Preprints on COVID-19 and SARS-CoV-2
Reminder: Please bear in mind that these are early stage research which have not gone through a rigorous peer review process, and should not be regarded as conclusive clinical guidance or be reported in news media as established fact.
ARTICLE | doi:10.20944/preprints202302.0126.v1
Subject: Life Sciences, Molecular Biology Keywords: Omicron; SARS-CoV-2; piRNAs; coronavirus genome; translation; replication
Online: 7 February 2023 (08:54:49 CET)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused the COVID-19 pandemic still able to infect the population in many countries. The Omicron strain is the most mutated variant of SARS-CoV-2. The high transmissibility of the strain and the ability to evade immunity require a priority study of its properties in order to quickly create effective means of preventing it. The present work is devoted to the study of in silico interaction of piRNAs with the genome of the SARS-CoV-2 (gRNA) in order to identify endogenous piRNAs and propose synthetic piRNAs with high antiviral activity for drug development. The studies were carried out using proven bioinformatic methods of interaction of the entire SARS-CoV-2 genome with more than eight million piRNAs. Binding sites (BSs) of piRNAs in the 5'UTR were located with overlapping nucleotide sequences called clusters of BSs. Several clusters of BSs were found in the nsp3, nsp7, RNA-dependent RNA polymerase, endoRNAse, S surface glycoprotein, ORF7a and nucleocapsid. 16 synthetic piRNAs have been proposed that interact with gRNA with free binding energy from -170 kJ/mol to -175 kJ/mol, which can be used to create drugs that suppress the reproduction of SARS-CoV-2.
ARTICLE | doi:10.20944/preprints202302.0108.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: perceived stress; social support; health anxitety; coping; lockdown; COVID-19; international stu-dents; domestic students
Online: 7 February 2023 (02:22:04 CET)
Background: Our study aimed to examine how modulating variables such as social support, health anxiety, coping, gender, being separated from home, and lockdown can modify or amplify the effect of perceived stress as a starting variable in the point of view of the output variable, dissociation. Methods: A cross-sectional survey was conducted in online form at two points in time: the beginning and the later stage of the COVID-19 pandemic. Results: We received a total of 1711 responses. Perceived stress moderately correlated with dissociation in both International and Hungarian samples. Health anxiety showed a strong direct and indirect correlation with dissociation. Regarding social support, the support of family significantly decreased the dissociative experiences in the Hungarian sample through mediating the stress and directly as well. In the international sample, the goal-oriented coping strategy had a strong decreasing effect on all dissociation scales in the first measurement, through mediation of perceived stress. As to the Hungarian sample, positive thinking was found to decrease dissociation through decreasing perceived stress. Conclusion: The cause and effect relationship between stress and dissociation may be tinctured by health anxiety, coping and social support, influencing dissociacion directly and indirectly. Social support, mainly support of the family and problem-focused coping strategies seem to alleviate dissociation-provoking effect of stress.
REVIEW | doi:10.20944/preprints202212.0582.v2
Subject: Life Sciences, Immunology Keywords: COVID-19; copy number variation (CNV); virome; microbiome; endoretroviral genome (ERV); geographic disparity
Online: 6 February 2023 (11:15:27 CET)
Coronavirus disease 2019 (COVID-19), the emissary behind the worst global pandemic of the 21st century, is primarily a respiratory disease-causing virus called SARS-CoV-2 which is responsible for millions of new cases (incidence) and deaths (mortalities), worldwide. Many factors have played a role in the differential morbidity and mortality experienced by nations and ethnicities against SARS-CoV-2, such as the quality of primary medical health facilities or enabling economies. Nevertheless, the most important variable, i.e., the subsequent ability of individuals to be immunologically sensitive or resistant to the infection, was not properly discussed before. Therefore, an astounding issue arose when some developed countries experienced higher morbidity and mortality, compared with their relatively underdeveloped counterparts, despite having excellent medical health facilities. Hence this investigative review attempts to analyze the issue from an angle of previously undiscussed genetic, epigenetic, and molecular immune resistance mechanisms in correlation with the pathophysiology of SARS-CoV-2 and varied ethnicity-based immunological responses against it. The biological factors discussed here include the overall landscape of human microbiota, endogenous retroviral genes spliced into the human genome, copy number variation, and how they could modulate the innate and adaptive immune systems, which put a particular ethnic genetic architecture at a higher risk of SARS-CoV-2 infection than others. Considering an array of these factors in their entirety may help explain the geographic disparity of disease incidence, severity, and subsequent mortality associated with the disease while at the same time encouraging scientists to design new experimental approaches to investigation.
ARTICLE | doi:10.20944/preprints202302.0095.v1
Subject: Social Sciences, Education Studies Keywords: Mobile learning; mobile pedagogy, EdTech; digital immigrant; digital literacy
Online: 6 February 2023 (09:46:03 CET)
The sudden outbreak of the COVID-19 pandemic challenged education systems worldwide to quickly pivot their teaching-learning processes from in-person to virtual modes in order to control the spread of the virus. In a short period of time, teachers were forced to adopt new remote teaching methods to ensure the continuation of education. This paper examines how teachers in Pakistan leveraged mobile technology as an alternative teaching strategy to provide access to education during these unprecedented times. Through in-depth individual interviews with selected teachers, the study explores the potential of mobile technology to transform traditional teaching methods into interactive learning environments. The findings highlight the importance of embracing new pedagogical possibilities offered by mobile technology and the need for effective teacher professional development in the post-pandemic era. The study offers valuable insights into how mobile technology can be effectively utilized in education, even in the most challenging circumstances.
REVIEW | doi:10.20944/preprints202302.0085.v1
Subject: Medicine & Pharmacology, Other Keywords: SARS-CoV-2; COVID-19; Vaccines; Myocarditis; Pericarditis
Online: 6 February 2023 (07:51:04 CET)
Cardiac complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been well-identified since the beginning of the current coronavirus disease 2019 (COVID-19) pandemic. Such conditions can occur of various etiologies, such as respiratory failure and hypoxemia, direct cardiac tissue damage due to viral replication, indirect myocarditis as systemic inflammation, and the interaction of different medications. Recently, with the start of the COVID-19 vaccination programs, COVID-19 vaccine-associated cardiac adverse events (AEs) have emerged and are increasingly being reported. Although these AEs are usually mild and self-limited, they can sometimes cause severe, catastrophic outcomes. This review compares the pathophysiology, diagnosis, and treatment of the de novo SARS-CoV-2 infection-related and COVID-19 vaccine-related myocarditis and pericarditis.
ARTICLE | doi:10.20944/preprints202302.0078.v1
Subject: Mathematics & Computer Science, Information Technology & Data Management Keywords: COVID-19; Particle Filtering; Machine Learning; Epidemiologic Modeling; Compartmental Model; Projection and Intervention
Online: 6 February 2023 (02:55:38 CET)
COVID-19 transmission models have conferred great value in informing public health understanding, planning, and response. However, the pandemic also demonstrated the infeasibility of basing public health decision-making on transmission models with pre-set assumptions. No matter how favourably evidenced when built, a model with fixed assumptions is challenged by numerous factors that are difficult to predict. Ongoing planning associated with rolling back and re-instituting measures, initiating surge planning, and issuing public health advisories can benefit from approaches that allow state estimates for transmission models to be continuously updated in light of unfolding time series. A model being continuously regrounded by empirical data in this way can provide a consistent, integrated depiction of the evolving underlying epidemiology and acute care demand, offer the ability to project forward such a depiction in a fashion suitable for triggering the deployment of acute care surge capacity or public health measures, support quantative evaluation of tradeoffs associated with prospective interventions in light of the latest estimates of the underlying epidemiology. We describe here the design, implementation and multi-year daily use for public health and clinical support decision-making of a particle filtered COVID-19 compartmental model, which served Canadian federal and provincial governments via regular reporting starting in June 2020. The use of the Bayesian Sequential Monte Carlo algorithm of Particle Filtering allows the model to be re-grounded daily and adapt to new trends within daily incoming data – including test volumes and positivity rates, endogenous and travel-related cases, hospital census and admissions flows, daily counts dose-specific vaccinations administered, measured concentration of SARS-CoV-2 in wastewater, and mortality. Important model outputs include estimates (via sampling) of the count of undiagnosed infectives, the count of individuals at different stages of the natural history of frankly and pauci-symptomatic infection, the current force of infection, effective reproductive number, and current and cumulative infection prevalence. Following a brief description of model design, we describe how the machine learning algorithm of particle filtering is used to continually reground estimates of dynamic model state, support probabilistic model projection of epidemiology and health system capacity utilization and service demand and probabilistically evaluate trade-offs between potential intervention scenarios. We further note aspects of model use in practice as an effective reporting tool in a manner that is parameterized by jurisdiction, including support of a scripting pipeline that permits a fully automated reporting pipeline other than security-restricted new data retrieval, including automated model deployment, data validity checks, and automatic post-scenario scripting and reporting. As demonstrated by this multi-year deployment of Bayesian machine learning algorithm of particle filtering to provide industrial-strength reporting to inform public health decision making across Canada, such methods offer strong support for evidence-based public health decision making informed by ever-current articulated transmission models whose probabilistic state and parameter estimates are continually regrounded by diverse data streams.
ARTICLE | doi:10.20944/preprints202302.0060.v1
Subject: Life Sciences, Virology Keywords: vaccination; acceptance; Covid-19; epidemiology; Cameroon; urban area; rural area
Online: 3 February 2023 (06:23:26 CET)
The Covid-19 pandemic has rapidly evolved in December 2019 and to prevent its spread, effective vaccines has been produced and made available to the population. Despite their availability so far in Cameroon, the vaccination coverage remains low. This study aimed at describing the epidemiology of the acceptance of vaccines against Covid-19 in some urban and rural areas of Cameroon. A cross-sectional, descriptive and analytical survey was conducted from March 2021 to August 2021 targeting unvaccinated individuals from urban and rural area. After getting appropriate administrative authorizations and an ethical clearance from the Institutional Review Board (or Ethics Committee) of Douala University (N° 3070CEI-Udo/05/2022/M), a cluster sampling at many degrees was performed and a language adapted questionnaire was filled by each consenting participant. Data were analyzed using Epi info version 22.214.171.124 software and for P-values ˂ 0.05, the difference was considered as statistically significant. Out of 1053 individuals, 58.02% (611/1053) participants were residing in urban and 41.98% (442/1053) in rural areas. Good knowledge relative to Covid-19 was significantly higher in urban areas as compared to rural areas (97.55%vs.85.07, P<0.000). The proportion of respondents who intended to accept the anti Covid-19 vaccine was significantly higher in urban areas than rural areas (42.55%vs.33.26, p=0.0047). Conversely, the proportion of anti Covid-19 reluctant respondents thinking that the vaccine can induce a disease was significantly higher in rural areas than urban areas (54 (35.07 vs 8.84, P<0.0001). The significant determinants of anti-COVID-19 acceptance were the level of education (p=0.0001) and profession in the rural areas (p=<0.0001), and only the profession (p=0.0046) in the urban areas. This study globally shows that anti-COVID-19 vaccination remains a major challenge in urban as well as rural area in Cameroon. We should keep sensitizing and educate population about vaccine importance in preventing the COVID-19 spread.
ARTICLE | doi:10.20944/preprints202302.0027.v1
Subject: Life Sciences, Biochemistry Keywords: homocysteine; estrogen; bradykinin; magnesium; vitamin D; CD147
Online: 2 February 2023 (04:00:56 CET)
Brain fog with compromised ability to concentrate has been the most frequent Long Covid (LC) complaint. This is due to an increased TGF beta/IFN gamma with consequently increased bradykinin (BKN), especially in Caucasian females. Brain and lung blood vessels “leak.” This same ratio is increased in Alzheimer’s disease (AD), but decreased in Parkinson’s disease (PD), because CD4+ and CD8+ T cells are differentially affected by the invading associated viruses, e.g., SARS CoV2, HIV, …. In Covid-19 CD147 receptors on immune cells are critical in generating the increased TGF beta/IFN gamma and those on endothelial cells, platelets, and erythrocytes are critical to the abnormal microvascular blood flow. ACE2 receptors on pneumocytes and enterocytes enable pulmonary and GI entry, initiating gut dysbiosis. Epigenetics, methylation, magnesium, vitamin D, the B vitamins, and antioxidants suggest that these issues can be surmounted. Biochemical, physiologic, and epidemiologic data are analyzed to answer these questions. An LC model is presented and discussed in the context of the most recent research. Suggestions to avoid these and other worrisome concerns are included. Other topics discussed include estrogen, the gut microbiome, type 2 diabetes (T2D), and homocysteine.
ARTICLE | doi:10.20944/preprints202302.0017.v1
Subject: Behavioral Sciences, Clinical Psychology Keywords: Digital Mental Health; deprivation; service activity; Mental health concerns; ethnicity; time-series analysis; Covid-19; Text-based online therapy
Online: 2 February 2023 (01:30:05 CET)
The adoption of digital health technologies accelerated during Covid-19, with concerns over the equity of access due to digital exclusion. Using data from a text-based online mental health service for children and young people we explore the impact of the pandemic on service access and presenting concerns and whether differences were observed by sociodemographic characteristics in terms of access (gender, ethnicity and deprivation). We used interrupted time-series models to assess whether there was a change in the level and rate of service use during the Covid-19 pandemic (April 2020-April 2021) compared to pre-pandemic trends (June 2019-March 2020). Routinely collected data from 61221 service users were extracted for observation, those represented half of the service population as only those with consent to share their data were used. The majority of users identified as female (74%) and White (80%), with an age range between 13 and 20 years of age,. There was evidence of a sudden increase (13%) in service access at the start of the pandemic (RR 1.13 95% CI 1.02, 1.25), followed by a reduced rate (from 25% to 21%) of engagement during the pandemic compared to pre-pandemic trends (RR 0.97 95% CI 0.95,0.98). There was a sudden increase in almost all presenting issues apart from physical complaints. There was evidence of a step increase in the number of contacts for Black/African/Caribbean/Black British (38% increase; 95% CI: 1%-90%) and White ethnic groups (14% increase; 95% CI: 2%-27%) ), the sudden increase in service use at the start of the pandemic for the most (58% increase; 95% CI: 1%-247%) and least (47% increase; 95% CI: 6%-204%) deprived areas. During the pandemic, contact rates decreased, and referral sources change at the start. Findings on access and service activity align with other studies observing reduced service utilisation. The lack of differences in deprivation levels and ethnicity at lockdown suggests exploring equity of access to the anonymous service. The study provides unique insights into changes in digital mental health use during Covid-19 in the UK.
ARTICLE | doi:10.20944/preprints202301.0586.v1
Online: 31 January 2023 (12:04:19 CET)
COVID-19 is a pandemic triggered by the coronavirus SARS-CoV-2 whose peak occurred in the years 2020 and 2021. The main target of the virus is the lung and infection is associated to an accentuated inflammatory process involving mainly the innate arm of the immune system. Here, we described the induction of a pulmonary inflammatory process triggered by the intranasal (IN) instillation of UV-inactivated SARS-CoV-2 in C57BL/6 mice and then the evaluation of vitamin D (VitD) ability to control this process. The assays used to estimate the severity of lung involvement included total and differential number of cells in the BALF, histopathological analysis, quantification of T cell subsets and inflammatory mediators by RT-PCR, cytokine quantification in lung homogenates and flow cytometric analysis of cells recovered from lung parenchyma. IN instillation of inactivated SARS-CoV-2 triggered a pulmonary inflammatory process, consisting of various cell types and mediators, resembling the typical inflammation found in COVID-19 patients. This inflammatory process was significantly decreased by IN delivery of vitD, but not by its IP administration, suggesting that this hormone has therapeutic potential in COVID-19 if locally applied.
REVIEW | doi:10.20944/preprints202301.0576.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; vaccine; immunosuppressed; cancer; vaccine efficacy
Online: 31 January 2023 (06:26:20 CET)
The effect of SARS-CoV-2 pandemic has been subsided significantly following the rapid development of vaccine. However, patients with cancer and immunosuppressed state, who are more prone to mortality and morbidity due to this infection, were excluded from majority of the vaccine trials. Moreover, suggested dose modification for cancer and immunosuppressed patients are often not followed because of lack of awareness or unavailability of vaccination schedule. This review will try to bridge this knowledge gap by summarizing the current suggestions of dose modification of COVID-19 vaccine for patients with cancer and immunosuppression.
ARTICLE | doi:10.20944/preprints202301.0568.v1
Subject: Social Sciences, Other Keywords: cancer, pediatrics, psycho-oncology, family, COVID-19, risk, resilience
Online: 31 January 2023 (02:49:26 CET)
Previous literature highlights the impact of COVID-19 on family functioning. Less is known about the impact of the pandemic on families of pediatric cancer patients. In order to determine universal and unique risk and resilience factors of these families during the pandemic, a qualitative analysis was conducted on families currently receiving cancer treatment at a midwestern hospital. Results of the data analysis depict ways in which these families have been impacted by and have adapted to COVID-19. These findings suggest that families of pediatric cancer patients have unique experiences in the context of COVID-19, in addition to universal experiences outlined in previous literature.
ARTICLE | doi:10.20944/preprints202301.0549.v1
Subject: Social Sciences, Education Studies Keywords: childhood education; Hygiene; COVID-19; preventive behaviours; staying at home; mask wearing; hand washing; public goods
Online: 30 January 2023 (09:21:57 CET)
Childhood hygiene education has resulted in individuals engaging in hand washing and mask wearing to cope with COVID-19. Individuals can form sustainable development-related habits through childhood education.
Subject: Social Sciences, Political Science Keywords: catastrophes; COVID-19; civil unrests; inflation; public health; Health safety; Health crisis
Online: 28 January 2023 (04:52:49 CET)
Aim: Shockwaves have been felt all over the world as a result of war, inflation, food shortages, and the COVID-19 pandemic's long tail. The aim of the study is to correlate present global conflicts, pandemic and socio-economic crises with present healthcare sustainability, identifying possible threats and visualize future global health crises if all these catastrophes persist for long. Materials and Methods: PubMed, ALTAVISTA, Embase, Scopus, Web of Science, and the Cochrane Central Registers were prioritized to collect public health issues. Results: The global economic slowdown, sharp decline in financial asset values, decline in imports and exports, contraction of industrial production, rise in inflation, decrease in wages, rise in unemployment, damage to the social security caused by numerous natural calamities, human displacement due to pandemic and ongoing conflicts tear down not only the economic sector but also the health sector. It is already late for taking corrective measure by the participation every country, community or intelligence. Only healthcare issues, highlighted in this study, if focused in the highest platforms, could compel global leaders to forego conflicts and work together. Conclusion: The global health sector will be collapsed soon, if proper initiatives are not taken right now, which has already been grossly mistreated by the pandemic.
ARTICLE | doi:10.20944/preprints202301.0475.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: Parents; Healthcare workers; Children; C0VID-19 vaccine; Perception; Intention; Attitude
Online: 26 January 2023 (08:43:10 CET)
Abstract Background COVID-19 vaccination program among Adults in India is one of the highly successful vaccination drives globally. Indian children aged 15–18 years old became eligible for COVID-19 vaccination on 3rd January, 2022 followed by 12-14 years old children on 16th March, 2022. As parents are primary decision-makers for their children, we aimed to assess parents' perceptions and intentions regarding COVID-19 vaccination for children in India. Aim To assess parental perceptions and intention to get COVID-19 vaccination for their children (aged<18 years), Materials and Methods A cross-sectional anonymous web-based survey was designed. Healthcare workers of a tertiary care institute in Eastern U.P. having any children aged <18 years were the study population. They were recruited through snowball sampling and were sent the study questionnaire in Google form through email and WhatsApp. Cross-tabulation was performed by parents' intention to vaccinate their children against COVID-19 virus with socio-demographic characteristics and their risk perception toward COVID-19, trust in the healthcare system, and their history of vaccine hesitancy behavior routine childhood immunization. Bi-variate analysis was performed to find out the predictors of child vaccination intention among the parents. Results A total of 388 healthcare workers parents (HCWPs) having A child < 18 years of age completed the survey. Mean age of the parents were 40.28 ±11.34 years with majority(97.0%) completing recommended 2 doses of COVIID-19 vaccine. Around 91% of the parents agreed that COVID-19 vaccines are important for child’s health whereas about 89% agreed to the statement that COVID-19 vaccines are effective. A total 356 (91.7%) participants were willing to vaccinate their child against COVID-19, 91.3% of them liked to do so as soon as possible. The factors significantly associated with the stated likelihood of child vaccination among the participants were younger age, female gender, urban residence, absence of any chronic illness, lower monthly income, history of COVID-19 in child and the child/children completed with routine childhood vaccines. Parental concerns mainly centered around vaccine need, safety and side effects. Conclusion The healthcare worker parents(HCWPs) have good knowledge and positive attitude towards COVID-19 vaccination for children. Around 92% of them were willing to vaccinate their children with COVID vaccine currently, which implies very low vaccine hesitancy among the HCWPs . Further longitudinal studies are required to be conducted to assess the trend of parental acceptance of COVID vaccine.
ARTICLE | doi:10.20944/preprints202301.0204.v2
Subject: Medicine & Pharmacology, Other Keywords: Covid-19 vaccination; death rate; sick status days
Online: 26 January 2023 (03:53:33 CET)
Background The main reason for the worldwide massive covid vaccination in 2021 was to reduce the high mortality caused by the Covid-19 virus in 2020. It is time that in 2022 a rigorous analysis is done of the effectiveness of this massive vaccination. Methods In statistics, we have an accurate methodology to measure the impact of massive vaccination on public health. The mathematical relation between vaccinated/alive groups will be repeated between vaccinated/dead groups with high statistical certainty. This occurs because we are dealing with big numbers. Results Calculations were done for five periods of four weeks: weeks 35-38 (2021), weeks 39-42 (2021), weeks 43-46 (2031), weeks 47-50 (2021), and weeks 51(2021)-2(2022). Obtained results are confirming that the mortality of the vaccinated infected groups is higher on average by 14.5% than the mortality of non-vaccinated infected groups. Conclusions Results are suggesting the extension of the statistic between the vaccinated/alive group and the vaccinated/dead group for different age groups. These statistics will have higher statistical significance because of the elimination of the Simpson effect. Calculating the exact impact of covid-19 vaccination on the mortality rate is the necessary step to satisfy the first principle of medicine: “Primum non nocere”.
ARTICLE | doi:10.20944/preprints202301.0466.v1
Subject: Social Sciences, Finance Keywords: Adaptation, Challenges, Covid-19, Policy measures, SMEs, Syria
Online: 26 January 2023 (03:13:38 CET)
SMEs constitute the backbone of the Syrian economy which have suffered manifold challenges due to the continuous Syrian war. Covid-19 added further pressures on Syrian SMEs and force them to take certain adaptation strategies to survive. This paper aims to investigate the main challenges that face Syrian SMEs during the pandemic and illustrate how they respond to adversities emerged from governmental intervention to control the spread of the virus. It also discusses the measures initiated by the government to support SMEs during the pandemic. Through interviewing persons from the Syrian SMEs ecosystem, we find that high interest rates on SMEs loans, decline on demand as well as high inflation represent the main challenges. SMEs respond to these challenges by marketing products online, stock procurement, and strengthen connections with stakeholders. We recommend the Syrian authorities reduce lending rates and increase loan size available to SMEs to help them overcome the pandemic adversities. Moreover, SMEs will immensely benefit from training on digital tools to enhance their expansion and survival opportunities. Furthermore, bazars should be organized around the year to give SMEs the opportunity to gain continuous access to markets. In addition, incubation services should be revised, particularly, to SMEs with great potential to grow to create the suitable environment for them to scale and flourish.
ARTICLE | doi:10.20944/preprints202301.0465.v1
Subject: Social Sciences, Law Keywords: right to privacy; personal data; indemnity; sustainability of public finances; Covid-19
Online: 26 January 2023 (03:09:31 CET)
The basic constitutional freedoms and rights of a person and citizen are in principle unlimited: the full scope of their exercise is the rule, and the restriction determined by law can only be an exception based on explicit constitutional authority and the legitimate aim of the restriction determined by the Constitution. That being so, the restrictions - in addition to being based on constitutional authority and pursuing constitutional objectives - should be commensurate with the needs to achieve these objectives. This means that restrictive legal rules must be suitable for achieving the legitimate aim pursued, must not be stricter than necessary and must be balanced between the constitutionally guaranteed subjective right of the individual and the interests of society. In this scholar paper, the authors point out the economic and legal consequences of the violation of individual privacy and data protection rights caused by the public disclosure of personal data of people who, at a certain time, were obliged to self-isolate due to suspicion of Covid-19 virus infection.
REVIEW | doi:10.20944/preprints202301.0460.v1
Subject: Medicine & Pharmacology, Cardiology 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/preprints202301.0457.v1
Subject: Life Sciences, Virology Keywords: COVID-19; serological markers (IgM/IgG); Prevalence; private universities; Cameroon
Online: 25 January 2023 (11:27:36 CET)
Background: COVID-19 remains a rapidly evolving and deadly pandemic worldwide. This necessitates the continuous assessment of existing diagnostic tools for robust, up-to-date and cost-effective pandemic response strategy. We sought to determine the infection rate (PCR-positivity) and degree of spread (IgM/IgG) of SARS-CoV-2 in three university settings in Cameroon Method: Study volunteers were recruited from November 2020 to July 2021 among COVID-19 non-vaccinated students in three Universities from two regions of Cameroon (West and Centre). Molecular testing was performed by RT-qPCR on nasopharyngeal swabs and IgM/IgG antibodies in plasma were detected using the Abbott Panbio IgM/IgG rapid diagnostic test (RDT) at the Virology Laboratory of CREMER/IMPM/MINRESI. The molecular and serological profiles were compared and, p<0.05 considered statistically significant. Results: Amongst the 291 participants enrolled (mean age 22.59±10.43 years), 19.59% (57/291) were symptomatic and 80.41 %(234/2691) asymptomatic. Overall COVID-19 PCR-positivity rate was 21.31% (62/291), distributed as follows: 25.25% from UdM-Bangangte; 27.27% from ISSBA-Yaounde and 5% from IUEs/INSAM-Yaounde. Women were more affected than men (28.76% [44/153] vs. 13.04% [18/138], p<0.0007) and they significantly expressed more IgM+/IgG+ (15.69% [24/153] vs. 7.25% [10/138], p<0.01). Participants from Bangangté, the nomadic, and the “non-contact cases” mainly presented an active infection compared to those from Yaoundé (p= 0.05; p=0.05 and p=0.01 respectively). Overall IgG seropositivity (IgM-/IgG+ and IgM+/IgG+) was 24.4% (71/291). A proportion of 26.92% (7/26) presenting COVID-19 IgM+/IgG- had negative PCR versus 73.08% (19/26) with positive PCR, p<0.0001. Furthermore, 17.65% (6/34) with COVID-19 IgM+/IgG+ had negative PCR as compared to 82.35% positive PCR (28/34), p<0.0001. Lastly, 7.22% (14/194) with IgM-/IgG- had a positive PCR. Conclusion: This study calls for a rapid preparedness and response strategy in higher institutes in case of any future pathogen with pandemic or epidemic potentials. The observed disparity between IgG/IgM and viral profile supports prioritizing assays targeting the virus (nucleic acid or antigen) for diagnosis and antibody screening for sero-surveys
ARTICLE | doi:10.20944/preprints202301.0448.v1
Subject: Behavioral Sciences, Clinical Psychology Keywords: Impact of Event Scale-Revised (IES-R)/post-traumatic stress disorder (PTSD); cutoff point/cutoff score; psychiatric patients/the general public/healthy adults; psychometric evaluation/criterion validity; Coronavirus Disease-19/COVID-19; Arabic version/Arab/Saudi Arabia
Online: 25 January 2023 (05:02:13 CET)
The Impact of Event Scale-Revised (IES-R) is the most popular measure of post-traumatic stress disorder (PTSD), which has been recently validated in Arabic. This instrumental study aimed to determine optimal cutoff scores of the IES-R and its subscales in Arab samples of psychiatric patients (N = 168, 70.8% females) and healthy adults (N = 992, 62.7% females) from Saudi Arabia during the COVID-19 pandemic as an ongoing collective traumatic event. Based on a cutoff score of 14 of the Depression Anxiety Stress Scale 8-items (DASS-8), receiver operator curve (ROC) analysis revealed two optimal points of 39.5 and 30.5 for the IES-R in the samples (area under the curve (AUC) = 0.86 & 0.91, p values = 0.001, 95% CI: 0.80-0.92 & 0.87 to 0.94, sensitivity = 0.85 & 0.87, specificity = 0.73 & 0.83, Youden index = 0.58 & 0.70, respectively). Different cutoffs were detected for the six subscales of the IES-R, with numbing and avoidance expressing the lowest predictivity for distress. Meanwhile, hyperarousal followed by the irritability expressed stronger predictive capacity for distress than all subscales in both samples. In path analysis, pandemic-related irritability resulted from direct and indirect effects of key PTSD symptoms (intrusion, hyperarousal, and numbing). Irritability contributed to traumatic symptoms of sleep disturbance in both samples while the opposite was not true. The findings suggest usefulness of the IES-R at a score of 30.5 for detecting adults prone to trauma related distress, with higher scores needed for screening in psychiatric patients. Various PTSD symptoms may induce dysphoric mood, which represents a considerable burden that may induce circadian misalignment and more noxious psychiatric problems/ co-morbidities (sleep disturbance) in both healthy and diseased groups.
ARTICLE | doi:10.20944/preprints202212.0382.v2
Subject: Life Sciences, Immunology Keywords: Saccharomyces cerevisiae; beta-glucans; selenium; zinc; gut barrier; modulation; COVID-19; nutritional supplementation; allergy; inflammatory process
Online: 25 January 2023 (04:43:01 CET)
This study evaluated the anti-inflammatory effects, protection of gut barrier integrity, and stimulation of phagocytosis in peripheral cells of a nutritional supplement based on a synergistic combination of yeast-based ingredients with a unique 1,3/1,6-glucan complex and a consortium of postbiotic Saccharomyces cerevisiae rich in selenium and zinc. The anti-inflammatory effect in Caco-2 cells in the presence and absence of a pro-inflammatory challenge (tumour necrosis factor alpha [TNF-α]/interferon gamma [IFN-ɣ]) showed statistically significant reductions of IFN-ɣ induced protein-10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) levels vs. controls (p < 0.001). Disruption of the gut integrity in the presence or absence of Escherichia coli (ETEC H10407) showed transepithelial electrical resistance (TEER) values higher in the ABB C1® group after 6 hours of testing. Spontaneous build-up of the gut epithelium monolayer over 22 days was also greater in the ABB C1® condition vs. a negative control. ABB C1® showed a significantly higher capacity to stimulate phagocytosis as compared with controls of algae β-1,3-glucan and yeast β-1,3/1,6 glucan (p < 0.001). This study supports the mechanism of action by which ABB C1® may improve the immune response and be useful to prevent infection and allergy in clinical practice.
ARTICLE | doi:10.20944/preprints202301.0440.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: COVID-19 Vaccines; BNT162 Vaccine; ChAdOx1 nCoV-19; Side Effects and Adverse Reactions; Booster Immunizations; COVID-19; SARS-CoV-2
Online: 25 January 2023 (03:50:52 CET)
More than 600 Healthcare workers died due to COVID-19 infection until January 2022 in Ecuador. Even though the COVID-19 vaccines are safe, local, and systemic reactions were reported among physicians. This study aims to analyze the Adverse events (AEs) of COVID-19 vaccines with an emphasis on homologous and heterologous booster doses. An electronic survey was performed in Quito- Ecuador, directed to physicians who were vaccinated with the three doses of COVID-19 vaccines. 210 participants were analyzed after administering any doses of the vaccines. At least one AE was identified in 60.0% (126/210) of the sample after the first dose, 52.40% (110/210) after the second dose, and 75.2% (158/210) after the booster dose. The most frequent AEs were localized pain, myalgia, headache, and fever. At least one drug was used in 44.3% of the population after the first dose, 37.1% after the second dose, and 63.8% in the booster dose. Heterol-ogous booster produces more AEs compared with homologous booster (80.1% vs. 53.8%), and 77.3% of participants reported that interfered with daily activities. Similar studies agree that reactogenicity occurs mainly with heterologous vaccination compared to ho-mologous vaccination. This situation affected physicians’ performance in daily activities and led them to use medication for the symptoms
INTERESTING IMAGES | doi:10.20944/preprints202301.0439.v1
Subject: Behavioral Sciences, Social Psychology Keywords: parental health literacy; necessary health education; understanding treatment guidelines; medication non-adherence; healthcare; avoidable medical costs; global health burden; COVID-19 vaccine negligence
Online: 25 January 2023 (03:43:57 CET)
People must have particular personality traits and social resources, also known as health literacy, in order to access, comprehend, and use information to make decisions about their health. Patients' ability to engage in complex disease management and self-care is strongly related to their level of health literacy. It can help us stay healthy by preventing illness and effectively managing existing illnesses. People with low health literacy (LHL) may find it difficult to manage their condition and prevent illness, which may lead to increased use of healthcare services. Furthermore, LHL is associated with increased hospitalizations, increased use of emergency care, decreased use of preventative services, and a worsened ability to understand labels and health messages, a worsened state of health, higher mortality, and more expensive medical care.
ARTICLE | doi:10.20944/preprints202301.0433.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; Cohort; Mortality; Mexico
Online: 24 January 2023 (13:21:09 CET)
During the COVID-19 pandemic, the high prevalence of comorbidities in Mexico, as well as the disparities between public and private health subsystems, substantially contributed to the severe impact it had in the country. The objective of this study was to evaluate and compare risk factors present at admission for mortality of hospitalized patients with COVID-19. A 2-year retrospective cohort study of hospitalized adult patients with COVID-19 was conducted at a private tertiary care center. The study population consisted of 1,258 patients with a median age of 56 ± 16.5 years, of whom 1,093 recovered (86.8%) and 165 died (13.1%). In the univariate analysis, older age (p <0.001), comorbidities such as hypertension (p <0.001) and diabetes (p <0.001), signs and symptoms of respiratory distress, and markers of acute inflammatory response were significantly more frequent in non-survivors. The multivariate analysis showed that older age (p <0.001), the presence of cyanosis (p 0.005) and previous myocardial infarction (p 0.032) were independent predictors for mortality. In the studied cohort, risk factors present at admission associated with an increased risk of death were older age, cyanosis and a previous myocardial infarction, which can be used as valuable predictors for patients’ outcomes. To our knowledge, this is the first study analyzing predictors of mortality in COVID-19 patients attended on a private tertiary hospital in Mexico.
ARTICLE | doi:10.20944/preprints202301.0425.v1
Subject: Behavioral Sciences, Applied Psychology Keywords: COVID-19; SARS-CoV-2; vaccines; hesitancy; Africa
Online: 24 January 2023 (08:14:15 CET)
While vaccines are a well-established method of controlling the spread of infectious diseases, vaccine hesitancy jeopardizes curbing the spread of COVID-19. Through the Vaccine Information Network (VIN), this study explored barriers and motivators to COVID-19 vaccine uptake. We conducted 18 focus group discussions with male and female community members, stratified by country, age group, and—for Zimbabwe only—by HIV status. Participants’ median age across both countries was 40 years (interquartile range of 22–40) and most (65.9%) were female. We conceptualized the key themes within the World Health Organization’s Strategic Advisory Group of Experts on Immunization (SAGE) 3Cs (convenience, confidence, complacency) vaccine hesitancy model. Barriers to vaccine uptake—lack of convenience, low confidence, and high complacency—included inaccessibility of vaccines and vaccination sites, vaccine safety and development concerns, and disbelief in COVID-19’s existence. Motivators to vaccine uptake—convenience, confidence and low complacency—included accessibility of vaccination sites, user-friendly registration processes, trust in governments and vaccines, fear of dying from COVID-19 and knowing someone who had died or become infected with COVID-19. Overall, vaccine hesitancy in South Africa and Zimbabwe was influenced by inconvenience, a lack of confidence, and high complacency around COVID-19 vaccines.
ARTICLE | doi:10.20944/preprints202301.0413.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: zoonosis; Marek's disease; infections; vesicular enteritis; herpesvirus infection; breast cancer; COVID 19
Online: 23 January 2023 (11:55:46 CET)
Abstract. Marek's disease virus is an oncogenic avian herpesvirus and the problem of oncogenicity of this virus for humans remains unexplored. This pathology appeared in broiler chickens of 30 days and older, that is from now on the contact with poultry meat carries the risk of infecting people. This article analyzes the risks of the emergence of the epidemic potential of the Marek's disease virus in the Russian Federation taking into account the characteristics of modern pig and poultry farming. It was found that COVID 19 can serve as an additional factor in reducing the resistance of the population to herpesvirus infections. The COVID 19 epidemic is accompanied by folic acid deficiency which also increases the risk of contamination of diseases associated with DNA viruses, including an extended risk of animal viruse infection. Since, according to our estimates, Marek's disease occurred in at least 25% of broiler poultry farms in the Russian Federation, a possible expand in mortality from neoplasms of the reproductive system for the Russian Federation as a whole can contribute to the dynamics of oncological diseases of reproductive organs and breast cancer. Since 2011 a contagious form of intestinal pathology, vesicular enteritis, has widely spread at poultry farms in the Russian Federation. During periods of extending incidence of vesicular enteritis, we recorded cases of inflammation of the facial nerves and subfebrile temperature in contact persons, bursts of oncological diseases in veterinary personnel (ovarian cancer, breast cancer), abnormal and synchronous increases in the incidence of infectious larengotracheitis and Marek's disease in chickens under the age of 40 days which requires additional monitoring studies.
ARTICLE | doi:10.20944/preprints202301.0408.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: feline coronavirus; feline infectious peritonitis; FIP prevention; GS-441524; chronic enteritis; inflammatory bowel disease; IBD; antiviral; diarrhea; itraconazole.
Online: 23 January 2023 (09:43:21 CET)
After an incubation period of weeks to months up to 14% of cats infected with feline coronavirus (FCoV) develop feline infectious peritonitis (FIP): a potentially lethal pyogranulomatous perivasculitis. The aim of this study was to find out if stopping FCoV faecal shedding with antivirals prevents FIP. Guardians of cats from which FCoV had been eliminated at least 6 months earlier were contacted to find out the outcome of their cats: 27 households were identified containing 147 cats; 13 cats were treated for FIP and 109 others shed FCoV. A 4-7 day course of oral GS-441524 antiviral stopped faecal virus shedding. Follow-up was from 6 months to 3.5 years: 11 of 147 cats died, but none developed FIP. No FIP-recovered cat relapsed. Cats from 8 households recovered from chronic FCoV enteropathy. A previous field study of 820 FCoV-exposed cats was used as a retrospective control group: 37 of 820 cats developed FIP: the difference was statistically significant (p = 0.0038). Conclusions: early treatment of FCoV-infected cats with oral antivirals prevented FIP. Nevertheless, should FCoV be re-introduced into a household then FIP can result. Further work is required to establish the role of FCoV in cats with inflammatory bowel disease.
ARTICLE | doi:10.20944/preprints202301.0404.v1
Subject: Life Sciences, Virology Keywords: Omicron variant; Infectivity; Pathogenicity; Biothermodynamics; COVID-19; Viral evolution
Online: 23 January 2023 (08:53:40 CET)
The SARS-CoV-2 Hydra with many heads (variants) has been causing the COVID-19 pandemic for 3 years. The appearance of every new head (SARS-CoV-2 variant) causes a new pandemic wave. The last in the series is the XBB.1.5 “Kraken” variant. In the general public (social media) and in the scientific community (scientific journals), during the last several weeks since the variant has appeared, the question was raised of whether the infectivity of the new variant will be greater. This article attempts to provide the answer. Analysis of thermodynamic driving forces of binding and biosynthesis leads to the conclusion that infectivity of the XBB.1.5 variant could be increased to a certain extent. The pathogenicity of the XBB.1.5 variant seems to be unchanged compared to the other Omicron variants.
ARTICLE | doi:10.20944/preprints202301.0397.v1
Subject: Life Sciences, Microbiology Keywords: coranavirus; covid-19; diagnostic; epidemic; medical laboratory professionals; sars-cov-2
Online: 23 January 2023 (06:12:12 CET)
The disease COVID-19 is brought on by the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) First appeared in China in December 2019 and quickly spread around the world after being declared a worldwide pandemic by the World Health Organization in March 2020. COVID-19, Medical Laboratory Professionals, SARS-COV-2, Diagnostic, Importance and difficulties for testing were the selected terms to search the databases of PubMed and Google Scholar for previously published material. Many diagnostic tests are applied in corona virus detection like Droplet Digital PCR (ddPCR), Multiplex PCR, Loop-mediated Isothermal Amplification (LAMP) and more. There is a lack of availability of molecular and serologic tests that have been clinically validated or authorized by national or international regulatory bodies. Clinical laboratory experts are tackling threats to our global defense and wellness, including infectious diseases. The opportunity to express gratitude to the unsung medical laboratory heroes and COVID0-19 pandemic allies is now greater than ever. Each year, Medical Laboratory Professionals Week should honors those who contribute key diagnostic data that help save lives. This review article explore overall summary on testing methods including Important and Difficult Tasks for Medical Laboratories which will provide good message for better public health matter.
REVIEW | doi:10.20944/preprints202301.0388.v1
Subject: Life Sciences, Virology Keywords: SARS-CoV-2; Vaccine; Spike protein; Mutation; Conserved epitopes
Online: 23 January 2023 (02:03:42 CET)
Abstract: Over the years, several distinct pathogenic coronaviruses have emerged, including the pandemic SARS-CoV-2 which is difficult to curtail despite the availability of licensed vaccines. The difficulty in managing SARS-CoV-2 is linked to changes in the variants’ proteins, especially in the spike protein (S) used for viral entry. These mutations, especially in the S, enable the virus to evade the immune responses induced by natural infection or vaccination. However, some parts of the SP in the S1 subunit and the S2 subunit are considered conserved among coronaviruses. In this review, we will discuss the epitopes in the SARS-CoV-2 S1 and S2 subunit proteins that have been demonstrated by various studies to be conserved among coronaviruses and may be immunogenic for the development of vaccine. Considering the higher conservancy of the S2, we will further discuss the likely challenges that could limit the S2 subunit from inducing robust immune responses and the promising approaches to increase their immunogenicity.
ARTICLE | doi:10.20944/preprints202301.0359.v1
Subject: Medicine & Pharmacology, Other Keywords: monoclonal antibodies; tixagevimab/cilgavimab; immunocompromised
Online: 19 January 2023 (12:00:57 CET)
Objectives: Monoclonal antibodies (mAbs) have proven to be a valuable tool against COVID-19, mostly among subjects with risk factors for progression to severe illness. Tixagevimab/cilgavimab (TIX/CIL), a combination of two Fc-modified human monoclonal antibodies, has been recently approved to be employed as early treatment. Methods: Two groups of immunocompromised patients exposed to different early treatments (i.e., TIX/CIL vs. other mAbs [casirivimab/imdevimab, bamlanivimab/etesevimab, sotrovimab]) were compared in terms of clinical outcomes (hospitalization and mortality within 14 days from administration) and time to the negativity of nasal swabs. We used either Pearson’s chi-square or Fisher’s exact test for categorical variables, whereas the Wilcoxon rank–sum test was employed for continuous ones. Kaplan–Meier curves were produced to compare the time to nasopharyngeal swab negativity. Results: Early treatment with TIX/CIL was administered to 19 immunocompromised patients, while 89 patients received other mAbs. Most of them were solid organ transplant recipients or suffering from hematologic or solid malignancies. Overall, no significant difference was observed between the two groups in terms of clinical outcomes. In the TIX/CIL group, one patient (1/19, 5.3%), who was admitted to the emergency room within the first 14 days from treatment and was hospitalised due to COVID-19 progression, died. Regarding the time to nasal swab negativity, no significant difference (p=0.088) emerged. Conclusions: Early treatment of SARS-CoV-2 infection with TIX/CIL shows favourable outcomes in a small group of immunocompromised patients, reporting no significant difference when compared to similar patients treated with other mAbs.
ARTICLE | doi:10.20944/preprints202301.0263.v2
Subject: Social Sciences, Business And Administrative Sciences Keywords: Bed management; COVID-19; Emergency Department; Overcrowding; Efficiency; Hospital management
Online: 19 January 2023 (03:45:21 CET)
Overcrowding in the emergency department is a problem that generates several implications for bed management, which is deemed one of a hospital's most critical processes. Effective management of hospital production capacity includes bed management processes, which can be improved in order to leverage hospital performance. Thus, this study sought to understand how bed management works and identify the main factors that influence its management. The study was performed through a case study, with data collected from semi-structured interviews and bibliographic research, which were triangulated. Thematic content analysis of the interviews and cross-analysis were performed. As a result, the main factors that influence hospital Bed management were identified: communication between teams and units; definition of performance goals; decisions shared between units; occupation and discharge planning by the teams; length of stay; the role of the nurses; and COVID-19. The greatest difficulties in the management process are related to these factors. Additionally, suggestions are provided to mitigate such reported difficulties.
ARTICLE | doi:10.20944/preprints202301.0341.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Deep Learning; COVID-19; Clinical Informatics; Machine Learning; Transformer; Association Mining
Online: 19 January 2023 (02:00:16 CET)
Predicting Length of Stay (LoS) and understanding its underlying factors is essential to minimize the risk of hospital-acquired conditions, improve financial, operational, and clinical outcomes, and to better manage future pandemics. The purpose of this study is to forecast patients’ LoS using a deep learning model and analyze cohorts of risk factors minimizing or maximizing LoS. We employed various pre-processing techniques, SMOTE-N to balance data, and Tab-Transformer model to forecast LoS. Finally, Apriori algorithm was applied to analyze cohorts of risk factors influencing LoS at hospital. The Tab-Transformer outperformed the base Machine Learning models with an F1-score (.92), precision (.83), recall (.93), and accuracy (.73) for discharge dataset, and F1-score (.84), precision (.75), recall (.98), and accuracy (.77) for deceased dataset. The association mining algorithm was able to identify significant risk factors/indicators belonging to lab, X-Ray, and clinical data such as elevated LDH, and D-Dimer, lymphocytes count, and comorbidities such as hypertension and diabetes responsible for extending patients LoS. It also reveals what treatments has reduced the symptoms of COVID-19 patients leading to reduction in LoS particularly when no vaccines or medication such as Paxlovid were available.
ARTICLE | doi:10.20944/preprints202301.0338.v1
Subject: Social Sciences, Education Studies Keywords: Pedagogical Residency Program; Pedagogical Practice; Pandemic of Covid-19
Online: 19 January 2023 (01:25:53 CET)
This article aims to discuss the activities developed through the Pedagogical Residency Program for literacy of the Pedagogy course at UFF (Universidade Federal Fluminense) at INFES (Northwest Fluminense Institute of Higher Education) located in Santo Antônio de Pádua/Rio de Janeiro/Brazil, which due to the COVID-19 Pandemic, it started to be carried out remotely, in a virtual context, using digital technologies. We will describe the context and activities that were carried out within this new reality.
ARTICLE | doi:10.20944/preprints202301.0327.v1
Subject: Life Sciences, Virology Keywords: COVID-19; variant of concern; infectivity; pathogenicity; evolution; Gibbs energy
Online: 18 January 2023 (08:40:33 CET)
SARS-CoV-2 resembles the ancient mythical creature Hydra. Just like with the Hydra, when one head is cut, it is followed by appearance of two more heads, suppression of one SARS-CoV-2 variant causes appearance of newer variants. Unlike Hydra that grows identical heads, newer SARS-CoV-2 variants are usually more infective, which can be observed as time evolution of the virus at hand, which occurs through acquisition of mutations during time. The appearance of new variants is followed by appearance of new COVID-19 pandemic waves. With the appearance of new pandemic waves and determining of sequences, in the scientific community and general public the question is always raised of whether the new variant will be more virulent and more pathogenic. The two variants characterized in this paper, BA.5.2 and BF.7, have caused a pandemic wave during the late 2022. This paper gives full chemical and thermodynamic characterization of the BA.5.2 and BF.7 variants of SARS-CoV-2. Having in mind that Gibbs energy of binding and biosynthesis represent the driving forces for the viral life cycle, based on the calculated thermodynamic properties we can conclude that the newer variants are more infective than earlier ones, but that their pathogenicity has not changed.
ARTICLE | doi:10.20944/preprints202301.0324.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19 SOPs; Level of Compliance
Online: 18 January 2023 (07:54:44 CET)
Introduction: Since its emergence COVID-19 has become a global health threat. In Uganda, a number of COVID-19 Standard Operating Procedures (SOPs) have been put in place by the Ministry of Health Uganda, to mitigate the outbreak of the deadly COVID-19 pandemic among the population. Despite the putting in place COVID-19 SOPs, the deadly COVID-19 pandemic is still ravaging the population of Iganga District. This study investigated the level of compliance to guidelines for prevention of COVID-19 in public places in Iganga District so as to guide decision makers in making recommendations towards the entire public in order to prevent community acquisition and spread of COVID-19. Methodology: To deliver answers to the research objectives, the study adopted a cross-sectional survey design to guide the study process. Quantitative method of data collection using observational checklist were adopted for this study. The same data abstraction form helped to collect data from 3 public places which included: 3 markets, 5 public transport stations and 8 financial banks. Compliance was measured were the YES scored 1 and NO scored 0 and the ten indicators measured included: temperature screening, wearing of face masks, hand washing or sanitizing, physical distancing of at least 2 meters, information display on COVID-19, regular cleaning of public service places, cleaning of communal places, adequate ventilation, adequate waste management facilities and cleanliness of the work area. Overall a 4 point Likert scale used was: 0-2 poor, 3-5 fair, 6-8 good, 9-10 excellent were each indicator was equally important. Data was entered, cleaned and analyzed using Microsoft Excel 2019 spread sheet packages to generate tables and bar graphs. Results: Out of 5 public transportation stations studied, 80% were observed to be poorly compliant to covid-19 SOPs. On the other hand, out of 8 Financial Banks included in this study, 75% were observed to have excellent compliance levels to COVID-19 SOPs. Meanwhile, out of 3 Market places studied, 66.7% were observed to be poorly compliant to covid-19 SOPs. Conclusion; The results of the study revealed that; public places in Iganga district generally have low level of compliance to COVID-19 SOPs in terms of temperature screening, wearing of face masks, hand washing or sanitizing, social distancing of at least 2 meters and information display on COVID-19 Dos and Don’ts. Our findings suggest that there is a need to mobilize the population in Iganga district to comply with COVID-19 SOPs in terms of temperature screening, wearing of face masks, hand washing or sanitizing, social distancing of at least 2 meters and information display on COVID-19 Dos and Don’ts.
ARTICLE | doi:10.20944/preprints202301.0305.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Covid-19; Deoxy-D-glucose; molecular docking; ADMET
Online: 17 January 2023 (09:32:43 CET)
The outbreak of Coronavirus, as well as its emerging potential consequences, has become a global challenge worldwide, demanding effective and controlled therapeutic strategies. Potential drug candidates could achieve that with minimal toxicity. The current investigation selected 2-Deoxy-D-glucose prescribed by Defense Research and Development Organization (DRDO), India. The derivative and modified form was tested through in silico analysis against COVID-19 main protease complex with N3 inhibitor. The derived form of 2-Deoxy-D-glucose was generated by replacing the hydroxy group with a hydrogen atom, and Cypate 2-Deoxy-D-glucose was chosen as a derivative against the COVID-19 main protease complex. A molecular docking approach was adopted to identify the stable and competent form among the modified and derivative forms of 2-Deoxy-D-glucose based on binding energy. By further promoting the stabilized complex, these compounds' toxicity was also scrutinized through ADMET analysis to predict the potential candidate. The current investigation suggested that the modified version of 2-Deoxy-D-glucose was more stable with minimal toxicity against COVID-19 main protease.
ARTICLE | doi:10.20944/preprints202203.0290.v3
Subject: Life Sciences, Biotechnology Keywords: host-virus interactions; tissue-specific model; COVID-19; SARS-CoV-2; antiviral targets; flux balance analysis; flux variability analysis; reaction knockout; host-derived enforcement; metabolic modeling; virus mutations; software engineering; Python
Online: 17 January 2023 (01:50:23 CET)
COVID-19 is one of the deadliest respiratory diseases, and its emergence caught the pharmaceutical industry off guard. While vaccines have been rapidly developed, treatment options for infected people remain scarce, and COVID-19 poses a substantial global threat. This study presents a novel workflow to predict robust druggable targets against emerging RNA viruses using metabolic networks and information of the viral structure and its genome sequence. For this purpose, we implemented pymCADRE and PREDICATE to create tissue-specific metabolic models, construct viral biomass functions and predict host-based antiviral targets from more than one genome. We observed that pymCADRE reduces the computational time of flux variability analysis for internal optimizations. We applied these tools to create a new metabolic network of primary bronchial epithelial cells infected with SARS-CoV-2 and identified enzymatic reactions with inhibitory effects. The most promising reported targets were from the purine metabolism, while targeting the pyrimidine and carbohydrate metabolisms seemed to be promising approaches to enhance viral inhibition. Finally, we computationally tested the robustness of our targets in all known variants of concern, verifying our targets’ inhibitory effects. Since laboratory tests are time-consuming and involve complex readouts to track processes, our workflow focuses on metabolic fluxes within infected cells and is applicable for rapid hypothesis-driven identification of potentially exploitable antivirals concerning various viruses and host cell types.
ARTICLE | doi:10.20944/preprints202301.0250.v1
Subject: Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; Feline; Canine; seroprevalence; zoonosis
Online: 13 January 2023 (10:21:53 CET)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide since its emergence in 2019. The current global pandemic was driven by human-to-human transmission. Knowing the zoonotic origin of the disease and the potential capacity of the virus to adapt to other species, it is important to understand the extent of natural SARS-CoV-2 infection of animals, in particular cats and dogs in households that are in direct contact with their owners. Hong Kong and Seoul are two of the most densely-populated urban cities in Asia, where companion animals often live in close contact with humans. In this study, we screened sera from 1,040 cats and 855 dogs during the early phase of the pandemic in Hong Kong and Seoul for SARS-CoV-2 antibodies by using an ELISA that detects antibodies against the receptor binding domain (RBD) of the viral spike protein. Sera testing positive on ELISA were also tested for the presence of neutralizing antibodies using a surrogate virus neutralization (sVNT) and plaque reduction neutralization test (PRNT). Among feline sera, 4.51% and 2.54% of samples from Korea and Hong Kong, respectively, tested ELISA positive. However only 1.64% of samples from Korea and 0.18% from Hong Kong tested positive by sVNT, while only 0.41% of samples from Korea tested positive by PRNT. Among canine samples, 4.94% and 6.46% from Korea and Hong Kong, respectively, tested positive by ELISA, while only 0.29% sera from Korea were positive on sVNT and no canine sera tested positive by PRNT. These results confirm a low seroprevalence of SARS-CoV-2 exposure in companion animals in Korea and Hong Kong. The discordance between RBD-ELISA and neutralization tests may indicate possible ELISA cross-reactivity with other coronaviruses, especially in canine sera.
ARTICLE | doi:10.20944/preprints202301.0245.v1
Subject: Life Sciences, Other Keywords: COVID-19; glycated hemoglobin; glycemic changes; physical inactivity; chronic diseases; public health
Online: 13 January 2023 (09:18:55 CET)
The covid-19 pandemic has generated substantial changes in the lives of the population, such as increased physical inactivity, which can lead to overweight and, consequently, repercussions on glucose homeostasis. A population-based household epidemiological survey was conducted by stratified, multistage probability cluster sampling (October and December 2020) in Brazil. Participants were classified as physically active or inactive during leisure time according to the recommendations of the World Health Organization. HbA1c levels were categorized as normal (≤6.4%) or with glycemic changes (≥ 6.5%). The mediating variable was excess weight (overweight and obese). Multivariate logistic regression analyzes were performed to examine the association between physical inactivity and glycemic changes. Mediation was analyzed using the Karlson–Holm–Breen method to verify the influence of excess weight on the association. We interviewed 1,685 individuals, mostly women (52.4%), 35–59 years old (45.8%), race/ethnicity brown (48.1%), and excess weight (56.5%). The mean HbA1c was 5.68% (95% CI: 5.58-5.77). Individuals physically inactive were 2.62 times more likely to have glycemic alterations (OR:2.62.95% CI:1.29-5.33), and 26.87% of this association was mediated by excess weight (OR:1.30:95% CI:1.06-1.57). Physical inactivity in leisure time increases the chances of glycemic alterations, and part of this association can be explained by excess weight.
ARTICLE | doi:10.20944/preprints202301.0244.v1
Subject: Behavioral Sciences, Social Psychology Keywords: COVID-19; food insecurity; psychological impact; socioeconomics; food access; Nigeria
Online: 13 January 2023 (09:05:34 CET)
The COVID-19 disease has infected many countries with generalised impacts on the different income categories. To test this hypothesis, we carried out a survey among households (n = 412) representing different income groups in Nigeria. We used validated food insecurity experience and socio-psychologic tools. We analysed the data obtained using descriptive and inferential statistics. The earning capacities of the respondents range from US$145/month for the low-income earners to US$1945/month for high-income earners. A total of 173 households (42%) ran out of food during the COVID-19 pandemic. All categories of households have experienced increasing dependency from the general public and perception of increasing insecurity, with the high-income earners having the greatest shift. In addition, increasing levels of anger and irritations have been experienced with all categories. Of the socio-demographic variables, only gender (p = 0.012), level of education of household head (p = 0.000), work hours per day (p = 0.006), and family income based on society class (p = 0.000) were significantly associated with food security and hunger due to the COVID-19 pandemic. Household heads with medium (OR: 4.36, 95% CI: 2.64 – 7.21, p < 0.001) and high (OR: 30.27, 95% CI: 3.99 – 229.90, p < 0.001) family income based on society class were more likely to have satisfactory experience on food security and hunger than respondents with low family income. Irrespective of the social class of the respondents, some respondents had negative experiences such as movement/change of location within the same city (17.68%), begin a new relationship (14.43%), recent change of job/loss of job (11.55%), movement to another city (10.81%), and separation from spouse or long-term relationship (10.07%). However, 231 (60.16%) reported satisfaction with their jobs despite the pandemic. Psychological stress due to impact of COVID-19 was observed to be more in the low income earning group than others. It is recommended that socio-economic groups should be mapped and support systems should target each group as per the needed support in terms of health, social, economic, and mental wellness; the government should show political commitments and transparency in food security and counselling supports. National authorities should prioritize empirical-based interventions on resources allocation during crises.
BRIEF REPORT | doi:10.20944/preprints202301.0235.v1
Online: 13 January 2023 (04:33:23 CET)
The COVID-19 pandemic has posed an unprecedented challenge to healthcare and the available solutions are unsatisfactory. Classical homeopathy may have a role to play in alleviating this burden. Covid cases treated with homeopathy was curated with the intention to provide basic information for further studies. The results are promising although far from being definitive. 367 patients considered were for statistical analysis, the mean age of the participants was 42.75 years, and males and females were 166 and 201 respectively. The mean follow-up period was 6.5 (SD 5.3) days, with a median of 1 homeopathic remedy used per case. 192 patients were diagnosed by RT–PCR, 111 by the WHO clinical criteria and 64 via retrospective antibodies. According to the WHO criteria, 255 were confirmed cases, 61 were probable cases, and 51 were suspected cases. It was seen that 73.8% of covid patients improved under homeopathic treatment, even those among severe disease 78.6%. Correlational analyses showed that presence of fever was associated with more likelihood of improvement and increasing age and a greater number of homeopathic remedies required in a case were associated negatively with improvement. However, it was seen that severe cases were more likely to improve under homeopathic treatment.
REVIEW | doi:10.20944/preprints202301.0133.v2
Subject: Life Sciences, Immunology Keywords: COVID-19 vaccination; mRNA vaccines; Clinical Trials; Safety Assessment; Novel Technologies; Spike protein
Online: 12 January 2023 (03:16:56 CET)
Pharmacovigilance databases are showing evidence of injury in the context of the COVID-19 modified mRNA shots. According to recent publications, adverse event reports linked to the mRNA COVID-19 products largely point to the spike protein as an aetiological agent of adverse events, but we propose that the platform itself may be culpable. To assess the safety of current and future mRNA vaccines, further analysis on the risks due to the platform itself, and not specifically the expressed antigen. If harm can be exclusively and conclusively attributed to the spike protein, then it is possible that future mRNA vaccines expressing other antigens will be safe. If harms are attributable to the platform itself, then regardless of the toxicity, or lack thereof, of the chosen payload therein, the platform may be inherently unsafe, pending modification. In this work, we examine previous studies of RNA-based delivery by a lipid nanoparticle and break down the possible etiological elements of harm.
REVIEW | doi:10.20944/preprints202301.0195.v1
Subject: Medicine & Pharmacology, Other 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.
ARTICLE | doi:10.20944/preprints202301.0188.v1
Subject: Life Sciences, Virology Keywords: coronavirus; statistical analysis; extrapolation; parameter estimation; pandemic spreading
Online: 11 January 2023 (02:14:27 CET)
Monitored differential infection rates of past Corona waves are used to infer, a posteriori, the real time variation of the ratio of recovery to infection rate as key parameter of the SIR-epidemic model. From monitored Corona waves in five different countries it is found that this ratio exhibits a linear increase at early times below the first maximum of the differential infection rate before the ratios approach a nearly constant value close to unity at the time of the first maximum with small amplitude oscillations at later times. The observed time dependencies at early times and at times near the first maximum agree favorably well with the behavior of the calculated ratio for the Gaussian temporal evolution of the rate of new infections, although the predicted linear increase of the Gauss ratio at late times is not observed.
BRIEF REPORT | doi:10.20944/preprints202301.0137.v1
Subject: Life Sciences, Immunology Keywords: Covid-19; SARS-CoV-2 Spike protein; vaccine; HIV; IgA; IgG; neutralization
Online: 9 January 2023 (03:30:30 CET)
Vaccines against SARS-CoV-2 have been pivotal in overcoming the Covid-19 pandemic yet understanding the subsequent outcomes and immunological effects remain crucial, especially for at-risk groups e.g. people living with human immunodeficiency virus (HIV) (PLWH). In this study we report the longitudinal IgA and IgG antibody titers, as well as antibody-mediated angiotensin converting enzyme 2 (ACE2) binding blockade, against the SARS-CoV-2 spike (S) proteins after 1 and 2 doses of the ChAdOx1 nCoV-19 vaccine in a population of Black PLWH. Here, we report that PLWH (N = 103) did not produce an anti-S IgA response after infection or vaccination, however, anti-S IgG was detected in response to vaccination and infection, with the highest level detected for infected vaccinated participants. The anti-IgG and ACE2 blockade assays revealed that both vaccination and infection resulted in IgG production, however, only vaccination resulted in a moderate increase in ACE2 binding blockade to the ancestral S protein. Vaccination with a previous infection results in the greatest anti-S IgG and ACE2 blockade for the ancestral S protein. In conclusion, PLWH produce an anti-S IgG response to the ChAdOx1 nCoV-19 vaccine and/or infection, and ChAdOx1 nCoV-19 vaccination with a previous infection produced more neutralizing antibodies than vaccination alone.
ARTICLE | doi:10.20944/preprints202301.0066.v2
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: COVID-19; endothelial dysfunction; glycocalyx degradation; sydencan-1; and mortality
Online: 9 January 2023 (03:21:59 CET)
Background: Endotheliopathy is common pathologic findings in patients with acute and long COVID-19. It may be associated with disease severity and predispose to long-term complications. Plasma levels of a proteoglycan syndecan-1 are found to be significantly elevated in patients with COVID-19, but its roles in assessing the disease severity and predicting long-term outcome are not fully understood. Methods: 124 consecutive hospitalized patients with SARS-CoV2 infection were prospectively enrolled and blood samples were collected on admission (T1), 3-4 days following treatment (T2), and 1-2 days prior to discharge or death (T3). Plasma levels of syndecan-1 were determined using an immunosorbent assay; various statistical analyses were performed to determine the association between plasma syndecan-1 levels and disease severity or the 60-day mortality rate. Results: Compared with those in the healthy controls, plasma levels of syndecan-1 in patients with critical COVID-19 were significantly higher (p<0.0001). However, there was no statistically significant difference among patients with different disease severity (p>0.05), resulting from large individual variability. Longitudinal analysis demonstrated that while the levels fluctuated during hospitalization in all patients, plasma syndecan-1 levels were persistently elevated from baseline in critical COVID19 patients. Cox proportional hazard regression analyses revealed that elevated plasma levels of syndecan-1 (>260 ng/mL at T1, >1018 ng/mL at T2, and >461 ng/mL at T3) were significantly associated with the 60-day mortality rate. Conclusions: Endotheliopathy, marked by glycocalyx degradation and elevated plasma syndecan-1, occurs in nearly all hospitalized patients with SARS-CoV2 infection; the elevated plasma syndecan-1 is associated with increased mortality in COVID-19 patients.
ARTICLE | doi:10.20944/preprints202301.0130.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: COVID; Sars-COV-2; Gastroenteropancreatic cancers; vaccines; neuroendocrine tumors
Online: 9 January 2023 (01:16:01 CET)
The Coronavirus disease-19 (COVID-19) pandemic dramatically impacted on oncologic patients' care. Since the introduction of vaccines and the demonstration of their benefit on frail patients, COVID-19 vaccinations were indicated also for oncologic population. However, data about the impact of anticancer-treatments and the timing between vaccinations and systemic therapy de-livery were not available. We aimed to evaluate potential factors influencing the outcome of COVID-19 vaccination in cancer patients. We prospectively collected data of patients undergoing COVID-19 vaccination with gas-tro-entero-pancreatic and neuroendocrine neoplasms, treated at our Institute, between 03/2021 and 12/2021. We enrolled 46 patients, 63.1% males; at the time of data collection 86.9% received two-doses of Pfizer-BioNTech and the remains Moderna vaccine. All patients obtained a subsequent im-mune-response. A significantly lower values of IgG for patients treated with chemotherapy versus other anti-cancer agents (p=0.004). No significant effect on immune-response was reported for both vaccinations performed ≤7 vs >7 days from the last systemic treatment (p=0.77) and lymphocytes count (p=0.11). The findings suggest that the optimal timing for COVID-19 vaccination and lymphocytes count are not the issue but rather the quality of the subset of lymphocytes before the vaccination to deter-mine the efficacy level of immune-response in this population.
ARTICLE | doi:10.20944/preprints202301.0109.v1
Subject: Social Sciences, Education Studies Keywords: online environment; students; adaptation; counseling; support
Online: 6 January 2023 (02:13:25 CET)
The period of study in the online environment can be a very demanding trial for students and masters, especially for those who are not familiar with computer technology. This is largely due to a complex of factors that come from the changes to which they are subjected, such as: leaving the parental home and settling into another living environment (living in dormitories or other forms of accommodation) but also settling with an unfamiliar and very different educational environment from what they were familiar with. Along with all the changes occurring in the family and social plan, the students had to adapt to the educational system made exclusively online. Higher educa-tion institutions in Romania use, as a method of knowledge transmission, traditional learning methods, namely they use face-to-face lecture-type courses in a lecture hall or practical and ex-planatory activities in a seminar/laboratory room. The emergence of this pandemic forced higher education institutions to switch to an online teaching mode for all types of activities included in the educational process.
ARTICLE | doi:10.20944/preprints202301.0102.v1
Subject: Behavioral Sciences, Clinical Psychology Keywords: Asperger; Atypically development; Covid19; Children; Adolescents; typically development; Parents; Adaptation; Well-being; Multi-informant
Online: 5 January 2023 (09:19:13 CET)
Mental health could worsen in children and adolescents with autism spectrum disorder during the Covid19 pandemic. In addition, their parents could be more at risk for an increase in anxiety and depression symptomatology. This study aims to understand the adaptation and the psychosocial well-being in a sample of 16 males aged 10-21 years old with Asperger syndrome after the quarantine for Covid19 when they return to school and partially to their activities in September 2020, The approach adopted is multi-informant with a battery of questionnaires on psychological health and adaptation given by a secure online web data Qualtrics both to adolescents and also to their parents. Paralleling matched peers with typically development were assessed adopting the same methodology. The results evidenced several difficulties in Asperger’s psychological health, especially in anxiety and socialization. Also adaptation is put in crisis, even if they reported a good comprehension and adoption of the behaviors anti-Covid19. Parents of children with Asperger reported similar psychological difficulties and general health than those of the group of children typically developing. Some clinical indications could be discussed for psychologists who follow children and adolescents with Asperger.
BRIEF REPORT | doi:10.20944/preprints202301.0101.v1
Subject: Mathematics & Computer Science, Other Keywords: SI4CARE; TELEMEDICINE; ARTIFICIAL INTELLIGENCE; RURAL AREAS
Online: 5 January 2023 (09:11:00 CET)
The SI4CARE project is a transnational project which aims to develop both strategy and 1 action plans to improve health and social care in the Adriatic-Ionian region. Starting from the 2 survey of the status quo, each partner has developed some pilots to to support the development 3 and monitoring of the policy actions. In particular Partner number three, Municipality of Miglierina, 4 designed and developed a pilot related to the use of wearable device for monitoring elderly patients 5 in rural areas. With the collaboration of the complex unity of primary cares (UCCP) of the Reventino 6 area, the pilot is based on the use of smart wearable device to monitor some parameters of elderly 7 people after the vaccination for flu and covid. This paper focuses on the design and implementation 8 of the system and describe its application in the Municipality of Miglierina, the presentation of the 9 results and the discussion of the strengths and weaknesses will be presented in detail in a future work. 10 Finally, the possibility of extending the experiment to the other Adriatic-Ionian region is presented.
ARTICLE | doi:10.20944/preprints202301.0076.v1
Subject: Chemistry, Medicinal Chemistry Keywords: COVID-19; drug repurposing; long COVID; molecular docking; molecular dynamics; SARS-CoV-2
Online: 4 January 2023 (09:38:47 CET)
The novel coronavirus disease 19 (COVID-19) has resulted in an estimated 20 million excess deaths and the recent resurgence of COVID-19 in China is predicted to result in up to 1 million deaths over the next few months. With vaccines unable to halt transmission it is important to continue our quest for safe, effective, affordable drugs that will be available to all countries. Drug repurposing is one of the strategies being explored in this context. Recently, out of 7,817 approved drugs, 214 candidates were systematically down-selected using a combination of 11 filters including approval status, assay data against SARS-CoV-2, pharmacokinetic, pharmacodynamic and toxicity profiles. These drugs were subjected in this study to virtual screening against various targets of SARS-CoV-2 followed by molecular dynamic studies of the best scoring ligands against each target. The chosen molecular targets were Spike receptor binding domain, Nucleocapsid protein RNA binding domain, and key non-structural proteins 3, 5, 12, 13 and 14. Four drugs approved for other indications — alendronate, cromolyn, natamycin and treprostinil — look sufficiently promising from our in silicostudies to warrant further in vitro and in vivo investigations as appropriate to ascertain their extent of anti-viral activities.
ARTICLE | doi:10.20944/preprints202301.0037.v1
Subject: Behavioral Sciences, Social Psychology Keywords: COVID-19; Canada; Pandemic; Stress; Policies; Kübler-Ross Change curve
Online: 4 January 2023 (02:10:08 CET)
Coronavirus disease 2019 (COVID-19) was declared a pandemic in March 2020, which led to the implementation of non-pharmaceutical interventions that had inadvertent physical, mental and social effects. The purpose of this study was to examine the experiences and responses of Canadians to these interventions on Twitter using the Kübler-Ross Change Curve (KRCC) during the first six months of the pandemic. Tweets were analyzed using sentiment analysis, thematic content analysis and KRCC. The findings highlight that many Canadians attempted to adapt to the changes but had a predominantly negative outlook on policies due to the financial and social repercussions
ARTICLE | doi:10.20944/preprints202209.0430.v2
Subject: Medicine & Pharmacology, Obstetrics & Gynaecology Keywords: COVID-19 vaccines; menstruation; pregnancy outcomes; Influenza vaccines; VAERS; stillbirth; miscarriage
Online: 30 December 2022 (09:39:28 CET)
Objectives Assess rates of adverse events (AE) after COVID-19 vaccines experienced by women of reproductive age, focusing on pregnancy and menstruation, using data collected by the US Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS) database. Design Population-based retrospective cohort study. Setting US and global entries in US Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS). Participants CDC VAERS entries from January 1, 1998 to June 30, 2022. Interventions None. Main Outcome Measures A proportional reporting ratio analysis is performed using data in the VAERS system comparing adverse events (AE) reported post-COVID-19 vaccines with that of post-Influenza vaccines. Results COVID-19 vaccines, when compared to the Influenza vaccines, are associated with a significant increase in AE with all proportional reporting ratios of > 2.0: menstrual abnormalities, miscarriage, fetal chromosomal abnormalities, fetal malformation, fetal cystic hygroma, fetal cardiac disorders, fetal arrhythmias, fetal cardiac arrest, fetal vascular malperfusion, fetal growth abnormalities, fetal abnormal surveillance, fetal placental thrombosis, low amniotic fluid, preeclampsia, premature delivery, preterm premature rupture of membrane, fetal death/stillbirth, and premature baby death (all p values were much smaller than 0.05). When normalized by time-available, doses-given, or persons-received, all COVID-19 vaccine AE far exceed the safety signal on all recognized thresholds. Conclusions Pregnancy complications and menstrual abnormalities are significantly more frequent following COVID-19 vaccinations than Influenza vaccinations. A worldwide moratorium on the use of COVID-19 vaccines in pregnancy is advised until randomized prospective trials document safety in pregnancy and long-term follow-up in offspring.
ARTICLE | doi:10.20944/preprints202212.0578.v1
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: Type 1 diabetes; mental-health; COVID-19; adolescents; qualitative research; narratives; NVivo
Online: 30 December 2022 (09:16:21 CET)
Background: The global prevalence of anxiety and depressive symptoms in adolescents has increased considerably during the COVID-19 pandemic. Mental health problems may compromise glycemic control in young people with type 1 diabetes; however, evidence of improved glycemic control in adolescents with T1D appeared early during the pandemic. This qualitative study aimed to provide a more in-depth understanding of how the COVID-19 pandemic affected adolescents with type 1 diabetes routines, experiences, T1D management, behaviors, and mental health. Methods: 24 adolescents, aged 15-18 years, with DM1, joined the discussion of focus groups in the context of the summer camp for diabetes. Word frequency and thematic analysis were conducted on adolescents’ narratives. Results: The word Frequency Analysis identified 'friends', 'family', and 'home' as the most frequent terms. Seven themes were identified: (1) COVID-19 and T1D; (2) emotional reactions to the COVID-19 pandemic; (3) changes in daily life; (4) feelings of loss; (5) coping with the COVID-19 pandemic; (6) the COVID-19 pandemic as an opportunity; (7) return to (new) normality. Conclusions The COVID-19 pandemic may have represented a more stressful condition for adolescents with DM1, facing additional challenges compared to their healthy peers. The results offer directions to the diabetes care team for a customized intervention while the consequences of the pandemic on adolescents’ health continue.
ARTICLE | doi:10.20944/preprints202212.0577.v1
Online: 30 December 2022 (09:13:21 CET)
Background: Signaling by toll like receptors (TLRs) initiates important immune responses against viral infection. The role of TLRs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is not well elucidated. Thus, we investigated the interaction of TLRs agonists and SARS-COV-2 antigens with immune cells in vitro. Material & methods: 30 coronavirus disease 2019 (COVID-19) patients (15 severe and 15 moderate) and 10 age and sex matched control (HC) were enrolled. Peripheral blood mononuclear cells (PBMCs) were isolated and activated with TLR3, 7, 8 and 9 agonists, the spike protein (SP) of SARS-CoV-2 and the Receptor Binding Domain (RBD) unit of SP. Frequencies of CD3+IFN-β+ T cells, and CD3+IFN-g+ T cells was evaluated by flow cytometry. Interferon (IFN)-b gene expression was assessed by qRT-PCR. Results: The frequency of CD3+IFN-β+ T cells was higher in moderate and severe patients at baseline in comparison with HCs. Stimulation of PBMCs from moderate patients with SP and TLR8 agonist significantly upregulated the frequency of CD3+IFN-β+ T cells (P=0.0005 and 0.0024, respectively) when compared to non-stimulated (NS) samples. The greatest increase in CD3+IFN-b+ T cell frequency in PBMCs from severe patients was seen with TLR8 and TLR7 agonists when compared to NS (P= 0.003 and 0.0167, respectively). TLR stimulation did not significantly enhance the frequency of CD3+IFN-g+ T cells generated from PBMCs from moderate and severe patients compared with unstimulated controls. However, the frequency of CD3+IFN-ɣ+ T cells in PBMCs from moderate patients was upregulated by agonists of TLR3, 8 and 9, SP and RBD when compared with NS samples from HCs. The expression of the IFN-β gene after stimulation of CD3+T cells with the TLR8 agonist was also up-regulated in moderate than severe patients (moderate vs. severe: p=0.0006). In addition, stimulation of CD3+ T cells with SP, up-regulated the expression of IFN-β gene expression in cells from patients with moderate disease (moderate vs. severe: p=0.01). Conclusion: Stimulation of PBMCs from COVID-19 patients with a TLR8 agonist and with SP enhanced IFN-b protein and gene levels. This may potentiate immune responses against SARS-CoV-2 infection and prevent viral replication and spread.
REVIEW | doi:10.20944/preprints202208.0278.v2
Subject: Medicine & Pharmacology, General Medical Research Keywords: stress response system; sympathetic activity; HPA(Hypothalamic-Pituitary-Adrenal) axis; SARS-CoV-2; catecholamine; corticosteroids; clonidine; dexamethasone
Online: 30 December 2022 (02:43:54 CET)
We are in amidst of COVID-19 pandemic. Since Dec 2019, severe acute respiratory corona virus (SAR-CoV-2) has infected more than half a billion people killing nearly 7 million people worldwide. Now the BA.5 variant of SARS-CoV-2 is causing mayhem and driving the global surge. Epidemiologist are aware of the fact that this virus is capable of escaping immunity and likely to infect the same person multiple times despite adequate vaccination status. Elderly people of age more than 60 years and those with underlying health conditions are considered as high-risk who are likely to suffer complications and death. While it is tempting to frame complications and mortality from COVID-19 as a simple matter of too much of a virulent virus in too weak of a host, much more is at play here. Framing the pathophysiology of COVID-19 in the context of the Chrousos and Gold model of the central stress response system can shed insight into its complex pathogenesis. Understanding the mechanisms by which pharmacologic modulation of the central stress response system via administration of clonidine and/or dexamethasone may offer an explanation as to why a viral pathogen can be well tolerated and cleared by one host while inflaming and killing another.
ARTICLE | doi:10.20944/preprints202212.0534.v1
Subject: Earth Sciences, Environmental Sciences Keywords: Indoor air quality; forecasting; machine learning; IoT; Covid-19; environmental mapping; pandemic.
Online: 28 December 2022 (09:10:46 CET)
The current COVID19 pandemic has raised huge concerns for outdoor air quality due to expected lungs deterioration. These concerns include the challenges in the scalable prediction of harmful gases like carbon dioxide, iterative/repetitive inhaling due to mask and environmental temperature harshness. Even in the presence of air quality sensing devices, these challenges lead to failed planning and strategy against respiratory diseases, epidemics, and pandemics in severe cases. In this work, a dual time-series with bi-cluster sensor data-stream-based novel optimized regression algorithm was proposed with optimization predictors and optimization responses that use automated iterative optimization of the model based on the similarity coefficient index. The algorithm was implemented over SeReNoV2 sensor nodes data, i.e. multi-variate dual time-series of environmental and US Environmental Protection Agency standard sensor variables for air quality index measured from air quality sensors with geospatial profiling. The SeReNoV2 systems were placed at four locations that were 3 km apart to monitor air quality and their data was collected at Ubidots IoT platform over GSM. Results have shown that the proposed technique achieved a root mean square error (RMSE) of 1.0042 with a training time of 469.28 seconds for normal and RMSE of 1.646 in the training time of 28.53 seconds for optimization. The estimated R-Squared error of 0.03 with Mean-Square Error for temperature 1.0084 ᵒC and 293.98 ppm for CO2 was observed. Furthermore, the Mean-Absolute Error (MAE) for temperature 0.66226 ᵒC and 10.252 ppm for CO2 at a prediction speed of ~5100 observations/second for temperature 45000 observations/second for CO2 due to iterative optimization of the training time 469.28 seconds for temperature and 28.53 seconds for CO2 was very promising in forecasting COVID19 countermeasures before time.
BRIEF REPORT | doi:10.20944/preprints202212.0518.v1
Subject: Life Sciences, Immunology Keywords: immunoassay; epitope coverage; quantitative antibody binding; protein microarray; SARS-CoV-2 antibodies; humoral response; SARS-CoV-2 re-infection
Online: 27 December 2022 (10:43:18 CET)
The COVID-19 pandemic continues to affect individuals across the globe, with some individuals experiencing more severe disease than others. The relatively high frequency of re-infections and breakthrough infections observed with SARS-CoV-2 highlights the importance of extending our understanding of immunity to COVID-19. Here we aim to shed light on the importance of antibody titers and epitope utilization in protection from re-infection. Health care workers are highly exposed to COVID-19 and are therefore also more likely to become re-infected. We utilized quantitative, multi-antigen, multi-epitope SARS-CoV-2 protein microarrays to measure IgG and IgA titers against various domains of the nucleocapsid and spike proteins. Potential re-infections in a large, diverse health care worker cohort (N=300) during the second wave of the pandemic were identified by assessing the IgG anti-N titers before and after the second wave. We assessed epitope coverage and antibody titers between the 'single infection’ and ‘re-infection’ groups. Clear differences were observed in the breadth of the anti-N response before the second wave, with the epitope coverage for both IgG (p=0.019) and IgA (p=0.015) being significantly increased in those who did not become re-infected compared to those who did. Additionally, the IgG anti-N (p=0.004) and anti-S titers (p=0.018) were significantly higher in those not re-infected. These results highlight the importance of the breadth of elicited antibody epitope coverage following natural infection in protection from re-infection and disease in the COVID-19 pandemic.
REVIEW | doi:10.20944/preprints202212.0418.v2
Subject: Life Sciences, Immunology Keywords: COVID-19; B Cells; Neutrophils; T Cells; NK Cells; Innate; Adaptive; Cytokines; Chemokines; Adhesion Molecules; Antibody; Cluster of Differentiation; Receptors; Proteins; SARS-CoV-2; Serology
Online: 27 December 2022 (03:19:48 CET)
The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist, of which Middle East Respiratory Syndrome (MERS) and SARS-CoV (SARS) showed higher mortality rates without causing a pandemic. As of December 2022, SARS-CoV-2 has resulted in over 6.6 million deaths worldwide through an array of acute to chronic pathologies. Historical pandemics include smallpox and influenza with efficacious therapeutics utilized to reduce overall disease burden. Therefore, immune system process analysis is required to compare innate and adaptive immune system interactions. Lymphatic system organs include bone marrow and thymus using a network of nodes throughout which white blood cells traverse glycolipid membranes utilizing cytokines and chemokine gradients that affect cell development, differentiation, proliferation, and migration processes as well as genetic factors affecting cell receptor expression. Innate processes involve antigen-presenting cells and B lymphocyte cellular responses to pathogens relevant to other viral and bacterial infections but also in oncogenic diseases. Such processes utilize cluster of differentiation (CD) marker expression, major histocompatibility complexes (MHC), pleiotropic interleukins (IL) and chemokines. The adaptive immune system consists of Natural Killer (NK) and T cells. Other viruses are also contributory to cancer including human papillomavirus (cervical carcinoma ), Epstein-Barr virus (EBV) ( lymphoma), hepatitis B and C (hepatocellular carcinoma) and human T cell leukemia virus-1 (adult T-cell leukemia). Bacterial infections also increase the risk of developing cancer( e.g. H. pylori). Therefore, as the above factors can cause both morbidity and mortality along-side being transmitted within clinical and community settings, it is appropriate to now examine advances in single cell sequencing, FACS analysis and many other laboratory techniques that allow insights into discoveries of newer cell types. These developments offer improved clarity and understanding that over-lap with known autoimmune conditions that could be affected by innate B cell or T cell responses to SARS-CoV-2 infection. Thus, this review quantifies and outlines the nature of specific receptors and proteins relevant to clinical laboratories and medical research by documenting both innate and adaptive immune system cells within current coronavirus immunology case study data and other pathologies to date.
CASE REPORT | doi:10.20944/preprints202212.0502.v1
Subject: Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; minocycline; Kampo; Saiko-keishi-to
Online: 27 December 2022 (02:13:05 CET)
Since the beginning of 2020, tetracycline (TC), such as minocycline (MINO), has been used to inhibit coronavirus disease 2019 (COVID-19). Traditional Japanese Kampo medicine, such as Saiko-keishi-to (SKT), has recently received a lot of attention for its anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) effects. We describe a COVID-19 patient treated with MINO and SKT in anticipation of their anti-SARS-CoV-2 properties. A 90-year-old male patient with Alzheimer’s disease was referred to a medical clinic due to fever, appetite loss, and general malaise. Based on positive SARS-CoV-2 rapid antigen tests, he was diagnosed with COVID-19. He did not have COVID-19 pneumonia, but he had difficulty in eating on his own. As a result, he was referred to a hospital for admission. After admission, he was treated with molnupiravir to avoid aggravation. Seven days after his admission, he was discharged. After his discharge, he was referred to our hospital as an outpatient due to a prolonged mild fever and general malaise. As a precaution, a real-time reverse transcription-polymerase chain reaction (RT-PCR) test was performed, which yielded a positive result. Therefore, the aforementioned symptoms were thought to be caused by prolonged COVID-19. He was treated with MINO and SKT due to the anti-viral properties of these two drugs. The RT-PCR test became negative 7 days after receiving this treatment, and the fever and general malaise subsided.
COMMUNICATION | doi:10.20944/preprints202212.0493.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: SARS CoV-2; Variants; Epidemiology; Treatment Plans; Preventive Strategies
Online: 26 December 2022 (15:48:43 CET)
SARS-CoV-2 is severe acute respiratory syndrome coronavirus 2 which induces severe pneumonia that has considerable death rate. In this article, we summarised the evolution of SARS CoV-2 from alpha to omicron variant. The origin, transmission capability, and innate immunity potential of the Omicron variety remain unknown in the aftermath of its appearance. It's also unclear whether further varieties based on Omicron may emerge in the future. However, there is no question that the Omicron version of SARS-CoV-2 would not be the last. The COVID-19 pandemic has become more difficult to control due to the constant appearance of new SARS-CoV-2 mutations. We have discussed about the epidemiology, treatment plans for SARS CoV-2 and preventive strategies for future pandemic.
ARTICLE | doi:10.20944/preprints202212.0198.v2
Subject: Social Sciences, Business And Administrative Sciences Keywords: labour challenges; climate change; Ukraine War; high fuel costs; sustainability
Online: 26 December 2022 (09:13:10 CET)
This exploratory study examined the impacts of COVID-19 and emerging challenges and opportunities from aviation recovery. Using archival and secondary data analysis, the study found that there are several challenges to aviation recovery chief among them are labour challenges and extreme weather events, which have been responsible for traffic disruptions in major aviation markets such as Europe and the USA. Other emerging challenges include high debt, inflation, interest rates, fuel, cost of labour, and general operational costs. The study recommends several interventions to address the sector’s challenges, including adopting risk disaster preparedness and management to foster sustainability.
BRIEF REPORT | doi:10.20944/preprints202212.0469.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; SARS-CoV-2; Reinfection
Online: 26 December 2022 (03:53:55 CET)
Background: Repeated SARS-CoV-2 infections are plausible and related published data are scarce. We aimed to identify factors associated with the risk of recurrent (three episodes) laboratory-confirmed symptomatic SARS-CoV-2 infections. Methods: A retrospective cohort study was conducted and 1,700 healthcare workers were enrolled. We used risk ratios (RR) and 95% confidence intervals (CI) to evaluate factors associated with symptomatic SARS-CoV-2 infections. Results: We identified 14 participants with recurrent illness episodes. Therefore, the incidence rate was 8.5 per 10,000 person-months. In multiple model, vaccinated adults (vs. unvaccinated, RR = 1.05 [1.03 - 1.06]) and those with a severe first illness episode (vs mild disease, RR = 1.05 [1.01 - 1.10]) were at increased risk for repeated symptomatic SARS-CoV-2 reinfections. Increasing age showed a protective effect (per each additional year of age: RR = 0.98 [0.97 - 0.99]). Conclusions: Our results suggest that recurrent SARS-CoV-2 infections are rare events in adults and they seem to be determined, partially, by vaccination status and age.
ARTICLE | doi:10.20944/preprints202212.0454.v1
Subject: Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; Vaccine; Attenuation; Biothermodynamics; Gibbs energy; Permissiveness; Biosynthesis; Multiplication
Online: 23 December 2022 (08:15:06 CET)
Live attenuated vaccines have through history proved themselves as safe and efficient. Pasteur has developed a vaccine against rabies, through a long process of passage of the virus wild type through rabbits. The result was one of the most efficient attenuated live-virus vaccines. This paper suggests a method based on calculations of biothermodynamic properties of potential tissues for vaccine application, predilected host tissue and virus wild type. Gibbs energy of biosynthesis represents the thermodynamic driving force for virus multiplication. The attenuated strain of the virus should possess Gibbs energy of biosynthesis, which is less negative than the predilected target tissue, but more negative than the vaccine portal tissue. In that way, the attenuated virus strain should be able to multiply in the vaccine portal of entry tissue and cause an immune response, making it efficient. On the other hand, the attenuated strain cannot multiply in the predilected host tissue, making it safe. The attenuation is achieved by adding a gene to the virus, which encodes a ballast protein. Production of the ballast protein would make virus multiplication less favorable, since it would require energy, but be useless to the virus.
REVIEW | doi:10.20944/preprints202212.0441.v1
Online: 23 December 2022 (04:07:59 CET)
Unusual outbreak of Covid 19 has put the whole new challenges around the globe. In a short span of time, the world has been changed, lifestyles, social events, cultural, political events everything has been put on hold as number of countries has enforced partial or complete lockdown that resulted positive in context of controlling spread and contamination of COVID-19. Such activities have also put some effects on environment in both positive and negative way. In this study only positive impacts of COVID-19 on Environment have been highlighted that played role in regeneration of natural systems i.e., reduced air emissions, cleaner air, beaches &water bodies, reduced noise levels, biodiversity rehabilitation etc.
ARTICLE | doi:10.20944/preprints202212.0438.v1
Subject: Biology, Animal Sciences & Zoology Keywords: bovine respiratory disease; virome; bovine nidovirus; bovine coronavirus; bovine herpesvirus 1; bovine viral diarrhea virus 1; bovine respiratory syncytial virus; case control; odds ratio
Online: 23 December 2022 (03:30:02 CET)
Bovine respiratory disease (BRD) is a major health problem within the global cattle industry. This disease has a complex aetiology, with viruses playing an integral role. In this study, metagenomics was used to sequence viral nucleic acids in the nasal swabs of BRD affected cattle. Viruses detected included those well known for their association with BRD in Australia (bovine viral diarrhea virus 1), as well as viruses known to be present but not fully characterised (bovine coronavirus) and viruses that have not been reported in BRD affect cattle in Australia (bovine rhinitis, bovine influenza D, and bovine nidovirus). Nasal swabs from a case control study were subsequently tested for 10 viruses and the presence of at least one virus was found to be significantly associated with BRD. Some of the more recently detected viruses had inconsistent association with BRD. Full genome sequences for bovine coronavirus, a virus increasingly associated with BRD, and bovine nidovirus were complete. Both viruses belong to the Coronaviridae family, which are frequently associated with disease in mammals. This study has provided greater insights into the viral pathogens associated with BRD and highlighted the need for further studies to elucidate more precisely the roles viruses play in BRD.
ARTICLE | doi:10.20944/preprints202212.0431.v1
Subject: Life Sciences, Immunology Keywords: transcriptomics; COVID-19; tuberculosis; progression; non-coding RNA; hub proteins
Online: 23 December 2022 (01:24:48 CET)
The pandemic of COVID-19 ravaged most countries and made the healthcare system go for a toss. The impact of the disease is different in each patient and it progresses differently. Based on the severity, the COVID-19 infection is stratified into three main categories- mild, moderate, and severe. In this study, we performed a transcriptomic study of different stages and studied the progression of the disease. The study was based on an Indian population of 28 COVID-19 patients, which were classified into different groups. Our analysis has shown that as the disease progresses, the genes involved in the degranulation of the neutrophils and galactose metabolism increase. Furthermore, we identified the hub proteins in each stage. TB is one of the comorbidities of COVID-19 and a comparative study was done to identify the preserved module of genes in both. Enrichment analysis showed that the members of this module are significantly involved in translation and ribosome synthesis.
ARTICLE | doi:10.20944/preprints202212.0425.v1
Subject: Social Sciences, Education Studies Keywords: teacher motivation; work motivation; job satisfaction; COVID-19; Ghana
Online: 22 December 2022 (09:10:30 CET)
Teachers, particularly in developing contexts, were vulnerable populations during the COVID-19 pandemic. As natural parental figures for students, they had to reconcile the dual role of ensuring the safety and health of students and their own and family well-being. The external crisis of COVID-19 heightened the negative experiences of teachers in their work environments during both online and physical instruction. The qualitative phenomenological study involving thirty (30) secondary school teachers in Ghana took a comprehensive and fresh look at how COVID-19 impacted the work motivation of teachers. It was found that teachers suffered a great deal of stress in the wake of the pandemic and had face-mounting concerns about their working conditions. The low morale of teachers precipitated by COVID-19 made them develop attrition intentions. However, intrinsic and altruistic traits such as passion, the feeling of responsibility, and the desire to contribute to society and foster student development made teachers resilient towards the deleterious effects of the pandemic to promote optimal teaching. Future studies should investigate the installation of support structures that strengthen the motivation of teachers in unforeseen crises.
ARTICLE | doi:10.20944/preprints202212.0415.v1
Subject: Social Sciences, Other Keywords: stigma; news frame; monkeypox; COVID-19; The Washington Post; online news
Online: 22 December 2022 (03:42:16 CET)
Abstract: Background: Stigma in health can result in a broad range of vulnerabilities and risk for patients and healthcare providers. The media plays a role in people’s understanding of health and stigma is socially constructed through many communication channels including via media framing. Among health issues that were affected by stigma recently were the Monkeypox and Covid-19. Objectives: This research aims to examine how The Washington Post framed stigma around mon-keypox and COVID-19. Guided by the framing theory and stigma theory, online news coverage for monkeypox and COVID-19 were analyzed to understand the construction of social stigma through the media reporting. Methods: This research employed a qualitative content analysis to compare news framing in The Washington Post online news regarding monkeypox and COVID-19. Results: Based on endemic, reassurance, and sexual transmission frames, the The Washington Post predominantly defined Africa as the source of the disease, blames gay communities, and empha-sizes no need to worry about the spread of the monkeypox virus. For the COVID-19 coverage, The Washington Post described China as the source of the coronavirus and constructs the image of panic towards the spread of the virus. Conclusions: The shifts in stigma discourse essentially manifest racism, xenophobia, and sexism in public health. This research affirms that the media reinforces stigma phenomenon in health through framing and offers constructive suggestions for mitigating this issue.
ARTICLE | doi:10.20944/preprints202212.0410.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Heart rate variability; COVID-19; post-COVID-19 condition; long COVID; autonomic dysfunction; vagal nerve activity; symptomatology; lung function
Online: 22 December 2022 (03:13:53 CET)
Persistence of symptoms beyond three months after COVID-19 infection, often referred to as post-COVID-19 condition (PCC), is commonly experienced. It is hypothesized that PCC results from autonomic dysfunction with decreased vagal nerve activity, which can be indexed by low heart rate variability (HRV). The aim of this study was to assess the association of HRV upon admission with pulmonary function impairment and number of reported symptoms beyond three months after initial hospitalization for COVID-19 between February and December 2020. Follow-up took place three to five months after discharge and included pulmonary function tests and the assessment of persistent symptoms. HRV analysis was performed on one 10s electrocardiogram obtained upon admission. Analyses were performed using multivariable and multinomial logistic regression models. Among 171 patients who received follow-up, and with an electrocardiogram at admission, decreased diffusion capacity of the lung for carbon monoxide (DLCO) (41%) was most frequently found. After a median of 119 days (IQR 101-141), 81% of the participants reported at least one symptom. HRV was not associated with pulmonary function impairment or persistent symptoms three to five months after hospitalization for COVID-19.
ARTICLE | doi:10.20944/preprints202012.0817.v2
Subject: Life Sciences, Microbiology Keywords: COVID-19; OC43; coronavirus; pandemic; influenza; historical revisionism; corpus linguistics
Online: 21 December 2022 (09:56:55 CET)
COVID-19 is the first known coronavirus pandemic. Nevertheless, the seasonal circulation of the four milder coronaviruses of humans – OC43, NL63, 229E and HKU1 – raises the possibility that these viruses are the descendants of more ancient coronavirus pandemics. This proposal arises by analogy to the observed descent of seasonal influenza subtypes H2N2 (now extinct), H3N2 and H1H1 from the pandemic strains of 1957, 1968 and 2009, respectively. Recent historical revisionist speculation has focussed on the influenza pandemic of 1889-1892, based on molecular phylogenetic reconstructions that show the emergence of human coronavirus OC43 around that time, probably by zoonosis from cattle. If the “Russian influenza”, as The Times named it in early 1890, was not influenza but caused by a coronavirus, the origins of the other three milder human coronaviruses may also have left a residue of clinical evidence in the 19th century medical literature and popular press. In this paper, we search digitised 19th century British newspapers for evidence of previously unsuspected coronavirus pandemics. We conclude that there is little or no corpus linguistic signal in the UK national press for large-scale outbreaks of unidentified respiratory disease for the period 1785 to 1890.
ARTICLE | doi:10.20944/preprints202212.0386.v1
Subject: Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; seroprevalence; antibodies; vaccine; natural infection; French Polynesia
Online: 21 December 2022 (04:56:44 CET)
In French Polynesia, Wuhan, Delta and Omicron SARS-CoV-2 variants-of-concern (VOCs) caused epidemics with variable severities. We assessed the prevalence and titers of anti-SARS-CoV-2 antibodies related to natural infection and/or vaccination, from a representative sample (N=673) of the adult population of Tahiti recruited during November-December 2021 (after the Delta outbreak and just before the Omicron epidemic). Of the 673 participants tested, 644 (95.7%) had detectable antibodies against SARS-CoV-2-S and/or -N proteins resulting from natural infection and/or vaccination, and 388 (57.7%) were positive only for the detection of anti-N antibodies indicating natural infection. SARS-CoV-2 seroprevalence extrapolated to the adult population of Tahiti was estimated at 95.9%. Concentrations of anti-SARS-CoV-2-S antibodies significantly increased with age, number of self-reported SARS-CoV-2 infections (0 or ≥1), and number of COVID-19 vaccine doses (0, 1, 2, or 3) received by the participants. Elderly people, who are at higher risk of severe outcomes, had received more vaccine doses than younger individuals both in our sample and in the general population. The high level of antibody responses related to past infections and vaccination, especially booster doses, has likely contributed to reducing the severity of the Omicron outbreak in French Polynesia.
REVIEW | doi:10.20944/preprints202212.0155.v2
Subject: Life Sciences, Virology Keywords: covid-19; pandemic; immune evasion; first-line immunity; viral evolution; interferon; vaccinology
Online: 21 December 2022 (02:31:00 CET)
The COVID-19 pandemic and the recently-emerged highly transmissible SARS-CoV-2 Omicron variants have increased the demands for novel immunising and therapeutic approaches to protect the lives of patients with significant co-morbidities. Following a worldwide campaign of mass vaccination, there is still a significant demand to quell the harmful effects of the novel SARS-CoV-2 variants on people with serious co-morbidities, and there is still a dilemma of how we could prevent potentially catastrophic effects of future pandemics upon the human race. And the concerns intersect at a specific point; a gained evolutionary ability of several viruses over the previous centuries to go undetected during the first stages of infection by means of capping the 5' end of their genetic material, reducing the synthetic rate of Type I and Type III Interferons, temporarily inhibiting the apoptotic pathways of infected cells to facilitate a rapid viral replication, and inhibiting antigenic presentation. Type I and III Interferon-based viral immune evasion may be primarily associated with a delayed clearance of the viral load. Past clinical data also suggests that the SARS-CoV-2 spike glycoprotein is capable of inhibiting the V(D)J antibody gene rearrangement in developing B-lymphocytes, as well as diverse important cellular processes of DNA repair by downregulating the BRCA1 and 53BP1 genes. Furthermore, most traditional methods of vaccination do not particularly boost mucosal immunity and as a result, there is a visible gap that viruses can easily fill in, which implicates a reduced stimulation of a mucosal plasma cell production. Serum plasma antibodies do not cross the nasal epithelium and hence, offer little protection against mucosal inflammation, unlike the antibodies produced by mucosal plasma cells. We acknowledge the existence of a significant challenge to stimulate mucosal immune responses due to the high complexity of its structure-function axis. Nevertheless, over the past half century, numerous scientists developed ways of immunisation and early treatment worldwide that generally showed outstanding levels of success and insignificant risks of adverse events. An important example implicates the administration of human interferons I and III into the nasal mucosa to simulate local infection and train the innate immune system to robustly become activated and transmit essential signals before viruses silence it. Recently, it was discovered that specific plants secrete proteins that also stimulate the production of Type I Interferons. It might be that focusing on directly offering the immune system the information about the genetics and protein structure of the pathogen, rather than training its first-line mechanisms to develop faster, excessively increases its specificity, making it reach a level that brings the virus the opportunity to evolve and escape previously-developed host immune mechanisms. Naturally-selected polymorphic viruses had generated long-term evolutionary responses to deeply tackle the ability of the complex human immune system to neutralise viruses during the first stages of cellular infection. It is until the scientific community realises this that we will probably continue to face serious epidemics and pandemics of respiratory diseases over the coming several decades.
ARTICLE | doi:10.20944/preprints202212.0330.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: Covid-19; machine learnin; , ICU; admission
Online: 19 December 2022 (08:42:28 CET)
Optimizing intensive care resources using predicting modeling is paramount for fighting the COVID-19 pandemic. In this paper, we model the admission of COVID-19 patients in intensive care units (ICU) in Colombia using openly available data gathered from 18 March 2020 to 14 October 2020. After an intensive preprocessing of the data, we trained four different machine learning models using four different strategies for handling the imbalanced features. Our findings show that our best model (XGBoost) effectively predicts an Area Under the Curve (AUC-ROC) of 0.94, in line with the state-of-the-art results obtained in other predictive models obtained with medical data.
ARTICLE | doi:10.20944/preprints202212.0318.v1
Subject: Behavioral Sciences, Clinical Psychology Keywords: antenatal depression; Edinburgh Postnatal Depression Scale; COVID-19; women; mental health; pregnancy
Online: 19 December 2022 (03:56:31 CET)
Globally, the impact of COVID-19 on mental health has been significant. Pregnant women are known to be a vulnerable population in relation to mental health. In Australia, there was an unprecedented demand during the pandemic for mental health services, including services for pregnant women. Maternal mental health has unique and enduring features that can significantly shape a child’s overall development and poor maternal mental health can have considerable social and economic costs. This cross-sectional study evaluated antenatal depression and COVID-19 related distress in a sample of two hundred and sixty-nine pregnant women residing in Australia aged between 20 and 43 (M = 31.79, SD = 4.58), as part of a larger study. Social media advertising was used to recruit participants between September 2020 and November 2021. Prevalence rates for antenatal depression were found to be higher in this study (16.4%) compared with previous Australian prevalence rates (7%). COVID-19 distress in relation to having a baby during a COVID-19 outbreak significantly predicted antenatal depression, B = 1.46, p < .001. Results from this study suggest that mothers and families may have increased mental health vulnerabilities as a consequence of the pandemic for some time yet.
REVIEW | doi:10.20944/preprints202212.0296.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: atherosclerosis; COVID-19; inflammation; cardiovascular system; cytokines; endothelium; lipoproteins; renin-angiotensin system; atheroma; autoimmunity; vasa vasorum.
Online: 16 December 2022 (06:32:21 CET)
The article describes how atherosclerosis and coronavirus disease 19 (COVID-19) may affect each other. The features of this comorbid pathogenesis at various levels (vascular, cellular and molecular) are considered. A bidirectional influence of these conditions is described: the presence of cardiovascular diseases affects different individual susceptibility to viral infection. In turn, SARS-CoV-2 can have a negative effect on the endothelium and cardiomyocytes, causing blood clotting, secretion of pro-inflammatory cytokines, and thus exacerbating the development of atherosclerosis. In addition to the established entry into cells via ACE2 принимая во внимание его влияние на, other mechanisms of SARS-CoV-2 entry are currently under investigation, for example, through CD147. Pathogenesis of comorbidity can be determined by the influence of the virus on various links which are meaningful for atherogenesis: generation of oxidized forms of LDL, launch of a cytokine storm, damage to the endothelial glycocalyx, and mitochondrial injury. The transformation of a stable plaque into an unstable one plays an important role in the pathogenesis of atherosclerosis complications and can be triggered by COVID-19. The impact of SARS-CoV-2 on large vessels such as aorta is more complex than previously thought considering its impact on vasa vasorum. Current information on the mutual influence of the medicines used in the treatment of atherosclerosis and acute COVID-19 is briefly summarized
REVIEW | doi:10.20944/preprints202212.0273.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: Mint; Menthol; Digestion; Respiration; COVID-19; Sport; Pain
Online: 15 December 2022 (07:25:06 CET)
Mint and to a lesser extent menthol have been used since antiquity for medicinal purposes. Key components of mint and menthol use such as composition and intake, safety and traditional uses are discussed prior to a review of clinical and human performance outcomes in the areas of digestive and respiratory health; antibacterial and anti-fungal properties, nocioception, migraine and headache and emerging evidence regarding COVID 19. Evidence suggests benefit for patients with irritable bowel syndrome and related digestive issues, with analgesic and respiratory effects also noted. Perceptual characteristics relating to thermal comfort and sensation, taste sensitivity and alertness are also considered; these effects are predominantly driven by stimulation of transient receptor potential melastatin 8 (TRPM8) activity resulting in sensations of cooling and freshness, with lesser influence on thirst. Finally, sport performance is considered as a domain that may further elucidate some of the aforementioned underpinning outcomes due to its systemic and dynamic nature, especially when performed in hot environmental conditions.
ARTICLE | doi:10.20944/preprints202212.0242.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: resilience; nurse; ICU; nursing care; Health Care System; Covid-19
Online: 14 December 2022 (03:03:34 CET)
Introduction. The outbreak of the COVID pandemic was a period of uncer-tainty and tension for healthcare managers, resulting from the lack of knowledge, i.e. about the transmission of the virus, but also from the lack of uniform organisational and treatment procedures. It was the period where the ability to prepare to a crisis situation, to adapt to the existing conditions and to draw conclusion from the situa-tion were critical to keep ICUs operating. The aim of this study was to show the prep-aration of an ICU in Poland to ensure resilience, and also the methods of reacting dur-ing the COVID-19 pandemic on both central and local level. Methods. Based on the EC and WHO guidelines on resilience a matrix of 6 elements and 13 standards as-signed to them was created, with a series of questions from a survey questionnaire. Results. Good management in resilient systems is free access to any resource. A free and transparent flow of information and also well motivated human resources in an appropriate number. Conclusion. Appropriate preparation, adaptation to the existing situation and effective management of crisis situations is an important element of ICU resilience.
ARTICLE | doi:10.20944/preprints202212.0234.v1
Subject: Life Sciences, Virology Keywords: reassortant virus; recombinant virus; chimeric virus; genetic engineering; reverse genetic; SARS-CoV-2; COVID-19
Online: 13 December 2022 (08:47:51 CET)
Due to the fact that to date, the question of the origin of SARS-CoV-2 has not been resolved yet, the author analyzed the main advances in the development of genetic engineering of viruses that took place before the onset of the COVID-19 pandemic. The first artificial genetically modified viruses could appear in nature in the mid-1950s. The technique of nucleic acid hybridization was developed by the end-1960s. In the late 1970s, a method called the "reverse genetics" emerged to synthesize RNA and DNA molecules. In the early 1980-s, it became possible to combine the genes of different viruses and insert the genes of one virus into the genome of another virus. Since that time, the production of vector vaccines began. Currently, by modern technologies one can assemble any virus based on the nucleotide sequence available in the virus database or designed by a computer as a virtual model.Scientists around the world are invited to answer the call of Neil Harrison and Jeffrey Sachs of Columbia University, for a thorough and independent investigation into the origin of SARS-CoV-2. Only a full understanding of the origin of the new virus can minimize the likelihood of a similar pandemic in the future.
ARTICLE | doi:10.20944/preprints202212.0232.v1
Subject: Life Sciences, Virology Keywords: coronavirus; genome; recombination; COVID-19; reservoir host; secondary host; phylogenetic support; tree reconstruction
Online: 13 December 2022 (07:44:48 CET)
Phylogenetic trees of coronaviruses are difficult to interpret because they undergo frequent ge-nomic recombination. Here, we propose a new method, named coloured genomic bootstrap (CGB) barcodes, to highlight the polyphyletic origins of human sarbecoviruses and understand their host and geographic ori-gins. The results indicate that SARS-CoV and SARS-CoV-2 contain genomic regions of mixed an-cestry originating from horseshoe bat (Rhinolophus) viruses. First, different regions of SARS-CoV share exclusive ancestry with five Rhinolophus viruses from Southwest China (RfYNLF/31C: 17.9%; RpF46: 3.3%; RspSC2018: 2.0%; Rpe3: 1.3%; RaLYRa11: 1.0%) and 97% of its genome can be related to bat viruses from Yunnan (China), supporting its emergence in Rhinolophus species of this province. Second, different regions of SARS-Cov-2 share exclusive ancestry with eight Rhi-nolophus viruses from Yunnan (RpYN06: 5.8%; RaTG13: 4.8%; RmYN02: 3.8%), Laos (RpBA-NAL103: 3.3%; RmarBANAL236: 1.7%; RmBANAL52: 1.0%; RmBANAL247: 0.7%), and Cam-bodia (RshSTT200: 2.3%), and 98% of its genome can be related to bat viruses from northern Laos and Yunnan, supporting its emergence in Rhinolophus species of this region. Although CGB barcodes are very useful to retrace the origins of human sarbecoviruses, further investigations are needed to better apprehend the diversity of coronaviruses in bats from Cambo-dia, Laos, Myanmar, Thailand and Vietnam.
BRIEF REPORT | doi:10.20944/preprints202212.0219.v1
Subject: Life Sciences, Immunology Keywords: SARS-CoV-2 breakthrough infections; vaccines; anti-spike antibody levels; humoral response; IgG specific salivary antibodies
Online: 13 December 2022 (02:28:02 CET)
SARS-CoV-2 breakthrough infections, associated with waning immunity, increase systemic antibody levels. In this study, we analyzed the impact of the infection timing on the magnitude of the systemic humoral response and whether breakthrough infections also boost antibody levels in the salivary compartment. We observed that the combination of infection plus vaccination, regardless of infection timing, produced a sharp increase of systemic antibodies, being higher in subjects infected after third doses. Moreover, despite high systemic antibody levels, breakthrough infections after dose 3 occurred and boosted antibody levels in the salivary compartment. These results lead to rethink the current vaccination strategies against COVID-19 and the use of salivary anti-SARS-CoV-2 antibodies for disease surveillance and vaccination follow-up.
ARTICLE | doi:10.20944/preprints202212.0206.v1
Subject: Life Sciences, Biochemistry Keywords: Cell-to-cell fusion; proprotein convertases; metalloproteases; mutagenesis; PCSK9; protease inhibitors; SARS-CoV-2; shedding; SKI-1/S1P; SREBP-2.
Online: 12 December 2022 (14:20:01 CET)
Proprotein convertases activate various envelope glycoproteins and participate in cellular entry of many viruses. We recently showed that the convertase furin is critical for the infectivity of SARS-CoV-2. This study investigated the implication of the two cholesterol-regulating convertases SKI-1 and PCSK9 in SARS-CoV-2 entry. We used cell-to-cell fusion assays in HeLa cells and pseudoparticle entry into Calu-3 cells. SKI-1 increases cell-to-cell fusion by enhancing the activation of SREBP-2, whereas PCSK9 reduces cell-to-cell fusion by promoting the cellular degradation of ACE2. Metalloprotease activation is sensitive to enhanced cholesterol levels resulting from SKI-1-activated SREBP-2 that leads to enhanced S2’ formation. However, high metalloprotease activity results in S2’ shedding into a new C-terminal fragment (S2”), leading to reduced cell-to-cell fusion. Indeed, S-mutants that increase S2’’ formation, abolish S2’ and cell-to-cell fusion, as well as pseudoparticles entry, indicating that the formation of S2’’ prevents SARS-CoV-2 cell-to-cell fusion and entry. We next demonstrated that PCSK9 enhanced the cellular degradation of ACE2, thereby reducing cell-to-cell fusion. However, different from the LDLR, a canonical target of PCSK9, the C-terminal CHRD domain of PCSK9 is dispensable for the PCSK9-induced degradation of ACE2. Molecular modeling suggested binding of ACE2 to the Pro/Catalytic domains of mature PCSK9. Thus, both cholesterol-regulating convertases SKI-1 and PCSK9 can modulate SARS-CoV-2 entry via two independent mechanisms.
ARTICLE | doi:10.20944/preprints202212.0202.v1
Online: 12 December 2022 (13:12:15 CET)
A new variant of the SARS-CoV-2 Omicron BA.5 virus has displaced all previous variants of the virus around the world. Preliminary assessment of the effectiveness of drugs for the prevention and treatment of COVID-19 requires the availability of infection models in animals. In this study, we characterize the infection model SARS-CoV-2 Omicron BA.5 and its progeny sublineage BE.1 in hACE2-transgenic mice and in Syrian hamsters. Both sublineages turned out to be pathogenic for animals – the challenged animals showed weight loss, a high level of viral load and acute inflammation in the lungs. Part of BA.5-infected mice died after virus challenge, indicating that this virus variant is more pathogenic than the previous BA.1 variant but less pathogenic than Wuhan variant.
ARTICLE | doi:10.20944/preprints202212.0196.v1
Subject: Biology, Physiology Keywords: SARS-CoV-2; PCR persistent positive; respiratory infection; COVID-19
Online: 12 December 2022 (09:04:59 CET)
Background and Objectives: Most individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are asymptomatic or have mild symptoms of COVID-19, which usually resolve after few days. Regardless of symptoms, infected people can transmit the virus to others especially on the first days of infection. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) is used to confirm SARS-CoV-2 infection; some individuals show persistent PCR-positivity after recovering from COVID-19. In this study, 12 individuals who showed persistence of COVID-19 symptoms and of SARS-CoV-2 PCR-positivity were followed-up. Methods: nasopharyngeal samples were collected for SARS-CoV-2 detection by RT-qPCR; clinical and epidemiological data were analyzed. Results: that persistence of SARS-CoV-2 PCR positivity was associated with duration of symptoms (rs 0.81338), which varied between one and 49 days, with 75% of the individuals reporting symptoms for more than two weeks; 83.33% of cases remained positive after two weeks of onset of symptoms, despite decreases in viral load. Conclusion: neither RT-qPCR test nor a symptom-based approach alone are sufficient to evaluate discontinuation of patient isolation; other factors such as viral loads and symptom severity should also be considered. Additional studies are needed to understand how RT-PCR-positivity is related to symptoms and the risk of viral transmission, and to better support isolation guidelines.
REVIEW | doi:10.20944/preprints202212.0175.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: SARS-CoV-2; Poly(A); dexrazoxane; supramolecular self-assembly; base stacking
Online: 9 December 2022 (09:55:12 CET)
In 2018, the author identified a previously unknown/unreported association between dexrazoxane and poly(ADP-ribose) (PAR). Interestingly, PAR is a close structural analogue of the polyadenine nucleotide polymer, polyadenosine monophosphate (poly(A)). In this report, subsequent in silico modelling of the interaction between dexrazoxane and poly(A) reveals some notable differences from the previously reported interaction between dexrazoxane and PAR. Significantly, the supramolecular self-assembly of dexrazoxane and poly(A) is distinguished by vertically-orientated nonelectrostatic forces comparable to the stabilizing interactions between stacked bases within DNA. Notably, the vertical separation of 3.4 Å between each stack is consistent with solvent entropy as a dominant driving force in stabilising the interaction. Additionally, concomitant conformational analysis by the author reveals the existence of low energy planar conformers of dexrazoxane. This analysis enables an explanation for the considerable discrepancies and conflicts that exist within the reported pharmacokinetic data for dexrazoxane. Exploring the significance of the interaction between dexrazoxane and poly(A), the author illustrates that survival, translation and replication of the severe acute respiratory syndrome virus 2 (SARS-CoV-2) is absolutely dependent upon the mature and unhindered poly(A) tail of the SARS-CoV-2 genome. The proposition herein, that dexrazoxane, as a chameleonic agent sequesters the poly(A) tail of the SARS-CoV-2 genome by the catalysis of a supramolecular hybrid assembly establishes SARS-CoV-2 infected cells as deep compartments for the accumulation of dexrazoxane. Taken together, dexrazoxane or its demethylated analogue, represent a novel treatment to kill the SARS-CoV-2 virus by irreversible destabilization of the SARS-CoV-2 poly(A) tail.
ARTICLE | doi:10.20944/preprints202212.0149.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: international students, social support, depression, vital exhaustion
Online: 8 December 2022 (08:51:35 CET)
Background: Our study aimed to assess the differences between domestic and international students in terms of social support, vital exhaustion, and depression during the time of COVID-19. Methods: The online cross-sectional survey was conducted via Google Forms® at three time intervals during the pandemic. Results: Respectively 1320, 246, and 139 students completed our questionnaires in the different time intervals. International students reported significantly lower values of perceived social support. Women reached higher scores regarding vital exhaustion in both samples. Concerning depression, international female students had higher values than their male counterparts but the difference diminished with time. No differences could be found in the comparison of depression between domestic female and male students. Significant correlations were found between depression, perceived social support, and vital exhaustion. Discussion: International students perceive diminished social support just when they need more. Decreased levels of perceived social support may contribute to the development of their psychological problems.
ARTICLE | doi:10.20944/preprints202212.0122.v1
Subject: Life Sciences, Virology Keywords: COVID-19; Elemental composition; Gibbs energy of biosynthesis; Gibbs energy of binding; Variant of concern (VOC)
Online: 7 December 2022 (09:19:10 CET)
RNA viruses exhibit a great tendency to mutate. Starting from 2019, the wild type that was labeled Hu-1 has during the last 3 years evolved to produce several dozen new variants, as a consequence of mutations. Mutations cause changes in empirical formulas of new virus strains, which lead to change in thermodynamic properties of biosynthesis and binding. These changes cause changes in the rate of reactions of binding of virus antigen to the host cell receptor and the rate of virus multiplication in the host cell. Changes in thermodynamic and kinetic parameters lead to changes in biological parameters of infectivity and pathogenicity. SARS-CoV-2 has starting from in 2019, until today, evolved towards increase in infectivity and maintaining constant pathogenicity, or for some variants a slight decrease in pathogenicity. In the case of Omicron BQ.1, BQ.1.1, XBB and XBB.1 variants pathogenicity is identical as in the Omicron BA.2.75 variant. On the other hand, infectivity of the Omicron BQ.1, BQ.1.1, XBB and XBB.1 variants is greater than those of previous variants. This will most likely result in the phenomenon of asymmetric coinfection, that is circulation of several variants in the population, some being dominant.
ARTICLE | doi:10.20944/preprints202212.0102.v1
Subject: Life Sciences, Other Keywords: Physical inactivity; work from home; sleep; Covid-19 and public health.
Online: 6 December 2022 (11:33:34 CET)
To examine the association of sleep quality and work from home with physical inactivity (PI) in leisure time during Covid-19 pandemic. A population-based household survey was conducted in two Bra-zilian municipalities from October to December 2020. Leisure-time physical activity (PA) was self-reported, and individuals who practiced less than 150 minutes of moderate PA or 75 minutes of vigorous PA weekly were classified as PI. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). WFH was assessed by: "Currently, how is your work routine regarding location? Associations were investigated using logistic regression and directed acyclic graphs (DAG) for the multivariate models. A total of 1,750 adults were interviewed, 69.1% were PI and 51.9% had poor sleep quality. Furthermore, 79.8% were not in WFH. In multivariate analysis, leisure PI was associated with poor sleep quality (OR:1.59: 95% CI: 1.02-2.48), and not being in WFH (OR:1.62: 95% CI: 1.05-2.50). When performing the combined analysis between these two factors, and who were not in WFH were four times more likely to be PI at leisure (OR=4.22;95%CI:2.05-8.65). The results indicate a high prevalence of PI, with poor quality sleep and non-WFH associated with leisure PI. These combined factors exacer-bated the occurrence of PI.
ARTICLE | doi:10.20944/preprints202212.0073.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: SARS-COV-2; respiratory tests; Xpert® Xpress COV-2 plus; Xpert(2) Xpress COV-2/Flu/RSV plus; diagnostic evaluation; novel target
Online: 5 December 2022 (10:17:58 CET)
The Xpert® Xpress SARS-CoV-2 and Xpert® Xpress SARS-CoV-2/Flu/RSV tests were rapidly developed and widely used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In response to emerging genetic variability, a new SARS-CoV-2 target (RNA-dependent RNA-polymerase) has been added to both tests: Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus test. A rapid evaluation of both tests was performed in South Africa, using residual respiratory specimens. Residual respiratory specimens (n=125) were used to evaluate the Xpert® Xpress CoV-2 plus test and included 50 genotyped specimens. The Xpert® Xpress CoV-2/Flu/RSV plus test was assessed using 45 genotyped SARS-CoV-2 specimens, ten influenza A, ten Influenza B and twenty respiratory syncytial virus specimens. Results were com-pared to in-country standard of care tests. Genotyped specimens tested the performance of the test under pressure from circulating SARS-CoV-2 variants of concern. Reference material was included to assess the test limits and linearity. The Xpert® Xpress CoV-2 plus test performance compared to reference results across residual respiratory specimens was good (positive per-centage agreement (PPA)=95.2%, negative percentage agreement (NPA)=95.0%) The Xpert® Xpress CoV-2/Flu/RSV plus test showed good performance across all residual respiratory specimens (PPA=100%, NPA=98.3%). All genotyped variants of concern were detected by both tests. The Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus tests can be used to diagnose SARS-CoV-2, and to diagnose and differentiate SARS-CoV-2, influenza A, influenza B and respiratory syncytial virus respectively. The NPA was lower than the recommended 99%, but was influenced by the low number of negative specimens tested. The variants of concern assessed did not affect test performance. It is recommended that sites perform their own assessments compared to in-country standard of care tests.
ARTICLE | doi:10.20944/preprints202212.0067.v1
Subject: Mathematics & Computer Science, Applied Mathematics Keywords: COVID-19; Disease-behaviour dynamics model; Prophylactic attitude; Vaccination; Perceived disease prevalence
Online: 5 December 2022 (08:28:57 CET)
In this age of mass media and, in particular, social media-driven perception of reality, coupling disease and prophylactic opinion dynamics models can provide better insights into disease evolution than using a disease model alone. We develop in this work two disease-opinion dynamics models based on the epidemiology of the new coronavirus disease (COVID-19) and the availability or not of imperfect vaccines. We assume that susceptibility to infection decreases with the level of prophylactic attitude (personal hygiene, social distancing), and changes in prophylactic attitudes of susceptible individuals occur in response to perceived disease prevalence and vaccination coverage and efficacy in the population. We derive and discuss the disease-free equilibriums and reproduction numbers in the introduced models. We further assess the impacts of the distribution of opinions at disease introduction, the ability to detect presymptomatic, asymptomatic and symptomatic positive COVID-19 cases, the behavioural responses to the outbreak and the introduction of vaccination, and the effects of distortions of disease prevalence by public policy and mass media on disease dynamics. The insights highlighted from the proposed models are expected to make informative contributions to public policy in a context of opinion fluxes in response to perceived disease prevalence.
REVIEW | doi:10.20944/preprints202212.0066.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: Sickle Cell Disease; COVID-19; SARS-CoV-2; Vaso-occlusive Crisis; Pain; Thromboxane; Prostaglandin D2; Thrombo-inflammation; Acute Chest Syndrome; Ramatroban
Online: 5 December 2022 (08:00:45 CET)
People with sickle cell disease (SCD) are at greater risk of severe illness and death from respiratory infections, including COVID-19 than people without SCD (Centers for Disease Control and Prevention, USA). Vaso-occlusive crises (VOC) in SCD and severe SARS-CoV-2 infection are both characterized by thrombo-inflammation mediated by endothelial injury, complement activation, inflammatory lipid storm, platelet activation, platelet-leukocyte adhesion, and activation of the coagulation cascade. Notably, lipid mediators, including thromboxane A2, significantly increase in severe COVID-19 and SCD. In addition, the release of thromboxane A2 from endothelial cells and macrophages stimulates platelets to release microvesicles which are harbingers of multicellular adhesion and thrombo-inflammation. Currently, there are limited therapeutic strategies targeting platelet-neutrophil activation and thrombo-inflammation in either SCD or COVID-19 during acute crisis. However, due to many similarities between the pathobiology of thrombo-inflammation in SCD and COVID-19, therapies targeting one disease may likely be effective in the other. Therefore, the preclinical and clinical research spurred by the COVID-19 pandemic, including clinical trials of anti-thrombotic agents, are potentially applicable to VOC. Here, we first outline the parallels between SCD and COVID-19; second, review the role of lipid mediators in the pathogenesis of these diseases and lastly, examine the therapeutic targets and potential treatments for the two diseases.
ARTICLE | doi:10.20944/preprints202212.0061.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Covid-19; Neutrophil-Lymphocyte ratio (NLR); severe covid pneumonia
Online: 5 December 2022 (06:26:50 CET)
With covid infection having a periodic occurrence and each wave affecting millions of people, there is an urgent need for healthcare providers to develop readily available biological markers to predict the severity and mortality of COVID-19 infection at an early stage of the disease to predict the most optimal management. The Neutrophil – lymphocyte Ratio (NLR) and Platelet-lymphocyte ratio (PLR), are novel inflammatory markers suggested to predict the severity of illness in COVID -19 patients. We evaluated a retrospective cohort of 224 patients with covid 19 illnesses from August 2020 to October 2020. We categorized the patients into 'mild' and 'moderate to severe as per the severity of their illnesses. The optimal cut-off values of the continuous NLR, PLR, and Age were calculated by applying the receiver operating characteristic (ROC) curve analysis. Sensitivity, specificity, and likelihood ratios were calculated from ROC analysis. The results showed that Age, Hb, and NLR are significant predictors of the severity of illness. So we quantified the predictive contribution of those variables by its Z- score and showed that NLR is the strongest predictor followed by Age.ROC curve analysis revealed NLR to be an excellent predictor of disease severity (sensitivity 88.30% and specificity 82.60%) at a cut-off of > 4.24. A cut-off of 165.63 was obtained for PLR, which showed good predictive value for the severity of illness. A NLR > 6 was used as a predictor for mortality due to covid illness with good sensitivity and specificity. Conclusion: NLR and PLR can be used as prognostic markers to identify the severity of covid illness and the probability of mortality in the future in low-resource settings. Given its low cost, easily available, accessible, and reproducible data, it can be used as a useful marker to assist the physician in early referral and treatment of covid 19 infected patients.
ARTICLE | doi:10.20944/preprints202212.0036.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: lung ultrasound; infants; children; COVID-19; SARS-CoV-2; multisystem inflammatory syndrome.
Online: 2 December 2022 (02:29:22 CET)
It is already well known that infants and children infected with COVID-19 develop mild to mod-erate forms of the disease, with fever and oropharyngeal congestion being the most common symptoms. Nevertheless, there are cases in which the patients accuse respiratory symptoms. These cases need lung evaluation, which can be done using lung ultrasound (LUS), because it is a non-irradiating and repeatable imaging technique. 19 children with COVID-19 pneumonia were eval-uated using LUS. The LUS score (LUSS) for each patient varied between 1 to 8 points from a max-imum of 36 points. The arithmetic mean was 4.47 ± 2.36 (S.D), while 95% CI for the Arithmetic mean was 3.33 to 5.61. The lung changes were correlated with their biomarkers, specifically in-flammatory markers. The correlation between LUSS and LDH, D-dimers and IL-6 was a strong positive one with r=0.66 (p=0.01, 95% CI 0.147 to 0.896) between the LUSS and LDH level at symptomatic infants and children (with cough present) and r=0.66 (p=0.01, 95% CI 0.140 to 0.895) between LUSS and D-dimers level at symptomatic infants and children (with cough pre-sent). The results suggest that LUS could be a good imaging technique that can be used both in ini-tial evaluation of children with respiratory diseases, and, also in their follow-up, correlated with symptoms and biomarkers.
REVIEW | doi:10.20944/preprints202212.0032.v1
Subject: Medicine & Pharmacology, Other Keywords: ACE2; Ang II; angiotensin(1-7); AT1R; Cathepsin; cell entry; COVID-19; Endocytosis; ERK1/2; Furin; IL-1β; IL-6; MAPK; MasR; NF-κB; PLC; PKC; RAS; RBD; SARS-CoV2; S protein; TMPRSS2; TNF-α
Online: 2 December 2022 (02:19:48 CET)
Since the spread of the deadly virus SARS-CoV2 in late 2019, researchers have restlessly been seeking for unraveling how the virus factually enters the host cells. Some proteins on each side of the interaction between the virus and the host cells are involved as the major contributors to this process: 1- the nano-machine Spike protein on behalf of the virus, 2- angiotensin converting enzyme II, the mono-carboxypeptidase and the key component of renin angiotensin system on behalf of the host cell, 3- some host proteases and proteins exploited by SARS-CoV2, In this review, the complex process of SARS-CoV2 entrance into the host cells with the contribution of the involved host proteins as well as the sequential conformational changes in the Spike protein tending to increase the probability of complexification of the latter with angiotensin converting enzyme II, the receptor of the virus on the host cells, are discussed. Besides, the release of the catalytic ectodomain of angiotensin converting enzyme II as its soluble form in the extracellular space and its positive or negative impact on the infectivity of the virus are considered.
ARTICLE | doi:10.20944/preprints202212.0024.v1
Subject: Mathematics & Computer Science, Probability And Statistics Keywords: Positive Poisson distribution, Under dispersion, Bayesian analysis, prediction, index of infectivity.
Online: 1 December 2022 (10:25:33 CET)
Background. COVID-19 efforts were often ineffective in controlling the spread of the pandemic. Identifying ineffective controls during a pandemic is thus vital. Method. Utilizing publicly available data on COVID deaths in the counties of US states, we create an index to capture and interpret ineffectiveness in the efforts to reduce the spread of the pandemic in US counties. This index is based on the Intervened Poisson Distribution (IPD) introduced originally by Shanmugam. Motivation for the research idea occurred while we noticed the data dispersion of the COVID deaths is smaller than the average only in some counties. Under-dispersed data is common in statistical modeling. A novel approach we adapted in this article includes the estimation of an intervention parameter estimated through iterative non-linear optimization. Results. Twenty-five counties in California, Idaho, Minnesota, Mississippi, Montana, Nebraska, North Carolina, North Dakota, Texas, and Utah were found to be ineffective in controlling for fatalities based on the expected probability distribution. A review of the policies enacted in these areas would provide insight into ineffective prevention efforts, and some of these issues are documented in current literature. Conclusion. The IPD index an innovate way to document efficacy of interventions during pandemics. The IPD may identify ineffective efforts prior to statistical models intended to evaluate efficacy of efforts.
ARTICLE | doi:10.20944/preprints202210.0057.v2
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; BNT162b2; vaccination; S-RBD; SARS-CoV-2; seroconversion
Online: 1 December 2022 (10:22:30 CET)
The humoral response of the COVID-19 vaccine varies from person to person. It largely depends on prior SARS-CoV-2 infection, obtaining an adequate immune response, and leaving a trace of changing antibody concentration over time. We retrospectively analyzed five clinical cases from selected patients and employees of the oncology hospital. All mild COVID-19 convalescents received the BNT162b2-Comirnaty mRNA vaccine three or four times. The levels of SARS-CoV-2 IgM- and IgG-specific antibodies, as well as S-RBD antibodies, were analyzed for two years. The concentration of antibodies was assessed in the laboratory using the chemiluminescent immunoassay CLIA, MAGLUMI. Results: (1) Active autoimmune disease stabilized the level of IgG-specific antibodies after systemic mRNA vaccination for at least six months. (2) Post-vaccination IgG and S-RBD levels decreased when vaccination was performed within three months of onset. (3) The booster dose administered only increased the S-RBD antibody levels. Declining IgG-specific antibodies were observed. (4) The S-RBD IgG levels were not correlated with the SARS-CoV-2 IgG levels in the vaccinated convalescents. (5) Subsequent reinfection with SARS-CoV-2 after vaccination three times released a more significant specific antibody response. Based on the collected data, we suggest that monitoring S-RBD antibodies is sensitive but not equivalent to a specific humoral response for SARS-CoV-2 IgG. We suggested that administering at least three doses of the mRNA vaccine should serve as the basis for immunization. The three-month interval may be the best alternative to an immunization schedule for non-immunocompromised people.
ARTICLE | doi:10.20944/preprints202212.0008.v1
Subject: Biology, Other Keywords: COVID-19; molecular docking; ADMET; marine natural products; Chrysophaentin A; Hymenidin
Online: 1 December 2022 (03:51:30 CET)
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have triggered a recent pandemic of respiratory disease and affected almost every country all over the world. A large amount of natural bioactive compounds is under clinical investigation for various diseas-es. Especially, marine natural compounds are gaining more attention in the new drug develop-ment process. The present study has aimed to identify potential marine-derived inhibitors against the target proteins of COVID-19 using a computational approach. Currently, 16 marine clinical-level compounds were selected for computational screening against the four SARS-CoV-2 main proteases. Computational screening resulted from the best drug candidates for each target based on the binding affinity scores and amino acid interactions. Among these, five marine-derived compounds namely Chrysophaentin A (-6.6 kcal/mol), Geodisterol sulfates (-6.6 kcal/mol), Hymenidin (-6.4 kcal/mol), Plinabulin (-6.4 kcal/mol) and Tetrodotoxin (-6.3 kcal/mol) expressed the minimized binding energy and molecular interactions such as covalent and hydrophobic interactions to the SARS CoV-2 Main Protease. Using Molecular dynamic stud-ies, the Root-Mean-Square Deviation (RMSD), Root-Mean-Square Fluctuation (RMSF), Radius of Gyration (ROG), and Hydrogen bonds (H-Bonds) values were calculated for SARS-CoV-2 Main Protease with Hymenidin docked complex. Additionally, in silico Druglikeness and pharmaco-kinetic property assessments of the compounds demonstrated favorable druggability. These re-sults suggested that marine natural compounds are capable of fighting SARS-CoV-2. Further, in vitro and in vivo studies need to be carried out to confirm their inhibitory potential.
ARTICLE | doi:10.20944/preprints202211.0546.v1
Subject: Mathematics & Computer Science, Other Keywords: COVID-19; pandemic; Italy; daily confirmed deaths; all-cause excess mortality; peak comparison; public health; epidemiology; health informatics
Online: 29 November 2022 (09:18:41 CET)
During a sanitary crisis, excess mortality measures the number of all-cause deaths, beyond what we would have expected if that crisis had not occurred. The high number of COVID-19 deaths started a debate in Italy with two opposite positions: those convinced that COVID-19 deaths were not, by default, excess deaths, because many COVID-19 deaths were not correctly registered, with the most part attributable to other causes and to the overall crisis conditions, and those who presented the opposite hypothesis. We analyzed the curve of the all-cause excess mortality, during the period January 5, 2020 – August 28, 2022, compared to the curve of the daily confirmed COVID-19 deaths, investigating the association between excess mortality and the recurrence of COVID-19 waves in Italy. We compared the two curves looking for the corresponding highest peaks and we found that 5 out of the 6 highest peaks (83.3%) of the excess mortality curve have occurred, on average, just a week before the concomitant COVID-19 waves hit their highest peaks of daily deaths (Mean 6.4 days; SD 2.4 days). This temporal correspondence between the moments when the excess mortality peaked and the highest peaks of the COVID-19 deaths provides further evidence that the all-cause excess mortality wave has been mostly driven by COVID-19 deaths