration but transported from sites which are over 400km apart were assessed. All sequences were compared to previous sequences from Ghana and representative sequences from regions where our patients had previously travelled. Complete genomes were obtained for three (3) sequences and with another near complete genome with a coverage of 95.6%. Sequences with coverage in excess of 80% were found to belong to three lineages namely A, B.1 and B.2. Our sequences clustered in two different clades with the majority falling within a clade composed of sequences from sub-Saharan Africa. Less RNA fragmentation was seen in sample KATH23 which was collected 9km compared with sample TTH6 which was collected and transported over a distance of 400km to the testing site. The clustering of several sequences from sub-Saharan Africa suggests regional circulation of the viruses in the subregion. Importantly, there may be the need to decentralize testing sites and build more capacity across Africa to boost the sequencing output of the subregion.
ARTICLE | doi:10.20944/preprints202009.0323.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: COVID-19; lockdown; CNN; DLNN; GRU; mental anxiety; hybrid approach
Online: 15 September 2020 (02:56:33 CEST)
COVID-19 and new concept, lockdown, change social life of all classes of humans. Children partially feel the changes of daily life and this situation has been children’s free mind. Children are under a new type of restriction imposed on them by their parents. Normally they prefer play with their their friends than study and always waiting for holidays. They heard a new jargon i.e. lockdown where everything stands still. Very often they see peoples in the roads and few vehicles are moving in the roads. However, a peculiar thing happens now that they sit in front of computer to hear the virtual classes that are taken by the teachers. This also happens when there is no lockdown since COVID-19 still affects people. The environment is totally changed and they do not find any proper answers from the parents about the scenario.This study has been made an attempt to carry out the mental affairs of children in West Bengal, India. Several families are surveyed for collecting responses mostly from rural areas as well as urban areas for the time-period from April, 2020 to July, 2020. An effort has been given in this paper to predict the stress, depression and anxiety faced by children during the COVID-19. A Deep Learning Neural Network (DLNN) based method is applied to understand the stress level, depression level and anxiety level amongst the children. A hybrid DLNN has been presented in this research that combines both Convolutional Layer and Gated-Recurrent Unit (GRU) for obtaining the prediction of the mental health of children. The model obtains an accuracy of 89.57% for defeminizing mental anxiety of children.
ARTICLE | doi:10.20944/preprints202009.0321.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: CoViD-19; COVID; Mortality; Weekly Cycle; Weekly Mortality Cycle
Online: 14 September 2020 (12:03:12 CEST)
Background. The Weekly Mortality Cycle among CoViD-19 patients has been studied.Methods. Mortality data obtained from the 'Worldometer' website were analyzed with a comparison of absolute values, percentages, and p-value. Results. For patients suffering from CoViD-19, the most favorable or the safest days of the week were Sundays and Mondays. Conclusion. The weekly cycle with decreased mortality on Sundays and Mondays is a unique phenomenon observed among victims of CoViD-19. Presumably the decreased mortality on certain days of the week related to the optimized therapeutic protocols used on the "safest days".
CONCEPT PAPER | doi:10.20944/preprints202009.0320.v1
Subject: Keywords: reciprocal personal/public protection; mask discriminating mouth and nose; mouth cover; mask; face covering; source control; source classification; Covid-19; active source; liquid droplets
Online: 14 September 2020 (11:45:27 CEST)
Reciprocal Personal/Public Protection (RPPP) featured with source control is introduced, Mask Discriminating Mouth and Nose (MDMN) is employed to serve the purpose, which includes polymer based mouth cover with optional nose cover. The new knowledge that mouth is a primary, active and dominant source of the virus has been well established, which is the base of MDMN. Source classification and related source control tools are discussed, mouth cover is recommended as the tool prioritized to use. Liquid droplets is identified as a hard issue related to mask, liquid droplets, mask fitting, comfort and facial recognition constitute real challenges of mask in addition to efficiency, All of these have been addressed with MDMN. Comparisons between MDMN and masks/face covering are taken on four aspects: efficiency and efficacy, tolerance and comfort, cost and waste, and civil rights and public interest. Mouth cover is recommended to replace the face covering and act as both a personal tool and a public utensil, mouth cover with nose cover can provide better protection than N95 etc. RPPP with MDMN, could be an alternative for lockdown, a parallel strategy to vaccine, and a collectively living way during the pandemic era. MDMN, featured with high efficiency protection, high degree comfort, easy wearing, tight-fitting, easy facial recognition & communication, reusability, cost-effective, environment friendly and scale manufacturing more readily and widely etc., is a simple and sustainable solution, which is essential for ordinary people to keep wearing it properly for protection.
ARTICLE | doi:10.20944/preprints202009.0304.v1
Subject: Earth Sciences, Environmental Sciences Keywords: COVID-19; waste generation; waste collection; gap assessment; emergency plans
Online: 13 September 2020 (23:54:22 CEST)
The nationwide lockdown imposed to control the spread of novel coronavirus induced dramatic alterations in different sectors of the Nepalese governance including Solid Waste Management (SWM) practices. This study identifies SW collection gaps in nine major cities of Nepal, and highlights the municipal and public hearings on SW management practices before and during the lockdown with a view to emphasize the linkage between Covid-19 and SWM. It includes information on solid waste workers safety practices, collection coverage dynamics, types of vehicles operated for collection and alternative methods adopted by households to manage SW during the collection gaps. It was found that although the coverage of the collection service was similar during the pandemic, there was drastic decrease in the collection frequency leading to a collection gap of 560.58 tons/day and no proper measures were adopted in more than 50% of the households surveyed for SWM during the collection gap. The study reveals poor occupational health and safety practices among the solid waste workers due to unavailability of safety gears and equipment, in spite of being aware of the modes of transmission of the virus. The pandemic exacerbated the challenges of smooth SWM making its significance as an essential service more apparent. This highlights the need of a timely strategic emergency management framework to be developed by the government to continue the invaluable public service without any hindrance.
REVIEW | doi:10.20944/preprints202009.0274.v1
Subject: Keywords: COVID-19, Bangladesh, Challenges, Initiatives, Controversial issue
Online: 12 September 2020 (15:28:26 CEST)
Since the first coronavirus patient was identified in Bangladesh on March 8, the most controversial issue is about the exact level of the infection in Bangladesh. Conformity with the population density the number of COVID-19 tests is inadequate. As the number of tests increases, so does the number of infections, making it difficult to predict the spread of COVID-19 in Bangladesh. In this case, the unplanned initiatives are particularly responsible in other for unplanned measures, lack of public awareness, and lack of proper knowledge. In this case, the Ministry of Health has made three major mistakes, three important features of the medical system in Bangladesh have been mentioned. It is more effective to prevent COVID-19 by isolating the infected person by further testing COVID-19 until effective treatment is available and to provide adequate and effective masks and personal protective equipment (PPE). In this case, the COVID-19 testing kit invention has received a good response in many countries of the world. This study focuses on the comprehensive data verification, selection, and evaluation of COVID-19 in Bangladesh and its implications for the future, what to do to address and prevent the COVID-19 challenge, and effective treatment against the coronavirus (COVID-19). It is hopeful that the discussion of the material mentioned in this research paper will help to strike a balance between the government, citizens, and experts which will be feasible in improving the current situation in COVID-19 Bangladesh and reducing its severity.
ARTICLE | doi:10.20944/preprints202006.0299.v4
Subject: Social Sciences, Other Keywords: COVID-19; coronavirus; pandemic; science; social science; bibliometric analysis
Online: 12 September 2020 (09:49:40 CEST)
The COVID-19 pandemic caused by the novel coronavirus emerged in Wuhan City, Hubei province of China at the end of 2019, has radically transformed the lives of people around the world. Due to its fast spreading, it is currently considered as a worldwide health, social and economic concern. The lack of knowledge on this area has encouraged academic sphere for extensive research, which is reflected in exponentially growing scientific literature in this area. However, current state of COVID-19 research reveals only early development of knowledge, while a comprehensive and in-depth overview remains neglected. Accordingly, the main aim of this paper is to fill the aforementioned gap in the literature and provide an extensive bibliometric analysis of COVID-19 research across science and social science research landscape, using innovative and sophisticated bibliometric approaches (e.g. Venn diagram, Biblioshiny descriptive statistics, VOSviewer co-occurrence network analysis, Jaccard distance cluster analysis, text mining based on logistic regression). The bibliometric analysis is based on the Scopus database including all relevant and latest information on COVID-19 related publications (n=16,866) in the first half of 2020. The empirical results indicate that there is still a lack of publications of COVID-19 and its implications in less-explored (non-health) sciences, especially in social sciences. Accordingly, the findings emphasize an importance of a comprehensive and in-depth approach considering different scientific disciplines in COVID-19 research. The understanding of the evolution of emerging scientific knowledge on COVID-19 is beneficial not only for scientific community but also for evidence-based policymaking in order to prevent and address the COVID-19 pandemic.
ARTICLE | doi:10.20944/preprints202008.0329.v2
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; Geospatial Regression; Health Disparities; Public Health
Online: 11 September 2020 (09:48:57 CEST)
COVID-19 is a potentially fatal viral infection. This study investigates geography, demography, socioeconomics, health conditions, hospital characteristics, and politics as potential explanatory variables for death rates at the state and county levels. Data from the Centers for Disease Control and Prevention, the Census Bureau, Centers for Medicare and Medicaid, Definitive Healthcare, and USAfacts.org were used to evaluate regression models. Yearly pneumonia and flu death rates (state level, 2014-2018) were evaluated as a function of the governors’ political party using repeated measures analysis. At the state and county level, spatial regression models were evaluated. At the county level, we discovered a statistically significant model that included geography, population density, racial and ethnic status, three health status variables along with a political factor. State level analysis identified health status, minority status, and the interaction between governors’ parties and health status as important variables. The political factor, however, did not appear in a subsequent analysis of 2014-2018 pneumonia and flu death rates. The pathogenesis of COVID-19 has greater and disproportionate effect within racial and ethnic minority groups, and the political influence on the reporting of COVID-19 mortality was statistically relevant at the county level and as an interaction term only at the state level.
ARTICLE | doi:10.20944/preprints202009.0249.v1
Online: 11 September 2020 (08:20:18 CEST)
The world is currently experiencing COVID-19, one of the worst pandemics that have happened in this century, affecting 10.7 million people worldwide. It has caused massive growth in the number of employees working from home. However, employees have minimal cybersecurity resources unlike organizations with security teams protecting them against attacks. Hence, cybersecurity plays an important role as users can be easily targeted by cybercriminals. This paper examines how cyberattacks have increased during this pandemic and shows how greatly they have affected health organizations, individuals and social networking applications. Results of the attacks include data breaches, false announcements and operations being disrupted. Attacks occurring during this pandemic and how they were handled are also critically discussed. The existing contributions do touch on related attacks but do not provide in-depth solutions regarding the issues. Even though there are many works and findings that were done previously, technology is ever evolving. Therefore, we need to be well versed with current and future issues and provide the latest mechanisms to prevent cybersecurity threats from occurring. On our share, we intend to present our findings on the challenges being faced by the population and its increasing threats as well as presenting unique solutions that can help organizations or related persons understand or spread awareness on the importance of cybersecurity. Through the research performed in this paper, it is found that there are many ways these issues can be alleviated. However, the issue is that there is significant lack of action and investment in terms of actual implementation and application of the available solutions.
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: COVID-19; SARS-CoV-2; hepatic encephalopathy; CIGB-258
Online: 11 September 2020 (05:49:43 CEST)
Hepatic encephalopathy is a complex life-threatening neuropsychiatric syndrome, which can be associated with acute inflammation. It can be found in cases of acute liver failure caused by a viral infection. Reports of patients infected with SARS-CoV-2 have described hepatic encephalopathy. Therapy with immunomodulators can be an effective choice for this clinical condition. CIGB-258 is an immunomodulatory peptide with anti-inflammatory properties derived from cellular stress protein 60 (HSP60). We report a case of a 55-years-old woman diagnosed with COVID-19 and hepatic encephalopathy characterized by episodes of anxiety, delirium, confusion and seizure, according to her clinical history, laboratory and radiological data. Levels of aspartate aminotransferase, alanine aminotransferase , plasma ammonia and alkaline phosphatase were increased and inflammatory biomarkers such as interleukin 6 and 10 were over the normal range. The patient received an intravenous administration of 1 mg of CIGB-258, every 12 hours during four days, followed by 1 mg daily for another three days without adverse reactions. Neurological symptoms disappeared completely at by the fourth days after starting therapy, and inflammatory biomarkers noticeably decreased, but not all of them reach the normal values. This case highlights the outcomes of a severe COVID-19 patient with hepatic encephalopathy, treated with CIGB-258. The patient recovered successfully and the liver enzymes, plasma ammonia and biomarkers associated with hyperinflammation were reduced. These results support clinical investigations of CIGB-258 as a therapeutic agent in COVID-19.TRIAL REGISTRATION: RPCEC00000313
ARTICLE | doi:10.20944/preprints202009.0242.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COPD; COVID-19; prevalence; prognosis
Online: 11 September 2020 (05:47:59 CEST)
Patients with COPD have a higher prevalence of coronary ischemia and other factors that put them at risk for COVID-19-related complications. We aimed to explore the impact of COVID-19 in a large population-based sample of patients with COPD in Castilla-La Mancha, Spain. We analyzed clinical data in electronic health records from January 1st to May 10th, 2020 by using Natural Language Processing through the SAVANA Manager® clinical platform. Out of 31,633 COPD patients, 793 had a diagnosis of COVID-19. The proportion of patients with COVID-19 in the COPD population (2,51%; CI95% 2,33 – 2,68) was significantly higher than in the general population aged > 40 years (1,16%; 95%CI 1,14 – 1,18); P < .001. Compared with COPD-free individuals, COPD patients with COVID-19 showed significantly poorer disease prognosis, as evaluated by hospitalizations (31,1 % vs 39,8%: OR 1,57; 95%CI 1,14 – 1,18) and mortality (3,4% vs 9,3%: OR 2,93; 95%CI 2,27 – 3,79). Patients with COPD and COVID-19 were significantly older (75 vs. 66 years), predominantly male (83% vs 17%), smoked more frequently, and had more comorbidities than their non-COPD counterparts. Pneumonia was the most common diagnosis among COPD patients hospitalized due to COVID-19 (59%); 19% of patients showed pulmonary infiltrates suggestive of pneumonia and heart failure. Mortality in COPD patients with COVID-19 was associated with older age and prevalence of heart failure (P<0.05). COPD patients with COVID-19 showed higher rates of hospitalization and mortality, mainly associated with pneumonia. This clinical profile is different from exacerbations caused by other respiratory viruses in the winter season.
BRIEF REPORT | doi:10.20944/preprints202009.0229.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; pneumonia; low-dose whole-lung irradiation; SpO2
Online: 10 September 2020 (08:36:57 CEST)
Purpose: Novel coronavirus disease (COVID-19) is the current global concern. Radiotherapy (RT), commonly employed in cancer management, has been considered one of the potential treatments for COVID-19 pneumonia. Here, we present the final report of the pilot trial evaluating the efficacy and safety of low-dose whole-lung irradiation (LD-WLI) in patients with COVID-19 pneumonia. Methods and Materials: We enrolled patients with moderate COVID-19 pneumonia who were older than 60 years. Participants were treated with LD-WLI in a single fraction of 0.5 or 1.0Gy along with the national protocol of COVID-19. The primary endpoints were improvement of SpO2, the number of hospital/ICU stay days, and the number of intubations after RT and the secondary endpoints were alterations of the c-reactive peptide, interleukin-6, ferritin, procalcitonin, and D-dimer. The response rate (RR) was defined as a rise in SpO2 upon RT with rising or constant trend in the next two days, and clinical recovery (CR) included patients who were discharged from the hospital or acquired SpO2 ≥93% on room air. Results: Between 21 May 2020 and 2 July 2020, ten patients were enrolled. The median age was 75 years, 80% were male, and 80% had comorbidities. The first five patients received a single 0.5Gy-WLI, and others received 1.0Gy. Patients were followed for 2-14 days (median 5.5 days). Following one day, nine patients experienced an improvement in SpO2. Five patients were discharged (median 6th day, range 2nd-14th day), and four patients died (median 7th day, range 3rd-10th day). Overall, the RR and CR were 60.0% and 55.5%, respectively. The RR and CR rates of 0.5- and 1.0Gy group were 80% vs 40% and 75% vs 40%, respectively. No acute radiation-induced toxicity was recorded. Conclusions: LD-WLI with a single 0.5Gy fraction seems to be a more appropriate dose to warrant further evaluation in a large-scale, randomized trial.
ARTICLE | doi:10.20944/preprints202009.0228.v1
Subject: Engineering, General Engineering Keywords: multilayer perceptron; support vector machine; COVID19; SarsCov2; forecasting; machine learning; public health; pandemic
Online: 10 September 2020 (08:05:49 CEST)
This paper presents a Multilayer Perceptron and Support Vector Machine algorithms approach to predict the number of COVID19 infections in different countries of America. It intends to serve as a tool for decision-making and tackling the pandemic that the world is currently facing. The models were trained and tested using open data from the European Union repository where a time series of confirmed contagious cases was modeled until May 25, 2020. The hyperparameters as number of neurons per layer were set up using a tabu list algorithm. The countries selected to carry out the study were Brazil, Chile, Colombia, Mexico, Peru and the United States. The metrics used are Pearson's correlation coefficient (CP), Mean Absolute Error (MAE), and Mean Percentage Error (MPE). For the testing stage we obtained the following results: Brazil, CP=0.65, MAE=2508 and MPE=17%; Chile, CP=0.64, MAE=504, MPE=16%; Colombia, CP=0.83, MAE=76, MPE=9%; Mexico, CP=0.77, MAE=231, MPE=9%; Peru, CP=0.76, MAE=686, MPE=18% and the United States of America, CP=0.93, MAE=799, MPE=4%. This resulted in powerful machine learning tools although it is necessary to use specific algorithms depending on the data and the stage of the country’s pandemic.
Subject: Keywords: health innovation; technological innovation; social innovation; public health; global health; Ebola; Covid-19
Online: 10 September 2020 (06:15:43 CEST)
Health innovations are generally oriented on a techno-economic vision. In this perspective, technologies are seen as an end in themselves, and there is no arrangement between the technical and the social values of innovation. This vision prevails in sanitary crises, in which management is carried out based on the search for punctual, reactive, and technical solutions to remedy a specific problem without a systemic/holistic, sustainable, or proactive approach. This paper attempts to contribute to the literature on the epistemological orientation of innovations in the field of public health. Taking the Covid-19 and Ebola crises as examples, the primary objective is to show how innovation in health is oriented towards a techno-economic paradigm. Second, we propose a repositioning of public health innovation towards a social paradigm that will put more emphasis on the interaction between social and health dimensions in the perspective of social change.
ARTICLE | doi:10.20944/preprints202009.0213.v1
Subject: Social Sciences, Geography Keywords: twitter; discourse analysis; Covid-19; Coronavirus; disinformation; misinformation; social media activity; downplay
Online: 10 September 2020 (03:28:01 CEST)
Misinformation can amplify humanity's most significant challenges. As the novel coronavirus spreads across the world, concerns regarding the spreading of misinformation about it and also people downplaying the severity of it are also growing. This article investigates social media activity in May 2020, specifically Twitter, with respect to COVID-19, the themes of tweets, where the discussion is emerging from, disinformation shared about the virus, and its relationship with COVID-19 incidence rate at the state and county level. A geodatabase of all geotagged COVID-19 related tweets was compiled. Multiscale Geographically Weighted Regression was employed to examine the association between social media activity, population, and the spatial variability of disease incidence; our results suggest that MGWR could explain 96.7% of the variations. Moreover, Covid-19 related twitter dataset content analysis reveals a meaningful strong spatial relationship that exists between social media activity and known cases of COVID-19. Discourses analysis was conducted on tweets to index tweets downplaying the Pandemic or disseminating disinformation; the discourses analysis findings suggest that states in where twitter users spread more misinformation and showed more resistance to pandemic management measures in May are experiencing a surge in the number of cases in July.
Subject: Medicine & Pharmacology, General Medical Research Keywords: SARS-CoV-2 COVID-19; lung damage mechanisms; leukecyte recruitment; viral infection; immune response; temperature and humidity; interstitial pressure change
Online: 9 September 2020 (11:32:55 CEST)
To understand lung damage caused by COVID-19, we deduced two-phase lung damage mechanisms. After the lungs are infected with SARS-CoV-2 virus, the affected lung tissue swells and surface properties of pulmonary capillaries change, resulting in an increased flow resistance of affected capillaries. If a sufficient number of capillaries are affected by the infection, the swelling and increased cell wall adhesion collectively raise pulmonary vascular resistance. The increased vascular resistance further increases the dwell times of WBCs in affected capillaries and nearly capillaries. When pulmonary pressure is sufficiently higher, WBCs are forced to squeeze into interstitial spaces or alveolar spaces when local pressures are higher than what the capillaries can withstand. When more and more WBCs are dynamically retained, the flow resistance of more capillaries rises, pulmonary vascular resistance rises, and pulmonary pressure rises. The rise in the pulmonary pressure in turn results in elevated capillary pressures. When capillary pressures around the alveoli are sufficiently high, they cause interstitial pressures to change from normally negative values to positive values. The positive pressures cause fluid leakage to the alveolar space and thus degrade lung function. Tissue swelling, and occupation of WBCs in interstitial spaces and alveolar spaces further reduce compressible volume, and thus cause further rise in the pulmonary vascular resistance and pulmonary pressure. When the pulmonary pressure has reached a critical point as in the second phase, the blood breaks capillary walls and squeezes through interstitial spaces to reach alveolar spaces, resulting in irreversible lung damages. The available free volume in the thorax cage, organ usable capacities, temperature and humid are expected to have great impacts on degree of lung damages. The free volume in the thorax cage, lung usable surplus capacity, and other organ usable capacities determine the arrival time of last-phase irreversible damage. The mechanisms imply that the top priority for protecting lungs is maintaining pulmonary micro-circulation and preserving organ functions in the entire disease course while controlling viral reproduction should be stressed in the earliest time possible. The mechanisms also explain leukecytes are recruited and migrated into inflamed tissues by increasing their dwell times caused by increased local flow resistance.
ARTICLE | doi:10.20944/preprints202008.0267.v2
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; intensive care; trends; United Kingdom; mortality; mechanical ventilation
Online: 9 September 2020 (09:28:49 CEST)
Rationale: Examining trends in patient characteristics, processes of care and outcomes, across an epidemic, provides important opportunities for learning. Objectives: To report and explore changes in admission rates, patient characteristics, processes of care and outcomes for all patients with COVID-19 admitted to intensive care units (ICUs) in England, Wales and Northern Ireland. Methods: Population cohort of 10,287 patients with COVID-19 in the Case Mix Programme national clinical audit from 1 February to 2 July, 2020. Analyses were stratified by time period (pre-peak, peak, post-peak) and geographical region. Multivariable logistic regression was used to estimate differences in 28-day mortality, adjusting for patient characteristics over time. Main results: Admissions to ICU peaked simultaneously across regions on 1 April, with ongoing admissions peaking ten days later. Compared with pre- and post-peak periods, patients admitted during the peak were slightly younger but had greater respiratory and renal dysfunction. Use of invasive ventilation and renal replacement reduced over time. Twenty-eight-day mortality reduced from 43.5% (95% CI 41.6% to 45.5%) pre-peak to 34.3% (95% CI 32.3% to 36.2%) post-peak; a difference of −8.8% (95% CI: −5.2%, −12.3%) after adjusting for patient characteristics. London experienced the highest admission rate and had higher mortality during the peak period but a greater reduction in post-peak mortality. Conclusion: This study highlights changes in patient characteristics, processes of care and outcomes, during the UK COVID-19 epidemic. After adjusting for the changes in patient characteristics and first 24-hour physiology, there was substantial improvement in 28-day mortality over the course of the epidemic.
ARTICLE | doi:10.20944/preprints202009.0190.v1
Subject: Social Sciences, Geography Keywords: human mobility; COVID-19 spread; global pandemic; social restriction policy; Australia
Online: 8 September 2020 (11:31:16 CEST)
Policy induced decline of human mobility has been recognised to be effective in controlling the COVID-19 spread especially in the initial stage of the outbreak, although the relationship among mobility, policy implementation, and virus spread remains contentious. Coupling data of confirmed COVID-19 cases with Google mobility data in Australia, we present a state-level empirical study to: 1) inspect the temporal variation of COVID-19 spread and the change of mobility adherent to social restriction policies; 2) examine the extent that different types of mobility are associated with the COVID-19 spread in eight Australian states/territories; and 3) analyse the time-lag effect of mobility restriction on the COVID-19 spread. We find that social restriction policies implemented in the early stage of the pandemic controlled the COVID-19 spread effectively; the restriction of human mobility has a time-lag effect on growth rates, and the strength of the mobility-spread correlation increases up to seven days after policy implementation but decreases afterwards. The association between mobility and COVID-19 spread varies across space and time, and subjects to the types of mobility. Thus, it is important for governments to consider the degree to which lockdown conditions can be eased by accounting for this dynamic mobility-spread relationship.
Subject: Earth Sciences, Environmental Sciences Keywords: Sustainable intensification; crop diversification; COVID-19; food security; nutrition security; water security
Online: 8 September 2020 (10:21:33 CEST)
The COVID-19 pandemic is adversely impacting food and nutrition security and requires urgent attention from policymakers. Sustainable intensification of agriculture is one strategy that attempts to increase food production without adversely impacting the environment, by shifting from water-intensive crops to other climate-resistant and nutritious crops. This paper focuses on the Indian state of Andhra Pradesh by studying the impact of shifting 20% of the area under paddy and cotton cultivation to other crops like millets and pulses. Using FAO’s CROPWAT model, along with monsoon forecasts and detailed agricultural data, we simulate the crop water requirements across the study area. We simulate a business-as-usual base case and compare it to multiple crop diversification strategies using various parameters – food, calories, protein production, as well as groundwater and energy consumption. Results from this study indicate that reduced paddy cultivation decreases groundwater and energy consumption by around 9-10%., and a calorie deficit between 4-8% - making up this calorie deficit requires a 20-30% improvement in the yields of millets and pulses. We also propose policy interventions to incentivize the cultivation of nutritious and climate-resistant crops as a sustainable strategy towards strengthening food and nutrition security while lowering the environmental footprint of food production.
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV-2; zinc; zn; zinc-deficiency; cytokine storm
Online: 8 September 2020 (10:09:19 CEST)
Since the discovery of the first reported case with Zinc-deficiency in Iran1 by Prasad et al. in 1961, the knowledge on Zinc has increased significantly. Zinc is the second most abundant common trace mineral in the human body, responsible for vital biological functions from cell growth and development to cell homeostasis and immune response 2,3. Up to a fifth of the global population is estimated to suffer from different degrees of Zinc deficiency4. In the western world, Zinc deficiency is more prevalent among the geriatric population3, vegans/vegetarians, and people with certain underlying conditions4such as liver cirrhosis, inflammatory bowel disease, and various auto-immune disorders4,5. Zinc and Zinc deficiency has been associated with several infectious diseases 2,3. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is responsible for the ongoing pandemic belongs to the family of coronaviruses. SARS-CoV-2 has a high genetic similarity to another family member, SARS-CoV, which caused the first major epidemic of the 21st century6,7. Currently, there is no evidence linking the anti- SARS-CoV-2 response and the element Zinc. Herein and in light of the SARS-CoV-2 pandemic, we marshal the evidence associating the element Zinc with the anti-viral and antibacterial immune response as well as the cytokine storm and lung injury. Such a revisit of the precedent evidence may inspire further investigation assessing the relationship between Zincemia status and the anti-viral response in SARS-CoV-2 patients.
Subject: Keywords: SARS-CoV-2; S-protein; RBD; COVID-19; neutralizing antibodies; serology; T-cells; vaccines; animal models; Operation Warp Speed
Online: 7 September 2020 (12:29:06 CEST)
Multiple preventive vaccines are being developed to counter the COVID-19 pandemic. The leading candidates have now been evaluated in non-human primates (NHPs) and human Phase 1 and/or Phase 2 clinical trials. Several vaccines have already advanced into Phase 3 efficacy trials, while others will do so before the end of 2020. Here, we summarize what is known of the antibody and T-cell immunogenicity of these vaccines in NHPs and humans. To the extent possible, we compare how the vaccines have performed, taking into account the use of different assays to assess immunogenicity and inconsistencies in how the resulting data are presented. We also summarize the outcome of SARS-CoV-2 challenge experiments in immunized macaques, while noting variations in the protocols used, including but not limited to the virus challenge doses.
Subject: Life Sciences, Virology Keywords: COVID-19; thermal inversion; PM2.5 air pollution; desert dust intrusions
Online: 7 September 2020 (04:28:12 CEST)
A probe of a patient, seeking help in an emergency ward of a French hospital in late December 2019 because of Influenza like symptoms, was retrospectively tested positive to COVID-19. Despite the early appearance of the virus in Europe, the prevalence and virulence appeared to be low for several weeks, before the spread and severity of symptoms increased exponentially, yet with marked spatial and temporal differences. Here, we compare the possible linkages between peaks of fine particulate matter (PM2.5) and the sudden, explosive increase of hospitalizations and mortality rates in the Swiss Canton of Ticino, and the Greater Paris and London regions. We also discuss the influence of Saharan dust intrusions on the COVID-19 outbreak observed in early 2020 on the Canary Islands. We find that high PM2.5 concentrations – possibly favored by air temperature inversions or Saharan dust intrusions – are not only modulating but even more so boosting severe outbreaks of COVID-19. We conclude that the overburdening of the health services and hospitals as well as the high over-mortality observed in various regions of Europe in spring 2020 can be linked to peaks of PM2.5 and likely particular weather situations that have favored the spread and enhanced the virulence of the virus. In the future, we recommend to monitor not only the prevalence of the virus, but also to consider the occurrence of weather situations that can lead to sudden, very explosive COVID-19 outbreaks.
ARTICLE | doi:10.20944/preprints202004.0281.v2
Online: 7 September 2020 (04:15:59 CEST)
Spike (S) protein of Coronaviruses help in receptor attachment and virus entry into the host cells. While S protein is required for virus entry, it is also important as an immunogen as it is the most accessible part of the virus architecture. S protein form knob like structures (viral spikes) protruding outwards in the form of homotrimers containing an S1 and S2 as monomers. Mutations in structural proteins of virus play crucial role in determining virulence and also in many instances influencing emergence of antibody escape variants and cellular tropism. In this paper we have performed in depth analyses of spike protein sequences from various parts of the world and tried to correlate the data with possible functional relevance of such mutations.
ARTICLE | doi:10.20944/preprints202009.0154.v1
Subject: Life Sciences, Biochemistry Keywords: COVID-19; Knowledge; Practices; Perception; Veterinarians students; Nigeria
Online: 7 September 2020 (03:52:58 CEST)
Background: The novel Coronavirus SARS-CoV-2 (COVID-19) is a global pandemic with an increasing public health concern. Due to the non-availability of a vaccine against the disease, non-pharmaceutical interventions constitute major preventive and control measures. However, inadequate knowledge about the disease and poor perception might limit compliance. Aim: This study examined COVID-19-related knowledge, practices, perceptions and associated factors amongst undergraduate veterinary medical students in Nigeria. Methods: A cross-sectional web survey was employed to collect data from 437 consenting respondents using pre-tested self-administered questionnaire (August 2020). Demographic factors associated with the knowledge and adoption of recommended preventive practices towards COVID-19 were explored using multivariate logistic regression at P ≤ 0.05.Results: The respondents’ mean knowledge and practice scores were 22.7 (SD ± 3.0) and 24.1 (SD ± 2.9), respectively with overall 63.4% and 88.8% displaying good knowledge and satisfactory practice levels. However, relatively lower proportions showed adherence to avoid touching face or nose (19.5%), face mask-wearing (58.1%), and social distancing (57.4%). Being in the 6th year of study (OR = 3.18, 95%CI: 1.62-6.26, P = 0.001) and female (OR = 2.22, 95% CI = 1.11-4.41, P = 0.024) were significant positive predictors of good knowledge and satisfactory practices, respectively. While only 30% of the respondents perceived the pandemic as a scam or a disease of the elites (24.0%), the respondents were worried about their academics being affected negatively (55.6%). Conclusion: The study revealed good knowledge and satisfactory preventive practices towards COVID-19 among Nigerian Veterinary students; albeit with essential gaps in the key non-pharmaceutical preventive measures recommended by the WHO. Therefore, there is a need to step up enlightenment and targeted campaigns about COVID-19 pandemic.
REVIEW | doi:10.20944/preprints202009.0153.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Virus; Vaccine; SARS-CoV-2; Coronavirus; Covid-19; Covid-19 vaccine
Online: 7 September 2020 (03:46:59 CEST)
This tutorial is organized into three major sections—viruses, vaccines and the race for a Covid-19 vaccine. The goal is to provide enough background on viruses, history of vaccines, and the science of vaccinology founded on the principles of immunity. The hope is that this will enable us to understand the challenges, methods and prospects for developing a safe and effective vaccine against SARS-CoV-2. Many important viruses such as smallpox, HIV, HCV and SARS-CoV-2 which is responsible for causing the Coronavirus disease 2019 (Covid-19) are presented in detail, which is then followed by a description of different vaccine development methods and strategies. The tutorial then discusses different candidate SARS-CoV-2 vaccines and provides specific details of many of the prospective vaccines on the leader-board which are undergoing clinical trials. The tutorial concludes with a realistic projection for a safe and effective vaccine against SARS-CoV-2 based on the historical scientific record.
ARTICLE | doi:10.20944/preprints202006.0031.v3
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: Deep learning; Convolutional Neural Network; Coronavirus; COVID-19; radiology; CT scan; Medical image analysis; Automatic medical diagnosis; lung CT scan dataset
Online: 5 September 2020 (03:36:20 CEST)
COVID-19 is a severe global problem, and AI can play a significant role in preventing losses by monitoring and detecting infected persons in early-stage. This paper aims to propose a high-speed and accurate fully-automated method to detect COVID-19 from the patient's CT scan images. We introduce a new dataset that contains 48260 CT scan images from 282 normal persons and 15589 images from 95 patients with COVID-19 infections. At the first stage, this system runs our proposed image processing algorithm to discard those CT images that inside the lung is not properly visible in them. This action helps to reduce the processing time and false detections. At the next stage, we introduce a novel method for increasing the classification accuracy of convolutional networks. We implemented our method using the ResNet50V2 network and a modified feature pyramid network alongside our designed architecture for classifying the selected CT images into COVID-19 or normal with higher accuracy than other models. After running these two phases, the system determines the condition of the patient using a selected threshold. We are the first to evaluate our system in two different ways. In the single image classification stage, our model achieved 98.49% accuracy on more than 7996 test images. At the patient identification phase, the system correctly identified almost 234 of 245 patients with high speed. We also investigate the classified images with the Grad-CAM algorithm to indicate the area of infections in images and evaluate our model classification correctness.
Online: 4 September 2020 (12:32:58 CEST)
As part of a plethora of global efforts to minimize the negative effects of the SARS-CoV2 (COVID-19) pandemic, we developed two different mechanisms that, after further development, could potentially be of use in the future in order to increase the capacity of ventilators with low-cost devices based on single-use-bag-valve mask systems. We describe the concept behind the devices and report a characterization of them. Finally, we make a description of the solved and unsolved challenges and propose a series of measures in order to better cope with future contingencies.
BRIEF REPORT | doi:10.20944/preprints202007.0141.v3
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; pneumococcal vaccine; vaccination; cross-reactivity; protection; molecular mimicry; CRM197; rubella vaccine
Online: 4 September 2020 (10:45:26 CEST)
Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, some are conjugated to CRM197, a modified diphtheria toxin, and all contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. All of these proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. CRM197 is also present in Hib and meningitis vaccines. Equivalent similarities were found at lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable.
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; Treatment outcome; Data Collection; Pharmaceutical Preparations; Outcome Assessment; Health Care
Online: 4 September 2020 (10:12:02 CEST)
Human infection caused by the SARS-CoV-2 virus, called COVID-19, is a new pandemic with devastating effects worldwide. Science seeks the rational and systematic explanation of phenomena. In pandemics, decisions on prevention and treatment of people should be consistently taken, supported by scientific knowledge and ethical principles to produce more good than harm. At first, prospective observational studies to systematically collect patient data, correlating protective or therapeutic interventions with outcomes to assess effectiveness and safety, should be prioritized as the most appropriate type of study. The proposed protocol in this article aims to provide doctors with information on the reduction of harm in early COVID-19 patients by applying individualized interventionist or expectant therapeutic strategies, respecting the autonomy and preferences of physicians and patients in clinical decision-making. The evaluation of the clinical status, besides laboratory confirmation of COVID-19, comprises an individualized symptom score for each patient, a global self-perception scale of the severity of the disease, a clinical progression scale developed by the WHO for clinical studies in COVID-19 and, at the first consultation, doctors´ overall impression on the clinical prognosis. The analysis of anonymized data should preferably use descriptive and inferential statistical resources. The case report form is available for free use in the protocol, along with examples of patient informed consent forms for the prescription of off-label medications and authorization to use the data. Their results may be useful to indicate interventions that are candidates for efficacy trials, in randomized controlled trials, with a higher chance of success. It respects the autonomy and preferences of doctors and patients to decide the best options for treatment in uncertain situations. It also allows the gathering of useful information for future more rigorous clinical trials, trying to link science, ethics, and personal clinical experience.
REVIEW | doi:10.20944/preprints202009.0076.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: severe acute respiratory syndrome coronavirus 2; SARS-CoV-2; coronavirus disease 2019; COVID-19; viral infection; virus-host interaction
Online: 4 September 2020 (03:19:43 CEST)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing pandemic of coronavirus disease 2019 (COVID-19). The worldwide transmission of COVID-19 from human to human is spreading like wildfire, affecting almost every country in the world. In the past 100 years, the globe did not face microbial pandemic similar in scale to COVID-19. Taken together, both previous outbreaks of other members of the coronavirus family (SARS-CoV and MERS-CoV) did not produce even 1% of the global harm already inflicted by COVID-19. There are also four other CoVs capable of infecting humans (HCoVs), which circulate continuously in the human population, but their phenotypes are generally mild, and these HCoVs received relatively little attention. These dramatic differences between infection with HCoVs, SARS-CoV, MERS-CoV, and SARS-CoV-2 raise many questions, such as: Why is COVID-19 transmitted so quickly? Is it due to the some specific features of the viral structure? Are there some specific human (host) factors? Are there some environmental factors? The aim of this review is to collect and concisely summaries the possible and logic answers to these questions.
ARTICLE | doi:10.20944/preprints202009.0075.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: COVID-19 infection; CT-scan; oncological patients
Online: 4 September 2020 (03:14:13 CEST)
Background The acknowledgment of computed tomography (CT) defined diagnosis in high prevalence northern Italy may identify more patients with Coronavirus Disease-2019 (COVID 19) infection, than RT-PCR alone. Methods We retrospectively reviewed 148 chest CT scans of oncological patients who were referred to the Radiological Unit of Policlinico S. Marco from 1st of February 2020 to 30th of April 2020, during the Covid-19 outbreak in Bergamo area. Therefore, we analyzed RT-PCR tests of these 148 patients. Results Among 32 patients with diagnosis of COVID-19 infection: 17 patients were asymptomatic or had mild symptoms (53.1%), while 15 developed severe disease (46.8%). The incidence of COVID-19 infection is 22.9%, the mortality rate is 18.8%. Severe COVID-19 disease is associated with higher median age. We did not find any correlation between disease severity and sex, smoke or cardiovascular comorbidities. Remarkably, patients who were on treatment developed milder disease than cancer patients who were not on treatment. Conclusions The acceptance of CT-defined diagnosis in high prevalence area like Bergamo highlighted a larger number of COVID-19 oncological population than RT-PCR alone, in particular asymptomatic and mild symptomatic patients. We observed that actively treated patients had milder disease, according to previous studies that suggested a protective role of immunosuppression.
REVIEW | doi:10.20944/preprints202009.0063.v1
Subject: Keywords: COVID-19; disease severity; laboratory findings; biochemistry findings; immunology; hematology
Online: 3 September 2020 (07:35:46 CEST)
Aim: Abnormal laboratory findings have been shown to be associated with severe COVID-19. However, all aspects of this association have not been reviewed systematically. Therefore, the aim of this meta-analysis was to explore crucial laboratory parameters in severe COVID-19 infection. Methods: We performed the literature review of scientific articles indexed in electronic databases. Scientific search engines were used to perform the electronic literature search. After the removal of duplicates and selection of articles of interest, 30 studies were eligible to include. If heterogeneity was high (I2>50%), a random-effects model was applied to combine the data. Otherwise, a fixed-effects model was used.Results: A total of 5586 individuals were assessed (1555 patients with severe COVID-19 infection and 3452 with non-severe infection). Platelets, lymphocytes and serum albumin were significantly lower in severe patients while other biochemical and immunological parameters including prothrombin time, ALT, AST, total bilirubin, LDH, procalcitonin, CRP, IL-6, and IgA were significantly higher in patients with severe infection. Neutrophil and monocyte counts as well as hemoglobin level, D-dimer, hypersensitive troponin I, IL-2R, IgG and IgM levels were different between two groups; however, the difference was not statistically significant (All P-values >0.05). Conclusions: Lymphopenia, elevated liver enzymes, and high levels of inflammatory biomarkers are associated with severe COVID-19 infection.
REVIEW | doi:10.20944/preprints202009.0058.v1
Subject: Biology, Other Keywords: Emerging infectious diseases; coronaviruses; COVID-19; SARS-CoV; SARS-CoV-2; MERS-CoV; zoonotic diseases
Online: 3 September 2020 (04:54:38 CEST)
The ongoing global pandemic caused by coronavirus disease 2019 (COVID-19) has once again demonstrated the significance of the Coronaviridae family in causing human disease outbreaks. As SARS-CoV-2 was first detected in December 2019, information on its tropism, host range, and clinical presentation in animals is limited. Given the limited information, data from other coronaviruses may be useful to inform scientific inquiry, risk assessment and decision-making. We review the endemic and emerging alpha- and betacoronavirus infections of wildlife, livestock, and companion animals, and provide information on the receptor usage, known hosts, and clinical signs associated with each host for 15 coronaviruses discovered in people and animals. This information can be used to guide implementation of a One Health approach that involves human health, animal health, environmental, and other relevant partners in developing strategies for preparedness, response, and control to current and future coronavirus disease threats.
REVIEW | doi:10.20944/preprints202009.0056.v1
Subject: Behavioral Sciences, Developmental Psychology Keywords: COVID-19; Impacts; Nurturing Care; Early Childhood Development (ECD); Maternal, Newborn, and Child Health; Child Growth Development; Early Brain Development; Vulnerable Children and Families
Online: 3 September 2020 (04:54:37 CEST)
In Kenya, millions of children have limited access to nurturing care. With the COVID-19 pandemic, it is anticipated that vulnerable children will bear the biggest brunt of the direct and indirect impacts of the pandemic. This review aimed to deepen understanding of the effects of COVID-19 on nurturing care from conception to four years of age, a period where the care of children is often delivered through caregivers or other informal platforms. The review has drawn upon the empirical evidence from previous pandemics and epidemics, and anecdotal and emerging evidence from the ongoing COVID-19 crisis. Multifactorial impacts fall into five key domains: direct health; health and nutrition systems, economic, social and child protection, and child development and early learning. The review proposes program and policy strategies to guide the re-orientation of nurturing care, prevent the detrimental effects associated with deteriorating nurturing care environments, and support the optimal development of the youngest and most vulnerable children. These include the provision of cash transfers and essential supplies for vulnerable households, and strengthening of community-based platforms for nurturing care. Further research on COVID-19 and the ability of children’s ecology to provide nurturing care is needed, as is further testing of new ideas.
REVIEW | doi:10.20944/preprints202009.0040.v1
Subject: Life Sciences, Molecular Biology Keywords: Coronaviruses; COVID-19; Pakistan; current situation; human physiology; diagnosis; treatment
Online: 2 September 2020 (09:59:45 CEST)
Coronavirus that is also known as COVID-19 disease is produced by SARSCoV-2. This causative agent is highly contagious and can cause potentially fatal pneumonia worldwide with serious public health concerns. In the beginning among infected individuals, most of them were those who were mainly shown to the wet animal market in a big city of China known as Wuhan. So, it was suggested that this was almost certainly the zoonotic source of COVID-19illness. The transitional source of origin and their mode of transmission to humans were not known obviously. Conversely, from human to human rapidly transformation have been confirmed generally. Currently, there is no availability of FDA approved clinically antiviral drugs and/or vaccines to be used against the COVID-19. Afterward, SARS-CoV and MERS-CoV, the occurrence of SARS-CoV-2 has been manifested as the third sketch of an enormously pathogenic coronavirus into human population globally. In this review, we provide a brief overview of the history of COVID-19 in Pakistan up-to 18th weeks after beginning, current situation, epidemiology, and its impact on the human population. Moreover, we focused on physiological variation during the incubation period, genome analysis of SARS-CoV2, supportive treatment approaches, and safety measures in the Pakistani population, which may be supportive for combating the risk of COVID-19 epidemic. We also reviewed the future approaches for the development of therapeutic interventions and vaccines to cope with the COVID-19 epidemic.
ARTICLE | doi:10.20944/preprints202007.0558.v2
Subject: Chemistry, Medicinal Chemistry Keywords: COVID-19; protein protein interactions; virtual screening; docking; molecular dynamics; zinc
Online: 2 September 2020 (09:48:48 CEST)
The outbreak of COVID-19, the disease caused by SARS-CoV-2, continues to affect millions of people around the world. The absence of a globally distributed effective treatment makes the exploration of new mechanisms of action a key step to address this situation. Stabilization of non-native Protein-Protein Interactions (PPIs) of the nucleocapsid protein of MERS-CoV has been reported as a valid strategy to inhibit viral replication. In this study, the applicability of this unexplored mechanism of action against SARS-CoV-2 is analyzed. During our research, we were able to find three inducible interfaces of SARS-CoV-2 N protein NTD, compare them to the previously reported MERS-CoV stabilized dimers, and identify those residues that are responsible for their formation. A drug discovery protocol implemented consisting of docking, molecular dynamics and MM-GBSA enabled us to find several compounds that might be able to exploit this mechanism of action. In addition, a common catechin skeleton was found among many of these molecules, which might be useful for further drug design. We consider that our findings could motivate future research in the fields of drug discovery and design towards the exploitation of this previously unexplored mechanism of action against COVID-19.
COMMUNICATION | doi:10.20944/preprints202009.0031.v1
Online: 2 September 2020 (06:09:34 CEST)
Each sport has its specific rules, which determine what is allowed (or not) impacting directly on the sport demands. Studies involving physiological and time-motion measurements have shown that soccer is a highly demanding sport. The new coronavirus disease 2019 (COVID-19) has been a world health crisis. Soccer seasons were interrupted worldwide to avoid spreading the virus. Leagues resumed the season (no fans at the arenas) after several weeks of interruption, causing overlay of schedule. This overlay (e.g., games every Sunday and Wednesday) will cause accumulated fatigue on players, raising the risk of injuries. Considering this condensed calendar, the Fédération Internationale de Football Association (FIFA) has changed (temporarily) up to five substitutions during elite games (instead of three as the regular rule allows). Considering the already published scientific evidence, clearly, the change in the soccer substitution rule due to COVID-19 is insufficient. Implementing unlimited substitutions may benefit soccer players' health, coaches’ jobs, more entertainment for fans and sponsors (e.g., keeping intensity during all game, including on the second half) and eventually prolonging the useful life of the players. A real game-changer!
ARTICLE | doi:10.20944/preprints202009.0029.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: diabetes mellitus; hypertension; obesity; Coronavirus; mechanism; COVID-19; viral interaction
Online: 2 September 2020 (05:37:46 CEST)
The pandemic of coronavirus disease (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on SARS-CoV-2, Middle East respiratory syndrome (MERS-CoV), and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. We hope to highlight gaps in knowledge that require further studies pertinent to COVID-19 in patients with diabetes mellitus, hypertension and obesity.
ARTICLE | doi:10.20944/preprints202009.0028.v1
Online: 2 September 2020 (05:27:55 CEST)
The soccer injury rate is distinctly higher during matches than the training sessions. Rules determine how to play, generating specific kinds of fatigue which is associated with the injury incidence. No research has evaluated the impact of potential rule-induced physical demands in soccer or comparing sports. Understanding the differences might be useful for enhancing rules (e.g., safer sport). Therefore, the aims of this study were: a) to described the differences in the rule-induced physical demands of soccer, futsal, basketball, and handball; and b) to evaluate whether soccer rule-induced physical demands are different than the other invasion intermittent team sports, focusing the impact of the substitutions rules. Data were collected from different sports rules (i.e., soccer, futsal, basketball, and handball), and performed hypothetical corrections to equate the other team sports to the soccer (i.e., court dimensions/number of players). The data showed that soccer has higher rule-induced physical demands: lower substitutions, higher dimensions in absolute (eight to 15 times), and relative (four to eight times) values. Hypothetical corrections showed that soccer has remarkably large differences. Therefore, we conclude that soccer has remarkably higher rule-induced physical demands than other team sports, and allowing unlimited substitutions in soccer is a must.
REVIEW | doi:10.20944/preprints202009.0026.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: COVID-19; herbs; spices; nutrition; nutrients; immunomodulatory
Online: 2 September 2020 (05:06:56 CEST)
Corona Virus disease 2019 (COVID-19) is a new strain of coronavirus that causes respiratory illnesses with a start of flu like symptoms. This disease is fatal and is spread all over the world. The Scientist are working day and night to find vaccine or a cure. World Health Organisation has declared COVID-19 as pandemic . In the view of the pandemic many treatments are being tried on the patients and various treatment modalities are being followed, the traditional medicine has shown a major role to manage this disease. The traditional medicines include the use of herbs, nutrition and spices that are freely available in Asian countries. These are used in day to day life by Asian population . In this paper we have compiled and reviewed the role of various herbs and spices such as Oregano, Ashwagandha, Ginseng, Basil, Sage, Curcumin, Fenugreek, Ginger and Garlic in building immunity and also in curing pathogenic invasions based on evidence based researches. As there is no cure available for COVID-19 till now so supportive therapy is playing a major role for the patients to fight with this pandemic. The AYUSH ministry has also promoted the use of above herbs for a patient suffering from this disease. The corona virus is present in respiratory system as shown by different studies and it has different strains. The guidelines laid by the ICMR and WHO shows that use of herbs, spices and nutrients can be helpful to manage this virus by increasing the immunity in patients. Hence we are not claiming any cures but the herbs and spices used in day to day life are very much effective in management of COVID-19. World Health Organisation (WHO) has recognised the use of alternative and traditional medicine in the management of COVID-19 but the herbs should be used in prescribed amounts and overdose of them can be harmful for health [1,3]. Therefore the present article will enlighten the readers about the role of herbs, spices and nutrients in improving the conditions in COVID-19.
ARTICLE | doi:10.20944/preprints202009.0006.v1
Subject: Life Sciences, Biophysics Keywords: COVID-19; SARS-CoV-2; protein design; complementarity; competitive inhibitor; homology-based threading in rational protein design
Online: 1 September 2020 (11:22:49 CEST)
COVID-19 is characterized by an unprecedented abrupt increase in transmission rate relative to its endemic evolutionary ancestor, SARS-CoV (2003). The complex molecular cascade of events related to the viral pathogenicity is triggered by the Spike protein upon interacting with the ACE2 receptor on human lung cells through its receptor binding domain (RBDSpike). One potential therapeutic strategy to combat COVID-19 could thus be limiting the infection by blocking this key interaction. In this current study, we adapt a protein design approach to predict and propose non-virulent structural mimics of the RBDSpike, potentially serving as its competitive inhibitors in binding to ACE2. RBDSpike is an independently foldable protein domain, resilient to conformational changes upon mutations and therefore an attractive target for strategic re-design. Interestingly, in spite of displaying an optimal shape fit between their interacting surfaces (attributed to a consequently high mutual affinity), the RBDSpike – ACE2 interaction appears to have a quasi-stable character due to a poor electrostatic match at their interface. Structural analyses of homologous complexes reveal that the RBDSpike has an unusually high degree of solvent-exposed hydrophobic residues, attributed to key evolutionary changes, making it inherently ‘reaction-prone’. The designed mimics, aimed to block the viral entry by occupying the available binding sites on ACE2, are tested to have signatures of stable high-affinity binding with ACE2, overriding the native quasi-stable feature. The results show the apt of directly adapting natural examples in rational protein design, wherein, homology-based threading coupled with strategic ‘hydrophobic ↔ polar’ mutations potentially serves as a breakthrough.
REVIEW | doi:10.20944/preprints202009.0002.v1
Subject: Keywords: cardiovascular disease; human reproduction system; meteorological factor; SARS-COV-2; antigen testing
Online: 1 September 2020 (09:46:24 CEST)