Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: cannabis; cannabinergic; drug; FDA-approved; medical conditions; pharmaceutical-grade; phytocannabinoid
Online: 31 August 2020 (10:38:32 CEST)
Despite the surge in the research of cannabis chemistry and its biological and medical activity, only a few cannabis-based pharmaceutical-grade drugs have been developed and marketed to date. Not many of these drugs are Food and Drug Administration (FDA)-approved and some are still going through regulation processes. Active compounds including cannabinergic compounds (i.e., molecules targeted to modulate the endocannabinoid system) or analogs of phytocannabinoids (cannabinoids produced by the plant) may be developed into single-molecule drugs. However, since in many cases treatment with whole plant extract is preferred over treatment with a single purified molecule, some more recently developed cannabis-derived drugs contain several molecules. Different combinations of active plant ingredients (API) from cannabis with proven synergy may be identified and developed as drugs to treat different medical conditions. However, possible negative effects between cannabis compounds should also be considered, as well as the effect of the cannabis treatment on the endocannabinoid system. FDA registration of single, few or multiple molecules as drugs is a challenging process and certain considerations that should be reviewed in this process, including issues of drug-drug interactions, are also discussed here.
ARTICLE | doi:10.20944/preprints202310.0311.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: cannabis; Δ⁹-THC; induced psychosis; schizophrenia
Online: 6 October 2023 (11:10:47 CEST)
Psychosis can be defined as a combination of psychopathological symptoms including delusions and/or hallucinations without insight. Psychotic disorders may configure a primary psychiatric illness or represent the result of a functional/structural brain damage induced by substance use, neurological diseases or other medical conditions. They are multifactorial disorders in which genetic, environmental and gene-environment interaction factors contribute to the expressiveness of the symptoms. Among the environmental factors, psychotropic substances represent the most important removable facilitators of psychosis. In our study, we compared the prevalence of substance induced psychosis between a sample of patients affected by cannabis use disorder and a sample of patients affected by cocaine use disorder analyzing retrospectively the data of outpatients with no personal or family history of psychiatric illnesses.
REVIEW | doi:10.20944/preprints202208.0418.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: cannabidiol; Δ-9-tetrahydrocannabinol; cancer; nausea; vomiting; pain management; antitumor; marijuana
Online: 24 August 2022 (10:42:56 CEST)
Cannabis has been used as an herbal remedy for thousands of years and recent research indicates promising new uses in medicine. Researchers have been particularly interested in the potential uses of cannabinoids in treating cancer due their ability to regulate cancer-related cell cycle pathways, leading to many beneficial effects such as tumor growth prevention, cell cycle obstruction, and cell death. The aim of this review is to summarize current knowledge on mechanisms of cannabinoids and their role in treating chemotherapy-induced nausea and vomiting, relieving cancer-associated pain, and obstructing tumor cell growth.
REVIEW | doi:10.20944/preprints201812.0032.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: cannabis; cannabinoids; THC; CBD, drug-drug interactions; pharmacokinetic; cytochrome P450; UDP- glucuronosyltransferases; glucoprotein-P
Online: 3 December 2018 (16:07:43 CET)
Endocannbinoids system (ECS) engrossed a considerable interest as potential therapeutic targets in various carcinomas and cancer related conditions alongside with neurodegenerative diseases. Cannabinoids are implemented in several physiological processes such as appetite stimulation, energy balance, pain modulation and the control of chemotherapy induced nausea and vomiting (CINV). However, pharmacokinetics and pharmacodynamics interactions could be perceived in drug combinations, so in this short review we tried to shed the light over the potential drug interactions of medicinal cannabis. Hitherto, few data have been provided to the healthcare practitioners about the drug-drug interactions of cannabinoids with other prescription medications. In general, cannabinoids are usually well tolerated, but the bidirectional effects may be expected with concomitant administered agents via affected membrane transporters (glycoprotein p, breast cancer resistance proteins) and metabolizing enzymes (Cytochrome P450 and UDP- glucuronosyltransferases). The caveats should be undertaken to closely monitor the responses of cannabis users with certain drugs to guard their safety, especially for the elderly and people with chronic diseases or kidney and liver conditions.
ARTICLE | doi:10.20944/preprints202001.0159.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: proteomics metabolomics; cannabis sativa
Online: 16 January 2020 (08:45:38 CET)
Recently we have seen a relaxation of the historic restrictions on the use and subsequent research on the Cannabis plants, generally classified as Cannabis sativa and Cannabis indica. What research has been performed to date has centered on chemical analysis of plant flower products, namely cannabinoids and various terpenes that directly contribute to phenotypic characteristics of the female flowers. In addition, we have seen many groups recently completing genetic profiles of various plants of commercial value. To date, no comprehensive attempt has been made to profile the proteomes of these plants. We report herein our progress on constructing a comprehensive draft map of the Cannabis proteome. To date we have identified over 17,000 potential protein sequences. Unfortunately, no annotated genome of Cannabis plants currently exists. We present a method by which “next generation” DNA sequencing output and shotgun proteomics data can be combined to produce annotated FASTA files, bypassing the need for annotated genetic information altogether in traditional proteomics workflows. The resulting material represents the first comprehensive annotated protein FASTA for any Cannabis plant. Using this annotated database as reference we can refine our protein identifications, resulting in the confident identification of 13,000 proteins with putative function. Furthermore, we demonstrate that post-translational modifications play an important role in the proteomes of Cannabis flower, particularly lysine acetylation and protein glycosylation. To facilitate the evolution of analytical investigations into these plant materials, we have created a portal to host resources we have developed from proteomic and metabolomic analysis of Cannabis plant material as well as our results integrating these resources. All data for this project is available to view or download at www.CannabisDraftMap.Org
REVIEW | doi:10.20944/preprints202204.0054.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Medical Cannabis; history of cannabis; medicine; cannabinoids
Online: 7 April 2022 (04:14:19 CEST)
The cannabis plant has been known for millennia for its properties such as textile fiber, food, recreational and medicinal use. Since the origin of its domestication in Asia, cannabis has been transported to the rest of the continents by merchants, nomads, settlers, and slaves, who have also carried with them valuable knowledge about its uses. Its medical use was one of the major contributions of this plant in the various civilizations through which it passed. This article aims to understand its origins, dissemination, and medical use over the years to the present day.
ARTICLE | doi:10.20944/preprints202007.0499.v1
Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: adolescents; cannabis; cognition; working memory; executive functions
Online: 22 July 2020 (05:42:03 CEST)
The developmental phase of adolescence is characterized by a multitude of neurocognitive and psychosocial changes and is therefore considered one of the most critical developmental periods of life. Experimentation on the use of substances often begins in adolescence and so does the addiction process. Most research in human subjects shows that chronic cannabis abuse is the cause of the impairment of some cognitive functions, affecting the performance on divided attention, verbal memory and working memory. In this study, we wanted to investigate how the abuse of cannabis (chronic, occasional and absence use) can influence global cognitive functioning, also through executive functions. From the statistical analyzes of our study, it emerges that the group of subjects who use chronic cannabis (group 1) has a significant drop in working memory tasks compared to the group that does not use it (group 3). In addition, the goal of future studies by our group is to verify the permanent alteration of cognitive processes affected through revaluations with calendar follow-up (controlled).
ARTICLE | doi:10.20944/preprints202004.0315.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: COVID-19; SARS-CoV2; ACE2 receptor; medical cannabis; CBD
Online: 19 April 2020 (02:45:50 CEST)
With the rapidly growing pandemic of COVID-19 caused by the new and challenging to treat zoonotic SARS-CoV2 coronavirus, there is an urgent need for new therapies and prevention strategies that can help curtail disease spread and reduce mortality. Inhibition of viral entry and thereby spread constitute plausible therapeutic avenues. Similar to other respiratory pathogens, SARS-CoV2 is transmitted through respiratory droplets, with potential for aerosol and contact spread. It uses receptor-mediated entry into the human host via angiotensin-converting enzyme II (ACE2) that is expressed in lung tissue, as well as oral and nasal mucosa, kidney, testes, and the gastrointestinal tract. Modulation of ACE2 levels in these gateway tissues may prove a plausible strategy for decreasing disease susceptibility. Cannabis sativa, especially one high in the anti-inflammatory cannabinoid cannabidiol (CBD), has been proposed to modulate gene expression and inflammation and harbour anti-cancer and anti-inflammatory properties. Working under the Health Canada research license, we have developed over 800 new Cannabis sativa lines and extracts and hypothesized that high-CBD C. sativa extracts may be used to modulate ACE2 expression in COVID-19 target tissues. Screening C. sativa extracts using artificial human 3D models of oral, airway, and intestinal tissues, we identified 13 high CBD C. sativa extracts that modulate ACE2 gene expression and ACE2 protein levels. Our initial data suggest that some C. sativa extract down-regulate serine protease TMPRSS2, another critical protein required for SARS-CoV2 entry into host cells. While our most effective extracts require further large-scale validation, our study is crucial for the future analysis of the effects of medical cannabis on COVID-19. The extracts of our most successful and novel high CBD C. sativa lines, pending further investigation, may become a useful and safe addition to the treatment of COVID-19 as an adjunct therapy. They can be used to develop easy-to-use preventative treatments in the form of mouthwash and throat gargle products for both clinical and at-home use. Such products ought to be tested for their potential to decrease viral entry via the oral mucosa. Given the current dire and rapidly evolving epidemiological situation, every possible therapeutic opportunity and avenue must be considered.
ARTICLE | doi:10.20944/preprints202309.1958.v1
Subject: Social Sciences, Sociology Keywords: regulatory regimes; control devices; cannabis; rights extension; rights denial
Online: 28 September 2023 (13:12:07 CEST)
This article analyzes laws, normative reforms and regulations surrounding the practices and mechanisms of control over the consumption, cultivation and commercialization of cannabis. On the one hand, I investigate regulatory practices that deny rights for the consumption of cannabis classified as recreational. On the other hand, I study regulatory practices that extend rights for the production, consumption and commercialization of cannabis classified as medicinal and industrial. The empirical moment is composed of four stages and methodological tools. First, I conduct an analysis of state policies. Then, I analyze nine laws and codes on cannabis regulation from 1970 to the present. Next, I perform five semi-structured interviews. Finally, I develop two life stories of former people deprived of their liberty for cannabis cultivation and trade. In this way, I trace forms of regulation on multiple demands, knowledge, interests and beliefs. This research focuses on state regulation. Cannabis regulatory regimes are conceived as constructions of political, social and economic truths, meanings and rights. In sum, the answer to the question of how collective demands around cannabis are regulated in Ecuador stipulates that state action reinforces stigmatization and criminalization. In addition, it legitimizes moral entrepreneurs and counter-movements around cannabis.
CASE REPORT | doi:10.20944/preprints202011.0668.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: marijuana; medicinal cannabis (MC); chronic pain (CP); cannabidiol (CBD); tetrahydrocannabinol (THC)
Online: 26 November 2020 (11:22:28 CET)
Rationale:First discovered in 1990, the endocannabinoid system (ECS) was initially shown to have an intimate relationship with central areas of the nervous system associated with pain, reward, and motivation. Recently, however, the ECS has been extensively implicated in the cardiovascular system with contractility, heart rate, blood pressure, and vasodilation. Emerging data demonstrates modulation of the ECS plays an essential role in cardio metabolic risk, atherosclerosis, and can even limit damage to cardiomyocytes during ischemic events.Patient Concerns:This case describes a 63-year-old male who presented to a primary care physician for a medical cannabis (MC) consult due to unstable angina (UA) not relieved by morphine or cardiac medications; having failed all first- and second-line poly-pharmaceutical therapies. The patient reported frequent, unprovoked, angina and exertional dyspnea.Diagnosis:Having a complex cardiac history, the patient first presented 22 years ago after a suspected myocardial infarction (MI). He re-presented in 2010 and underwent stent placement at that time for inoperable triple-vessel coronary artery disease (CAD) which was identified via percutaneous transluminal coronary angioplasty. UA developed on follow up and, despite medical management over the past 6 years, his UA became progressively debilitating.Interventions and Outcomes:In conjunction with his standard cardiac care, patient had a gradual lessening of UA related pain, including frequency and character, after using an edible form of medical cannabis (MC) (1:1 CBD:THC). Following continued treatment, he ceased long term morphine treatment and describes the pain as no longer crippling. As demonstrated by his exercise tolerance tests, the patient experienced an improved functional capacity and reported an increase in his daily functioning, and overall activity.Lessons:This case uniquely highlights MC in possibly reducing the character, quality, and frequency of UA; while concordantly improving functional cardiac capacity in a patient with CAD. Additional case reports are necessary to verify this.
REVIEW | doi:10.20944/preprints202010.0551.v2
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: cannabinoids; Δ9-tetrahydrocannabinol; cannabidiol; non-cannabinoids; flavonoids; terpenes; secondary metabolites
Online: 26 November 2020 (11:13:18 CET)
The Cannabis plant (Cannabis sativa L.) produces an estimated 545 chemical compounds of different biogenetic classes. In addition to economic value, many of these phytochemicals have medicinal and physiological activity. The plant is most popularly known for its two most prominent and most studied secondary metabolites— Δ9-Tetrahydrocannabinol (Δ9-THC) and Cannabidiol (CBD). Both Δ9-THC and CBD have a wide therapeutic window across many ailments and form part of a class of secondary metabolites called cannabinoids—of which approximately over 104 exist. This review will focus on non-cannabinoid metabolites of Cannabis sativa that also have therapeutic potential, some of which share medicinal properties similar to those of cannabinoids. The most notable of these non-cannabinoid phytochemicals are flavonoids and terpenes. We will also discuss future directions in cannabis research and development of cannabis-based pharmaceuticals. Caflanone, a flavonoid molecule with selective activity against the human viruses including the coronavirus SARS-COV2, and certain cancers, is one of the most promising non-cannabinoid molecules that is being advanced into clinical trials. As validated by thousands of years of the use of cannabis for medicinal purposes, vast anecdotal evidence abounds on the medicinal benefits of the plant. These benefits are attributed to the many phytochemicals in this plant, including non-cannabinoids. The most promising non-cannabinoids with potential to alleviate global disease burdens are discussed.
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Cannabis; Metabolite; Principal Component Analysis; Random Forest
Online: 5 September 2020 (07:51:50 CEST)
The many strains of Cannabis spp. are associated with many effects on users and contain many different potentially psychoactive metabolites, but the links between metabolite profiles and user effects are unclear. Here we take a statistical approach to linking cause (i.e. metabolites) to effects in Cannabis spp. through the prism of strains, using quantitative data for metabolite composition and user effects. We find that species (indica vs. sativa) explains <2% of the variability in metabolite profiles, while strain explains 1/3 of variability, indicating species is nonindicative of metabolite composition, while strain is approximately indicative. Using random forests we generate a table of potential metabolite-effect links. We also find that effect-weighted metabolite composition can effectively be described in terms of four values representing the concentrations of pairs or triplets of particular compounds.
ARTICLE | doi:10.20944/preprints202212.0245.v1
Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: cannabis; tobacco; co-use; simultaneous use; mixing
Online: 14 December 2022 (06:30:42 CET)
Introduction: Increasing cannabis legalization raises concerns that tobacco use, frequently used with cannabis, will also increase. This study investigated the association between legal status of cannabis in place of residence and prevalence of cannabis and tobacco co-use, simultaneous use, and mixing by comparing the prevalence among adults in Canada (prior to cannabis legalization) vs. adults in US states that had legalized recreational cannabis vs. US states that had not as of September 2018. Methods: Data were drawn from the 2018 International Cannabis Policy Study, conducted with respondents aged 16-65 in Canada and the US recruited from non-probability consumer panels. Differences in the prevalence of co-use, simultaneous use, and mixing between tobacco and different cannabis products were examined using logistic regression models by legal status of place of residence among past 12-month cannabis consumers (N=6744). Results: Co-use and simultaneous use in the past 12 months were most common among respondents in US legal states. Among cannabis consumers, co-use and simultaneous use were less common in US legal states, while mixing was less frequent in US states with both legal and illegal cannabis compared to Canada. Use of edibles was associated with lower odds of all three outcomes, while smoking dried herb or hash was associated with higher odds. Conclusions: The proportion of cannabis consumers who used tobacco was lower in legal jurisdictions despite higher prevalence of cannabis use. Edible use was inversely associated with co-use suggesting that edible use does not appear to be associated with increased tobacco use.
REVIEW | doi:10.20944/preprints202012.0766.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Cannabis; marijuana; marihuana; tissue culture; review; regeneration; floral reversion; micropropagation; TDZ; DKW
Online: 30 December 2020 (17:24:27 CET)
The recent legalization of Cannabis sativa L. in many regions has revealed a need for effective propagation and biotechnologies for the species. Micropropagation affords researchers and producers methods to rapidly propagate insect/disease/virus free clonal plants, store germplasm, and forms the basis for other biotechnologies. Despite this need, research in the area is limited due to the long history or prohibitions and restrictions. Existing literature has multiple limitation: many publications use hemp as a proxy for drug-type Cannabis when it is well established that there is significant genotype specificity, studies using drug-type cultivars are predominantly op-timized using a single cultivar, most protocols have not been replicated by independent groups, and some attempts demonstrate a lack of reproducibility across genotypes. Due to culture decline and other problems the multiplication phase of micropropagation (stage 2) has not been fully developed in many reports. This review will provide a brief background on the history and botany of Cannabis as well as a comprehensive and critical summary of Cannabis tissue culture. Special attention will be paid to current challenges faced by researchers, the limitations of existing Cannabis micropropagation studies, and recent developments and future directions of Cannabis tissue culture technologies.
ARTICLE | doi:10.20944/preprints202009.0124.v1
Subject: Biology And Life Sciences, Plant Sciences Keywords: cannabis; dark period; flower initiation; photoperiod; tissue culture
Online: 5 September 2020 (07:29:39 CEST)
Most commercial Cannabis sativa L. (cannabis) genotypes are short-day plants and cultivators typically use a 12.0 h uninterrupted dark period to induce flowering; however, scientific information is lacking to prove this is the optimal dark period for all genotypes, and cultivar specific photoperiods may increase productivity. Tissue culture can be used for research requiring multiple treatments, proper replication, and in a controlled environment on a smaller scale compared to greenhouse and indoor facilities. To determine whether cannabis explants can flower under varied photoperiods in vitro, explants were grown under one of six photoperiod treatments: 12.0, 13.2, 13.8, 14.4, 15.0, and 16.0 h for four weeks. The percentage of flowering explants was highest under 12.0 and 13.2 h treatments. There were no treatment effects on the fresh weight, final height, or growth index of the explants. The results suggest an uninterrupted dark period of at least 10.8 h (i.e. 13.2 h photoperiod) is needed to induce the flowering of this genotype. In vitro flowering could provide a unique and high throughput approach to study floral/seed development and secondary metabolism in cannabis under highly controlled conditions. Further research should determine if this response is the same on a whole plant level.
ARTICLE | doi:10.20944/preprints202007.0234.v1
Subject: Chemistry And Materials Science, Applied Chemistry Keywords: cannabis; THC; CBD; microwave assisted extraction; continuous flow
Online: 11 July 2020 (09:04:17 CEST)
Cannabis is a flowering plant that has long been used for medicinal, therapeutic, and recreational purposes. Cannabis contains more than 500 different compounds, including a unique class of terpeno-phenolic compounds known as cannabinoids; Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most prevalent cannabinoids and have been associated with the therapeutic and medicinal properties of the cannabis plant. In this paper, continuous flow microwave assisted extraction (MAE) is presented and compared with other methods for commercial cannabis extraction. The practical issues of each extraction method are discussed. The main advantages of MAE are: continuous-flow method which allows for higher volumes of biomass to be processed in less time than existing extraction methods, improved extraction efficiency leading to increased final product yields, improved extract consistency and quality because the process does not require stopping and restarting material flows, and ease of scale-up to industrial scale without the use of pressurised batch vessels. Moreover, due to the flexibility of changing the operation conditions, MAE eliminates additional steps required in most extraction methods, such as biomass decarboxylation, winterisation, which typically adds at least a half day to the extraction process. Another factor that sets MAE apart is the ability to achieve high extraction efficiency even at the industrial scale. Whereas the typical recovery of active compounds using supercritical CO¬2 remains around 70-80%, via MAE up to 95% of the active compounds from cannabis biomass can be recovered at the industrial scale.
COMMUNICATION | doi:10.20944/preprints202206.0117.v2
Subject: Engineering, Other Keywords: Gold nanoparticles; nanomaterials; self-assembled nanoparticles; Cannabis indica
Online: 10 June 2022 (03:27:31 CEST)
Gold nanoparticles have been increasingly used in several electronic, material fabrication, and biomedical applications. Several methods have been reported to prepare gold nanoparticles of various shapes and sizes with different photophysical properties. Although useful to prepare gold nanoparticles, most of the methods are not stable enough and undergo degradation, if stored at room temperatures (up to 30 °C) for a few days. In this paper, we report a novel environmentally friendly method to synthesize self-assembled gold nanoparticles in cruciform shapes by using leaf extract of Cannabis indica as a reducing agent without the aid of any polymers or additional chemicals. The nanoparticles are found to be stable for more than a month when stored at room temperature (30 °C). They were able to form stable conjugates with bovine α-lactalbumin protein that may possess anti-cancerous properties.
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Cannabis sativa; Germplasm preservation; Droplet vitrification; Conventional vitrification; Tissue culture
Online: 19 July 2021 (18:13:48 CEST)
Cannabis has developed into a multi-billion dollar industry that relies on clonal propagation of elite genetics with desirable agronomic and chemical phenotypes. While the goal of clonal propagation is to produce genetically uniform plants, somatic mutations can accumulate during growth and compromise long-term genetic fidelity. Cryopreservation is a process in which tissues are stored at cryogenic temperatures, halting cell division and metabolic processes to facilitate high fidelity germplasm preservation. In this study, a series of experiments were conducted to optimize various stages of cryopreservation and develop a protocol for long-term germplasm storage of Cannabis sativa. The resulting protocol uses a standard vitrification procedure to cryopreserve nodal explants from in vitro shoots as follows: Nodes were cultured for 17 hours in a pre-culture solution (PCS), followed by a 20 minute treatment in a loading solution (LS), and a 60 minute incubation in plant vitrification solution 2 (PVS2). The nodes were then flash frozen in liquid nitrogen, re-warmed in an unloading solution at 40°C, and cultured on basal MS culture medium in the dark for 5 days followed by transfer to standard culture conditions. This protocol was tested across 13 genotypes to assess the genotypic variability. The protocol was successful across all 13 genotypes, but significant variation was observed in tissue survival (43.3-80%) and regrowth of shoots (26.7-66.7%). Plants grown from cryopreserved samples were morphologically and chemically similar to control plants for most major traits, but some differences were observed in the minor cannabinoid and terpene profiles. While further improvements are likely possible, this study provides a functional cryopreservation system that works across multiple commercial genotypes for long-term germplasm preservation.
HYPOTHESIS | doi:10.20944/preprints202012.0178.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: fNIRS; EEG; tDCS; rTMS; tACS; CUD; Cerebellum
Online: 8 December 2020 (06:46:27 CET)
Cannabis is the most widely cultivated, trafficked and abused illicit drug (“WHO | Cannabis,” n.d.; “World Drug Report 2020,” n.d.). In 2018, an estimated 192 million people aged 15-64 years used cannabis for nonmedical purposes globally (Degenhardt et al., 2013). The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated that, across the globe, there were more than 22·1 million people with cannabis dependence (Degenhardt et al., 2018). Moreover, the same study calculated that cannabis dependence could be accounted for 646 thousand Disability Adjusted Life Years, globally. Importantly, cannabis dependence mostly affects young adults (20-24 years), and thus has significant negative impact on the growth and productivity of not only these individuals but also to the societies and nations (Degenhardt et al., 2013). In addition to the dependence syndrome, cannabis use is associated with increased risk of psychosis, cognitive dysfunction, academic problems, and road side accidents (Volkow et al., 2014). A review showed a fairly consistent associations between cannabis use and both lower educational attainment and increased reported use of other illicit drugs (Macleod et al., 2004). In the United States, Cannabis Use Disorder (CUD) is an escalating problem in young adults by legalization (Cerdá et al., 2020) where National Survey on Drug Use and Health reported increased prevalence from 5.1% in 2015 to 5.9% in 2018 in 18-25 year olds (“2019 NSDUH Detailed Tables | CBHSQ Data,” n.d.). The psychoactive effects are due to type 1 cannabinoid receptor (CB1), the cannabinoid binding protein, that are highly expressed in the cerebellar cortex (Marcaggi, 2015). CB1 is primarily found in the molecular layer at the most abundant synapse type in the cerebellum (Marcaggi, 2015) that can shape the spike activity of cerebellar Purkinje cell (Brown et al., 2019). Moreover, granule cell to Purkinje cell synaptic transmission can trigger endocannabinoid release (Alger and Kim, 2011), which may be important for information processing by cerebellar molecular layer interneurons (Dorgans et al., 2019). This suggests that endocannabinoids could be essential to neurocognitive aspects of cerebellar function (Di Marzo et al., 2015),(Marcaggi, 2015),(Alger and Kim, 2011). Accumulating evidence also suggests cerebellar modulation of the reward circuitry and social behaviour, via direct cerebellar innervation of the ventral tegmental area (VTA) including dopamine cell bodies (A1) in the VTA (Carta et al., 2019). The VTA-dopamine (DA) signalling in the nucleus accumbens (NAc) and the medial prefrontal cortex (mPFC) (Lohani et al., 2019) play a key role in motivatedbehaviours and cognition. Cerebellar neuropathological changes can result in aberrant dopaminergic activity in the NAc and mPFC (ROGERS et al., 2011),(Lohani et al., 2019). Therefore, there is a critical need to determine how cerebellum modulate limbic VTA-DA signalling. Cerebellar Non-Invasive Brain Stimulation (NIBS) is postulated to be most relevant in CUD since endocannabinoids are essential to cerebellar function that includes reward-related behaviours, information processing, and cognitive control. (Di Marzo et al., 2015),(Marcaggi, 2015),(Alger and Kim, 2011). Furthermore, cerebellar NIBS can facilitate training of cognitive control in CUD during a during visual cue reactivity paradigm using a mobile virtual reality (VR) interface that can also allow remote delivery of cerebellar NIBS in conjunction with VR-based cognitive training for home-based intervention. Specifically, transcranial electrical stimulation (tES) can be translatable to low-cost (<$150) mobile devices that can be used in a low resource home-based setting (Carvalho et al., 2018).
REVIEW | doi:10.20944/preprints202310.0234.v2
Cannabis and Endometriosis: The roles of the gut microbiota and theendocannabinoid system
Subject: Medicine And Pharmacology, Reproductive Medicine Keywords: endometriosis, endocannabinoids, CB1, CB2
Online: 9 October 2023 (15:10:17 CEST)
There is a growing interest in the endocannabinoid system and the gut microbiota. Both areas have been suggested to play a role in endometriosis, however this is yet to be studied comprehensively. The purpose of this narrative review is to identify the gaps in endometriosis research in the context of these two areas. It underscores the limited knowledge regarding the involvement of the endocannabinoid system and gut microbiota in endometriosis. Further research in these areas is essential to unlock the therapeutic potential of cannabis and enhance the understanding of endometriosis pathogenesis.
REVIEW | doi:10.20944/preprints202111.0463.v2
Subject: Environmental And Earth Sciences, Paleontology Keywords: taxonomy; biogeography; evolution; domestication; dispersal; pollen; archaeology; hemp; drugs
Online: 2 December 2021 (08:55:17 CET)
Cannabis is among the oldest human domesticates and has been subjected to intensive artificial (human-mediated) selection throughout history to create a wide array of varieties and biotypes for diverse uses, including fibre, food, biofuel, medicine and drugs. This paper briefly reviews the available literature on the taxonomy, evolutionary origin and domestication of this plant, as well as its worldwide dispersal, in both its wild and cultivated forms. Emphasis is placed on Europe and especially on the Iberian Peninsula. Today, it is accepted that Cannabis is a monospecific genus with two subspecies, C. sativa subsp. sativa and C. sativa subsp. indica, originating in Europe and Asia, respectively, by allopatric differentiation after geographic isolation fostered by Pleistocene glacial-interglacial cycles. Palynological and phylogeographic evidence situates the Cannabis ancestor on the NE Tibetan Plateau during the mid-Oligocene. The timing and place of domestication is still a matter of debate between contrasting views that defend single or multiple Neolithic domestication centres situated in different parts of the Eurasian supercontinent, notably central/southeastern China and the Caucasus region. Recent meta-analyses have suggested that wild Cannabis may have already been spread across Europe in the Pleistocene, and its domestication could have occurred during the European Copper/Bronze ages. According to the available reviews and meta-analyses, pre-anthropic dispersal of Cannabis into the Iberian Peninsula seems to have occurred only in postglacial times, and the earlier signs of cultivation date to the Early Medieval Ages. However, the palynological and archaeological evidence used to date is insufficient for a sound assessment, and the development of thorough Iberian databases to address further meta-analysis is essential for more robust conclusions. Some clues are provided for these achievements to be fulfilled.
ARTICLE | doi:10.20944/preprints202309.1091.v1
Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: inflammation; T. gondii; cannabis use; eosinophils counts
Online: 18 September 2023 (13:25:31 CEST)
The aim of our study was to evaluate the impact of T. gondii status on eosinophils count (PNE), eosinophil to lymphocyte ratio (ELR) and eosinophil to neutrophil to lymphocytes ratio (ENLR) before and after can-nabis cessation in patients with psychiatric disorders. One hundred and eighty-eight patients were includ-ed in the study. T. gondii, PNE, ELR, ENLR, and urinary cannabis were measured at baseline and after 4 weeks of cannabis cessation. Highest PNE (p = .02), ELR (p = .03) and ENLR levels (p = .031) and highest increase of PNE (p = .044), and ENLR (p = .036) levels were found in patients after cannabis cessation only in the Toxo+ group. At four weeks, significant interactions between cannabis and T. gondii status for PNE (p = .038), and for ENLR (p = .043) levels were found, as well as for the evolution between baseline and 4 weeks for ENLR level (p = .049). After cannabis cessation, we found a positive correlation between negative symptoms and PNE levels at 4 weeks in the Toxo+ group. This study shows that the increase of inflammation after cannabis cessation might be modulated by T. gondii seropositivity status in patient after cannabis cessation.
REVIEW | doi:10.20944/preprints202009.0417.v1
Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: schizophrenia; stress; drug policy; environment; contaminants; pesticides; fungi; prohibition
Online: 18 September 2020 (04:21:43 CEST)
Background: Most modern studies about human marijuana use have been made under a set of arbitrary cultural standards and policies not related to drug harm potential, loosely called Prohibition. Here we asked if potential health hazards generated by Prohibition are addressed in research design and analysis. Methods: For this, we have searched PubMed database (from inception to December 2017) for citations of prevalent contaminants of illegal street cannabis: fungi and pesticides. In addition, we performed full text evaluation of 23 studies selected from, and including, 2 meta-analysis reviews investigating potential health hazards from cannabis use. Results: Different combinations of the keywords cannabis, prohibition, pesticides, fungi, contaminants, cancer, schizophrenia, psychosis, show that these words coincide in less than 1% of the cannabis human studies within the database. In the scope of 141 abstracts in which the terms, cannabis and pesticides coincide, none is directed to distinguish cannabis and pesticide adverse effects on CNS. A similar picture emerges when fungi is the paired word. Full text evaluation shows that all but one of the studies analyzed, completely neglect or comment on the nature of cannabis source, legal status, or contamination as a confounding factor. Discussion: Our results show a potential bias on scientific investigation that may affect data reliability in informing about the health hazards of cannabis use. This finding suggests that other aspects of the Prohibition environment may also go unacknowledged. Conclusion: Prohibition related health risks usually go unacknowledged and unaccounted for in biomedical research on Cannabis.
COMMUNICATION | doi:10.20944/preprints202309.2141.v1
Subject: Biology And Life Sciences, Plant Sciences Keywords: protoplast, Cannabis sativa, regeneration, AIP, phenylpropanoid, tissue culture
Online: 3 October 2023 (03:11:20 CEST)
De novo regeneration of Cannabis sativa L. (cannabis) using tissue culture techniques remains unreliable and infrequent. Conventional methods for the regeneration and transformation of cannabis have not achieved the reliability and replicability needed to be integrated into research and breeding programs. Protoplast systems are effective for gene expression studies, transformation and genome editing technologies, and opens the possibility of somatic hybridization to create interspecific hybrids. To date, leaf-derived protoplast have been isolated for transient gene expression studies, but attempts at protoplast-to-plant regeneration have not been reported. The present study aims to test the efficacy of using a callus culture system, as an abundant source for protoplast isolation and lays the groundwork for a protoplast-to-plant regeneration system. Using hypocotyl-derived callus cultures, which are known to have relatively greater regenerative potential, the efficacy of protoplast isolation and initial cell division were assessed. In this study, the effect of 2-aminoindane-2-phosphonic acid (AIP) in callus culture media and the effect of subculture frequency on protoplast yield were assessed. This study found that inclusion of AIP at 1 mM resulted in a 334% increase in protoplast yield compared with AIP-free medium, representing the first known use of AIP in cannabis tissue culture. Inclusion of AIP led to a 28% decrease in total soluble phenolics and 52% decrease in tissue browning compared to the control medium. Lastly, a two-phase culture system for protoplast regeneration was tested. At a concentration of 2.0×10^5 protoplasts per mL, division was observed, providing the first know report of cell division from cannabis protoplasts and setting the stage for future development of a protoplast-to-plant regeneration system.
CASE REPORT | doi:10.20944/preprints202307.1427.v1
Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: Cannabis use disorder, Virtual reality therapy, Psychotic disorder, Case report, Addiction intervention, Relational treatment.
Online: 20 July 2023 (11:23:33 CEST)
Considering the harmful effects of cannabis on individuals with a severe mental disorder and the limited effectiveness of current interventions, this case report showcases the beneficial results of a 10-session Avatar intervention for cannabis use disorder (CUD) on a polysubstance user with a comorbid schizoaffective disorder. Virtual reality allowed the creation of an Avatar representing a person significantly related to the patient’s drug use. Avatar intervention for CUD aims to combine exposure, relational, and cognitive behavioral therapies while practicing real-life situations and learning how to manage negative emotions and cravings. Throughout therapy and later on, Mr. C managed to maintain abstinence from all substances. Also, an improvement in the severity of CUD as well as a greater motivation to change consumption, were observed after therapy. As observed by his mother, his psychiatrist, and himself, the benefits of Avatar intervention for CUD extended to other spheres of his life. The drastic results observed in this patient could be promising as an alternative to the current treatment available for people with a dual diagnosis of cannabis use disorder and psychotic disorder, which generally lack effectiveness. A single-blind randomized control trial comparing the treatment with a classical intervention in a larger sample is currently underway to evaluate whether the results are reproducible on a larger sample.
ARTICLE | doi:10.20944/preprints202202.0235.v1
Subject: Social Sciences, Sociology Keywords: adolescence; substance use; cannabis use; ordered logistic regression; fuzzy set theory; fuzzy set qualitative comparative analysis; Boolean functions.
Online: 18 February 2022 (11:49:13 CET)
The literature on substance use usually extracts conclusions from data with correlational methods. Our study shows the usefulness of complementing ordered logistic regression (OLR) and fuzzy set qualitative comparative analysis (fsQCA) to assess factors inducing cannabis consumption in a sample of 1,935 teenagers. OLR showed a significant influence of gender (odd ratio (OR) =0.383, p<0.0001), parental monitoring (OR=0.587, p=0.0201); religiousness (OR=0.476, p=0.006); parental tolerance to substance use (OR=42.01, p<0.0001) and having close peers that consume substances (OR=5.60, p<0.0001). FsQCA has allowed fitting linkages between factors from a complementary perspective. (1) Coverage (cov) and consistency (cons) attained by solutions explaining use (cons=0.808, cov=0.357) are clearly lower than by recipes of non-use (cons=0.952, cov=0.869) (2) The interaction of gender, a tolerant family to use and the attitude toward substances by peers is very consistent to explain cannabis use. (3) The most important recipe explaining resistance to cannabis is simply parental disagreement with substance consumption (cons=0.956, cov=0.861) (4) Factors as gender, religiosity, parental monitoring and age show also a relevant impact on attitude toward cannabis use. However, whereas some of them impact symmetrically on use and non-use this does not follow in factors such as parental monitoring or age.
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: systematic review; cannabis; neuroimaging; age-of-onset psychosis; psychosis; schizophrenia
Online: 14 May 2021 (09:58:14 CEST)
Acute exposure to cannabis has been associated with an array of cognitive alterations, increased risk for neuropsychiatric illness, and other neuropsychiatric sequelae including the emergence of acute psychotic symptoms. However, the brain alterations associating cannabis use and these behavioral and clinical phenotypes remains disputed. To this end, neuroimaging can be a powerful technique to non-invasively study the impact of cannabis exposure on brain structure and function in both humans and animal models. While chronic exposure studies provide insight into how use may be related to long-term outcomes, acute exposure may reveal interesting information regarding the immediate impact of use and abuse on brain circuits. Understanding these alterations could reveal the connection with symptom dimensions in neuropsychiatric disorders and, more specifically with psychosis. The purpose of the present review is to: 1) provide an update on the findings of pharmacological neuroimaging studies examining the effects of administered cannabinoids and 2) focus the discussion on studies that examine the sensitive window for the emergence of psychosis. Current literature indicates that cannabis exposure has varied effects on the brain, with the principal compounds in cannabis (delta-9-tetrahydrocannabinol and cannabidiol) altering activity across different brain regions. Importantly, we also discorvered critical gaps in the literature, particularly regarding sex-dependent responses and long-term effects of chronic exposure. Certain networks often characterized as dysregulated in psychosis, like the default mode network and limbic system, were also impacted by THC exposure, identifying areas of particular interest for future work investigating the potential relationship between the two.
ARTICLE | doi:10.20944/preprints201807.0197.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Cannabis, obesity, body mass index, CB1R, AEA, 2-AG, meta-analysis, theory, causation
Online: 11 July 2018 (11:49:02 CEST)
Obesity is treatment-resistant, and is linked with a number of serious, chronic diseases. Adult obesity rates in the United States have tripled since the early 1960s. Recent reviews show that an increased ratio of omega-6 to omega-3 fatty acids contributes to obesity rates by increasing levels of the endocannabinoid signals AEA and 2-AG, overstimulating CB1R and leading to increased caloric intake, reduced metabolic rates, and weight gain. Cannabis, or THC, also stimulates CB1R and increases caloric intake during acute exposures. The present meta-analysis reveals significantly reduced body mass index and rates of obesity in Cannabis users, in conjunction with increased caloric intake. We provide for the first time a causative explanation for this paradox, in which rapid and long-lasting downregulation of CB1R following acute Cannabis consumption reduces energy intake and storage and increases metabolic rates, thus reversing the impact on body mass index of elevated dietary omega-6/omega-3 ratios.
ARTICLE | doi:10.20944/preprints202106.0532.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Cannabis Sativa L.; Aeroponics; Roots; Campesterol; Stigmasterol; β-Sitosterol; Epi-friedelanol; Friedelin
Online: 22 June 2021 (08:27:11 CEST)
Cannabis Sativa L. has been used for a long time to obtain food, fiber and as a medicinal and psychoactive plant. Today the nutraceutical potential of C. Sativa is being increasingly reappraised; however, C. Sativa roots remain poorly studied, despite citations in the scientific literature. In this direction, we identified and quantified the presence of valuable bioactives (namely β-sitosterol, stigmasterol, campesterol, friedelin and epi-friedelanol) in the root extracts of C. Sativa, a finding which might pave the way to the exploitation of the therapeutic potential of C. Sativa in all its parts. To facilitate roots harvesting and processing, aeroponic (AP) and aeroponic elicited cultures (AEP), have been set up and compared to soil-cultivated plant (SP): interestingly a considerable overgrowth of the plants - particularly of roots - and a significant increase (up to 20 fold in the case of β-sitosterol) in the total content of the above roots’ bioactive molecules have been observed in AP and AEP. In conclusion aeroponics, an easy, standardised, free of contaminant cultivation tecchnique, allows an ease harvesting/processing of roots along with a greater production of their secondary bioactive metabolites which could be utilized in the formulation of health promoting and health care products.
ARTICLE | doi:10.20944/preprints202101.0163.v1
Subject: Biology And Life Sciences, Plant Sciences Keywords: Cannabis sativa; PPFD; light intensity; light response curve; indoor; sole source; cannabinoid; terpene
Online: 8 January 2021 (14:04:08 CET)
Since the recent legalization of medical and recreational use of cannabis (Cannabis sativa L.) in many regions worldwide, there has been high demand for research to improve yield and quality. With the paucity of scientific literature on the topic, this study investigated the relationships between light intensity (LI) and photosynthesis, inflorescence yield, and inflorescence quality of cannabis grown in an indoor environment. After growing vegetatively for 2 weeks under a canopy-level photosynthetic photon flux density (PPFD) of ≈ 425 μmol·m-2·s-1 and an 18-h light/6-h dark photoperiod, plants were grown for 12 weeks in a 12-h light/12-h dark ‘flowering’ photoperiod under canopy-level PPFDs ranging from 120 to 1800 μmol·m-2·s-1 provided by light emitting diodes. Leaf light response curves varied both with localized (i.e., leaf-level) PPFD and temporally, throughout the flowering cycle. Therefore, it was concluded that the leaf light response is not a reliable predictor of whole- plant responses to LI, particularly crop yield. This may be especially evident given that dry inflorescence yield increased linearly with increasing canopy-level PPFD up to 1800 μmol·m-2·s-1, while leaf-level photosynthesis saturated well below 1800 μmol·m-2·s-1. The density of the apical inflorescence and harvest index also increased linearly with increasing LI, resulting in higher-quality marketable tissues and less superfluous tissue to dispose of. There were no LI treatment effects on cannabinoid potency, while there were minor LI treatment effects on terpene potency. Commercial cannabis growers can use these light response models to determine the optimum LI for their production environment to achieve the best economic return; balancing input costs with the commercial value of their cannabis products.
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: cananbis sativa; marijuana; hemp; microbiome; endophytes; secondary metabolites; Cannabinoids
Online: 15 January 2020 (07:04:25 CET)
Plants, including Cannabis (Cannabis sativa subsp. sativa) host distinct beneficial microbial communities on and inside their tissues, designated the plant microbiota from the moment that they are planted into the soil as seed. They contribute to plant growth promotion, facilitating mineral nutrient uptake, inducing defense resistance against pathogens, higher yield and modulating plant secondary metabolites. Understanding the microbial partnerships with Cannabis has the potential to affect agricultural practices by improving plant fitness and the production yield of cannabinoids. Much less is known about this beneficial Cannabis-microbe partnership, and the complex relationship between the endogenous microbes associated with various tissues of the plant, particularly, the role that cannabis may play in supporting or enhancing them. This review will focus on Cannabis microbiota studies and the effect of endophytes on the elicitation of secondary metabolites production in Cannabis plants. The aim of this review is to shed light on the importance of Cannabis microbiome and how cannabinoid compounds concentration can be stimulated through symbiotic and or mutualistic relationships with endophytes.
ARTICLE | doi:10.20944/preprints202309.1295.v1
Subject: Biology And Life Sciences, Agricultural Science And Agronomy Keywords: cannabis; breeding; phenotype; correlations
Online: 20 September 2023 (02:35:37 CEST)
Cannabis (Cannabis sativa L.) stands as a historically significant and culturally important plant, embodying economic, social, and medicinal relevance for human societies. However, years of prohibition and stigmatization have hindered the cannabis research community, which is hugely undersized and suffers from a scarcity of understanding of cannabis genetics and how key traits are expressed or inherited. In this study, we conducted a comprehensive phenotypic characteriza-tion of 176 drug-type cannabis accessions, representative of Canada's legal market. We assessed germination methods, evaluated various traits including agronomic, morphological, and canna-binoid profiles, and uncovered significant variation within this population. Notably, yield dis-played a negative correlations with maturity-related traits but positive correlation with fresh biomass. Additionally, the potential THC content showed positive correlation with maturi-ty-related traits but negative correlation with yield. Significant different were observed between plants derived from regular female seeds and feminized seeds, as well as between plants derived from cuttings and seeds for different traits. This study advances our understanding of cannabis cultivation, offering insights into germination practices, agronomic traits, morphological charac-teristics, and biochemical diversity. These findings establish a foundation for precise breeding and cultivar development, enhancing cannabis's potential in the legal market.
ARTICLE | doi:10.20944/preprints202209.0143.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Salmonella; novel antibacterial agents; cannabidiol; co-therapy; bacterial genetics
Online: 12 September 2022 (09:55:22 CEST)
New generation antibiotics are needed to combat the development of resistance to antimicrobials. One of the most promising new classes of antibiotics is cannabidiol (CBD). It is a non-toxic and low-resistance chemical that can be used to treat bacterial infections. The antibacterial activity of Cannabis sativa L. byproducts, specifically CBD, has been of growing interest in the field of novel therapeutics. As research continues to define and characterize the antibacterial activity that CBD possesses against a wide variety of bacterial species it is important to examine potential interaction between CBD and common therapeutics such as broad-spectrum antibiotics. Here, we show that CBD-antibiotic co-therapy can effectively fight S. typhimurium via membrane integrity disruption. This research serves to examine the potential synergy between CBD and three broad-spectrum antibiotics for potential antibiotic-CBD co-therapy. In this study, we reveal that Salmonella typhimurium (S. typhimurium) growth is inhibited at very low dosages of CBD-antibiotic. This interesting finding demonstrates that CBD and CBD-antibiotic co-therapies are viable novel alternatives to combating Salmonella typhimurium.
ARTICLE | doi:10.20944/preprints202307.1840.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: MTT assay; cell toxicity; cytokine gene expression; nanoencapsulation; dynamic light scattering; topical formulation
Online: 27 July 2023 (03:54:21 CEST)
Industrial hemp (Cannabis sativa L.), due to its bioactive compounds (terpenes and cannabinoids), has gained an increasing interest in different fields, including medical purposes. The evaluation of the safety profile of hemp essential oil (EO) and its encapsulated form (nanoemulsion, NE) is a relevant aspect for potential therapeutic applications. This study aimed to evaluate the toxicolog-ical effect of hemp EOs and NEs from cultivars Carmagnola CS and Uso 31, on three cell lines se-lected as models for topical and inhalant administration, by evaluating the cytotoxicity and the cytokine expression profiles. Results show that EOs and their NEs have comparable cytotoxicity, if considering the quantity of EO present in the NE. Moreover, cells treated with EOs and NEs showed, in most of the cases, lower levels of pro-inflammatory cytokines compared to Etoposide used as positive control, and the basal level of inflammatory cytokines was not altered, suggest-ing a safety profile of hemp EOs and their NEs to support their use for medical applications.
ARTICLE | doi:10.20944/preprints202103.0327.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: cannabis; UV; cannabinoid; yield
Online: 11 March 2021 (16:18:09 CET)
Cannabis (Cannabis Sativa L.) is now legally produced in many regions worldwide. Cannabis flourishes under high light intensities (LI); making it an expensive commodity to grow in controlled environments, despite its exceptionally high market value. It is commonly believed that cannabis secondary metabolite levels may be enhanced both by increasing LI and by exposing crops to ultraviolet radiation (UV). However, there is sparse scientific evidence to guide cultivators. Therefore, the impact of LI and UV on yield and quality must be elucidated to enable cultivators to optimize their lighting protocols. We explored the effects of LI, ranging from 350 to 1400 μmol m-2 s-1 and supplemental UV spectra on cannabis yield and potency. There were no spectrum effects on inflorescence yield, but harvest index under UVA+UVB was reduced slightly (1.6%) vs. the control. Inflorescence yield increased linearly from 19.4 to 57.4 g/plant and harvest index increased from 0.565 to 0.627, as LI increased from 350 to 1400 μmol m-2 s-1. Although there were no UV spectrum effects on total equivalent Δ9-tetrahydrocannabinol (T-THC) content in leaves, the neutral form, THC, was 30% higher in UVA+UVB vs. control. While there were no LI effects on inflorescence T-THC content, the content of the acid form (THCA) increased by 20% and total terpenes content decreased by 20% as LI increased from 350 to 1400 μmol m-2 s-1. High LI can substantially increase cannabis yield and quality, but we found no commercially-relevant benefits of adding supplemental UV radiation to indoor cannabis production.
ARTICLE | doi:10.20944/preprints202310.1852.v1
Subject: Biology And Life Sciences, Plant Sciences Keywords: bioinformatics; cannabis; hemp; hop latent viroid; molecular diagnostics; plant pathogens
Online: 30 October 2023 (09:54:14 CET)
The increased cultivation of Cannabis sativa L. in North America, represented by high Δ9-tetrahydrocannabinol-containing (high-THC) cannabis genotypes and low THC-containing hemp genotypes, has been impacted by an increasing number of plant pathogens. These include fungi which destroy roots, stems and leaves, in some cases causing a build-up of populations and mycotoxins in the inflorescences that can negatively impact quality. Viroids and viruses have also increased in prevalence and severity and can reduce plant growth and product quality. Rapid diagnosis of the occurrence and spread of these pathogens is critical. Techniques in the area of molecular diagnostics have been applied to study these pathogens in both cannabis and hemp. These include polymerase chain reaction (PCR)-based technologies, including RT-PCR, multiplex RT-PCR, RT-qPCR, and ddPCR, as well as whole genome sequencing (NGS) and bioinformatics. In this study, examples of how these technologies have enhanced the rapidity and sensitivity of pathogen diagnosis on cannabis and hemp will be illustrated. These molecular tools have also enabled studies on the diversity and origins of specific pathogens, specifically viruses and viroids, and these will be illustrated. Comparative studies on the genomics and metabolomics of healthy and diseased plants are urgently needed to provide insight into their impact on quality and composition of cannabis and hemp-derived products. Management of these pathogens will require monitoring of their spread and survival using the appropriate technologies to allow accurate detection, followed by appropriate implementation of disease control measures.
ARTICLE | doi:10.20944/preprints202106.0317.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Cannabis sativa; potency; ultraviolet; indoor; sole source; terpene
Online: 11 June 2021 (11:31:18 CEST)
It is commonly believed that exposing Cannabis sativa (cannabis) plants to ultraviolet (UV) radiation can enhance Δ9-tetrahydrocannabinol (Δ9-THC) concentrations in female inflorescences and associated foliar tissues. However, a lack of published scientific studies has left knowledge-gaps in the effects of UV on cannabis that must be elucidated before UV can be utilized as a horticultural management tool in commercial cannabis production. In this study we investigated the effects of UV exposure level on photosynthesis, growth, inflorescence yield, and secondary metabolite composition of two indoor-grown cannabis cultivars: ‘Low Tide’ (LT) and ‘Breaking Wave’ (BW). After growing vegetatively for 2 weeks under a canopy-level photosynthetic photon flux density (PPFD) of ≈225 μmol·m–2·s–1 in an 18-h light/6-h dark photoperiod, plants were grown for 9 weeks in a 12-h light/12-h dark “flowering” photoperiod under a canopy-level PPFD of ≈400 µmol·m–2·s–1 and 3.5 h·d–1 of supplemental UV radiation with UV photon flux densities (UV-PFD) ranging from 0.01 to 0.8 μmol·m–2·s–1 provided by light-emitting diodes (LEDs) with a peak wavelength of 287 nm (i.e., biologically-effective UV doses of 0.16 to 13 kJ·m–2·d–1). The severity of UV-induced morphology (e.g., whole-plant size and leaf size reductions, leaf malformations, and stigma browning) and physiology (e.g., reduced leaf photosynthetic rate and reduced Fv/Fm) symptoms worsened as UV exposure level increased. While the proportion of dry inflorescence yield that was derived from apical tissues decreased in both cultivars with increasing UV exposure level, total dry inflorescence yield only decreased in LT. The equivalent Δ9-THC and cannabidiol (CBD) concentrations also decreased in LT inflorescences with increasing UV exposure level. While the total terpene content in inflorescences decreased with increasing UV exposure level in both cultivars, the relative concentrations of individual terpenes varied by cultivar. The potential for using UV to enhance cannabis quality must still be confirmed before it can be used as a production tool for modern, indoor-grown cannabis cultivars.
ARTICLE | doi:10.20944/preprints202203.0367.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Salmonella; Novel Antibacterial Agents; Cannabinoids
Online: 28 March 2022 (14:30:09 CEST)
Products derived from Cannabis sativa have gained increased interest and popularity. As these products become common amongst the public, the heath and potential therapeutic values associated with hemp have become a premier focus of research. While the psychoactive and medicinal properties of Cannabis products have been extensively highlighted in literature, the antibacterial properties of CBD have not been explored in depth. This research serves to examine the antibacterial potential of CBD against Salmonella newington and Salmonella typhimurium. In this study we observed bacterial response to CBD exposure through biological assays, bacterial kinetics, and fluorescence microscopy. Additionally, comparative studies between CBD and ampicillin were conducted against Salmonella typhimurium and Salmonella newington to determine comparative efficacy. Furthermore, we observed potential resistance development of our Salmonella spp. against CBD treatment.
ARTICLE | doi:10.20944/preprints202104.0417.v1
Subject: Biology And Life Sciences, Plant Sciences Keywords: Light-emitting diodes; PPFD; DLI; growth; morphology
Online: 15 April 2021 (13:12:44 CEST)
Although the vegetative stage of indoor cannabis production can be relatively short in duration, there is a high energy demand due to higher light intensities (LI) than the clonal propagation stage and longer photoperiods than the flowering stage (i.e., 16 – 24 hours vs. 12 hours). While electric lighting is a major component of both energy consumption and overall production costs, there is a lack of scientific information to guide cultivators in selecting a LI that corresponds to their vegetative stage production strategies. To determine the vegetative plant responses to LI, clonal plants of ‘Gelato’ were grown for 21 days with canopy-level photosynthetic photon flux densities (PPFD) ranging between 135 and 1430 µmol·m-2·s-1 on a 16-hour photoperiod (i.e., daily light integrals of ≈ 8 to 80 mol·m-2·d-1). Plant height and growth index responded quadratically; the number of nodes, stem thickness, and aboveground dry weight increased asymptotically; and internode length and water content of aboveground tissues decreased linearly with increasing LI. Foliar attributes had varying responses to LI. Chlorophyll content index increased asymptotically, leaf size decreased linearly and specific leaf weight increased linearly with increasing LI. Generally, PPFD levels of ≈ 900 µmol·m-2·s-1 produced compact, robust plants that are commercially relevant, while PPFD levels of ≈ 600 µmol·m-2·s-1 promoted plant morphology with more open architecture – to increase airflow and reduce the potential foliar pests in compact (i.e., indica-dominant) genotypes.
REVIEW | doi:10.20944/preprints201911.0260.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: sepsis; endocannabinoid system; cannabinoids; cannabis sativa; THC; CBD
Online: 22 November 2019 (09:32:28 CET)
Critically ill patients with sepsis require a multidisciplinary approach, as this situation implies multiorgan distress, with most of the bodily biochemical and cellular systems being affected by the condition. Moreover, sepsis is characterized by a multitude of biochemical interactions and by dynamic changes of the immune system. At the moment, there is a gap in our understanding of the cellular, genetic, and molecular mechanisms involved in sepsis. One of the systems intensely studied in recent years is the endocannabinoid signaling pathway, as light was shed over a series of important interactions of cannabinoid receptors with biochemical pathways, specifically for sepsis. Furthermore, a series of important implications on inflammation and the immune system that are induced by the activity of cannabinoid receptors stimulated by the delta-9-tetrahidrocannabinol and cannabinol have been noticed. The aim of this review paper was to present, in detail, the important mechanisms modulated by the endocannabinoid signaling pathway, as well as of the molecular and cellular links it has with sepsis. At the same time, we wish to present the possible implications of cannabinoids in the most important biological pathways involved in sepsis, such as inflammation, redox activity, immune system, and epigenetic expression.
ARTICLE | doi:10.20944/preprints202305.1512.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: cannabidiol; delta-9-hydrocannabinol; CBD; THC; THP-1 macrophages; Cannabis sativa; inflammation; lipopolysaccharide
Online: 22 May 2023 (11:00:01 CEST)
Inflammation is the response of the innate immune system to any type of injury. Although acute inflammation is critical for survival, dysregulation of innate immune response leads to chronic in-flammation. Many synthetic anti-inflammatory drugs have side effects, and thus, natural an-ti-inflammatory compounds are still needed. Cannabis sativa L. may provide a good source of in-flammation-reducing molecules. Here, we tested the anti-inflammatory properties of cannabis ex-tracts and pure cannabinoids in lipopolysaccharide (LPS)-induced inflammation in human THP-1 macrophages. We found that pre-treatment with cannabidiol (CBD), delta-9-tetrahydrocannabinol (THC), or extracts containing high levels of CBD or THC reduce the level of induction of various cytokines. The CBD was more efficient than THC, and the extracts were more efficient than pure cannabinoids. Finally, IL-6, IL-10 and monocyte chemoattractant protein-1 (MCP-1) were most sensitive to pre-treatments with CBD and THC, while IL-1β, IL-8 and TNF-α were less responsive. Thus, our work demonstrates the potential of use of cannabinoids or/and cannabis extracts for the reduction of inflammation and establishes IL-6 and MCP-1 as the sensitive markers for the analysis of the effect of cannabinoids on inflammation in macrophages.
REVIEW | doi:10.20944/preprints202111.0050.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: cannabinoids; cannabis-derived phytocannabinoids; neuroprotection; resveratrol; Parkinson’s disease
Online: 2 November 2021 (12:15:49 CET)
Currently, there are no pharmacological treatments able to reverse nigral degeneration in Parkinson’s disease (PD), hence the unmet need for the provision of neuroprotective agents. Cannabis-derived phytocannabinoids (CDCs) and resveratrol (RSV) may be useful neuroprotective agents for PD due to their anti-oxidative and anti-inflammatory properties. To evaluate this, we undertook a systematic review of the scientific literature to assess the neuroprotective effects of CDCs and RSV treatments in pre-clinical in vivo animal models of PD. The literature databases MEDLINE, EMBASE, PsychINFO, PubMed and Web of Science core collection were systematically searched to cover relevant studies. A total of 1034 publications were analyzed, of which 18 met the eligibility criteria for this review. Collectively, the majority of neurotoxin-induced PD rodent studies demonstrated that treatment with CDCs or RSV produced a significant improvement in motor function and mitigated the loss of dopaminergic neurons. Biochemical analysis of rodent brain tissue suggested that neuroprotection was mediated by anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms. This review highlights the neuroprotective potential of CDCs and RSV for in vivo models of PD, and therefore suggests their potential translation to human clinical trials to either ameliorate PD progression and/or be implemented as a prophylactic means to reduce the risk of development of PD.
ARTICLE | doi:10.20944/preprints202108.0460.v1
Subject: Biology And Life Sciences, Horticulture Keywords: Cannabis; cannabinoids; nutrients; nitrogen (N); phosphorus (P); potassium (K); yield; response surface methodology
Online: 24 August 2021 (08:40:44 CEST)
Following legalization, cannabis has quickly become an important horticultural crop in Canada and increasingly so in other parts of the world. However, due to previous legal restrictions on cannabis research there are limited scientific data on the relationship between nitrogen (N), phosphorus (P), and potassium (K) supply (collectively: NPK) and the crop yield and quality. This study examined the response of a high delta-9-tetrahydrocannabinol (THC) Cannabis sativa cultivar grown in deep-water culture with different nutrient solution treatments varying in their concentrations (mg L-1) of N (70, 120, 180, 250, 290), P (20, 40, 60, 80, 100) and K (60, 120, 200, 280, 340) according to a central composite design. Results demonstrated that inflorescence yield responded quadratically to N and P, with the optimal concentrations predicted to be 194 and 59 mg L-1, respectively. Inflorescence yield did not respond to K in the tested range. These results can provide guidance to cultivators when formulating nutrient solutions for soilless cannabis production and demonstrates the utility of surface response design for efficient multi-nutrient optimization.
ARTICLE | doi:10.20944/preprints202112.0493.v1
Subject: Chemistry And Materials Science, Analytical Chemistry Keywords: water-assisted laser desorption/ionization; SpiderMass; cannabinoids; mass spectrometry; plants; in vivo
Online: 30 December 2021 (19:02:18 CET)
In the recent years, Cannabis and hemp-based products have become increasingly popular for various applications ranging from recreational use, edibles, beverages to health care products and medicines. The rapid detection and differentiation of phytocannabinoids is, therefore, essential to assess the potency, therapeutic and nutritional values of cannabis cultivars. Here, we implemented the SpiderMass technology for the in vivo detection of cannabidiol acid (CBDA) and tetrahydrocannabinol acid (THCA) and other endogenous organic plant compounds to access distribution gradients within the plants and differentiate cultivars. The SpiderMass system is composed of an IR- laser handheld microsampling probe connected to the mass spectrometer through a transfer tube. The analysis was performed in situ on different plant organs from freshly cultivated Cannabis plants in only a few seconds. SpiderMass analysis easily discriminated the two acid phytocannabinoid isomers by MS/MS and the built statistical models differentiated between four Cannabis cultivars. Different abundancies of acid phytocannabinoids were also found along the plant as well as between different cultivars. All together, these results introduce the direct analysis by SpiderMass as a compelling analytical alternative for forensic and hemp industrial analysis.
ARTICLE | doi:10.20944/preprints202305.2024.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: hemp; dairy goats; fatty acid profile
Online: 30 May 2023 (02:43:38 CEST)
Hemp (Cannabis sativa L.) is an annual plant belonging to the family of Cannabaceae with several varieties characterised by different fatty acid profiles, content in flavonoids, polyphenols and cannabinoid compounds. Hemp is mostly used in livestock nutrition as oil or as protein cake, not as inflorescences. The aim of this study was to evaluate the effect of dietary hemp inflorescences on milk yield and composition in grazing goats. Twenty goats (Camosciata delle Alpi), after kidding, were equally divided into two groups (G: Grazing and GH: grazing and hemp), homogeneous for milk yield in the previous lactation, parity and live weight. For three months, all goats were fed on a permanent pasture and received 700/head/day of concentrate (barley, oats and faba bean); diet of group GH was supplemented with 20 g/head/day of hemp inflorescences. Pasture DM intake was estimated according to previous research performed in the same area. In addition, goats’ body weight did not change along the trial meaning that their energy requirements were guaranteed. Individual milk yield was daily registered and samples collected every 20 days for chemical com-position (Milkoscan) and fatty acid profile (Gas Chromatography). The data were analysed by ANOVA (GLM procedure of SAS, 2000), for repeated measure. No significant differences were found for milk yield and chemical composition. Lauric acid (C12:0) was significantly higher in milk of group GH (4.83% vs 4.32%; P<0.01) as well as total conjugated linoleic acids (CLAs) (0.435% vs 0.417%; P<0.01).
ARTICLE | doi:10.20944/preprints202109.0179.v1
Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: ovarian cancer; cannabis; phytocannabinoids; apoptosis; cytotoxicity; cell cycle; MAPK4; PARP1
Online: 9 September 2021 (11:57:38 CEST)
Ovarian cancer (OC) is the most lethal gynecologic malignancy. Cannabis sativa is being used to treat different medical conditions. We sought to examine the effectiveness of combinations of cannabis compounds against OC. Cytotoxic activity was determined by XTT assay on HTB75 and HTB161 cell lines. Apoptosis and cell cycle were determined by fluorescence-activated cell sorting (FACS). Gene expression was determined by quantitative PCR. The two most active fractions, F5 and F7, from a high Δ9–tetrahydrocannabinol (THC) cannabis strain extract and their standard mix (SM) showed cytotoxic activity against OC cells. The most effective phytocannabinoid combination was THC+cannabichromene (CBC)+cannabigerol (CBG). F5, F7 and SM affected cell cycle, led to cell apoptosis and to a marked reduction in cell migration. Moreover, these fractions act in synergy with niraparib, and were ~50 fold more cytotoxic to OC cells than to normal keratenocytes. Niraparib+F7 treatment was effective on OC patient's cells. F7 and the niraparin+fraction (F5 and F7) treatments reduced Mitogen-Activated Protein Kinase 4 (MAPK4) gene expression; this reduction may act in synergy with the niraparib inhibition of Poly (ADP-ribose) polymerase 1 (PARP1) activity. Combinations of cannabis compounds and niraparib should be examined for efficacy in pre-clinical studies and clinical trials.
COMMUNICATION | doi:10.20944/preprints202112.0040.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Cannabis sativa L.; Humulus lupulus L.; Humulus japonicus Siebold & Zucc.; sex chromosomes; DNA repeats; transposons; genome sequencing
Online: 3 December 2021 (09:25:39 CET)
Heteromorphic sex chromosomes are rarely found in plants. They were observed only in 47 species from phylogenetically distant families, suggesting that the evolution of sex chromosomes was independent in these species. It was shown that DNA repeat sequences are one of the major factors driving sex chromosomes evolution, and an accumulation or elimination of the repetitive DNA elements are closely linked with the formation of differences in the sex chromosomes. The goal of this study was to characterize the transposon composition in male and female plants of Cannabis sativa L., Humulus lupulus L. and Humulus japonicus Siebold & Zucc. For the first time, the male and female genomes of H. japonicus as well as male genomes of H. lupulus and C. sativa have been sequenced (there were no open data about them). The analysis of genome-wide sequencing data with using Repeatexplorer2 and author’s scripts was carried out. It was shown that accumulation of Ty3-gypsy may be associated with speciation in Cannabaceae family which is the opposite of the theory of speciation throw whole-genome duplication. Moreover, the sex-specific DNA repeat clusters in C. sativa and H. japonicus were found. The analysis also revealed that the concentration of Tekay, Retand and Ikeros repeats in the Y chromosome of C. sativa is lower than in the X chromosome and the Angela concentration is higher in the Y chromosome.
BRIEF REPORT | doi:10.20944/preprints202211.0033.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Clustering; COVID-19; Long COVID; disease severity
Online: 2 November 2022 (01:02:16 CET)
The increasing number of people living with Long COVID requires the development of more personalized care, as for now limited treatment options and rehabilitation programs adapted to the variety of Long COVID presentations are available. Our objective was to design an easy-to-use Long COVID classification to help stratifying people with Long COVID. Individual characteristics and a detailed set of 62 self-reported persisting symptoms together with quality of life indexes 12 months after initial COVID-19 infection were collected in a cohort of SARS-CoV-2 infected people in Luxembourg. A hierarchical ascendant classification (HAC) was used to identify clusters of people. We identified 3 patterns of Long COVID symptoms with a gradient in disease severity. Cluster-Mild encompassed almost 50% of the study population and was composed of participants with less severe initial infection, fewer comorbidities, and fewer persisting symptoms (mean=2.9). Cluster-Moderate was characterized by a mean of 11 persisting symptoms and a poor sleep and respiratory quality of life. Cluster-Severe was characterized by a higher proportion of women and smokers as in the other clusters, with a higher number of Long COVID symptoms, in particular of vascular, urinary, and skin symptoms. Our study evidenced that Long COVID can be stratified in 3 sub-categories in terms of severity. If replicated in other populations, this simple classification will help clinicians to personalize the care of people with Long COVID.
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/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.
Online: 21 July 2020 (13:46:45 CEST)
Today, we are all threatened by an unprecedented pandemic: COVID-19. How different is it from other coronaviruses? Will it be attenuated or become more virulent? Which animals may be its original host? In this study, we analyzed 377 publicly available complete genome sequences for the COVID-19 virus, the previously known flu-causing coronaviruses (HCov-229E, HCov-OC43, HCov-NL63 and HCov-HKU1) and the lethal, pathogenic P3/P4 viruses, SARS, MERS, Victoria, Lassa, Yamagata, Ebola, and Dengue. We found strong similarities between the current circulating COVID-19 and SARS and MERS, as well as COVID-19 in rhinolophines and pangolins. On the contrary, COVID-19 shares little similarity with the flu-causing coronaviruses and the other P3/P4 viruses. Strikingly, we observed divergence of COVID-19 strains isolated from human hosts has steadily increased from December 2019 to March 2020, suggesting COVID-19 is actively evolving in human hosts. From all existing human COVID-19 genome sequences, we calculated the first common model that represents the shared sequences of the human COVID-19 strains, which provides important information for vaccine and antibody development. Geographic and time-course analysis of the evolutionary trees of the human COVID-19 reveals possibly heterogeneous evolutional paths among strains from 21 countries. This finding has important implications to the management of COVID-19 and the development of vaccines.
REVIEW | doi:10.20944/preprints202004.0361.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; pandemic; asymptomaticspread; early-stage COVID-19 mitigation
Online: 20 April 2020 (06:18:33 CEST)
Background: Early-stage interventions in a potential pandemic are important tounderstand as they can make the difference between runaway exponential growththat is hard to turn back and stopping the spread before it gets that far. COVID-19 is an interesting case study because there have been very different outcomesin different localities. These variations are best studied after the fact if precisionis the goal; while a pandemic is still unfolding less precise analysis is of value inattempting to guide localities in the early stages to learn lessons of those that pre-ceded them. Methods: I examine three factors that could differentiate strategy: asymptomaticspread, differences in use of the Bacillus Calmette-Guerin (BCG) tuberculosis vac-cine and cloth face masks.Results:Differences in disease progression as well as the possibility of alternativestrategies to prevent COVID-19 from entering the runaway phase or damping itdown later can be elucidated by a study of asymptomatic infection. A study todemonstrate not only what fraction are asymptomatic but how contagious they arewill also inform policy on universal mask wearing. Conclusions: While a COVID-19 outbreak is at a level that makes accurate trace-and test possible, investigation of asymptomatic transmission is viable and shouldbe attempted to enhance understanding of spread and variability in the disease aswell as policy options for slowing the spread.
COMMUNICATION | doi:10.20944/preprints202102.0306.v1
Subject: Public Health And Healthcare, Public, Environmental And Occupational Health Keywords: Quarantine; COVID-19; Physical activity
Online: 12 February 2021 (14:39:16 CET)
The COVID-19 pandemic which have affected every part of the world have been deemed a public health concern and classified as a pandemic. The government imposing travel bans and quarantine measures have been found to be effective in preventing and reducing the spread of COVID-19. A reduction in physical activity and increase in the consumption of unhealthy foods have been observed to be some of the major implications of quarantine. Adequate physical activity and increased access to healthy foods would help in improving the psychological wellbeing of individuals thereby preventing the development of cardiovascular diseases.
REVIEW | doi:10.20944/preprints202103.0416.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2; CoVID-19 Dignosis; CoVID-19 Chemistry & Biology
Online: 16 March 2021 (11:54:28 CET)
CoVID-19 is a multi-symptomatic disease which has made a global impact due to its ability to spread rapidly, and its relatively high mortality rate. Beyond the heroic efforts to develop vaccines, which we will not discuss, the response of scientists and clinicians to this complex problem has reflected the need to detect CoVID-19 rapidly, to diagnose patients likely to show adverse symptoms, and to treat severe and critical CoVID-19. Here we aim to encapsulate these varied and sometimes conflicting approaches and the resulting data in terms of chemistry and biology. In the process we highlight emerging concepts, and potential future applications that may arise out of this immense effort.
ARTICLE | doi:10.20944/preprints202205.0216.v2
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Bioimpedance; COVID-19; E-health; Health Care Personnel; Pathophysiology; Post-COVID syndrome; Rheography
Online: 23 May 2022 (05:26:58 CEST)
At present, there are no hardware or biochemical systems allow to assess the severity of post-COVID syndrome in vivo. The hardware of the proposed biotechnical system is based on routine transthoracic electrical impedance rheography, which makes it possible to register the frequency characteristics of the patient's bioimpedance response to controlled stress stimulation, thereby simultaneously fixing the characteristics of his productive heart, the state of the hemomicrocirculatory bed, the efficiency of the gas transport function of his blood, and also reliably assess personal reactivity and adaptive potential. Subsequent mathematical approximation of the obtained biometric data by an original neural network makes it possible to rank the results obtained and automatically generate a program of medical rehabilitation for a particular patient, depending on the severity of his post-COVID syndrome. The study results proved two reliable physiological signs confirming the presence of latent post-COVID complications: a decrease in the base impedance value for light exercise and an increase in the length of the systolic arc of the rheocardiogram.
REVIEW | doi:10.20944/preprints202307.0921.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Covid-19; SARS-CoV-2; epidemiology
Online: 13 July 2023 (10:34:33 CEST)
We provide a summary of various epidemiological parameters related to COVID-19 such as incubation period, serial interval and other parameters. Understanding these parameters is important for developing prevention strategies. SARS-CoV-2 can be transmitted by droplets and close contact, but there is evidence of airborne transmission. Aerosol-generating procedures have been identified as one of the specific risk factors for healthcare workers. Super-spreading events refer to situations where a small number of individuals cause the majority of infections. The basic reproductive number (R0) and the spread parameter (k) are used to characterise the transmissibility of the disease. Estimated values for R0 range from 2 to 3 and the estimated value for k is 0.1.The duration of infectiousness depends on viral load and shedding. Viral load varies according to factors such as clinical spectrum, type of variant and vaccination status. The relationship between viral load and infectivity is not fully understood.With regard to the frequency of symptoms and signs of COVID-19, fever, cough, fatigue and dyspnoea are common. The prevalence of olfactory and gustatory dysfunction (OGD) varies between studies and countries. Age and comorbidities are factors associated with olfactory dysfunction.Estimates of the proportion of asymptomatic patients range from 6% to 96%. Asymptomatic transmission is considered likely and is important for control measures.We reviewed the quantitative semiology of COVID-19 is reported on sensitivity, specificity and likelihood ratios of signs.Finally, we also review risk factors for COVID-19 (including health care workers), co-infections, and epidemiology of variants..
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.
REVIEW | doi:10.20944/preprints202307.0699.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19 infection; pandemic; clinical manifestations; complications; Long-COVID
Online: 11 July 2023 (09:47:37 CEST)
Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2), later renamed Coronavirus Disease 2019 (COVID-19) was first identified in Wuhan, China, in early December 2019. Initially, the China office of the World Health Organization was informed of numerous cases of pneumonia of unidentified etiology in Wuhan, Hubei Province on December 31, 2019. This would subsequently result in a global pandemic with over 76 million confirmed cases of COVID-19 and 6.9 million deaths reported to the WHO. We have analyzed most of the data published since the beginning of the pandemic to compile this comprehensive review of SARS-CoV-2. We look at the core ideas, such as the etiology, epidemiology, pathogenesis, clinical symptoms, diagnostics, histopathologic findings, consequences, therapies, and vaccines. We have also included the long-term effects and myths associated with some therapeutics of COVID-19. This study comprehensively assesses of the SARS-CoV-2 virology, vaccines, medicines, and significant variants identified during the pandemic. Our review article is intended to provide medical practitioners with a better understanding of the fundamental sciences, clinical treatment, and prevention of COVID-19. As of June 2023, this paper contains the most recent data made accessible.
ARTICLE | doi:10.20944/preprints202306.0338.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: COVID-19; ACE2; severity; post-COVID-19 patients; comorbidity.
Online: 5 June 2023 (14:36:06 CEST)
ACE2 impact on the severity of COVID-19 is widely discussed but still controversial. To estimate its role in aspects of the main risk factors and comorbidities, we involved post-COVID-19 patients in Ternopil region (Ukraine). Recruitment period was July 2020 to December 2021. Medical records, treatment modalities and outcomes were recorded and analyzed. Serum human ACE2 protein was measured with Cusabio ELISA kits (Houston, TX, USA). Statistical analysis was performed with SPSS21.0 software (SPSS Inc., Chicago, IL, USA). The level of ACE2 serum protein was significantly higher (p < 0.001) in patients with mild symptoms compared to more severe course of disease, and inversely had changed from 1 to 90 days after recovery. In patients with mild COVID-19, ACE2 level significantly decreased over time, while among critical patients, it increased by 34.1percent. Such results could be explained by ACE2 shedding from tissues into circulation. Loss of the membrane-bound form of the enzyme decreases the virus entry into cells. Our studies did not identify any sex-related ACE2 serum levels correlation. The most common comorbidities were hypertension, cardiovascular diseases, respiratory diseases and diabetes mellitus. All comorbidities except respiratory diseases contribute to the severity of disease and correlate with ACE2 blood serum level.
ARTICLE | doi:10.20944/preprints202009.0321.v2
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: CoViD-19; Mortality; Weekly Cycle; Weekly Mortality Cycle; Pandemic
Online: 17 December 2020 (11:40:15 CET)
Background. The Weekly Mortality Cycle among CoViD-19 patients has been studied.Methods. Mortality data obtained from the 'Worldometer' website were analyzed with a comparison of absolute values, percentages, and p-value. Results. For patients suffering from CoViD-19, the most favorable or the safest days of the week were Sundays and Mondays. Conclusion. The weekly cycle with decreased mortality on Sundays and Mondays is a unique phenomenon observed among victims of CoViD-19. Presumably the decreased mortality on certain days of the week related to the optimized therapeutic protocols used on the "safest days".
BRIEF REPORT | doi:10.20944/preprints202012.0607.v1
Online: 24 December 2020 (08:54:34 CET)
The Saudi government has undertaken rapid and swift actions, such as suspending Omrah and holding international flights. Such affirmative actions enhanced citizens and residents’ confidence in the government officials’ ability to fight the pandemic. However, there are more than 361,178 reported cases of Covid-19 with 6131 deaths as of December 22, 202. As nurses are the largest component of the health care workforce in Saudi Arabia, it is important that they are trained and have the skills and resources to adapt, whether on the frontline of a crisis or in a clinical environment. Nurses play a key function in fulfilling the needs of medical treatment by being the most important part of the health care delivery system.
REVIEW | doi:10.20944/preprints202012.0173.v1
Online: 7 December 2020 (15:36:05 CET)
Culture, gender and religion are closely linked each other’s, profoundly affect the role of each person within the Society, and also affect the ability to access to the health resources. We are now living a worldwide crisis due to the SARS-CoV-2 pandemic. In order to appropriately tackle it, an alliance between science, politics and citizens is needed. In this article, we summarize current evidences of how religions can represent, on one hand, a risk moment for spreading the virus (in relation with overcrowded events), on the other, a precious opportunity to engage people, and in particular minorities, in fighting the pandemic. To win this fight, we need a multicultural approach that takes into account every aspect of human life, and among these religion, which influences so much culture, everyday life and well-being.
REVIEW | doi:10.20944/preprints202006.0102.v1
Subject: Medicine And Pharmacology, Dentistry And Oral Surgery Keywords: COVID-19; COVID pandemic; COVID and dental practise; dental public health; infection control
Online: 7 June 2020 (15:44:33 CEST)
Background: SARS-CoV-2 has resulted in a global pandemic, COVID-19. The disease has spread outrageously from Wuhan, china to rest of the world affecting millions of people. The human transmission is mainly known to occur by aerosols. As almost every dental procedure is associated with aerosol production, oral health care professionals are at a high risk of getting the infection. An attempt has been made to render cohesive practical suggestions for dental professionals amid COVID-19 outbreak. Objectives: The paper aims at providing evidence based information in managing dental patients during this pandemic. Material and Methods: The paper provides a broad overview of predominant findings based on electronic database search regarding COVID-19 outbreak and its effect on dental practice. Conclusion: Dental care should not be neglected due to the pandemic. Thorough knowledge about the disease and its prevention will not only help us in providing care to these patients but will also help in preventing the nosocomial spread of infection.
ARTICLE | doi:10.20944/preprints202007.0129.v1
Online: 7 July 2020 (16:26:57 CEST)
The effect of the COVID-19 pandemic in a developing country like Bangladesh is enormous. A research conducted by South Asian network of Economic Modelling predicted that the pandemic could double the poverty. But it is not that only the socioeconomic condition is dropping in Bangladesh, the impact of COVID-19 pandemic is manifold. The poor condition of Bangladesh's health sector has also been exposed due to the pandemic. People are not getting proper treatment due to lack of isolation beds, oxygen, ICU etc. The health sector of Bangladesh is not much developed and now with this pandemic it has become impossible to provide treatment facility for all the patients. Education sector, which is the backbone of a country,has also been greatly affected by the pandemic. We know that different types of cultural occasions are an inherited tradition of Bangladesh, COVID-19 have not even spared these traditions, all the cultural programes and festivals have been cancelled due to this pandemic.In this paper, our aim is to present the present status of all these sectors.
BRIEF REPORT | doi:10.20944/preprints202003.0436.v1
Subject: Public Health And Healthcare, Health Policy And Services Keywords: COVID-19; corona virus; India
Online: 29 March 2020 (11:31:15 CEST)
Novel Coronavirus infection mediated pandemic started in China in December 2019 and is still killing 1000s of people throughout the world. The second most populous country, India too is fighting against this infectious disease. The country is taking effective measures to curb the pandemic by exerting extensive campaigning on sanitation and strict social distancing measures to quell the explosion of the infection rate. The future of the COVID-19 infections in India still remain unpredictable, so precautionary methods need to be continued until the growth rate of new cases drop below one.
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: patient; COVID-19; asymptomatic contact
Online: 9 March 2020 (10:34:58 CET)
An outbreak caused by coronavirus disease 2019 (COVID-19) occurred in Wuhan City, Hubei Province, China, in December 2019. Up to March 2, 2020, at least 80180 cases have been reported. Most of the patients had a history of visiting Hubei Province or contacting with people who had ever stayed in or passed by Hubei Province, or exposed to symptoms. Some patients got infected only from asymptomatic contacts. This study aimed to report the epidemic features and lab identification of a patient confirmed with COVID-19 infection only from asymptomatic contact.
CASE REPORT | doi:10.20944/preprints202006.0269.v1
Online: 21 June 2020 (11:59:21 CEST)
Understanding the clinical conditions and outcomes of Covid-19 infected patients with immunodeficiency like HIV will be an information for improving management and treatment modalities. It was reported a patient of HIV plus clinical confirmed Covid-19 in this presentation.
ARTICLE | doi:10.20944/preprints202104.0120.v1
Subject: Environmental And Earth Sciences, Environmental Science Keywords: Pre-COVID-19; Post-COVID-19; Secondary Schools; Water Demand; Groundwater; Nigeria
Online: 5 April 2021 (12:22:37 CEST)
The prevalence of corona virus and the novel COVID-19 disease in the entire globe has exacerbated different impact on socioeconomic spectrum in the world, including water use pattern. Thus a research was conducted to examine the comparative use of water during pre- and post-COVID-19 lockdown pattern among post-primary schools in Iwo, Osun State, Nigeria. A survey was conducted among fifteen schools which were randomly selected, but with eight public and seven private schools for the investigation. Both descriptive and inferential statistical techniques were used in data analysis. The results revealed that the major source of water to the schools investigated is ground water which is obtained through hand-dug wells and boreholes. It was further discovered that there was increase in water use during post-COVID-19 lockdown era as a result of the directive by the government that clean water should be provided for hand-washing by all schools regardless of the owner to curtail the spread of COVID-19 disease in the country. One sample t-test also revealed that there was a significant difference in water use at (p<0.01) level. It is recommended that the government and other stakeholders in water sector to ensure that all-time and non-seasonal dependent source of water be provided rather than ground water source which is susceptible to variations in water yields from seasonal variations. This will enable continuous clean water supply, for all purposes, including COVID-19 protocols.
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.
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.
SHORT NOTE | doi:10.20944/preprints202004.0363.v2
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Covid-19; SARS-Cov-2; inflammation; neutrophil
Online: 22 April 2020 (06:23:01 CEST)
Covid-19 is often related to hyperinflammation that drives lung or multi-organ injury. The immunopathological mechanisms that cause excessive inflammation following SARS-Cov-2 infection are under investigation while different approaches to limit hyperinflammation in affected patients are being proposed. Here, a computational protein-protein interaction network approach was used on recently available data to identify possible Covid-19 inflammatory mechanisms and bioactive genes. First, network analysis of putative SARS-Cov-2 cellular receptors and their directly associated proteins, led to the mining of a robust neutrophil response signature and multiple relevant inflammatory genes. Second, analysis of RNA-seq datasets of lung epithelial cells infected with SARS-Cov-2 revealed that infected cells specifically expressed neutrophil-attracting chemokines, further supporting the likely role of neutrophils in Covid-19 inflammation. Third, analysis of RNA-seq datasets of bronchoalveolar lavage fluid from Covid-19 patients, identified neutrophil-specific genes and chemokines. Different immunoregulatory and neutrophil-relevant molecules mined here such as, TNFR, IL8, CXCR1, CXCR2, ADAM10, GPR84, MME-neprilysin, ANPEP and LAP3 are druggable and might be therapeutic targets in efforts to limit SARS-Cov-2 inflammation in severe clinical cases. The role of neutrophils in Covid-19 needs to be studied further.
REVIEW | doi:10.20944/preprints202301.0460.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: COVID-19 mRNA vaccines; Myo-pericarditis and COVID-19 mRNA vaccines; Multisystem-Inflammatory-Syndrome and COVID-19 mRNA vaccines; arrhythmias and COVID-19 mRNA vaccines; Pathogenesis of myocarditis following COVID-19 mRNA vaccines; MIS-A; MIS-C; MIS-V; Myocarditis; COVID-19 mRNA vaccine Adverse Events.
Online: 26 January 2023 (02:50:29 CET)
Each injection of any known vaccine results in a strong expression of pro-inflammatory cytokines. This is the result of the innate immune system activation, without which no adaptive response to the injection of vaccines is possible. COVID-19 mRNA vaccines would not escape this rule. Unfortunately, the degree of inflammation produced by these vaccines is variable, probably depending on the genetic background and previous immune experiences, which through epigenetic modifications, could have made the innate immune system of each individual tolerant or reactive to subsequent immune stimulations.We hypothesize that we can move from a limited pro-inflammatory condition to conditions of increasing expression of pro-inflammatory cytokines that can culminate in multisystem hyperinflammatory syndromes following COVID-19 mRNA vaccines (MIS-V). We have graphically represented this idea in a hypothetical inflammatory pyramid (IP) and we have correlated the time factor to the degree of inflammation produced after the injection of vaccines. Furthermore, we have placed the clinical manifestations within this hypothetical IP, correlating them to the degree of inflammation produced. Surprisingly, excluding the possible presence of an early MIS-V, the time factor and the complexity of clinical manifestations are correlated to the increasing degree of inflammation: symptoms, heart disease and syndromes (MIS-V).
ARTICLE | doi:10.20944/preprints202007.0228.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: Superspreaders; COVID-19; Influencers
Online: 11 July 2020 (04:19:54 CEST)
Since the first confirmed case of COVID-19, information was spreading in large amounts over social media platforms. Information spreading about the COVID-19 pandemic can strongly influence people’s behavior. Therefore, identifying information superspreaders (or influencers) during the COVID-19 pandemic is an im- portant step towards understanding public reactions and information dissemination. In this work, we present an analysis over a large Arabic tweets collected during the COVID-19 pandemic. The presented study con- struct a network from users’ behaviors to identify information superspreaders during the month of March, 2020. We employed both HITS and PageRank algorithms to analyze the influence of information spreading, and compared the ranking of the users. The results show that both HITS and PageRank discovered a similar subset of superspreaders with 40% were found to be verified Twitter accounts.
ARTICLE | doi:10.20944/preprints202003.0308.v1
Online: 20 March 2020 (07:01:44 CET)
Novel coronavirus (COVID-19) can lead to multiple organ injuries such as acute respiratory distress syndrome (ARDS), acute renal injury (AKI) and so on. ACE2 is an important part of the renin-angiotensin system (RAS) and a key protein needed for COVID-19 to invade cells. First of all, we searched the HPA, GTEx and FANTOM5 Databases and found that the expression of ACE2 in kidney tissue was significantly higher than that in lung tissue. Then, by searching the Nephroseq Database, it is further verified that ACE2 is highly expressed in renal tissue and plays a protective role in renal tissue. However, current studies have found that the incidence of AKI caused by COVID-19 is much lower than that of ARDS. Because of this, we further searched the proteins interacting with ACE2 protein through the STING Database and analyzed the expression of tissue protein mRNA in the HPA Database. It was noted that AGTR2 mRNA was highly expressed in lung tissue, but low in kidney tissue, and hard tissue specificity in lung tissue. Through further research, it is found that AGTR2 plays a major role in the development of pulmonary fibrosis. Therefore, AGTR2 may be a key protein in COVID-19 pneumonia, and AGTR2 may be a potential new therapeutic target for the treatment of COVID-19 patients.
ARTICLE | doi:10.20944/preprints202306.1401.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: COVID-19; booster; vaccine uptake
Online: 21 June 2023 (03:53:52 CEST)
Hispanic/Latino communities have suffered a disproportionate burden due to the COVID-19 pandemic. Although Puerto Rico has one of the highest COVID-19 primary series vaccination rates nationwide, this estimate contrasts with the low uptake of booster doses (32.7%). This study aimed to assess health belief correlates of COVID-19 vaccine booster uptake. PR-CEAL recruited 787 participants via an online survey between December 2021 and January 2022. Sociodemographic characteristics and questions framed using the Health Belief Model were assessed. Analyses included adjusted Poisson regression models to estimate prevalence ratios (PR) of booster refusal. Overall, 22% of participants planned (10%) or refused (12%) the vaccine booster. Participants with lower income [PR=1.92; 95%CI=1.30, 2.84], in disagreement with vaccine benefits [PR=4.16; 95%CI=3.06, 5.64], and in agreement with booster concerns [PR=2.93; 95%CI=2.12, 4.04], efficacy [PR=2.76; 95%CI=2.00, 3.82], and safety [PR=2.97; 95%CI=2.15, 4.08] were significantly more likely to refuse the booster. Booster vaccination refusal was associated with lower perceived vaccine benefits and higher barriers among adults in Puerto Rico. Results informed CEAL team intervention strategies for public health campaigns to increase booster vaccine uptake.
ARTICLE | doi:10.20944/preprints202005.0151.v3
Subject: Computer Science And Mathematics, Information Systems Keywords: deep learning; CNN; DenseNet; COVID-19; transfer learning
Online: 18 February 2022 (14:44:55 CET)
COVID-19 has a severe risk of spreading rapidly, the quick identification of which is essential. In this regard, chest radiology images have proven to be a practical screening approach for COVID-19 aﬀected patients. This study proposes a deep learning-based approach using Densenet-121 to detect COVID-19 patients eﬀectively. We have trained and tested our model on the COVIDx dataset and performed both 2-class and 3-class classification, achieving 96.49% and 93.71% accuracy, respectively. By successfully utilizing transfer learning, we achieve comparable performance to the state-of-the-art method while using 15x fewer model parameters. Moreover, we performed an interpretability analysis using Grad-CAM to highlight the most significant image regions at test time. Finally, we developed a website that takes chest radiology images as input and detects the presence of COVID-19 or pneumonia and a heatmap highlighting the infected regions. Source code for reproducing results and model weights are available.
ARTICLE | doi:10.20944/preprints202211.0480.v1
Subject: Public Health And Healthcare, Health Policy And Services Keywords: COVID-19 death rates; COVID-19 vaccines; hydroxychloroquine; ivermectin; rates of COVID-19 testing; containment measures; social distancing; travel restriction,
Online: 25 November 2022 (10:16:41 CET)
Objectives to assess COVID-19 mortality rates per country population. To determine what if any independent country-specific variables from 9 different databases were correlated. Design population based retrospective cohort study. Setting analysis of global COVID-19 treatment and containment strategies using data from 9 worldwide websites. Participants 108 countries worldwide. Interventions none. Main Outcome Measures were COVID-19 death rates per country population analyzed by univariate and multivariate analysis. The main outcome parameters were to determine if there are any correlations between the percentage of countrywide COVID-19 deaths/population by the countries’ percent vaccinated. Secondary outcome measures include the effect of other independent variables on COVID-19 death rates per country population including: health expenditures per capita, annual income per capita, COVID-19 tests per 1000 people, stringency index (a measure of each countries containment strategies), hydroxychloroquine score (a measure of each countries use), ivermectin score (a measure of each countries use), hypertension, obesity, diabetes, and specific countries and geographic locations. Results COVID-19 vaccination rates ranged from 0-99% in 108 countries. Univariate analysis demonstrates the following independent variables to correlate with COVID-19 deaths/population (correlation coefficient, p value): countrywide COVID-19 vaccination rates (+0.2936, p=0.002); healthcare costs per capita (+0.3212, p=0.0007), income per capita (+0.3051, p=0.0013), COVID-19 tests per 1000 population (+0.6981 p=0.0307); stringency index (+0.3098, p=0.0011); hydroxychloroquine index (-0.1337, p=0.0678); and ivermectin index (-0.1383, p=0.1535). Conclusions Increasing rates of COVID-19 vaccination are associated with increase COVID-19 death rates per country population (p=0.002). Other variables associated include healthcare costs per capita (+0.3212, p=0.0007), income per capita (+0.3051, p=0.0013), COVID-19 tests per 1000 population (+0.6981 p=0.0307); and stringency index (+0.3098, p=0.0011).
REVIEW | doi:10.20944/preprints202308.2002.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: COVID-19; SARS-CoV-2; hypertension; blood pressure; endothelial dysfunction; long-covid; post covid
Online: 30 August 2023 (08:59:30 CEST)
Hypertension is one of the most common and significant cardiovascular risk factor. With the emergence of COVID-19, concerns have arisen about its potential to exacerbate cardiovascular morbidity and mortality. Several theories have emerged linking hypertension with COVID-19. However, the relationship between SARS-CoV-2 infection and long-term risk of hypertension remains insufficiently explored. Therefore, our study aimed to investigate the impact of COVID-19 infection on blood pressure and long-term risk of hypertension developing. A comprehensive search was conducted in the PubMed and SCOPUS databases up to 10th August 2023 for relevant papers. The analysis included 35 eligible articles. The majority of the latest studies pointed to increase BP after COVID-19 infection. However, several observations contradicted the influence of SARS-CoV-2 on the hypertension development or suggesting a transient effect. The possible role of the loss of angiotensin-converting enzyme 2, cytokine storm, increased sympathetic activity, and endothelial dysfunction were considered. On the other hand, BP changes following COVID-19 could be a consequence of lifestyle changes, which often accompanied COVID-19 infection. Our findings highlight the urgent need for comprehensive research on the COVID-19 and hypertension link. These insights are crucial for implementing effective prevention and management strategies for individuals with the history of COVID-19 infection.
ARTICLE | doi:10.20944/preprints202005.0161.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: COVID 19; mortality; Iran; pandemic
Online: 9 May 2020 (10:08:24 CEST)
Background: Corona virus disease was first reported in Wuhan City, Hubei province, China. Soon the corona virus disease has spread to many countries. World health organization has described the situation as Pandemic. By 12 March 2020, corona virus disease has affected 125 countries around the world. Corona virus was first confirmed in Iran on 19 February 2020. Objective: The aim of writing this small article is to determine the mortality rate of corona virus disease in different cities of Iran. This article will give readers an idea of different ways to control spread of corona virus disease in Iran. Methods: Author has collected the data of daily confirmed cases from different diagnostic centers and hospitals across the country from 19 February 2020 to 1 April 2020. Results: Mortality rate of corona virus disease is roughly 4%. Conclusions: Mortality rate could rise if COVID 19 infection is not controlled.
REVIEW | doi:10.20944/preprints202004.0128.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: COVID-19; Cancer Survivors; Cardiovascular
Online: 8 April 2020 (11:49:56 CEST)
Coronavirus disease 2019 (COVID-19) has been declared a global pandemic by the World Health Organization on March 11, 2020. COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-Cov-2). Although primarily a respiratory disease, cardiovascular complications of COVID-19 have been increasingly recognized. In addition, higher fatality has been reported in COVID-19 patients with underlying cardiovascular diseases. Cancer survivors have a considerably increased risk for premature cardiovascular diseases, mainly due to cardiotoxic cancer treatments. Therefore, it is foreseeable that cancer survivors will be more vulnerable to cardiovascular complications caused by COVID-19. In this review, three scenarios for increased cardiovascular complications of COVID-19 in cancer patients are proposed. In the first scenario, cardiotoxic cancer treatment and COVID-19 synergize to exacerbate direct myocardial damage. In the second scenario, cardiotoxic cancer treatment leads to a reduced cardiac reserve in cancer survivors, making them more vulnerable to COVID-19 in a “two-hit” model. The third scenario suggests that several shared risk factors may aggravate cardiovascular complications caused by both cancer treatment and COVID-19. Taken together, cancer survivors may be more vulnerable to cardiovascular complications when challenged by the COVID-19, and special cardiovascular care should be given to these patients.
HYPOTHESIS | doi:10.20944/preprints202004.0013.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; azithromycin; bee
Online: 2 April 2020 (11:06:47 CEST)
The pharmacology of azithromycin, and the actions of certain bee products, suggest the possibility of overlap with the pathophysiology of COVID-19 at several points in the disease process. First, intercellular epithelial tight junctions of the respiratory tract serve as a critical barrier to invaders. Pathophysiological factors capable of disrupting this epithelial barrier include viral virulence factors such as those observed for other coronaviruses; virulence factors derived from potentially synergistic pathogens such as Candida albicans and Porphyramonas gingivalis; and imbalances in the host inflammatory response. Azithromycin, and to a lesser extent, certain bee products, appear to have actions that oppose such processes. Second, the matrikine PGP or its derivatives may contribute to risk in individuals at high risk for serious COVID-19 infection, especially during reactivation; but azithromycin is capable of modulating PGP in some contexts. Third, the most serious COVID-19 infections are associated with massive upregulation of inflammatory cytokines such as IL-6, TNF alpha, and other inflammatory cytokines. The anti inflammatory actions of azithromycin and bee derived products such as melittin are potentially capable of modulating these processes, as well. Azithromycin is already in current use as a treatment for COVID-19; however, it's utility as a protector of epithelial barrier function would be most likely to be realized in prophylactic context rather than in a treatment context. Similarly, since the anti inflammatory effects of bee products take time, their effectiveness of melittin and other bee products would be expected to be maximized in a prophylactic context. In the context of the current pandemic, prophylaxis with azithromycin, bee products, or both, might be warranted for individuals at high risk for serious COVID-19 infection.
ARTICLE | doi:10.20944/preprints202107.0620.v1
Subject: Biology And Life Sciences, Horticulture Keywords: COVID-19, Gardening Industry, COVID-19, gardening industry, horticulture, nursery and landscape, business survey
Online: 28 July 2021 (10:26:00 CEST)
The COVID-19 pandemic has forced businesses to alter the way they operate. This includes, but may not be limited to, changing hours of operation, working with limited staff, and restricting customer access indoors. This could result in several challenges for businesses. In this study, we evaluate the impacts of COVID-19 on the horticultural industry and identify the challenges for businesses). Based on our research findings, the major challenges faced by businesses were not having enough employees and inventory to keep up with consumer demand during COVID-19. We also evaluate the effect of the pandemic on the sales of different plants, gardening products/services, and the overall revenues of businesses. For different types of plants included in the survey, landscape herbaceous flowers, landscape shrubs, and landscape trees showed the most significant increase in sales. In addition, for different gardening products/services, container plants, small plants, and soil & compost showed the most significant increase in sales. 64% of the businesses indicated higher overall sales compared to same season previous year. Over 46% of the businesses reported increased sales in 2020 under COVID-19. These findings imply a greater demand potential for plants and gardening products/services from consumers, in light of this pandemic.
ARTICLE | doi:10.20944/preprints202009.0367.v1
Subject: Computer Science And Mathematics, Mathematics Keywords: lattice model; computer simulation; COVID-19
Online: 17 September 2020 (03:04:02 CEST)
Susceptible, infective, recovered, and hospitalized/isolated individuals are placed on the cells of a nxn square lattice, where each cell is occupied by a single individual or is vacant. At discrete time units (typically one day each) all susceptibles and infectives execute a random movement and when a coincidence of the two types occurs the susceptible is converted to infective status according to some probability. Infectives are labelled by the number of days since originally infected. At each time increment the age label of the infectives is increased by one unit. When the label reaches a number like 15 or 20 days the susceptibles recover with some probability or become isolated/hospitalized. Upon reaching some age the latter types either recover or die. Probabilities for the movements and conversions from one status to another are implemented by random numbergeneration. Simulations were carried out to investigate the effect of several probability and age parameters, the size of population (proportional to nxn) and density (related to fraction of occupied cells), and the size of the movements. Mid-term gradual conversion of susceptibles to isolated was explored as intervention policy.
CONCEPT PAPER | doi:10.20944/preprints202004.0432.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: SARS CoV-2; COVID-19; Nitazoxanide; Azithromycin; Interferons
Online: 24 April 2020 (09:24:23 CEST)
Azithromycin has been shown to have a clinical efficacy against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2); ivermectin has also demonstrated a remarkable experimental efficacy with a potential to be used for Coronavirus disease 2019 (COVID-19). Further, BCG vaccination is being considered for clinical trials aiming to test its potential for lowering COVID-19 morbidity and mortality. This article illustrates some structural and functional relationships that may gather these drugs and the author, basing on a combined pathophysiological and pharmacological approach, recommends the FDA-approved antidiarrhea drug; nitazoxanide, which has been previously suggested but unfortunately ignored, to be tested in combination with azithromycin for their potential activity against SARS CoV-2 soonest. The author recommends testing their combined administration as early during the clinical course of COVID-19 as possible. Further, basing on the same represented concept, the author recommends more trials for interferons to be tested against SARS CoV-2 especially in severe and critical cases.
ARTICLE | doi:10.20944/preprints202310.2035.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; body mass index; vaccination; evolution
Online: 31 October 2023 (08:28:08 CET)
Body mass index has been studied as one of the factors that negatively influences COVID-19. In this work we intend to analyze this influence. A representative sample of the population of Beira Interior was used (around 2%), to which immunity research and a socio-demographic survey were carried out. It was found that obesity influences the vaccination rate, and all other variables analyzed were not influenced by the body mass index.
ARTICLE | doi:10.20944/preprints202105.0711.v1
Subject: Engineering, Electrical And Electronic Engineering Keywords: pneumonia; Resnet; residual; PEPX-Resnet; COVID-19
Online: 31 May 2021 (08:29:00 CEST)
Pneumonia is a leading cause of death worldwide, and one of the most significant approaches to diagnose pneumonia is Chest X-ray (CXR) since it was used in clinical scenes. Convolutional neural networks (CNNs) have been widely used in computer vision community. Along with the development of CNNs, we want to make use of CNNs to recognize CXR of people who get pneumonia and make classification. It is important, especially during epidemic period. In this paper, we present a new type of residual learning framework, PEPX-Resnet, which makes use of a type of lightweight residual, and apply this network to CXR dataset. The result shows that PEPX-Resnet is easier to optimize and can have better results, especially for COVID-19 cases. PEPX-Resnet could reach higher accuracy, f1 score and some other evaluations for CXR dataset.
ARTICLE | doi:10.20944/preprints202106.0152.v1
Online: 7 June 2021 (08:29:46 CEST)
Fighting against the COVID-19 pandemic caused by the SARS-CoV-2 virus is one of the most critical challenges facing the global health system today. The possibility to identify the group of persons in the cohort of people under 50 years old, who are sensitive to the COVID-disease by non-invasive methods, is a very perspective approach for estimating the epidemiological state of the human population. The study aimed to identify the features of people's faces with COVID-19 that the most correlate with disease severity could serve as one of these approaches. For this aim, 525 photos of patients' faces with different outcomes of COVID-19 disease were analyzed using the Dlib face recognition convolutional neural network pre-trained for face recognition. Face descriptor vectors were obtained using the convolutional neural network. Facial features were found that predict a person's sensitivity to the SARS-CoV-2 virus (disease severity), and the contribution of each of the features to the risk of developing a severe form of COVID in a person was found. The accuracy of the binary classification of the individual severity of the COVID-19 course using the k-nearest neighbors algorithm on the test dataset was accuracy - 84%, AUC - 0.90.
Online: 17 May 2021 (17:06:31 CEST)
The most severe threat that the Covid-19 pandemic poses to the global economy is the need to choose between human lives and livelihoods. Bangladesh must assess the implications of such impacts on Bangladesh's macro-financial scenario to maintain the economy's current high growth trajectory. The paper outlines the major Covid-19 shock wave transmission channels to the four major sectors of the Bangladesh economy. Authorities around the world have taken every precaution possible to halt the spread of the pandemic. An aggregate transmission framework that includes these four sectors is required to contain the impact of Covid-19 can propagate through these sectors and eventually impact macro-financial stability.
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.
SHORT NOTE | doi:10.20944/preprints202007.0526.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; Unreported COVID-19 Death; Provisional COVID-19 Death; Death Reporting Discrepancy; Bangladesh
Online: 22 July 2020 (11:32:05 CEST)
Objective: We aim to assess the reporting discrepancy and the difference between confirmed and unreported COVID-19-like death counts.Study Design: The study is based on time-series data.Methods: We used publicly available data to explore the differences between confirmed death counts and deaths with Codiv-19 symptoms between March 8, 2020, and July 11, 2020, in Bangladesh.Results: During the week ending May 9, 2020, the unreported COVID-19-like death count was higher than the confirmed COVID-19 death count; however, it was lower in the following weeks. On average, unreported COVID-19-like death counts were similar to the confirmed COVID-19 death counts during the same period. However, the reporting authority neither considers these deaths nor adjusts for potential seasonal influenza or other related deaths, which might produce incomplete COVID-19 data and respective mortality rates. Conclusions: Documenting unreported deaths with COVID-19 symptoms needs to be included in provisional death counts because it is essential to estimate a robust COVID-19 mortality rate and to offer data-driven pandemic response strategies. An urgent initiative is needed to prepare an acceptable guideline for COVID-19 death reporting.
REVIEW | doi:10.20944/preprints202311.1317.v1
Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; long-COVID; post-COVID; cytokine storm; ACE-2
Online: 21 November 2023 (10:45:28 CET)
The coronavirus disease 2019 (COVID-19), instigated by the zoonotic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), rapidly transformed from an outbreak in Wuhan, China, into a widespread global pandemic. A significant post-infection condition, known as ‘long- COVID’, emerges in a substantial subset of patients, manifesting with a constellation of over 200 reported symptoms that span multiple organ systems. This condition, also known as 'post-acute sequelae of SARS-CoV-2 infection' (PASC), presents a perplexing clinical picture with far-reaching implications, often persisting long after the acute phase. While initial research focused on the immediate pulmonary impact of the virus, the recognition of COVID-19 as a multiorgan disruptor has unveiled a gamut of protracted and severe health issues. This review provides a summary of the primary effects of long COVID on the cardiovascular, nervous, and respiratory systems. It also delves into the mechanisms underlying these impacts and underscores the critical need for a comprehensive understanding of long COVID's pathogenesis.
CONCEPT PAPER | doi:10.20944/preprints202005.0298.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Covid 19; coronavirus; pre-hotspots
Online: 18 May 2020 (08:01:52 CEST)
COVID-19 Pandemic management has become the top priority of Government Institutions globally, which is justifiable seeing the high mortality of the disease. In India, Lockdowns by National, State and Local level administrations have greatly reduced the spread of the SARS COV-2 Virus. Some areas with a greater proportion of COVID-19 patients have been declared hotspots with increased restrictions on public activities through law enforcement. But quite often delay in identification of these hotspots leads to community transmission of the Virus thus aggravating the problem. A method to identify the areas which are at risk of becoming the next hotspot for the disease is the need of the hour. In this Research document we will find the probable risk factors and make an appropriate scale to measure the vulnerability of an area, identified by its Postal code. To help with this a Pan India survey by the title of “Survey on General Indian population on the level of preparedness for COVID-19 pandemic” was launched and received around 1250 submissions, with the acquired data we will evaluate the risk factors and make appropriate scale to identify ‘pre-hotspots’.
ARTICLE | doi:10.20944/preprints202206.0024.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: second COVID-19 booster; vaccination; COVID-19; willingness; predictors; general population
Online: 2 June 2022 (04:07:07 CEST)
Given the concerns of waning immunity from the primary COVID-19 vaccines and the first booster dose, we conducted an on-line cross-sectional study in May 2022 to investigate willingness to receive a second COVID-19 booster dose or a new COVID-19 vaccine and its associated factors. Overall, 22.7% of participants were willing to be vaccinated, 39.3% were unsure, but tend to be willing, 25.8% were unsure, 4.9% were unsure, but tend to be unwilling, and 7.4% were unwilling to be vaccinated. The main reasons against accepting a second COVID‐19 booster dose or a new COVID-19 vaccine COVID-19 dose included concerns about the side effects, the opinion that further vaccination is unnecessary, and effectiveness uncertainties. Males, younger individuals, participants without a previous COVID-19 diagnosis, and those with good/very good self-perceived physical health were significantly more frequently willing to receive a second COVID‐19 booster dose or a new COVID-19 vaccine. Also, increased fear of the COVID-19, increased trust in COVID-19 vaccination and decreased fear of a second booster dose or a new COVID-19 vaccine were associated with increased willingness. Our results show some hesitancy and unwillingness toward further COVID-19 vaccination and indicate that fear of COVID-19 and trust in COVID-19 vaccination affect public opinion
ARTICLE | doi:10.20944/preprints202205.0248.v1
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: COVID-19; sentiment analysis; deep learning
Online: 19 May 2022 (03:42:40 CEST)
The Covid-19 also known as the Coronavirus is a viral disease from the SARS-CoV-2 family of virus, as at December 2019 the first case of this virus infection was identified at Wuhan, China, this seemingly isolated case soon became a global pandemic, whose effect was felt globally which also had colossal effects on both health, economic and politics . As at the time of this research about 4.5 million people have died of the Coronavirus and over 215 million people already infected by it. This pandemic stood out not just for its scale but for how social media was a major contribution to its spread as well as to curbing it. The power of social media was used to spread misinformation as well as to spread awareness on the subject, with both having massive impact on the people. In this paper we will be running a sentimental analysis on twitter under the keyword “Covid-19 and Coronavirus”, twitter is a powerful social media tool that is known for its ability to keep trends in the form of tweets, we will be drawing correlations between the peaks of tweet with the peak of infection. We will also be analyzing to know what the impact of these tweets are having on the rate of the infection and vice versa. We will also be analyzing what people are tweeting most about, what are the talking points, comparing both real time and past tweets with real time infection and death rates using deep different learning methods to access what information can be derived from it.
ARTICLE | doi:10.20944/preprints202004.0281.v2
Online: 7 September 2020 (04:15:59 CEST)
Spike (S) protein of Coronaviruses help in receptor attachment and virus entry into the host cells. While S protein is required for virus entry, it is also important as an immunogen as it is the most accessible part of the virus architecture. S protein form knob like structures (viral spikes) protruding outwards in the form of homotrimers containing an S1 and S2 as monomers. Mutations in structural proteins of virus play crucial role in determining virulence and also in many instances influencing emergence of antibody escape variants and cellular tropism. In this paper we have performed in depth analyses of spike protein sequences from various parts of the world and tried to correlate the data with possible functional relevance of such mutations.
REVIEW | doi:10.20944/preprints202301.0195.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; COVID-19 vaccines; capillary leak syndrome
Online: 11 January 2023 (09:41:36 CET)
Systemic capillary leak syndrome (SCLS) is an uncommon, potentially life-threatening disorder defined as recurrent attacks of pseudo-shock. This syndrome occurs due to the disruption of endothelial cells, which leads to increased vascular permeability, causing intravascular fluid to leak into the extravascular space and albumin to be retained in the interstitial space. SCLS can lead to hypovolemia, peripheral hypoperfusion, and acute renal insufficiency. The syndrome is presented with fever, generalized edema, pleural effusions, dyspnea, hypovolemia, hemoconcentration, prerenal azotemia, shock, and syncope. After ruling out other causes of hypovolemic shock, the diagnosis of SCLS can be considered on the presence of the classical triad of hypotension, hemoconcentration, and hypoalbuminemia. Eliminating the precipitating factors is the cornerstone of SCLS management. It is advisable to be very cautious and weigh the risks and benefits of vaccination of people with a history of this condition. This review will discuss and compare different aspects of SLCS after SARS-CoV-2 infection and COVID-19 vaccination.
REVIEW | doi:10.20944/preprints202303.0097.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Bivalent COVID-19 vaccine; COVID-19 vaccination booster; COVID-19; Omicron; SARS-CoV-2
Online: 6 March 2023 (07:00:00 CET)
The severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) Omicron variant of concern has been the dominant cause of worldwide COVID-19 cases since 2022. All the Omicron sublineage viruses have demonstrated high transmissibility and an ability to escape vaccine-induced immunity. While first-generation vaccines, including monovalent vaccines, continue to provide protection against severe disease, hospitalization and mortality, their efficacy against Omicron sub variants remains sparse. These vaccines have also been associated with rapidly waning protection against primary COVID-19 and COVID-19 reinfections conferred by evolving Omicron sublineages.. This led to the development and deployment of updated vaccines and the introduction of the bivalent booster. Through this review, we highlight the brief journey of the variants of concern leading to the dominance of Omicron and the effectiveness of the key vaccines against these variants, including the updated (bivalent) boosters.
COMMUNICATION | doi:10.20944/preprints202005.0132.v1
Subject: Biology And Life Sciences, Virology Keywords: risk perception; coronavirus; covid-19; risk communication; global health
Online: 7 May 2020 (15:12:32 CEST)
The ongoing COVID-19 pandemic is shaking the foundations of public health governance all over the world. Researchers are challenged by informing and supporting authorities on acquired knowledge and practical implications. This commentary applies established theories of risk perception research to COVID-19 and reflects on the role of risk perceptions in these unprecedented times. Moreover, it calls for utilizing the knowledge on risk perception to improve health risk communication, build trust and contribute to a collaborating governance.
ARTICLE | doi:10.20944/preprints202307.0240.v1
Subject: Social Sciences, Psychology Keywords: Locomotion; regulatory modes; resilience; COVID-19; Covid-19 anxiety.
Online: 4 July 2023 (13:48:34 CEST)
The COVID-19 pandemic has exerted a significant impact on mental health globally. The uncertainty, fear, and stress associated with this crisis have contributed to a heightened prevalence of anxiety, depression, and various other mental health disorders. In this scenario, the present study aimed at investigating the relationship between locomotion regulatory mode, resilience, and COVID-19 anxiety. It is worth noting that previous extensive research has established a significant correlation between high levels of locomotion and diverse positive psychological conditions, such as optimism, reduced hopelessness, and positive affect. A total of 243 participants completed measures of locomotion regulatory mode, resilience, and COVID-19 anxiety. In line with our hypotheses, individuals' locomotion regulatory mode was negatively, although non significatively, associated with COVID-19 anxiety. Furthermore, resilience was found to mediate the relationship between locomotion regulatory mode and COVID-19 anxiety, indicating that individuals displaying high locomotion may be better equipped to cope with the stress and uncertainty of the COVID-19 pandemic due to their greater levels of resilience. Taken together, these findings highlight the importance of considering both locomotion and resilience in managing anxiety related to COVID-19 and suggest that interventions aimed at enhancing resilience may be beneficial particularly for individuals with low locomotion regulatory mode.
ARTICLE | doi:10.20944/preprints202306.0832.v1
Subject: Social Sciences, Education Keywords: universities; international students; Covid-19; Scotland
Online: 12 June 2023 (12:51:02 CEST)
A sense of crisis pervaded the university sector as Covid-19 spread, with worries about possible significant loss of income and students in its wake. This analysis examines several years of financial and student data through the pandemic (2020-2022) for Scottish universities. It shows that far from losing money or students, universities in Scotland gained both, and accelerated income growth during Covid. The University of Glasgow stands out not only among Scottish universities but also in the Russell Group in increasing income and student numbers faster than other institutions, becoming over the course of the pandemic, the third largest university in the UK and the largest in Scotland by student numbers. The driver of income growth for all Scottish universities is expanded intakes of international students, who primarily come from Asia and Africa. Across 2021 and 2022, Scottish Universities earned income totalling £1.7 billion from international tuition fee alone. Universities across the UK are increasingly dependent on yet continuing to actively pursue international tuition fees as a primary source of income. This paper documents the situation for Scotland, considering the implications of this growth trajectory in terms of: concentrating financial dependence on a single income source; rising casualisation of staff as a means of managing higher student numbers; impacts on learning and working conditions as students numbers rapidly expand; a shifting composition of students in higher education. It concludes with reflections on: a blurring boundary between the practices and values of profit-making companies and those of the charitable university sector; the ethical and colonial implications in international student recruitment and targeting of ‘new markets’ in the Global South; and the implications of all this for the shape, health and purpose of the university sector in Scotland.