Viral Infection Spreading and Mutation in Cell Culture

A new model of viral infection spreading in cell cultures is proposed taking into account virus mutation. This model represents a reaction-diffusion system of equations with time delay for the concentrations of uninfected cells, infected cells and viral load. Infection progression is characterized by the virus replication number Rv, which determines the total viral load. Analytical formulas for the speed of propagation and for the viral load are obtained and confirmed by numerical simulations. It is shown that virus mutation leads to the emergence of a new virus variant. Conditions of the coexistence of the two variants or competitive exclusion of one of them are found, and different stages of infection progression are identified.

SARS-CoV-2 Omicron: evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern

Genetically distinct viral variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been recorded since January 2020. Over this time global vaccine programs have been introduced, contributing to lowered COVID-19 hospitalisation and mortality rates, particularly in the first world. In late 2021, the Omicron (B.1.1.529) virus variant emerged, with significant genetic differences and clinical effects from other variants of concern (VOC). This variant a demonstrated higher number of polymorphisms in the gene encoding the Spike (S) protein, and there has been displacement of the dominant Delta variant. We assessed the impact of Omicron infection on the ability of: serum from vaccinated and/or previously infected individuals; concentrated human IgG from plasma donors, and licensed monoclonal antibody therapies to neutralise the virus in vitro. There was a 17 to 27-fold reduction in neutralisation titres across all donors who had a detectable neutralising antibody titre to the Omicron variant. Concentrated pooled human IgG from convalescent and vaccinated donors had greater breadth of neutralisation, although the potency was still reduced 16-fold. Of all therapeutic antibodies tested, significant neutralisation of the Omicron variant was only observed for Sotrovimab, with other monoclonal antibodies unable to neutralise Omicron in vitro. These results have implications for ongoing therapy of individuals infected with the Omicron variant.

The Petasites hybridus CO2 Extract (Ze 339) Blocks SARS-CoV-2 Replication In Vitro

The coronavirus disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), has spread worldwide, affecting over 250 million people and resulting in over five million deaths. Antivirals that are effective are still limited. The antiviral activities of the Petasites hybdridus CO2 extract Ze 339 were previously reported. Thus, to assess the anti-SARS-CoV-2 activity of Ze 339 as well as isopetasin and neopetasin as major active compounds, a CPE and plaque reduction assay in Vero E6 cells was used for viral output. Antiviral effects were tested using the original virus (Wuhan) and the Delta variant of SARS-CoV-2. The antiviral drug remdesivir was used as control. Pre-treatment with Ze 339 in SARS-CoV-2-infected Vero E6 cells with either virus variant significantly inhibited virus replication with IC50 values of 0.10 and 0.40 μg/mL, respectively. The IC50 values obtained for isopetasin ranged between 0.37 and 0.88 μM for both virus variants, and that of remdesivir ranged between 1.53 and 2.37 μM. In conclusion, Ze 339 as well as the petasins potently inhibited SARS-CoV-2 replication in vitro of the Wuhan and Delta variants. Since time is of essence in finding effective treatments, clinical studies will have to demonstrate if Ze339 can become a therapeutic option to treat SARS-CoV-2 infections.

The Petasites hybridus CO2-extract (Ze 339) blocks SARS-CoV-2 replication in vitro

The coronavirus disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), has spread worldwide, affecting over 250 million people and resulting in over five million deaths. Antivirals that are effective are still limited. The antiviral activities of the Petasites hybdridus CO2-extract Ze 339 were previously reported. Thus, to assess the anti-SARS-CoV-2 activity of Ze 339 as well as isopetasin and neopetasin as major active compounds, a CPE- and plaque reduction assay in Vero E6 cells was used for viral output. Antiviral effects were tested using the original virus (Wuhan) and the Delta variant of SARS-CoV-2. The antiviral drug remdesivir was used as control. Pre-treatment with Ze 339 in SARS-CoV-2 infected Vero E6 cells with either virus variant significantly inhibited virus replication with IC50 values of 0.10 and 0.40 μg/mL, repectively. The IC50 values obtained for isopetasin ranged between 0.37-0.88 μM for both virus variants, that of remdesivir between 1.53-2.37 μM. In conclusion, Ze 339 as well as the petasins potently inhibited SARS-Cov-2 replication in vitro of the Wuhan and Delta variants. Since time is of essence in finding effective treatments, clinical studies will have to demonstrate if Ze339 can become a therapeutic option to treat SARS-CoV-2 infections.

Detection and abundance of SARS-CoV-2 in wastewater in Liechtenstein, and the estimation of prevalence and impact of the B.1.1.7 variant

The new coronavirus 2 (SARS-CoV-2) is known to be also shed through feces, which makes wastewater-based surveillance possible, independent of symptomatic cases and unbiased by any testing strategies and frequencies. We investigated the entire population of the Principality of Liechtenstein with samples from the wastewater treatment plant Bendern (serving all 39,000 inhabitants). Twenty-four-hour composite samples were taken once or twice a week during a period of 6 months from September 2020 to March 2021. Viral RNA was concentrated using the PEG centrifugation method followed by reverse transcription quantitative PCR. The aim of this research was to assess the suitability of COVID-19 fragments to relate the viral wastewater signal to the incidences and assess the impact of the emerging B.1.1.7. variant. The viral load in the wastewater peaked at almost 9 × 108 viral fragments per person equivalent (PE) and day on October 25, and showed a second peak on December 22 reaching a viral load of approximately 2 × 108 PE−1d−1. Individual testing showed a lag of 4 days and a distinct underestimation of cases at the first peak when testing frequency was low. The wastewater signal showed an immediate response on the implementation of non-pharmaceutical interventions. The new virus variant B.1.1.7. was first detected in wastewater on December 23, while it was first observed with individual testing not before January 13, 2021. Further, our data indicate that the emergence of new virus variant may change the wastewater signal, probably due to different shedding patterns, which should be considered in future models.

Classroom concept as a response to the COVID-19 pandemic: An antivirus built-environment approach

This discussion is based on the COVID-19 pandemic, which causes children to be vulnerable to infection due to their still-developing organs and immune system. The nature of the virus to survive in the environment encourages the existence of variants of the virus, making vaccines the only way to stop the virus from spreading internally. Based on the latest research by WHO, a new virus variant has been found with the potential for transmission and effects that are more severe than the previous virus. The COVID-19 pandemic has had an impact on changing educational activities to distance through the use of technology. Children are a golden phase to learn and get to know something that tends to be through direct interaction. However, this is less effective because of children who need to be supervised and tend to be given natural direction and the children’s homes’ different psychological conditions and conditions. This study aims to analyze the concept of an excellent class to minimize the risk of spreading COVID-19 and other virus variants in the future so that it is safe for the health of users, namely children. It conducts a concept-based framework with an antivirus built-environment approach supported with simulation, literature and precedent review. In the discussion, the concept of an antivirus built-environment class is supported by an understanding of biophilic built-environment, especially biomimetics and direct use of nature, as well as the existence of spatial shift standards due to the risk of spread, government regulations on learning systems, healthy space and climate conditions in Indonesia. Biomimetics translates the character and work system of viruses biologically with the help of antivirus software tools because of the similarities in their properties. Antivirus built-environment on the class concept is realized in the form of scanning incoming users with the help of technology and room protection. The application of this concept, when discovered, is expected to prevent the accumulation of users from minimizing interactions that are at risk of spreading the virus, nourish users with the help of nature, and provide a place for children’s learning activities.

The effects of social isolation and the COVID-19 pandemic on air quality around the world

In December 2019, a new virus variant was discovered in China, belonging to the coronavirus family, whose associated respiratory syndrome became known as COVID-19. Due to the ease of transmission, lethality and lack of knowledge about this new disease, several countries chose to adopt measures of social distancing, in addition to restrictions on travel and the performance of activities considered non-essential. Thus, the present study aimed to carry out a bibliographic survey about the main effects of social isolation on air quality, in some regions around the world, through consultation of scientific articles, national and international research institutes, as well such as satellite imagery. The results showed that the effects of these measurements were observed on air quality in different parts of the world, with a reduction in the levels of some of the main air pollutants, such as NO2, CO2, CO and particulate matter. In contrast, some studies showed that the concentration of O3 increased in certain regions. It was possible to conclude that the improvements observed were temporary, as they did not result from structural measures, but from transitory situations; and that the adoption of public policies to restrict the emission of pollutants is essential to reduce the incidence and aggravation of associated respiratory diseases, avoiding the overload of health systems, especially in the current pandemic scenario.

Az alapellátásban kezelt COVID–19-fertőzött gyermekek tünettani és epidemiológiai jellemzői

Összefoglaló. Bevezetés: A COVID–19-pandémia kapcsán számos tanulmány vizsgálta a tünetek gyakoriságát és a járványterjedés jellemzőit gyermekkorban, kevés azonban az alapellátás adatait összefoglaló publikáció. Közleményünkben 12 házi gyermekorvosi praxis 545 SARS-CoV-2-fertőzött betegének adatait elemeztük a 2. (n = 293) és a 3. (n = 252) járványhullámban. Célkitűzés: A gyermekkori fertőzések tünettanának és epidemiológiai jellemzőinek összehasonlítása korcsoportok és járványhullámok között. Módszer: Valamennyi alapellátó praxis egységes retrospektív adatgyűjtést végzett ugyanazon paraméterek regisztrálásával. Eredmények: A 10 év alatti betegekben a láz, a nátha és a köhögés dominált (30–50%), míg a 10 év felettiekben magas arányban regisztráltunk általános tüneteket is (30–40% fejfájás, gyengeség, szaglászavar). A 2. hullámban a 11–18 évesek (68%), a 3. hullámban a 0–10 évesek (53%) voltak többségben. A 3. hullámban szignifikánsan emelkedett a légúti tünetek előfordulása, az általános tünetek gyakorisága jelentősen csökkent, és szignifikánsan nőtt a családon belüli expozíció aránya (36% vs. 58%) a 2. hullámmal összehasonlítva. A gyermekről családtagra történő továbbterjedés 24% és 16% volt a két járványhullámban, és mértékét az életkor befolyásolta. Megbeszélés: A klinikai kép az életkorral és a feltételezett vírusvariánssal mutatott összefüggést: 10 év alatt a légúti tünetek domináltak, 10 év felett szignifikánsan több általános tünetet regisztráltunk a 0–10 évesekhez képest. A 3. járványhullámban az alfa-variáns terjedésével gyakoribbá váltak a légúti tünetek, az iskolabezárások következtében megváltozott az életkori megoszlás, és megemelkedett a családi expozíció okozta fertőzések aránya. A fertőzés továbbadása háztartáson belül mindkét hullámban alacsony maradt. Következtetés: A COVID–19 klinikai megjelenését és terjedési jellemzőit jelentősen befolyásolta az érintett gyermekpopuláció életkori összetétele, a cirkuláló vírusvariáns és az aktuális korlátozó intézkedések. Orv Hetil. 2021; 162(44): 1751–1760. Summary. Introduction: During the COVID-19 pandemic, a large number of publications examined the frequency of symptoms and the mode of transmission in childhood but only a few community-based studies have been published. In our paper, 545 pediatric COVID-19 patients’ data were collected by 12 primary care pediatricians in the second (n = 293) and third (n = 252) waves of the pandemic. Objective: To compare the frequency of symptoms and household transmission in different age groups and between the two waves. Method: Patients’ data and disease characteristics were recorded retrospectively in the same manner by all participating pediatricians. Results: In patients of <10 years of age, fever, rhinorrhea and cough were registered the most frequently (30–50%), in contrast to patients of >10 years, where high frequency of general symptoms was found (30–40% headache, weakness, anosmia). In the third wave, the ratio of the age group 11–18 years declined from 68% to 47%, the frequency of respiratory symptoms increased significantly, while the ratio of general symptoms decreased. Household exposition was more frequent in the third wave (36% vs. 58%), while the transmission rate from children to family members was 24% and 16%, respectively, and it varied with age. Discussion: Clinical manifestation showed relation to age and virus variant: the older age associated with higher frequency of general symptoms and the spread of the alpha variant led to the predominance of respiratory symptoms over general complaints. Prolonged school closures affected the age distribution and increased the frequency of household exposition. Secondary household transmission remained low. Conclusion: Clinical and epidemiological characteristics of pediatric COVID-19 disease were highly influenced by age, dominant virus variant and mitigation measures. Orv Hetil. 2021; 162(44): 1751–1760.

A SARS-CoV-2 spike ferritin nanoparticle vaccine protects hamsters against Alpha and Beta virus variant challenge

The emergence of SARS-CoV-2 variants of concern (VOC) requires adequate coverage of vaccine protection. We evaluated whether a SARS-CoV-2 spike ferritin nanoparticle vaccine (SpFN), adjuvanted with the Army Liposomal Formulation QS21 (ALFQ), conferred protection against the Alpha (B.1.1.7), and Beta (B.1.351) VOCs in Syrian golden hamsters. SpFN-ALFQ was administered as either single or double-vaccination (0 and 4 week) regimens, using a high (10 μg) or low (0.2 μg) dose. Animals were intranasally challenged at week 11. Binding antibody responses were comparable between high- and low-dose groups. Neutralizing antibody titers were equivalent against WA1, B.1.1.7, and B.1.351 variants following two high dose vaccinations. Dose-dependent SpFN-ALFQ vaccination protected against SARS-CoV-2-induced disease and viral replication following intranasal B.1.1.7 or B.1.351 challenge, as evidenced by reduced weight loss, lung pathology, and lung and nasal turbinate viral burden. These data support the development of SpFN-ALFQ as a broadly protective, next-generation SARS-CoV-2 vaccine.