Covid-19 Sentry

Contents

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

From Preprints

• Inflammation durably imprints memory CD4+ T cells -
  Adaptive immune responses are induced by vaccination and infection, yet little is known about how CD4+ T cell memory differs when primed in these two contexts. Notably, viral infection is generally associated with higher levels of systemic inflammation than is vaccination. To assess whether the inflammatory milieu at the time of CD4+ T cell priming has long-term effects on memory, we compared Spike-specific memory CD4+ T cells in 22 individuals around the time of the participants’ third SARS-CoV-2 mRNA vaccination, with stratification by whether the participants’ first exposure to Spike was via virus or mRNA vaccine. Multimodal single-cell profiling of Spike-specific CD4+ T cells revealed 755 differentially expressed genes that distinguished infection- and vaccine-primed memory CD4+ T cells. Spike-specific CD4+ T cells from infection-primed individuals had strong enrichment for cytotoxicity and interferon signaling genes, whereas Spike-specific CD4+ T cells from vaccine-primed individuals were enriched for proliferative pathways by gene set enrichment analysis. Moreover, Spike-specific memory CD4+ T cells established by infection had distinct epigenetic landscapes driven by enrichment of IRF-family transcription factors, relative to T cells established by mRNA vaccination. This transcriptional imprint was minimally altered following subsequent mRNA vaccination or breakthrough infection, reflecting the strong bias induced by the inflammatory environment during initial memory differentiation. Together, these data suggest that the inflammatory context during CD4+ T cell priming is durably imprinted in the memory state at transcriptional and epigenetic levels, which has implications for personalization of vaccination based on prior infection history.
  🖺 Full Text HTML: Inflammation durably imprints memory CD4+ T cells
• An Atlas of Adaptive Evolution in Endemic Human Viruses -
  Through antigenic evolution, viruses like seasonal influenza evade recognition by neutralizing antibodies elicited by previous infection or vaccination. This means that a person with antibodies well-tuned to an initial infection will not be protected against the same virus years later and that vaccine-mediated protection will decay. It is not fully understood which of the many endemic human viruses evolve in this fashion. To expand that knowledge, we assess adaptive evolution across the viral genome in 28 endemic viruses, spanning a wide range of viral families and transmission modes. We find that surface proteins consistently show the highest rates of adaptation, and estimate that ten viruses in this panel undergo antigenic evolution to selectively fix mutations that enable the virus to escape recognition by prior immunity. We compare overall rates of amino acid substitution between these antigenically-evolving viruses and SARS-CoV-2, showing that SARS-CoV-2 viruses are accumulating protein-coding changes at substantially faster rates than these endemic viruses.
  🖺 Full Text HTML: An Atlas of Adaptive Evolution in Endemic Human Viruses
• Breakthrough infections by SARS-CoV-2 variants boost cross-reactive hybrid immune responses in mRNA-vaccinated Golden Syrian Hamsters -
  Hybrid immunity to SARS-CoV-2 provides superior protection to re-infection. We performed immune profiling studies during breakthrough infections in mRNA-vaccinated hamsters to evaluate hybrid immunity induction. mRNA vaccine, BNT162b2, was dosed to induce binding antibody titers against ancestral spike, but inefficient serum virus neutralization of ancestral SARS-CoV-2 or variants of concern (VoCs). Vaccination reduced morbidity and controlled lung virus titers for ancestral virus and Alpha but allowed breakthrough infections in Beta, Delta and Mu-challenged hamsters. Vaccination primed T cell responses that were boosted by infection. Infection back-boosted neutralizing antibody responses against ancestral virus and VoCs. Hybrid immunity resulted in more cross-reactive sera. Transcriptomics post-infection reflects both vaccination status and disease course and suggests a role for interstitial macrophages in vaccine-mediated protection. Therefore, protection by vaccination, even in the absence of high titers of neutralizing antibodies in the serum, correlates with recall of broadly reactive B- and T-cell responses.
  🖺 Full Text HTML: Breakthrough infections by SARS-CoV-2 variants boost cross-reactive hybrid immune responses in mRNA-vaccinated Golden Syrian Hamsters
• The COVID-19 mRNA vaccine Comirnaty induces anaphylactic shock in an anti-PEG hyperimmune large animal model: Role of complement in cardiovascular, hematological, and inflammatory mediator changes -
  Background: Comirnaty, Pfizer-BioNTech's polyethylene-glycol (PEG)-containing Covid-19 vaccine, can cause hypersensitivity reactions (HSRs) in a small fraction of immunized people which can, very rarely, culminate in life-threatening anaphylaxis. A role of anti-PEG antibodies (Abs) has been proposed, but causality has not yet been proven in an animal model. This study aimed to provide such evidence using anti-PEG hyperimmune pigs (i.e., pigs displaying very high levels of anti-PEG Abs). We also sought to find evidence for the role of complement (C) activation and thromboxane A2 (TXA2) release in blood as contributing effects to anaphylaxis. Methods: Pigs (n=6) were immunized with 0.1 mg/kg PEGylated liposome (Doxebo) i.v. the rise of anti-PEG IgG and IgM was measured in serial blood samples with ELISA. After 2-3 weeks, during the height of seroconversion, the animals were injected i.v. with 1/3 human vaccine dose (HVD) of Comirnaty, and the hemodynamic (PAP, SAP), cardiopulmonary (HR, EtCO2,), hematological parameters (WBC, granulocyte, lymphocyte, and platelet counts) and blood immune mediators (anti-PEG IgM and IgG Abs, C3a and TXA2) were measured as endpoints of HSRs. Results: A week after immunization of 6 pigs with Doxebo, the level of anti-PEG IgM and IgG rose 5-10-thousands-fold in all animals, and they all developed anaphylactic shock to i.v. injection of 1/3 HVD of Comirnaty. The reaction, starting within 1 min, led to the abrupt decline of SAP along with maximal pulmonary hypertension, decreased pulse pressure amplitude, tachycardia, granulo- and thrombocytopenia, and paralleling rises of plasma C3a and TXB2 levels. These vaccine effects were not observed in non-immunized pigs. Conclusions: Consistent with previous studies with PEGylated nano-liposomes, these data show a causal role of anti-PEG Abs in the anaphylaxis to Comirnaty. The reaction involves C activation, and, hence, it represents C activation-related pseudo-allergy (CARPA). The setup provides the first large-animal model for mRNA-vaccine-induced anaphylaxis in humans.
  🖺 Full Text HTML: The COVID-19 mRNA vaccine Comirnaty induces anaphylactic shock in an anti-PEG hyperimmune large animal model: Role of complement in cardiovascular, hematological, and inflammatory mediator changes
• Stress, Genetics and Mood: Impact of COVID-19 on a College Freshman Sample -

  Objectives: Use a longitudinal approach to study the impact of the Covid-19 pandemic on the emergence of symptoms of depression and/or anxiety in college freshmen. Define the interplay between genetic risk and psychosocial factors in shaping vulnerability or resilience to pandemic stress. Methods: University of Michigan freshmen were characterized at baseline using multiple psychological instruments. They were genotyped and polygenic risk score for depression (MDD-PRS) was calculated. Daily physical activity was captured. They were sampled at multiple time points throughout the freshman year on clinical rating scales, including GAD-7 and PHQ-9 for anxiety and depression, respectively. The 2019-2020 cohort (N=122) was compared to an earlier cohort (N=106) to assess the impact of the pandemic. Results: Across cohorts, 25%-57% of freshmen developed significant symptoms of anxiety or depression. In the 2019-2020 cohort, measures of anxiety and depression increased significantly after the onset of COVID-19. Physical activity was dramatically reduced by the pandemic and was associated with the emergence of mood symptoms. Low MDD-PRS subjects exhibited lower relative risk for depression/anxiety during a typical freshman year, but they were more negatively impacted by the pandemic than High MDD-PRS subjects. Conversely, a cluster of psychological indices at baseline predicted resilience in High MDD-PRS subjects who did not develop a mood disorder post-stress. Conclusions: The pandemic had a profound impact on college freshmen triggering depression and anxiety symptoms. Pandemic stress overrode the advantage conferred by “genetic resilience”. By contrast, “psychosocial resilience” was protective even in the face of high genetic risk and pandemic stress.

  🖺 Full Text HTML: Stress, Genetics and Mood: Impact of COVID-19 on a College Freshman Sample
• Power users: Canadian sex workers’ use of technology post COVID -
  Background: The transition from physical to online advertising by sex workers in Canada has been well documented. However, few studies use rigorous sampling methods. This study considers how a technically sophisticated group of advertisers from a large Canadian sex work classifieds site used multiple online resources to promote or provide services during the COVID-19 pandemic. Methods: Advertisers were identified from internal chat names found in a collection of 891695 ads downloaded between September 15, 2021 and September 22, 2022. Advertisers qualified for the study if they used a URL as part of their contact information and were actively advertising between August 23 and September 22, 2022. A random sample of 1000 of these advertisers were selected for further study out of which 783 had accessible contact URLs. Thematic analysis was performed on downloaded website texts and ad metadata was used to identify demographic and behavioral variables. Results: Almost all (99%) sampled advertisers provided in person services and most (70%) provided online services. They advertised more frequently, were more affluent and were more likely to be trans-female, White, and collective. Themes of security, health, identity, and social networks were identified. Advertisers emphasized physical, emotional, and financial security. Most workers did not work in isolation and many participated in extensive social networks. Conclusions: Rigorous sampling methods are feasible in sex work research. The sampled advertisers represented distinct subgroups underlining the need for researchers to provide context for samples used in research. Advertisers showed considerable adaptability in the wake of the COVID-19 pandemic.
  🖺 Full Text HTML: Power users: Canadian sex workers’ use of technology post COVID
• Dynamical nonequilibrium molecular dynamics simulations identify allosteric sites and positions associated with drug resistance in the SARS-CoV-2 main protease -
  The SARS-CoV-2 main protease (Mpro) plays an essential role in the coronavirus lifecycle by catalysing hydrolysis of the viral polyproteins at specific sites. Mpro is the target of drugs, such as nirmatrelvir, though resistant mutants have emerged that threaten drug efficacy. Despite its importance, questions remain on the mechanism of how Mpro binds its substrates. Here, we apply dynamical nonequilibrium molecular dynamics (D-NEMD) simulations to evaluate structural and dynamical responses of Mpro to the presence and absence of a substrate. The results highlight communication between the Mpro dimer subunits and identify networks, including some far from the active site, that link the active site with a known allosteric inhibition site, or which are associated with nirmatrelvir resistance. They imply that some mutations enable resistance by altering the allosteric behaviour of Mpro. More generally, the results show the utility of the D-NEMD technique for identifying functionally relevant allosteric sites and networks including those relevant to resistance.
  🖺 Full Text HTML: Dynamical nonequilibrium molecular dynamics simulations identify allosteric sites and positions associated with drug resistance in the SARS-CoV-2 main protease
• Epidemiological drivers of transmissibility and severity of SARS-CoV-2 in England -

  As the SARS-CoV-2 pandemic progressed, distinct variants emerged and dominated in England. These variants, Wildtype, Alpha, Delta, and Omicron were characterized by variations in transmissibility and severity. We used a robust mathematical model and Bayesian inference framework to analyse epidemiological surveillance data from England. We quantified the impact of non-pharmaceutical interventions (NPIs), therapeutics, and vaccination on virus transmission and severity. Each successive variant had a higher intrinsic transmissibility. Omicron (BA.1) had the highest basic reproduction number at 8.3 (95% credible interval (CrI) 7.7-8.8). Varying levels of NPIs were crucial in controlling virus transmission until population immunity accumulated. Immune escape properties of Omicron decreased effective levels of immunity in the population by a third. Furthermore, in contrast to previous studies, we found Alpha had the highest basic infection fatality ratio (2.9%, 95% CrI 2.7-3.2), followed by Delta (2.2%, 95% CrI 2.0-2.4), Wildtype (1.2%, 95% CrI 1.1-1.2), and Omicron (0.7%, 95% CrI 0.6-0.8). Our findings highlight the importance of continued surveillance. Long-term strategies for monitoring and maintaining effective immunity against SARS-CoV-2 are critical to inform the role of NPIs to effectively manage future variants with potentially higher intrinsic transmissibility and severe outcomes.

  🖺 Full Text HTML: Epidemiological drivers of transmissibility and severity of SARS-CoV-2 in England
• Psychiatric Residential Treatment Facilities for Child Behavioral Health Services in North Carolina Medicaid -

  Background: Psychiatric residential treatment facilities (PRTFs) are a type of non-hospital inpatient treatment setting for children with severe behavioral health disorders. PRTFs are a restrictive and costly form of care that can potentially be avoided with community-based behavioral health services. Methods: Statewide Medicaid enrollment and claims data for 2015 to 2022 were used to describe PRTF utilization in North Carolina. We examined annual episodes of care in PRTFs and compared trends before and during the COVID-19 public health emergency. Results: From 2015 to 2022, 10,038 children insured by North Carolina Medicaid entered a PRTF across 10,966 episodes of care. In the past five years (2018-2022), care in PRTFs resulted in Medicaid expenditures of over $550 million total, or over $100 million per year. In 2022, 42% of children who entered PRTFs were in foster care and 44% of children were placed in PRTFs outside of North Carolina. Limitations: Analysis limited to data collected for administrative purposes. Conclusions: Current trends indicate ongoing overrepresentation of children in foster care placed in PRTFs and increased out-of-state PRTF placements. Coordinated efforts in future research, policy, and practice are needed to determine the cause of these trends and identify solutions.

  🖺 Full Text HTML: Psychiatric Residential Treatment Facilities for Child Behavioral Health Services in North Carolina Medicaid
• Individual costs and societal benefits of interventions during the COVID-19 pandemic -

  Individual and societal reactions to an ongoing pandemic can lead to social dilemmas: In some cases, each individual is tempted to not follow an intervention, but for the whole society it would be best if they did. Now that in most countries the extent of regulations to reduce SARS-CoV-2 transmission is very small, interventions are driven by individual decision-making. Assuming that individuals act in their best own interest, we propose a framework in which this situation can be quantified, depending on the protection the intervention provides to a user and to others, the risk of getting infected, and the costs of the intervention. We discuss when a tension between individual and societal benefits arises and which parameter comparisons are important to distinguish between different regimes of intervention use.

  🖺 Full Text HTML: Individual costs and societal benefits of interventions during the COVID-19 pandemic
• Predicting the public health impact of bivalent vaccines and nirmatrelvir-ritonavir against COVID-19 -

  Background: Uptake of COVID-19 bivalent vaccines and oral medication nirmatrelvir-ritonavir (Paxlovid) has remained low across the United States. Assessing the public health impact of increasing uptake of these interventions in key risk groups can guide further public health resources and policy. Methods: This modeling study used person-level data from the California Department of Public Health on COVID-19 cases, hospitalizations, deaths, and vaccine administration from July 23, 2022 to January 23, 2023. We modeled the impact of additional uptake of bivalent COVID-19 vaccines and nirmatrelvir-ritonavir during acute illness in different risk groups defined by age (50+, 65+, 75+ years) and vaccination status (everyone, primary series only, previously vaccinated). We predicted the number of averted COVID-19 cases, hospitalizations, and deaths and number needed to treat (NNT). Results: For both bivalent vaccines and nirmatrelvir-ritonavir, the most efficient strategy (based on NNT) for averting severe COVID-19 was targeting the 75+ years group. We predicted that perfect coverage of bivalent boosters in the 75+ years group would avert 3,920 hospitalizations (95%UI: 2,491-4,882; 7.8% total averted; NNT 387) and 1,074 deaths (95%UI: 774-1,355; 16.2% total averted; NNT 1,410). Perfect uptake of nirmatrelvir-ritonavir in the 75+ years group would avert 5,644 hospitalizations (95%UI: 3,947-6,826; 11.2% total averted; NNT 11) and 1,669 deaths (95%UI: 1,053-2,038; 25.2% total averted; NNT 35). Conclusions: These findings suggest prioritizing uptake of bivalent boosters and nirmatrelvir-ritonavir among the oldest age groups would be efficient and have substantial public health impact in reducing the burden of severe COVID-19, but would not address the entire burden of severe COVID-19.

  🖺 Full Text HTML: Predicting the public health impact of bivalent vaccines and nirmatrelvir-ritonavir against COVID-19
• Evaluating the Association of Depressive Disorder Symptoms and Moral Injuries in Healthcare Workers during COVID-19 Pandemic -

  Abstract Background: Moral injury occurs when negative distressing emotions appear and are suppressed. This could lead to several mental health problems such as depression and post-traumatic stress disorder, and result in long-lasting emotional, behavioral, and social problems. Moral injury, a term more commonly used in war contexts, has come into the spotlight during COVID-19 pandemic. We aimed to evaluate the rate of moral injury and its association with psychological injuries during this healthcare crisis. Methods: We assessed the rates of depression, anxiety, stress, and their association with moral injury among 333 nurses, medical interns, and residents between December 2020 and January 2021. This study was done using validated versions of Depression Anxiety Stress Scales (DASS-21) and Moral Injury Symptom Scale-Healthcare Professionals (MISS-HP) scores. Results: Totally 333 healthcare professionals participated in this study, mostly aged between 26 to 30 years old. Nearly half of the participants had a clinically significant moral injury. The average scores of anxiety and stress were significantly higher in women. The participants who were single showed higher rates of depression and moral injury than married ones. Moreover, anxiety, stress, depression, and moral injury were higher in nurses than other healthcare professionals. The scarcity of personal protective equipment at the workplace and giving care to patients with end-stage COVID-19 diagnosis were among the factors associated with a higher risk of developing mental health problems. Conclusion: The results of this study showed that anxiety, stress, depression, and moral injury were prevalent among healthcare professionals during COVID-19 pandemic. Also, the rates of anxiety, stress, and depression were associated with moral injuries.

  🖺 Full Text HTML: Evaluating the Association of Depressive Disorder Symptoms and Moral Injuries in Healthcare Workers during COVID-19 Pandemic
• Laboratory biomarkers associated with mortality in COVID-19 patients in Addis Ababa, Ethiopia -

  Background: Laboratory biomarkers are amongst the best imperative predictors of disease outcomes in hospital-admitted COVID-19 patients. Although data is available in this regard at a global level, there is a paucity of information in Ethiopia. Thus, this study aimed to assess the laboratory biomarkers association with death among COVID-19 patients in Ethiopia. Methods: A health facility-based longitudinal study was conducted from 2020 to 2022 among RT-PCR-confirmed COVID-19 patients admitted and on treatment follow-up at COVID-19 treatment hospitals in Addis Ababa. A robust Poisson regression model was fitted to assess the association between demographic, clinical, and laboratory factors and death. Significance was determined at p<0.05, and variables with p < 0.15 in bivariate analyses were included in the final multivariable models. Incidence rate ratio (IRR) with a 95% confidence interval (CI) was used to describe associations. Results: Of the 2357 COVID-19 patients, 248 (10.5%) died. The median age of participants was 59 (IQR= 45- 70) years, and the majority (64.9%) of them were male. Lower median RBC was observed among those who died at 4.58 (4.06-5.07) as compared to those who survived at 4.69 (4.23-5.12) whereas high median (IQR) WBC was a predictor of mortality with 11.2 (7.7-15.9). After adjusting for confounders, death was associated with age >74 years having adjusted incidence rate ratio [aIRR (95%CI): 2.46 (1.40-4.34)], and critical clinical situations [aIRR (95% CI): 4.04 (2.18-7.52)]. Conclusion: Our results demonstrate that abnormal liver function tests, abnormal white blood cells, age of the patients, and clinical status of the patients during admission are associated with unfavorable outcomes of COVID-19. Hence, timely monitoring of these laboratory results at the earliest phase of the disease was highly commendable.

  🖺 Full Text HTML: Laboratory biomarkers associated with mortality in COVID-19 patients in Addis Ababa, Ethiopia
• Defining the Subtypes of Long COVID and Risk Factors for Prolonged Disease -

  Objective- To empirically derive a long COVID case definition consisting of significantly increased signs, symptoms, and diagnoses to support clinical, public health, research, and policy initiatives related to the pandemic. Design- Case-Crossover Population-based study Setting- Veterans Affairs medical centers across the United States between January 1 2020 and August 18 2022. Participants- 367148 individuals with positive COVID-19 tests and preexisting ICD-10-CM codes recorded in the VA electronic health record were enrolled. Trigger- SARS-CoV2 infection documented by positive laboratory test. Case Window- One to seven months following positive COVID testing. Main Outcomes and Measures- We defined signs, symptoms, and diagnoses as being associated with long COVID if they had a novel case frequency of at least 1 to 1000 and they were significantly increased in our entire cohort after a positive COVID test when compared to case frequencies before COVID testing. We present odds ratios with confidence intervals for long COVID signs, symptoms, and diagnoses, organized by ICD10-CM functional groups and medical specialty. We used our definition to assess long COVID risk based upon a patients9 demographics, Elixhauser score, vaccination status, and COVID disease severity. Results- We developed a long COVID definition consisting of 323 ICD-10-CM diagnosis codes grouped into 143 ICD-10-CM functional groups that were significantly increased in our 367148 patient post-COVID population. In our long COVID definition at a proportion of at least 59.7 percent (based on all COVID positive patients). Patients with more severe cases of COVID-19 and multiple comorbidities were more likely to develop long COVID. Conclusions and Relevance- An actionable, empirical definition for long COVID can help clinicians screen for and diagnose long COVID, allowing identified patients to be admitted into appropriate monitoring and treatment programs. An actionable long COVID definition can also support public health, research and policy initiatives. COVID patients with low oxygen saturation levels or multiple co-comorbidities should be preferentially watched for the development of long COVID.

  🖺 Full Text HTML: Defining the Subtypes of Long COVID and Risk Factors for Prolonged Disease
• Viral rebound among patients receiving COVID-19 convalescent plasma for treatment of Covid-19 in Uganda. -

  Background: Viral rebound has been reported in people infected with COVID-19 treated with nirmatrelvir/ritonavir, and some cases been reported in patients who did not receive any antiviral treatment. Since the course of COVID-19 has not yet been well defined, we evaluated the incidence of viral rebound among COVID-19 patients treated with COVID-19 Convalescent Plasma (CCP) in Uganda. Methods: In the CCP trail, 136 patients were enrolled between 21st September 2020 and 2nd December 2020 who presented to the Mulago National Referral COVID-19 treatment unit. Patients with a positive SARS-CoV-2 reverse transcriptase (RT)-PCR test irrespective of disease severity were hospitalized and randomized to receive either COVID-19 CCP plus standard of care (SOC) or SOC alone. SARS-CoV-2 RT-PCR was done at baseline and on days 3, 5, 7, 14 and 28 post randomisation or until two consecutive negative RT-PCR results were obtained, whichever occurred first. We analysed for occurrence of viral rebound. Viral rebound was defined as a positive SARS-CoV-2 RT-PCR test following a prior negative test. Findings: 20% of the participants had viral rebound. Viral rebounders were predominantly male. The median age was 45-64 years and they had at least one co-morbidity. There was no difference in the rebound rates in the study arms, and participants with hypertension had more rebound rates compared to those with other co-morbidities. Interpretation: Viral RNA rebound was common among patients receiving CCP. Viral rebound may be a result of the biphasic nature of COVID-19 infection, and not a consequence of the therapeutic interventions.

  🖺 Full Text HTML: Viral rebound among patients receiving COVID-19 convalescent plasma for treatment of Covid-19 in Uganda.

From Clinical Trials

• The Standard of Care Combined With Glucocorticoid in Elderly People With Mild or Moderate COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Glucocorticoid
  Sponsor:   Huashan Hospital
  Not yet recruiting

• Investigation of the Effect on Cognitive Skills of COVID-19 Survivors - Condition:   COVID-19
  Intervention:   Other: green walking and intelligence gam
  Sponsors:   Bayburt University;   Karadeniz Technical University
  Completed

• Conducting Clinical Trials of the Medicine “Rutan Tablets 0.1g” No. 10 in the Complex Therapy of COVID-19 - Condition:   Patients With COVID-19
  Interventions:   Drug: The drug “Rutan 0.1”.;   Other: Basic treatment
  Sponsor:   Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan
  Completed

• The Effect of Special Discharge Training in the COVID-19 - Condition:   COVID-19 Pneumonia
  Intervention:   Other: COVID-19 Discharge Education
  Sponsor:   Kilis 7 Aralik University
  Completed

• Arginine Replacement Therapy in COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Arginine Hydrochloride
  Sponsor:   Emory University
  Not yet recruiting

• Effectiveness of a Second COVID-19 Vaccine Booster in Chinese Adults - Condition:   COVID-19
  Interventions:   Biological: Intramuscularly administered Ad5-nCoV vaccine;   Biological: Aerosolized Ad5-nCoV;   Biological: DelNS1-2019-nCoV-RBD-OPT1;   Biological: SYS6006
  Sponsor:   Jiangsu Province Centers for Disease Control and Prevention
  Not yet recruiting

• Studying the Efficiency of the Natural Preparation Rutan in Children in the Treatment of COVID-19, ARVI - Condition:   COVID-19 Respiratory Infection
  Interventions:   Drug: Rutan 25 mg;   Other: Control group
  Sponsor:   Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan
  Completed

• A Pilot Study Evaluating the Efficacy of the Vielight Neuro RX Gamma in the Treatment of Post COVID-19 Cognitive Impairment - Condition:   Post COVID-19 Cognitive Impairment
  Interventions:   Device: Vielight Neuro RX Gamma active device;   Device: Vielight Neuro RX Gamma sham device
  Sponsor:   Vielight Inc.
  Not yet recruiting

• PAxlovid loNg cOvid-19 pRevention triAl With recruitMent In the Community in Norway - Conditions:   Post COVID-19 Condition, Unspecified;   SARS-CoV2 Infection;   COVID-19
  Interventions:   Drug: Nirmatrelvir/ritonavir;   Drug: Placebo
  Sponsors:   Haukeland University Hospital;   University of Bergen
  Not yet recruiting

• Use of a Hypochlorous Acid Spray Solution in the Treatment of COVID-19 Patients : COVICONTROL Study . - Condition:   SARS CoV 2 Infection
  Interventions:   Other: Spray with Hypochlorous Acid Group;   Other: Spray with Placebo Group
  Sponsor:   University of Monastir
  Recruiting

• Role of Vit-D Supplementation on BioNTech, Pfizer Vaccine Side Effect and Immunoglobulin G Response - Condition:   COVID-19 Respiratory Infection
  Intervention:   Combination Product: Vitamin-D
  Sponsor:   Sulaimany Polytechnic university
  Completed

• Telerehabilitation Program and Detraining in Patients With Post-COVID-19 Sequelae - Condition:   COVID-19 Acute Respiratory Distress Syndrome
  Intervention:   Other: Telerehabilitation program
  Sponsor:   Campus docent Sant Joan de Déu-Universitat de Barcelona
  Completed

• COVID-19 Vaccine Uptake Amongst Underserved Populations in East London - Conditions:   COVID-19;   Influenza;   Vaccination Refusal
  Intervention:   Device: Patient Engagement tool
  Sponsors:   Queen Mary University of London;   Social Action for Health
  Not yet recruiting

• REVERSE-Long COVID-19 With Baricitinib Pilot Study - Condition:   Post-Acute COVID-19 Syndrome
  Intervention:   Drug: Baricitinib 4 MG
  Sponsors:   Vanderbilt University Medical Center;   Emory University;   University of California, San Francisco;   University of Minnesota;   Vanderbilt University;   Yale University
  Not yet recruiting

• Post Covid-19 Dysautonomia Rehabilitation Randomized Controlled Trial - Conditions:   Post-Acute COVID-19 Syndrome;   Dysautonomia
  Interventions:   Procedure: Rehabilitation;   Procedure: Standard of Care
  Sponsors:   Evangelismos Hospital;   National and Kapodistrian University of Athens;   LONG COVID GREECE;   414 Military Hospital of Special Diseases
  Recruiting

From PubMed

• Elucidating Atomistic Insight into the Dynamical Responses of the SARS-CoV-2 Main Protease for the Binding of Remdesivir Analogues: Leveraging Molecular Mechanics To Decode the Inhibition Mechanism - To combat mischievous coronavirus disease followed by continuous upgrading of therapeutic strategy against the antibody-resistant variants, the molecular mechanistic understanding of protein-drug interactions is a prerequisite in the context of target-specific rational drug development. Herein, we attempt to decipher the structural basis for the inhibition of SARS-CoV-2 main protease (M^(pro)) through the elemental analysis of potential energy landscape and the associated thermodynamic and…

• Risk connectedness between crude oil, gold and exchange rates in China: Implications of the COVID-19 pandemic - This study examined the risk connectedness and its asymmetry between oil, gold, and foreign exchange under the realized volatility, spillover index framework, and high-frequency data during the COVID-19 pandemic. It was found that: (1) At the beginning of the pandemic outbreak, the total volatility spillover in the system declined, which may indicate that the pandemic cuts the trading activities in the financial markets by inhibiting personnel mobility, then, the spillover experienced a…

• Prognostic immune markers identifying patients with severe COVID-19 who respond to tocilizumab - CONCLUSIONS: We found that tocilizumab has pleiotropic effects and that clinical response to this drug remain heterogenous. Our data suggest that it is possible to identify patients who will respond to treatment and that the administration of tocilizumab is able to restore the immune balance through the re-establishment of different cell populations affected by SARS-COV-2 infection, highlighting the importance of temporal examination of the pathological features from the diagnosis.

• Immunogenicity of NVX-CoV2373 in PREVENT-19: A Phase 3, Randomized, Placebo-Controlled Trial in Adults in the United States and Mexico - CONCLUSIONS: NVX-CoV2373 elicited robust humoral immune responses against ancestral SARS-CoV-2 virus 2 weeks following the second vaccination in adult PREVENT-19 participants, consistent with previously reported high vaccine efficacy. PREVENT-19 ClinicalTrials.gov number, NCT04611802.

• Hydroxychloroquine and azithromycin alter the contractility of living porcine heart slices - The cardiotoxicity risk of hydroxychloroquine (HCQ) and azithromycin (AZM) has been the subject of intensive research triggered by safety concerns in COVID-19 patients. HCQ and AZM have been associated with QT interval prolongation and drug-induced arrhythmias, however other cardiotoxicity mechanisms remain largely unexplored. Our group has pioneered the living heart slice preparation, an ex-vivo platform that maintains native cardiac tissue architecture and physiological electrical and…

• Thrombotic thrombocytopenic purpura following ChAdOx1 nCov-19 vaccination: A case report - Vaccine-associated thrombotic thrombocytopenic purpura (TTP) is a rare type of acquired TTP recently reported after COVID-19 vaccination. Merely four cases are ascribed to the ChAdOx1 nCoV-19 vaccine in the medical literature till the preparation of this study. In this case report, we describe a 43-year-old man who developed symptoms of TTP four days after receiving the second dose of the ChAdOx1 nCoV-19 vaccine. Peripheral blood smear demonstrated multiple schistocytes. Given a high plasmic…

• Honokiol Inhibits SARS-CoV-2 Replication in Cell Culture at a Post-Entry Step - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019, and the resulting pandemic has already caused the death of over 6 million people. There are currently few antivirals approved for treatment of the 2019 coronavirus disease (COVID-19), and more options would be beneficial, not only now but also to increase our preparedness for future coronavirus outbreaks. Honokiol is a small molecule from magnolia trees for which several biological effects have been reported, including…

• Marked elevations in lung and plasma ceramide in COVID-19 linked to microvascular injury - The pathogenesis of the marked pulmonary microvasculature injury, a distinguishing feature of COVID-19 acute respiratory distress syndrome (COVID-ARDS), remains unclear. Implicated in the pathophysiology of diverse diseases characterized by endothelial damage, including ARDS and ischemic cardiovascular disease, ceramide and in particular palmitoyl ceramide (C16:0-ceramide) may be involved in the microvascular injury in COVID-19. Using deidentified plasma and lung samples from COVID-19 patients,…

• Inhibition of SARS-CoV-2-mediated thromboinflammation by CLEC2.Fc - Thromboinflammation is the major cause of morbidity and mortality in COVID-19 patients, and post-mortem examination demonstrates the presence of platelet-rich thrombi and microangiopathy in visceral organs. Moreover, persistent microclots were detected in both acute COVID-19 and long COVID plasma samples. However, the molecular mechanism of SARS-CoV-2-induced thromboinflammation is still unclear. We found that the spleen tyrosine kinase (Syk)-coupled C-type lectin member 2 (CLEC2), which was…

• In silico identification and validation of phenolic lipids as potential inhibitor against bacterial and viral strains - The recurrence of coronavirus disease and bacterial resistant strains has drawn attention to naturally occurring bioactive molecules that can demonstrate broad-spectrum efficacy against bacteria as well as viral strains. The drug-like abilities of naturally available “anacardic acids” (AA) and their derivatives against different bacterial and viral protein targets through in-silico tools were explored. Three viral protein targets [P DB: 6Y2E (SARS-CoV-2), 1AT3 (Herpes) and 2VSM (Nipah)] and four…

• Potential role of PIM1 inhibition in the treatment of SARS-CoV-2 infection - CONCLUSION: 2-pyridone PIM1 inhibitor could hinder cellular entry of SARS-CoV-2 and modulate several pathways implicated in immunity, suggesting a potential benefit in the development of anti-SARS-CoV-2 therapeutic approach.

• SARS-CoV-2 inhibition and specific targeting of infected cells by VSV particles carrying the ACE2 receptor - No abstract

• Understanding how transmembrane domains regulate interactions between human BST-2 and the SARS-CoV-2 accessory protein ORF7a - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID, replicates at intracellular membranes. Bone marrow stromal antigen 2 (BST-2; tetherin) is an antiviral response protein that inhibits transport of viral particles after budding within infected cells. RNA viruses such as SARS-CoV-2 use various strategies to disable BST-2, including use of transmembrane ‘accessory’ proteins that interfere with BST-2 oligomerization. ORF7a is a small, transmembrane protein…

• Harringtonine: A more effective antagonist for Omicron variant - Fusion with host cell membrane is the main mechanism of infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we propose that a new strategy to screen small-molecule antagonists blocking SARS-CoV-2 membrane fusion. Using cell membrane chromatography (CMC), we found that harringtonine (HT) simultaneously targeted SARS-CoV-2 S protein and host cell surface TMPRSS2 expressed by the host cell, and subsequently confirmed that HT can inhibit membrane fusion. HT effectively…

• A new cellular interactome of SARS-CoV-2 nucleocapsid protein and its biological implications - There is still much to uncover regarding the molecular details of SARS-CoV-2 infection. As the most abundant protein, coronavirus nucleocapsid (N) protein encapsidates viral RNAs, serving as the structural component of ribonucleoprotein and virion, and participates in transcription, replication, and host regulations. Virus-host interaction might give clues to better understand how the virus affects or is affected by its host during infection and identify promising therapeutic candidates….

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