Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: coronavirus; epidemiology; 2019-nCoV; COVID-19
Online: 10 June 2020 (05:17:01 CEST)
There is a current pandemic of a new type of coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The number of confirmed infected cases has been rapidly increasing. This paper analyzes the characteristics of SARS-CoV-2 in comparison with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and influenza. COVID-19 is similar to the diseases caused by SARS-CoV and MERS-CoV virologically and etiologically, but closer to influenza in epidemiology and virulence. The comparison provides a new perspective for the future of the disease control, and offers some ideas in the prevention and control management strategy. The large number of infectious people from the origin, and the highly infectious and occult nature have been two major problems, making the virus difficult to eradicate. We thus need to contemplate the possibility of long-term co-existence with COVID-19.
REVIEW | doi:10.20944/preprints202003.0410.v2
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: Coronavirus; 2019-nCoV; COVID-19; bat, pangolin
Online: 30 March 2020 (08:16:22 CEST)
The world is puzzling over the origin of the current outbreak of the coronavirus disease (COVID-19) that is caused by a novel coronavirus-2019 (2019-nCoV). As of 26th March 2020, the World Health Organization has reported 46,2,684 confirmed cases and 20,834 confirmed deaths in total due to COVID-19. To this end, two unique mammals namely bats and pangolins are being investigated for their potential link to COVID-19. However, the evidence so far gathered in this context is far from clear. This paper aimed to: (i) enlighten the major aspects of life of bats and pangolins; (ii) briefly discusses their potential link to COVID-19; and also (iii) to highlight the way forward. The outcomes may contribute to future research on the subject.
ARTICLE | doi:10.20944/preprints202003.0302.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-2019; SARS-CoV-2; 2019-nCoV; repositioning; UPR/Autophagy; real-world evidence; pathways
Online: 20 March 2020 (03:55:55 CET)
More than 179,000 individuals have fallen ill of the Coronavirus disease (COVID-19) caused by the SARS-CoV-2 virus, which first emerged in China less than four months ago in December 2019. As of today, there exist no approved treatments against COVID-19. Vaccines are being developed, but they will take time, at least one year, to reach the population. Drug repositioning represents a fast track because already approved medicines have been broadly tested through multiple trials. We developed a repositioning strategy that mostly leads to candidates that are commonly used. The advantages are that they will facilitate proof of concept in humans through a “real-world evidence” approach and should be rapidly available to the population. We focus on the established research results that the unfolded protein response (UPR) and autophagy pathways of the host cells are essential to the life cycle of previously known coronaviruses. We performed the relevant bioinformatics analysis to understand and confirm if SARS-CoV-2 may interact with these druggable pathways. Based on these considerations, we prioritized two additional druggable pathways, which are important to the viral life cycle and tightly connected to UPR/autophagy signaling: the mitochondrial permeability transition pores (MPTP) and NLRP-3 inflammasome pathways. These four important pathways are perturbed in most major common diseases and have therefore been targeted by numerous broadly prescribed drugs. We have identified 97 approved drugs that are known to modulate these four identified pathways, and which represent, therefore, interesting repositioning candidates. Although it is indisputable that these drugs should never be used for immediate self-medication against COVID-19, we notice that some of them could also be prescribed to individuals who have COVID-19 comorbidities (e.g., hypertension). It is debated if these comorbidities are linked to the pathology itself (e.g., hypertension) or the drugs used to treat the pathology (e.g., sartans). Therefore, relevant preclinical tests and massive electronic health records (i.e., real-world evidence) must be used to pre-screen them and check the COVID-19 prognosis of individuals taking these drugs.
ARTICLE | doi:10.20944/preprints202005.0020.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; , 2019-nCoV; Heparin; Ivermectin; Spike Shielding
Online: 2 May 2020 (16:21:32 CEST)
The disease of COVID-19 comprises the most serious against human health worldwide with a high rate of virulence and mortality. The disease is caused by the 2019-nCoV virus from the beta coronavirus family. The virus makes use of its surface glycoprotein named S protein or spike to enter the human cells. The virus attached to its receptor named angiotensin-converting enzyme 2 on host cells surface via its receptor-binding domain and its fusion is mediated by cleavage at S2' site that is carried out by surface protease. Vaccines or drugs interfering with S protein binding or cleavage sites could be considered as drugs to get rid of the infection. In the current work and though docking and molecular dynamic experiments we have checked more than 100 drugs with high enough molecular weights for their shielding potency toward S protein binding sites and processing S2' sites. Our results indicate the shielding potency of: fidaxomicin > ivermectin > heparin > azithromycin > clarithromycin > eryhthromycin > niclosamide > ritonavir. Considering affluent reports regarding the complex disturbance in the immune system and multi-organ involvement in the disease there is no single or binary drug regime for cure expectedly and instead, we claim the multi-drug regime should be the choice in this context. Accordingly, we suggest our extracted drugs as an adjuvant for clinical trials.
BRIEF REPORT | doi:10.20944/preprints202005.0006.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: 2019-nCoV; intermediate host; ACE2 receptor; COVID-19
Online: 2 May 2020 (12:11:38 CEST)
The recent 2019-nCoV outbreak, spreading infection around the globe is jeopardizing the public health and global economy. The virus was reported to have emerged from an animal market in Wuhan, China at the end of 2019 and presumed to have originated from bats and eventually transmitted in humans. The entry of the virus into human cells is triggered by a series of molecular events initiated with the binding of a receptor-binding domain of viral spike protein to human Ace2 cell surface receptor. Based on the comparative sequence analysis of the well-known binding hotspots of human Ace2, cross-interacting potential of 2019-nCoV was predicted, which suggests Ace2 of wild animals like tiger, bear, orangutan, etc.; aquatic mammals like whale and dolphins; and domestic animals like cat, horse, goat, sheep, dog etc. as potential target. However, the recognition of Ace2 of bats, rats and mice by the 2019-nCoV spike protein remains under question. The study indicates that 2019-nCoV might have broad host range and may thus intensify the gravity of 2019-nCoV outbreak
ARTICLE | doi:10.20944/preprints202003.0291.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: co-infection; coronavirus disease 2019; COVID-19; influenza
Online: 19 March 2020 (02:00:47 CET)
Background: On late December 2019, a viral pneumonia known as coronavirus disease 2019 (COVID-19), was originated from China and spread very rapidly in the world. Therefore, COVID-19 became a global concern and health problem. Methods: We presented four patients in this study. They were selected from patients who presented with pneumonia symptoms and were suspicious for COVID-19 and referred to the intended centers for COVID-19 diagnosis and management of Shiraz University of Medical Sciences in the south of Iran. Two nasopharyngeal and oropharyngeal throat swab samples were collected from each patient and tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection by real-time reverse-transcriptase–polymerase-chain-reaction (RT-PCR), and also samples were sent for influenza viruses and all the respiratory panel. Results: In the present report, four patients were diagnosed in the starting days of COVID-19 disease in our center in south of Iran with co-infection of SARS-CoV-2 and influenza virus. Conclusions: This co-infection of COVID-19 and influenza highlights the importance of considering SARS-CoV-2 PCR assay regardless of other positive findings for other pathogens in the primary test during the epidemic.
ARTICLE | doi:10.20944/preprints202003.0286.v1
Subject: Medicine And Pharmacology, Pharmacy Keywords: COVID-2019; SARS-CoV-2; repurposing; network bioinformatics
Online: 18 March 2020 (08:50:10 CET)
The COVID-2019 disease caused by the SARS-CoV-2 virus (aka 2019-nCoV) has raised significant health concerns in China and worldwide. While novel drug discovery and vaccine studies are long, repurposing old drugs against the COVID-2019 epidemic can help identify treatments, with known preclinical, pharmacokinetic, pharmacodynamic, and toxicity profiles, which can rapidly enter Phase 3 or 4 or can be used directly in clinical settings. In this study, we presented a novel network based drug repurposing platform to identify potential drugs for the treatment of COVID-2019. We first analysed the genome sequence of SARS-CoV-2 and identified SARS as the closest disease, based on genome similarity between both causal viruses, followed by MERS and other human coronavirus diseases. Using our AutoSeed pipeline (text mining and database searches), we obtained 34 COVID-2019-related genes. Taking those genes as seeds, we automatically built a molecular network for which our module detection and drug prioritization algorithms identified 24 disease-related human pathways, five modules and finally suggested 78 drugs to repurpose. Following manual filtering based on clinical knowledge, we re-prioritized 30 potential repurposable drugs against COVID-2019 (including pseudoephedrine, andrographolide, chloroquine, abacavir, and thalidomide) . We hope that this data can provide critical insights into SARS-CoV-2 biology and help design rapid clinical trials of treatments against COVID-2019.
ARTICLE | doi:10.20944/preprints202003.0226.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-2019; Mpro; 6LU7; medicinal plant compounds; docking
Online: 13 March 2020 (03:19:02 CET)
COVID-19, a new strain of coronavirus (CoV), was identified in Wuhan, China, in 2019. No specific therapies are available and investigations regarding COVID-19 treatment are lacking. Liu et al. (2020) successfully crystallised the COVID-19 main protease (Mpro), which is a potential drug target. The present study aimed to assess bioactive compounds found in medicinal plants as potential COVID-19 Mpro inhibitors, using a molecular docking study. Molecular docking was performed using Autodock 4.2, with the Lamarckian Genetic Algorithm, to analyse the probability of docking. COVID-19 Mpro was docked with several compounds, and docking was analysed by Autodock 4.2, Pymol version 220.127.116.11 Edu, and Biovia Discovery Studio 4.5. Nelfinavir and lopinavir were used as standards for comparison. The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, epicatechin-gallate, zingerol, gingerol, and allicin were -8.37, -10.72, -9.41, -8.58, -8.47, -8.17, -7.99, -7.89, -7.83, -7.31, -7.05, -7.24, -6.67, -5.40, -5.38, and -4.03 kcal/mol, respectively. Therefore, nelfinavir and lopinavir may represent potential treatment options, and kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate appeared to have the best potential to act as COVID-19 Mpro inhibitors. However, further research is necessary to investigate their potential medicinal use.
BRIEF REPORT | doi:10.20944/preprints202003.0221.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: COVID-19; 2019-nCoV; diagnostics; antibodies; structural vaccinology
Online: 12 March 2020 (15:02:49 CET)
The appearance of the novel betacoronavirus 2019-nCoV represents a major threat to human health, and its diffusion around the world is predicted to have dramatic economic consequences. The knowledge of the 3D structures of 2019-nCoV proteins can facilitate the development of diagnostic and therapeutic molecules. Herein, we apply our energy-based method for the prediction of potential epitopes on viral proteins to design peptide-based molecules that can subsequently be used in diagnostic and therapeutic applications. We discuss these aspects in the paper.The designs have not been tested. Our aim is to share information that can be useful in the development of novel biomolecules with potential interesting activities against 2019-nCoV.
REVIEW | doi:10.20944/preprints202006.0041.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: SARS-CoV-2; COVID-19; 2019-nCOV; Shedding; Detection
Online: 4 June 2020 (17:34:28 CEST)
There is a new public health crisis threatening the world with the emergence and spread of novel coronavirus (SARS-CoV-2). The outbreak of coronavirus disease 2019 (COVID-19), which originated in Wuhan, China, in December 2019, has been declared a public health emergency of international concern by WHO. Most patients infected with SARS-CoV-2 exhibited symptoms of fever, cough, myalgia, fatigue and shortness of breath. Many infected people may be asymptomatic. It is generally believed that airway exposure to respiratory droplets from an infected patient is the main transmission route of this disease. However, apart from respiratory source, other source specimens like faecal matter and urine could be possible for COVID-19 infectivity. The spreading other routes of the virus has been alarming sign, both for public and health care professionals. Understanding the spreading routes of SARS-CoV-2 is crucial for patient management and defining biosafety strategies for public and health care workers.
REVIEW | doi:10.20944/preprints202004.0019.v2
Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; Coronavirus; 2019-nCoV; SARS
Online: 3 April 2020 (15:23:50 CEST)
OBJECTIVE: Recent worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of respiratory coronavirus disease 2019 (COVID-19), is a current, ongoing life-threatening crisis and international public health emergency. The early diagnosis and management of the disease remains a major challenge. In this review, we aim to summarize the updated epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus SARS-CoV-2.MATERIALS AND METHODS: A broad search of the literature was performed in “PubMed” “Medline” “Web of knowledge”, and “Google Scholar” World Health Organization-WHO” using the keywords “severe acute respiratory syndrome coronavirus”, “2019-nCoV”, “COVID-19, “SARS”, “SARS-CoV-2” “Epidemiology” “Transmission” “Pathogenesis” “Clinical Characteristics”. We reviewed and documented the information obtained from literature on epidemiology, pathogenesis and clinical appearances of SARS-CoV-2 infection.RESULTS: The global cases of COVID-19 as of April 2, 2020 have risen to more than 900,000 and morbidity has reached more than 47,000. The incidence rate for COVID-19 has been predicted to be higher than the previous outbreaks of other coronavirus family members, including those of SARS-CoV and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The main clinical presentation of SARS-CoV-2 infection ranges from asymptomatic stages to severe lower respiratory infection in the form of pneumonia. Most of the patients also presented with fever, cough, sore throat, headache, fatigue, myalgia and breathlessness.Individuals at higher risk for severe illness include elderly people and patients with a weakened immune system or that are suffering from a underlying chronic medical condition like hypertension, diabetes, cancer, respiratory illness or cardiovascular diseases.CONCLUSIONS: SARS-Cov-2 has emerged as a worldwide threat, currently affecting 170 countries and territories across the globe. There is still much to be understood regarding SARS-CoV-2 about its virology, epidemiology and clinical management strategies; this knowledge will be essential to both manage the current pandemic and to conceive comprehensive measures to prevent such outbreaks in the future.
BRIEF REPORT | doi:10.20944/preprints202003.0394.v2
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Covid-19; SARS-CoV-2; ACE2; Coronavirus; 2019-nCoV
Online: 30 March 2020 (08:25:51 CEST)
The recent outbreak of novel coronavirus (SARS-CoV-2 or 2019-nCoV) and its spread to the whole world is currently posing one of the major threats to human health and the world economy. It has been suggested that SARS-CoV-2 is similar to SARS-CoV based on the genome sequence comparison. Despite the genomic similarity between SARS-CoV and SARS-CoV-2, the spike glycoprotein and receptor binding domain in SARS-CoV-2 shows considerable difference compared to SARS-CoV, due to the presence of several point mutations. We analyzed the receptor binding domain (RBD) from recently published 3D structure of spike glycoprotein of SARS-CoV-2 and compared with RBD of SARS-CoV. The observations highlight few important features of RBD in the light of the recently published findings from the 3D structures of spike glycoprotein and its complex with human angiotensin-converting enzyme 2 (ACE2) (Yan, R., et al. (2020); Wrapp, D., et al. (2020); Walls, A. C., et al. (2020)).
HYPOTHESIS | doi:10.20944/preprints202003.0042.v1
Subject: Biology And Life Sciences, Virology Keywords: COVID -19; 2019-nCoV; spike (S) protein; zorubicin; aclarubicin
Online: 3 March 2020 (11:41:51 CET)
The novel coronavirus (2019-nCoV) is a human and animal pathogen recently emerged in the city of Wuhan in Hubei province of China, causing a spectrum of severe respiratory illnesses. Corona viruses makes entry in to human cells through its spike (S) protein that binds to cell surface receptors. Wide spread of 2019-nCoV has been attributed to relatively high affinity of S protein to its receptor. Although S protein is a highly importantdrug target, unavailability of a high-resolution crystal structure and solvent accessible binding surface has made it a tedious target for current rapid virtual screening. A homology model of the receptor binding domain (RBD) of 2019 -n CoV S protein that is reasonably acceptable for drug screening was prepared using a high resolution crystal structure of SARS corona virus (SARS CoV)S protein. Data obtained from RBD- receptor docking experiments and published molecular dynamics experiments were used to map a RBD-receptor interaction hotspot that can be used for designing small molecule inhibitors. The hot spot was then used for virtual screening of more than 3000 drugs approved by U.S Food and Drug Administration (FDA) and other authorities for human use. Two anthracycline class drugs (zorubicin and aclarubicin) and a food dye (E 155) were predicted to be potent inhibitors of RBD – receptor interaction. Results of present study provide evidence for the potential of these compounds asprophylactic medications or for use to reduce disease severity of COVID -19.
BRIEF REPORT | doi:10.20944/preprints202002.0167.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: 2019-nCoV; Immune; B cell; T cell; COVID-19
Online: 13 February 2020 (10:53:40 CET)
The outbreak of the 2019 Novel Coronavirus (2019-nCoV) has rapidly spread from Wuhan, China to multiple countries, causing staggering number of infections and deaths. A systematic profiling of the immune vulnerability landscape of 2019-nCoV is lacking, which can bring critical insights into the immune clearance mechanism, peptide vaccine development, and antiviral antibody development. In this study, we predicted the potential of all the 2019-nCoV viral proteins to induce class I and II MHC presentation and form linear antibody epitopes. We showed that the enrichment for T cell and B cell epitopes is not uniform on the viral genome, with several focused regions that generate abundant epitopes and may be more targetable. We showed that genetic variations in 2019-nCoV, though fewer for the moment, already follow the pattern of mutations in related coronaviruses, and could alter the immune vulnerability landscape of this virus, which should be considered in the development of therapies. We create an online database to broadly share our research outcome. Overall, we present an immunological resource for 2019-nCoV that could significantly promote both therapeutic development and mechanistic research.
BRIEF REPORT | doi:10.3390/sci2030055
Subject: Public Health And Healthcare, Health Policy And Services Keywords: coronavirus; COVID-19; 2019-nCoV; novel (new) coronavirus; pandemic control
Online: 14 July 2020 (00:00:00 CEST)
The world is currently facing a serious pandemic of coronavirus disease 2019 (COVID-19) which started in Wuhan, China, and was then transmitted rapidly to other countries. Countries applied different methods and procedures in an attempt to prevent or reduce and/or control the incidence of cases and manage existing ones. This paper discusses the methods and procedures applied by Kuwait to control this epidemic, and how effective they have been. The State of Kuwait followed WHO, European CDC, US CDC, and/or other countries’ institutional guidelines, and is still working on containing the disease, given the rising number of cases among Kuwaitis returning from affected areas such as the UK and USA, and migrant workers who bear the highest burden, given their cramped living conditions.
REVIEW | doi:10.20944/preprints202004.0367.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19; drugs; 2019-nCoV; clinical trials; SARS-CoV-2
Online: 20 April 2020 (15:53:56 CEST)
The emergence of new type of viral pneumonia cases in China, on December 31, 2019; identified as the cause of human coronavirus, labeled as "COVID-19," took a heavy toll of death and reported cases of infected people all over the world, with the potential to spread widely and rapidly, achieved worldwide prominence but arose without the procurement guidance. There is an immediate need for active intervention and fast drug discovery against the 2019-nCoV outbreak. Herein, the study provides numerous candidates of drugs (either alone or integrated with another drugs) which could prove to be effective against 2019-nCoV, are under different stages of clinical trials. This review will offer rapid identification of a number of repurposable drugs and potential drug combinations targeting 2019-nCoV and preferentially allow the international research community to evaluate the findings, to validate the efficacy of the proposed drugs in prospective trials and to lead potential clinical practices.
ARTICLE | doi:10.20944/preprints202004.0280.v1
Subject: Medicine And Pharmacology, Urology And Nephrology Keywords: COVID-19; 2019-nCoV; male reproductive system; a retrospective study
Online: 16 April 2020 (13:50:47 CEST)
A novel and highly pathogenic coronavirus (2019-nCoV)-induced pneumonia spread worldwide in a short time. However, studies on the effects of 2019-nCoV on the male reproductive system are limited. The aim of this study is to describe the clinical characteristics of the male reproductive system of COVID-19 patients and to explore the presence of 2019-nCoV in semen. Retrospective, single-center case series of 112 male patients with confirmed COVID-19 who were admitted to Renmin Hospital of Wuhan University from January 2 to March 7, 2020. Demographic data, symptoms and signs related to the male reproductive system, throat swabs and semen samples were collected and analyzed. 2019-nCoV RNA measured in throat swab and semen samples. The organ distribution of ACE2 mRNA and protein in human tissue on The Human Protein Atlas portal and investigated immunohistochemistry (IHC) images of the testis. The HPA dataset revealed relatively high levels of ACE2 protein and RNA expression in the testis. A total of 3 severe COVID-19 patients (2.7%) presented with orchidoptosis, while no patients experienced other symptoms or signs related to the male reproductive system. The analysis of 2019-nCoV RNA in semen included 17 patients with fertility needs. Among these patients, 9 (52.9%) remained positive for 2019-nCoV according to throat swab analysis, and 8 (47.1%) became negative. In the semen 2019-nCoV analysis, all 17 patients were negative for the N gene and ORF1ab gene. In view of the potential impairment, long-term follow-up for male COVID-19 patients with fertility needs is of great significance.
REVIEW | doi:10.20944/preprints202012.0356.v1
Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; Comorbidities; Clinical characteristics; Pathobiology; 2019-nCov
Online: 14 December 2020 (18:16:00 CET)
Globally, the COVID-19 pandemic has brought the world to a standstill with the infected cases surpassing millions. The causative agent of COVID-19, the SARS-CoV-2 is a novel coronavirus that emerged from the wet animal market in Wuhan, China in early December 2019. Soon after, human-to-human transmission increased the rate of infection making the disease widespread with new hotspots emerging around the world.The epidemiological reports based on clinical characteristics including age, gender, symptoms (both severe and non-severe), and the conditions requiring intensive medical care, along with case fatality revealed that people with co-existing health conditions like diabetes, hypertension, cigarette smoking, and others with cardiovascular and kidney diseases were more susceptible to COVID-19 infection with poor prognosis in cases related to the severity of symptoms and requiring ICU, medical ventilators with a high fatality rate. Even people with immunosuppressed conditions like HIV and cancer, alongwith old age and pregnant women are vulnerable to COVID-19 infection and can cause severe health complications.It is extremely important to have a comprehensive idea of the underlying pathophysiology related to these health conditions which makes them more susceptible to contract SARS-CoV-2 infection in correlation with the development of severe symptoms. This review will provide an extensive viewpoint related to COVID-19 patients having coexisting health conditions together with the association between the prognosis of the disease and the pathogenesis of the SARS-CoV-2 infection, based on the current information available.
ARTICLE | doi:10.20944/preprints202008.0730.v1
Subject: Business, Economics And Management, Business And Management Keywords: risk management and early measures; Novel Corona Virus (COVID-2019); GHS
Online: 31 August 2020 (17:56:33 CEST)
This research paper is mainly aimed to elaborate the initial risk management and measures which government of Pakistan took towards Novel Corona Virus (COVID-2019). This initial response and planning was devised after the early outbreak of COVID-2019 in Wuhan, China in early time of January 2020. Pakistan devised a comprehensive plan that not to evacuate their student from Wuhan, China. The government of Pakistan in compliance with the National Institute of Health (NIH) devised and documented comprehensive plans such as the flight operations postponed related to Umerah pilgrims, which were intended to go to sacred places of KSA (The Kingdom of Saudi Arabia). The process of visa, immigration policy totally changed and the government of Pakistan notified it officially that, no new visas of visit, student, and business would be issued in due course of uncertainty due to COVID-2019. The government of Pakistan also announced medical emergency and notified through the country’s provinces the process of testing and treatment of COVID-2019. The government of Pakistan also allocated funds for medical supplies and named out the particular country’s best laboratories. The government of Pakistan also locked down all the cities with the emergency announcement that people should stay inside the home in quarantine or self-isolation. NIH (The National Institute of Health) played a vital role in executing the planning to cope with COVID – 2019). The National Institute of Health responded as “The Centre for Disease Control”. In aid to the government, the national army of Pakistan responded in a proactive manner towards planed execution. The medical corps of Pakistan army dedicated themselves to treat the suspected patients of COVID – 2019. Due to plans, policies being documented, implemented in such a way productive way that from February 28, 2020 to till date there is not much critical situation and issues are not present. There are much productive results as there is not much boom in a rise of COVID-2019 patients. This lockdown under the authority of the provinces resulted in fruitful outcomes. Background: On January 02, 2020, authorities of the People Republic of China elaborated that they have encountered with a novel type of infectious viral disease 2019. Later on January 12, the authorities from China elaborated the related sequence of Corona Virus diseases 2019 names as COVID – 2019. When COVID-2019 being identified in Wuhan, Hubei China, as an early response the Government of Pakistan in support of the National Institute of Health (Field Epidemiology & Disease Surveillance Division) published a health advisory about novel coronavirus. Methods: According to Global Health Security Index, Pakistan is ranked as 105th country among 195 countries in GHS index. Overall Score of Pakistan is 35.5. The score of Early Detection and Reporting for Epidemics of Potential International Concern is 41.7. A Graphical depiction of the COVID-19 cases placed until April 10, 2020 as well as a graph trend line of recovered as well as death rate is also depicted. According to the graphical facts of Government of Pakistan and World meters, the recovery rate of COVID-19 is about 98 percent and 2.1 percent death rate is reported against the total cases. Trend analysis with line graph was drawn based on available data from official dashboard web portal of the government of Pakistan and worldometers.info. Data figures were incorporated from March to August 18, 2020 in MS Excel and then subsequently deployed to draw trend analysis from managing risk to recovery. Results: The line graph showed a slowdown in the COVID-19 cases and high rate of recoveries from COVID-19 in Pakistan. On March 11, 2020, there were 20 confirmed cases of coronavirus reported in Pakistan. No death was recorded in very first seven days, on March 18, 2020 only two deaths were reported. On August 18, 2020, there were 272128 recoveries, 6201 deaths, total confirmed cases 290445, and total test were 2340072 in Pakistan. As a results, we can report that due to early measures taken by government of Pakistan no mass scale destruction in terms of death and cases been recorded in Pakistan. Conclusions: To till date, the government of Pakistan tried its level best to minimize the coronavirus cases as much as they can. However, the ending of the potential attack of an outbreak would depend upon the well organized and coordinated approach at all levels such as true directed decisions, fully preparedness, as well implementation and evaluation of continuous decisions. As the recovery rate of the cases is 98 percent and merely death rate is 2.1 percent, concluded that in future it would be a good sign to stop the potential outbreak. Also, lock down as well as precautionary measurement taken by the provincial governments resulted a decline number of COVID-19 cases in the country. Another good sign is that merely 4 percent population of Pakistan is of more than 60 years of old it can be concluded that there are less chances of mass death due to outbreak of COVID-19.
ARTICLE | doi:10.20944/preprints202005.0135.v1
Subject: Biology And Life Sciences, Virology Keywords: Coronavirus disease 2019 (COVID-19); Oral and maxillofacial; Urgency and emergency;
Online: 7 May 2020 (15:29:53 CEST)
The World Health Organization has defined the outbreak of the new coronavirus as a public health emergency of international concern. The average age of patients affected by the disease caused by the virus ranges from 49 to 59 years. The symptoms of coronavirus disease 2019 (COVID-19) infection include fever, cough, acute respiratory disease, and, in severe cases, the disease may progress to pneumonia and renal failure that may lead to death. Many oral and maxillofacial hospital procedures produce aerosol and droplets contaminated by blood, bacteria, and viruses. The purpose of this study is to gather recommendations from health authorities and scientific articles in order to educate surgeons regarding the procedures to assist and treat in oral and maxillofacial surgeries. The objective is to prevent the transmission of COVID-19 during the treatment of patients in urgent and emergency situations. The study’s methodology used the guidelines provided by the Brazilian College of Oral and Maxillofacial Surgery, in addition to the recommendations and epidemiologic data from national and international health authorities. The implementation of special precautions in oral and maxillofacial surgeries may elucidate questions related to the transmission of the disease by asymptomatic carriers and help control the spread of the virus.
ARTICLE | doi:10.20944/preprints202004.0058.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: coronavirus disease 2019 (COVID-19); school closure; time series analysis; Japan
Online: 6 April 2020 (13:11:12 CEST)
Background: Coronavirus disease 2019 (COVID-19) pandemic are causing significant damages to many nations. For mitigating its risk, Japan’s Prime Minister called on all elementary, junior high and high schools nationwide to close beginning March 1, 2020. However, its effectiveness in decreasing disease burden has not been investigated. Methods: We used daily data on the report of COVID-19 and coronavirus infection incidence in Japan until March 31, 2020. Time series analysis were conducted using Bayesian method. Local linear trend models with interventional effect were constructed for number of newly reported cases of COVID-19, including asymptomatic infections. We considered that the effects of intervention start to appear 9 days after the school closure; i.e., on March 9. Results: The intervention of school closure did not appear to decrease the incidence of coronavirus infection. If the effectiveness of school closure began on March 9, mean coefficient α for effectiveness of the measure was calculated to be 0.08 (95% credible interval -0.36 to 0.65), and the actual reported cases were more than predicted, yet with rather wide credible interval. Sensitivity analyses using different dates also showed similar results. Conclusions: School closure carried out in Japan did not show the effectiveness to mitigate the transmission of novel coronavirus infection.
HYPOTHESIS | doi:10.20944/preprints202003.0138.v1
Subject: Biology And Life Sciences, Virology Keywords: 2019-nCoV; SARS-CoV-2; COVID-19; ADE; antibody depedendent enhancement
Online: 8 March 2020 (15:35:27 CET)
Background: In 80% of patients, COVID-19 presents as mild disease1,2. 20% of cases develop severe (13%) or critical (6%) illness. More severe forms of COVID-19 present as clinical severe acute respiratory syndrome, but include a T-predominant lymphopenia3, high circulating levels of proinflammatory cytokines and chemokines, accumulation of neutrophils and macrophages in lungs, and immune dysregulation including immunosuppression4. Methods: All major SARS-CoV-2 proteins were characterized using an amino acid residue variation analysis method. Results predict that most SARS-CoV-2 proteins are evolutionary constrained, with the exception of the spike (S) protein extended outer surface. Results were interpreted based on known SARS-like coronavirus virology and pathophysiology, with a focus on medical countermeasure development implications. Findings: Non-neutralizing antibodies to variable S domains may enable an alternative infection pathway via Fc receptor-mediated uptake. This may be a gating event for the immune response dysregulation observed in more severe COVID-19 disease. Prior studies involving vaccine candidates for FCoV5,6 SARS-CoV-17-10 and Middle East Respiratory Syndrome coronavirus (MERS-CoV) 11 demonstrate vaccination-induced antibody-dependent enhancement of disease (ADE), including infection of phagocytic antigen presenting cells (APC). T effector cells are believed to play an important role in controlling coronavirus infection; pan-T depletion is present in severe COVID-19 disease3 and may be accelerated by APC infection. Sequence and structural conservation of S motifs suggests that SARS and MERS vaccine ADE risks may foreshadow SARS-CoV-2 S-based vaccine risks. Autophagy inhibitors may reduce APC infection and T-cell depletion12 13. Amino acid residue variation analysis identifies multiple constrained domains suitable as T cell vaccine targets. Evolutionary constraints on proven antiviral drug targets present in SARS-CoV-1 and SARS-CoV-2 may reduce risk of developing antiviral drug escape mutants. Interpretation: Safety testing of COVID-19 S protein-based B cell vaccines in animal models is strongly encouraged prior to clinical trials to reduce risk of ADE upon virus exposure.
ARTICLE | doi:10.20944/preprints202002.0380.v3
Subject: Social Sciences, Psychology Keywords: Infodemiology; COVID-19 infodemic; social contagion; collective perceptual bias; collective behavioral propensities; psychological typhoon eye effect
Online: 16 March 2020 (15:12:33 CET)
Less aligned emphasis has been given to the COVID-19 infodemic coordinating with the COVID-19 outbreak. Global profusion of tangled monikers and hashtags has found their ways in daily communication and contributed to backlash against Chinese. Official naming efforts against infodemic should be meet with a fair share of identification. Based on brief critical reviews on previous multifarious naming practices, we punctuate heuristic introspection in scientific conventions and sociocultural paradigms. Infodemiological analysis promises to articulate that people around the globe are divided in their favor stigmatized monikers in the public and scientific communities because of perceptual bias. There is no positive correlation between the degree of infection in their territories and collective perceptual bias to COVID-19. The official portfolio “COVID-19” and “SARS-CoV-2” has not become de facto standard usages, but full-fledged official names are excepted to duly contribute to the resilience of negative perceptual bias and collective behavioral propensities.
ARTICLE | doi:10.20944/preprints202008.0163.v1
Subject: Environmental And Earth Sciences, Atmospheric Science And Meteorology Keywords: Coronavirus disease 2019 (COVID-19), temperate sub-continental climate, Lombardy, temperature, solar radiation
Online: 6 August 2020 (11:39:41 CEST)
The coronavirus disease 2019 (COVID-19) pandemic is the defining global health and socioeconomic crisis of our time and represents the greatest challenge faced by the world since the end of the Second World War. The academic literature indicates that climatic features, specifically the temperature and absolute humidity, are very important factors affecting infectious pulmonary disease epidemics (e.g., SARS, MERS); however, the influence of climatic parameters on COVID-19 remains extremely controversial. The goal of this study is to quantify the existing relationship between several daily climate parameters (temperature, relative humidity, accumulated precipitation, solar radiation, wind direction and intensity, and evaporation), local morphological parameters, and new daily positive swabs for COVID-19, which represents the only parameter that can be statistically used to quantify the pandemic. The daily deaths parameter was not considered because it is not reliable due to frequent administrative errors. Daily data on meteorological conditions and new cases of COVID-19 were collected for the Lombardy area from March 1, 2020, to April 20, 2020. This region in Italy exhibited the largest number of official deaths in the world per million inhabitants, with a value of approximately 1700 per million on june 30, 2020. Moreover, the apparent lethality was approximately 17% in this area, mainly due to the considerable housing density and the extensive presence of industrial and craft areas. The Mann-Kendall test and multivariate statistical analysis showed that none of the considered climatic variables exhibited statistically significant relationships with the epidemiological evolution of COVID-19, at least in the spring months in temperate subcontinental climate areas, with the exception of solar radiation, which was directly related and showed an otherwise low explained variability of approximately 20%. Furthermore, the average temperatures of two highly representative meteorological stations of Molise and Lucania, the most weakly affected by the pandemic. The temperatures at these stations were approximately 1.5°C lower than that in the cities in Lombardy of Bergamo and Brescia, again confirming that a significant relationship between the increase in temperature and decrease in virology from COVID-19 was not evident, at least in the Italian peninsula.
ARTICLE | doi:10.20944/preprints202010.0271.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: 2019-nCoV; COVID-19; excess mortality; all-cause deaths; case fatality ratio; CFR; epidemiology
Online: 13 October 2020 (10:27:10 CEST)
Since identified as the pathogen responsible for an outbreak of severe respiratory distress in Wuhan, China, the 2019-nCoV coronavirus has caused over 30M cases and 1M deaths globally. Sporadic cases were identified in several states in the US from early January, and large-scale community transmission is believed to have started in late February, leading to a first spike in COVID-19 deaths and overall mortality in late April, and a second spike later in the summer. I show here that the dynamics of the pandemic were different in different regions of the US, showing a north-south pattern, with a first pandemic wave mainly in northern regions, followed by a second wave mainly in southern regions. Analysis of overall mortality data shows that the increase in mortality correlates well with COVID-19 incidence in most regions, and that from April through August COVID-19 deaths accounted for a substantial proportion of all deaths in all parts of the US.
REVIEW | doi:10.20944/preprints202004.0225.v2
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: Coronavirus disease 2019; COVID-19; children; diabetes; type 1 diabetes; type 2 diabetes; recommendations
Online: 15 May 2020 (04:54:43 CEST)
Recent reports suggest that the clinical course of coronavirus disease 2019 (COVID-19) in previously healthy children is usually milder as compared to adults. However, children with comorbid conditions such as diabetes are at increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as morbidity and mortality due to COVID-19. Experience in adults with diabetes shows that they are prone to faster metabolic decompensation, develop diabetes-related complications, and have a poor prognosis when hospitalized with COVID-19. Data on children are limited. The aim of this mini-review is to discuss the possible risks to children and adolescents with diabetes during the current pandemic and the special considerations in management in those affected with COVID-19. The challenges for children who develop new-onset type 1 diabetes during the COVID-19 lockdown, especially in accessing healthcare, are also discussed.
REVIEW | doi:10.20944/preprints202004.0525.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; evolution of SARS-CoV-2; replication; emerging disease 2019 and diagnostic tools
Online: 30 April 2020 (10:39:54 CEST)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an etiologic agent of the respiratory disease in humans that is known as coronavirus disease 2019 (COVID19). The first outbreak of the disease was initially documented in Wuhan, Hubei Province, China in late December 2019 where people had experienced SARS pneumonia-like symptoms with unknown etiology. Since then it has been observed that COVID-19 positive patients have been showing mild to severe upper respiratory illness symptoms. The type of virus is known to make its transfer from animals to humans and for the concerned virus; researchers have claimed its origin from bat coronavirus at whole-genome level with a 96 % sequence identity. The COVID-19 virus is very contagious and communicable in nature and has been spread throughout the globe since its first outbreak in China. On March 9, 2020, WHO declared it as a Pandemic, and within a month it was already reported to have shown its presence in 213 countries and territories or areas. As of April 29, 2020, this novel virus infected 3,218,183 people and caused 228,029 mortalities worldwide with a variable mortality rate from 3-13 % across the planet and also varied by age and gender. Diagnosis of the disease is a key component in understanding and controlling the spread of the virus and several techniques have been devised including RT-PCR, ELISA, and sequencing-based approaches. To cure COVID-19 patients as of now we do not have proven to be a safe and effective treatment. Therapeutic options currently under investigation in various parts of the world. However, there are various effective therapeutic targets to repurpose the present antiviral therapy for developing potential interventions against SARS-CoV-2. Boosting the immune system can also help to prevent and spread of COVID-19 using various medication and exercises. In this review, our goal to summarize and discussed the present scientific advancements to fight against this novel pandemic.
REVIEW | doi:10.20944/preprints202003.0001.v2
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: emerging coronavirus; 2019-nCoV; SARS-CoV-2; COVID-19; diagnosis; vaccines; therapy; one health
Online: 13 April 2020 (02:29:00 CEST)
In the past decades, several new diseases have emerged in new geographical areas, with pathogens including Ebola, Zika, Nipah, and coronaviruses (CoVs). Recently, a new type of viral infection has emerged in Wuhan City, China, and initial genomic sequencing data of this virus does not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed as severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Although Coronavirus disease 2019 (COVID-19) is suspected to originate from an animal host (zoonotic origin) followed by human-to-human transmission, the possibility of other routes such as food-borne transmission should not be ruled out. Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Compared to other emerging viruses such as Ebola virus, avian H7N9, SARS-CoV, or MERS-CoV, SARS-CoV-2 has shown relatively low pathogenicity and moderate transmissibility. Codon usage studies suggest that this novel virus may have been transferred from an animal source such as bats. Early diagnosis by real-time PCR and next-generation sequencing has facilitated the identification of the pathogen at an early stage. Since, no antiviral drug or vaccine exists to treat or prevent SARS-CoV-2, potential therapeutic strategies that are currently being evaluated predominantly stem from previous experience with treating SARS-CoV, MERS-CoV, and other emerging viral diseases. In this review, we address epidemiological, diagnostic, clinical, and therapeutic aspects, including perspectives of vaccines and preventive measures that have already been globally recommended.
BRIEF REPORT | doi:10.20944/preprints202003.0295.v1
Subject: Biology And Life Sciences, Virology Keywords: Wuhan 2019-nCoV; ACE2; DNA methylation; epigenetics; profiling; lung tissue; age; gender; COVID-19; coronavirus
Online: 19 March 2020 (02:51:45 CET)
Background: Coronavirus disease 2019 (COVID-19) has emerged as a global threat to human health and disease risk increases with advancing age. The regulation of the ACE2 gene that codes for COVID-19 host receptor ACE2 has been shown to be under epigenetic regulation. Here, we examined whether intensive DNA methylation profiling of the ACE2 gene differed by human host tissue and cell type, gender, and age. Results: Accessing four public datasets, we observed unique human cell-type-specific ACE2 DNA methylation patterns. In human lung tissues, gender differences in DNA methylation at 2 sites related to the ACE2 gene were identified. Further, in freshly isolated airway epithelial cells, DNA methylation near the transcription start site of the ACE2 gene associated with biological age. Conclusion: Epigenetic profiling of host tissue may permit discovery of age and gender-related potential risk factors for COVID-19. How perturbations in ACE2 methylation relate to clinical severity across the ages and gender needs to be determined to guide screening tools and potential epigenetic modification targeting to alleviate COVID-19 morbidity in the elderly.
COMMUNICATION | doi:10.20944/preprints202002.0418.v2
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: virtual screening; molecular docking; drug repurposing; drug repositioning; anti-viral drugs; Coronavirus; COVID-19; 2019-nCoV; SARS-CoV-2
Online: 9 March 2020 (02:29:04 CET)
SARS-CoV-2 is the betacoronavirus responsible for the COVID-19 pandemic. It was listed as a potential global health threat by WHO due to high mortality, high basic reproduction number and lack of clinically approved drugs and vaccines for COVID-19. The genomic sequence of the virus responsible for COVID-19, as well as the experimentally determined three dimensional structure of the Main protease (Mpro) are available. The reported structure of the target Mpro was utilized in this study to identify potential drugs for COVID-19 using molecular docking based virtual screening of all approved drugs. The results of this study confirm preliminary reports that some of the drugs approved for treatment of other viral infections have the potential for treatment of COVID-19. Selected antiviral drugs, approved for human therapeutic applications, were ranked for potential effectiveness against COVID-19, based on predicted binding energy to the target Mpro of SARS-CoV-2, and novel candidates for drug repurposing were identified in this study. In addition, potential mechanisms for beneficial off target effects of some drugs in clinical trials were identified by using molecular docking.
ARTICLE | doi:10.20944/preprints202004.0240.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: COVID19; 2019-nCov, 3CLpro inhbitors
Online: 15 April 2020 (10:00:52 CEST)
The novel coronavirus 2019 (nCov-2019/Covid-2019/2019-nCov) has become a pandemic in a very short span of time. It has caused significant loss to human lives, economy, daily life. The key development against the nCov-2019 remains apprehended when it comes to discovery of its vaccine or medicines for the treatment. Drugs used for the treatment of HIV ( inhibitors of HIV protease) are being largely used for the treatment of nCov-2019. Therefore, we conducted a study by docking a set of natural compounds with reported protease activity against HIV or SARS coronavirus against the protease of nCov-2019. The Bavachinin ranked the top among natural compounds with binding energy of -7.74±0.152 Kcal/mol, RMSD 0.823±0.024 Å, predicted pKd 5.59 and predicted dG of -7.56 Kcal/mol. The finding infers that these three compounds could have the potential to inhibit the nCov-2019 protease. The finding was supported with reputed research publications.
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: 2019-nCoV; ACE2; HLA-DRB1
Online: 17 February 2020 (15:25:43 CET)
A novel coronavirus (2019-nCoV) was first identified in Wuhan, Hubei Province, and then spreads to the other Provinces of China. 2019-nCoV was reported to share the same receptor, Angiotensin-converting enzyme 2 (ACE2), with SARS-CoV. Previous studies have found ACE2 is abundantly present in humans in the epithelia of the lung and small intestines, and they found ACE2 expression in the basal layer of the non-keratinizing squamous epithelium in nasal and oral mucosa and the nasopharynx. Here based on the public single-cell RNA-Seq datasets, we analyzed the ACE2 expression in the nasal, mouth, lung, and colon tissues. We find that the number of ACE2-expressing cells in the nasal tissue and mouth is comparable to the number of ACE2-expressing cells in the lung tissue and colon. We also find that ACE2 tends to be co-expressed with HLA-DRB1, which plays a central role in the immune system by presenting peptides derived from extracellular proteins, in the nasal, mouth, lung, and colon tissues at single-cell resolution. We hope this provides valuable information for virus-prevention strategy and therapeutic strategy development.
ARTICLE | doi:10.20944/preprints202002.0221.v1
Online: 16 February 2020 (14:56:57 CET)
ACE2, the putative receptor for the novel coronavirus (2019-nCoV), played an important role in cell entry of 2019-nCoV. However, it is not yet clear what cell types within the human body express ACE2. Here, a systematic analysis was undertaken using published single cell datasets. In total, our study analyzed 229652 cells, from five different organs, derived from 88 donors. The top ACE2 expressing cells include proximal tubule cells in the kidney and enterocytes in the intestine. Other major ACE2 expressing cells in the kidney include podocytes, intercalated cells and endothelial cells. Our results offer a comprehensive atlas of ACE2 expression at the single cell level and unravel the enormous potential targets of 2019-nCoVinfection beyond the lung.
ARTICLE | doi:10.20944/preprints202002.0194.v1
Online: 14 February 2020 (10:52:21 CET)
Recently, it was confirmed that ACE2 is the receptor of 2019-nCoV, the pathogen causing the recent outbreak of severe pneumonia in China. It is confused that ACE2 is widely expressed across a variety of organs and is expressed moderately but not highly in lung, which, however, is the major infected organ. It remains unclear why it is the lung but not other tissues among which ACE2 highly expressed is mainly infected. We hypothesized that there could be some other genes playing key roles in the entry of 2019-nCoV into human cells. Here we found that AGTR2 (angiotensin II receptor type 2), a G-protein coupled receptor, has interaction with ACE2 and is highly expressed in lung with a high tissue specificity. More importantly, simulation of 3D structure based protein-protein interaction reveals that AGTR2 shows a higher binding affinity with the Spike protein of 2019-nCov than ACE2 (energy score: -15.7 vs. -6.9 [kcal/mol]). Given these observations, we suggest that AGTR2 could be a putative novel gene for the the entry of 2019-nCoV into human cells but need further confirmation by biological experiments. Finally, a number of compounds, biologics and traditional Chinese medicine that could decrease the expression level of AGTR2 were predicted.
REVIEW | doi:10.20944/preprints202306.1457.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Coronavirus disease 2019; COVID-19; Stroke; Cerebral vein thrombosis; Intracranial hemorrhage; Anticoagulation; Mechanical thrombectomy; Intravenous thrombolysis
Online: 20 June 2023 (15:13:35 CEST)
Not in the history of transmissible illnesses has there been an infection as strongly associated with acute cerebrovascular disease as the novel human coronavirus, SARS-CoV-2. While the risk of stroke has known associations with other viral infections, such as influenza and human immunodeficiency virus, the risk of ischemic and hemorrhagic stroke related to SARS-CoV-2 is unprecedented. Furthermore, the coronavirus disease 2019 (COVID-19) pandemic has so profoundly impacted psychosocial behaviors and modern medical care that we have witnessed shifts in epidemiology and have adapted our treatment practices to reduce transmission, address delayed diagnoses, and mitigate gaps in health care. In this narrative review, we summarize the history and impact of the COVID-19 pandemic on cerebrovascular disease, and lessons learned regarding the management of patients as we endure this period of human history.
ARTICLE | doi:10.20944/preprints202009.0436.v1
Subject: Biology And Life Sciences, Ecology, Evolution, Behavior And Systematics 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/preprints202008.0104.v1
Subject: Social Sciences, Behavior Sciences Keywords: coronavirus disease 2019 (COVID-19); pandemic; infectious disease; psychological (mental) consequences; mental distress; outbreak; epidemiological study
Online: 4 August 2020 (16:16:23 CEST)
Background: Coronavirus disease 2019 (COVID-19) is an ongoing pandemic and life-threatening highly infectious disease. The people of Bangladesh are at high risk of COVID-19 and have already experienced various socio-economic, health and psychological (mental) consequences. Particularly, mental health problems are dominantly reported in the literature and should be controlled. The main objective of this epidemiological study is to assess the mental distress and identify its determinants using online-based survey. Such information is urgently needed to develop feasible strategies for Bangladesh. Methods: An online survey was conducted for this study from May 01 to May 05, 2020. A total of 240 respondents provided self-reported online responses. Respondent’s mental distress was measured by the General Health Questionnaire 12 (GHQ-12) and by the self-rated mental health (SRMH) question. Various kinds of statistical analyses ranging from simple to multivariable logistic recession were performed using SPSS 23.0. Results: About 31.3% and 48.3% of respondents were mentally distressed by GHQ-12 and SRMH question, respectively. Logistic regression analysis revealed that mental distress was significantly higher among those respondents, whose usual activity was affected by the coronavirus (OR = 6.40, 95% CI: 1.87 - 21.90, p<0.001) and whose financial stress was increased due to lockdown (OR = 2.12, 95% CI: 1.01 – 4.46, p<0.05) on GHQ-12. Female sex (OR = 1.97, 95% CI: 1.03 – 3.75, p<0.05) and respondents with poor mental health before the outbreak (OR = 3.38, 95% CI: 1.18 – 9.72, p<0.05) were also significantly affected by mental distress on SRMH. Conclusions: At least thirty percent of the respondents were found to be mentally distressed. Some of the study findings, particularly significant determinants, should be considered while developing strategies to reduce the burden of mental distress among study respondents or similar group in Bangladesh.
BRIEF REPORT | doi:10.20944/preprints202211.0421.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: coronavirus disease 2019; COVID-19; severe acute respiratory syndrome coronavirus 2; SARS-CoV-2, prediabetes; new-onset diabetes; diabetes; HbA1c; long COVID
Online: 22 November 2022 (10:39:38 CET)
Studies have shown that COVID-19 patients with prediabetes frequently present with high plasma glucose levels on hospital admission. However, whether the glycemic abnormalities are temporary or persist after recovery from the illness is unclear. We conducted a prospective cohort study of 69 COVID-19 patients with prediabetes (HbA1c 5.7-6.4%) who were admitted to a tertiary care hospital in Chennai, India, from May to October 2020 and were discharged alive. Over a mean follow-up of 146.6 (SD: 72.5) days, the mean fasting plasma glucose rose by 16.8 mg/dl (from 119.3-136.1 mg/dl), 2-hr post-prandial glucose by 61.0 mg/dl (from 176.2-237.2 mg/dl), and HbA1c by 0.6% (5.9-6.5%). Of the 49 (84.5%) patients who were discharged with glucose-lowering medications, 40 (81.6%) continued taking them at the first follow-up visit (mean of 50.1 days from admission), and 39 (79.6%) continued taking them at the second follow-up visit (mean of 114.3 days from first the follow-up visit). In addition, 12.1% of patients developed new-onset diabetes after recovery from the illness. Continuous monitoring of glycemia and detecting new-onset diabetes in COVID-19 patients with prediabetes after recovery are essential, as the metabolic effects of SARS-CoV-2 persist for several months.
ARTICLE | doi:10.20944/preprints202210.0446.v1
Subject: Public Health And Healthcare, Nursing Keywords: acute myocardial infarction; coronavirus disease 2019 (COVID-19); island communities; point-of-care testing; spatial care paths
Online: 28 October 2022 (09:30:44 CEST)
Abstract: Our goal is to create point-of-care (POC) strategies that accelerate decision making, increase efficiency, improve outcomes, and enhance standards of care in island communities faced with global warming, rising oceans, population migration, and intensifying weather disasters. We assessed needs in the Bantayan Archipelago and mainland Cebu Province, Visayas Islands, Philippines, to map POC diagnostics, rescue times, and spatial care paths. Significant deficiencies were lack of cardiac troponin testing for rapid diagnosis of acute myocardial infarction, absence of blood gas and pH testing for support of critically ill patients, and geographic gaps prolonging patient transfers and delaying treatment. Strengths comprised primary care that can be facilitated by POC testing, logical inter-island transfers for which decision making and triage could be accelerated with onboard diagnostic testing, and healthcare small-world networks amenable to POC advances, such as pre-hospital testing, that avoid overloading emergency rooms. Healthcare resources must be distributed to archipelago islands, not concentrated in large metropolitan areas inaccessible for emergency interventions. We conclude that a point-of-need focus will help improve public health, decrease disparities in mortality among rural islanders versus urban dwellers, and pave the way for heightened resilience in anticipation of the adverse impact of global warming on vulnerable coastal areas.
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: COVID-19; 2019 novel coronavirus; SARS-CoV-2; Deep Transfer Learning; Convolutional Neural Network; Machine Learning; CGAN
Online: 5 May 2020 (04:14:58 CEST)
The coronavirus disease 2019 (COVID-19) is the fastest transmittable virus caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The detection of COVID-19 using artificial intelligence techniques and especially deep learning will help to detect this virus in early stages which will reflect in increasing the opportunities of fast recovery of patients worldwide. This will lead to release the pressure off the healthcare system around the world. In this research, classical data augmentation techniques along with CGAN based on a deep transfer learning model for COVID-19 detection in chest CT scan images will be presented. The limited benchmark datasets for covid-19 especially in chest CT images is the main motivation of this research. The main idea is to collect all the possible images for covid-19 that exists until the very writing of this research and use the classical data augmentations along with CGAN to generate more images to help in the detection of the COVID-19. In this study, five different deep convolutional neural network-based models (AlexNet, VGGNet16, VGGNet19, GoogleNet, and ResNet50) have been selected for the investigation to detect the coronavirus infected patient using chest CT radiographs digital images. The classical data augmentations along with CGAN improve the performance of classification in all selected deep transfer models. The Outcomes show that ResNet50 is the most appropriate deep learning model to detect the COVID-19 from limited chest CT dataset using the classical data augmentation with testing accuracy of 82.91%.
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: 2019 novel coronavirus; COVID-19; SARS-CoV-2; Deep Transfer Learning; Convolutional Neural Network; Machine Learning; GAN
Online: 7 April 2020 (10:59:04 CEST)
The coronavirus (covid-19) pandemic is putting healthcare systems across the world under unprecedented and increasing pressure according to the World Health Organization (WHO). With the advances in computer algorithms and especially Artificial Intelligence, the detection of this type of virus in the early stages will help in fast recovery and help in releasing the pressure off healthcare systems. In this paper, a GAN with deep transfer learning for coronavirus detection in chest x-ray images is presented. The lack of benchmark datasets for covid-19 especially in chest x-rays images is the main motivation of this research. The main idea is to collect all the possible images for covid-19 that exists until the writing of this research and use the GAN network to generate more images to help in the detection of the virus from the available x-rays images with the highest accuracy possible. The dataset used in this research was collected from different sources and it is available for researchers to download and use it. The number of images in the collected dataset is 307 images for four different types of classes. The classes are the covid-19, normal, pneumonia bacterial, and pneumonia virus. The dataset is divided into 90% for the GAN and the training and the validation phase, while 10% used in the testing phase. The GAN helps in generating more images from the original dataset to be 30 times larger than the originally collected dataset. The GAN also help in overcoming the overfitting problem and made the proposed model more robust. Three deep transfer models are selected in this research for investigation. The models are the Alexnet, Googlenet, and Restnet18. Those models are selected based on their small number of layers on their architectures, which will reflect in reducing the complexity of the models and the consumed memory and time. Using a combination of GAN and deep transfer models prove it is efficiency according to validation, testing accuracy, and performance measurements such as precision, recall, and F1 score. Three case scenarios are tested through the paper, the first scenario which includes 4 classes from the dataset, while the second scenario includes 3 classes and the third scenario includes 2 classes. All the scenarios include the covid-19 class as it is the main target of this research to be detected. In the first scenario, the Googlenet is selected to be the main deep transfer model as it achieves 80.6% in testing accuracy. In the second scenario, the Alexnet is selected to be the main deep transfer model as it achieves 85.2% in testing accuracy, while in the third scenario which includes 2 classes(covid-19, and normal), Googlenet is selected to be the main deep transfer model as it achieves 100% in testing accuracy and 99.9% in the validation accuracy. All the performance measurement strengthen the obtained results through the research. Finally, this research may be considered one of the first trails to use GAN and deep transfer models together to help in detecting coronaviruses (covid-19) within the absence of a benchmark dataset around the world, especially in x-rays chest images.
ARTICLE | doi:10.20944/preprints202003.0440.v1
Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; 2019-nCoV; novel corona virus; drug repurposing; chloroquine; high-risk group; asymptomatic
Online: 30 March 2020 (07:24:16 CEST)
COVID-19 (2019-nCoV) is a pandemic disease with an estimated mortality rate of 3.4% (estimated by the WHO as of March 3, 2020). Until now there is no antiviral drug and vaccine for COVID-19. The current overwhelming situation by COVID-19 patients in hospitals is likely to increase in the next few months. About 15 percent of patients with serious disease in COVID-19 require immediate health services. Rather than waiting for new anti-viral drugs or vaccines that take a few months to years to develop and test, several researchers and public health agencies are attempting to repurpose medicines that are already approved for another similar disease and have proved to be fairly effective. This study aims to identify FDA approved drugs that can be used for drug repurposing and identify biomarkers among high- risk and asymptomatic groups. In this study gene-disease association related to COVID-19 reported mild, severe symptoms and clinical outcomes were determined. The high-risk group was studied related to SARS-CoV-2 viral entry and life cycle by using Disgenet and compared with curated COVID-19 gene data sets from the CTD database. The overlapped gene sets were enriched and the selected genes were constructed for protein-protein interaction networks. Through interactome, key genes were identified for COVID-19 and also for high risk and asymptomatic groups. The key hub genes involved in COVID-19 were VEGFA, TNF, IL-6, CXCL8, IL10, CCL2, IL1B, TLR4, ICAM1, MMP9. The identified key genes were used for drug-gene interaction for drug repurposing. The chloroquine, lenalidomide, pentoxifylline, thalidome, sorafenib, pacitaxel, rapamycin, cortisol, statins were proposed to be probable drug repurposing candidates for the treatment of COVID-19. However, these predicted drug candidates need to be validated through randomized clinical trials. Also, a key gene involved in high risk and the asymptomatic group were identified, which can be used as probable biomarkers for early identification.
SHORT NOTE | doi:10.20944/preprints202002.0310.v1
Subject: Biology And Life Sciences, Virology Keywords: 2019-nCoV; phylogenetic tree; phylogenetic profile
Online: 23 February 2020 (02:32:54 CET)
Background: The seventh novel human infecting Betacoronavirus that causes pneumonia (2019 novel coronavirus, 2019-nCoV) originated in Wuhan, China. The evolutionary relationship between 2019-nCoV and the other human respiratory illness-causing coronaviruses is unclear. We sought to characterize the relationship of the translated proteins of 2019-nCoV with other species of Orthocoronavirinae.Methods: A phylogenetic tree was constructed from the genome sequences. A cluster tree was developed from the profiles retrieved from the presence and absence of homologs of ten 2019-nCoV proteins. The combined data were used to characterize the relationship of the translated proteins of 2019-nCoV to other species of Orthocoronavirinae.Results: Our analysis reliably suggests that 2019-nCoV is most closely related to BatCoV RaTG13 and belongs to subgenus Sarbecovirus of Betacoronavirus, together with SARS coronavirus and Bat-SARS-like coronavirus. The phylogenetic profiling cluster of homolog proteins of one annotated 2019-nCoV protein against other genome sequences revealed two clades of ten 2019-nCoV proteins. Clade 1 consisted of a group of conserved proteins in Orthocoronavirinae comprising Orf1ab polyprotein, Nucleocapsid protein, Spike glycoprotein, and Membrane protein. Clade 2 comprised six proteins exclusive to Sarbecovirus and Hibecovirus. Two of six Clade 2 nonstructural proteins, NS7b and NS8, were exclusively conserved among 2019-nCoV, BetaCoV_RaTG, and BatSARS-like Cov. NS7b and NS8 have previously been shown to affect immune response signaling in the SARS-CoV experimental model. Thus, we speculate that knowledge of the functional changes in the NS7b and NS8 proteins during evolution may provide important information to explore the human infective property of 2019-nCoV.
CASE REPORT | doi:10.20944/preprints202002.0156.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: 2019-nCoV; Chest CT; Epidemic; Diagnosis
Online: 12 February 2020 (09:14:56 CET)
An outbreak of novel coronavirus(2019-nCoV) that began in Wuhan, China, is rapidly spreading to all over China, and gradually to multiple countries. Regarding to put the epidemic prevention and spread under the control, early identification and diagnosis play a critical role. Patients with initially no or mild symptoms of Novel Coronavirus Pneumonia (2019-nCoV), namely “stealth” infection, often lack of typical clinical evidence to establish the diagnosis. Based on the clinical analysis of 4 cases in stealth infection, the results of this study highlight that early diagnosis requires a combination of epidemiological history, clinical manifestations, early chest CT examination, and 2019-nCoV RNA test (nucleic acid test), with particular emphasis on definite epidemiological history and early chest CT findings when positive nucleic acid tests lag behind.
ARTICLE | doi:10.20944/preprints202002.0063.v1
Subject: Computer Science And Mathematics, Computer Science Keywords: Transportation; dynamic graph model; 2019-nCoV
Online: 5 February 2020 (11:33:39 CET)
Since the outbreak of 2019 novel coronavirus (2019-nCoV) at the hardest-hit city of Wuhan, the fast-moving spread has killed over three hundred people and infected more than ten thousands in China1. There are more than one hundred cases outside of China, affecting a dozen of countries globally2. The genome sequence of 2019-nCoV has been reported and fast diagnostic kits, effective treatment as well as preventive vaccines are rapidly being developed3. Initial fast-growing confirmed cases triggered lock-down of Wuhan as well as nearby cities in Hubei Province. Mathematical models have been proposed by scientists around the world to project the numbers of infected cases in the coming days 4,5. However, major factors such as transportation and cultural customs have not been weighed enough. Our model is not set out for precise prediction of the number of infected cases, rather, it is meant for a glance of the dynamics under a public epidemic emergency situation and of different contributing factors. We hope that our model and simulation would provide more insights and perspective information to public health authorities around the globe for better informed prevention and containment solution.
ARTICLE | doi:10.20944/preprints202002.0047.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: 2019-nCoV; therapeutic strategies; drug; ACE2
Online: 4 February 2020 (10:59:25 CET)
Most recently, an outbreak of severe pneumonia caused by the infection of 2019-nCoV, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Many important aspects about 2019-nCoV remain largely unknown, among which, the limitation of antiviral therapies represents one of the most critical problems. More recently, it was confirmed that human ACE2 is the receptor for the entry of 2019-nCoV into lower respiratory tract epithelial cells. Give this observation, it is thus expected that the virus could be inhibited if we decrease the expression of ACE2. Here by screening two databases, Connectivity Map (CMap) and our JeaMoon Map (JMap), we identified a number of candidate agents that decrease ACE2 expression. CMap analysis identified 5 compounds, among which, Azathioprine is a possible therapeutic strategy for anti-2019-nCoV. Moreover, JMap analysis revealed a number of comounds, biologics, and traditional Chinese medicine, among which, Andrographis, Urtica, Sambucus, Astragalus, valproic acid, butyrate, and epoxomicin represent the most significant and possible strategies for anti-2019-nCoV therapies. This study provides a number of clues and possible therapeutic strategies for 2019-nCoV prevention and treatment.
REVIEW | doi:10.20944/preprints202103.0490.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Covid-19; Long Covid-19; Long Haulers Covid; Post Covid-19 Syndrome; Post-Acute Covid-19; Corona Virus; SARS-Cov-2; Novel Corona Virus 2019; Post-Acute SARS-CoV-2; PASC, Post-Acute Sequelae of COVID-19; Late Sequelae COVID-19
Online: 18 March 2021 (17:16:52 CET)
Introduction: Despite more than one year passed since the first cases of SARS-CoV-2 were reported, there is still no consensus on the definition and clinical management of post-acute-COVID-19. The condition has heterogeneously been named as Chronic COVID syndrome, Post COVID-19 Syndrome, post-acute sequela of SARS-CoV-2 (PASC), and the more familiar long COVID. Method: In order to capture all relevant published studies, we undertook a multi-step search with no language restriction. The following four-step search strategy was utilized: First, a preliminary (limited) search was conducted on January 20, 2021, in Google Scholar and PubMed to identify the appropriate keywords. Then, on January 30, 2021, we adopted a search strategy of electronic databases from Cochrane Library, PsycINFO, PubMed, Embase, Scopus, and Web of sciences, using those keywords. Then, after duplicate removal, we screened all titles, abstracts, and full texts. This resulted in 66 eligible studies. Subsequently, after a forward and backward search of their references and citations an additional 54 publications were found, resulting in a total of 120 publications that formed the basis of the present analysis. The titles, abstracts, and full-texts of non-English articles were translated using Google Translate for further evaluation. We conducted our scoping review based on the PRISMA-ScR Checklist.Results: We found only one randomized clinical trial in our search. Of the 67 original studies, 22 were cohort and 28 were cross-sectional studies totaling 74.6% of the original studies. Of the total of 120 publications, 59 (49.1%) focused on signs and symptoms, 28 (23.3%) were focused on management, and 13 (10.8%) focused on pathophysiology. Ten (9%) publications focused on imaging studies. Ninety-one percent of the original investigations came from high and upper-middle-income countries, highlighting the scarcity of reports originating from low-income and lower-middle-income countries.Conclusion: The predominant symptoms among those with the so-called “Long COVID” were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness. The ambiguity and controversies in its definition have impaired proper recognition and management of those requiring additional support following the resolution of the acute phase of this infection. This has resulted in long-standing distress for the patients and their families. Our findings highlight the need for a multidisciplinary approach, support, and rehabilitation for these patients in terms of long-term mental and physical health.
ARTICLE | doi:10.20944/preprints202304.0971.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: 2019-nCoV; COVID-19; RT-PCR; SARS-CoV-2; Community-acquired pneumonia; Chest CT; microwave radiometry; temperature measurement
Online: 26 April 2023 (08:02:32 CEST)
Background. Chest CT is widely regarded as a dependable imaging technique for detecting pneumonia in COVID-19 patients, but there is growing interest in microwave radiometry (MWR) of the lungs as a possible substitute for diagnosing lung involvement. Aim. The aim of the study is to examine the utility of the MWR approach as a screening tool for diagnosing pneumonia with complications in patients with COVID-19. Methods. Our study involved two groups of participants. The control group consisted of 50 individuals (24 male and 26 female) between the ages of 20 to 70 years who underwent clinical evaluations and had no known medical conditions. The main group included 142 participants (67 men and 75 women) between the ages of 20 to 87 years who were diagnosed with COVID-19 complicated by pneumonia and were admitted to the emergency department between June 2020 to June 2021. Skin and lung temperatures were measured at 14 points, including 2 additional reference points, using a previously established method. Lung temperature data were obtained with the MWR2020 (RTM-01-RES) (MMWR LTD, Edinburgh, UK), a CE Class I device. All participants underwent clinical evaluations, laboratory tests, chest CT scans, MWR of the lungs, and reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2. Results. The MWR exhibits a high predictive capacity as demonstrated by its sensitivity of 98.6% and specificity of 84.0%. Conclusions. MWR of the lungs can be a valuable substitute for chest CT in diagnosing pneumonia in patients with COVID-19, especially in situations where chest CT is unavailable or impractical.
REVIEW | doi:10.20944/preprints202004.0469.v1
Subject: Biology And Life Sciences, Virology Keywords: severe acute respiratory syndrome coronavirus-2; COVID-2019; epidemiology; pathobiology; clinical profile; phyloanalysis; artificial intelligence; diagnosis; vaccines; therapeutics
Online: 26 April 2020 (08:15:23 CEST)
The technology-driven world of the 21st century is currently confronted with a major threat to humankind in the form of the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As of April 22, 2020, COVID-19 has claimed 169, 006 human lives and had spread to over 200 countries with more than 2,471,136 confirmed cases. The perpetually increasing figures associated with COVID-19 are disrupting the social and economic systems globally. The losses are unmatched and significantly higher compared to those from previously encountered pathogenic infections. Previously, two CoVs (SARS-CoV and Middle East respiratory syndrome-CoV) affected the human population in 2002 and 2012 in China and Saudi Arabia, respectively. Based on genomic similarities, animal-origin CoVs, primarily those infecting bats, civet cats, and pangolins, were presumed to be the source of emerging human CoVs, including the SARS-CoV-2. The cohesive approach amongst virologists, bioinformaticians, big data analysts, epidemiologists, and public health researchers across the globe has delivered high-end viral diagnostics. Similarly, vaccines and therapeutics against COVID-19 are currently in the pipeline for clinical trials. The rapidly evolving and popular technology of artificial intelligence played a major role in confirming and countering the COVID-19 pandemic using digital technologies and mathematical algorithms. In this review, we discuss the noteworthy advancements in the mitigation of the COVID-19 pandemic, focusing on the etiological viral agent, comparative genomic analysis, population susceptibility, disease epidemiology, animal reservoirs, laboratory animal models, disease transmission, diagnosis using artificial intelligence interventions, therapeutics and vaccines, and disease mitigation measures to combat disease dissemination.
REVIEW | doi:10.20944/preprints202003.0271.v2
Subject: Medicine And Pharmacology, Ophthalmology Keywords: Coronavirus; 2019-nCOV; SARS-CoV-2; transmission; infection; conjunctiva; eye
Online: 24 March 2020 (06:42:35 CET)
The outbreak of recently identified 2019 novel coronavirus (2019-nCOV) infection has become a world-wide health threat. Currently, more information is needed for further understanding the transmission, clinical characteristics, and infection control procedures of 2019-nCOV. Recently, the role of the eye in transmitting 2019-nCOV has been intensively discussed. Previous investigations about other high infectious human COVs, that is, severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), may provide helpful information. In this review, we describe the genomics and morphology of human CoVs, the epidemiology, systemic and ophthalmic manifestations, mechanisms of human CoVs infection, and infection control procedures. The role of the eye in the transmission of SARS-CoV and 2019-nCOV is discussed. Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of ocular surface and upper respiratory tract is connected by nasolacrimal duct and share same entry receptors for some respiratory viruses. The eye is rarely involved in human CoVs infection, conjunctivitis is quite rare in patients with SARS-CoV and 2019-nCoV infection, and COV RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with SARS-CoV and 2019-nCoV infection is also very low, which imply that the eye is neither a preferred organ of human COVs infection, nor is a preferred gateway of entry for human COVs to infect respiratory tract. However, pathogens exposed to the ocular surface might be transported to nasal and nasopharyngeal mucosa by constant tear rinsing through lacrimal duct, and then cause respiratory tract infection. Considering close doctor-patient contact is quite common in ophthalmic practice which are apt to transmit human COVs by droplets and fomites, hand hygiene and personal protection are still highly recommended for health care workers to avoid hospital-related viral transmission during ophthalmic practice.
Subject: Biology And Life Sciences, Food Science And Technology Keywords: citrus flavnoids; naringin; immunoregulation; ACE2; 2019-nCoV
Online: 23 February 2020 (09:49:10 CET)
The most recent outbreak of 2019 novel coronavirus, named as COVID-19, caused pneumonia epidemic in Wuhan with 2,121 deaths cases as of February 20th 2020. Identification of effective antiviral agents to combat the novel coronavirus is urgently needed. Citrus fruit peel or wild citrus are rich in flavonoid, and is clinically documented for roles in relief of cough and promotion of digestive health. Therefore, citrus fruits are assumed to possess antivirus activities or enhance the host immunity. A previous study found that hesperetin could act as a high potent inhibitor of SARS-CoV 3CLpro. We determined six flavonoid compounds content of in three citrus species by using LC-MS technique. The content of naringin and naringenin was at higher levels in pummelo. Hesperetin and hesperidin were highly accumulated in mandarin and sweet orange. The subsequent in vitro and in vivo experiments indicated that naringin could inhibit the expression of the proinflammatory cytokines (COX-2, iNOS, IL-1β and IL-6) induced by LPS in Raw macrophage cell line, and may restrain cytokine through inhibiting HMGB1 expression in a mouse model. The results revealed that naringin may have a potential application for preventing cytokine storm. We simulated molecular docking to predict the binding affinity of those flavonoids to bind Angiotensin-converting enzyme 2 (ACE 2), which is a receptor of the coronavirus. Consideration of the potential anti-coronavirus and anti-inflammatory activity of flavonoids, the citrus fruit or its derived phytochemicals are promising in the use of prevention and treatment of 2019-nCoV infection.
ARTICLE | doi:10.20944/preprints202002.0132.v2
Subject: Biology And Life Sciences, Virology Keywords: 2019-nCoV; SARS-CoV-2; novel corona virus; Wuhan pneumonia
Online: 18 February 2020 (11:52:25 CET)
The rapid development of 2019-2020 Wuhan seafood market pneumonia currently posed a major public health concern in China. Genome sequencing identified a novel beta-coronavirus closely related to SARS-CoV, named 2019-nCoV by WHO, as the cause of this pandemic disease. Viruses with single stranded RNA genome are prone to evolve quickly by accumulation of mutations, such as SNV, INDEL and cross viral recombination, aiding fast transmission among hosts and cross species. Here we collected related genome sequences and investigated variations shared by different strains of 2019-nCoV, identified reoccurrence of SNV mutations in clusters of patients, an indication of rapid evolution of 2019-nCoV at the transmission from animal host to human. The information collected herein would help to understand the dynamics of current pandemic.
HYPOTHESIS | doi:10.20944/preprints202001.0358.v3
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: SARS-CoV-2 (2019-nCoV); Baicalin; Scutellarin; Hesperetin; Nicotianamine; Glycyrrhizin
Online: 10 March 2020 (05:09:22 CET)
SARS-CoV-2 (2019-nCoV), a novel coronavirus, caused the pneumonia outbreak in China and continue to expand. The host receptor for 2019-nCoV Angiotensin-converting enzyme 2 (ACE2), is the same as the host receptor for SARS-CoV. Targeting ACE2 holds the promise for preventing and inhibiting 2019-nCoV infection. Chinese Medicine herbs could be a valuable pool for identifying active compounds for treating infection of 2019-nCoV. In this study, we summarize several active compounds, including baicalin, Scutellarin, Hesperetin, Nicotianamine and glycyrrhizin that could have potential anti-2019-nCoV effects. We conduct molecular docking to predict their capacity for binding ACE2, which may prevent the 2019-nCoV infection. We propose that these selected compounds worth further investigation for preventing 2019-nCoV.
REVIEW | doi:10.20944/preprints202009.0076.v1
Subject: Medicine And Pharmacology, Pathology And 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/preprints202004.0171.v2
Subject: Biology And Life Sciences, Virology Keywords: protein functional domains; short linear motifs; coronaviruses; COVID-19; severe acute respiratory syndrome-related coronavirus; 2019-nCoV; virus outbreak
Online: 16 May 2020 (18:54:17 CEST)
Although phylogenetic analysis shows coronaviruses (CoV) share similar genome sequences, CoVs encode different number of proteins (5 to 14), which has implication on viral pathogenicity and infection. Here, we aimed to identify (in-silico) the similarities between different members of coronavirus family. The analysis included 50 coronavirus proteomes, including SARS-CoV-2 (COVID-19), to find the variation of the number of protein functional motifs and domain in each coronavirus. For this role, we used the experimentally validated domain (motif) that known to be crucial for viral infection. Although human CoVs are classified within one genus, we found variations among them. SARS-CoV-1, SARS-CoV-2 and MERS-CoV encode different type of domains, which has implications on the molecular interactions triggered by each virus within human cells. Secondly, we used functional motifs to reconstruct the potential molecular pathways or interactions triggered by SARS-CoV-2 proteins within human cell.
REVIEW | doi:10.20944/preprints202005.0260.v2
Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV; SARS-like coronavirus; 2019-nCoV; SARS-CoV-2; angiotensin-converting enzyme 2 (ACE2); RdRp; Remdesivir; and neutralizing antibody
Online: 10 July 2020 (16:21:17 CEST)
SARS-CoV-2 is a newly emerging, highly transmissible, and pathogenic coronavirus in humans, which has caused global public health emergency and economic crisis. To date, millions of infections and thousands of deaths have been reported worldwide, and the numbers continue to rise. Currently, there is no specific drug or vaccine against this deadly virus; therefore, there is a pressing need to understand the mechanism through which this virus enters the host cell. Viral entry into the host cell is a multistep process in which SARS-CoV-2 utilizes the receptor binding domain of the spike glycoprotein (S) to recognize ACE2 receptors on the human cells; this initiates host cell entry by promoting viral-host cell membrane fusion through large scale conformational changes in the S protein. Receptor recognition and fusion are critical and essential steps of viral infections and are key determinants of the viral host range and cross-species transmission. In this review, we summarize the current knowledge on the origin and evolution of SARS-CoV-2 and the roles of key viral factors. We discuss the RNA dependent RNA polymerase structure of SARS-CoV-2, its significance in drug discovery, and explain the receptor recognition mechanisms of coronaviruses. We provide a comparative analysis of the SARS-CoV and SARS-CoV-2 S proteins, receptor-binding specificity, and discuss the differences in their antigenicity based on biophysical and structural characteristics.
REVIEW | doi:10.20944/preprints202003.0343.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: coronavirus; 2019-nCoV; SARS-CoV-2; animal coronaviruses; COVID-19; bat coronavirus; zoonoses; epidemiology; transmission; diagnosis; antivirals; prevention and control
Online: 23 March 2020 (07:19:35 CET)
After the appearance of first cases of ‘pneumonia of unknown origin’ in the Wuhan city, China, during late 2019, the disease progressed fast. Its cause was identified as a novel coronavirus, named provisionally 2019-nCoV. Subsequently, an official name was given as SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) by the International Committee on Taxonomy of Viruses (ICTV) study group. The World Health Organization (WHO) named the Coronavirus disease-2019 as COVID-19. The epidemics of COVID-2019 have been recorded over 113 countries/territories/areas apart from China and filched more than 4292 humans, affecting severely around 1,18,326 cases in a short span. The status of COVID-2019 emergency revised by the WHO within 42 days from Public Health International Emergency (January 30, 2020) to a pandemic (March 11, 2020). Nonetheless, the case fatality rate (CFR) of the current epidemic is on the rise (between 2-4%), relatively is lower than the previous SARS-CoV (2002/2003) and MERS-CoV (2012) outbreaks. Even though investigations are on its way, the researchers across the globe have assumptions of animal-origin of current SARS-CoV-2. A recent case report provides evidence of mild COVID-2019 infection in a pet dog that acquired COVID-2019 infection from his owner in Hong Kong. The news on travellers associated spread across the globe have also put many countries on alert with the cancellation of tourist visa to all affected countries and postponement of events where international visits were required. A few diagnostic approaches, including quantitative and differential real-time polymerase chain reaction assays, have been recommended for the screening of the individuals at risk. In the absence of any selective vaccine against SARS-CoV-2, re-purposed drugs are advocated in many studies. This article discourse the current worldwide situation of COVID-2019 with information on virus, epidemiology, host, the role of animals, effective diagnosis, therapeutics, preventive and control approaches making people aware on the disease outcomes.
REVIEW | doi:10.20944/preprints202106.0007.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: computerized tomography; coronavirus disease 2019; echocardiography; lung ultrasound
Online: 1 June 2021 (09:31:10 CEST)
Coronavirus Disease 2019 (COVID-19) is the pandemic challenge of the last year. Cardiovascular involvement is one of the main characteristics of this disease. Due to endothelial damage, consequent phlogosis may increase a thrombosis risk. Cardiac injury may occur in different ways. However, an ischemic involvement of the cardiovascular system is rarely implied. In this regard, direct and indirect effects of COVID-19 are described. Nonetheless, the possible evaluation of the cardiovascular system may require different modalities. The cardiovascular evaluation may be different in emergency compared to critical care, requiring different tools for each setting. The aim of this review is to explore these modalities according to the different involvement of the cardiovascular system..
ARTICLE | doi:10.20944/preprints202009.0446.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases 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.
ARTICLE | doi:10.20944/preprints202007.0407.v1
Subject: Computer Science And Mathematics, Algebra And Number Theory Keywords: SEIR Dynamic Model; 2019-nCoV; Treatment; Vaccination; Economical
Online: 19 July 2020 (10:45:26 CEST)
In this paper, drug treatment and vaccination are compared healthy and economically. In this comparison, in addition to comparing economic costs, it has paid attention to patients' recovery. To reach the goal, the prevalence of Covid-19 virus in New York is modeled by using the SEIR dynamic model. The SEIR dynamic model is used to model the period of epidemic diseases. Then, three disease control scenarios are evaluated economically. Treatment and vaccination are two important issues in controlling epidemic diseases. To control the disease, each of these two methods has economic costs and benefits. The main purpose of this paper is to compare the two methods of vaccination and treatment economically. Although the results of the study show that vaccination can be effective in preventing the epidemic of the disease than treatment, but due to the high cost and genetic mutation of the virus, vaccination is not the optimal method for both health and the economy in the long term.
REVIEW | doi:10.20944/preprints202004.0395.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: coronavirus disease 2019; chloroquine; drug repurposing; HIV; Africa
Online: 22 April 2020 (08:33:34 CEST)
The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2, has been declared by the World Health Organization (WHO) as a pandemic. Unfortunately, finding a vaccine or developing drugs from the scratch is a time-consuming luxury given the widespread and high fatality rates of the virus. In the short term, repurposing of drugs already in use seem to be the most rational step to quickly and effectively curb the virus. Several antiviral agents had been proposed as possible remedies, but the 4-aminoquinolines, Chloroquine (CHQ) and hydroxychloroquine (HCHQ) appear to be generating more interest. They are generic, cheaply available and have proven efficacy against malaria parasites in Africa. The human immunodeficiency virus (HIV), on the other hand, targets the immune system thereby reducing the patient’s ability to fight infections. Sadly, 68% of the global HIV burden occur in Africa. It is therefore anticipated that incidence of severe forms of COVID-19 could occur in Africa because of associated endemic conditions that compromise the immune system. With CHQ and HCHQ being considered for clinical use against COVID-19, there is a need to highlight their potential merits and confounding variables in the subgroup of patients with or without HIV.
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: 2019-nCoV; epidemiology; causes; prevention and control; review
Online: 6 February 2020 (08:54:11 CET)
The 2019-nCoV has been identified as the cause of an outbreak of respiratory illness in Wuhan, Hubei Province, China beginning in December 2019. This epidemic had spread to 19 countries with 11,791 confirmed cases, including 213 deaths, as of January 31, 2020. The World Health Organization declared it as a Public Health Emergency of International Concern. This study analyzed and discussed 70 research articles published until January 31, 2020 for a better understanding of the epidemiology, causes, clinical diagnosis, prevention and control of this virus. Studies thus far have shown origination in connection to a seafood market in Wuhan, but specific animal association has not been confirmed. The reported symptoms include fever, cough, fatigue, pneumonia, headache, diarrhea, hemoptysis, and dyspnea. Preventive measures such as masks, hand hygiene practices, avoidance of public contact, case detection, contact tracing, and quarantines are effective for reducing the transmission. To date, no specific antiviral treatment is proven effective, hence, infected people primarily rely on symptomatic treatment and supportive care. Although these studies had relevance to control a public emergency, more research need to be conducted to provide valid and reliable ways to manage this kind of public health emergency in both short- and long- term.
REVIEW | doi:10.20944/preprints202001.0364.v2
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: 2019-nCoV; SARS-CoV; drought; bat; green light
Online: 4 February 2020 (10:31:47 CET)
The new coronavirus (2019-nCoV) in Wuhan has caused virus outbreaks in many provinces and cities in China, and several neighboring countries were also affected. In recent years, coronavirus several outbreaks around the world were reported, however researchers could not predict its onset. Coincidentally, the birthplace of another coronavirus (SARS-CoV) that causes serious public health problems is also in China. This review compares and analyzes the external environment, natural hosts, intermediate hosts, and susceptible populations when these two coronaviruses occurred. Based on the analysis results, we found that the 2019-nCov virus outbreak in Wuhan was not an accidental phenomenon, but a result of a combination of factors. At the same time, through the conclusions of these analyses, we will be able to get a glimpse of the trajectories of new coronaviruses and curb the virus outbreak in future.
ARTICLE | doi:10.20944/preprints202004.0441.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Corona Virus Disease 2019; pulmonary vesicle; prognosis; surgical treatment
Online: 24 April 2020 (12:06:33 CEST)
Background: The Corona Virus Disease 2019 (COVID-19) is spreading globally now. However, the clinical presentation that predict prognosis of the patients are still largely unknow. Methods: We enrolled 393 patients infected with COVID-19 and 30 patients with common pulmonary bulla and reviewed their clinical features to evaluate the potential prognostic value of pulmonary vesicles, especially in the patients with severe symptoms. One COVID-19 patient with vesicles was treated by bullectomy for last resort, and its characteristics of the patient’s perioperative laboratory tests was analyzed. The pathological findings of bullectomy were described and compared with those of common bulla cases. Results: Patients infected with COVID-19 showed more dependence on ventilator, occurrence of super resistant bacteria, and prone to vesicle formation than common bulla (p<0.05). Disease severity is associated with age, sex, and usage of ventilator, ECMO and antibiotics, super resistance bacteria and vesicle formation (p<0.05). The average mortality rate of COVID-19 patients was 4.10% (25.4% in severe patients, 0.00% in mild patients). Interestingly, the mortality rate further increased in severe patients with pulmonary vesicles than those without pulmonary vesicles (35.7% vs 22.4%, p=0.0442). One COVID-19 patient with vesicles underwent bullectomy and had a poor prognosis, who showed diffuse alveolar damage and extensive necrosis in bullectomy specimen. Conclusions: Patients infected with COVID-19 are more prone to form pulmonary vesicles showed on chest CT scans, as an important poor prognosis factor, especially in the severe patients.
REVIEW | doi:10.20944/preprints202004.0321.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: 2019 Novel Coronavirus; plants; antiviral compounds; plant recombinant vaccines
Online: 19 April 2020 (04:15:18 CEST)
The proposal of novel drugs and approaches for effective treatment of the novel coronavirus is a necessity after the quick outbreak of the disease. Since the commencement of the coronavirus spread, enormous efforts have been made to protect, alleviate and cure the disease, though no specific treatment has been approved. While there have been convincing results in the use of chemical drugs and interferon therapy, such therapeutic approaches have various drawbacks and lack the required performance for the treatment of the new coronavirus. Medicinal plant species can provide a solution as a source of natural antiviral compounds by the accumulation of secondary metabolites and lectins as well as acting as a platform to express the viral immunogenic proteins. This study reviews the advantages and the results of previous research for the treatment of the novel coronavirus disease and previous generations of similar coronaviruses. Several plant-derived anti coronavirus compounds have been nominated that could be targeted for further research due to the similarity of the coronavirus disease in 2003 and the current coronavirus. This review regards plant species such as Scutellaria baicalensis (Baikal skullcap), and Utrica dioica (Stinging nettle) as suitable candidates for the new coronavirus antiviral research. Furthermore, the use of plants such as Nicotiana tabacum (Tobacco) for the expression of the coronavirus viral antigens can be a target for the future vaccinal research of the new coronavirus due to the efficiency of expression and intrinsic antiviral properties.
ARTICLE | doi:10.20944/preprints202003.0160.v1
Subject: Biology And Life Sciences, Virology Keywords: influenza-like illness; 2019-nCoV; person-to-person transmission
Online: 10 March 2020 (05:18:19 CET)
The ongoing pandemic of the 2019 novel coronavirus disease (COVID-19) raises a global health crisis, which has resulted in 75,778 confirmed cases with 2130 deaths in China and beyond. Atypical symptom renders it challenging to earlier recognize the 2019-nCoV carrier with the potential ability of equivalent transmission. Therefore, it is needed to gain full spectrum of COVID-19. Here we report clustered COVID-19 cases of person-to-person transmission. The symptoms of typical pneumonia are shared by the two familial members, namely son (Patient 1) and father (Patient 2). Unexpectedly, an influenza-like illness (ILI) is also caused in Patient 3 having close contact with Patient 1 at personal dinner party. Combined with clinical and epidemiological study, chest computed tomography (CT) and molecular diagnosis demonstrate that all the three cases tested positive for COVID-19 with distinct symptoms by human-to-human transmission. To the best of knowledge, it closes in part (if not all), a missing gap of clinical repertoires of COVID-19 outbreaks and underlines the possibility that neglection of cryptic/asymptomatic/mild cold-like syndromes gives biased screen in the earlier stage of COVID-19 cases.
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: 2019-nCoV; coronavirus; peptide vaccine; CD4+ epitope; CD8+ epitope
Online: 8 February 2020 (05:56:31 CET)
In this report, we demonstrate that it is possible to design epitope-based peptide vaccine candidates to counteract the novel China coronavirus (2019-nCoV) by using an approach similar to the one used in cancer neoantigen vaccination therapy. We identified multiepitope peptide vaccine candidates against 2019-nCov that can potentially trigger both CD4+ and CD8+ T cell immune response with increased efficiency due to the presence of CD4+ and CD8+ T cell epitopes and a cathepsin-sensitive linker. Furthermore, we suggest that the peptide design strategy should incorporate population-specific HLA alleles in order to optimize binding specificity of the peptides. We refer to this as populationalized vaccinomics.
COMMUNICATION | doi:10.20944/preprints202007.0443.v1
Subject: Chemistry And Materials Science, Nanotechnology Keywords: Coronavirus disease 2019; COVID-19 pandemic; HIV/AIDS; Nanoantivirals; Smart nanomaterials; Synergistic oxidant @ reductant agents, antiviral coatings; Oxidizer and Reductant Nano agents; Nanomedicine
Online: 19 July 2020 (20:56:28 CEST)
Research on the chemical mechanism and reciprocal behavior of the coronavirus relate to living organisms, engaging in the give and take of electrochemical mediators, is a very important, controversial and vital issue. What we should accept is the chemical identity of this scenario, and not preferably a characteristic of a biological system. This chemical reaction should be familiar, referring to the theory of chemical pathways involved in DNA/proteins in the body against aggressive guests (such as viruses). From the point of view of a chemist, this simple reaction is nothing more than an oxidation-reduction reaction (redox-stress signaling) which conducted and carried out by coronavirus in a biointerface medium. Thereby, oxidizing as well as reducing reagents should be very constructive, promoting development in such chemical process. We understand redox reactions as switchable thiol/disulfide exchanges (formation and cleavage of inherent disulfide bonds), then, we can hugely profit from redox-responsive nano-surfaces equipped with multiple new ionic and covalent interactions. This game-changing idea can substantiate by surface modified-nanoparticles to play powerful roles in synthesis of nano oxidizers as well as reducing agents in nanomedicine. Chemists and pharmacists must then explore new thoughts and present modern experiences/approaches of preparation nanoparticles and nanocomposites to create novel vaccines as well as coronavirus drugs. In this regard, this experience can also be so helpful for HIV/AIDS, which is caused by viruses.
REVIEW | doi:10.20944/preprints202304.0042.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: Fatty liver disease; NAFLD; coronavirus disease 2019; SARS-CoV-2
Online: 4 April 2023 (09:31:42 CEST)
The global population is currently experiencing the impact of the SARS-CoV-2 coronavirus, which has caused the Coronavirus Disease 2019 (COVID-19) pandemic. By our profound comprehension of COVID-19, encompassing the involvement sequence of the respiratory tract, gastrointestinal system, and cardiovascular apparatus, the multiorgan symptoms of this infectious disease have been discerned. Metabolic-associated fatty liver disease (MAFLD) is a pervasive public health concern, intricately linked with metabolic dysregulation and estimated to afflict one-fourth of the global adult population. The burgeoning focus on the association between COVID-19 and metabolic dysfunction-associated fatty liver disease (MAFLD) is justified by the potential role of the latter as a risk factor for both SARS-CoV-2 infection and the subsequent emergence of severe COVID-19 symptoms. Investigations have suggested that changes in both innate and adaptive immune responses among metabolic dysfunction-associated fatty liver disease (MAFLD) patients may play a role in determining the severity of COVID-19. The remarkable similarities observed in the cytokine pathways implicated in both diseases imply the existence of shared mechanisms governing the chronic inflammatory responses characterizing these conditions. The effect of metabolic dysfunction-associated fatty liver disease (MAFLD) on the severity of COVID-19 illness remains uncertain, as indicated by conflicting results in cohort investigations.
ARTICLE | doi:10.20944/preprints202006.0326.v1
Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: 2019-nCoV; 3CLpro protein; Cat's Claw; Uncaria tomentosa; Molecular Modeling
Online: 28 June 2020 (09:05:54 CEST)
COVID-19 is a novel severe acute respiratory syndrome coronavirus. Presently, there is no effective treatment for COVID-19. As part of the worldwide efforts to find efficient therapies and preventions, it has been reported the crystalline structure of the SARS-CoV-2 main protease Mpro (also called 3CLpro) bound to a synthetic inhibitor which represents a major druggable target. The druggability of Mpro could be used for discovering drugs to treat coronavirus disease 2019. It was carried out a multi-level computational study to evaluate the potential anti-viral properties of the components of the medicinal herb Uncaria tomentosa (Cat´s claw) focusing on the inhibition of Mpro. The in-silico approach starts with protein-ligand docking of 26 Cat’s claw key components followed by ligand pathway calculations, molecular dynamics simulations and MM-GBSA calculation of the free energy of binding for the best docked candidates. The structural bioinformatics approaches led to the identification of three bioactive compounds of Uncaria tomentosa (Speciophylline, Cadambine and Proanthocyanidin B2) with potential therapeutic effects by strong interaction with 3CLpro. Additionally, in silico drug-likeness indices for these components were calculated and show good predicted therapeutic profiles of these phytochemicals. Our findings suggest the potential effectiveness of Cat's claw as complementary and/or alternative medicine for COVID-19 treatment.
ARTICLE | doi:10.20944/preprints202005.0186.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Coronavirus disease 2019; SARS-CoV-2; ACE2; RBD; Molecular modelling
Online: 11 May 2020 (04:08:26 CEST)
The outbreak across the globe due to coronavirus disease 2019 (COVID-19) has spread abruptly by infected humans worldwide. The continuous efforts by scientists is on way to understand how pandemic of COVID-19 resembles and differs from serve acute respiratory syndrome coronavirus (SARS-CoV) at transcriptomic and genomic level. The SARS-CoV and COVID-19 exploits the angiotensin converting enzyme 2 (ACE2) receptor to gain entry inside the cells.We analyzed the entry COVID-19 into host cell due to receptor binding domain (RBD) of spike glycoprotein. The proposed simulation data shows similar ternary structures from two viruses shares approximately 80 percent identity in amino acid sequences. Our molecular modeling investigation signifies that angiotensin converting enzyme 2 (ACE2) has stronger interaction with COVID -19 RBD. The Amino acid phenylaniline F486 LOOP plays vital role due to its penetration into hydrophobic pocket in ACE2.The said investigation of S-Glycoprotein RBD of COVID-19 or SARS-CoV-2 via ACE2 provides post genome analysis of protein-protein interaction for rapid assessing transmission of infected patients by deadly CoVID-19. The scientific data extracted implies early guidance to control and viral prevention of CoVID-19.
ARTICLE | doi:10.20944/preprints202003.0206.v2
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: 2019 novel coronavirus infection; corons; SARS-CoV; interferon; systems biology
Online: 23 March 2020 (10:27:57 CET)
As the outbreak of COVID-19 has accelerated, an urgent need for finding strategies to combat the virus is growing. Thus, gaining more knowledge on the pathogenicity mechanisms of SARS-CoV-2, the causing agent of COVID-19, and its interaction with the immune system is of utmost importance. Although this novel virus is not well known yet, its structural and genetic similarity with SARS-CoV as well as the comparable pattern of age-mortality relations suggest that the previous findings on SARS can be applicable for COVID-19. Therefore, a systems biology study was conducted to investigate the most important signaling pathways activated by the virus. The results were then validated through a literature review on COVID-19 and the other closely related viruses, SARS and MERS. Interferons have shown to play a crucial role in the defense against coronavirus diseases. CoV can impede the interferon induction in humans. Moreover, STAT1, a key protein in the interferon-mediated immune response, is antagonized by the virus. This could explain the increased response threshold of immune cells to IFNs during CoV infections. A vivid correlation between the innate immune response threshold and the fatality rates in COVID-19 can be found. Differences in the dynamics of the interferon-related innate immune responses in children, adults, and elderly may explain the reported fatality rates. The increased mortality rates in the elderly can be explained by the higher threshold of interferon-mediated immune responses. Earlier induction of interferons in children and their less developed immune system could contribute to their near to zero fatality rate. Administration of interferon-inducing agents, such as poly (ICLC), could reduce the mortality of SARS at the very early stages of the disease. Interferon-γ combination with an interferon-I might induce synergistic effects and maximize the benefits. However, in-depth research is needed to validate it and determine the optimum dosage and timing to prevent unwanted results. Such interventions can act as a double-edged sword and aid the imbalance of the immune reactions, which may occur at the later stages of the disease. With the advancement of the disease and the virus overload, the responses would shift toward immnopathogenic over-reactions and probably cytokine storm. Moderating the activity of the immune system and supportive care in such conditions might be the optimum approach.
HYPOTHESIS | doi:10.20944/preprints202002.0254.v2
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: 2019-nCoV; novel coronavirus pneumonia; docking; ACE2; viral main protease
Online: 23 February 2020 (02:09:52 CET)
The 2019 novel coronavirus (2019-nCoV) causes novel coronavirus pneumonia (NCP). Given that approved drug repurposing becomes a common strategy to quickly find antiviral treatments, a collection of FDA-approved drugs can be powerful resources for new anti-NCP indication discoveries. In addition to synthetic compounds, Chinese Patent Drugs (CPD), also play a key role in the treatment of virus related infections diseases in China. Here we compiled major components from 38 CPDs that are commonly used in the respiratory diseases and docked them against two drug targets, ACE2 receptor and viral main protease. According to our docking screening, 10 antiviral components, including hesperidin, saikosaponin A, rutin, corosolic acid, verbascoside, baicalin, glycyrrhizin, mulberroside A, cynaroside, and bilirubin, can directly bind to both host cell target ACE2 receptor and viral target main protease. In combination of the docking results, the natural abundance of the substances, and botanical knowledge, we proposed that artemisinin, rutin, glycyrrhizin, cholic acid, hyodeoxycholic acid, puerarin, oleanic acid, andrographolide, matrine, codeine, morphine, chlorogenic acid, and baicalin (or Yinhuang Injection containing chlorogenic acid and baicalin) might be of value for clinical trials during a 2019-nCov outbreak.
ARTICLE | doi:10.20944/preprints202002.0051.v3
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Wuhan 2019-nCov; ACE2; expression; susceptibility; race; age; gender; smoking; single cell
Online: 2 March 2020 (01:38:52 CET)
In current severe global emergency situation of 2019-nCov outbreak, it is imperative to identify vulnerable and susceptible groups for effective protection and care. Recently, studies found that 2019-nCov and SARS-nCov share the same receptor, ACE2. In this study, we analyzed five large-scale bulk transcriptomic datasets of normal lung tissue and two single-cell transcriptomic datasets to investigate the disparities related to race, age, gender and smoking status in ACE2 gene expression and its distribution among cell types. We didn’t find significant disparities in ACE2 gene expression between racial groups (Asian vs Caucasian), age groups (>60 vs <60) or gender groups (male vs female). However, we observed significantly higher ACE2 gene expression in former smoker’s lung compared to non-smoker’s lung. Also, we found higher ACE2 gene expression in Asian current smokers compared to non-smokers but not in Caucasian current smokers, which may indicate an existence of gene-smoking interaction. In addition, we found that ACE2 gene is expressed in specific cell types related to smoking history and location. In bronchial epithelium, ACE2 is actively expressed in goblet cells of current smokers and club cells of non-smokers. In alveoli, ACE2 is actively expressed in remodelled AT2 cells of former smokers. Together, this study indicates that smokers especially former smokers may be more susceptible to 2019-nCov and have infection paths different with non-smokers. Thus, smoking history may provide valuable information in identifying susceptible population and standardizing treatment regimen.
ARTICLE | doi:10.20944/preprints202002.0378.v3
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Coronavirus Disease 2019; SARS-CoV-2; clinical features; laboratory; outcomes; epidemic.
Online: 11 March 2020 (10:35:01 CET)
Introduction: An epidemic of Coronavirus Disease 2019 (COVID-19) begun in December 2019 in China, causing a Public Health Emergency of International Concern. Among raised questions, clinical, laboratory, and imaging features have been partially characterized in some observational studies. No systematic reviews have been published on this matter. Methods: We performed a systematic literature review with meta-analysis, using three databases to assess clinical, laboratory, imaging features, and outcomes of COVID-19 confirmed cases. Observational studies, and also case reports, were included and analyzed separately. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95%CI). Results: 660 articles were retrieved (1/1/2020-2/23/2020). After screening by abstract/title, 27 articles were selected for full-text assessment. Of them, 19 were finally included for qualitative and quantitative analyses. Additionally, 39 case report articles were included and analyzed separately. For 656 patients, fever (88.7%, 95%CI 84.5-92.9%), cough (57.6%, 40.8-74.4%) and dyspnea (45.6%, 10.9-80.4%) were the most prevalent manifestations. Among the patients, 20.3% (95%CI 10.0-30.6%) required intensive care unit (ICU), with 32.8% presenting acute respiratory distress syndrome (ARDS) (95%CI 13.7-51.8), 6.2% (95%CI 3.1-9.3) with shock and 13.9% (95%CI 6.2-21.5%) of hospitalized patients with fatal outcomes (case fatality rate, CFR).Conclusion: COVID-19 brings a huge burden to healthcare facilities, especially in patients with comorbidities. ICU was required for approximately 20% of polymorbid, COVID-19 infected patients and this group was associated with a CFR of over 13%. As this virus spreads globally, countries need to urgently prepare human resources, infrastructure, and facilities to treat severe COVID-19.
SHORT NOTE | doi:10.20944/preprints202002.0289.v5
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: COVID-19; proton affinity; calcium oxalate; isoleucine; valine; glycine; prophylactic approach
Online: 14 June 2020 (17:43:37 CEST)
The current pneumonia epidemic could evolve into a pandemic on a global scale if not effectively contained. The COVID-19 virus possesses a 61-amino acid open reading frame resembling SARS-CoV virulence factor - ORF6 peptide. The isoleucine content is 15.9% in ORF6 of SARS-CoV versus 16.4% of that in SARS-CoV-2. Given the proton affinity in the carbonyl oxygen in isoleucine, augmented proton traffic can enhance proton-ion antiport and prompt cell swelling. Calorie restriction has been confirmed in animal studies to extend lifespan, and its underlying mechanism is not fully known. As the content of essential amino acids in the open reading frame of SARS-CoV-2 reaches 57.4%, a starch/vitamin diet served for short period of time does not give rise to essential amino acids and halts virion production, which could be adopted as prophylactic approach of many viral infections. Plant-based diet or fasting/boiled rice water can also minimize the intake of essential amino acids or all amino acids respectively. Furthermore, several proteins of SARS-CoV-2 possess high valine plus glycine content which is implicated in heart disease, justifying the aforementioned approaches.
HYPOTHESIS | doi:10.20944/preprints202004.0153.v1
Subject: Biology And Life Sciences, Virology Keywords: Severe acute respiratory syndrome coronavirus 2; 2019-nCoV; COVID-19; angiotensin converting enzyme 2; Receptor; Live Attenuated Oral Vaccine; Intestine; proximal and distal enterocytes; herd immunity
Online: 9 April 2020 (13:10:50 CEST)
Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2/2019-nCoV) infection is an emerging pandemic. The virus binds to angiotensin converting enzyme 2 (ACE2) and TMPRSS2 which are abundantly expressed on various human cells including lung epithelial cells and intestinal cells and the virus can infect these cells. Currently no specific treatments or vaccines are available for this disease. A per oral live attenuated vaccine can be beneficial in SARS-Cov-2 infection because the attenuated virus initially infects the gut, stimulates the mucosa associated immune system sparing the respiratory system during the initial immune response. The live virus can also spread in the community boosting herd immunity.
COMMUNICATION | doi:10.20944/preprints202003.0125.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: 2019-nCoV; Darunavir; ACE-2; Receptor Binding Domain; Metastable Conformation; FDA database
Online: 7 March 2020 (16:28:05 CET)
The transnational spread of coronavirus (2019-nCoV) first detected in Wuhan is causing global panic; thus, accelerated research into clinical intervention is of high necessity. The spike glycoprotein structure has been resolved, and its affinity to human angiotensin-converting enzyme 2 (ACE-2) has been experimentally validated. Here, using computational methods, a metastable conformation of 2019-nCoV-RBD/ACE-2 complex has been revealed and FDA-database of approved drugs have been docked into the interface. Darunavir has been discovered as high ligand affinity candidate capable of disrupting communication between 2019-nCoV-RBD and ACE-2. Darunavir, in addition to its previously known anti-HIV protease inhibitor is now repurposeable for the treatment 2019-nCoV disease acting via disruption of cellular recognition, binding and invasion.
ARTICLE | doi:10.20944/preprints202106.0291.v1
Subject: Business, Economics And Management, Business And Management Keywords: Cryptocurrency; Coronavirus Disease 2019; Time-Varying Parameter Vector Autoregression; Portfolio Weight; Hedging Effectiveness
Online: 10 June 2021 (12:07:58 CEST)
This paper examines interlinkages and hedging opportunities between nine major cryptocurrencies for the period between 30 September 2015 and 4 June 2020, which notably includes the coronavirus disease 2019 (COVID-19) outbreak lasting from early 2020 through the end of the sample period. The results of dynamic conditional correlation (DCC) analysis using a minimum connectedness approach show a high degree of correlation between cryptocurrencies throughout the sample period. However, the correlations reach their minimum values during the COVID-19 pandemic, which indicates that cryptocurrencies acted as a hedge or safe haven during the stressful period of the COVID-19 pandemic. The weight of cryptocurrencies was significantly reduced and their hedging effectiveness varied greatly during the pandemic, which indicates that investors’ preferences changed during the COVID-19 period.
ARTICLE | doi:10.20944/preprints202103.0243.v1
Subject: Environmental And Earth Sciences, Atmospheric Science And Meteorology Keywords: wildfires; summer 2019-2010; WRF-Chem; pollutant transport; air quality effect; health impact
Online: 9 March 2021 (09:03:10 CET)
The 2019-2020 summer wildfire event on the east coast of Australia was a series of major wildfires occurring from November 2019 to end of January 2020 across the states of Queensland, New South Wales (NSW), Victoria and South Australia. The wildfires were unprecedent in scope and the extensive extend of the wildfires has caused smoke pollutants transported not only to New Zealand but across the Pacific Ocean to South America. At the height of the wildfires, smoke plumes were injected into the stratosphere at height up to 25km and hence transported across the globe. Based on meteorological and air quality simulation using WRF-Chem model, air quality monitoring data collected during the bushfire period and remote sensing data from MODIS and CALIPSO satellites, the extend of the wildfires and the pollutant transport, and their impacts on air quality and health on exposed population in NSW can be analysed. The results showed that WRF-Chem model using Fire Emission Inventory from NCAR (FINN) predicts the dispersion and transport of pollutants and the predicted concentration of PM2.5 and other pollutants from wildfires reasonably well when compared with ground-based and satellite data. The impact on health endpoints such as mortality, respiratory and cardiovascular diseases hospitalisation across the modelling domain is then estimated. The estimated health impact is comparable with previous study based only on observation data, but the results in this study provide much more detailed spatially and temporally with regards to the health impact from the 2019-2020 wildfire.
COMMUNICATION | doi:10.20944/preprints202004.0146.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Coronavirus Disease 2019; SARS-CoV-2; main protease; molecular docking-based virtual screening
Online: 9 April 2020 (09:34:45 CEST)
Coronavirus Disease 2019 (Covid-19) was first described in December 2019 in Wuhan, Hubei Province, China; and produced by a novel coronavirus designed as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Covid-19 has become a pandemic reaching over 1.3 million confirmed cases and 73,000 deaths. Several efforts have been done to identify pharmacological agents that can be used to treat patients and protect healthcare professionals. The sequencing of the virus genome not only has offered the possibility to develop a vaccine, but also to identified and characterize the virus proteins. Among these proteins, main protease (Mpro) has been identified as a potential therapeutic target, since it is essential for the processing other viral proteins. Crystal structures of SARS-CoV-2 Mpro and inhibitors has been described during the last months. To describe additional compounds that can inhibit SARS-CoV-2 Mpro, in this study we performed a molecular docking-based virtual screening against a library of experimental and approved drugs. Top 10 hits included Pictilisib, Nimorazole, Ergoloid mesylates, Lumacaftor, Cefuroxime, Cepharanhine, and Nilotinib. These compounds were predicted to have higher binding affinity for SARS-CoV-2 Mpro than previously reported inhibitors for this protein, suggesting a higher potential to inhibit virus replication. Since the identified drugs have both pre-clinical and clinical information, we consider that these results may contribute to the identification of treatment alternative for Covid-19. Nevertheless, in vitro and in vivo confirmation should be performed before these compounds could be translated to the clinic.
REVIEW | doi:10.20944/preprints202001.0381.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: 2019-nCoV; nCoV; China; Wuhan; coronavirus; virology; epidemiology; clinical guidance; literature survey; review
Online: 31 January 2020 (05:36:32 CET)
There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from China and has now spread to 17 other countries. Governments are under increase pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites, and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.
ARTICLE | doi:10.20944/preprints202202.0055.v2
Subject: Social Sciences, Psychology Keywords: Coronavirus disease 2019/COVID-19; Internet Gaming Disorder Scale9—Short form (IGDS9-SF); university students; factorial structure/psychometric properties/structural validity/validation; cultur*/collectivisti*/individualis*; invariance; gender; game type
Online: 21 March 2022 (11:04:57 CET)
The prevalence of internet gaming disorders (IGD) is considerably high among youth, especially with social isolation imposed by the ongoing COVID-19 pandemic. IGD adversely affects mental health, quality of life, and academic performance. The Internet Gaming Disorder Scale (IGDS9-SF) is designed to detect IGD according to DSM-IV diagnostic criteria. However, inconsistent results are reported on its capacity to diagnose IGD evenly across different cultures. To ensure the suitability of the IGDS9-SF as a global measure of IGD, this study examined the psychometric properties of the IGDS9-SF in a sample of Sri Lankan university students (N = 322, mean age =17.2 ± 0.6, range = 16-18 years, 56.5% males) and evaluated its measurement invariance across samples from Sri Lanka, Turkey, Australia, and the USA. Among Sri Lankan students, a unidimensional structure expressed good fit, invariance across different groups (e.g., gender, ethnicity, and income), adequate criterion validity (strong correlation with motives of internet gaming, daily gaming duration, and sleep quality), and good reliability (alpha = 0.81). Males and online multiplayers expressed higher IGD levels, greater time spent gaming, and more endorsement of gaming motives (e.g., Social and Coping) than females and offline players. Across countries, the IGDS9-SF was invariant at the configural, metric, and scalar levels, albeit strict invariance was not maintained. The lowest and highest IGD levels were reported among Turkish and American respondents, respectively. In conclusion, the IGDS9-SF can be reliably used to measure IGD among Sri Lankan youth. Because the scale holds scalar invariance across countries, its scores can be used to compare IGD levels in the studied countries.
ARTICLE | doi:10.20944/preprints202306.1717.v1
Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: post-traumatic stress disorder; trauma; depression; physical disabilities; intensive care unit; coronavirus disease 2019
Online: 25 June 2023 (05:15:40 CEST)
The Coronavirus Disease 2019 (COVID-19) pandemic has had a major impact on the mental and physical health of hospitalized patients. In our study we focused on the onset of symptoms correlated with Post-traumatic stress disorder (PTSD), depression and physical disabilities in patients admitted to the Intensive Care Unit (ICU) because of a severe respiratory distress related to COVID-19 (COVID Group) compared with patients admitted to the same ICU for trauma and other medical conditions than COVID-19 (No-COVID Group). The physical symptoms and the level of disability were evaluated with the Glasgow Outcome Scale-Extended (GOS-E), the Quality of Life after Brain Injury (QOLIBRI) and the 3 levels version of EQ-5D (EQ-5D-3L) questionnaire; psychiatric symptoms were investigated using the Impact of Event Scale-Revised 22-item (IES-R), the Patient Health Questionnaire, 9-Item Version (PHQ-9) and the Generalized Anxiety Disorder Assessment, 7-items version (GAD-7). These questionnaires were administered 6 months after discharge. Patients in the No-COVID Group showed statistically significant more severe scores in all the physical assessments while similar relevant PTSD and depressive symptoms were reported in both groups. The results of the present study underline the psychopathological impact of being hospitalized in ICU because of COVID-19 even after 6 months from discharge ,suggesting the importance of assessing the psychiatric effects of COVID-19 in the long term in order to create supportive measures.
ARTICLE | doi:10.20944/preprints202105.0429.v1
Subject: Medicine And Pharmacology, Other Keywords: Acute lymphoblastic leukemia; Deep convolutional neural networks; Ensemble image classifiers; C-NMC-2019 dataset.
Online: 19 May 2021 (07:42:23 CEST)
Although automated Acute Lymphoblastic Leukemia (ALL) detection is essential, it is challenging due to the morphological correlation between malignant and normal cells. The traditional ALL classification strategy is arduous, time-consuming, often suffers inter-observer variations, and necessitates experienced pathologists. This article has automated the ALL detection task, employing deep Convolutional Neural Networks (CNNs). We explore the weighted ensemble of deep CNNs to recommend a better ALL cell classifier. The weights are estimated from ensemble candidates' corresponding metrics, such as accuracy, F1-score, AUC, and kappa values. Various data augmentations and pre-processing are incorporated for achieving a better generalization of the network. We train and evaluate the proposed model utilizing the publicly available C-NMC-2019 ALL dataset. Our proposed weighted ensemble model has outputted a weighted F1-score of 88.6%, a balanced accuracy of 86.2%, and an AUC of 0.941 in the preliminary test set. The qualitative results displaying the gradient class activation maps confirm that the introduced model has a concentrated learned region. In contrast, the ensemble candidate models, such as Xception, VGG-16, DenseNet-121, MobileNet, and InceptionResNet-V2, separately produce coarse and scatter learned areas for most example cases. Since the proposed ensemble yields a better result for the aimed task, it can experiment in other domains of medical diagnostic applications.
ARTICLE | doi:10.20944/preprints202002.0071.v1
Subject: Biology And Life Sciences, Virology Keywords: 2019-nCoV; novel corona virus; Wuhan virus; drug; vaccine; spike protein; epitope; vaccine design
Online: 5 February 2020 (15:34:15 CET)
The recent outbreak of the new virus in Wuhan city, China from the sea food market has led to the identification of a new strain called the corona virus and named as novel corona virus (2019-nCoV) belonging to Coronaviridae family. This has created major havoc and concern due to the mortality of 250 persons and affecting more than 10,000 people. This virus causes sudden fever, pneumonia and also kidney failure. In this study a computational approach is proposed for drug and vaccine design. The spike protein sequences were collected from a protein database and analysed with various bioinformatics tools to identify suitable natural inhibitors for the N-terminal receptor binding domain of spike protein. Also, it is attempted to identify suitable vaccine candidates by identifying B-Cell and T-cell epitopes. In the drug design, the tanshinone Iia and methyl Tanshinonate were identified as natural inhibitors based on the docking score. In the vaccine design, B-cell epitope VLLPLVSSQCVNLTTRTQLPPAYTN was found to have the highest antigenicity. FVFLVLLPL of MHC class-I allele and FVFLVLLPL of MHC class-II allele were identified as best peptides based on a number of alleles and antigencity scores. The present study identifies natural inhibitors and putative antigenic epitopes which may be useful as effective drug and vaccine candidates for the eradication of novel corona virus.
ARTICLE | doi:10.20944/preprints202202.0333.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: antibody; BNT162b2; coronavirus disease 2019; severe acute respiratory syndrome coronavirus 2; vaccine hesitancy; vaccine booster
Online: 25 February 2022 (10:01:23 CET)
This was a retrospective cohort study, which aimed to investigate the factors associated with hesitancy to receive the third dose of coronavirus disease 2019 (COVID-19) vaccine. A paper-based questionnaire survey was administered to all participants. Accordingly, the study included participants who provided answer in the questionnaire whether they have an intent to receive the third dose of vaccine. Data on sex, age, area of residence, adverse reactions after the second vaccination, whether the third vaccination was desired, and reasons to accept or hesitate booster vaccination were retrieved. Among the 2439 participants with mean (±SD) age of 52.6±18.9 years, and median IgG-S antibody titer of 324.9 (AU/mL), 97.9% of participants indicated their intent to accept a third vaccination dose. The logistic regression revealed that younger age (OR=0.98; 95% CI: 0.96-1.00) and higher antibody level (OR=2.52; 95% CI: 1.27-4.99) are positively associated with the third vaccine hesitancy. The efficacy of the COVID-19 vaccine and concerns about adverse reactions had significant impact on the third vaccination behavior. A rapid increase in the booster dose rate is needed to control the pandemic, and specific approaches should be taken in these groups that are likely to hesitate the third vaccine, subsequently increasing booster contact rate.
ARTICLE | doi:10.20944/preprints202008.0675.v1
Subject: Environmental And Earth Sciences, Geophysics And Geology Keywords: wave impact assessment; characteristic wave height; Salento peninsula; Taranto Gulf; Mediterranean Sea; November 2019 storm
Online: 30 August 2020 (15:53:07 CEST)
The storm of November 12th-13th, 2019 provoked the displacements of boulders in a central Mediterranean rocky coast; with reference to a selected area, prone to the boulder production and geomorphologically monitored for years, a field-oriented study approach was applied for the phenomenon, by collating data concerning pre-storm locations and kinematics of these boulders. The number of displaced boulders is 11, that is, in terms of morphological imprint of a specific storm, one of the major study cases for the Mediterranean. In addition, based on widely used hydrodynamic equations, the minimum wave height required to displace the boulders is assessed. The values conform with the expected values for the wave climate dominating during the causative meteorological event and give a measure of the energy of the storm slamming the coast. Boulder dislodgements usually have plays a key role in determining the rate of the coastal recession, likely also in the investigated area. In view of an adverse climate evolution with a possible increase of energy and frequency of severe storms, the results deriving from the study of this morphodynamics should be considered for the hazard assessment and coastal management.
ARTICLE | doi:10.20944/preprints202007.0023.v1
Subject: Business, Economics And Management, Economics Keywords: coronavirus pandemic (2019+); cycle; Hodrick-Prescott filter; output gap; Polish economy; secular stagnation; sustainability; trend
Online: 3 July 2020 (08:46:44 CEST)
The research problem was formulated as a question: are demand-supply shocks affecting the opening up of a negative or positive output gap? The hypothesis was formulated: demand-supply shocks have a significant impact on the opening up and deepening of the negative output gap, thereby causing real GDP to shrink or potential GDP to grow. The spatial range applies to Poland and the time period - 2008:Q1-2019:Q4. The methodology consists of three stages: the first is the decomposition of the time series using the TRAMO/SEATS on the components: seasonality, trend-cycle, irregular; the second - the decomposition of the trend-cycle component using the Hodrick-Prescott filter into two separate components; the third is the calculation of the output gap; forecast with VECM and IRF approximation. The ouput gap is in the range of - 11% to +10%. After cleaning it, the shock elements are between -2.2% and 2%. Demand-supply shocks open up and widen the negative output gap. Based on forecasts, the output gap will be positive by the end of 2022, close to 0% (optimal scenario), rising to 5% (optimistic scenario) and negative, deepening to -4% (pessimistic scenario). Two of these scenarios point to a growing risk of secular stagnation.
ARTICLE | doi:10.20944/preprints202003.0159.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: bat SARS-like CoV; SARS-CoV; 2019-nCoV; phylogeny; spike protein; viral and host fusion
Online: 10 March 2020 (03:49:10 CET)
A novel coronavirus (2019-nCoV) that is initially found to trigger human severe respiratory illness in Wuhan City of China, 2019, has been recognized as a public health emergency of international concern. In the past two months, this deadly agent has caused 77,785 cases with 2,666 deaths via rapid person-to-person transmission and reached at least 25 countries. However, its evolutionary origin is poorly understood. Here we show integrative evidence that 2019-nCoV is a possible progenitor for SARS-CoV with bat origin. Our finding underscores the importance of tracing origin in the efficient monitoring, and effectively preventing the interspecies transmission of such emerging/re-emerging coronaviruses.
ARTICLE | doi:10.20944/preprints202203.0277.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Long Covid; post Covid; Post-acute COVID
Online: 21 March 2022 (08:25:20 CET)
Abstract: COVID-19 Long Haulers, an estimated 3% to 12% of people infected globally with coronavirus having latter devasting symptoms 12 weeks after the initial infection is on the rise. We conducted a collaborative study with the long covid patient organization in Greece in order to estimate the prevalence, symptoms and problems that adult long haulers experience and then propose a management plan for these patients. Symptoms were obtained from 208 patients using unstructured qualitative free text entries in an anonymized online questionnaire. The majority of respondents (68.8%) were not hospitalized and had been diagnosed more than six months ago with lingering symptoms (66,8%). Eighteen different symptoms (fatigue, tachycardia, shortness of breath, parosmia etc) were mentioned in both hospitalized and community patients. Interestingly, patients with initial mild symptoms suffer from the same persistent symptoms as those who were hospitalized. Awareness of long covid sequelae seems to be low even among medical doctors. Treatment options incorporating targeted rehabilitation programs are either not available or still excluded from the management plan of long covid patients. Since long COVID is a multi-systemic entity, we propose a holistic interventional approach using a multidisciplinary medical team in order to securely and effectively diagnose and treat these specific patients. Academic and medical community must collaborate with long covid patients’ organizations so as to provide personalized medicine.
ARTICLE | doi:10.20944/preprints202112.0413.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: long COVID; COVID 19 vaccination; COVID awareness
Online: 24 December 2021 (23:40:18 CET)
Background Recently, a surge of COVID 19 was observed globally, regionally and nationally. With increasing numbers of cases, the frequency of long COVID is on the rise. Management and control of long COVID depend on changes in respect of human behaviors and requires an understanding of knowledge, attitudes, and practices (KAP) regarding health threats. MethodsA descriptive cross sectional study using online survey to gather data on the socio-economic background, knowledge, attitudes and practices on long-term complications of COVID. Results: Out of 201 respondents, 89.2% participants have heard about long-term complications of COVID 19. Only 35.9% have demonstrated adequate knowledge in the questions relating to co-morbidities and risk factors of COVID-19. A total of 92.2% believe that they should adhere to preventive measures following vaccination. Less than 60 % were following the advice on avoiding unnecessary travel and crowded places. Further, less than 50% were following COVID preventive measures. ConclusionAlthough the majority of participants have heard about long-term complications and common symptoms, the knowledge regarding co-morbidities that can lead to severe disease and long COVID was not satisfactory. The attitudes of the participants indicated increasing concern about long COVID. Practices indicate lack of adherence to key measures such as avoiding crowded places. These findings highlight the need for further increasing of awareness.
ARTICLE | doi:10.20944/preprints202302.0293.v1
Subject: Environmental And Earth Sciences, Environmental Science Keywords: Black carbon; Aethalometer; Black summer wildfires 2019-2020; Radiative forcing; Aerosol direct effect; Aerosol indirect effect
Online: 17 February 2023 (03:17:15 CET)
The emission of black carbon (BC) particles, which cause atmospheric warming by affecting radiation budget in the atmosphere, is the result of an incomplete combustion process of organic materials. The recent wildfire event during the summer 2019-2020 in South-Eastern Australia was unprecedented in scale. The wildfires lasted for nearly 3 months over large areas of the two most populated states of New South Wales and Victoria. This study on the emission and dispersion of BC emitted from the biomass burnings of the wildfires using the Weather Research Forecast – Chemistry (WRF-Chem) model is aimed to determine the extent of the BC spatial dispersion and ground concentration distribution and the effect of BC on air quality and radiative transfer at the top of the atmosphere, the atmosphere and on the ground. The predicted aerosol concentration and AOD are compared with the observed data from the New South Wales Department of Planning and Environment (DPE) aethalometer and air quality network and from remote sensing data. The BC concentration as predicted from WRF-Chem model is in general less than the observed data as measured from the aethalometer monitoring network, but the spatial pattern corresponds well, and the correlation is relatively high. The total BC emission into the atmosphere during the event and the effect on radiation budget were also estimated. This study shows that the summer 2019-2020 wildfires affect not only the air quality and health impact on the east coast of Australia but also short-term weather in the region via aerosol interactions with radiation and cloud.
ARTICLE | doi:10.20944/preprints202002.0381.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: 2019-nCoV; corona virus; glycopeptide; N-linked glycans; antibody; cryo-EM structure; crystal structures; epitope prediction
Online: 25 February 2020 (13:44:15 CET)
Corona viruses hijack human enzymes to assembly sugar coat on Spike glycoproteins. The mechanism that human antibodies may uncover the antigenic viral peptide epitopes hidden by sugar coat are unknown. In this study, we analyzed the high-resolution Cryo-EM structure of Spike glycoproteins. The results showed that electron densities of glycans cover most of the SARS-CoV Spike receptor binding domain except FSPDGKPCTPPALNCYWPLNDYGFYTTTGIGYQ. The glycosylated 2019-nCoV Spike protein by homology structure modeling showed a similar exposed sequence YQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQ. Other surface-exposed domains included those located on Central Helix, between amino acids 967 and 1016 of SARS-CoV, and 985 to 1034 of 2019-nCoV Spike protein. As the majority of antibody paratopes bind to peptide portion with or without sugar modification, we propose a snake-catcher model that a minimal length of peptide is first clamped by a paratope, and the binding is either strengthened by sugars close to peptide, or not interfered by sugar modification.
ARTICLE | doi:10.20944/preprints202002.0372.v1
Subject: Biology And Life Sciences, Virology Keywords: structural genomics; protein-protein interactions; structural bioinformaticscomparative modeling; functional annotation; antiviral design; SARS-CoV-2; 2019-nCoV
Online: 25 February 2020 (11:24:10 CET)
During its first month, the recently emerged 2019 Wuhan novel coronavirus (SARS-CoV-2) has already infected many thousands of people in mainland China and worldwide and took hundreds of lives. However, the swiftly spreading virus also caused an unprecedentedly rapid response from the research community facing the unknown health challenge of potentially enormous proportions. Unfortunately, the experimental research to understand the molecular mechanisms behind the viral infection and to design a vaccine or antivirals is costly and takes months to develop. To expedite the advancement of our knowledge we leverage the data about the related coronaviruses that is readily available in public databases, and integrate these data into a single computational pipeline. As a result, we provide a comprehensive structural genomics and interactomics road-maps of SARS-CoV-2 and use these information to infer the possible functional differences and similarities with the related SARS coronavirus. All data are made publicly available to the research community at http://korkinlab.org/wuhan .
REVIEW | doi:10.20944/preprints202002.0007.v1
Subject: Biology And Life Sciences, Virology Keywords: molecular diagnostics; molecular epidemiology; HIV; HBV; HCV; HPV; Zika virus; Dengue virus; tuberculosis; SARS; MERS; nCov-2019
Online: 3 February 2020 (03:47:27 CET)
Infectious diseases are a global health problem affecting billions of people. Developing rapid and sensitive diagnostic tools is key for successful patient management and curbing disease spread. Currently available diagnostics are very specific and sensitive but time-consuming and require expensive laboratory settings and well-trained personnel; thus, they are not available in resource-limited areas, for the purposes of large-scale screenings and in case of outbreaks and epidemics. Developing new, rapid, and affordable point-of-care diagnostic assays is urgently needed. This review focuses on CRISPR-based technologies and their perspectives to become platforms for point-of-care nucleic acid detection methods and as deployable diagnostic platforms that could help to identify and curb outbreaks and emerging epidemics. We describe the mechanisms and function of different classes and types of CRISPR-Cas systems, including pros and cons for developing molecular diagnostic tests and applications of each type to detect a wide range of infectious agents. Many Cas proteins (Cas9, Cas12, Cas13, Cas14) have been leveraged to create highly accurate and sensitive diagnostic tools combined with technologies of signal amplification and fluorescent, potentiometric, colorimetric, or lateral flow assay detection. In particular, the most advanced platforms -- SHERLOCK/v2, DETECTR, or CRISPR-Chip -- enable detection of attomolar amounts of pathogenic nucleic acids with specificity comparable to that of PCR but with minimal technical settings. Further developing CRISPR-based diagnostic tools promises to dramatically transform molecular diagnostics, making them easily affordable and accessible virtually anywhere in the world. The burden of socially significant diseases, frequent outbreaks, recent epidemics (MERS, SARS and the ongoing coronoviral nCov-2019 infection) urgently need the developing of express-diagnostic tools. Recently devised CRISPR-technologies represent the unprecedented opportunity to reshape epidemiological surveillance and molecular diagnostics.
ARTICLE | doi:10.20944/preprints202308.1497.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Coronavirus disease-2019 (COVID-19); Emergency Use Authorization (EUA); false negative (FN); false omission rate (RFO); point-of-care testing (POCT); prevalence boundary (PB); rapid antigen test (RAgT); repeated testing; sensitivity and specificity; tier
Online: 22 August 2023 (07:25:00 CEST)
Abstract: A prevalence boundary (PB) marks the point in prevalence where the false omission rate, RFO=FN/(TN+FN), exceeds the tolerance limit for missed diagnoses. Objectives were to mathematically analyze rapid antigen test (RAgT) performance, determine why PBs are breeched, and evaluate the merits of testing three times over five days, now required by the US Food and Drug Administration for asymptomatic persons. Equations were derived to compare test performance patterns, calculate PBs, and perform recursive computations. An independent July 2023 FDA-university-commercial evaluation of RAgTs provided performance data used in theoretical calculations. Tiered sensitivity/specificity comprise: Tier-1) 90%, 95%; Tier-2) 95%, 97.5%; and Tier-3) 100%, ≥99%, respectively. Repeating a T2 test improves the PB from 44.6% to 95.2% (RFO 5%). In the FDA-university-commercial evaluation, RAgTs generated sensitivity of 34.4%, which improved to 55.3% when repeated, then 68.5% with the third test. With RFO=5%, PBs were 7.37/10.46/14.22%, respectively. PB analysis suggests RAgTs should achieve clinically proven sensitivity of 91.0-91.4%. When prevalence exceeds PBs, missed diagnoses can perpetuate virus transmission. Repeating low-sensitivity RAgTs delays diagnosis. In homes, high-risk settings, and hotspots, PB breaches may prolong contagion, defeat mitigation, facilitate new variants, and transform outbreaks into endemic disease. Molecular diagnostics can help avoid these potential vicious cycles
ARTICLE | doi:10.20944/preprints202305.0836.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Long covid; Post covid; Sleep disorders
Online: 11 May 2023 (09:42:22 CEST)
Objectives: To examine the long term impact of COVID-19 on sleep patterns and development of sleep disorders. Methods: Using the centralized Massachusetts General Brigham (MGB) Research Patient Data Registry (RPDR), SARS-CoV2 positive patients were surveyed about their sleep patterns before and after the viral infection. Information related to co-morbid conditions and medications were obtained through chart review. Results: Two hundred and forty five completed surverys were analysed. Average age was 53.3 ± 16.3 years, and participants were predominantly Non-Hispanic White (84.1%) and female (74.3%). Average BMI (kg/m2) was 29.9 ± 6.9, and a greater proportion was non-smokers (63.2%). After COVID-19, there was an increase in the percentage of participants reporting difficulty initiating (31 ± 46% vs. 39 ± 49%, P=0.01), and maintaining sleep (43 ± 49% vs. 57 ± 49%, P<0.001), and use of sleep aids (24 ± 43% vs. 30 ± 45% P=0.003) with an incidence rate of 24.3%, 37.4%, and 12.3% respectively. In addition, there was an increase in daytime fatigue and the need for napping (58 ± 49% vs. 36 ± 48%, P <0.0001) with an incidence of 8% and 23% respectively. The sleep symptoms persisted beyond 12 months among 28% of the participants and were predominantly seen among women. Conclusions: Infection with SARS-CoV2 has negative effects on sleep, and a significant proportion of adults experience insomnia and daytime sleepiness beyond 12 months after recovering from the initial infection.
ARTICLE | doi:10.20944/preprints202307.1945.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: memory loss; long COVID; post COVID; depression; mental confusion; COVID-19
Online: 27 July 2023 (13:28:13 CEST)
Long Covid is a term used for patients who have recovered from COVID-19 but exhibit persistent cognitive dysfunction, including mental confusion, difficulties in attention, impairment in executive functions and slow movements, among other common symptoms. A study was conducted with 65 patients who had a positive RT-PCR diagnosis and reported symptoms of cognitive impairment, such as memory loss and attention difficulties after recovery. The patients underwent neuropsychological evaluation and completed questionnaires on cognition, mood, and quality of life. During the cognitive screening, 71% of the patients showed alterations, with deficits in visual memory (69%), language (54%), visuospatial construction (49%), verbal episodic memory (37%), executive functions (36%), attentional abilities (34%), and premorbid intelligence (12%). It is important to highlight the need for treatments and further studies to understand the long-term side effects of this disease.
ARTICLE | doi:10.20944/preprints202208.0227.v1
Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: COVID-19; depression; anxiety; post-acute COVID-19 syndrome; post-COVID
Online: 12 August 2022 (04:56:33 CEST)
Background: This study aimed to examine the course of Depression and anxiety in COVID-19 survivors with a psychiatric history compared with those without a psychiatric history. Methods: A web-based cross-sectional survey for COVID-19 survivors was conducted from July to September 2021. 6016 COVID-19 survivors, the accuracy of whose responses was determined to be assured, were included in analyses. Exposures included psychiatric history and time since COVID-19 infection, and the main outcomes and measures included severity of depression and anxiety, as assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Results: Mean severity of PHQ-9 and GAD-7 were significantly higher in participants with a psychiatric history than in those without a psychiatric history. Two-way analysis of covariance for PHQ-9 showed a significant main effect of the presence of psychiatric history and a significant interaction effect of psychiatric history × time since infection. Two-way analysis of covariance for the GAD-7 score revealed a significant main effect of the presence of psychiatric history and time since COVID-19 infection and the interaction effect of these factors. Conclusions: The course of depression and anxiety was more severe in COVID-19 survivors with a psychiatric history than in those without a psychiatric history.