The starting point of the work is that an analysis of the value bases of critical social issues is difficult to carry out in any qualified sense from an unstructured basis and that attempts to do so easily result in relatively superficial discussions of particular issues. Instead, we suggest how this might be viewed from a more holistic ethical and systems theological perspective.  In doing so, we review a new framework that aims to distil relevant issues regarding necessary trade-offs and how this can be done. Broadly speaking, this consists of a kind of Socratic dialogue that systematically examines the value base of the decisions that need to be made, as well as whether the effects of the decisions become unacceptable and thus need to be modified vis-a-vis the normative system embraced by the decision-maker. We discuss the role of theologians in this and emphasize that they should take a larger place in discussions on how to deal with complex societal crises, and the main point of this work is therefore to demonstrate the importance of a systematic and transparent method for filtering out critical components from ethical and theological standpoints, and to clarify the effects of the trade-offs between fundamental values that are made in real decision-making situations.

Angiotensin-converting enzyme 2 (ACE2) has been identified as the cellular entry receptor for the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High ACE2 tissue expression and low glycine levels were suggested to increase susceptibility for SARS-CoV-2 infection and increasing circulating ACE2 has been proposed as one possible strategy to combat COVID-19. In humans, aerobic physical exercise induces an increase in plasma ACE2 in some individuals. However, it is not clear whether glycine and ACE2 levels depend on intrinsic exercise capacity or on exercise training. We used rats selectively bred for high intrinsic exercise capacity (HCR) or low exercise capacity (LCR) and tested the influence of this genetic predetermination and/or aerobic exercise on metabolites, ACE2 tissue expression and circulating ACE 2. ACE2 expression was measured in different tissues in the sedentary animals and again after 4 weeks of high-intensity aerobic exercise in both LCRs and HCRs. Sedentary HCRs exhibited significantly higher circulating ACE2 concentrations compared to LCRs, but a lower expression of ACE2 in all investigated tissues except for adipose tissue. Body weight was negatively correlated with serum ACE2 and positively correlated with ACE2 expression in the heart. Aerobic exercise caused a significant decrease in ACE2 expression in the lung, heart, muscle, and kidney both in LCRs and HCRs. Our results suggest that ACE2 expression, circulating ACE2 and glycine serum concentration are related to aerobic intrinsic exercise capacity and can be influenced with exercise. These results may support the hypothesis that physically fit individuals have a lower susceptibility for COVID-19 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 as a highly infectious virus that spread rapidly and was declared a pandemic by the World Health Organization (WHO) in March of 2020.1 SARS-CoV-2 infection causes respiratory disease (Coronavirus Disease; COVID-19), and during the initial infection wave of the pandemic, disease severity ranged from asymptomatic to mild upper respiratory disease, to severe pneumonia resulting in hospitalization and death.1 To date, over 750 million cases of COVID-19 and almost 7 million deaths due to the disease have been confirmed (WHO COVID-19 Dashboard). Virus-like particles are nanoparticles made up of existing viral structural proteins that will assemble into a particle form. The hepatitis B virus core antigen (∆HBcAg) is a stable VLP that will maintain its ability to fold into a viral particle following incorporation of foreign epitopes into its protein sequence. In this project, we produced a vaccine against SARS-CoV-2 that was composed of three SARS-CoV-2 Spike protein epitopes inserted into the ∆HBcAg VLP. These insertions included Spike epitopes predicted to induce a humoral and/or cell-mediated immune response. The immunogenicity of the resultant vaccine was tested utilizing a K18-hACE2 transgenic C57BL/6 mouse model. Mice were challenged with live SARS-CoV-2 three weeks after the final booster dose and the vaccine was evaluated for protective efficacy. Results of these studies showed epitope-specific humoral and cell-mediated immune responses, but these responses were insufficient in protecting against SARS-CoV-2 infection. / Doctor of Philosophy / Coronaviruses have caused gastrointestinal and respiratory disease in humans and a variety of veterinary species for decades. In response to the onset of the COVID-19 (Coronavirus Disease) pandemic in late 2019, we created a vaccine against the virus that causes this disease: the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infects human cells by attaching via one of its surface proteins (the Spike protein) to the human ACE2 receptor (angiotensin converting enzyme 2). After this binding occurs, the virus can enter the cell and begin to replicate, resulting in cellular damage, organ-level dysfunction, and clinical disease. An effective vaccine against SARS-CoV-2 would induce antibodies that bind to this Spike protein, thereby blocking its ability to infect host cells and preventing the downstream effects of infection. Our vaccine consisted of a protein from the hepatitis B virus (∆HBcAg), which naturally folds into a virus-like particle (VLP). This VLP can be used as a stable backbone and foreign epitopes can be inserted into the particle for presentation to the immune system as a vaccine. We inserted three SARS-CoV-2 Spike protein epitope into the ∆HBcAg backbone and tested the vaccine's ability to elicit an immune response and protect against infection with live SARS-CoV-2. Results from these studies showed an antibody response to the vaccine and higher levels of anti-viral cytokines in vaccinated mice compared to controls, but incomplete protection against disease. Additionally, we identified areas for vaccine optimization that will inform future studies utilizing this type of vaccine platform.

La supervivencia de los organismos superiores depende de que sus células se organicen y actúen de manera sincronizada para cumplir funciones específicas, para lo cual es fundamental la comunicación intercelular. Este proceso es básico para la vida de todas las células, pero es la razón de ser en las neuronas que están especializadas en recibir información, procesarla y comunicarla a otras células. En el sistema nervioso, la principal forma de comunicación se realiza a través de la sinapsis química, en la que una neurona libera un mensajero químico, el neurotransmisor, que es reconocido por un receptor presente en otra célula permitiéndole responder al mensaje. La acetilcolina es uno de los principales neurotransmisores utilizados por las neuronas, y sus receptores, tanto metabotrópicos como ionotrópicos, están expresados en muchos tipos celulares. Los receptores ionotrópicos de acetilcolina, llamados receptores nicotínicos, son canales catiónicos pentaméricos que pertenecen a la familia de receptores Cys-loop. El receptor nicotínico de acetilcolina α7 es un homopentámero que exhibe propiedades funcionales particulares fundamentales para su rol neuromodulador, incluyendo la elevada permeabilidad al Ca2+ y la capacidad para transformar respuestas ionotrópicas transitorias en eventos más sostenidos de señalización metabotrópica. Es uno de los receptores nicotínicos más abundantes en el sistema nervioso, aunque también se encuentra presente en otros tejidos. En el sistema nervioso central cumple un rol importante en procesos de cognición, atención y memoria, al regular la liberación de neurotransmisores, mediar la transmisión sináptica rápida y modular la excitabilidad neuronal. Una disminución de su actividad se ha asociado con diversos desórdenes neurológicos y neurodegenerativos, incluyendo esquizofrenia, autismo y enfermedad de Alzheimer. El receptor α7 también se expresa en células no neuronales, tales como -entre otras-, los astrocitos, la microglía, los linfocitos B y T, las células epiteliales, los macrófagos, cumpliendo un rol importante en inmunidad, inflamación y neuroprotección. Las acciones neuromoduladoras, neuroprotectoras y antinflamatorias sistémicas del receptor nicotínico de acetilcolina α7 junto a sus propiedades únicas de activación, desensibilización, permeabilidad al Ca2+ y rol dual ionotrópico-metabotrópico, lo han convertido en un blanco farmacológico emergente muy importante en diversos desórdenes neurológicos, neurodegenerativos e inflamatorios. Este trabajo de tesis se basó en el estudio de los aspectos moleculares relacionados a diferentes tipos de modulación de las funciones ionotrópicas y metabotrópicas del receptor nicotínico de acetilcolina α7 humano. Para ello se utilizaron principalmente técnicas electrofisiológicas a nivel de canal único y de corrientes macroscópicas, en conjunto con análisis de proteínas por western blot y ensayos de movimiento de Ca2+ intracelular. El capítulo I se centró en el estudio de la modulación de las funciones ionotrópicas y metabotrópicas del receptor α7 por eventos de fosforilación/desfosforilación. Se demostró que favorecer el estado desfosforilado de las tirosinas del dominio intracelular de α7 potencia la actividad ionotrópica del receptor. A nivel de corrientes unitarias, el efecto potenciador involucró un aumento en la frecuencia y duración de los episodios de activación, mientras que a nivel de corrientes macroscópicas se manifestó por una disminución en la velocidad de decaimiento de la corriente, y un aumento en la tasa de recuperación desde el estado desensibilizado. Por el contrario, la desfosforilación de las tirosinas tuvo un efecto negativo en la actividad metabotrópica del receptor, estudiada por western blot a partir de la vía de ERK 1/2. Además, a diferencia de lo observado para las tirosinas, las alteraciones en el estado de fosforilación de serinas y treoninas del dominio intracelular no ocasionaron cambios importantes en la actividad ionotrópica de α7 en las condiciones experimentales aquí utilizadas. En síntesis, los resultados presentados en este capítulo ponen en evidencia que la fosforilación de las tirosinas, si bien es absolutamente necesaria para la actividad metabotrópica de α7 mediada por la vía ERK 1/2, actúa como un modulador negativo de la actividad ionotrópica del receptor. El capítulo II abordó el estudio de la asociación funcional entre un fragmento peptídico de la glicoproteína S del SARS-CoV-2 (Y674-R685) y el receptor nicotínico de acetilcolina α7 humano. La asociación entre SARS-CoV-2 y los receptores nicotínicos fue propuesta en forma de hipótesis al comienzo de la pandemia. Más adelante, simulaciones de dinámica molecular mostraron que el fragmento Y674-R685 no solo tiene afinidad por α7, sino que penetra profundamente en el bolsillo de unión a agonista del receptor. En este capítulo, en primer lugar, se demostró que el fragmento Y674-R685 actúa como un agonista silente de α7, ya que es capaz de provocar corrientes unitarias y macroscópicas del receptor, pero solo en presencia de un modulador alostérico positivo. Por otro lado, se demostró que Y674-R685 también ejerce una modulación negativa de α7, que se evidenció por una profunda disminución, dependiente de la concentración, en la duración de los episodios de activación de los canales potenciados y en la amplitud de las respuestas macroscópicas provocadas por la acetilcolina. De esta manera, utilizando distintos enfoques electrofisiológicos, se develó la existencia de una interacción funcional entre el fragmento Y674-R685 de la glicoproteína S del SARS-CoV-2 y el receptor α7 que proporciona las bases moleculares para seguir explorando la participación de los receptores nicotínicos en la fisiopatología de la COVID-19. El capítulo III se basó en el estudio del receptor α7 como blanco del cannabidiol, lo cual resulta de gran interés debido al uso expandido de este fitocannabinoide para tratar diferentes condiciones patológicas gracias a sus propiedades terapéuticas y a la ausencia de efectos psicoactivos. Para ello se exploró el efecto del cannabidiol en las funciones ionotrópicas y metabotrópicas de α7 mediante técnicas electrofisiológicas y ensayos de movimiento de Ca2+ intracelular. En lo que respecta a las funciones ionotrópicas, se demostró que el cannabidiol produce una rápida disminución de la actividad del canal a nivel de corrientes unitarias evidenciada por la reducción en la frecuencia de los episodios de activación. Este efecto fue dependiente de la concentración y se dio con una CI50 en el rango submicromolar, lo que indica una potente modulación negativa. Por otra parte, el cannabidiol también produjo una modulación negativa en la función metabotrópica de α7 que se evidenció por una marcada disminución en las respuestas de Ca2+ intracelular tras la activación del receptor. Estos resultados demuestran que el cannabidiol ejerce una modulación negativa de α7 de relevancia farmacológica que debe tenerse en cuenta a la hora de evaluar los posibles usos terapéuticos del fitocannabinoide. En conjunto, los resultados presentados en esta tesis amplían el entendimiento de los aspectos moleculares relacionados con la modulación de las funciones ionotrópicas y metabotrópicas del receptor nicotínico de acetilcolina α7 en distintas condiciones, a saber, fisiológicas (eventos de fosforilación/desfosforilación), patológicas (fragmento peptídico derivado de la glicoproteína S del SARS-CoV-2) y terapéuticas (cannabidiol). / The survival of higher organisms depends on the ability of their cells to be well organized and to behave in a synchronized manner to fulfill specific functions for which intercellular communication is of pivotal importance. This process is basic for the life of all cells, but it is the raison d'être in neurons that are specialized in receiving information, processing it, and communicating it to other cells. In the nervous system, the main form of communication is carried out via the chemical synapse, in which a neuron releases a chemical messenger, the neurotransmitter, which is identified by a receptor present in another cell, allowing it to respond to the message. Acetylcholine is one of the main neurotransmitters used by neurons, and its receptors, both metabotropic and ionotropic, are expressed in many cell types. Ionotropic acetylcholine receptors, called nicotinic receptors, are pentameric cation channels belonging to the Cys-loop receptor family. The α7 nicotinic acetylcholine receptor is a homopentamer with particular functional properties critical to its neuromodulatory role, including high Ca2+ permeability and the ability to transform transient ionotropic responses into more sustained metabotropic signaling events. It is one of the most abundant nicotinic receptors in the nervous system, although it is also present in other tissues. In the central nervous system, it plays an important role in cognition, attention, and memory, by regulating the release of neurotransmitters, mediating rapid synaptic transmission, and modulating neuronal excitability. A decrease in α7 activity has been associated with various neurological and neurodegenerative disorders, such as schizophrenia, autism, and Alzheimer's disease. The α7 receptor is also expressed in non-neuronal cells; namely, astrocytes, microglia, B and T lymphocytes, epithelial cells, and macrophages, and plays an important role in immunity, inflammation, and neuroprotection. The neuromodulatory, neuroprotective, and systemic anti-inflammatory actions of α7, together with its unique activating, desensitizing, Ca2+ permeability, and dual ionotropic-metabotropic properties, have made the receptor a very important emerging drug target in various neurological, neurodegenerative, and inflammatory disorders. This P.D. thesis work was based on the study of molecular aspects related to different types of modulation of the ionotropic and metabotropic functions of the human α7 nicotinic acetylcholine receptor. To this end, electrophysiological techniques at the single channel and macroscopic current levels were mainly used, as well as protein analysis by western blot and intracellular Ca2+ movement assays. Chapter I focused on the study of α7 receptor ionotropic and metabotropic function modulation by phosphorylation/dephosphorylation events. It was shown that favoring the dephosphorylated state of α7 intracellular domain tyrosine residues potentiates its ionotropic activity. At the single-channel level, this potentiating effect involved an increase in the frequency and duration of activation episodes, while at the macroscopic level it was manifested by a decrease in the rate of current decay and by an increase in the rate of recovery from the desensitized state. In contrast, tyrosine dephosphorylation had a negative effect on receptor metabotropic activity, studied by western blot from ERK 1/2 pathway. In addition, unlike what was observed for tyrosine residues, alterations in the phosphorylation status of serine and threonine residues present in the intracellular domain did not cause any significant changes in α7 ionotropic activity under the experimental conditions used. Summing up, the results collected in this chapter show that tyrosine phosphorylation, although it is absolutely necessary for α7 metabotropic activity mediated by ERK 1/2 pathway, acts as a negative modulator of receptor ionotropic activity. Chapter II focused on the study of the functional association between a peptide fragment of SARS-CoV-2 S glycoprotein (Y674-R685) and human α7 nicotinic acetylcholine receptor. The association between SARS-CoV-2 and nicotinic receptors was hypothesized at the beginning of the pandemic. Later, molecular dynamics simulations showed that the Y674-R685 fragment not only has affinity for α7 but also penetrates deep into its agonist-binding pocket. In this chapter, it was firstly stated that the Y674-R685 fragment acts as a silent α7 agonist, since it is capable of triggering single-channel and macroscopic currents, but only in the presence of a positive allosteric modulator. On the other hand, it was shown that Y674-R685 also exerts α7 negative modulation, which was evidenced by a profound concentration-dependent decrease in the duration of acetylcholine-induced activation episodes from potentiated channels and macroscopic responses. In this way, using different electrophysiological approaches, the existence of functional interaction between SARS-CoV-2 S glycoprotein Y674-R685 fragment and α7 receptor was revealed, which provides the molecular bases to further explore nicotinic receptor participation in COVID-19 pathophysiology. Chapter III was based on the study of the α7 receptor as a target of cannabidiol, which is of great interest due to the expanded use of this phytocannabinoid to treat different pathological conditions thanks to its therapeutic properties and the absence of psychoactive effects. To this end, the effect of cannabidiol on α7 ionotropic and metabotropic functions was explored using electrophysiological techniques and intracellular Ca2+ movement assays. Regarding ionotropic functions, it was shown that cannabidiol produces a rapid decrease in single-channel activity evidenced by the reduction in activation episodes frequency. This concentration-dependent effect occurred with an IC50 in the submicromolar range, indicating a potent negative modulation. On the other hand, cannabidiol also produced a negative modulation in α7 metabotropic function that was evidenced by a marked decrease in intracellular Ca2+ responses after receptor activation. These results demonstrate that cannabidiol exerts α7 negative modulation of pharmacological relevance that must be taken into account when evaluating possible therapeutic uses of the phytocannabinoid. Taken together, the results presented in this thesis broaden the understanding of molecular aspects related to the modulation of α7 nicotinic acetylcholine receptor ionotropic and metabotropic functions under different conditions, namely physiological (phosphorylation/dephosphorylation events), pathological (SARS-CoV-2 S glycoprotein fragment) and therapeutic (cannabidiol).

Background: In the second year of the COVID-19 pandemic, highly effective and safe vaccines became available. Since patients with rheumatic diseases show increased susceptibility to infections and typical medications raise the risk of severe COVID-19, high vaccination coverage is of significant importance to these patients. Methods: Consecutive patients with different rheumatic diseases were asked for their vaccination status regarding COVID-19, influenza and Streptococcus pneumoniae during their routine consultations. Any reported vaccination was validated with their personal vaccination card and/or by reviewing the CovPass smartphone app. Reasons for not having a COVID-19 vaccination were documented. Results: A total of 201 patients (mean age 62.3 ± 14.1 years) were included, the majority of them (44.3%) with rheumatoid arthritis, followed by spondyloarthritis (27.4%) and connective tissue diseases (21.4%). Vaccination coverage for SARS-CoV-2 was 80.1%; 85.6% got at least the first vaccination shot. Both valid influenza and pneumococcus coverage were associated with a higher probability of SARS-CoV-2 vaccination (odds ratio (OR) 6.243, 95% confidence interval (CI) 2.637–14.783, p < 0.0001 and OR 6.372, 95% CI 2.105–19.282, p = 0.0003, respectively). The main reason for a missing SARS-CoV-2 vaccination (70%) was being sceptical about the vaccine itself (i.e., the subjective impression that the vaccine was not properly tested and fear of unwanted side effects). Conclusions: Vaccination coverage against SARS-CoV-2 is high in patients with rheumatic diseases. Nevertheless, there are unmet needs regarding vaccination education to further increase vaccination rates.

At the beginning of 2020, the SARS-CoV-2 virus, known more commonly as COVID-19, created a pandemic. To slow its spread, healthcare workers were heavily encouraged to vaccinate themselves. However, nurses have been less likely to be vaccinated against COVID-19 than physicians. Four common themes have been associated with vaccine hesitancy among nurses, namely certain demographic variables (e.g., younger age and female sex), fears of the vaccine, conspiracy theories and news sources, and medical and psychological histories that pertain to receiving the COVID-19 vaccine. Thus, this study aimed to identify whether these factors apply to Florida nurses' decisions to get vaccinated after the height of the pandemic. To approach this problem, sixty-five participants were surveyed through a Qualtrics cross-sectional questionnaire. The results revealed that approximately 18.5% of participants were not vaccinated. Trends in the data revealed that older age and a postgraduate education level were associated with receiving the vaccine. Non-vaccinated participants had less confidence in the vaccine's ability to reduce the risk of hospitalization, death, and infection, and they had a stronger fear of side effects and the vaccine's rapid development. Several vaccinated and non-vaccinated participants also believed vaccine conspiracy theories, such as that vaccine safety data is falsified. Many non-vaccinated nurses also received SARS-CoV-2 information from social media or their patients, whereas many vaccinated nurses received information from government news sources or physicians. Non-vaccinated nurses also tended to have more discomfort towards hypodermic injections than vaccinated nurses. These conclusions are generalizable to the nurses of this study and may not be generalizable to all nurses. However, because nurses are on the frontlines of the healthcare field and have an essential role in informing the public about health, the results of this study can help inform vaccine education interventions should a future pandemic occur.

Bakgrund: Under slutet av 2019 bröt en ny epidemi ut med ett nytt coronavirus som orsakar feber och luftvägsbesvär. Under våren 2020 benämndes epidemin som en pandemi. Resurser har fördelats för att kunna ta hand om det stora antalet människor som insjuknat i covid-19.  Anestesisjuksköterskor har under pandemin omplacerats för att vårda intensivvårdspatienter med covid- 19. Intensivvård och anestesisjukvård är två olika men nära besläktade utbildningar. Syfte: Syftet med denna undersökning var att beskriva anestesisjuksköterskors upplevelse av att vårda intensivvårdspatienter med covid-19. Metod: En kvalitativ design med deskriptiv ansats. Åtta anestesisjuksköterskor som uppfyllde urvalskriterierna har intervjuats. Data har analyserats med kvalitativ innehållsanalys. Resultat: Anestesisjuksköterskorna upplevde det som att bli inkastad i något okänt med bristande introduktion. Stora delar av omvårdnaden lämnades över till undersköterskor erfarna inom intensivvård som hjälpte till att leda omvårdnadsarbetet runt patienten. Ett gott samarbete bland kollegor var viktigt för att känna trygghet. Anestesisjuksköterskorna upplevde stress och oro över att arbeta med en ny patientgrupp, medicinteknik och läkemedelshantering.  Anestesisjuksköterskorna kände stolthet över att kunna hjälpa till i en pandemi och göra sitt bästa. De nämnde det som positivt att de hade utvecklats i sin yrkesroll. Diskussion: Arbetets fynd talar om en påfrestande arbetssituation präglad av mycket stress och oro på grund av avsaknad av intensivvårdsspecifik kompetens. Tidigare forskning beskriver att kompetens är ett fenomen som påverkas av utbildning, arbetslivserfarenhet och kvalificering för det speciella yrkesutövan. Slutsats: Patientsäkerheten och omvårdnad av patienten kan brista när personalen saknar kompetens och tid för att utöva sitt arbete. Politiker och chefer behöver mobilisera en sjukvård som klarar av en ny pandemi för att kunna upprätthålla god patientvård- och säkerhet.  Nyckelord: Anestesisjuksköterska, omvårdnad, covid- 19/SARS- CoV-2, pandemi, patientsäkerhet. Keywords: Nurse anaesthetists, nursing, covid-19/SARS-CoV-2, pandemic, patient safety

The current Coronavirus disease 2019 (COVID-19) outbreak, caused by a virus called severe acute respiratory syndrome 2 (SARS-CoV-2), has become a global health emergency. Recent findings in case studies assert that the transmigration of SARS-CoV-2 to the nervous system implicates severe neurotropic pathologies, including the onset of the rare autoimmune disease called Guillain-Barré syndrome (GBS). GBS is recognized as several disorders characterized by immune-mediated polyradiculoneuropathy, which is typically preceded by an infection or other immune stimulation. The symptoms of GBS initially present as acute symmetrical ascending paresthesia, weakness, and paralysis. This meta-analysis serves to help understand the predisposing factors (such as gender, age, comorbidities) and the clinical features of COVID-19- induced GBS. Most patients affected were 40 years or older and comprised 78.2% of all the cases. Males comprised most of the cases (62.8%; n=76). The patient mortality was 9.1%, intensive care unit (ICU) admission was 46.6%, and the need for mechanical ventilation was 35.8%. It was found that concomitant GBS and COVID-19 patients most often presented with increased cerebral spinal fluid (CSF) protein levels (88%; n=106), hyporeflexia or areflexia (87.6%) (n=106), lower limb strength and sensation impairment (91.7%; n=111), upper limb strength and sensation impairment (83.5; n=101), and somatic sensation impairment (73.6%; n=89). It is postulated that COVID-19 triggers the onset of GBS through a “cytokine release storm” (CRS) that occurs in the early stages of the disease. The same cytokines and chemokines involved in this CRS caused by COVID-19 contribute to the onset of GBS. Predisposing factors which influence this concomitance include male gender and older age. Most of the reported symptoms included abnormal limb functions (including paresthesia, weakness, and paralysis) and absent or weak deep tendon reflexes. The most common variant of GBS observed was AIDP, and the most significant laboratory finding among patients was high CSF protein levels.

The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2, or SARS-CoV-2, has been ongoing for over two years. The virus spreads easily and is more unpredictable than well-known viruses like the flu, making it important to have reliable combative measures before we fully drop non-vaccine preventive actions, like mask-wearing.Therefore, we used computational protein modeling to investigate the interactions of three nonstructural proteins (abbreviated Nsp) encoded in the viral RNA genome– Nsp3, Nsp5, and Nsp6 – which are involved in the viral life cycle, with human P-type polyamine transporting ATPases ATP13A2 and ATP13A3, whose disease symptoms when mutated mimic certain COVID-19 complications. Understanding these interactions can help shed light on the mechanism of unexpected symptoms seen in COVID-19 and provide an avenue through which to treat infections. Additionally, papain-like protease (PLpro) and 3-chymotrypsin-like protease (3CLpro), which correspond to Nsp3 and Nsp5, respectively, are highly conserved between SARS-CoV and SARS-CoV-2 and thus make good potential drug targets due to their active sites and presumable lower ability to tolerate mutations (reducing the likelihood of treatments becoming ineffective), although the potential effects on the human proteasome would need to be further investigated. In addition, Nsp6 may help the virus evade host defenses by limiting the ability of autophagosomes to deliver viral particles to lysosomes, so limiting its interactions may increase the ability of the host cell to target its viral invader. One compound in particular, Haloperidol, showed promising results; predicted docking (via computational molecular docking software) to Nsp6 alone, as well as to Nsp6-heteroprotein complexes suggested strong binding, indicating a potential strong interaction that could impact the viral protein function and thus the viral life cycle.

The purpose of this study was to focus on whether solely obesity (measured by BMI) leads to an increased risk of COVID-19 mortality in terms of excess in-hospital deaths. As the grim milestone of one million deaths in the United States from COVID-19 was reached, one could assume the disease would continue to coexist with humanity in the long term. While vaccination continued to limit the spread of COVID-19, it was essential to investigate risk factors that may exacerbate the severity of the illness in humans. Obesity is already a global pandemic affecting 40% of Americans and over 650 million people worldwide. Obesity is connected to an entire range of clinical conditions including some of the leading causes of death worldwide making it a more generalizable statistic. Furthermore, the purpose of this study was to conduct a systemic review of major risk factors between obesity and COVID-19, and this analysis shall ascertain which factors have the most predictive value in determining mortality and severity of the condition. Ten research studies of 3,780,926 COVID-19 patient cases were included. Meta-analysis results indicate a pooled OR of 0.93 (0.71-1.23, p = 0.627) for in-hospital mortality of obese patients relative to non-obese patients when adjusted for confounders. All comorbidities associated with the development of severe disease were found to have an equal chance of leading to mortality. In other words, obesity did not lead to a statistically significant risk of dying from COVID-19.