Covid-19 Sentry

Contents

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

From Preprints

• Tracking SARS-CoV-2 genomic variants in wastewater sequencing data with LolliPop -

  During the COVID-19 pandemic, wastewater-based epidemiology has progressively taken a central role as a pathogen surveillance tool. Tracking viral loads and variant outbreaks in sewage offers advantages over clinical surveillance methods by providing unbiased estimates and enabling early detection. However, wastewater-based epidemiology poses new computational research questions that need to be solved in order for this approach to be implemented broadly and successfully. Here, we address the variant deconvolution problem, where we aim to estimate the relative abundances of genomic variants from next-generation sequencing data of a mixed wastewater sample. We introduce LolliPop, a computational method to solve the variant deconvolution problem by simultaneously solving least squares problems and kernel-based smoothing of relative variant abundances from wastewater time series sequencing data. We derive multiple approaches to compute confidence bands, and demonstrate the application of our method to data from the Swiss wastewater surveillance efforts.

  🖺 Full Text HTML: Tracking SARS-CoV-2 genomic variants in wastewater sequencing data with LolliPop
• Impact of SARS-CoV-2 on the microbiota of pregnant women and their infants -

  The microbiome inherited at birth exerts marked effects on immune programming with long-term health consequences. Here, we demonstrated that the gut, vaginal, and oral microbial diversity of pregnant women with SARS-CoV-2 infection is reduced, and women with early infections exhibit a different vaginal microbiota composition compared to healthy controls at the time of delivery. Accordingly, infants born to pregnant women with early SARS-CoV-2 infection exhibit a unique oral microbiota dominated by Streptococcus species. Together, we demonstrated that SARS-CoV-2 infections during pregnancy, particularly early infections, are associated with lasting changes in the microbiome of pregnant women compromising the initial microbial seed of their infant. Our results highlight the importance of further exploring the impact of SARS-CoV-2 on the infant9s microbiome-dependent immune programming.

  🖺 Full Text HTML: Impact of SARS-CoV-2 on the microbiota of pregnant women and their infants
• BIOLOGICAL RHYTHMS IN COVID-19 VACCINE EFFECTIVENESS -

  Importance Circadian rhythms affect fundamental immune processes, but how this translates to clinical outcomes like real-world vaccine effectiveness is unclear. Objective To examine associations between Coronavirus Infectious Disease 2019 (COVID-19) vaccination timing and effectiveness. Design, Setting, and Participants Retrospective cohort study of database records from Maccabi Healthcare Services (MHS), a major Israeli Health Maintenance Organization (HMO). We included all individuals over 12 with at least one timestamped vaccine dose and no documented COVID-19 infection prior to completing the initial 2-dose immunization series (n=1,515,754, 99.2% receiving BNT162b2). Database records spanned December 19, 2020, to April 25, 2022, encompassing two spikes in COVID infection dominated by the delta (B.1.617.2) and omicron (B.1.1.529) SARS-CoV-2 variants. Main Outcomes and Measures Outcomes included COVID-19 breakthrough infection and COVID-19 associated emergency department (ED) visits. Our main comparison was between patients vaccinated exclusively during morning hours (8:00-11:59), afternoon (12:00-15:59), or evening hours (16:00-19:59). We employed Cox multivariate regression to adjust for differences in age, sex, and co-morbidities. Results. Breakthrough infections differed based on vaccination time, with lowest rates associated with late morning to early afternoon, and highest rates with evening vaccination. Vaccination timing remained significant after adjustment for patient age, sex, and co-morbidities (HR=0.88 afternoon vs. evening, [95% CI 0.87-0.90]). Results were consistent in patients who received the basic two-dose vaccine series and who received booster doses. The association between COVID immunization time and infection risk followed a sinusoidal pattern, consistent with a biological rhythm in vaccine effectiveness that modifies clinical effectiveness by 8.6-25% depending on the vaccine dose (initial vaccine series, first booster, or second booster). The benefits of daytime vaccination were concentrated in younger and elderly patients. In contrast to breakthrough infections, COVID-19 related ED visits correlated with age and medical comorbidities but not with time of vaccination. Conclusions and Relevance We report a significant association between the time of COVID-19 vaccination and its clinical effectiveness in terms of breakthrough infection. These data have implications for mass vaccination programs.

  🖺 Full Text HTML: BIOLOGICAL RHYTHMS IN COVID-19 VACCINE EFFECTIVENESS
• Longitudinal proteomic investigation of COVID-19 vaccination -

  Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac) at a 28-day interval. Using TMT-based proteomics, we identified 1715 serum and 7342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC9s potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning.

  🖺 Full Text HTML: Longitudinal proteomic investigation of COVID-19 vaccination
• Substantial Neutralization Escape by the SARS-CoV-2 Omicron Variant BQ.1.1 -
  Omicron BA.5 has been the globally dominant SARS-CoV-2 variant and has demonstrated substantial neutralization escape compared with prior variants. Additional Omicron variants have recently emerged, including BA.4.6, BF.7, BA.2.75.2, and BQ.1.1, all of which have the Spike R346T mutation. In particular, BQ.1.1 has rapidly increased in frequency, and BA.5 has recently declined to less than half of viruses in the United States. Our data demonstrate that BA.2.75.2 and BQ.1.1 escape NAbs induced by infection and vaccination more effectively than BA.5. BQ.1.1 NAb titers were lower than BA.5 NAb titers by a factor of 7 in two cohorts of individuals who received the monovalent or bivalent mRNA vaccine boosters. These findings provide the immunologic context for the rapid increase in BQ.1.1 prevalence in regions where BA.5 is dominant and have implications for both vaccine immunity and natural immunity.
  🖺 Full Text HTML: Substantial Neutralization Escape by the SARS-CoV-2 Omicron Variant BQ.1.1
• Low neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1, and XBB.1 by 4 doses of parental mRNA vaccine or a BA.5-bivalent booster -
  The newly emerged SARS-CoV-2 Omicron BQ.1.1, XBB.1, and other sublineages have accumulated additional spike mutations that may affect vaccine effectiveness. Here we report neutralizing activities of three human serum panels collected from individuals 1-3 months after dose 4 of parental mRNA vaccine (post-dose-4), 1 month after a BA.5-bivalent-booster (BA.5-bivalent-booster), or 1 month after a BA.5-bivalent-booster with previous SARS-CoV-2 infection (BA.5-bivalent-booster-infection). Post-dose-4 sera neutralized USA-WA1/2020, BA.5, BF.7, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 SARS-CoV-2 with geometric mean titers (GMTs) of 1533, 95, 69, 62, 26, 22, and 15, respectively; BA.5-bivalent-booster sera improved the GMTs to 3620, 298, 305, 183, 98, 73, and 35; BA.5-bivalent-booster-infection sera further increased the GMTs to 5776, 1558,1223, 744, 367, 267, and 103. Thus, although BA.5-bivalent-booster elicits better neutralization than parental vaccine, it does not produce robust neutralization against the newly emerged Omicron BA.2.75.2, BQ.1.1, and XBB.1. Previous infection enhances the magnitude and breadth of BA.5-bivalent-booster-elicited neutralization.
  🖺 Full Text HTML: Low neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1, and XBB.1 by 4 doses of parental mRNA vaccine or a BA.5-bivalent booster
• Preliminary report: Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, KD-414, in healthy adult participants: a non-randomized, open-label phase 2/3 clinical study in Japan -

  Background: In the prolonged COVID-19 pandemic, there remains a high need for the development of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine that can be used more safely and effectively to prevents the disease onset or severe disease. To satisfy such unmet need, we are currently developing the inactivated whole particle SARS-CoV-2 vaccine (KD-414) and conducted a phase 2/3 study in healthy adults in Japan to accumulate more immunogenicity and safety data of KD-414 using the dose selected based on the results of the phase 1/2 study. Methods: In an open-label uncontrolled phase 2/3 study, adults aged 18 years or older without a history of COVID-19 or COVID-19 vaccination received two intramuscular doses of KD-414 at a 28-day intervals, followed by one intramuscular dose 13 weeks after the second dose as the primary immunization. Safety data were collected after the first dose of KD-414 in all participants to evaluate the safety profile. In predetermined immunogenicity analysis subjects, the neutralizing antibody titers against the pseudovirus SARS-CoV-2 (Wuhan) before the first vaccination and after each vaccination with KD-414 were evaluated. Results: A total of 2500 adults aged 18 years or older were enrolled; 2474 of them received the vaccination up to the second dose, and 2081 completed the third vaccination. Regarding the safety, no deaths or serious adverse reactions were recorded from the first vaccination until 28 days after the third vaccination with KD-414. The incidence of adverse reactions (number of participants with onsets/number of participants in the safety analysis set) was 80.6% (2015/2500). Adverse reactions with an incidence of 10% or more included injection site pain, malaise, headache, injection site erythema, myalgia, and injection site induration. A total of 11 events of grade 3 or higher adverse reactions that prevented daily activities in 9 participants. There was no increasing tendency in the incidence of adverse reactions responding to the vaccinations. To evaluate immunogenicity, 295 first comers enrolled from five age ranges were allocated to the immunogenicity analysis subjects; 291 participants received the vaccination up to the second dose, and 249 participants completed the third vaccination. The geometric mean titers (95% confidence interval [CI]) of neutralizing antibody titers against pseudovirus SARS-CoV-2 (Wuhan) 28 days after the second vaccination and 28 days after the third vaccination with KD-414 were 139.6 (118.9 - 164.0) and 285.6 (244.3 - 334.0), respectively, showing an approximately two-fold increase after the third vaccination compared to that after the second vaccination. The geometric mean titers (95% CI) of neutralizing antibody titers after the third vaccination were 327.6 (269.8 - 397.9), 272.2 (211.5 - 350.4) and 128.0 (51.6 - 317.7) in participants aged 18 to 40 years, 41 to 64 years, and 65 years or older, respectively, showing an age-dependency. Conclusion: This study confirmed the favorable safety profile of KD-414 as a result of three vaccinations of KD-414 administered to over 2000 healthy Japanese participants aged 18 years or older. There were no particular differences in the types and incidences of adverse reactions between vaccinations, and no tendency of an increase in adverse reactions with an increase in the number of vaccinations. Similar to the phase 1/2 study, neutralizing antibody responses appeared to be age-dependent and the highest titers were observed in the age group of 18 - 40 years. A phase 3 study in adults aged 18 - 40 years (jRCT2031210679) and a phase 2/3 study in children aged 6 months - 18 years (jRCT2031220032) are currently ongoing.

  🖺 Full Text HTML: Preliminary report: Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, KD-414, in healthy adult participants: a non-randomized, open-label phase 2/3 clinical study in Japan
• Context-dependent responses to the spread of COVID-19 among national and international students during the first lockdown -
  Restriction to minimize social contacts (often called social distancing) are necessary to prevent the spread of the SARS-CoV-2 virus, but they can greatly impact individuals’ mental well-being. In general, emotional responses are modulated by contextual information such that negative emotions are enhanced when experienced within aversive contexts. In this online survey study, we investigated 850 university students during March/April 2020 (first lockdown in the Netherlands), comparing the psychological impact of social distancing when living in a familiar (national students) or in unfamiliar (international students) and therefore likely more aversive context. Four factors (worry, perceived risk of infection, physical distancing, social distancing) were identified, describing how students felt and reacted to the virus. International students showed higher levels in these measures than national students. We then used structural equation modelling (SEM) to compare how these virus-related factors were predicted by health anxiety (fear of contamination, body vigilance, healthy anxiety, anxiety sensitivity), emotional distress (depression, state anxiety), and personal traits (intolerance of uncertainty, trait anxiety) questionnaires. The virus-related factors were mainly predicted by health anxiety across international students, while emotional distress and individual traits played a role across national students. In sum, the familiar context may have been less aversive than the unfamiliar foreign context, and the individual characteristics (traits) predicted the responses to the virus. Living in an unfamiliar and more uncertain context seemed to drive individuals’ health-focused responses to the virus. These results also suggest having living in a foreign country is associated with psychological burdens and this should be considered by universities for mental well-being plans of these students.
  🖺 Full Text HTML: Context-dependent responses to the spread of COVID-19 among national and international students during the first lockdown
• Prevalence and pattern of adverse events following COVID 19 vaccination among adult population in Sokoto metropolis, northwest, Nigeria -

  Background: COVID-19 still poses a major public health challenge worldwide and vaccination remains one of the major interventions to control the disease. Different types of vaccines approved by the World Health Organization (WHO) are currently in use across the world to protect against the disease. As all vaccines are associated with some adverse reactions (ARs), this study assessed the prevalence and pattern of adverse events following immunization (AEFI) after receiving COVID-19 vaccine among the adult population in Sokoto metropolis, North-west, Nigeria Methods: We conducted a cross-sectional study among 230 adults in Sokoto metropolis who received COVID-19 vaccine. Data was collected using a structured questionnaire administered via personal phone calls to respondents who were  selected via a systematic sampling technique. For data analysis, IBM SPSS version 25.0 was used. Results:  The Majority of the participants [183 (79.7%)] experienced AEFI.  The most common adverse events were body weakness [157(85%)], fever [111(60.3%)] and headache [103(56%)]. Up to half of the respondents that experienced AEFI said it occurred within minutes and a few hours, whereas 75 (40.8%) said it was within 2-3 days. Up to 66.3 of the adverse reactions were mild and lasted between a few hours (37.5%) and one day (31.5%); however, 15.2% of the respondents had severe reactions of which 22.7% were admitted to a health facility. The development of AEFI was linked to the absence of an underlying medical condition, a previous history of AEFI, and a history of drug reaction.  Conclusion: The majority of respondents reported adverse events following COVID-19 vaccination, with body weakness, fever, and headache being the most common AEFIs. The underlying medical condition as well as a history of adverse drug reactions were predictors of the development of adverse reactions following COVID-19 vaccination. Service providers at each COVID-19 vaccination point should always take the time to explain to vaccine recipients that adverse reactions are possible; however, they should reassure them that most ARs resolve within a few hours to a few days.

  🖺 Full Text HTML: Prevalence and pattern of adverse events following COVID 19 vaccination among adult population in Sokoto metropolis, northwest, Nigeria
• DiSCERN - Deep Single Cell Expression ReconstructioN for improved cell clustering and cell subtype and state detection -
  Single cell sequencing provides detailed insights into biological processes including cell differentiation and identity. While providing deep cell-specific information, the method suffers from technical constraints, most notably a limited number of expressed genes per cell, which leads to suboptimal clustering and cell type identification. Here we present DISCERN, a novel deep generative network that reconstructs missing single cell gene expression using a reference dataset. DISCERN outperforms competing algorithms in expression inference resulting in greatly improved cell clustering, cell type and activity detection, and insights into the cellular regulation of disease. We used DISCERN to detect two unseen COVID-19-associated T cell types, cytotoxic CD4 + and CD8 + Tc2 T helper cells, with a potential role in adverse disease outcome. We utilized T cell fraction information of patient blood to classify mild or severe COVID-19 with an AUROC of 81 % that can serve as a biomarker of disease stage. DISCERN can be easily integrated into existing single cell sequencing workflows and readily adapted to enhance various other biomedical data types.
  🖺 Full Text HTML: DiSCERN - Deep Single Cell Expression ReconstructioN for improved cell clustering and cell subtype and state detection
• Inactivation of Influenza A virus by pH conditions encountered in expiratory aerosol particles results from localized conformational changes within Haemagglutinin and Matrix 1 proteins. -
  Multiple respiratory viruses including Influenza A virus (IAV) can be transmitted via expiratory aerosol particles, and many studies have established that indoor environmental conditions can affect viral infectivity during this transmission. Aerosol pH was recently identified as a major factor influencing the infectivity of aerosol-borne IAV and SARS-CoV-2, and for indoor room air, modelling indicates that small exhaled aerosols will undergo rapid acidification (pH below 5.5). However, there is a fundamental lack of understanding as to the mechanisms leading to viral inactivation within an acidic aerosol micro-environment. Here, we identified that transient exposure to acidic conditions impacted the early stages of the IAV infection cycle, which was primarily attributed to loss of binding function of the viral protein haemagglutinin. Viral capsid integrity was also partially affected by transient acidic exposures. The structural changes associated with loss of viral infectivity were then characterized using whole-virus hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS), and we observed discrete regions of unfolding in the external viral protein haemagglutinin and the internal matrix protein 1. Viral nucleoprotein structure appeared to be unaffected by exposure to acidic conditions. Protein analyses were complemented by genome and lipid envelope characterizations, and no acid-mediated changes were detected using our whole-virus methods. Improved understanding of the fate of respiratory viruses within exhaled aerosols constitutes a global public health priority, and information gained here could aid the development of novel strategies or therapeutics to control the airborne persistence of seasonal and/or pandemic influenza in the future. This study also provides proof-of-concept that HDX-MS is a highly effective method for characterization of both internal and external proteins for whole enveloped viruses such as IAV.
  🖺 Full Text HTML: Inactivation of Influenza A virus by pH conditions encountered in expiratory aerosol particles results from localized conformational changes within Haemagglutinin and Matrix 1 proteins.
• Post-COVID Phenotypic Manifestations are Associated with New-Onset Psychiatric Disease: Findings from the NIH N3C and RECOVER Studies -

  Acute COVID-19 infection can be followed by diverse clinical manifestations referred to as Post Acute Sequelae of SARS-CoV2 Infection (PASC). Studies have shown an increased risk of being diagnosed with new-onset psychiatric disease following a diagnosis of acute COVID-19. However, it was unclear whether non-psychiatric PASC-associated manifestations (PASC-AMs) are associated with an increased risk of new-onset psychiatric disease following COVID-19. A retrospective EHR cohort study of 1,603,767 individuals with acute COVID-19 was performed to evaluate whether non-psychiatric PASC-AMs are associated with new-onset psychiatric disease. Data were obtained from the National COVID Cohort Collaborative (N3C), which has EHR data from 65 clinical organizations. EHR codes were mapped to 151 non-psychiatric PASC-AMs recorded 28-120 days following SARS-CoV-2 diagnosis and before diagnosis of new-onset psychiatric disease. Association of newly diagnosed psychiatric disease with age, sex, race, pre-existing comorbidities, and PASC-AMs in seven categories was assessed by logistic regression. There was a significant association between six categories and newly diagnosed anxiety, mood, and psychotic disorders, with odds ratios highest for cardiovascular (1.35, 1.27-1.42) PASC-AMs. Secondary analysis revealed that the proportions of 95 individual clinical features significantly differed between patients diagnosed with different psychiatric disorders. Our study provides evidence for association between non-psychiatric PASC-AMs and the incidence of newly diagnosed psychiatric disease. Significant associations were found for features related to multiple organ systems. This information could prove useful in understanding risk stratification for new-onset psychiatric disease following COVID-19. Prospective studies are needed to corroborate these findings.

  🖺 Full Text HTML: Post-COVID Phenotypic Manifestations are Associated with New-Onset Psychiatric Disease: Findings from the NIH N3C and RECOVER Studies
• An optimised method for recovery and quantification of laboratory generated SARS-CoV-2 aerosols by plaque assay. -
  We present an optimised method for the recovery of laboratory generated SARS-CoV-2 aerosols and quantification by plaque assays. This method allows easy incorporation into existing standard operating procedures of biological containment level 3 (CL3) laboratories.
  🖺 Full Text HTML: An optimised method for recovery and quantification of laboratory generated SARS-CoV-2 aerosols by plaque assay.
• Site of vulnerability on SARS-CoV-2 spike induces broadly protective antibody to antigenically distinct omicron SARS-CoV-2 subvariants -
  The rapid evolution of SARS-CoV-2 Omicron variants has emphasized the need to identify antibodies with broad neutralizing capabilities to inform future monoclonal therapies and vaccination strategies. Herein, we identify S728-1157, a broadly neutralizing antibody (bnAb) targeting the receptor-binding site (RBS) and derived from an individual previously infected with SARS-CoV-2 prior to the spread of variants of concern (VOCs). S728-1157 demonstrates broad cross-neutralization of all dominant variants including D614G, Beta, Delta, Kappa, Mu, and Omicron (BA.1/BA.2/BA.2.75/BA.4/BA.5/BL.1). Furthermore, it protected hamsters against in vivo challenges with wildtype, Delta, and BA.1 viruses. Structural analysis reveals that this antibody targets a class 1 epitope via multiple hydrophobic and polar interactions with its CDR-H3, in addition to common class 1 motifs in CDR-H1/CDR-H2. Importantly, this epitope is more readily accessible in the open and prefusion state, or in the hexaproline (6P)-stabilized spike constructs, as compared to diproline (2P) constructs. Overall, S728-1157 demonstrates broad therapeutic potential, and may inform target-driven vaccine design against future SARS-CoV-2 variants.
  🖺 Full Text HTML: Site of vulnerability on SARS-CoV-2 spike induces broadly protective antibody to antigenically distinct omicron SARS-CoV-2 subvariants
• mRNA bivalent booster enhances neutralization against BA.2.75.2 and BQ.1.1 -
  The emergence of the highly divergent SARS-CoV-2 Omicron variant has jeopardized the efficacy of vaccines based on the ancestral spike. The bivalent COVID-19 mRNA booster vaccine within the United States is comprised of the ancestral and the Omicron BA.5 spike. Since its approval and distribution, additional Omicron subvariants have been identified with key mutations within the spike protein receptor binding domain that are predicted to escape vaccine sera. Of particular concern is the R346T mutation which has arisen in multiple subvariants, including BA.2.75.2 and BQ.1.1. Using a live virus neutralization assay, we evaluated serum samples from individuals who had received either one or two monovalent boosters or the bivalent booster to determine neutralizing activity against wild-type (WA1/2020) virus and Omicron subvariants BA.1, BA.5, BA.2.75.2, and BQ.1.1. In the one monovalent booster cohort, relative to WA1/2020, we observed a reduction in neutralization titers of 9-15-fold against BA.1 and BA.5 and 28-39-fold against BA.2.75.2 and BQ.1.1. In the BA.5-containing bivalent booster cohort, the neutralizing activity improved against all the Omicron subvariants. Relative to WA1/2020, we observed a reduction in neutralization titers of 3.7- and 4-fold against BA.1 and BA.5, respectively, and 11.5- and 21-fold against BA.2.75.2 and BQ.1.1, respectively. These data suggest that the bivalent mRNA booster vaccine broadens humoral immunity against the Omicron subvariants.
  🖺 Full Text HTML: mRNA bivalent booster enhances neutralization against BA.2.75.2 and BQ.1.1

From Clinical Trials

• Safety and Efficacy of Medications COVID-19 - Condition:   Severe Covid-19
  Intervention:   Drug: Oral bedtime melatonin
  Sponsor:   Hospital San Carlos, Madrid
  Completed

• Use of Multiple Doses of Convalescent Plasma in Mechanically Intubated Patients With COVID-19 - Condition:   COVID-19
  Intervention:   Biological: Multiple doses of anti-SARS-CoV-2 Convalescent Plasma
  Sponsors:   Hospital Regional Dr. Rafael Estévez;   Complejo Hospitalario Dr. Arnulfo Arias Madrid;   Hospital Santo Tomas;   Hospital Punta Pacífica, Pacífica Salud;   Insituto Conmemorativo Gorgas de Estudios para la Salud;   Sociedad Panameña de Hematología;   Institute of Scientific Research and High Technology Services (INDICASAT AIP);   University of Panama;   Sistema Nacional de Investigación de Panamá
  Completed

• A Phase III of COVID-19 Vaccine EuCorVac-19 in Healthy Adults Aged 18 Years and Older - Condition:   COVID-19
  Interventions:   Biological: EuCorVac-19;   Biological: ChAdOx1
  Sponsor:   EuBiologics Co.,Ltd
  Recruiting

• Open Multicenter Study for Assessment of Efficacy and Safety of Molnupiravir in Adult Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Molnupiravir (Esperavir);   Drug: Standard of care
  Sponsor:   Promomed, LLC
  Completed

• Open Multicentre Study of the Safety and Efficacy Against COVID-19 of Nirmatrelvir/Ritonavir in the Adult Population - Condition:   COVID-19
  Interventions:   Drug: nirmatrelvir/ritonavir;   Drug: Standard of care
  Sponsors:   Promomed, LLC;   Sponsor GmbH
  Completed

• Study Evaluating GS-5245 in Participants With COVID-19 Who Have a High Risk of Developing Serious or Severe Illness - Condition:   COVID-19
  Interventions:   Drug: GS-5245;   Drug: GS-5245 Placebo
  Sponsor:   Gilead Sciences
  Recruiting

• Effects of Respiratory Muscle Training in Individuals With Long-term Post-COVID-19 Symptoms - Conditions:   Covid19;   Post-acute COVID-19 Syndrome
  Interventions:   Other: Inspiratory + expiratory muscle training group;   Other: Inspiratory + expiratory muscle training sham group;   Other: Exercise training program
  Sponsors:   Universidad Complutense de Madrid;   Colegio Profesional de Fisioterapeutas de la Comunidad de Madrid
  Recruiting

• Recombinant COVID-19 Vaccine (CHO Cell, NVSI-06-09) Phase III Clinical Trial - Conditions:   COVID-19;   Coronavirus Infections
  Interventions:   Biological: LIBP-Rec-Vaccine;   Biological: BIBP-Rec-Vaccine;   Biological: placebo
  Sponsors:   National Vaccine and Serum Institute, China;   China National Biotec Group Company Limited;   Lanzhou Institute of Biological Products Co., Ltd;   Beijing Institute of Biological Products Co Ltd.
  Not yet recruiting

• OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients: a Randomized Factorial Controlled Strategy Trial - Conditions:   COVID-19;   Immunodeficiency
  Interventions:   Drug: Paxlovid 5 days;   Drug: Paxlovid 10 days;   Drug: Tixagevimab and Cilgavimab
  Sponsors:   ANRS, Emerging Infectious Diseases;   University Hospital, Geneva
  Not yet recruiting

• A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Combined Modified RNA Vaccine Candidates Against COVID-19 and Influenza - Conditions:   Influenza, Human;   COVID-19
  Interventions:   Biological: bivalent BNT162b2 (original/Omi BA.4/BA.5);   Biological: qIRV (22/23);   Biological: QIV
  Sponsors:   BioNTech SE;   Pfizer
  Not yet recruiting

• Study to Evaluate Safety, Tolerability, Efficacy and Pharmacokinetics of ASC10 in Mild to Moderate COVID-19 Patients - Condition:   SARS CoV 2 Infection
  Interventions:   Drug: ASC10;   Drug: Placebo
  Sponsor:   Ascletis Pharmaceuticals Co., Ltd.
  Not yet recruiting

• A Phase I/II Study of GLB-COV2-043 as a COVID-19 Vaccine Booster - Condition:   COVID-19
  Interventions:   Drug: GLB-COV2-043;   Drug: BNT162b2/COMIRNATY®
  Sponsor:   GreenLight Biosciences, Inc.
  Not yet recruiting

• Safety and Efficacy of Intranasal Administration of Avacc 10 Vaccine Against COVID-19 in Healthy Volunteers - Condition:   COVID-19
  Interventions:   Biological: Avacc 10;   Combination Product: Outer Membrane Vesicles (OMV) : OMV alone in vehicle;   Other: Placebo
  Sponsors:   Intravacc B.V.;   Novotech (Australia) Pty Limited
  Not yet recruiting

• The Phase Ⅱ/Ⅲ Trial of LYB001 - Condition:   COVID-19
  Interventions:   Biological: LYB001;   Biological: Placebo
  Sponsor:   Yantai Patronus Biotech Co., Ltd.
  Not yet recruiting

• Nitric Oxide Nasal Spray (NONS) To Treat and Prevent the Exacerbation of Infection in Individuals With Mild COVID-19 - Condition:   SARS-CoV-2 Infection
  Intervention:   Drug: Nitric Oxide
  Sponsors:   Sanotize Research and Development corp.;   Glenmark Pharmaceuticals Ltd. India
  Completed

From PubMed

• Lupus anticoagulant-hypoprothrombinemia syndrome with severe bleeding diathesis after coronavirus disease 2019: a case report - Acquired antibodies against factor II (prothrombin) are rare and most commonly associated with severe liver disease or vitamin K antagonist treatment. In very rare cases, these antibodies and associated hypoprothrombinemia are found in patients with lupus anticoagulant (LAC), an antiphospholipid antibody that inhibits phospholipid-dependent coagulation tests. This uncommon entity, called lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS), may cause both severe, life-threatening bleeding…

• HLA-C dysregulation as a possible mechanism of immune evasion in SARS-CoV-2 and other RNA-virus infections - One of the mechanisms by which viruses can evade the host’s immune system is to modify the host’s DNA methylation pattern. This work aims to investigate the DNA methylation and gene expression profile of COVID-19 patients, divided into symptomatic and asymptomatic, and healthy controls, focusing on genes involved in the immune response. In this study, changes in the methylome of COVID-19 patients’ upper airways cells, the first barrier against respiratory infections and the first cells…

• Evidence of a Sjögren’s disease-like phenotype following COVID-19 - CONCLUSION: Overall, our study shows a direct association between SARS-CoV-2 and SjD. Hallmark features of SjD salivary glands were histologically indistinguishable from convalescent COVID-19 subjects. The results potentially implicate that SARS-CoV-2 could be an environmental trigger for SjD.

• Modulation of type I interferon responses potently inhibits SARS-CoV-2 replication and inflammation in rhesus macaques - Type-I interferons (IFN-I) are critical mediators of innate control of viral infections, but also drive recruitment of inflammatory cells to sites of infection, a key feature of severe COVID-19. Here, and for the first time, IFN-I signaling was modulated in rhesus macaques (RMs) prior to and during acute SARS-CoV-2 infection using a mutated IFNα2 (IFN-modulator; IFNmod), which has previously been shown to reduce the binding and signaling of endogenous IFN-I. In SARS-CoV-2-infected RMs, IFNmod…

• Sulfated endospermic nanocellulose crystals prevent the transmission of SARS-CoV-2 and HIV-1 - Biomaterials with antimicrobial activity are gaining attention due to their biodegradability and efficacy in interacting with a wide range of microorganisms. A new cellulose nano-biomaterial, endospermic nanocellulose crystals (ENC) obtained from parenchymal tissue of ivory nut endosperm, has a natural capacity as a universal binder. This feature is enhanced when it is chemically functionalized, and can be exploited in the fight against microbes. We tested the ability of sulfated ENC in aqueous…

• SARS-CoV-2 infection causes prolonged cardiomyocyte swelling and inhibition of HIF1α translocation in an animal model COVID-19 - Recovered COVID-19 patients often display cardiac dysfunction, even after a mild infection. Most current histological results come from patients that are hospitalized and therefore represent more severe outcomes than most COVID-19 patients face. To overcome this limitation, we investigated the cardiac effects of SARS-CoV-2 infection in a hamster model. SARS-CoV-2 infected hamsters developed diastolic dysfunction after recovering from COVID-19. Histologically, increased cardiomyocyte size was…

• Temporal Transcriptome Analysis of SARS-CoV-2-Infected Lung and Spleen in Human ACE2-Transgenic Mice - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed…

• Spectroscopic details on the molecular structure of pyrimidine‑2‑thiones heterocyclic compounds: computational and antiviral activity against the main protease enzyme of SARS-CoV-2 - Computational tools in investigating of spectral heterocyclic compounds ranges based on pyrimidine‑2‑thiones, take some importance in identifying their molecular and electronic behavior. Some charcoal heterocyclic compounds were previously synthesized in our laboratory and their experimental results were compared with the computational evaluation. Computational spectroscopic analytical items (IR, NMR and UV-Vis) were calculated using the more popular DFT methods and the predicted results were…

• Corrigendum to ‘Replication of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E is inhibited by the drug FK506’ Virus Research (2012) 165/1 [112-117]: Corrigendum - No abstract

• Anti-SARS-CoV-2 and cytotoxic activity of two marine alkaloids from green alga Caulerpa cylindracea Sonder in the Dardanelles - Caulerpa cylindracea Sonder is a green alga belonging to the Caulerpaceae family. This is the first chemical investigation of C. cylindracea in the Dardanelles which resulted in the isolation of four compounds, caulerpin (1), monomethyl caulerpinate (2), beta-sitosterol (3), and palmitic acid (4). Their structures were elucidated by spectroscopic analyses including 1D- and 2D NMR and mass. The isolated compounds 1 and 2 were tested against the SARS-CoV-2 viral targets spike protein and main…

• Withholding methotrexate after vaccination with ChAdOx1 nCov19 in patients with rheumatoid or psoriatic arthritis in India (MIVAC I and II): results of two, parallel, assessor-masked, randomised controlled trials - BACKGROUND: There is a necessity for an optimal COVID-19 vaccination strategy for vulnerable population groups, including people with autoimmune inflammatory arthritis on immunosuppressants such as methotrexate, which inhibit vaccine-induced immunity against SARS-CoV-2. Thus, we aimed to assess the effects of withholding methotrexate for 2 weeks after each dose of ChAdOx1 nCov-19 (Oxford-AstraZeneca) vaccine (MIVAC I) or only after the second dose of vaccine (MIVAC II) compared with continuation…

• In silico analyses of betulin: DFT studies, corrosion inhibition properties, ADMET prediction, and molecular docking with a series of SARS-CoV-2 and monkeypox proteins - We report detailed computational studies of betulin - a pentacyclic naturally occuring triterpene, which is a precursor for a broad family of biologically active derivatives. The structure, electronic, and optical properties of betulin were studied by the density functional theory (DFT) calculations in gas phase. The reactivity and the reactive centers of betulin were revealed through its global reactivity descriptors and molecular electrostatic potential (MEP). The DFT calculations were also…

• Irradiation accelerates SARS-CoV-2 infection by enhancing sphingolipid metabolism - Cancer patients who receive radiotherapy have a high risk of SARS-CoV-2 infection, but the concrete reason remains unclear. Herein, we investigated the influence of irradiation on the vulnerability of cancer cells to SARS-CoV-2 using S pseudovirions and probed the underlying mechanism via RNA-seq and other molecular biology techniques. Owing to the enhancement of sphingolipid metabolism, irradiation accelerated pseudovirion infection. Mechanistically, irradiation induced the expression of acid…

• LY3041658/ interleukin-8 complex structure as targets for IL-8 small molecule inhibitors discovery using a combination of in silico methods - Since interleukin-8 (IL-8/CXCL8) and its receptor, CXCR1 and CXCR2, were known in the early 1990s, biological pathways related to these proteins were proven to have high clinical value in cancer and inflammatory/autoimmune conditions treatment. Recently, IL-8 has been identified as biomarker for severe COVID-19 patients and COVID-19 prognosis. Boyles et al. (mAbs 12 (2020), pp. 1831880) have published a high-resolution X-ray crystal structure of the LY3041658 Fab in a complex human CXCL8. They…

• Chemical Compositions of Clove (Syzygium aromaticum (L.) Merr. & L.) Extracts and Their Potentials in Suppressing SARS-CoV-2 Spike Protein-ACE2 Binding, Inhibiting ACE2, and Scavenging Free Radicals - COVID-19 is initiated by binding the SARS-CoV-2 spike protein to angiotensin-converting enzyme 2 (ACE2) on host cells. Food factors capable of suppressing the binding between the SARS-CoV-2 spike protein and ACE2 or reducing the ACE2 availability through ACE2 inhibitions may potentially reduce the risk of SARS-CoV-2 infection and COVID-19. In this study, the chemical compositions of clove water and ethanol extracts were investigated, along with their potentials in suppressing SARS-CoV-2 spike…

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