- Case of Myocarditis, Pericarditis, and Fatal Aortic Dissection following Covid-19 mRNA Vaccination -
We present a case study of a 34-year-old male who was in apparent good health prior to his COVID-19 mRNA vaccination. Sixteen days after his first dose, he experienced acute inflammation, sudden thoracic aortic dissection, and pericardial tamponade, rapidly leading to his death. Studies suggest that young males, in particular, appear to be at increased risk of adverse cardiac events following COVID-19 mRNA vaccination. However, we propose that certain information gaps exist in the criteria that inform both public health agencies and the public on incidence rates in certain presentations of even severe myocarditis and cardiac adverse events following COVID-19 vaccination, as is often mentioned within COVID-19 vaccine myocarditis studies and is evident within the findings of this young man’s important case presentation.
- In silico assessment of immune cross protection between BCoV and SARS-CoV-2 -
Background: Humans have long shared infectious agents with cattle, and the bovine-derived human common cold OC-43 CoV is a not-so-distant example of cross-species viral spill over of coronaviruses. Human exposure to the Bovine Coronavirus (BCoV) is certainly common, as the virus is endemic in most high-density cattle-raising regions. Since BCoVs are phylogenetically close to SARS-CoV-2, it is possible that cross-protection against COVID-19 occurs in people exposed to BCoV. Methods: This article shows an in silico investigation of human cross-protection to SARS-CoV-2 due to BCoV exposure. We determined HLA recognition and human B lymphocyte reactivity to BCoV epitopes using bioinformatics resources. A retrospective geoepidemiological analysis of COVID-19 was then performed to verify if BCoV/SARS-CoV-2 cross-protection could have occurred in the field. Brazil was used as a model for the epidemiological analysis of the impact of livestock density, as a proxy for human exposure to BCoV, on the prevalence of COVID-19 in people. Results: As could be expected from their classification in the same Betacoronavirus genus, we show that several human B and T epitopes are shared between BCoV and SARS-CoV-2. This raised the possibility of cross-protection of people from exposure to the bovine coronavirus. Analysis of field data added partial support to the hypothesis of viral cross-immunity from human exposure to BCoV. There was a negative correlation between livestock geographical density and COVID-19. Whole-Brazil data showed areas in the country in which COVID-19 prevalence was disproportionally low (controlled by normalization by transport infrastructure). Areas with high cattle density had lower COVID-19 prevalence in these low-risk areas. Conclusions: These data are hypothesis-raising indications that cross-protection is possibly being induced by human exposure to the Bovine Coronavirus.
- No Substitute for the Real Thing? Physical and Digital Cultural Participation in Denmark during the COVID-19 Pandemic: A Research Note -
In this research note, we analyze the impact of the COVID-19 pandemic on cultural participation. We use rich survey data from Denmark to construct pooled time-series cross-sectional data for each month of the years 2019-2021 and report three findings. First, participation in physical cultural activities (e.g., attending a concert or a museum) plummeted during two lockdowns and did not return to its pre-pandemic level by the end of 2021. Second, participation in digital activities (e.g., reading a digital book or following a museum on social media) did not change much during the pandemic. Overall, we find little evidence of substitution from physical to digital cultural participation during the COVID-19 lockdown in Denmark. Third, socioeconomic gradients in cultural participation decreased during the pandemic for physical cultural participation, but did not change for digital cultural participation. We end by discussing what we can learn from our results about how social disruptions affect patterns of cultural participation and inequality.
- Stratification in Parents’ Selection of Developmentally Appropriate Books for Children: Register-based Evidence from Danish Public Libraries -
This paper studies socioeconomic gradients in selecting developmentally appropriate children’s books from public libraries. I draw on research on developmental gradients in parental inputs to hypothesize that families with high socioeconomic status (SES) are more likely to select books that match children’s developmental stage in order to best improve children’s learning environments. In contrast to previous survey-based research, I use behavioral data on the actual books families have selected from libraries. Based on Danish registry data that cover all books borrowed from public libraries in 2020, I find that highly educated families are more likely to use libraries and borrow more books when they use libraries, but they do not select a larger share of developmentally appropriate books; in fact, they select a slightly lower share. In contrast, I find only a weak positive income gradient for the amount of books borrowed and the share of developmentally appropriate books. The supplementary analyses show that results are robust across families with children of different ages and to account for nonrandom selection into the sample of library users, socioeconomic differences in children’s reading skills, and the impact of library lockdowns due to Covid-19. I conclude that stratification in library book selection is more prominent concerning the voraciousness with which highly educated parents provide reading inputs (more books) than how discriminating they are in terms of selecting developmentally appropriate books.
- No Utilitarians in a Pandemic? Shifts in Moral Reasoning during the COVID-19 Global Health Crisis -
The COVID-19 pandemic poses many real-world moral dilemmas, which can pit the needs and rights of the many against the needs and rights of the few. We investigated the influence of this contemporary global crisis on moral judgments in older adults, who are at greatest personal risk from the pandemic. We hypothesized that during this pandemic, individuals would give fewer utilitarian responses to hypothetical dilemmas, accompanied by higher levels of confidence and emotion elicitation. Our pre-registered analysis (https://osf.io/g2wtp) involved two waves of data collection, before (2014) and during (2020) the COVID-19 pandemic, regarding three categories of moral dilemmas (personal rights, agent-centered permissions, and special obligations). While utilitarian responses considered across all categories of dilemma did not differ, participants during the 2020 wave gave fewer utilitarian responses to dilemmas involving personal rights; that is, they were less willing to violate the personal rights of others to produce the best overall outcomes.
- The global and specific cardiovascular burden of spike-based Covid-19 1 Vaccination -
Aims: The aim of this investigation was to determine whether the global and cardiovascular 10 burden associated with spike-based Covid-19 vaccination has continued to increase. 11 Methods and results: An updated analysis of spontaneously reported individual cases with 12 ADRs and their fatal outcomes associated with Covid-19 vaccines, as well as adverse 13 cardiovascular events caused by the spike-inducing vaccine Tozinameran, was performed. 14 Data were retrieved from the EudraVigilance web reports of the European Medicines Agency 15 (EMA). All evaluated adverse events correspond to the search terms of the EudraVigilance 16 based on clinical characterisation. 17 The total number of individual cases (n=2256506; i.e. 2338/day) with adverse effects that were 18 fatal in 2.3% (n=51740; i.e. 54 deaths/day), as well as the wide range of reports of 19 cardiovascular adverse effects, have revealed the unusual magnitude and specificity of these 20 events. 21 Tachycardia, arrhythmia, atrial fibrillation/flatter, bradyarrhythmia and impaired stimulus 22 formation and conduction (n=57438 combined) dominated the cardiovascular side effect profile 23 of Tozinameran, followed by blood pressure increase (n=25907), myo-/pericarditis (n=23775), 24 heart failure, cardiomyopathy, cardiac flatter/fibrillation, cardiac arrest, circulatory collaps 25 (n=16778 combined) and coronary artery disease/myocardial infarction (n=9912). The 26 importance of acute cardiovascular reactions is underlined by the fact that deaths caused by 27 them accounted for at least one third (35%) of all deaths associated with Tozinameran’s side 28 effects 29 Based on individual assessment, ARBs are currently recommended in the treatment of spike-30 induced symptoms. 31 Conclusions: The spectrum of side effects of spike-based Covid-19 vaccines is more extensive 32 and severe than is generally known, Adverse cardiovascular events convincingly reflect the 33 mode of spike action, namely down-regulating of the cardiovascular protective enzyme ACE2 34 resulting in increasing Ang II concentrations. A fundamental re-evaluation of the benefit-risk 35 assessment of these novel vaccines is mandatory. Health professionals should be educated about 36 the consequences of spike-induced ACE2 downregulation, the resulting symptoms and 37 therapeutic options.
- 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.
- CD4+ and CD8+ T cells are required to prevent SARS-CoV-2 persistence in the nasal compartment -
SARS-CoV-2 is the causative agent of COVID-19 and continues to pose a significant public health threat throughout the world. Following SARS-CoV-2 infection, virus-specific CD4+ and CD8+ T cells are rapidly generated to form effector and memory cells and persist in the blood for several months. However, the contribution of T cells in controlling SARS-CoV-2 infection within the respiratory tract are not well understood. Using C57BL/6 mice infected with a naturally occurring SARS-CoV-2 variant (B.1.351), we evaluated the role of T cells in the upper and lower respiratory tract. Following infection, SARS-CoV-2-specific CD4+ and CD8+ T cells are recruited to the respiratory tract and a vast proportion secrete the cytotoxic molecule Granzyme B. Using antibodies to deplete T cells prior to infection, we found that CD4+ and CD8+ T cells play distinct roles in the upper and lower respiratory tract. In the lungs, T cells play a minimal role in viral control with viral clearance occurring in the absence of both CD4+ and CD8+ T cells through 28 days post-infection. In the nasal compartment, depletion of both CD4+ and CD8+ T cells, but not individually, results in persistent and culturable virus replicating in the nasal compartment through 28 days post-infection. Using in situ hybridization, we found that SARS-CoV-2 infection persisted in the nasal epithelial layer of tandem CD4+ and CD8+ T cell-depleted mice. Sequence analysis of virus isolates from persistently infected mice revealed mutations spanning across the genome, including a deletion in ORF6. Overall, our findings highlight the importance of T cells in controlling virus replication within the respiratory tract during SARS-CoV-2 infection.
- Adaptive advantage of deletion repair in the N terminal domain of the SARS-CoV-2 spike protein in variants of concern -
Mutations within the N-terminal domain (NTD) of the spike (S) protein play a pivotal role in the emergence of successful SARS-CoV-2 viral lineages. This study investigates the influence of novel combinations of NTD lineage-defining mutations found in the Alpha, Delta, and Omicron variants on viral success. We performed comparative genomics of more than 10 million public SARS-CoV-2 samples to decipher the transmission success of different NTD markers. Additionally, we characterized the viral phenotype of such markers in a surrogate in vitro system. We found that viruses bearing repaired deletions SDeltaH69/V70 and SDeltaY144 in Alpha background were associated with increased transmission rates. After the emergence of the Omicron BA.1 lineage, Alpha viruses harbouring both repaired deletions still showed increased transmission compared to their BA.1 counterparts. Remarkably, Alpha viruses with the SDeltaH69/V70 repair displayed the highest emergence rate, while those in BA.1 exhibited the lowest. Moreover, repaired deletions were more frequently observed among older individuals infected with Alpha, but not with BA.1. In vitro biological characterization of Omicron BA.1 spike deletion repair patterns revealed substantial differences with Alpha. In BA.1, SDeltaV143/Y145 repair enhanced fusogenicity and susceptibility to neutralization by vaccinated individuals' sera. In contrast, the SDeltaH69/V70 repair did not significantly alter these traits but reduced viral infectivity. Simultaneous repair of both deletions led to lower fusogenicity. These findings highlight the intricate genotype-phenotype landscape of the spike NTD in SARS-CoV-2, which impacts viral biology, transmission efficiency, and susceptibility to neutralization. Overall, this study advances our comprehension of SARS-CoV-2 evolution, carrying implications for public health and future research.
- In COVID-19 health messaging, loss framing increases anxiety with little-to-no concomitant benefits: Experimental evidence from 84 countries -
The COVID-19 pandemic (and its aftermath) highlights a critical need to communicate health information effectively to the global public. Given that subtle differences in information framing can have meaningful effects on behavior, behavioral science research highlights a pressing question: Is it more effective to frame COVID-19 health messages in terms of potential losses (e.g., “If you do not practice these steps, you can endanger yourself and others”) or potential gains (e.g., “If you practice these steps, you can protect yourself and others”)? Collecting data in 48 languages from 15,929 participants in 84 countries, we experimentally tested the effects of message framing on COVID-19-related judgments, intentions, and feelings. Loss- (vs. gain-) framed messages increased self-reported anxiety among participants cross-nationally with little-to-no impact on policy attitudes, behavioral intentions, or information seeking relevant to pandemic risks. These results were consistent across 84 countries, three variations of the message framing wording, and 560 data processing and analytic choices. Thus, results provide an empirical answer to a global communication question and highlight the emotional toll of loss-framed messages. Critically, this work demonstrates the importance of considering unintended affective consequences when evaluating nudge-style interventions.
- A Global Experiment on Motivating Social Distancing during the COVID-19 Pandemic -
Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e. a controlling message) compared to no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly-internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared to the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly-internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing: Controlled motivation was associated with more defiance and less long-term behavioral intentions to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges.
- A global test of brief reappraisal interventions on emotions during the COVID-19 pandemic -
The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion regulation strategy which modifies how one thinks about a situation. Participants from 87 countries/regions (N = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vs. both control conditions) had consistent effects in reducing negative emotions and increasing positive emotions across different measures. Reconstrual and repurposing had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world to build resilience during the pandemic and beyond.
- Correlates of Health-Protective Behavior During the Initial Days of the COVID-19 Outbreak in Norway -
The coronavirus outbreak manifested in Norway in March 2020. It was met with a combination of mandatory changes (closing of public institutions) and recommended changes (hygiene behavior, physical distancing). It has been emphasized that health-protective behavior such as increased hygiene or physical distancing are able to slow the spread of infections and flatten the curve. Drawing on previous health-psychological studies during the outbreak of various pandemics, we investigated psychological and demographic factors predicting the adoption and engagement in health-protective behavior and changes in such behavior, attitudes, and emotions over time. We recruited a non-representative sample of Norwegians (n = 8676) during a 15-day period (March 12–26 2020) at the beginning of the COVID-19 outbreak in Norway. Employing both traditional methods and exploratory machine learning, we replicated earlier findings that engagement in health-protective behavior is associated with specific demographic characteristics. Further, we observed that increased media exposure, perceiving measures as effective, and perceiving the outbreak as serious positively was related to engagement in health-protective behavior. We also found indications that hygiene and physical distancing behaviors were related to somewhat different psychological and demographic factors. Over the sampling period, reported engagement in physical distancing increased, while experienced concern or fear declined. Contrary to previous studies, we found no or only small positive predictions by confidence in authorities, knowledge about the outbreak, and perceived individual risk, while all of those variables were rather high. These findings provide guidance for health communications or interventions targeting the adoption of health-protective behaviors in order to diminish the spread of COVID-19.
- Evaluation of the cross reactivity of neutralising antibody response in vaccinated human and convalescent hamster sera against SARS-CoV-2 variants up to and including JN.1 using an authentic virus neutralisation assay -
New vaccines, therapeutics and immunity elicited by natural infection create evolutionary pressure on SARS-CoV-2 to evolve and adapt to evade vaccine-induced and infection-elicited immunity. Vaccine and therapeutics developers thus find themselves in an “arms race” with the virus. The ongoing assessment of emerging SARS-CoV-2 variants remains essential as the global community transitions from an emergency response to a long-term management plan. Here, we describe how an authentic virus neutralisation assay using low passage clinical virus isolates has been employed to monitor resistance of emerging virus variants to neutralising antibodies from humans and experimentally infected hamsters. Sera and plasma from people who received three doses of a vaccine as well as those who received a bivalent booster were assessed against SARS-CoV-2 variants, up to and including JN.1. Contemporary or recent virus variants showed substantial resistance to neutralisation by antibodies from those who had received three doses of an ancestral vaccine but were still effectively neutralised by antibodies from individuals who had received a bivalent booster (ancestral/BA.1). In our recent studies, however, the JN.1 VOI was found to be significantly more resistant to neutralisation by antibodies from those who had received the ancestral/BA.1 bivalent boost. Convalescent sera from hamsters that had been experimentally infected with one of seven virus variants (ancestral, BA.1, BA.4, BA.5.2.1, XBB.1.5, XBB.1.16, XBB.2.3) were also tested here. The recent contemporary variant, BA.2.86, was effectively neutralised by sera from hamsters infected with XBB.1.5 and XBB.1.16 but it was not neutralised by sera from those infected with BA.5.2.1. These data support the recommendations given by the WHO that a new vaccine was required and should consist of an XBB sub-lineage antigen.
- Comparing frequency of booster vaccination to prevent severe COVID-19 by risk group in the United States -
There is a public health need to understand how different frequencies of COVID-19 booster vaccines may mitigate the risk of severe COVID-19, while accounting for waning of protection and differential risk by age and immune status. By analyzing United States COVID-19 surveillance and seroprevalence data in a microsimulation model, here we show that more frequent COVID-19 booster vaccination (every 6-12 months) in older age groups and the immunocompromised population would effectively reduce the burden of severe COVID-19, while frequent boosters in the younger population may only provide modest benefit against severe disease. In persons 75+ years, the model estimated that annual boosters would reduce absolute annual risk of severe COVID-19 by 199 (uncertainty interval: 188-229) cases per 100,000 persons, compared to a one-time booster dose. In contrast, for persons 18-49 years, the model estimated that annual boosters would reduce this risk by 14 (11-19) cases per 100,000 persons. Those with prior infection had lower benefit of more frequent boosting, and immunocompromised persons had larger benefit. Scenarios with emerging variants with immune evasion increased the benefit of more frequent variant-targeted boosters. This study underscores the benefit of considering key risk factors to inform frequency of COVID-19 booster vaccines in public health guidance and ensuring at least annual boosters in high-risk populations.
Long COVID-19 [11C]CPPC Study - Conditions: COVID Long-Haul
Interventions: Drug: [11C]CPPC Injection; Drug: [11C]CPPC Injection
Sponsors: Johns Hopkins University; Radiological Society of North America
Not yet recruiting
Thrombohemorrhagic Complications of COVID-19 - Conditions: COVID-19 (Coronavirus Disease 2019)
Interventions: Diagnostic Test: Prevention algorithm
Sponsors: Volgograd State Medical University
Active, not recruiting
Combined Use of Immunoglobulin and Pulse Steroid Therapies in Severe Covid-19 Patients - Conditions: Pulse Steroid and Immunoglobulins Drugs in Covid 19 Patients
Interventions: Drug: pulse steroid and nanogam
Sponsors: Konya City Hospital
Completed
Beneficial Effects of Natural Products on Management of Xerostomia - Conditions: Xerostomia; Diabetes Mellitus; Hypertension; Post COVID-19 Condition
Interventions: Other: (Manuka honey-green tea- ginger)
Sponsors: British University In Egypt
Completed
Eficacia Ventilatoria y Remolacha - Conditions: SARS CoV 2 Infection; Muscle Disorder; Fatigue
Interventions: Dietary Supplement: Remolacha
Sponsors: Hospital de Mataró
Recruiting
Diet and Fasting for Long COVID - Conditions: Long Covid19; Long COVID
Interventions: Other: Low sugar diet and 10-12 hour eating window; Other: Low sugar diet, 8 hour eating window and fasting
Sponsors: Pacific Northwest University of Health Sciences
Recruiting
The Effectiveness of a Health Promotion Program for Older People With Post-Covid-19 Sarcopenia - Conditions: Post COVID-19 Condition
Interventions: Other: Protein powder and Resistance exercise
Sponsors: Mahidol University; National Health Security Office, Thailand
Not yet recruiting
Chronic-disease Self-management Program in Patients Living With Long-COVID in Puerto Rico - Conditions: Long Covid19
Interventions: Other: “Tomando control de su salud” (Spanish Chronic Disease Self-Management)
Sponsors: University of Puerto Rico; National Institutes of Health (NIH)
Recruiting
Treatment of Persistent Post-Covid-19 Smell and Taste Disorders - Conditions: Post-covid-19 Persistent Smell and Taste Disorders
Interventions: Drug: Cerebrolysin; Other: olfactory and gustatory trainings
Sponsors: Sherifa Ahmed Hamed
Completed
A Study to Evealuate Safety and Immunogenicity of TI-0010 SARS-CoV-2 Vaccine in Healthy Adults - Conditions: COVID-19; COVID-19 Immunisation
Interventions: Biological: TI-0010; Biological: Placebo
Sponsors: National Drug Clinical Trial Institute of the Second Affiliated Hospital of Bengbu Medical College; Therorna
Recruiting
Anti-COVID-19 Potential of Withaferin-A and Caffeic Acid Phenethyl Ester - CONCLUSION: Wi-A and CAPE possess multimodal anti-COVID-19 potential, and their combination (Wi-ACAPE) is expected to provide better activity and hence warrant further attention in the laboratory and clinic.
Recurrent viral capture of cellular phosphodiesterases that antagonize OAS-RNase L - Phosphodiesterases (PDEs) encoded by viruses are putatively acquired by horizontal transfer of cellular PDE ancestor genes. Viral PDEs inhibit the OAS-RNase L antiviral pathway, a key effector component of the innate immune response. Although the function of these proteins is well-characterized, the origins of these gene acquisitions are less clear. Phylogenetic analysis revealed at least five independent PDE acquisition events by ancestral viruses. We found evidence that PDE-encoding genes were…
Inhibitory Activity of Flavonoid Scaffolds on SARS-CoV-2 3CLpro: Insights from the Computational and Experimental Investigations - The emergence of the COVID-19 situation has become a global issue due to the lack of effective antiviral drugs for treatment. Flavonoids are a class of plant secondary metabolites that have antiviral activity against SARS-CoV-2 through inhibition of the main protease (3CL^(pro)). In this study, 22 flavonoids obtained from natural sources and semisynthetic approaches were investigated for their inhibitory activity against SARS-CoV-2 3CL^(pro), along with cytotoxicity on Vero cells. The…
Triterpenoidal Saponins from the Leaves of Aster koraiensis Offer Inhibitory Activities against SARS-CoV-2 - Triterpenoidal saponins have been reported to be able to restrain SARS-CoV-2 infection. To isolate antiviral compounds against SARS-CoV-2 from the leaves of Aster koraiensis, we conducted multiple steps of column chromatography. We isolated six triperpenoidal saponins from A. koraiensis leaves, including three unreported saponins. Their chemical structures were determined using HR-MS and NMR data analyses. Subsequently, we tested the isolates to assess their ability to impede the entry of the…
Assessing Genomic Mutations in SARS-CoV-2: Potential Resistance to Antiviral Drugs in Viral Populations from Untreated COVID-19 Patients - Naturally occurring SARS-CoV-2 variants mutated in genomic regions targeted by antiviral drugs have not been extensively studied. This study investigated the potential of the RNA-dependent RNA polymerase (RdRp) complex subunits and non-structural protein (Nsp)5 of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to accumulate natural mutations that could affect the efficacy of antiviral drugs. To this aim, SARS-CoV-2 genomic sequences isolated from 4155 drug-naive individuals from…
An Investigation of Severe Influenza Cases in Russia during the 2022-2023 Epidemic Season and an Analysis of HA-D222G/N Polymorphism in Newly Emerged and Dominant Clade 6B.1A.5a.2a A(H1N1)pdm09 Viruses - In Russia, during the COVID-19 pandemic, a decrease in influenza circulation was initially observed. Influenza circulation re-emerged with the dominance of new clades of A(H3N2) viruses in 2021-2022 and A(H1N1)pdm09 viruses in 2022-2023. In this study, we aimed to characterize influenza viruses during the 2022-2023 season in Russia, as well as investigate A(H1N1)pdm09 HA-D222G/N polymorphism associated with increased disease severity. PCR testing of 780 clinical specimens showed 72.2% of them to…
Antivirals for Broader Coverage against Human Coronaviruses - Coronaviruses (CoVs) are enveloped positive-sense single-stranded RNA viruses with a genome that is 27-31 kbases in length. Critical genes include the spike (S), envelope (E), membrane (M), nucleocapsid (N) and nine accessory open reading frames encoding for non-structural proteins (NSPs) that have multiple roles in the replication cycle and immune evasion (1). There are seven known human CoVs that most likely appeared after zoonotic transfer, the most recent being SARS-CoV-2, responsible for…
Emerging Therapeutic Potential of Polyphenols from Geranium sanguineum L. in Viral Infections, Including SARS-CoV-2 - The existing literature supports the anti-inflammatory, antioxidant, and antiviral capacities of the polyphenol extracts derived from Geranium sanguineum L. These extracts exhibit potential in hindering viral replication by inhibiting enzymes like DNA polymerase and reverse transcriptase. The antiviral properties of G. sanguineum L. seem to complement its immunomodulatory effects, contributing to infection resolution. While preclinical studies on G. sanguineum L. suggest its potential…
Excess phosphate promotes SARS‑CoV‑2 N protein‑induced NLRP3 inflammasome activation via the SCAP‑SREBP2 signaling pathway - Hyperphosphatemia or severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can promote cardiovascular adverse events in patients with chronic kidney disease. Hyperphosphatemia is associated with elevated inflammation and sterol regulatory element binding protein 2 (SREBP2) activation, but the underlying mechanisms in SARS‑CoV‑2 that are related to cardiovascular disease remain unclear. The present study aimed to elucidate the role of excess inorganic phosphate (PI) in SARS‑CoV‑2…
Quercetin inhibits SARS-CoV-2 infection and prevents syncytium formation by cells co-expressing the viral spike protein and human ACE2 - CONCLUSION: These findings suggest that at low 3-digit micromolar concentrations of quercetin could impair SARS-CoV-2 infection of human cells partly by blocking the fusion process that promotes its propagation.
The temporal association of CapZ with early endosomes regulates endosomal trafficking and viral entry into host cells - CONCLUSIONS: These results indicate that the temporal association of CapZ with EEs facilitates early-to-late endosome transition (physiologically) and the release of the viral genome from endocytic vesicles (pathologically).
Longitudinal plasma proteomics reveals biomarkers of alveolar-capillary barrier disruption in critically ill COVID-19 patients - The pathobiology of respiratory failure in COVID-19 consists of a complex interplay between viral cytopathic effects and a dysregulated host immune response. In critically ill patients, imatinib treatment demonstrated potential for reducing invasive ventilation duration and mortality. Here, we perform longitudinal profiling of 6385 plasma proteins in 318 hospitalised patients to investigate the biological processes involved in critical COVID-19, and assess the effects of imatinib treatment. Nine…
Drug repurposing platform for deciphering the druggable SARS-CoV-2 interactome - The coronavirus disease 2019 (COVID-19) pandemic has heavily challenged the global healthcare system. Despite the vaccination programs, the new virus variants are circulating. Further research is required for understanding of the biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and for discovery of therapeutic agents against the virus. Here, we took advantage of drug repurposing to identify if existing drugs could inhibit SARS-CoV-2 infection. We established an…
Mechanistic Understanding of the Modes of Ca2+ Ion Binding to the SARS-CoV-1 Fusion Peptide and Their Role in the Dynamics of Host Membrane Penetration - The SARS-CoV-1 spike glycoprotein contains a fusion peptide (FP) segment that mediates the fusion of the viral and host cell membranes. Calcium ions are thought to position the FP optimally for membrane insertion by interacting with negatively charged residues in this segment (E801, D802, D812, E821, D825, and D830); however, which residues bind to calcium and in what combinations supportive of membrane insertion are unknown. Using biological assays and molecular dynamics studies, we have…
Pharmacokinetics of recombinant human annexin A5 (SY-005) in patients with severe COVID-19 - Objective: Annexin A5 is a phosphatidylserine binding protein with anti-inflammatory, anticoagulant and anti-apoptotic properties. Preclinical studies have shown that annexin A5 inhibits pro-inflammatory responses and improves organ function and survival in rodent models of sepsis. This clinical trial aimed to evaluate the pharmacokinetic (PK) properties of the recombinant human annexin A5 (SY-005) in severe COVID-19. Methods: This was a pilot randomized, double-blind, placebo-controlled trial….