Investigation of variants in genetics and virulence of Porcine Epidemic Diarrhea Virus after serial passage on Vero cells.

Porcine epidemic diarrhea virus (PEDV) is a highly contagious intestinal virus. However, the current PEDV vaccine, which is produced from classical strain G1, offers low protection against recently emerged strain G2. This study aims to develop a better vaccine strain by propagating the PS6 strain, a G2b subgroup originating from Vietnam, on Vero cells until the 100th passage. As the virus was propagated, its titer increased, and its harvest time decreased. Analysis of the nucleotide and amino acid variation of the PS6 strain showed that the P100PS6 had 11, 4, and 2 amino acid variations in the 0 domain, B domain, and ORF3 protein, respectively, compared to the P7PS6 strain. Notably, the ORF3 gene was truncated due to a 16-nucleotide deletion mutation, resulting in a stop codon. The PS6 strain's virulence was evaluated in 5-day-old piglets, with P7PS6 and P100PS6 chosen for comparison. The results showed that P100PS6-inoculated piglets exhibited mild clinical symptoms and histopathological lesions, with a 100% survival rate. In contrast, P7PS6-inoculated piglets showed rapid and typical clinical symptoms of PEDV infection, and the survival rate was 0%. Additionally, the antibodies (IgG and IgA) produced from inoculated piglets with P100PS6 bound to both the P7PS6 and P100PS6 antigens. This finding suggested that the P100PS6 strain was attenuated and could be used to develop a live-attenuated vaccine against highly pathogenic and prevalent G2b-PEDV strains.

Sars-Cov-2 Vaccine from Infected Plant Attenuated Virus Using Acer Cincinatum (Vine Maple)

Purpose of study Proposal for an oral (or if required, parenteral) COVID-19 vaccination based upon this described technology. Investigational theory under study for the past 9 months of COVID-19 growing season. Coronavirus can attack and infect plant species. It was found that SARS-CoV-2 can infect various plant species. Others have found plants, for example tobacco as a good growth medium for Coronavirus and SARS-CoV-2. This current study has found various plants species infected with SARS-CoV-2 by rPCR. As the plants were located beside a well used hiking trail for humans, and were infected along the trail including various species with SARS-CoV-2, hypothesized that human airborne contact had caused infection in the bordering plants. Humans were observed to be coughing while walking on the trail, and were not wearing masks. The plant leaves developed small circular colonies of the virus, which became self-limited at several millimeters in diameter. All of the plants were clear of these lesions before the COVID-19 Pandemic. The plants 'immune' system produced antiviral agents, including lectins which limited the growth of the colonies and prevent death of the leaf and whole plant. The fungal cultures of the 'spots' were negative. The rPCR of all spots tested in the present series was positive for SARS-CoV-2. Hypothesis, that self-augmentation of the virus occurred by the natural culturing in plant leaves that produce antiviral agents as part of their 'immune system.' Hypothesis, a symbiotic type relationship developed between the plant using its chemical immune system, and the virus allowed to replicate in an augmented fashion to allow both the virus and the host to survive and grow. As the top candidates for the oral vaccine are nontoxic, hypothesis involves the maceration of the infected leaves, mixing with a nontoxic adjuvant and flavoring to promote assimilation and palatability, with the proposed route of entry being mastication, thus exposing the oral-nasal mucosa to the vaccine, with the probable best of immunity to usual exposure to the SARS-CoV-2 virus, that is the oral-nasal mucosal and upper airway route. As many types of animals are now infected with SARS-CoV-2, it is further hypothesized that this oral vaccine could also be mass produced to add to various animals by feedstock and oral route. Methods used Hypotheses formed through observations. Testing of observations by pPCR, viral cell culture, fungal culture, light and electron microscopy. Summary of results pPCR SARS-CoV-2 positive, cell culture 'lysis experiment' positive, EM and light microscopy positive, fungal culture negative. Conclusions TABLE OF HYPOTHESES AND STUDY RESULTS (HYPOTHETICAL, OBSERVED, PROVEN) 1. The first hypothesis that the virus is attenuated by the plant, using its innate chemical immune system. Similarly, Pasteur used chemical such as phenol to attenuate viruses for wome of the first successful vaccines. Observed. 2. Hypothesis, the plants 'immune' system produced antiviral agents, including lectins, flavonoids, and others, which limited the growth of the colonies and prevent death of the leaf and whole plant. Proven. 3. Hypothesis is that the nontoxic plants, such as Vine Maple sp.(Acer cincinatum), could be used to produce and oral plant attenuated vaccine. Hypothesis. 4. Hypothesis involves the maceration of the infected leaves, mixing with a nontoxic adjuvant and flavoring to promote assimilation and palatability, with the proposed route of entry being mastication, thus exposing the oral-nasal mucosa to the vaccine, with the probable best of immunity to usual exposure to the SARS-CoV-2 virus, that is the oral-nasal mucosa, upper airway. (Figure Presented).

Attenuation of a Highly Pathogenic Porcine Deltacoronavirus Strain CZ2020 by a Serial Passage In Vitro

Porcine deltacoronavirus (PDCoV) is an emerging swine coronavirus that causes severe diarrhea to pigs of all ages, especially the suckling piglets under one-week-old. We previously isolated a highly pathogenic PDCoV strain, CZ2020, from a diarrheal piglet and have passaged it for over 100 passages. The adaptability of the CZ2020 increased gradually in vitro as the passage increased. Amino acid mutations were observed in pp1a, pp1ab, spike, envelop, and membrane proteins, and the spike protein accounts for 66.7% of all amino acid mutations. Then, the high passage strains, CZ2020-F80 and CZ2020-F100, were selected for evaluation of the pathogenicity in three-day-old piglets to examine whether these amino acid changes affected their virulence. At 2 days postchallenge (DPC), 2/5 piglets started to show typical diarrhea, and at 4 DPC, severe diarrhea was observed in the CZ2020-challenged piglets. Viral RNA could be detected at 1 DPC in rectal swabs and reached its highest at 4 DPC in the CZ2020-challenged group. CZ2020-F80- and CZ2020-F100-challenged groups have one piglet exhibiting mild diarrhea at 4 and 6 DPC, respectively. Compared with the CZ2020-challenged group, the piglets in CZ2020-F80- and F100-challenged groups had lower viral loads in rectal swabs, intestines, and other organs. No obvious histopathological lesions were observed in the intestines of CZ2020-F80- and F100-challenged piglets. Virulent PDCoV infection could also induce strong interferons and proinflammatory cytokines in vitro and in vivo. These data indicate that the strains, CZ2020-F80 and CZ2020-F100, were significantly attenuated via serial passaging in vitro and have the potential for developing attenuated vaccine candidates.

Elevated FAI Index of Pericoronary Inflammation on Coronary CT Identifies Increased Risk of Coronary Plaque Vulnerability after COVID-19 Infection.

Inflammation is a key factor in the development of atherosclerosis, a disease characterized by the buildup of plaque in the arteries. COVID-19 infection is known to cause systemic inflammation, but its impact on local plaque vulnerability is unclear. Our study aimed to investigate the impact of COVID-19 infection on coronary artery disease (CAD) in patients who underwent computed tomography angiography (CCTA) for chest pain in the early stages after infection, using an AI-powered solution called CaRi-Heart®. The study included 158 patients (mean age was 61.63 ± 10.14 years) with angina and low to intermediate clinical likelihood of CAD, with 75 having a previous COVID-19 infection and 83 without infection. The results showed that patients who had a previous COVID-19 infection had higher levels of pericoronary inflammation than those who did not have a COVID-19 infection, suggesting that COVID-19 may increase the risk of coronary plaque destabilization. This study highlights the potential long-term impact of COVID-19 on cardiovascular health, and the importance of monitoring and managing cardiovascular risk factors in patients recovering from COVID-19 infection. The AI-powered CaRi-Heart® technology may offer a non-invasive way to detect coronary artery inflammation and plaque instability in patients with COVID-19.

COVID-19 Vaccines: Fabrication Techniques and Current Status

The year 2020 was the most challenging period due to the havoc caused by the outbreak of novel coronavirus SARS-CoV-2. Scientists and researchers all around the world have endeav-ored every possible approach to find solutions in context to therapeutics and vaccines to control the spread of this life-threatening virus. The acceleration instigated by the outbreak of SARS-CoV-2 and its mutated strains has leveraged the use of numerous platform technologies for the development of vaccines against this unfathomable disease. Vaccines could play an important role in miti-gating the effects of COVID-19 and reducing the ongoing health crisis. Various innovative plat-forms like proteins, nucleic acids, viruses, and viral vectors have been exploited to fabricate vaccines depicting almost 90% of efficacy like BNT162b2, AZD1222, Ad5-nCoV, etc. Some of these vaccines are multipotent and have shown potent activity against newly emerged malicious strains of SARS-CoV-2 like B.1.351 and B.1.1.7. In this review article, we have gathered key findings from various sources of recently popularized vaccine candidates, which will provide an overview of potential vaccine candidates against this virus and will help the researchers to investi-gate possible ways to annihilate this menace and design new moieties.Copyright © 2022 Bentham Science Publishers.

Profile of healthcare workers who contracted COVID-19 after vaccination against SARS-CoV-2

Introduction: Being at high-risk for COVID-19, healthcare workers (HCW) were prioritized in the beginning of vaccination campaigns in Tunisia. The emergence of several variants raises the issue of resistance and postvaccination infection. Aim(s): To study epidemiological and clinical characteristics of COVID-19 infection in HCW who previously had COVID19 vaccine. Method(s): Retrospective descriptive study focusing on Rabta hospital's HCW who presented themselves for a reinstatement visit after post-vaccination COVID-19 infection, from 15 March to 31 December 2021. Result(s): There were 122 HCW with a mean age of 42.8 years, a sex ratio of 0.5, and an average professional seniority of 13.8 years. 32% worked full-time in COVID-19 wards and13.1% had a history of COVID-19 before vaccination. Half had received two doses of vaccine. They were vaccinated mainly with mRNA (66.4%), viral vector (19.9%) or attenuated virus (12.3%). Symptoms appeared, on average, 35 days after the last dose of vaccine and the disease was confirmed by RT-PCR after 3 days of the symptom's onset. The main symptoms described were asthenia (66.4%), cough (66.4%), headache (62.3%), anosmia (64.8%), ageusia (55.7%), fever (52.2%), diarrhea (40.2%) ans dyspnea (21.3%). They were mainly put on symptomatic treatment and home rest for 11 days. However, 15% had an extension of their sick-leave and 2.5% presented a severe form requiring hospitalization. On return to work, 59.8% reported the persistence of symptoms including cough (18.9%), asthenia (11.5%), dyspnea (9.8%), anosmia and ageusia (7.4%). Conclusion(s): Vaccinated HCW presented mainly a mild form of COVID-19. Vaccination is an important and promising means to end this pandemic.

The 21st century water quality challenges for managed aquifer recharge: towards a risk-based regulatory approach.

Sustained environmental and human health protection is threatened by ~350,000 chemicals available in global markets, plus new biological entities including coronaviruses. These water-quality hazards challenge the proponents of managed aquifer recharge (MAR) who seek to ensure the integrity of groundwater. A risk-based regulatory framework accounting for groundwater quality changes, adoption in subsurface attenuation zones, and use of advanced monitoring methods is required to support confidence in the sustainability of MAR.

La protection durable de l'environnement et de la santé humaine est menacée par ~350,000 substances chimiques disponibles sur les marchés mondiaux, à quoi s'ajoutent de nouvelles entités biologiques, incluant les coronavirus. Ces risques sur la qualité de l'eau sont un défi pour les partisans de la recharge raisonnée des aquifères (RRA) qui cherchent à assurer l'intégrité des eaux souterraines. Un cadre réglementaire basé sur les risques, tenant compte des changements de qualité des eaux souterraines, de l'adoption de zones d'atténuation souterraine, de l'utilisation de méthodes de contrôle avancées, est nécessaire pour soutenir la confiance dans la durabilité de la RRA.

La sostenibilidad del medio ambiente y la protección de la salud humana se ve amenazada por unas 350,000 sustancias químicas disponibles en los mercados mundiales, además de nuevas entidades biológicas como el coronavirus. Estos peligros para la calidad del agua suponen un desafío para los defensores de la recarga gestionada de acuíferos (MAR), que pretenden garantizar la integridad de las aguas subterráneas. Se necesita un marco normativo basado en el riesgo que tenga en cuenta los cambios en la calidad de las aguas subterráneas, la incorporación a las zonas de atenuación del subsuelo y el uso de métodos avanzados de control para respaldar la confianza en la sostenibilidad de la recarga acuífera gestionada.

A proteção sustentável do meio ambiente e da saúde humana está ameaçada por cerca de 350,000 produtos químicos disponíveis nos mercados globais, além de novas entidades biológicas, incluindo coronavírus. Esses riscos de qualidade da água desafiam os proponentes da recarga gerenciada de aquíferos (RGA) que buscam garantir a integridade das águas subterrâneas. Uma estrutura regulatória baseada em risco que considere as mudanças na qualidade das águas subterrâneas, a adoção em zonas de atenuação do subsolo e o uso de métodos avançados de monitoramento são necessários para apoiar a confiança na sustentabilidade da RGA.

Addendum: Predictive form of the FPM model

The article Oustaloup et al. (2021) has shown that the Fractional Power Model (FPM), A+Btm, enables well representing the cumulated data of COVID infections, thanks to a nonlinear identification technique. Beyond this identification interval, the article has also shown that the model enables predicting the future values on an unusual prediction horizon as for its range. The objective of this addendum is to explain, via an autoregressive form, why this model intrinsically benefits from such a predictivity property, the idea being to show the interest of the FPM model by highlighting its predictive specificity, inherent to non-integer integration that conditions the model. More precisely, this addendum establishes a predictive form with long memory of the FPM model. This form corresponds to an autoregressive (AR) filter of infinite order. Taking into account the whole past through an indefinite linear combination of past values, a first predictive form, said to be with long memory, results from an approach using one of the formulations of non-integer differentiation. Actually, as this first predictive form is the one of the power-law, tm, its adaptation to the FPM model, A+Btm, which generalizes the linear regression, A+Bt, is then straightforward: it leads to the predictive form of the FPM model that specifies the model in prediction. This predictive form with long memory shows that the predictivity of the FPM model is such that any predicted value takes into account the whole past, according to a weighted sum of all the past values. These values are taken into account through weighting coefficients, that, for m>−1 and a fortiori for m>0, correspond to an attenuation of the past, that the non-integer power, m, determines by itself. To confirm the specificity of the FPM model in considering the past, this model is compared with a model of another nature, also having three parameters, namely an exponential model (Liu et al. (2020);Sallahi et al. (2021)): whereas, for the FPM model, the past is taken into account globally through all past instants, for the exponential model, the past is taken into account only locally through one single past instant, the predictive form of the model having a short memory and corresponding to an AR filter of order 1. Comparative results, obtained in prediction for these two models, show the predictive interest of the FPM model.

Practicing Telemedicines in India

The great use of telecommunication technology propels new healthcare system of telemedicine through which diagnosis as well as treatment can be done in the remote areas. The ancient Greek language explain the terminology of telemedicine in the phrase of distance healing. As per WHO, Telemedicine is the delivery of health-care services, where distance is a critical factor, by all health-care professionals using information and communications technologies for the exchange of valid information for diagnosis, treatment and prevention of disease and injuries, research and evaluation, and the continuing education of health-care workers, with the aim of advancing the health of individuals and communities. Historically the concept of teleconsultation was evolved in the first half of twentieth century when the data of ECG was communicated through telephone lines, this can be traced as first evidence of this unique healthcare system. Further the introduction of electrical system of telegraph as well as evolution of telephone revolutionized this system of healthcare. when the Technology of telemedicine help both patients as well as service providers in multiple ways involving physicians, surgeons, pharmacists, paramedical staff, IT and electronics engineers, government, hospitals and end user public Location is now a days no problem and therefore there is no limitation of the availability of healthcare facilities to such location or remote location. The biggest role in such development is played by the communication technology which may provide healthcare services to every nook and corner of the location. It can decrease the health staff pressure because in India WHO guidelines ask to maintain the ratio 1:1000 of doctor and Indian public compared to present 0.62:1000 ratio of doctor and public. The great advantage of this system is that in case of epidemic or pandemic like COVID 19 Telemedicine can keep the health staff are well general public free from contagious infection (COVID-19). There are a number of networking communication modes that can be applied, which may improve the patient compliance,dosage regimen can be managed in better fashion thus increase the longevity of person life. Disasters management during pandemics present unique challenges which can be addressed effectively as happened during the lockdown. This technology-based practice can break the infectivity chain of the transmission of communicable diseases This chapter incorporates basic concept of telemedicine, its origin and types, communication technologies, services by telemedicine, types of telemedicine, tools of telemedicine, telemedicine software's and guidelines related to practicingtelemedicine in reference to Indian context. Copyright © RJPT All right reserved.

Attenuation and Degeneration of SARS-CoV-2 Despite Adaptive Evolution.

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) has followed similar trends as other RNA viruses, such as human immunodeficiency virus type 1 and the influenza A virus. Rapid initial diversification was followed by strong competition and a rapid succession of dominant variants. Host-initiated RNA editing has been the primary mechanism for introducing mutations. A significant number of mutations detrimental to viral replication have been quickly purged. Fixed mutations are mostly diversifying mutations selected for host adaptation and immune evasion, with the latter accounting for the majority of the mutations. However, immune evasion often comes at the cost of functionality, and thus, optimal functionality is still far from being accomplished. Instead, selection for antibody-escaping variants and accumulation of near-neutral mutations have led to suboptimal codon usage and reduced replicative capacity, as demonstrated in non-respiratory cell lines. Beneficial adaptation of the virus includes reduced infectivity in lung tissues and increased tropism for the upper airway, resulting in shorter incubation periods, milder diseases, and more efficient transmission between people.

Role of Renal Parenchyma Attenuation and Perirenal Fat Stranding in Chest CT of Hospitalized Patients with COVID-19.

BACKGROUND: Chest CT on coronavirus disease (COVID-19) has been extensively investigated. Acute kidney injury (AKI) has been widely described among COVID patients, but the role of kidney imaging has been poorly explored. The aim of this study is to clarify the role of opportunistic kidney assessment on non-enhanced chest CT. METHODS: We collected data on patients with COVID-19 consecutively admitted to our institution who underwent chest CT (including the upper parts of kidneys as per protocol). Three ROIs of 0.5-0.7 cm2 were positioned in every kidney. The values of renal parenchyma attenuation (RPA) and the presence of perirenal fat stranding (PFS) were analyzed. The primary and secondary outcomes were the occurrence of AKI and death. RESULTS: 86 patients with COVID-19 and unenhanced chest CT were analyzed. The cohort was split into CT RPA quartiles. Patients with a CT RPA <24 HU were more likely to develop AKI when compared with other patients (χ2 = 2.77, p = 0.014): at multivariate logistic regression analysis, being in the first quartile of CT RPA was independently associated with a four times higher risk of AKI (HR 4.56 [95% CI 1.27-16.44, p = 0.020). Within a mean 22 ± 15 days from admission, 32 patients died (37.2%). Patients with PFS were more likely to die as compared to patients without it (HR 3.90 [95% CI 1.12-13.48], p = 0.031). CONCLUSIONS: Detection of low RPA values and of PFS in COVID-19 patients independently predicts, respectively, the occurrence of AKI and an increased risk for mortality. Therefore, opportunistic kidney assessment during chest CT could help physicians in defining diagnostic and therapeutic strategies.

Cold-adapted SARS-CoV-2 variants with different temperature sensitivity exhibit an attenuated phenotype and confer protective immunity.

As novel SARS-CoV-2 Variants of Concern emerge, the efficacy of existing vaccines against COVID-19 is declining. A possible solution to this problem lies in the development of a live attenuated vaccine potentially able of providing cross-protective activity against a wide range of SARS-CoV-2 antigenic variants. Cold-adapted (ca) SARS-CoV-2 variants, Dubrovka-ca-B4 (D-B4) and Dubrovka-ca-D2 (D-D2), were obtained after long-term passaging of the Dubrovka (D) strain in Vero cells at reduced temperatures. Virulence, immunogenicity, and protective activity of SARS-CoV-2 variants were evaluated in experiments on intranasal infection of Syrian golden hamsters (Mesocricetus auratus). In animal model infecting with ca variants, the absence of body weight loss, the significantly lower viral titer and viral RNA concentration in animal tissues, the less pronounced inflammatory lesions in animal lungs as compared with the D strain indicated the reduced virulence of the virus variant. Single intranasal immunization with D-B4 and D-D2 variants induced the production of neutralizing antibodies in hamsters and protected them from infection with the D strain and the development of severe pneumonia. It was shown that for ca SARS-CoV-2 variants, the temperature-sensitive (ts) phenotype was not obligate for virulence reduction. Indeed, the D-B4 variant, which did not possess the ts phenotype but had lost the ability to infect human lung cells Calu-3, exhibited reduced virulence in hamsters. Consequently, the potential phenotypic markers of attenuation of ca SARS-CoV-2 variants are the ca phenotype, the ts phenotype, and the change in species specificity of the virus. This study demonstrates the great potential of SARS-CoV-2 cold adaptation as a strategy to develop a live attenuated COVID-19 vaccine.

Synthetic Platforms for Characterizing and Targeting of SARS-CoV-2 Genome Capping Enzymes.

Essential viral enzymes have been successfully targeted to combat the diseases caused by emerging pathogenic RNA viruses (e.g., viral RNA-dependent RNA polymerase). Because of the conserved nature of such viral enzymes, therapeutics targeting these enzymes have the potential to be repurposed to combat emerging diseases, e.g., remdesivir, which was initially developed as a potential Ebola treatment, then was repurposed for COVID-19. Our efforts described in this study target another essential and highly conserved, but relatively less explored, step in RNA virus translation and replication, i.e., capping of the viral RNA genome. The viral genome cap structure disguises the genome of most RNA viruses to resemble the mRNA cap structure of their host and is essential for viral translation, propagation, and immune evasion. Here, we developed a synthetic, phenotypic yeast-based complementation platform (YeRC0M) for molecular characterization and targeting of SARS-CoV-2 genome-encoded RNA cap-0 (guanine-N7)-methyltransferase (N7-MTase) enzyme (nsp14). In YeRC0M, the lack of yeast mRNA capping N7-MTase in yeast, which is an essential gene in yeast, is complemented by the expression of functional viral N7-MTase or its variants. Using YeRC0M, we first identified important protein domains and amino acid residues that are essential for SARS-CoV-2 nsp14 N7-MTase activity. We also expanded YeRC0M to include key nsp14 variants observed in emerging variants of SARS-CoV-2 (e.g., delta variant of SARS-CoV-2 encodes nsp14 A394V and nsp14 P46L). We also combined YeRC0M with directed evolution to identify attenuation mutations in SARS-CoV-2 nsp14. Because of the high sequence similarity of nsp14 in emerging coronaviruses, these observations could have implications on live attenuated vaccine development strategies. These data taken together reveal key domains in SARS-CoV-2 nsp14 that can be targeted for therapeutic strategies. We also anticipate that these readily tractable phenotypic platforms can also be used for the identification of inhibitors of viral RNA capping enzymes as antivirals.

Porcine epidemic diarrhea virus E protein inhibits type I interferon production through endoplasmic reticulum stress response (ERS)-mediated suppression of antiviral proteins translation.

Porcine epidemic diarrhea virus (PEDV) envelope protein (E) is recognized as a viroporin that plays important functions in virus budding, assembly and virulence. Our previous study found that PEDV E protein induces endoplasmic reticulum stress (ERS), as well as suppresses the type I interferon (IFN) response, but their link and underlying mechanism remain obscure. To better understand this relationship, we investigated the roles of PEDV E protein-induced ERS in regulating cellular type I IFN production. Our results showed that PEDV E protein localized in the ER and triggered ERS through activation of PERK/eIF2α branch, as revealed by the up-regulated phosphorylation of PERK and eIF2α. PEDV E protein also significantly inhibited both poly(I:C)-induced and RIG-I signaling-mediated type I interferon production. The PERK/eIF2α branch of ERS activated by PEDV E protein led to the translation attenuation of RIG-I signaling-associated antiviral proteins, resulting in the suppression of type I IFN production. However, PEDV E protein had no effect on the mRNA transcription of RIG-I-associated molecules. Moreover, suppression of ERS with 4-PBA, a widely used ERS inhibitor, restored the expression of RIG-I-signaling-associated antiviral proteins and mRNA transcription of IFN-ß and ISGs genes to their normal levels, suggesting that PEDV E protein blocks the production of type I IFN through inhibiting expression of antiviral proteins caused by ERS-mediated translation attenuation. This study elucidates the mechanism by which PEDV E protein specifically modulates the ERS to inhibit type I IFN production, which will augment our understanding of PEDV E protein-mediated virus evasion of host innate immunity.

A Study on the Nature of SARS-CoV-2 Using the Shell Disorder Models: Reproducibility, Evolution, Spread, and Attenuation.

The basic tenets of the shell disorder model (SDM) as applied to COVID-19 are that the harder outer shell of the virus shell (lower PID-percentage of intrinsic disorder-of the membrane protein M, PID_M) and higher flexibility of the inner shell (higher PID of the nucleocapsid protein N, PID_N) are correlated with the contagiousness and virulence, respectively. M protects the virion from the anti-microbial enzymes in the saliva and mucus. N disorder is associated with the rapid replication of the virus. SDM predictions are supported by two experimental observations. The first observation demonstrated lesser and greater presence of the Omicron particles in the lungs and bronchial tissues, respectively, as there is a greater level of mucus in the bronchi. The other observation revealed that there are lower viral loads in 2017-pangolin-CoV, which is predicted to have similarly low PID_N as Omicron. The abnormally hard M, which is very rarely seen in coronaviruses, arose from the fecal-oral behaviors of pangolins via exposure to buried feces. Pangolins provide an environment for coronavirus (CoV) attenuation, which is seen in Omicron. Phylogenetic study using M shows that COVID-19-related bat-CoVs from Laos and Omicron are clustered in close proximity to pangolin-CoVs, which suggests the recurrence of interspecies transmissions. Hard M may have implications for long COVID-19, with immune systems having difficulty degrading viral proteins/particles.

The value of EEG attenuation in the prediction of outcome in COVID-19 patients.

INTRODUCTION: During the COVID-19 pandemic, electroencephalography (EEG) proved to be a useful tool to demonstrate brain involvement. Many studies reported non-reactive generalized slowing as the most frequent pattern and epileptiform activity in a minority of patients. OBJECTIVE: To investigate the prevalence of diffuse unreactive background attenuation or suppression and its correlation with outcome in a cohort of COVID-19 patients. METHODS: The EEGs recorded during the first year of the COVID-19 pandemic were retrospectively evaluated to identify the main pattern and focus on the occurrence of a low-voltage background, either attenuated (10-20 µV) or suppressed (< 10 µV). We sought a correlation between in-hospital mortality and low-voltage EEG. In a subsample of patients, biomarkers of inflammation, hypoxemia and organ failure were collected. Brain imaging was also evaluated. RESULTS: Among 98 EEG performed in 50 consecutive patients, diffuse unreactive slowing was the most prevalent pattern (54%), followed by unreactive attenuation or suppression pattern (26%), being the latter significantly correlated with an unfavourable outcome (p = 0.0004). Survivors showed significantly lower interleukine-6 values compared to non-survivors. Patients with attenuated EEG and non-survivors also showed lower PaO2/FiO2 values. Neuroradiological findings were very heterogeneous with a prevalence of lesions suggestive of a microangiopathic substrate. CONCLUSIONS: EEG attenuation or suppression may be more frequent than previously reported and significantly associated with a poor outcome. SARS-CoV-2 infection may result in encephalopathy and reduced EEG voltage through mechanisms that are still unknown but deserve attention given its negative impact on prognosis.

Safety of the live at attenuated vaccine avishield IB GI-13 against infectious bronchitis in SPF chickens during laying period

Avian infectious bronchitis (IB) is an economically important, highly contagious, acute disease of Chickens caused by a single-stranded positive RNA Virus that belongs to the Coronaviridae family. The Virus can replicate in the oviduct and cause permanent damage in young hens resulting in the false layer occurrence. In laying hens, infectious bronchitis Virus (IBV) infections can cause a severe decline in egg production and a number of effects on egg quality and reduced hatchability. The most effective means of controlling IB in poultry is vaccination. In the areas with increased pressure of circulating field challenge Virus, live attenuated vaccines are also used during the laying period with the intention of keeping local protection of the respiratory tract at a high level. The vaccine strain IB V-173/11 contained in Avishield IB GI-13 vaccine is a strain that genetically (S1 gene) belongs to GI-13 lineage and antigenically to 793B IBV serotype. Viral infections of this serotype occur frequently in Europe and therefore most vaccination programs in broilers, layers and breeders along a live IBV vaccine of the Massachusetts serotype also include a live vaccine of the 793B serotype, GI-I3 lineage. In this paper, results of a safety evaluation of live attenuated IB vaccine strain V-173/11, when administered by spray method in a ten-fold maximum dose repeated by one maximum dose in 28-week-old specific pathogen free (SPF) layer Chickens are presented. As a control, non-vaccinated SPF layer chickens were included in the study. The vaccine is considered to be safe when used in laying period because no vaccinated chicken showed abnormal local or systemic reactions or signs of IB related disease, no chicken died from the causes attributable to the vaccine, egg quality was not altered, and there was no statistically significant difference in. egg production between the vaccinated and non-vaccinated group.

Spike protein-independent attenuation of SARS-CoV-2 Omicron variant in laboratory mice.

Despite being more transmissible, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant only causes milder diseases in laboratory animals, often accompanied by a lower viral load compared with previous variants of concern. In this study, we report the structural basis for a robust interaction between the receptor-binding domain of the Omicron spike protein and mouse ACE2. We show that pseudovirus bearing the Omicron spike protein efficiently utilizes mouse ACE2 for entry. By comparing viral load and disease severity among laboratory mice infected by a natural Omicron variant or recombinant ancestral viruses bearing either the entire Omicron spike or only the N501Y/Q493R mutations in its spike, we find that mutations outside the spike protein in the Omicron variant may be responsible for the observed lower viral load. Together, our results imply that a post-entry block to the Omicron variant exists in laboratory mice.

‘Old vaccines can fight new pandemics like COVID-19’

Speed read Vaccines against polio and measles can protect against COVID-19 These vaccines use live but attenuated, or weakened, viruses or germs Live attenuated vaccines can boost immunity against other viruses [NEW YORK] Inoculation with live attenuated vaccines (LAV) such as those used against TB, polio or measles can stimulate the immune system to provide protection against other infectious diseases, including COVID-19, says a new study. According to the authors of the study published in PNAS, older live attenuated vaccines could also afford protection from other emerging viruses. Plotkin, who developed the rubella vaccine and has worked on vaccines for anthrax, polio, rabies, and rotavirus, says because COVID-19 vaccines will not be widely available for populations in developing countries for many months, “a degree of resistance to the coronavirus could be induced in a significant part of the population by giving vaccines against other diseases like BCG and the vaccine against TB, which will stimulate the immune system and give partial protection.