Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
• From Patent Search

From Preprints

• Hidden evolutionary constraints dictate the retention of coronavirus accessory genes -
  Genetic innovation is fundamental to the ability of viruses to adapt in the face of host immunity. Coronaviruses exhibit many mechanisms of innovation given flexibility in genomic composition relative to most RNA virus families (1-5). Examples include the acquisition of unique accessory genes that can originate by capture of cellular genes or through duplication and divergence of existing viral genes (6-8). Accessory genes may be influential in dictating viral host range and cellular tropism, but little is known about how selection acts on these variable regions of virus genomes. We used experimental evolution of mouse hepatitis virus (MHV) with an inactive native phosphodiesterase, NS2, that encodes a complementing cellular AKAP7 gene (9), to simulate the capture of a host gene and found hidden patterns of constraint that determine the fate of coronavirus accessory genes. After courses of serial infection, AKAP7 was retained under strong selection but rapidly lost under relaxed selection. In contrast, the gene encoding inactive NS2, ORF2, remained intact, suggesting it is under cryptic evolutionary constraint. Guided by the retention of ORF2 and hints of similar patterns in related betacoronaviruses, we analyzed the evolution of SARS-CoV-2 ORF8, which arose via gene duplication (6) and contains premature stop codons in several globally successful lineages. As with MHV ORF2, the coding-defective SARS-CoV-2 ORF8 gene remains largely intact, mirroring patterns observed during MHV experimental evolution and extending these findings to viruses currently adapting to humans. Retention of inactive genes challenges assumptions on the dynamics of gene loss in virus genomes and can help guide evolutionary analysis of emerging and pandemic coronaviruses.
  🖺 Full Text HTML: Hidden evolutionary constraints dictate the retention of coronavirus accessory genes
• Antibodies utilizing VL6-57 light chains target a convergent cryptic epitope on SARS-CoV-2 spike protein driving the genesis of Omicron variants -
  Continued evolution of SARS-CoV-2 generates variants to challenge antibody immunity established by infection and vaccination. A connection between population immunity and genesis of virus variants has long been suggested but its molecular basis remains poorly understood. Here, we identify a class of SARS-CoV-2 neutralising public antibodies defined by their shared usage of VL6-57 light chains. Although heavy chains of diverse genotypes are utilized, convergent HCDR3 rearrangements have been observed among these public antibodies to cooperate with germline VL6-57 LCDRs to target a convergent epitope defined by RBD residues S371-S373-S375. Antibody repertoire analysis identifies that this class of VL6-57 antibodies is present in SARS-CoV-2-naive individuals and is clonally expanded in most COVID-19 patients. We confirm that Omicron specific substitutions at S371, S373 and S375 mediate escape of antibodies of the VL6-57 class. These findings support that this class of public antibodies constitutes immune pressure promoting the introduction of S371L/F-S373P-S375F in Omicron variants. The results provide further molecular evidences to support that antigenic evolution of SARS-CoV-2 is driven by antibody mediated population immunity.
  🖺 Full Text HTML: Antibodies utilizing VL6-57 light chains target a convergent cryptic epitope on SARS-CoV-2 spike protein driving the genesis of Omicron variants
• Threat awareness and counter-terrorism preparedness of Dutch hospitals: a cross-sectional survey -

  ABSTRACT Background Workplace violence, including violent extremism, is a growing concern in the healthcare environment. Furthermore, there has been a disproportionate rise in the rate of terrorist attacks on hospitals during the past two decades. Hospitals are vulnerable targets due to their easy accessibility and their high density of patients, staff and visitors. Nonetheless, little is known about the hospitals awareness of these risks, and to which extent these facilities protect themselves from violent extremism and terrorist attacks. Methods This was a cross-sectional survey study among emergency managers of acute care hospitals in the Netherlands. The questionnaire included 42 items across six themes: demographic (hospital) data; general and emergency department (ED) access control; ED security and preparedness; online security and offline transparency; violence, terrorism and warfare; and impact of the COVID-19 pandemic. Responses were collected and stored in a secured online database, and subsequently exported to an Excel spreadsheet for descriptive analysis. Continuous data were reported as means or as medians with interquartile ranges (IQR), using SPSS. Categorical data were reported as absolute numbers and as valid percentages. Results The questionnaire was completed on behalf of 33 out of 71 hospital organizations (46%), representing 38 out of 82 EDs (46%). Hospitals had broadly different policies with regards to patient and visitor registration, and the presence of security guards. Most hospitals had controlled vehicle access for the parking lot and ambulance bay, but this was not 24/7 in all hospitals. A paragraph on terrorist attacks was included in 34% of hospital disaster plans. Eighteen percent of hospitals had previous experience with acts of violent extremism and 55% of hospitals had sustained (attempted) cyberattacks. Whilst the likelihood of a physical terrorist attack was deemed low at 3.6 (median 4, IQR 2.6) on a 10-point Likert scale, the likelihood of a cyberattack was considered high at 7.3 (median 8, IQR 2.3). A significant proportion of emergency managers reported to experience an increased risk of violence since the onset of the COVID-19 pandemic. Conclusion Practice variation with regards to counter-terrorism defence measures in Dutch hospitals is high. The preparedness of hospitals for terrorist attacks or acts of violent extremism could be improved and may benefit from uniform, evidence based hospital security policies.

  🖺 Full Text HTML: Threat awareness and counter-terrorism preparedness of Dutch hospitals: a cross-sectional survey
• Nanobodies against SARS-CoV-2 non-structural protein Nsp9 inhibit viral replication by targeting innate immunity -
  Nanobodies are emerging as critical tools for drug design. Several have been recently created to serve as inhibitors of SARS-Cov-2 entry in the host cell by targeting surface-exposed Spike protein. However, due to the high frequency of mutations that affect Spike, these nanobodies may not target it to their full potential and as a consequence, inhibition of viral entry may not be efficient. Here we have established a pipeline that instead targets highly conserved viral proteins that are made only after viral entry into the host cell when the SARS-Cov-2 RNA-based genome is translated. As proof of principle, we designed nanobodies against the SARS-CoV-2 non-structural protein Nsp9, required for viral genome replication. To find out if this strategy efficiently blocks viral replication, one of these anti-Nsp9 nanobodies, 2NSP23, previously characterized using immunoassays and NMR spectroscopy for epitope mapping, was encapsulated into lipid nanoparticles (LNP) as mRNA. We show that this nanobody, hereby referred to as LNP-mRNA-2NSP23, is internalized and translated in HEK293 cells. We next infected HEK293-ACE2 cells with multiple SARS-CoV-2 variants and subjected them to LNP-mRNA-2NSP23 treatment. Analysis of total RNA isolated from infected cells treated or untreated with LNP-mRNA-2NSP23 using qPCR and RNA deep sequencing shows that the LNP-mRNA-2NSP23 nanobody protects HEK293-ACE2 cells and suppresses replication of several SARS-CoV-2 variants. These observations indicate that following translation, the nanobody 2NSP23 inhibits viral replication by targeting Nsp9 in living cells. We speculate that LNP-mRNA-2NSP23 may be translated into an innovative technology to generate novel antiviral drugs highly efficient across coronaviruses.
  🖺 Full Text HTML: Nanobodies against SARS-CoV-2 non-structural protein Nsp9 inhibit viral replication by targeting innate immunity
• Akaluc bioluminescence offers superior sensitivity to track in vivo dynamics of SARS-CoV-2 infection -
  Monitoring in vivo viral dynamics can improve our understanding of pathogenicity and tissue tropism. For positive-sense, single-stranded RNA viruses, several studies have attempted to monitor viral kinetics in vivo using reporter genomes. The application of such recombinant viruses can be limited by challenges in accommodating bioluminescent reporter genes in the viral genome. Conventional luminescence also exhibits relatively low tissue permeability and thus less sensitivity for visualization in vivo. Here we show that unlike NanoLuc bioluminescence, the improved method, termed AkaBLI, allows visualization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Syrian hamsters. By successfully incorporating a codon-optimized Akaluc luciferase gene into the SARS-CoV-2 genome, we visualized in vivo infection, including the tissue-specific differences associated with particular variants. Additionally, we could evaluate the efficacy of neutralizing antibodies and mRNA vaccination by monitoring changes in Akaluc signals. Overall, AkaBLI is an effective technology for monitoring viral dynamics in live animals.
  🖺 Full Text HTML: Akaluc bioluminescence offers superior sensitivity to track in vivo dynamics of SARS-CoV-2 infection
• Reference materials for SARS-CoV-2 molecular diagnostic quality control: validation of encapsulated synthetic RNAs for room temperature storage and shipping -
  The Coronavirus pandemic unveiled the unprecedented need for diagnostic tests to rapidly detect the presence of pathogens in the population. Real-time RT-PCR and other nucleic acid amplification techniques are accurate and sensitive molecular techniques that necessitate positive controls. To meet this need, Twist Bioscience has developed and released synthetic RNA controls. However, RNA is an inherently unstable molecule needing cold storage, costly shipping, and resource-intensive logistics. Imagene provides a solution to this problem by encapsulating dehydrated RNA inside metallic capsules filled with anhydrous argon, allowing room temperature and eco-friendly storage and shipping. Here, RNA controls produced by Twist were encapsulated (RNAshells) and distributed to several laboratories that used them for COVID-19 detection tests by amplification. One RT-LAMP procedure, four different RT-PCR devices and six different PCR kits were used. The amplification targets were genes E, N; RdRp, Sarbeco-E and Orf1a/b. RNA retrieval was satisfactory, and the detection was reproducible. RNA stability was checked by accelerated aging. The results for a 10-year equivalent storage time at 25 {degrees}C were not significantly different from those for unaged samples. This room temperature RNA stability allows the preparation and distribution of large strategic batches which can be stored for a long time and used for standardization processes between detection sites. Moreover, it makes it also possible to use these controls for single use and in the field where large differences in temperature can occur. Consequently, this type of encapsulated RNA controls, processed at room temperature, can be used as reference materials for the SARS-Cov-2 virus as well as for other pathogens detection.
  🖺 Full Text HTML: Reference materials for SARS-CoV-2 molecular diagnostic quality control: validation of encapsulated synthetic RNAs for room temperature storage and shipping
• homeRNA self-blood collection by exposed close contacts enables high-frequency temporal profiling of the pre-symptomatic host immune kinetics to respiratory viral infection -

  Background Host immunity is critical in determining outcomes of acute respiratory viral infections (ARVIs). However, detailed kinetics of host immune responses following natural exposures are poorly understood. Investigating the host response during the pre–symptomatic phase of viral infection is challenging, and prior work has largely relied on human challenge studies. In this prospective longitudinal study, we utilized a self-blood collection tool (homeRNA) to profile the host response during pre–symptomatic ARVIs in recently exposed adults and present a study framework for the conduct of large–scale longitudinal mechanistic studies. Methods We prospectively recruited non–symptomatic adults with recent exposure to ARVIs who subsequently tested negative (exposed uninfected) and positive for respiratory pathogens. Study participants performed self–collection of blood and nasal swabs across a 4–week observation window. Daily monitoring of symptoms, viral load, and blood transcriptional responses was performed for the first week followed by weekly monitoring of blood transcriptional responses and symptoms. Nasal swabs were assayed for respiratory pathogens including SARS–CoV–2. Immune kinetics from 132 longitudinal blood samples (8 SARS–CoV–2 infected and 4 exposed uninfected) were profiled at high temporal resolution for 773 host response genes. Findings 68 participants across 26 U.S. states completed the study between June 2021 – April 2022, with 97.6% of scheduled longitudinal blood collections (n=691), 97.9% of nasal swabs (n=466) and 97.2% of symptom surveys (n=688) returned. SARS-CoV-2 infection was confirmed in 25% of the participants (n=17) Expression of host immediate early genes (IEGs) involved in AP-1 transcriptional complex and prostaglandin biosynthesis along with genes encoding the early T-cell activation antigen (CD69), pyrogenic cytokines (IL-6, MIP-1β, and IFN-γ), cytotoxic cell receptors and granule proteins, and interferon-induced GTPases were detected in the periphery prior to onset of viral shedding in the nasal passage. Upon onset of viral shedding, robust induction of interferon stimulated genes (ISGs) were observed. We also observed elevated expression of the host defense peptides DEFA4, LCN2, LTF, BPI (HDPs) in exposed uninfected individuals. Interpretation Signatures of T–cell responses prior to nasal viral shedding followed by robust induction of innate ISGs upon onset of viral shedding suggests that T–cell derived immune memory may play a role in pathogen control during early phases of the infection. Elevated levels of HDPs in exposed uninfected individuals suggest a potential role for neutrophil–mediated immunity in host defense during pathogen exposure. Finally, we demonstrated that unsupervised self–collection and stabilization of blood using homeRNA can be used to study early host immune kinetics to natural ARVIs at a temporal resolution comparable to that of human challenge studies.

  🖺 Full Text HTML: homeRNA self-blood collection by exposed close contacts enables high-frequency temporal profiling of the pre-symptomatic host immune kinetics to respiratory viral infection
• Estimating the potential impact and diagnostic requirements for SARS-CoV-2 test-and-treat programs -

  Oral antivirals have the potential to reduce the public health burden of COVID-19. However, now that we have exited the emergency phase of the COVID-19 pandemic, declining SARS-CoV-2 clinical testing rates (average testing rates = ≪10 tests/100,000 people/day in low-and-middle income countries; <100 tests/100,000 people/day in high-income countries; September 2023) make the development of effective test-and-treat programs challenging. We used an agent-based model to investigate how testing rates and strategies affect the use and effectiveness of oral antiviral test-to-treat programs in four country archetypes of different income levels and demographies. We find that in the post-emergency phase of the pandemic, in countries where low testing rates are driven by limited testing capacity, significant population-level impact of test-and-treat programs can only be achieved by both increasing testing rates and prioritizing individuals with greater risk of severe disease. However, for all countries, significant reductions in severe cases with antivirals are only possible if testing rates were substantially increased with high willingness of people to seek testing. Comparing the potential population-level reductions in severe disease outcomes of test-to-treat programs and vaccination shows that test-and-treat strategies are likely substantially more resource intensive requiring very high levels of testing (>>100 tests/100,000 people/day) and antiviral use suggesting that vaccination should be a higher priority.

  🖺 Full Text HTML: Estimating the potential impact and diagnostic requirements for SARS-CoV-2 test-and-treat programs
• Adolescents’ future orientation and anticipatory emotion regulation in daily life during the COVID-19 pandemic: An experience sampling study -
  The COVID-19 pandemic posed a challenge to young people’s positive future orientation and mental health. The current study’s objective was to understand the role of daily-life future orientation and anticipatory emotion regulation in mental health during the pandemic. We used the Experience Sampling Method to investigate Belgian adolescents’ (aged 13 – 21) daily life future orientation and anticipatory emotion regulation in relation to psychopathology symptoms in 2020 (N = 136, 121 females) and 2021 (N = 53, 48 females). Adolescents generally perceived immediate future events more positively than negatively throughout the pandemic. However, differences in future orientation between phases of the pandemic were also observed. Higher psychopathology symptom levels were associated with looking forward to future events less and dreading them more early in the pandemic and with perceiving immediate future events as less positive in a later phase of the pandemic. Furthermore, the expected intensity and importance of immediate future events were related to anticipatory emotion regulation in daily life during the pandemic. The results suggest that adolescents with higher psychopathology symptoms perceived the immediate future more negatively during the first year of the COVID-19 pandemic. Therefore, clinical interventions to target future orientation during a crisis could be beneficial in supporting and improving young people’s mental health.
  🖺 Full Text HTML: Adolescents’ future orientation and anticipatory emotion regulation in daily life during the COVID-19 pandemic: An experience sampling study
• Antecedents and consequences of telework during the COVID-19 pandemic: A natural experiment in Japan -
  With the outbreak of the COVID-19 pandemic, companies around the world have been introducing telework. However, Japan stands out for its low rate of telework implementation, and it seems there may be cultural factors that have hindered telework use in Japan during the pandemic. In this study, we aim to clarify the antecedents and consequences of telework in Japan, making use of the natural experiment created by the COVID-19 pandemic to examine the following two questions: (1) What socio-psychological factors in workplaces were important for introducing telework in the first place? and (2) How did the implementation of telework subsequently influence socio-psychological factors in these workplaces? Three waves of an online survey were conducted among the same employees working for Japanese companies before and during the pandemic. We found that telework in Japan was more readily introduced in organizations characterized by meritocracy. We also found that the introduction of telework in Japanese companies did not have any negative effects but instead increased levels of independence, organizational commitment and perceived hierarchy mutability. We discuss how telework interacts with culture at both societal and organizational levels.
  🖺 Full Text HTML: Antecedents and consequences of telework during the COVID-19 pandemic: A natural experiment in Japan
• An ethnographic analysis virtual peer review panels -
  In the early months of the COVID-19 pandemic, many research funding organisations were faced with the choice of suspending or else continuing their decision-making processes, including peer review panels, virtually. Although seen part of a longer drive to make peer review more cost and time efficient, it is still not fully understood how peer review panels, more commonly operating in a face-to-face (F2F) setting, function in a virtual environment. Using a series of observation of 4 peer review panels conducted virtually during 2020 at the Research Council of Norway (Forskningsrådet), this research explores the move from face-to-face to virtual panel deliberation and how panellists behaved in this new environment. Despite the virtual panels arguably conducted more efficiently, saving time and money by panellists participating from their home-settings, a number of behaviours around the role of the Panel Chair, and the collective presence during the decision-making process, suggest alternations as to how panels reached and confirmed consensus in the virtual environment. Deliberate mechanisms to confirm consensus was required during panels thus suggesting a more onerous workload mid, and post-panel work for Panel Chairs and managers. In addition, whereas a majority of panel members had experience working together in the past, the introduction of new panel members was restricted in an online environment, leading to instances where new panel members would lead discussions, and present conflicting information during evaluations. These preliminary results indicate that more information is needed about how the virtual environment influences peer review processes before a more permanent change is adopted by funding agencies.
  🖺 Full Text HTML: An ethnographic analysis virtual peer review panels
• Virtual Simulated Placements in Healthcare Education: A scoping review -

  Abstract Introduction A virtual simulated placement (VSP) is a computer-generated version of a practice placement. COVID-19 drove increased adoption of virtual technology in clinical education. Accordingly, the number of VSP publications increased from 2020. This review aims to determine the scope of this literature to inform future research questions. Objective Assess the range and types of evidence related to VSPs across the healthcare professions. Inclusion criteria Studies that focussed on healthcare students participating in VSPs. Hybrid, augmented reality (AR) and mixed reality (MR) placements were excluded. Methods Fourteen databases were searched, limited to English, and dated from 1st January 2020. Supplementary searches were employed, and an updated search was conducted on 9th July 2023. Themes were synthesised using the PAGER framework to highlight patterns, advances, gaps, evidence for practice and research recommendations. Results Twenty-eight papers were reviewed. All VSPs were designed in response to pandemic restrictions. Students were primarily from medicine and nursing. Few publications were from developing nations. There was limited stakeholder involvement in the VSP designs and a lack of robust research designs, consistent outcome measures, conceptual underpinnings, and immersive technologies. Despite this, promising trends for student experience, knowledge, communication, and critical thinking skills using VSPs have emerged. Conclusion. This review maps the VSP evidence across medicine, nursing, midwifery and allied health. Before a systematic review is feasible across healthcare, allied health and midwifery research require greater representation. Based on the highlighted gaps, other areas for future research are suggested.

  🖺 Full Text HTML: Virtual Simulated Placements in Healthcare Education: A scoping review
• A nationwide study of 331 rare diseases among 58 million individuals: prevalence, demographics, and COVID-19 outcomes -

  Background: The Global Burden of Disease study has provided key evidence to inform clinicians, researchers, and policy makers across common diseases, but no similar effort with single study design exists for hundreds of rare diseases. Consequently, many rare conditions lack population-level evidence including prevalence and clinical vulnerability. This has led to the absence of evidence-based care for rare diseases, prominently in the COVID-19 pandemic. Method: This study used electronic health records (EHRs) of more than 58 million people in England, linking nine National Health Service datasets spanning healthcare settings for people alive on Jan 23, 2020. Starting with all rare diseases listed in Orphanet, we quality assured and filtered down to analyse 331 conditions with ICD-10 or SNOMED-CT mappings clinically validated in our dataset. We report 1) population prevalence, clinical and demographic details of rare diseases, and 2) investigate differences in mortality with SARs-CoV-2. Findings: Among 58,162,316 individuals, we identified 894,396 with at least one rare disease. Prevalence data in Orphanet originates from various sources with varying degrees of precision. Here we present reproducible age and gender-adjusted estimates for all 331 rare diseases, including first estimates for 186 (56.2%) without any reported prevalence estimate in Orphanet. We identified 49 rare diseases significantly more frequent in females and 62 in males. Similarly we identified 47 rare diseases more frequent in Asian as compared to White ethnicity and 22 with higher Black to white ratios as compared to similar ratios in population controls. 37 rare diseases were overrepresented in the white population as compared to both Black and Asian ethnicities. In total, 7,965 of 894,396 (0.9%) of rare-disease patients died from COVID-19, as compared to 141,287 of 58,162,316 (0.2%) in the full study population. Eight rare diseases had significantly increased risks for COVID-19-related mortality in fully vaccinated individuals, with bullous pemphigoid (8.07[3.01-21.62]) being worst affected. Interpretation: Our study highlights that National-scale EHRs provide a unique resource to estimate detailed prevalence, clinical and demographic data for rare diseases. Using COVID-19-related mortality analysis, we showed the power of large-scale EHRs in providing insights to inform public health decision-making for these often neglected patient populations.

  🖺 Full Text HTML: A nationwide study of 331 rare diseases among 58 million individuals: prevalence, demographics, and COVID-19 outcomes
• Mathematical modeling of SARS-CoV-2 variant substitutions in European countries: Transmission dynamics and epidemiological insights -

  Background: Countries across Europe have faced similar evolutions of SARS-CoV-2 VOCs, including the Alpha, Delta, and Omicron variants. Materials and Methods: We used data from GISAID and applied a robust, automated mathematical substitution model to study the dynamics of COVID-19 variants across Europe over a period of more than two years, from late 2020 to early 2023. This model identifies variant substitution patterns and distinguishes between residual and dominant behavior. We used weekly sequencing data from 19 European countries to estimate the increase in transmissibility (∆β) between consecutive SARS-CoV-2 variants. In addition, we focused on large countries with separate regional outbreaks and complex scenarios of multiple competing variants. Results: Our model accurately reproduced the observed substitution patterns between the Alpha, Delta, and Omicron major variants. We estimated the daily variant prevalence and calculated ∆β between variants, revealing that: (i) ∆β increased progressively from the Alpha to the Omicron variant; (ii) ∆β showed a high degree of variability within Omicron variants; (iii) a higher ∆β was associated with a later emergence of the variant within a country; (iv) a higher degree of immunization of the population against previous variants was associated with a higher ∆β for the Delta variant; (v) larger countries exhibited smaller ∆β, suggesting regionally diverse outbreaks within the same country; and finally (vi) the model reliably captures the dynamics of competing variants, even in complex scenarios. Conclusions: The use of mathematical models allows for the precise and reliable estimation of daily cases of each variant. By quantifying ∆β, we have tracked the spread of the different variants across Europe, highlighting a robust increase in transmissibility trend from Alpha to Omicron. On the other hand, we have shown that the country-level increases in transmissibility can always be influenced by the geographical characteristics of the country and the timing of the emergence of the variant.

  🖺 Full Text HTML: Mathematical modeling of SARS-CoV-2 variant substitutions in European countries: Transmission dynamics and epidemiological insights
• Evolution of SARS-CoV-2 in the RhineNeckar/Heidelberg Region 01/2021 07/2023 -

  At the beginning of 2021 the monitoring of the circulating variants of SARS-CoV-2 was established in Germany in accordance with the Corona Surveillance Act (discontinued after July 2023) to allow a better containment of the pandemic, because certain amino acid exchanges (especially) in the spike protein lead to higher transmission as well as a reduced vaccination efficacy. Therefore, our group performed whole genome sequencing applying the ARTIC protocol (currently V4) on Illumina9s NextSeq 500 platform (and starting in May 2023 on the MiSeq DX platform) for SARS-CoV-2 positive specimen from patients of the Heidelberg University Hospital (and associated hospitals) as well as the Public health office in Rhine-Neckar/Heidelberg region. Our group sequenced a total of 26,795 SARS-CoV-2-positive samples between January 2021 and July 2023 - valid sequences, according to the requirements for sequence upload to the German electronic sequencing data hub (DESH) operated by the Robert Koch Institute (RKI), could be determined for 24,852 samples, while the lineage/clade could be identified for 25,912 samples. While the year 2021 was very dynamic and changing regarding the circulating variants in the Rhine-Neckar/Heidelberg region with the initial non-variant of concerns, followed by A.27.RN and the rise of B.1.1.7 in winter/spring and its displacement by B.1.617.2 in spring/summer, which remained almost exclusive until the beginning of December and the first B.1.1.529 incidences, which rose to a proportion of 40 percent by the end of 2021 (and superseded B.1.617.2 by January 2022 with a proportion of over 90 percent). The years 2022 and 2023 were then dominated by B.1.1.529 and its numerous sublineages, especially BA.5 and BA.2, and more recently by the rise of recombinant variants, such as XBB.1.5. By the end of July 2023 (and since calendar week 20) the proportion of the recombinant variants amounted to 100 percent of all circulating variants in the Rhine-Neckar/Heidelberg region.

  🖺 Full Text HTML: Evolution of SARS-CoV-2 in the RhineNeckar/Heidelberg Region 01/2021 07/2023

From Clinical Trials

• Improving Post COVID-19 Syndrome With Hyperbaric Oxygen Treatments - Conditions: Post COVID-19 Condition; Post-COVID-19 Syndrome; Post-COVID Syndrome; COVID-19; Fatigue; Fatigue Syndrome, Chronic
  Interventions: Device: Monoplace Hyperbaric Chamber (Class III medical device).
  Sponsors: Sunnybrook Health Sciences Centre
  Not yet recruiting

• Education of Medical Staff to Post Acute Covid susTained sYmptoms - Conditions: Post-acute COVID-19 Syndrome
  Interventions: Other: Training in the management of functional disorders; Other: Reimbursement of 3 long consultations
  Sponsors: Assistance Publique - Hôpitaux de Paris; ANRS, Emerging Infectious Diseases
  Not yet recruiting

• Pharmacist Management of Paxlovid eVisits - Conditions: COVID-19; Quality of Care
  Interventions: Other: Pharmacist Care; Other: AFM Pool Care
  Sponsors: Kaiser Permanente
  Not yet recruiting

• ACTIVATE in Public Housing - Conditions: Pneumonia; Influenza; Varicella Zoster; Meningitis; COVID-19; Vaccine Hesitancy
  Interventions: Behavioral: Increasing Willingness and Uptake of Influenza, Pneumonia, Meningitis, HZV, and COVID-19 Vaccination
  Sponsors: Charles Drew University of Medicine and Science
  Not yet recruiting

• Effects of a Home-Based Exercise Intervention in Subjects With Long COVID - Conditions: Long COVID-19; Post-COVID-19 Syndrome
  Interventions: Other: home-based concurrent exercise
  Sponsors: University of Vienna
  Recruiting

• Early Awake Alterning Prone Positioning Combined With Non-invasive Oxygen Therapy in Patients With COVID-19. - Conditions: COVID-19 Pneumonia
  Interventions: Other: Prone position; Other: Standard treatment
  Sponsors: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
  Terminated

• tDCS in the Management of Post-COVID Disorders - Conditions: Long COVID
  Interventions: Device: Transcranial Direct Current Stimulation (tDCS); Behavioral: Motor Training; Behavioral: Cognitive Training
  Sponsors: Universidade Federal de Pernambuco; São Paulo State University
  Recruiting

• Equity Evaluation of Fact Boxes on Informed COVID-19 and Influenza Vaccination Decisions - Study Protocol - Conditions: COVID-19; Influenza
  Interventions: Other: Fact box
  Sponsors: Harding Center for Risk Literacy
  Not yet recruiting

• Study of the Vector Vaccine GamCovidVac-M (Altered Antigenic Composition) - Conditions: COVID-19
  Interventions: Biological: GamCovidVac-M vector vaccine for the prevention of COVID-19 with altered antigenic composition
  Sponsors: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
  Not yet recruiting

• Study of the Vector Vaccine GamCovidVac for the Prevention of COVID-19 With Altered Antigenic Profile With Participation of Adult Volunteers - Conditions: COVID-19
  Interventions: Biological: GamCovidVac vector vaccine for the prevention of COVID-19 (with altered antigenic profile)
  Sponsors: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
  Not yet recruiting

• Exercise Interventions in Post-acute Sequelae of Covid-19 - Conditions: COVID-19
  Interventions: Behavioral: Exercise
  Sponsors: University of Virginia
  Not yet recruiting

• Effects of Cacao FLAvonoids in LOng Covid Patients (FLALOC) - Conditions: Long Covid19; Fatigue Syndrome, Chronic
  Interventions: Dietary Supplement: Flavonoids
  Sponsors: Guillermo Ceballos Reyes; Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado
  Recruiting

• The Efficacy of the 2023-2024 Updated COVID-19 Vaccines Against COVID-19 Infection - Conditions: COVID-19; Vaccine-Preventable Diseases; SARS CoV 2 Infection; Upper Respiratory Tract Infection; Upper Respiratory Disease
  Interventions: Biological: Novavax COVID-19 vaccine (2023-2024 formula XBB containing); Biological: Pfizer COVID-19 mRNA vaccine (2023-2024 formula XBB containing)
  Sponsors: Sarang K. Yoon, DO, MOH; Westat; Novavax
  Not yet recruiting

• Motivational Interviewing for Vaccine Uptake in Latinx Adults - Conditions: Vaccine Hesitancy
  Interventions: Other: EHR alert; Behavioral: Motivational Interviewing; Behavioral: Warm hand off to nurse
  Sponsors: Boston College; East Boston Neighborhood Health Center; Harvard School of Public Health (HSPH); Boston Children’s Hospital; National Institute of Nursing Research (NINR)
  Not yet recruiting

• Clinical Trial to Evaluate the Safety of RQ-01 in SARS-CoV-2 Positive Subjects - Conditions: COVID-19; Infectious Disease; Symptomatic COVID-19 Infection Laboratory-Confirmed; SARS CoV 2 Infection
  Interventions: Combination Product: RQ-001; Other: Placebo
  Sponsors: Red Queen Therapeutics, Inc.; PPD
  Recruiting

From PubMed

• Anti-SARS-CoV-2 activity of cyanopeptolins produced by Nostoc edaphicum CCNP1411 - Despite the advances in contemporary medicine and availability of numerous innovative therapies, effective treatment and prevention of SARS-CoV-2 infections pose a challenge. In the search for new anti-SARS-CoV-2 drug candidates, natural products are frequently explored. Here, fifteen cyanopeptolins (CPs) were isolated from the Baltic cyanobacterium Nostoc edaphicum and tested against SARS-CoV-2. Of these depsipeptides, the Arg-containing structural variants showed the strongest inhibition of…

• Discovery of druggable potent inhibitors of serine proteases and farnesoid X receptor by ligand-based virtual screening to obstruct SARS-CoV-2 - The coronavirus, a subfamily of the coronavirinae family, is an RNA virus with over 40 variations that can infect humans, non-human mammals and birds. There are seven types of human coronaviruses, including SARS-CoV-2, is responsible for the recent COVID-19 pandemic. The current study is focused on the identification of drug molecules for the treatment of COVID-19 by targeting human proteases like transmembrane serine protease 2 (TMPRSS2), furin, cathepsin B, and a nuclear receptor named…

• Decoding Sepsis-Induced Disseminated Intravascular Coagulation: A Comprehensive Review of Existing and Emerging Therapies - Disseminated intravascular coagulation (DIC) is a recurrent complication of sepsis. Since DIC not only promotes organ dysfunction but also represents a strong prognostic factor, it is important to diagnose DIC as early as possible. When coagulation is activated, fibrinolysis is inhibited, blood thinners are consumed, and a condition is created that promotes blood clotting, making it more difficult for the body to remove fibrin or prevent it from being deposited in the blood vessels. This leads…

• Plant Cell-Engineered Gold Nanoparticles Conjugated to Quercetin Inhibit SARS-CoV-2 and HSV-1 Entry - Recent studies have revealed considerable promise in the antiviral properties of metal nanomaterials, specifically when biologically prepared. This study demonstrates for the first time the antiviral roles of the plant cell-engineered gold nanoparticles (pAuNPs) alone and when conjugated with quercetin (pAuNPsQ). We show here that the quercetin conjugated nanoparticles (pAuNPsQ) preferentially inhibit the cell entry of two medically important viruses-severe acute respiratory syndrome coronavirus…

• Phenotypic Test of Benzo[4,5]imidazo[1,2-c]pyrimidinone-Based Nucleoside and Non-Nucleoside Derivatives against DNA and RNA Viruses, Including Coronaviruses - Emerging and re-emerging viruses periodically cause outbreaks and epidemics around the world, which ultimately lead to global events such as the COVID-19 pandemic. Thus, the urgent need for new antiviral drugs is obvious. Over more than a century of antiviral development, nucleoside analogs have proven to be promising agents against diversified DNA and RNA viruses. Here, we present the synthesis and evaluation of the antiviral activity of nucleoside analogs and their deglycosylated derivatives…

• Functionalized Fullerene Potentially Inhibits SARS-CoV-2 Infection by Modulating Spike Protein Conformational Changes - The disease of SARS-CoV-2 has caused considerable morbidity and mortality globally. Spike proteins on the surface of SARS-CoV-2 allow it to bind with human cells, leading to infection. Fullerenes and their derivatives are promising SARS-CoV-2 inhibitors and drug-delivery vehicles. In this study, Gaussian accelerated molecular dynamics simulations and the Markov state model were employed to delve into the inhibitory mechanism of Fullerene-linear-polyglycerol-b-amine sulfate (F-LGPS) on spike…

• BNT162b2 vaccine induced variant-specific immunity, safety and risk of Omicron breakthrough infection in children aged 5 to 11 years: a cohort study - There is little information on BNT162b2 vaccine-induced variant-specific immunogenicity, safety data and dynamics of breakthrough infections in pediatric populations. We addressed these questions using a prospective two dose BNT162b2 (10 mcg) vaccination cohort study of healthy children 5-11 years in Singapore. Follow up included blood samples at scheduled visits, daily vaccination symptom diary and confirmation of SARS-CoV-2 infection. Surrogate virus neutralization test (sVNT) and…

• Author Correction: Calcium dobesilate reduces SARS-CoV-2 entry into endothelial cells by inhibiting virus binding to heparan sulfate - No abstract

• Structure-based development and preclinical evaluation of the SARS-CoV-2 3C-like protease inhibitor simnotrelvir - The persistent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants accentuates the great demand for developing effective therapeutic agents. Here, we report the development of an orally bioavailable SARS-CoV-2 3C-like protease (3CL^(pro)) inhibitor, namely simnotrelvir, and its preclinical evaluation, which lay the foundation for clinical trials studies as well as the conditional approval of simnotrelvir in…

• A community effort in SARS-CoV-2 drug discovery - The COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the “Billion molecules against Covid-19 challenge”, to identify small-molecule inhibitors against SARS-CoV-2 or relevant human…

• Reversible and irreversible inhibitors of coronavirus Nsp15 endoribonuclease - The emergence of SARS-CoV-2, the causative agent of COVID-19, has resulted in the largest pandemic in recent history. Current therapeutic strategies to mitigate this disease have focused on the development of vaccines and on drugs that inhibit the viral 3CL protease or RNA-dependent RNA polymerase enzymes. A less-explored and potentially complementary drug target is Nsp15, a uracil-specific RNA endonuclease that shields coronaviruses and other nidoviruses from mammalian innate immune defenses….

• Antiviral, virucidal and antioxidant properties of Artemisia annua against SARS-CoV-2 - Natural products are a rich source of bioactive molecules that have potential pharmacotherapeutic applications. In this study, we focused on Artemisia annua (A. annua) and its enriched extracts which were biologically evaluated in vitro as virucidal, antiviral, and antioxidant agents, with a potential application against the COVID-19 infection. The crude extract showed virucidal, antiviral and antioxidant effects in concentrations that did not affect cell viability. Scopoletin, arteannuin B and…

• 2-thiouridine is a broad-spectrum antiviral nucleoside analogue against positive-strand RNA viruses - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are causing significant morbidity and mortality worldwide. Furthermore, over 1 million cases of newly emerging or re-emerging viral infections, specifically dengue virus (DENV), are known to occur annually. Because no virus-specific and fully effective treatments against these or many other viruses have been approved, there is an urgent need for novel, effective therapeutic agents. Here, we identified 2-thiouridine (s2U) as…

• Distinct motifs in the E protein are required for SARS-CoV-2 virus particle formation and lysosomal deacidification in host cells - Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is a major public health concern, but the mechanisms underlying its viral particle formation are not well understood. In this study, we established a system for producing virus-like particles (VLPs) by expressing four structural proteins that make up SARS-CoV-2 virus particles in cells and used a spike (S) protein fused with the HiBiT peptide as a marker for evaluating VLP production. Using this system, we confirmed that the E protein…

• Evaluation of in vitro SARS-CoV-2 inactivation by a new quaternary ammonium compound: Bromiphen bromide - The pneumonia (COVID-19) outbreak caused by the novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which unpredictably exploded in late December of 2019 has stressed the importance of being able to control potential pathogens with the aim of limiting their spread. Although vaccines are well known as a powerful tool for ensuring public health and controlling the pandemic, disinfection and hygiene habits remain crucial to prevent infection from spreading and…

From Patent Search