Introduktion COVID-19 orsakas av viruset SARS-CoV-2. 3-chymotrypsin-liknande cysteinproteaset (3CLpro) är ett enzym som styr coronavirus replikation och är viktigt för viruset livscykel. Därför 3CL pro är en viktig måltavla för att hämma SARS-CoV-2. Syfte Syftet med detta projekt är att undersöka om proteashämmare kan vara en framkomlig väg för att ta fram antivirala läkemedel mot COVID-19. Metod Arbetet är en litteraturstudie och databasen PubMed har använts för att hitta vetenskapliga artiklar med hjälp av olika sökord, såsom SARS-CoV 2 and protease inhibitors, SARS-CoV-2 and 3CL-pro, MERS-CoV and 3CLpro inhibitors och SARS-CoV and 3CLpro. Totalt valdes 10 vetenskapliga artiklar ut som grund för att undersöka om några proteashämmare finns rapporterade och hur de utvärderats, dvs i prekliniska studier eller kliniska studier. Resultat  Peptidomimetiska alfa-ketoamider är effektiva bredspektrum hämmare för att hämma 3CL pro i SARS-CoV-2 och enterovirus, t.ex. alfa-ketoamiderna (13a och 13b) som även visade goda farmakokinetiska egenskaper i prekliniska studier. Även läkemedelskandidater (11a och 11b) har utvärderats i prekliniska studier och både visade hög SARS-CoV-2 3CL-pro hämmande aktivitet. Två nya studier visade att genomsekvensen för SARS-CoV-2 3CLpro är mycket lik den för SARS-CoV-1 än MERS-CoV. Herbacetin, rhoifolin pectolinarin och Biflavonoid amentoflavon 9 visade en effektiv hämning av SARS-CoV-1 3CL pro. Herbacetin, isobavachalcone, quercetin 3 ‐ β ‐ d ‐ glukosid, helikrysetin och enterovirushämmare (6b, 6c och 6d) visat sig ha hämmande aktivitet och kunde hämma den enzymatiska aktiviteten hos MERS-CoV 3CL pro. De redan framtagna HIV-proteashämmarna lopinavir och ritonavir har utvärderats i kliniska prövningar och både visade ingen skillnad mot standardbehandling samt minskade inte dödlighet. Slutsats Slutsatsen som kan dras av studien är att det finns flera proteashämmare i preklinisk fas mot SARS-COV-2 3CL-pro samt finns flera proteashämmare mot SARS-CoV-1 och MERS-CoV. Proteashämmare kan vara ett möjligt läkemedel mot COVID-19 i framtiden, men det tar lång tid för att utveckla ett nytt läkemedel.

Following the detection of SARS-CoV-2 RNA fragments in wastewater in March 2020, the use of wastewater-based epidemiology is rapidly emerging as a non-invasive approach to assessing community wide COVID-19 prevalence. Wastewater-based epidemiology is promoted as a complement to clinical testing in terms of improving public health authorities’ preparedness and supporting them in taking required interventions to protect the public health.  To utilize the occurrence of SARS-CoV-2 in wastewater in a public health context and evaluate trends in viral prevalence on a community level, robust data interpretation is required. This master's thesis work examines what is currently known about the factors that influence the concentrations of SARS-CoV-2 in wastewater, as well as the impact of alternative normalization approaches on the relationship between viral wastewater data and clinical case numbers. The work is divided into two parts where this report provides a state-of-the-art review as well as an overview of key findings in the accompanied scientific paper.  The study involved collection of wastewater samples from two different sized wastewater treatment plants (WWTPs) in Luleå municipality, between January and March 2021.  Concentrations of SARS-CoV-2 RNA were quantified in each sample as well as concentrations of total nitrogen (TN), total phosphorus (TP) and pepper mild mottle virus (PMMoV). Average daily WWTP flow and environmental data (precipitation and temperature) were continuously measured over the sampling period. The population size was estimated based on mass loads of TN and TP and literature values of the domestic contribution of these parameters to the sewer system. The viral wastewater data was normalized using the estimations of population size, census data, WWTP flow and PMMoV. The impact of the alternative normalization approaches was evaluated using statistical analyses to explore the relationship to clinical case numbers.  The result showed that the strength of the correlation between the different normalization approaches and clinical case data differed between the WWTPs. However, within each WWTP the differences in correlation between the different normalization approaches and clinical cases were not significant. Moreover, normalization using WWTP flow (i.e., viral loads) showed a stronger correlation to clinical cases compared to population and PMMoV normalized viral loads. However, when comparing wastewater data between the two catchment areas, the normalization approaches utilizing population (either census or TN and TP estimated population) or PMMoV better reflect the number of clinical cases. Additionally, according to time-shifted analysis, wastewater data of SARS-CoV-2 RNA predated an increase in clinical cases by 0-2 and 5-8 days, respectively, for the larger and smaller WWTPs.

Introduction: The coronavirus is an RNA virus with a lipid envelope. The initially known coronaviruses are (MERS-CoV and SARS-CoV) which caused fatal endemics in 2002 and 2012. At the end of 2019, a new variant of coronavirus called SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) was discovered in Wuhan in China. SARS-CoV-2 has caused serious diseases especially in the older groups with millions of infections and deaths. The World Health Organization (WHO) identified Covid-19 as a global health emergency on 30 January 2020 and classified it as a pandemic on March 11, 2020. Several companies started developing a vaccine to stop the spread of SARS-CoV-2. Several vaccination programs have been approved and are currently used against Covid-19. Objectives: The work aimed to investigate the safety and efficacy of the approved mRNA-based vaccines against SARS-CoV-2. Method: The work was based on reviewing published, scientific articles that examined safety and efficacy of mRNA-based vaccines (Pfizer BionTech BNT162b and mRNA-1273 Modern). In total there were five clinical trials selected from Pubmed. Two studies examined the safety and efficacy of mRNA-1273 Moderna and three other studies examined the safety and effectiveness of the Pfizer BionTech BNT162b. Results: Both vaccines have shown good safety and efficacy and were well tolerated in patients in different ages. mRNA-based vaccines have shown mild to moderate symptoms that were higher after dose 2 and disappeared after a few days. Both Pfizer BionTech and Modern mRNA-1273 have shown efficiencies over 90%.

Background: Vaccination against SARS-CoV-2 significantly reduces the transmissibility of the virus and the likelihood of a severe course of COVID-19, and is thus a critical component in overcoming the current pandemic. The factors associated with adverse reactions after vaccination against SARS-CoV-2 have not yet been sufficiently evaluated. Methods: We used the Disease Analyzer database (IQVIA) to identify 531,468 individuals who received a total of 908,869 SARS-CoV-2 vaccinations in 827 general practices in Germany between April and September 2021. Cox regression models were used to analyze the frequency of vaccination-related side effects reported within 14 days after SARS-CoV-2 vaccination, as well as subjects’ demographic characteristics and comorbidities. Results: The total number of side effects documented was 28,287 (3.1% of all vaccinations). Pain in the limb (24.3%), fatigue (21.0%), dizziness (17.9%), joint pain (15.7%), fever (9.5%), nausea (7.5%), and myalgia (6.4%) were the most common side effects documented among the 12,575 vaccinations with definite side effects. In the multivariate regression analysis, young age was associated with much higher odds of reported side effects (OR18–30 years: 4.45, OR31–40 years: 3.50, OR41–50 years: 2.89). In addition, pre-existing comorbidities such as dementia (OR: 1.54), somatoform disorder (OR: 1.53), anxiety disorder (OR: 1.43), depression (OR: 1.37), chronic respiratory tract disease (OR: 1.27), hypertension (OR: 1.20), and obesity (1.14) significantly increased the odds of side effects. Finally, the male sex was associated with increased odds of reported side effects (OR: 1.17). Conclusion: Our study, based on a large outpatient database from Germany, identified young age, male sex, and pre-existing comorbidities such as dementia, somatoform disorders, anxiety disorders, and depression as factors associated with vaccine-related adverse events diagnosed in GP practices. These data could help to identify subgroups needing particular advice and care in the context of SARS-CoV-2 vaccinations.

Introduction: Community mitigation strategies (CMS) have demonstrated to be effective in the reduction of transmission and incidence of COVID-19, especially in the population with symptoms associated with the disease. The aim of this study was to evaluate the association between the presence of COVID-19 symptoms and adherence to CMS in Latin American adults. Methods: We carried out a secondary analysis of a database developed by the University of Maryland and Facebook social network during the COVID-19 pandemic. We included Latin American adults that used the Facebook platform and participated in a survey conducted from April 23 to May 23, 2020. The principal outcome variable was reported compliance with the three main CMS (physical distancing, use of face masks, and hand washing). The exposure variable included symptoms suspicious for COVID-19 defined as the presence of three or more symptoms of an acute clinical case of COVID-19. We performed generalized linear models of the Poisson family with a logarithmic link function to evaluate the association between the presence of COVID-19 symptoms and reported compliance with CMS. We calculated crude and adjusted prevalence ratios (PR) with their 95% confidence intervals (95%CI). Results: We analyzed 1,310,690 adults from Latin America; 48.1% were male and 42.9% were under 35 years of age. The prevalence of suspicious symptoms of COVID-19 was 18.5% and reported compliance with the three CMS was 45.3%. The countries with the highest proportion of reported compliance with the three CMS were Peru, Bolivia and Panama, while those with the lowest reported compliance were Costa Rica, Nicaragua and Honduras. In the adjusted model, people with suspicious symptoms for COVID-19 had a 14% lower compliance with the three CMS (aPR = 0.86; 95%CI: 0.85–0.87; p < 0.001). Conclusions: Less than half of the participants complied with the CMS, and those presenting suspicious symptoms for COVID-19 had lower reported compliance with the three CMS. / University of Maryland / Revisión por pares

PURPOSE OF REVIEW: This review article aims to explore the GI changes induced by SARS-CoV-2 and how gut microbial homeostasis can influence these changes and affect the lung-gut axis and its relationship with the induction of the cytokine release syndrome in severe COVID-19 patients. RECENT FINDINGS: Coronavirus disease 2019 (COVID-19) affects not only the respiratory system but can produce multi-systemic damage. The expression of angiotensin-converting enzyme 2 (ACE-2) receptors in the gastrointestinal (GI) tract, the high prevalence of GI symptoms in severely ill COVID-19 patients, and the abnormalities described in the gut microbiome in these patients have raised concerns about the influence of GI tract as a risk factor or as a potential modulator to reduce the severity of COVID-19. Understanding the mechanisms by which gut dysbiosis may influence viral transmission and disease progression in COVID-19 may help in shaping how accessible therapies, like diet modulation, can potentially help beat the devastating consequences of COVID-19.

BACKGROUND: Telepresence robots provide real-time audio, video, and mobility features, allowing faculty and students to engage in learning experiences without being physically present. PROBLEM: With multiple students and faculty members needing to quarantine due to the COVID-19 pandemic, a flexible learning environment was essential. APPROACH: The telepresence robots were used as an innovative approach for both faculty and students to engage in learning experiences offered in a variety of settings. OUTCOME: Feedback was obtained from faculty and students about the use of and satisfaction with telepresence robots. The robots were easy to use and posed only a few technological challenges, which were easily overcome. CONCLUSIONS: Telepresence robots were effective tools in overcoming teaching and learning barriers caused by the COVID-19 pandemic. The telepresence robots have many applications, including use in clinical and community settings.

During the past three years, we assisted to the rise of a new pathogen that afflicted the world with a global pandemic. Working in an era of rapid change has posed important challenges and the focus of research has shifted more and more toward topics of greater social utility. However, this period has also brought a new role for wastewater highlighting how it can provide insight into the health of a community. This is the approach of Wastewater-based Epidemiology (WBE). The work presented here aimed to deepen this approach not only at the theoretical level but also contributing with an ongoing monitoring of about 30 months. The main objectives were (i) to collect information on the recently discovered SARS-CoV-2 virus, its biology, transmission mechanism, and role in wastewater treatment plants (WWTP); (ii) set up a surveillance system that would allow to monitor SARS-CoV-2 infections over time, obtaining early information on its spread among the population to support the Health Authority. Starting from a detailed study of the shedding mechanisms of SARS-CoV-2 in the feces of infected patients, we moved on to the evaluation of the viral concentrations in the sewage system and the wastewater entering the WWTP. The possibility of a faecal-oral transmission route of the virus was investigated by evaluating the data about viability and infectivity in wastewater. The natural processes of decay of the virus in wastewater and the reduction of its concentration in the different treatment stages of WWTPs were explored in literature and with experimental data. At the same time, we developed a SARS-CoV-2 surveillance system in wastewater by applying different detection methods. Some practical and scientific aspects of the analysis protocol have been studied in depth such as the choice of the type of sample, the storage temperatures, and the pre-heat treatments aimed at making the analysis safer for the operator. The choice of the concentration method was evaluated to comply with the low concentration of the viral titer and therefore the crucial importance of this phase of the protocol. During the monitoring campaign, we further investigated aspects related to data processing and developed normalization approaches. Samples from WWTPs in the province of Trento were analysed weekly and sampling frequencies and curve smoothing methods deriving from those data were evaluated. The trend curves thus obtained were compared with those deriving from clinical data provided by the local Health Authority and signals of early warnings of virus diffusion trends in the population were highlighted. With the alternation of the different variants of the virus and the evidence of their importance in the development of new waves of infection, a PCR based genotyping method has been devised to rapidly identify the already known variants. In conclusion, this research project addressed a broad spectrum of aspects related to the WBE approach in contrasting the COVID-19 emergency and confirmed that wastewater could be a valuable source of information and management support for this and other emerging pathogens or micropollutants.

<p dir="ltr">The recent global pandemic, COVID-19, has revealed to all the importance of understanding the complex relationship between viruses and hosts. Before COVID-19, I started my study of viral protein-host lipid interactions in the hemorrhagic fevers Ebola and Marburg viruses. These viruses contain a matrix protein that interacts with the plasma membrane to facilitate the formation of both authentic viruses and virus-like particles. My goal was to understand the limitations of their specific host lipid interactions. However, when the COVID-19 pandemic began, so to be our swift response in the development of a biosafety level 2 compatible model. This model can be used for studying severe acute respiratory distress syndrome 2 (SARS-CoV-2) assembly, egress, and entry. This model enabled exponentially greater access to more facilities to study the intricacies of SARS-CoV-2 assembly. With more access to studying the virus in a safe model, our goal is to push the understanding of viral assembly faster. I then began to take apart the individual pieces of the model and started to look at understanding the roles that they play independently. The membrane protein is the most abundant structural protein and I studied the specific lipid interactions of the soluble fraction of the protein. Physicians observed nucleocapsid protein mutations in the clinic with the increasing number of SARS-CoV-2 variants that are on the rise. The microscopy data collected can give us more insight into perhaps how the nucleocapsid protein induces the formation of filopodia structures at the plasma membrane. The envelope protein proved to be a challenge, but I determined a specific envelope and ceramide interaction in cells. The envelope protein was also causing the formation of microvesicles for an undefined function. I was able to determine the subcellular localization of the protein to the mitochondria. The localization to the mitochondria appears to induce depolarization of the mitochondria membrane action potential and induces the increase in mitochondria dysfunction signal, cytochrome c. Although the mitochondria were dysfunctional, there was no increase in apoptosis signal in the presence of the protein alone.</p>

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