16 April, 2022

From Preprints

Hijacking of Cellular Functions by SARS-CoV-2. Permeabilization and Polarization of the Host Lipid Membrane by Viroporins. -

As all viral infections, SARS-CoV-2 acts at multiple levels hijacking fundamental cellular functions and assuring its replication and immune system evasion. In particular, it has been observed that the viral 3’ Open Reading Frame (ORF3) codes for a hydrophobic protein which embeds in the cellular membrane, where it acts as an ion viroporin and is related to strong inflammatory response. Here we report equilibrium and enhanced sampling molecular dynamic simulation of the SARS-CoV-2 ORF3 in a model lipid bilayer, showing how the protein permeabilizes the lipid membrane, via the formation of a water channel, which in turn assures ion transport. We report the free energy profile for both K+ and Cl- transfer from the cytosol to the extracellular domain. The important role of ORF3 in the viral cycle, and its highly conservation among coronaviruses, may also make it a target of choice for future antiviral development, further justifying the elucidation of its mechanism at the atomistic level.

🖺 Full Text HTML: Hijacking of Cellular Functions by SARS-CoV-2. Permeabilization and Polarization of the Host Lipid Membrane by Viroporins.

Transmission of SARS-CoV-2 in standardised First Few X cases and household transmission investigations: a systematic review and meta-analysis -

We aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies Household Transmission Investigations (HHTI) protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines. We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for 9Unity-aligned9 First Few X cases (FFX) and HHTIs published between 1 December 2019 and 26 July

Standardised early results were shared by WHO Unity Studies collaborators (to 1 October 2021). We used a bespoke tool to assess investigation methodological quality. Values for hSAR and 95% confidence intervals (CIs) were extracted or calculated from crude data. Heterogeneity was assessed by visually inspecting overlap of CIs on forest plots and quantified in meta-analyses. Of 9988 records retrieved, 80 articles (64 from databases; 16 provided by Unity Studies collaborators) were retained in the systematic review and 62 were included in the primary meta-analysis. hSAR point estimates ranged from 2%-90% (95% prediction interval: 3%-71%; I2=99.7%); I2 values remained >99% in subgroup analyses, indicating high, unexplained heterogeneity and leading to a decision not to report pooled hSAR estimates. FFX and HHTI remain critical epidemiological tools for early and ongoing characterisation of novel infectious pathogens. The large, unexplained variance in hSAR estimates emphasises the need to further support standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs in time and place, to guide evidence- based pandemic preparedness and response efforts for SARS-CoV-2, influenza and future novel respiratory viruses.

🖺 Full Text HTML: Transmission of SARS-CoV-2 in standardised First Few X cases and household transmission investigations: a systematic review and meta- analysis

A delayed modulation of solar radiation on the COVID-19 transmission reflects an incubation period -

Laboratory experiments have revealed the meteorological sensitivity of the coronavirus disease 2019 (COVID-19) virus. However, no consensus has been reached about how outdoor meteorological conditions modulate the virus transmission as it is also constrained by non-meteorological conditions. Here, we find that statistically, non- meteorological factors constrain the growth rate of cumulative confirmed cases least when the cases in a country arrive around 1300–3200. The least-constrained growth rate correlates with the ultraviolet flux and temperature significantly (correlation coefficients r=-0.55±0.09 and -0.40±0.10 at p<0.01, respectively), but not with precipitation, humidity, and wind. The ultraviolet correlation exhibits a delay of about seven days, providing a meteorological measure of the incubation period. Our work reveals a seasonality of COVID-19 and a high risk of a pandemic resurgence in winter, implying a need for seasonal adaption in public policies.

🖺 Full Text HTML: A delayed modulation of solar radiation on the COVID-19 transmission reflects an incubation period

Inconsistent directions of change in case severity across successive SARS-CoV-2 variant waves suggests an unpredictable future -

Objective To determine how the severity of successively dominant SARS-CoV-2 variants has changed over the course of the COVID-19 pandemic. Design Prospective cohort analysis. Setting Community- and hospital- sequenced COVID-19 cases in the NHS Greater Glasgow and Clyde (NHS GG&C) Health Board (1.2 million people). Participants All sequenced non- nosocomial adult COVID-19 cases in NHS GG&C identified to be infected with the relevant SARS-CoV-2 lineage during the following analysis periods. B.1.177/Alpha analysis: 1st November 2020 - 30th January 2021 (n = 1640). Alpha/Delta analysis: 1st April - 30th June 2021 (n = 5552). AY.4.2 Delta/non-AY.4.2 Delta analysis: 1st July - 31st October 2021 (n = 9613). Non-AY.4.2 Delta/Omicron analysis: 1st - 31st December 2021 (n = 3858). Main outcome measures Admission to hospital, admission to ICU, or death within 28 days of first positive COVID-19 test Results In the B.1.177/Alpha analysis, 300 of 807 (37.2%) B.1.177 cases were recorded as hospitalised or having a more severe outcome, compared to 232 of 833 (27.9%) Alpha cases. After adjusting for the following covariates: age, sex, time of positive test, comorbidities and partial postcode, the cumulative odds ratio was 1.51 (95% central credible interval 1.08-2.11) for Alpha versus B.1.177. In the Alpha/Delta analysis, 113 of 2104 (5.4%) Alpha cases were recorded as hospitalised or having a more severe outcome, compared to 230 of 3448 (6.7%) Delta cases. After adjusting for the above covariates plus number of vaccine doses and reinfection, the cumulative odds ratio was 2.09 (95% central credible interval 1.42-3.08) for Delta versus Alpha. In the non-AY.4.2 Delta/AY.4.2 Delta analysis, 845 of 8644 (9.8%) non-AY.4.2 Delta cases were recorded as hospitalised or having a more severe outcome, compared to 101 of 969 (10.4%) AY.4.2 Delta cases. After adjusting for the previously stated covariates, the cumulative odds ratio was 0.99 (95% central credible interval 0.76-1.27) for AY.4.2 Delta versus non-AY.4.2 Delta. In the non-AY.4.2 Delta/Omicron analysis, 30 of 1164 (2.6%) non- AY.4.2 Delta cases were recorded as hospitalised or having a more severe outcome, compared to 26 of 2694 (1.0%) Omicron cases. After adjusting for the previously listed covariates, the median cumulative odds ratio was 0.49 (95% central credible interval 0.22-1.06) for Omicron versus non-AY.4.2 Delta. Conclusions The direction of change in disease severity between successively emerging SARS-CoV-2 variants of concern was inconsistent. This heterogeneity in virulence between variants, coupled with independent evolutionary emergence, demonstrates that severity associated with future SARS-CoV-2 variants is inherently unpredictable.

🖺 Full Text HTML: Inconsistent directions of change in case severity across successive SARS-CoV-2 variant waves suggests an unpredictable future

At least three doses of leading vaccines essential for neutralisation of SARS-CoV-2 Omicron variant -

Plasma samples taken at different time points from donors who received either AstraZeneca (Vaxzevria) or Pfizer (Comirnaty) or Moderna (Spikevax) coronavirus disease-19 (COVID-19) vaccine were assessed in virus neutralization assays against Delta and Omicron variants of concern and a reference isolate (VIC31). With the Pfizer vaccine there was 6-8-fold reduction in 50% neutralizing antibody titres (NT50) against Delta and VIC31 at 6 months compared to 2 weeks after the second dose; followed by 25-fold increase at 2 weeks after the third dose. Neutralisation of Omicron was only consistently observed 2 weeks after the third dose, with most samples having titres below the limit of detection at earlier timepoints. Moderna results were similar to Pfizer at 2 weeks after the second dose, while the titres for AstraZeneca samples derived from older donors were 7-fold lower against VIC31 and below the limit of detection against Delta and Omicron. Age and gender were not found to significantly impact our results. These findings indicate that vaccine matching may be needed, and that at least a third dose of these vaccines is necessary to generate sufficient neutralising antibodies against emerging variants of concern, especially Omicron, amidst the challenges of ensuring vaccine equity worldwide.

🖺 Full Text HTML: At least three doses of leading vaccines essential for neutralisation of SARS-CoV-2 Omicron variant

Suspected Cardiovascular Side Effects of two Covid-19 Vaccines -

Fatalities or cardiovascular side effects of vaccines were rather uncommon in the past. So far, numerous reports of side effects and deaths associated with Covid-19 vaccination have been accepted behind the background of the pandemic situation and the priority vaccinated elderly population at the beginning of the vaqccination campaign. Cardiac and heart circulatory disturbances resp. cardiovascular side effects associated with the application of Covid-19 vaccines have not been recognized up to now with the exception of thrombotic/embolic side effects and cases of myo-/pericarditis. But the mechanism of action suggests that downregulation of ACE2 by non-neutralised spike proteins may have cardiovascular effects. The objective of this analysis was to determine the total number of reported adverse events and fatalities and to record suspected important cardiovascular adverse events up to the cut-off date in European countries. Therefore, a current review/analysis of spontaneously reported fatalities as well as of adverse events after application of Covid-19 vaccines has been performed. Data were retrieved from the EudraVigilance web reports of the European Medicines Agency (EMA), partly also from the safety reports of the German PEI. Covid-19 vaccine-associated suspected side effects and related deaths are alarming. Surprisingly, numerous cardiovascular reactions were reported, many of which were life-threatening. Cardiac and heart circulatory caused fatalities alone accounted for about 33% of all ComirnatyR vaccine-related deaths. The second most important side effects were vascular thrombotic/embolic side effects, often also associated with serious consequences. Based on their quality and quantity, these side effects seem to be characteristic for spike-producing vaccines and do not appear to be substance-specific. Further investigations are needed to clarify the approximately 3.5 times more frequent cases of sinus vein thrombosis and the some different frequent cases of thrombotic/embolic events after VaxzevriaR. The hypothesis could be confirmed. Because of their importance and their sometimes life-threatening consequences, cardiovascular side effects need to be better communicated. Limitations of the investigation result from the individual reporting and recording procedure, the lack of detailed individual information and the lack of an appropriate comparison population.

🖺 Full Text HTML: Suspected Cardiovascular Side Effects of two Covid-19 Vaccines

Barriers and Enablers to Clothing Repair and Repurpose in UK Citizens -

This research aims to explore the barriers and enablers of clothing repair and repurpose in UK citizens. Using the Behaviour Change Wheel approach, the study aims to develop am intervention to encourage repair and repurpose, which can ultimately contribute to slow and sustainable fashion consumption. This study also investigates the impact of Covid-19 on repair and repurpose behaviour.

🖺 Full Text HTML: Barriers and Enablers to Clothing Repair and Repurpose in UK Citizens

The COVID States Project #83: Executive Approval -

The Covid States Project has been tracking trends in executive approval of management of the COVID-19 outbreak throughout the pandemic. We find: ● Generally, there has been a downward trend for approval of all governors since the beginning of the pandemic. ● Republican respondents in particular have trended downwards in their approval of governors. Republican approval of Democratic governors has dropped from a high of 57% in April 2020, to 19% in April, 2022. Approval of Republicans for Republican governors has fallen almost as quickly, from a high of 77% in April 2020, to 44% currently. ● In the early stages of the pandemic, President Trump had notably low approval for his handling of the pandemic, far below the average approval levels of governors. President Biden has generally had approval levels above those of President Trump, peaking in the spring of 2021, and declining steadily since. This decline has been somewhat faster than the decline in approval of governors, reaching a nadir in April 2022 one point below that of the average governor at 38%.

🖺 Full Text HTML: The COVID States Project #83: Executive Approval

Pre-Pandemic COVID-19 in New York City: A descriptive analysis of COVID-19 illness prior to February 29, 2020 -

Background: On January 30, 2020 the COVID-19 pandemic was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization. Almost a month later on February 29, 2020, the first case in New York City (NYC) was diagnosed. Methods: Three-hundred-sixty persons with COVID-like illness was reported to the NYC Department of Health and Mental Hygiene (DOHMH) before February 29, but 37 of these tested negative and 237 were never tested for SARS-COV-2. Records of 86 persons with confirmed COVID-19 and symptom onset prior to February 29, 2020 were reviewed by four physician-epidemiologists. Case-patients were classified as likely early onset COVID-19, or insufficient evidence to determine onset. Clinical and epidemiological factors collected by DOHMH and supplemented with emergency department records were analyzed. Results: Thirty-nine likely early onset COVID-19 cases were identified. The majority had severe disease with 69% presenting to an ED visit within 2 weeks of symptom onset. The first likely COVID-19 case on record had symptom onset on January 28, 2020. Only 7 of the 39 cases (18%) had traveled internationally within 14 days of onset (none to China). Conclusions: SARS-CoV-2 and COVID-19 was in NYC before being classified as a PHEIC, and eluded surveillance for another month. The delay in recognition limited mitigation effort and by the time that city and state-wide mandates were enacted 16 and 22 days later there was already community transmission.

Whole-body metabolic modelling predicts isoleucine dependency of SARS-CoV-2 replication -

We aimed at investigating host-virus co-metabolism during SARS-CoV-2 infection. Therefore, we extended comprehensive sex-specific, whole-body organ resolved models of human metabolism with the necessary reactions to replicate SARS-CoV-2 in the lung as well as selected peripheral organs. Using this comprehensive host-virus model, we obtained the following key results: 1. The predicted maximal possible virus shedding rate was limited by isoleucine availability. 2. The supported initial viral load depended on the increase in CD4+ T-cells, consistent with the literature. 3. During viral infection, the whole-body metabolism changed including the blood metabolome, which agreed well with metabolomic studies from COVID-19 patients and healthy controls. 4. The virus shedding rate could be reduced by either inhibition of the guanylate kinase 1 or availability of amino acids, e.g., in the diet. 5. The virus variants achieved differed in their maximal possible virus shedding rates, which could be inversely linked to isoleucine occurrences in the sequences. Taken together, this study presents the metabolic crosstalk between host and virus and emphasis the role of amino acid metabolism during SARS-CoV-2 infection, in particular of isoleucine. As such, it provides an example of how computational modelling can complement more canonical approaches to gain insight into host- virus crosstalk and to identify potential therapeutic strategies.

🖺 Full Text HTML: Whole-body metabolic modelling predicts isoleucine dependency of SARS-CoV-2 replication

SARS-CoV-2 Omicron BA.1 variant infection of human colon epithelial cells -

Omicron B.1.1.529 became the predominant SARS-CoV-2 variant in early 2022, causing a new wave of public anxiety. Compared to the ancestral strain, Omicron has 50 mutations, with over 30 mutations in the spike protein. These differences likely underlie the changes in Omicron biology noted in other studies, including an attenuation in the lung parenchyma, compared to the ancestral SARS-CoV-2 strain and other variants, as well as a preference for endosomal entry, in place of the TMPRSS2-mediated membrane fusion pathway. This raises questions on Omicron tropism and infectivity in various target organ systems, including the gastrointestinal (GI) tract. Up to 70% of COVID-19 patients report GI symptoms, including nausea, vomiting, and diarrhea. Here, we show that in the context of donor intrinsic genetic heterogeneity, the SARS-CoV-2 Omicron variant infects human colonoids similarly, if not less effectively, than the ancestral WT (WA1) strain or the Delta variant. Additionally, we note a higher ratio of viral RNA to infectious virus titer, which may suggest that Omicron is potentially less infectious in the intestine. This study lays the foundation for further work defining mechanisms mediating intestinal infection and pathogenesis by Omicron.

🖺 Full Text HTML: SARS-CoV-2 Omicron BA.1 variant infection of human colon epithelial cells

Epidemiology of infections with SARS-CoV-2 Omicron BA.2 variant in Hong Kong, January-March 2022 -

Hong Kong reported 12,631 confirmed COVID-19 cases and 213 deaths in the first two years of the pandemic but experienced a major wave predominantly of Omicron BA.2.2 in early 2022 with over 1.1 million reported SARS-CoV-2 infections and more than 7900 deaths. Our data indicated a shorter incubation period, serial interval, and generation time of infections with Omicron than other SARS-CoV-2 variants. Omicron BA.2.2 cases without a complete primary vaccination series appeared to face a similar fatality risk to those infected in earlier waves with the ancestral strain.

🖺 Full Text HTML: Epidemiology of infections with SARS-CoV-2 Omicron BA.2 variant in Hong Kong, January-March 2022

Relative infectivity of the SARS-CoV-2 Omicron variant in human alveolar cells -

With the emergence of multiple highly transmissible SARS-CoV-2 variants during the recent pandemic, the comparison of their infectivity has become a substantially critical issue for public health. However, a direct assessment of these viral characteristics has been challenging due to the lack of appropriate experimental models and efficient methods. Here, we integrated human alveolar organoids and single-cell transcriptome sequencing techniques to facilitate the evaluation. In a proof-of-concept study using the assay with four highly transmissible SARS-CoV-2 variants, including GR (B.1.1.119), Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (BA.1), a rapid evaluation of the relative infectivity was possible. Our results demonstrate that the Omicron (BA.1) variant is 3-5-fold more infectious to human alveolar cells than the other SARS-CoV-2 variants at the early phase of infection. To our knowledge, this study provides the first direct measurement of the infectivity of the Omicron variant and new experimental procedures that can be applied for monitoring newly emerging viral variants.

🖺 Full Text HTML: Relative infectivity of the SARS- CoV-2 Omicron variant in human alveolar cells

Development of highly specific singleplex and multiplex real-time reverse transcription PCR assays for the identification of SARS-CoV-2 Omicron BA.1, BA.2 and Delta variants -

The Omicron variant of SARS-CoV-2 (B.1.1.529), first identified during November 2021, is rapidly spreading throughout the world, replacing the previously dominant Delta variant. Omicron has a high number of mutations in the spike gene, some of which are associated with greatly increased transmissibility and immune evasion. The BA.1 sublineage has been most prevalent but there is recent evidence that the BA.2 sublineage is increasing in proportion in many countries. Genome sequencing is the gold standard for Omicron identification but is relatively slow, resource intensive, of limited capacity and often unavailable. We therefore developed a simple, rapid reverse transcription PCR (RT-PCR) method for sensitive and specific detection of the Omicron variant, including both the BA.1 and BA.2 sublineages. The assay targets a total of 5 nucleotide mutations in the receptor binding domain of the spike gene that give rise to 4 amino acid substitutions at G339D, S371L, S373P and S375F. The forward primer was designed as a double-mismatch allele specific primer (DMAS) with an additional artificial mismatch located four nucleotides from the 3′ end to enhance binding specificity. Assay specificity was confirmed by testing a wide range of previously-sequenced culture-derived viral isolates and clinical samples including the Alpha, Beta and Delta variants and ′wild type′ SARS-CoV-2. Respiratory syncytial virus and influenza A were also tested. The assay can be run in singleplex format, or alternatively as a multiplex RT-PCR to enable Omicron and Delta variants to be detected and distinguished within the same reaction by means of probes labelled with different fluorescent dyes. Sublineages BA.1 and BA.2 can be differentiated if required. The methods presented here can readily be established in any PCR laboratory and should provide valuable support for epidemiologic surveillance of Omicron infections, particularly in those regions that lack extensive sequencing facilities.

🖺 Full Text HTML: Development of highly specific singleplex and multiplex real-time reverse transcription PCR assays for the identification of SARS-CoV-2 Omicron BA.1, BA.2 and Delta variants

Determinants of Spike Infectivity, Processing and Neutralization in SARS-CoV-2 Omicron subvariants BA.1 and BA.2 -

The SARS-CoV-2 Omicron variant rapidly outcompeted other variants and currently dominates the COVID-19 pandemic. Its enhanced transmission, immune evasion and pathogenicity is thought to be driven by numerous mutations in the Omicron Spike protein. Here, we examined the impact of amino acid changes that are characteristic for the BA.1 and/or BA.2 Omicron lineages on Spike function, processing and susceptibility to neutralization. Individual mutations of S371F/L, S375F and T376A in the ACE2 receptor-binding domain as well as Q954H and N969K in the hinge region 1 impaired infectivity, while changes of G339D, D614G, N764K and L981F moderately enhanced it. Most mutations in the N-terminal region and the receptor binding domain reduced sensitivity of the Spike protein to neutralization by sera from individuals vaccinated with the BNT162b2 vaccine or therapeutic antibodies. Our results represent a systematic functional analysis of Omicron Spike adaptations that allowed this SARS-CoV-2 variant to overtake the current pandemic.

🖺 Full Text HTML: Determinants of Spike Infectivity, Processing and Neutralization in SARS-CoV-2 Omicron subvariants BA.1 and BA.2

From Clinical Trials

Randomized Controlled Clinical Trial to Evaluate The Efficacy and Safety of Healthtone as Prophylaxis for COVID-19 - Condition: COVID-19
Intervention: Dietary Supplement: Rhea® Health Tone
Sponsor: Indonesia University
Completed

Functional Capacity in Patients Post Mild COVID-19 - Condition: COVID-19
Intervention: Device: Cardiopulmonary exercise test (CPET)
Sponsor: Rambam Health Care Campus
Recruiting

Circuit Training Program in Post COVID-19 Patients - Condition: COVID-19
Interventions: Other: Circuit Training Exercise Program; Other: Aerobic Training Exercise Program
Sponsor: Riphah International University
Not yet recruiting

The Effect of Home-based Rehabilitation Program After COVID-19 Infection - Condition: COVID-19
Interventions: Behavioral: Add-on telerehabilitation and home-based rehabilitation; Behavioral: Home-based rehabilitation alone
Sponsor:
National Taiwan University Hospital
Recruiting

Efficacy, Safety and Immunogenicity Study of COVID-19 Protein Subunit Recombinant Vaccine - Condition: COVID-19
Interventions: Biological: SARS-CoV-2 protein subunit recombinant vaccine; Biological: placebo
Sponsors: PT Bio Farma; Faculty of Medicine, Universitas Indonesia, Jakarta; Faculty of Medicine, Diponegoro University, Semarang; Faculty of Medicine, Universitas Andalas, Padang; Faculty of Medicine, Universitas Hassanudin, Makassar
Not yet recruiting

A Study to Evaluate the Effectiveness and Safety of SCTV01E (a Recombinant Protein COVID-19 Vaccine) in Population Aged ≥12 Years - Conditions: COVID-19; SARS-CoV-2 Infection
Interventions: Biological: SCTV01E; Biological: CoronaVac; Biological: Sinopharm inactivated COVID-19 vaccine; Biological: other approved COVID-19 vaccines
Sponsor: Sinocelltech Ltd.
Not yet recruiting

A Study to Evaluate the Immunogenicity and Safety of SCTV01C and SCTV01E (Two Recombinant Protein COVID-19 Vaccines) in Population Aged ≥12 Years - Conditions: COVID-19; SARS-CoV-2 Infection
Interventions: Biological: SCTV01C; Biological: SCTV01E; Biological: mRNA vaccine manufactured by Pfizer or Moderna; Biological: Sinopharm inactivated COVID-19 vaccine
Sponsor: Sinocelltech Ltd.
Not yet recruiting

A Study to Evaluate the Immunogenicity and Safety of Two Recombinant Protein COVID-19 Vaccines in Population Aged ≥18 Years as Booster Vaccines - Conditions: COVID-19; SARS-CoV-2 Infection
Interventions: Biological: SCTV01C; Biological: SCTV01E; Biological: Sinopharm inactivated COVID-19 vaccine; Biological: mRNA-1273
Sponsor: Sinocelltech Ltd.
Not yet recruiting

A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine in Population Aged ≥18 Years - Conditions: SARS-CoV-2 Infection; COVID-19
Interventions: Biological: SCTV01E; Biological: Comirnaty
Sponsor: Sinocelltech Ltd.
Not yet recruiting

Safety and Efficacy of Enoxaparin and Hydroxychloroquine in COVID-19 - Condition: COVID-19 Pandemic
Intervention: Drug: Enoxaparin, Hydroxychloroquine
Sponsor: Beni-Suef University
Completed

Evaluate the Safety and Immunogenicity of Ad5 COVID-19 Vaccines for Booster Use in Children Aged 6-17 Years. - Condition: COVID-19
Interventions: Biological: 1 Nebulized inhalation for booster groups; Biological: 2 Nebulized inhalation for booster groups; Biological: 3 Nebulized inhalation for booster groups; Biological: 4 Nebulized inhalation for booster groups; Biological: 5 Intramuscular injection for booster groups; Biological: 6 Intramuscular injection for booster groups; Biological: 7 Intramuscular injection for booster groups; Biological: 8 Intramuscular injection for booster groups; Biological: 9 Intramuscular injection for booster groups; Biological: 10 Intramuscular injection for booster groups; Biological: 11 Nebulized inhalation for booster groups; Biological: 12 Nebulized inhalation for booster groups; Biological: 13 Nebulized inhalation for booster groups; Biological: 14 Nebulized inhalation for booster groups; Biological: 15 Intramuscular injection for booster groups; Biological: 16 Intramuscular injection for booster groups; Biological: 17 Intramuscular injection for booster groups; Biological: 18 Intramuscular injection for booster groups; Biological: 19 Intramuscular injection for booster groups; Biological: 20 Intramuscular injection for booster groups; Biological: 21 Nebulized inhalation for primary groups; Biological: 22 Nebulized inhalation for primary groups; Biological: 23 Nebulized inhalation for primary groups; Biological: 24 Nebulized inhalation for primary groups
Sponsor:
Seventh Medical Center of PLA General Hospital
Not yet recruiting

Clinical Evaluation of Rapid RNA Test for Covid-19 - Condition: COVID-19
Intervention: Diagnostic Test: rapid RT-LAMP test to detect SARS-COV-2 RNA
Sponsors: University of Southampton; West Hertfordshire Hospitals NHS Trust; University of Oxford
Completed

Non-inferiority Trial on Treatments in Early COVID-19 - Condition: COVID-19
Interventions: Drug: Sotrovimab; Drug: Tixagevimab Cilgavimab; Drug: Nirmatrelvir Ritonavir
Sponsors: Azienda Ospedaliera Universitaria Integrata Verona; Agenzia Italiana del Farmaco; Azienda Sanitaria-Universitaria Integrata di Udine
Recruiting

Neutralizing Power of Anti-SARS-CoV-2 (Anti-COVID-19) Serum Antibodies - Conditions: COVID-19; SARS CoV 2 Infection
Intervention:
Other: Collection of biological samples
Sponsor: Centre Hospitalier Régional d’Orléans
Not yet recruiting

Immunogenicity and Safety Study of Recombinant Two-Component COVID-19 Vaccine (CHO Cell)(ReCOV) - Condition: COVID-19
Interventions: Biological: Recombinant two-component COVID-19 vaccine (CHO cell); Biological: COVID-19 Vaccine (Vero Cell), Inactivated
Sponsor: Jiangsu Rec- Biotechnology Co., Ltd.
Not yet recruiting

From PubMed

Colonization of nasal cavities by Staphylococcus epidermidis mitigates SARS-CoV-2 nucleocapsid phosphoprotein- induced interleukin (IL)-6 in the lung - Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can trigger excessive interleukin (IL)-6 signalling, leading to a myriad of biological effects including a cytokine storm that contributes to multiple organ failure in severe coronavirus disease 2019 (COVID-19). Using a mouse model, we demonstrated that nasal inoculation of nucleocapsid phosphoprotein (NPP) of SARS-CoV-2 increased IL-6 content in bronchoalveolar lavage fluid (BALF). Nasal administration of liquid…

Food phytochemicals, epigallocatechin gallate and myricetin, covalently bind to the active site of the coronavirus main protease in vitro - SARS-CoV-2 main protease is a possible target for protection against viral infection. This study examined the inhibitory effect of food phytochemicals on the main protease of SARS-CoV-2 by determining a cleaved product after chromatographic separation. First, 37 phytochemicals, including glycosides and metabolites, were screened at 20 µM; epigallocatechin gallate, myricetin, theaflavin, herbacetin, piceatannol, myricitrin, and isothiocyanates inhibited the enzyme in varying degrees. The IC(50)…

Mitoxantrone dihydrochloride, an FDA approved drug, binds with SARS-CoV-2 NSP1 C-terminal - One of the major virulence factors of SARS-CoV-2, NSP1, is a vital drug target due to its role in host immune evasion through multiple pathways. NSP1 protein is associated with inhibiting host mRNA translation by binding to the small subunit of ribosome through its C-terminal region. Previously, we have shown the structural dynamics of the NSP1 C-terminal region (NSP1-CTR) in different physiological environments. So, it would be very interesting to investigate the druggable compounds that could…

Insights into the binding and covalent inhibition mechanism of PF-07321332 to SARS-CoV-2 M^pro - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been causing the COVID-19 pandemic, resulting in several million deaths being reported. Numerous investigations have been carried out to discover a compound that can inhibit the biological activity of the SARS-CoV-2 main protease, which is an enzyme related to the viral replication. Among these, PF-07321332 (Nirmatrelvir) is currently under clinical trials for COVID-19 therapy. Therefore, in this work, atomistic and electronic…

Antiviral activities of natural compounds and ionic liquids to inhibit the Mpro of SARS-CoV-2: a computational approach - The recalcitrant spread of the COVID-19 pandemic produced by the novel coronavirus SARS-CoV-2 is one of the most destructive occurrences in history. Despite the availability of several effective vaccinations and their widespread use, this line of immunization often faces questions about its long-term efficacy. Since coronaviruses rapidly change, and multiple SARS-CoV-2 variants have emerged around the world. Therefore, finding a new target-based medication became a priority to prevent and…

Blocking key mutated hotspot residues in the RBD of the omicron variant (B.1.1.529) with medicinal compounds to disrupt the RBD-hACE2 complex using molecular screening and simulation approaches - A new variant of SARS-CoV-2 known as the omicron variant (B.1.1.529) reported in South Africa with 30 mutations in the whole spike protein, among which 15 mutations are in the receptor-binding domain, is continuously spreading exponentially around the world. The omicron variant is reported to be highly contagious with antibody-escaping activity. The emergence of antibody-escaping variants is alarming, and thus the quick discovery of small molecule inhibitors is needed. Hence, the current study…

Titanium dioxide and fluoropolymer-based coating for smart fabrics with antimicrobial and water-repellent properties - In the coronavirus disease 2019 pandemic, protective clothing is required for medical staff at risk of infection. This study proposes functional smart fabrics with antimicrobial and water-repellent properties, using titanium dioxide (TiO(2)) and fluoropolymer-based precursors as coating materials. Experimental results indicated a uniform distribution of TiO(2) particles with an average size below 200 nm throughout the fabric. A zone of inhibition test revealed that the fabric inhibited bacterial…

Identification of (2R,3R)-2-(3,4-dihydroxyphenyl)chroman-3-yl-3,4,5-trihydroxy benzoate as multiple inhibitors of SARS-CoV-2 targets; a systematic molecular modelling approach - Coronavirus disease of 2019 (COVID-19) is a zoonotic disease caused by a new severe acute respiratory syndrome (SARS- CoV-2) which has quickly resulted in a pandemic. Recent anti-COVID-19 drug discoveries are leaning towards repurposing phytochemicals which have been previously reported for SARS and MERS-CoV outbreaks. However, they have been either virtually screened or tested so far against mono targets and the potent derivatives of virtually sorted lead molecules remain elusive. We aimed to…

Flavonoids of Salvadora persica L. (meswak) and its liposomal formulation as a potential inhibitor of SARS- CoV-2 - Several studies are now underway as a worldwide response for the containment of the COVID-19 outbreak; unfortunately, none of them have resulted in an effective treatment. Salvadora persica L. (Salvadoraceae), commonly known as meswak, is one of the popular plants used by Muslims as an oral hygiene tool. It is documented that the meswak possesses antiviral activity, but no report discusses its use for coronavirus treatment. Herein, a mixture of 11 flavonoids prepared from the aqueous plant…

The inhibition of Mpro, the primary protease of COVID-19, by Poria cocos and its active compounds: a network pharmacology and molecular docking study - Poria cocos is a traditional Chinese medicine (TCM) that can clear dampness, promote diuresis, and strengthen the spleen and stomach. Poria cocos has been detected in many TCM compounds that are used for COVID-19 intervention. However, the active ingredients and mechanisms associated with the effect of Poria cocos on COVID-19 remain unclear. In this paper, the active ingredients of Poria cocos, along with their potential targets related to COVID-19, were screened using TCMSP, GeneCards, and…

Revisiting activity of some glucocorticoids as a potential inhibitor of SARS-CoV-2 main protease: theoretical study - The global breakout of COVID-19 and raised death toll has prompted scientists to develop novel drugs capable of inhibiting SARS-CoV-2. Conducting studies on repurposing some FDA-approved glucocorticoids can be a promising prospective for finding a treatment for COVID-19. In addition, the use of anti-inflammatory drugs, such as glucocorticoids, is a pivotal step in the treatment of critical cases of COVID-19, as they can provoke an inflammatory cytokine storm, damaging lungs. In this study, 22…

Translational Control of COVID-19 and Its Therapeutic Implication - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19, which has broken out worldwide for more than two years. However, due to limited treatment, new cases of infection are still rising. Therefore, there is an urgent need to understand the basic molecular biology of SARS-CoV-2 to control this virus. SARS- CoV-2 replication and spread depend on the recruitment of host ribosomes to translate viral messenger RNA (mRNA). To ensure the translation of their…

Computational prediction of the molecular mechanism of statin group of drugs against SARS-CoV-2 pathogenesis - Recently published clinical data from COVID-19 patients indicated that statin therapy is associated with a better clinical outcome and a significant reduction in the risk of mortality. In this study by computational analysis, we have aimed to predict the possible mechanism of the statin group of drugs by which they can inhibit SARS-CoV-2 pathogenesis. Blind docking of the critical structural and functional proteins of SARS-CoV-2 like RNA-dependent RNA polymerase, M-protease of 3-CL-Pro,…

A Houttuynia Cordata-based Chinese herbal formula improved symptoms of allergic rhinitis during the COVID-19 pandemic - CONCLUSION: ZYF has potential effects to relieve nasal symptoms for AR during the COVID-19 pandemic.

Inhibition of endocytic recycling of ACE2 by SARS-CoV-2 S protein partially explains multiple COVID-19 related diseases caused by ACE2 reduction - No abstract

From Patent Search

SYSTEM FOR MONITORING COVID-19 PATIENTS USING A VIRTUAL TELEPRESENCE ROBOT - Attached Separately - link

MASCARA FACIAL PARA LA INHALACION DE SUBSTANCIAS NEBULIZADAS, CON SISTEMA DE ASPIRACION INCORPORADO - - link

MACHINE LEARNING TECHNIQUE TO ANALYZE THE WORK PRESSURE OF PARAMEDICAL STAFF DURING COVID 19 - Machine learning technique to analyse the work pressure of paramedical staff during covid 19 is the proposed invention that focuses on identifying the stress levels of paramedical staff. The invention focuses on analysing the level of stress that is induced on the paramedical staff especially during pandemic. - link

一种吡咯烷酮中间体的合成方法 - 本发明涉及药物中间体合成技术领域，尤其是一种吡咯烷酮中间体的合成方法，包括以下步骤：化合物1溶液和有机锂试剂溶液泵入连续反应器，反应生成锂氢交换中间体，再泵入卤代乙腈与中间态发生反应生成化合物2；化合物2用固定床反应装置内进行氢化反应，后处理得到化合物3；将化合物3的溶液和氨水溶液泵入连续反应器生成酰胺化合物4；化合物4和脱水剂使用恒流泵泵入连续化反应器，生成化合物5或其氨基上有保护基的中间体；应用串联连续反应技术，将传统釜式数步反应改进为连续化工艺，解决了传统釜式反应的放大效应问题，降低了含金属试剂以及高压氢化等危险反应的安全风险进而避免了超低温反应釜和高压氢化釜等设备，提高了生产效率。 - link

一株表达新冠病毒S1蛋白单克隆抗体杂交瘤细胞系及中和活性抗体 - 本发明属于细胞工程与免疫学领域，具体涉及一株表达新冠病毒S1蛋白单克隆抗体杂交瘤细胞系及中和活性抗体。本发明筛选获得一株能高效稳定分泌表达新冠病毒S1蛋白单克隆抗体的杂交瘤细胞系以及其分泌的新冠病毒S1蛋白单克隆抗体；利用普通细胞培养皿培养本发明的重组杂交瘤细胞系，产量可达10mg/L，且纯度能达90%以上；本发明的单抗具有高中和活性，单抗浓度为0.00103μg/mL时即可抑制50％以上新冠假病毒活性，是目前所报告的新冠单抗中和活性最佳的。本发明提供的杂交瘤细胞系或单克隆抗体在新冠病毒的血清学检测、制备新冠病毒感染的试剂或药物及制备新冠病毒抗原或抗体检测的试剂中具有重要的应用价值。 - link

基于SARS-CoV-2的S蛋白的疫苗及其用途 - 本公开提供了基于SARS‑CoV‑2的S蛋白的疫苗及其用途，并具体涉及重组SARS‑CoV‑2刺突蛋白(S蛋白)及编码其的mRNA和DNA。本公开还涉及包含编码重组S蛋白的DNA序列的重组质粒。本公开的重组质粒经转录得到mRNA，其包含SEQ ID NO.12所示的序列。本公开进一步涉及包含前述mRNA的mRNA‑载体颗粒例如脂质纳米颗粒(LNP)和组合物例如疫苗组合物。 - link

CBD Covid 19 Protection - - link

一种双价可电离脂质化合物、组合物及其应用 - 本发明涉及核酸药物递送技术领域，特别是关于一种双价可电离脂质化合物、组合物及其应用。本发明提供多种可以递送核酸药物的可电离阳离子脂质，具备较强的可设计性、可生物降解性及高效的体内外转染效率，由其组成的脂质纳米递送系统用于递送mRNA，在细胞水平上，优于目前上市的产品，并且在动物水平也具有良好的递送效率，可以作为核酸药物的递送新的方法，促进核酸药物的发展。 - link

新冠肺炎CT图像分割方法及终端设备 - 本发明公开了一种新冠肺炎CT图像分割方法及终端设备，方法包括获取待分割新冠肺炎CT图像；将该图像输入至训练好的分割模型中，得到新冠肺炎病灶区域的图像；其中分割模型包括依次连接的多个下采样模块和下采样模块对应的上采样模块；每个采样模块均包括依次连接的第一提取单元和第二提取单元；上述两个提取单元的卷积模块均为结构重参数化卷积模块。本发明的结构重参数化卷积模块为训练时使用多分支结构，加强模型表达能力，推理时使用单路结构，加快推理速度，快速得出诊断结果。同时，为从不同尺度特征图中学习分层表示，加强模型对图像边缘信息提取，并使梯度更快回流，上采样每一侧输出都连接混合损失函数，实现图像的像素级分割。 - link

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