Covid-19 Sentry

Contents

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

From Preprints

• Electrostatic features for the Receptor binding domain of SARS-COV-2 wildtype and its variants. Compass to the severity of the future variants with the charge rule. -
  Electrostatic intermolecular interactions are important in many aspects of biology. We have studied the main electrostatic features involved in the interaction of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein with the human receptor Angiotensin-converting enzyme 2 (ACE2). As the principal computational tool, we have used the FORTE approach, capable to model proton fluctuations and computing free energies for a very large number of protein-protein systems under different physical-chemical conditions, here focusing on the RBD-ACE2 interactions. Both the wild-type and all critical variants are included in this study. From our large ensemble of extensive simulations, we obtain, as a function of pH, the binding affinities, charges of the proteins, their charge regulation capacities, and their dipole moments. In addition, we have calculated the pKas for all ionizable residues and mapped the electrostatic coupling between them. We are able to present a simple predictor for the RBD-ACE2 binding based on the data obtained for Alpha, Beta, Gamma, Delta, and Omicron variants, as a linear correlation between the total charge of the RBD and the corresponding binding affinity. This RBD charge rule should work as a quick test of the degree of severity of the coming SARS-CoV-2 variants in the future.
  🖺 Full Text HTML: Electrostatic features for the Receptor binding domain of SARS-COV-2 wildtype and its variants. Compass to the severity of the future variants with the charge rule.
• It hurts your heart: frontline healthcare worker experiences of moral injury during the COVID-19 pandemic -

  Background: Moral injury is defined as the strong emotional and cognitive reactions following events which clash with someones moral code, values or expectations. During the COVID-19 pandemic, increased exposure to potentially morally injurious events (PMIEs) has placed healthcare workers (HCWs) at risk of moral injury. Yet little is known about the lived experience of cumulative PMIE exposure and how NHS staff respond to this. Objective: We sought to rectify this knowledge gap by qualitatively exploring the lived experiences and perspectives of clinical frontline NHS staff who responded to COVID-19. Methods: We recruited a diverse sample of 30 clinical frontline HCWs from the NHS CHECK study cohort, for single time point qualitative interviews. All participants endorsed at least one item on the 9-item Moral Injury Events Scale (MIES) (Nash et al., 2013) at six month follow up. Interviews followed a semi-structured guide and were analysed using reflexive thematic analysis. Results: HCWs described being routinely exposed to ethical conflicts, created by exacerbations of pre-existing systemic issues including inadequate staffing and resourcing. We found that HCWs experienced a range of mental health symptoms primarily related to perceptions of institutional betrayal as well as feeling unable to fulfil their duty of care towards patients. Conclusion: These results suggest that a multi-facetted organisational strategy is warranted to prepare for PMIE exposure, promote opportunities for resolution of symptoms associated with moral injury and prevent organisational disengagement.

  🖺 Full Text HTML: It hurts your heart: frontline healthcare worker experiences of moral injury during the COVID-19 pandemic
• COVID-19 redux: clinical, virologic, and immunologic evaluation of clinical rebound after nirmatrelvir/ritonavir -

  Clinical rebound of COVID-19 after nirmatrelvir/ritonavir treatment has been reported. We performed clinical, virologic, and immune measurements in seven patients with symptomatic rebound, six after nirmatrelvir/ritonavir treatment and one without previous treatment. There was no evidence of severe disease or impaired antibody and T-cell responses in people with rebound symptoms.

  🖺 Full Text HTML: COVID-19 redux: clinical, virologic, and immunologic evaluation of clinical rebound after nirmatrelvir/ritonavir
• Immunogenicity following two doses of BBIBP-CorV vaccine and a third booster dose with viral vector and mRNA COVID-19 vaccines against delta and omicron variants in prime immunized adults with two doses of BBIBP-CorV vaccine -

  Coronavirus disease 2019 (COVID-19) booster vaccination is being comprehensively evaluated globally due to waning immunity and the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Therefore, this study aimed to evaluate antibody responses in individuals vaccinated with two doses of BBIBP-CorV vaccine and to explore the boosting effect of the different vaccine platforms in BBIBP-CorV-primed healthy adults, including viral vector vaccine (AZD122) and mRNA vaccines (BNT162b2 and mRNA-1273). The results showed that, in the BBIBP-CorV prime group, the total receptor-binding domain (RBD) immunoglobulin (Ig) and anti-RBD IgG levels waned significantly at 3 months after receiving the second dose. However, after the booster, RBD-specific binding antibody levels increased. Neutralizing antibody measured by a surrogate neutralization test showed of inhibition over 90% against the SARS-CoV-2 delta variant but less than 70% against omicron variant after the third dose on day 28. All booster vac-cines could induce the total IFN-ɣ T-cell response. The reactogenicity was acceptable and well tolerated without serious adverse events. This study supported administration of the third dose with either viral vector or mRNA vaccine for the BBIBP-CorV-primed individuals to stimulate antibody and T cell responses.

  🖺 Full Text HTML: Immunogenicity following two doses of BBIBP-CorV vaccine and a third booster dose with viral vector and mRNA COVID-19 vaccines against delta and omicron variants in prime immunized adults with two doses of BBIBP-CorV vaccine
• Misinformation in Germany during the COVID-19 pandemic: A cross-sectional survey on citizens’ perceptions and individual differences in the belief in false information -
  During the COVID-19 pandemic, citizens have been exposed to vast amounts of mis- and disinformation. This “infodemic” has undermined key behavioural and pharmacological measures to contain the pandemic—for instance, by increasing vaccine hesitancy. In a cross-sectional survey of residents of Germany, we investigated citizens’ perceptions of and ability to deal with misinformation across three Waves of data collection in 2020/21 (Ntotal = 3324). We observed three main results. First, there was a strong increase in the perceived prevalence of misinformation in classic and online media and in social interactions over the course of the pandemic. Second, some—but by no means all—respondents knew how to identify misinformation. Third, higher susceptibility to misinformation was associated with support for the far-right AFD party, reliance on tabloids, neighbours and social media for information and news, lower education, as well as migration background. To help people navigate the challenges of the infodemic, we propose a two-pronged approach, namely, to boost individuals’ abilities to discern false from accurate information, and to enrich citizens’ proximate environments (e.g., neighbourhoods with high rates of migration) with reliable, accessible and high-quality information.
  🖺 Full Text HTML: Misinformation in Germany during the COVID-19 pandemic: A cross-sectional survey on citizens’ perceptions and individual differences in the belief in false information
• Psychological Factors Shaping Public Responses to COVID-19 Digital Contact Tracing Technologies in Germany -
  Please cite the published version: Kozyreva, A., Lorenz-Spreen, P., Lewandowsky, S. et al. Psychological factors shaping public responses to COVID-19 digital contact tracing technologies in Germany. Sci Rep 11, 18716 (2021). https://doi.org/10.1038/s41598-021-98249-5 Abstract: Digital contact-tracing technologies are being used for epidemiological purposes at scale for the first time in response to the COVID-19 pandemic. This poses challenges for governments aiming at high and efficient uptake and for people weighing the advantages (e.g., public health) against the potential risks (e.g., loss of data privacy) of these unprecedented measures. Our cross-sectional survey with repeated measures across four samples in Germany (N = 4,357) focused on public perceptions of digital contact-tracing technologies and related attitudes toward privacy. We found that public acceptance of potential privacy-encroaching measures decreased over time. Levels of acceptability were high for all three hypothetical tracking apps representing a range of privacy encroachments. Intentions to download the actual tracking app (the Corona-Warn-App) that became available during our study were also high. However, this did not directly translate into actual uptake. Our results point to the crucial roles of trust in government and in the app’s security, as well as of concerns about the app’s effectiveness. A conflict between prosocial intentions and personal benefit on the one hand, and lack of trust in data security and the app’s effectiveness on the other, are at the heart of people’s decisions about whether to use digital contact-tracing technologies.
  🖺 Full Text HTML: Psychological Factors Shaping Public Responses to COVID-19 Digital Contact Tracing Technologies in Germany
• Nirmatrelvir plus ritonavir for early COVID-19 and hospitalization in a large US health system -

  Background: In the EPIC-HR trial, nirmatrelvir plus ritonavir led to an 88% reduction in hospitalization or death among unvaccinated outpatients with early COVID-19. Clinical impact of nirmatrelvir plus ritonavir among vaccinated populations is uncertain. Objective: To assess whether nirmatrelvir plus ritonavir reduces risk of hospitalization among outpatients with early COVID-19 in the setting of prevalent SARS-CoV-2 immunity and immune evasive SARS-CoV-2 lineages. Design: Population-based cohort study analyzed to emulate a clinical trial utilizing two-stage, inverse-probability weighted models to account for anticipated bias in testing and treatment. Setting: A large healthcare system providing care for 1.5 million patients in Massachusetts and New Hampshire during Omicron wave (January 1 to May 15, 2022) with staged access and capacity to prescribe nirmatrelvir plus ritonavir. Patients: 30,322 non-hospitalized adults (87.2% vaccinated) aged 50 and older with COVID-19 and without contraindications to nirmatrelvir plus ritonavir. Measurement: Primary outcome was hospitalization within 14 days of COVID-19 diagnosis. Results: During the study period, 6036 (19.9%) patients were prescribed nirmatrelvir plus ritonavir and 24,286 (80.1%) patients were not. Patients prescribed nirmatrelvir were more likely to be older, have more comorbidities, and be unvaccinated. Hospitalization occurred in 40 (0.66%) and 232 (0.96%) patients prescribed and not prescribed nirmatrelvir plus ritonavir, respectively. The adjusted risk ratio was 0.55 (95% confidence interval 0.38 to 0.80, p = 0.002). Observed risk reduction was greater among unvaccinated patients and obese patients. Limitations: Potential for residual confounding due to differential access and uptake of COVID-19 vaccines, diagnostics, and treatment. Conclusions: The overall risk of hospitalization was already low (<1%) following an outpatient diagnosis of COVID-19, but this risk was 45% lower among patients prescribed nirmatrelvir plus ritonavir. Funding: National Institutes of Health (P30 AI060354 and R01 CA236546).

  🖺 Full Text HTML: Nirmatrelvir plus ritonavir for early COVID-19 and hospitalization in a large US health system
• “Pandemic of the unvaccinated”? At midlife, white people are less vaccinated but still at less risk of Covid-19 mortality in Minnesota -

  Introduction: Recent research underscores the exceptionally young age distribution of Covid-19 deaths in the United States compared with international peers. This brief characterizes how high levels of Covid mortality at midlife ages (45-64) are deeply intertwined with continuing racial inequity in Covid-19 mortality. Methods: Mortality data from Minnesota in 2020-2022 were analyzed in June 2022. Death certificate data and published vaccination rates in Minnesota allow vaccination and mortality rates to be observed with greater age and temporal precision than national data. Results: Black, Hispanic, and Asian adults under age 65 were all more highly vaccinated than white populations of the same ages during most of Minnesota9s substantial and sustained Delta surge and all of the subsequent Omicron surge. However, white mortality rates were lower than those of all other groups. These disparities were extreme; at midlife ages (ages 45-64), during the Omicron period, more highly-vaccinated populations had COVID-19 mortality that was 164% (Asian-American), 115% (Hispanic), or 208% (Black) of white Covid-19 mortality at these ages. In Black, Indigenous, and People of Color (BIPOC) populations as a whole, Covid-19 mortality at ages 55-64 was greater than white mortality at 10 years older. Conclusions: This discrepancy between vaccination and mortality patterning by race/ethnicity suggests that, if the current period is a “pandemic of the unvaccinated,” it also remains a “pandemic of the disadvantaged” in ways that can decouple from vaccination rates. This result implies an urgent need to center health equity in the development of Covid-19 policy measures.

  🖺 Full Text HTML: “Pandemic of the unvaccinated”? At midlife, white people are less vaccinated but still at less risk of Covid-19 mortality in Minnesota
• Ascertainment rate of SARS-CoV-2 infections from healthcare and community testing in the UK -

  The proportion of SARS-CoV-2 infections ascertained through healthcare and community testing is generally unknown and expected to vary depending on natural factors and changes in test-seeking behaviour. Here we use population surveillance data and reported daily case numbers in the United Kingdom to estimate the rate of case ascertainment. We mathematically describe the relationship between the ascertainment rate, the daily number of reported cases, population prevalence, and the sensitivity of PCR and Lateral Flow tests as a function time since exposure. Applying this model to the data, we estimate that 20-40% of SARS-CoV-2 infections in the UK were ascertained with a positive test with results varying by time and region. Cases of the Alpha variant were ascertained at a higher rate than the wild type variants circulating in the early pandemic, and higher again for the Delta variant and Omicron BA.1 sub-lineage, but lower for the BA.2 sub-lineage. Case ascertainment was higher in adults than in children. We further estimate the daily number of infections and compare this to mortality data to estimate that the infection fatality rate increased by a factor of 3 during the period dominated by the Alpha variant, and declined in line with the distribution of vaccines.

  🖺 Full Text HTML: Ascertainment rate of SARS-CoV-2 infections from healthcare and community testing in the UK
• Tracking Policy Implications and Impacts of the COVID-19 Pandemic and Related Executive Actions on a Sampling of Foreign-born Early Career Researchers in the U.S. -
  The research sector in the United States is highly dependent upon foreign-born researchers. The COVID-19 pandemic and the associated Executive Actions (EAs) by two White house administrations have disrupted their careers. As an advocacy organization focused on early career researchers, the Future of Research has compiled a timeline and analyzed these EAs in detail. We also administered a survey to assess the impact of EAs and related policy changes on foreign-born early career researchers (ECRs), in order to understand the academic challenges of foreign-born trainees during the COVID-19 pandemic. We found that foreign-born ECRs in the United States experienced the greatest negative impact on their mental health, academic life, flexibility to leave and enter the United States and their sense of belonging. Based on these data, we recommend that universities and employers in the United States pay special attention to the precarious state of foreign-born ECRs and take steps to mitigate the negative effects of national policies on their academic experience. Supporting foreign-born ECRs both during and after the COVID-19 pandemic will ensure their career satisfaction and retention in the STEM research workforce, and ensure the continuity of research in the United States.
  🖺 Full Text HTML: Tracking Policy Implications and Impacts of the COVID-19 Pandemic and Related Executive Actions on a Sampling of Foreign-born Early Career Researchers in the U.S.
• Changes in adolescent mental and somatic health complaints throughout the COVID-19 pandemic: A three-wave prospective longitudinal study -
  Purpose: Measures taken to limit the spread of the COVID-19 may have had unintended consequences for the mental and somatic health of children and adolescents. Methods: A nationwide three-wave survey in a representative sample of 12 to 16 years olds in Norway, with baseline data collected in February 2019 (n=9240, 49% girls) and follow-ups in June 2020 (n=3564, 49% girls) and June 2021 (n=2540, 47% girls). Linear mixed-effects models were used to estimate change and identify predictors thereof in mental and somatic health complaints. Results: Following an initial stable trend from before the pandemic to the early phase, both mental health problems (predicted value at T1 0.56 [CI 0.55, 0.58], T1-T2 change -0.04 [ CI -0.07, -0.02], T2-T3 change 0.12 [ CI 0.09, 0.14] and somatic health complaints (predicted value at T1 0.59 [95% CI 0.58, 0.61], T1-T2 difference -0.09 [95% CI -0.11, -0.65], T2-T3 difference 0.18 [95% CI 0.15, 0.21]) increased significantly 15 months into the pandemic, when controlling for age in the models. When compared to boys, girls had a significantly more pronounced increase in mental health problems and somatic health; loneliness in the early stages of the pandemic significantly predicted health complaints one year later, both mental and somatic complaints. Conclusion: Our findings suggest that the prolonged situation of recurrent lockdowns has had an impact on adolescent health in general, and on the health of girls in particular. Much of the rise in mental and somatic health complaints can be attributed to an increase in loneliness.
  🖺 Full Text HTML: Changes in adolescent mental and somatic health complaints throughout the COVID-19 pandemic: A three-wave prospective longitudinal study
• Strategies for using antigen rapid diagnostic tests to reduce transmission of SARS-CoV-2 in low- and middle-income countries: a mathematical modelling study -

  Background Increasing the availability of antigen rapid diagnostic tests (Ag-RDTs) in low- and middle-income countries (LMICs) is key to alleviating global SARS-CoV-2 testing inequity (median testing rate in December 2021-March 2022 when the Omicron variant was spreading in multiple countries; high-income countries=600 tests/100,000 people/day; LMICs=14 tests/ 100,000 people/day). However, target testing levels and effectiveness of asymptomatic community screening to impact SARS-CoV-2 transmission in LMICs are unclear. Methods We used PATAT, an LMIC-focused agent-based model to simulate COVID-19 epidemics, varying the amount of Ag-RDTs available for symptomatic testing at healthcare facilities and asymptomatic community testing in different social settings. We assumed that testing was a function of access to healthcare facilities and availability of Ag-RDTs. We explicitly modelled symptomatic testing demand from non-SARS-CoV-2 infected individuals and measured impact based on the number of infections averted due to test-and-isolate. Findings Testing symptomatic individuals yields greater benefits than any asymptomatic community testing strategy until most symptomatic individuals who sought testing have been tested. Meeting symptomatic testing demand likely requires ~200-400 tests/100,000 people/day on average as symptomatic testing demand is highly influenced by non-SARS-CoV-2 infected individuals. After symptomatic testing demand is satisfied, excess tests to proactively screen for asymptomatic infections among household members yields the largest additional infections averted. Interpretation Testing strategies aimed at reducing transmission should prioritize symptomatic testing and incentivizing test-positive individuals to adhere to isolation to maximize effectiveness.

  🖺 Full Text HTML: Strategies for using antigen rapid diagnostic tests to reduce transmission of SARS-CoV-2 in low- and middle-income countries: a mathematical modelling study
• Predicting SARS-CoV-2 variant spread in a completely seropositive population using semi-quantitative antibody measurements in blood donors -

  Background SARS-CoV-2 serologic surveys estimate the proportion of the population with antibodies against historical variants which nears 100% in many settings. New analytic approaches are required to exploit the full information in serosurvey data. Method Using a SARS-CoV-2 anti-Spike (S) protein chemiluminescent microparticle assay, we attained a semi-quantitative measurement of population IgG titres in serial cross-sectional monthly samples of routine blood donations across seven Brazilian state capitals (March 2021-November 2021). In an ecological analysis (unit of analysis: age-city-calendar month) we assessed the relative contributions of prior attack rate and vaccination to antibody titre in blood donors. We compared blood donor anti-S titre across the seven cities during the growth phase of the Delta variant of concern (VOC) and use this to predict the resulting age-standardized incidence of severe COVID-19 cases. Results On average we tested 780 samples per month in each location. Seroprevalence rose to >95% across all seven capitals by November 2021. Driven proximally by vaccination, mean antibody titre increased 16-fold over the study. The extent of prior natural infection shaped this process, with the greatest increases in antibody titres occurring in cities with the highest prior attack rates. Mean anti-S IgG was a strong predictor (adjusted R2 =0.89) of the number of severe cases caused by the Delta VOC in the seven cities. Conclusions Semi-quantitative anti-S antibody titres are informative about prior exposure and vaccination coverage and can inform on the potential impact of future SARS-CoV-2 variants.

  🖺 Full Text HTML: Predicting SARS-CoV-2 variant spread in a completely seropositive population using semi-quantitative antibody measurements in blood donors
• Influencing Factors for the Persistence of SARS-Cov-2 (COVID-19) exposed in Environmental Matrices and Disinfection Methods: Systematic Review -

  Background : Since the COVID-19 pandemic has been pestilential over a considerable duration, global deployment and financial crisis could not be reversed as before. It brought up essentials to allow the nations back to work with effective preventive measures. This review intended to evaluate the persistence of SARS-CoV-2(COVID-19) exposed in the environmental matrices, influencing factors on the virus persistence and disinfection methods. Methods : Applying the PRISMA 2020 tool, MEDLINE/PubMed, HINARI, and Google Scholar were primarily explored. Data were extracted, entered into the modified data extraction forms and analysed narratively. Quality appraisal was done by the Mixed-Methods Appraisal Tool. The findings were presented descriptively.   Results : Persistence of SARS-CoV-2 was revealed <4 hours on aluminium, 4 hours on copper, 24 hours on cardboard, 44 hours on glass, 48 hours on stainless steel, 72 hours on plastic, 92 hours on polystyrene plastic, 1.1-1.2 hours in the air, 7 days (higher titer) to 3 days(lower titer) in wastewater. Virus decaying was noted 5-10 times faster at 27°C than at 10°C and 2-5 times faster with 65% relative humidity (RH) than with 40% and 100% RH. Virus infectivity was reduced by far-UVC-(222 nm) light for 90%-(8 minutes), 95%-(11 minutes), 99%-(16 minutes) and 99.99%-(25 minutes). Sodium hypochlorite (800 g/m 3 ) and ammonium-based detergents were remarkably effective for preliminary disinfection. Conclusions : This review identified the duration of SARS-CoV-2 survival in environmental matrices for both healthcare and non-healthcare settings. The study explored the impacts of environmental factors on the virus and effective disinfection methods to be considered accordingly to the findings.

  🖺 Full Text HTML: Influencing Factors for the Persistence of SARS-Cov-2 (COVID-19) exposed in Environmental Matrices and Disinfection Methods: Systematic Review
• High Mortality among Older Patients Hospitalized with COVID-19 during the First Pandemic Wave -

  Background: Understanding the local epidemiology, including mortality, of COVID-19 is important for guiding optimal mitigation strategies such as vaccine implementation, need for study of more effective treatment, and redoubling of focused infection control measures. Methods: A retrospective observational cohort study design was utilized. We included adult patients diagnosed in the hospital or emergency department with COVID-19 from March 8, 2020 through May 17, 2020 at Grady Memorial Hospital (Atlanta, GA). Medical chart data abstraction was performed to collect clinical, laboratory and outcome data. Death, defined as inpatient mortality or discharge to hospice, was the primary outcome. Results: Among 360 persons with laboratory-confirmed COVID-19, 50% were ≥ 60 years, and most (80%) were Black and had a BMI ≥25 kg/m2 (64%). A total of 53 patients (15%) had an outcome of death with the majority (n=46, 88%) occurring in persons ≥ 60 years. Persons ≥ 60 years were less likely to have typical COVID-19 symptoms while more likely to have multiple comorbidities, multifocal pneumonia, and to be admitted to intensive care. The death rate was 27% among persons ≥60 years versus 4% in those <60 years (p<.01). Furthermore, most deaths (n=40, 75%) occurred among residents of long-term care facilities (LCFs). Conclusions: We describe early COVID-19 cases among predominantly Black and older patients from a single center safety net hospital. COVID-19 related mortality occurred predominantly among older patients from LCFs highlighting the need for improved preparedness and supporting prioritization of vaccination efforts in such settings.

  🖺 Full Text HTML: High Mortality among Older Patients Hospitalized with COVID-19 during the First Pandemic Wave

From Clinical Trials

• Phase I Clinical Trial of GEN2-Recombinant COVID-19 Vaccine (CHO Cells) in Healthy People Aged 18 and Above - Condition:   COVID-19 Pneumonia
  Interventions:   Biological: Experimental Vaccine 1;   Biological: Experimental Vaccine 2;   Biological: Experimental Vaccine 3;   Biological: placebo
  Sponsors:   National Vaccine and Serum Institute, China;   Lanzhou Institute of Biological Products Co., Ltd;   Beijing Institute of Biological Products Co Ltd.
  Not yet recruiting

• COVID-19 Algorithm Treatment at Home - Condition:   COVID-19
  Interventions:   Drug: Recommended treatment schedule;   Drug: Usual care
  Sponsor:   Mario Negri Institute for Pharmacological Research
  Not yet recruiting

• Immunosuppression and COVID-19 Boosters - Condition:   COVID-19
  Interventions:   Biological: diphtheria and tetanus toxoids (adsorbed) vaccine;   Biological: COVID-19 vaccine
  Sponsors:   Kirby Institute;   Seqirus Pty Ltd, Australia;   Medical Research Future Fund (MRFF)
  Not yet recruiting

• Epidemiological Monitoring of COVID-19 Patients Hospitalized on Reunion Island - Condition:   COVID-19
  Intervention:   Other: telephone interview 24 months after hospitalization for Covid-19
  Sponsor:   Centre Hospitalier Universitaire de la Réunion
  Not yet recruiting

• Randomized, Single-blinded, Multicenter Trial Comparing the Immune Response to a 2nd Booster Dose of COVID-19 mRNA Vaccine (Pfizer-BioNTech) or Sanofi /GSK B.1.351 Adjuvanted Vaccine in Adults - Condition:   COVID-19 Vaccines
  Interventions:   Biological: 2nd booster with Comirnaty® (Pfizer-BioNTech);   Biological: CoV2 preS dTM adjuvanted vaccine (B.1.351), Sanofi/GSK
  Sponsors:   Assistance Publique - Hôpitaux de Paris;   IREIVAC/COVIREIVAC Network
  Recruiting

• Immunogenicity and Safety Study of Booster Vaccine With the COVID-19 Vaccine (Vero Cell), Inactivated, Omicron Strain - Condition:   COVID-19
  Intervention:   Biological: COVID-19 Vaccine (Vero Cell), Inactivated, Omicron Strain
  Sponsor:   Sinovac Biotech (Hong Kong) Limited
  Not yet recruiting

• Plerixafor in Acute Respiratory Distress Syndrome Related to COVID-19 (Phase IIb) - Conditions:   COVID-19 Acute Respiratory Distress Syndrome;   COVID-19
  Interventions:   Drug: Plerixafor 20 MG/ML [Mozobil];   Other: Placebo
  Sponsor:   4Living Biotech
  Not yet recruiting

• Effect of COVID-19 on Platelet Mitochondrial Bioenergetic, Antioxidants and Oxidative Stress in Infertile Men. - Condition:   Men Infertility, Post-COVID-19
  Intervention:   Other: diagnostic test and sperm analysis
  Sponsors:   Comenius University;   GYN-FIV
  Active, not recruiting

• Calcitriol Supplementation in COVID-19 Patients - Conditions:   COVID-19;   Vitamin D Deficiency
  Intervention:   Drug: Calcitriol
  Sponsor:   RenJi Hospital
  Not yet recruiting

• Olfactory Training in COVID-19 Associated Loss of Smell - Conditions:   COVID-19;   Hyposmia
  Intervention:   Device: Sniffin’ sticks Duftquartett
  Sponsor:   Medical University Innsbruck
  Not yet recruiting

• Psychological Impact of Medical Evacuations on Families of Patients Admitted to Intensive Care Unit for Severe COVID-19 - Conditions:   COVID-19;   Stress Disorders, Post-Traumatic
  Interventions:   Other: Revised Impact of Event Scale;   Other: Hospital Anxiety and Depression scale;   Other: 36-Item Short Form Survey;   Other: satisfaction survey;   Other: semi-directed interview with trusted person on the general experience of the patient’s medical evacuation;   Other: semi-directed interview with trusted person on the general experience of hospitalization in intensive care
  Sponsor:   Centre Hospitalier Metropole Savoie
  Completed

• Effects of Telerehabilitative Aerobic and Relaxation Exercises Patients With Type 2 Diabetes With and Without COVID-19 - Conditions:   COVID-19;   Type 2 Diabetes Mellitus
  Intervention:   Other: Aerobic and Relaxation Exercises
  Sponsor:   Bozyaka Training and Research Hospital
  Active, not recruiting

• COVID-19 Vaccine Uptake Trial - Conditions:   Vaccination Refusal;   COVID-19
  Interventions:   Other: Short Message Service (SMS) + Website Link Strategy;   Other: Phone Call with Peer Strategy
  Sponsor:   Washington University School of Medicine
  Not yet recruiting

• Cardiovascular Autonomic and Immune Mechanism of Post COVID-19 Tachycardia Syndrome - Conditions:   Post-acute COVID-19 Syndrome;   Postural Tachycardia Syndrome (POTS);   Long COVID;   SARS CoV 2 Infection
  Interventions:   Diagnostic Test: Determine the inflammatory and immune profile of post-COVID-19 POTS patients;   Diagnostic Test: Measurement of PNS activity by HRV (Heart rate Variation);   Diagnostic Test: Autonomic Symptoms assessment
  Sponsors:   Vanderbilt University Medical Center;   American Heart Association
  Recruiting

• Inhibition of Bradykinin in COVID-19 Infection With Icatibant - Condition:   SARS CoV 2 Infection
  Interventions:   Drug: Icatibant;   Drug: 0.9% Sodium Chloride Injection
  Sponsors:   Belfast Health and Social Care Trust;   Queen’s University, Belfast
  Recruiting

From PubMed

• Synergistic interactions of repurposed drugs that inhibit Nsp1, a major virulence factor for COVID-19 - Nsp1 is one of the first proteins expressed from the SARS-CoV-2 genome and is a major virulence factor for COVID-19. A rapid multiplexed assay for detecting the action of Nsp1 was developed in cultured lung cells. The assay is based on the acute cytopathic effects induced by Nsp1. Virtual screening was used to stratify compounds that interact with two functional Nsp1 sites: the RNA-binding groove and C-terminal helix-loop-helix region. Experimental screening focused on compounds that could be…

• A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants - A comprehensive understanding of host dependency factors for SARS-CoV-2 remains elusive. Here, we map alterations in host lipids following SARS-CoV-2 infection using nontargeted lipidomics. We find that SARS-CoV-2 rewires host lipid metabolism, significantly altering hundreds of lipid species to effectively establish infection. We correlate these changes with viral protein activity by transfecting human cells with each viral protein and performing lipidomics. We find that lipid droplet…

• Preadmission Statin Treatment and Outcome in Patients Hospitalized With COVID-19 - Preadmission statin therapy is associated with improved outcome in patients hospitalized with COVID-19. Whether inhibition of inflammation and myocardial injury are in part responsible for this observation has not been studied. The aim of the present study was to relate preadmission statin usage to markers of inflammation, myocardial injury, and clinical outcome among patients with established atherosclerosis who were admitted with COVID-19. Adult patients with a diagnosis of coronary artery…

• Quinic and digallic acids from Pistacia atlantica Desf. leaves extracts as potent dual effect inhibitors against main protease and RNA-dependent RNA polymerase of SARS-CoV-2 - CONCLUSION: This is the first time that a group of identified compounds from Pistacia atlantica Desf. leaves is studied for their potential activity against the novel virus by inhibiting two key enzymes in its life cycle, and no further studies have been published in this context.

• Multi-Targeted Molecular Docking and Drug-Likeness Evaluation of some Nitrogen Heterocyclic Compounds Targeting Proteins Involved in Development of COVID-19 - CONCLUSION: The outcome reveals that the designed nitrogen heterocyclics could contribute to developing potent inhibitory drug SARS-CoV-2 with strong multi-targeted inhibition ability and reactivity.

• Mechanism of Multi-Organ Injury in Experimental COVID-19 and Its Inhibition by a Small Molecule Peptide - Severe disease from SARS-CoV-2 infection often progresses to multi-organ failure and results in an increased mortality rate amongst these patients. However, underlying mechanisms of SARS- CoV-2-induced multi-organ failure and subsequent death are still largely unknown. Cytokine storm, increased levels of inflammatory mediators, endothelial dysfunction, coagulation abnormalities, and infiltration of inflammatory cells into the organs contribute to the pathogenesis of COVID-19. One potential…

• Overview of Breastfeeding Under COVID-19 Pandemic - During the global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pregnant and lactating women are at higher risk of infection. The potential of viral intrauterine transmission and vertical transmission by breastfeeding has raised wide concerns. Breastmilk is rich in nutrients that contribute to infant growth and development, and reduce the incidence rate of infant illness and death, as well as inhibit pathogens…

• Priming With Rhinovirus Protects Mice Against a Lethal Pulmonary Coronavirus Infection - Rhinoviruses (RV) have been shown to inhibit subsequent infection by heterologous respiratory viruses, including influenza viruses and severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). To better understand the mechanisms whereby RV protects against pulmonary coronavirus infection, we used a native murine virus, mouse hepatitis virus strain 1 (MHV-1), that causes severe disease in the lungs of infected mice. We found that priming of the respiratory tract with RV completely prevented…

• 2-deoxy-D-glucose as India’s Response to COVID-19: A Commitment or Conceit? - 2-deoxy-d-glucose (2-DG) has recently been approved for the treatment of moderate to severe COVID-19 patients in India. Here we discuss whether this is a well-thought-out step towards the long-term management of COVID-19 or a decision taken at the spur of the moment. 2-DG, an anticancer drug, also has immunomodulatory functions. Several studies have shown 2-DG to inhibit viral replication and cytokine storm. However, these findings are mostly on cells and animal models. The clinical trial that…

• Sonic hedgehog pathway for the treatment of inflammatory diseases: implications and opportunities for future research - The Sonic hedgehog (Shh) signaling pathway is an essential pathway in the human body that plays an important role in embryogenesis and tissue homeostasis. Aberrant activation of this pathway has been linked to the development of different diseases, ranging from cancer to immune dysregulation and infections.Uncontrolled activation of the pathway through sporadic mutations or other mechanisms is associated with cancer development and progression in various malignancies, such as basal cell…

• Treatment with metformin glycinate reduces SARS-CoV-2 viral load: An in vitro model and randomized, double-blind, Phase IIb clinical trial - The health crisis caused by the new coronavirus SARS-CoV-2 highlights the need to identify new treatment strategies for this viral infection. During the past year, over 400 coronavirus disease (COVID-19) treatment patents have been registered; nevertheless, the presence of new virus variants has triggered more severe disease presentations and reduced treatment effectiveness, highlighting the need for new treatment options for the COVID-19. This study evaluates the Metformin Glycinate (MG) effect…

• Metformin alleviates prolonged isoflurane inhalation induced cognitive decline via reducing neuroinflammation in adult mice - With the widespread use of volatile anesthetic agents in the prolonged sedation for COVID-19 pneumonia and ARDS, there is an urgent need to investigate the effects and treatments of lengthy low-concentration inhaled anesthetics exposure on cognitive function in adults. Previous studies showed that general anesthetics dose- and exposure length-dependently induced neuroinflammatory response and cognitive decline in neonatal and aging animals. The anti-diabetes drug metformin has…

• Small-Molecule Thioesters as SARS-CoV-2 Main Protease Inhibitors: Enzyme Inhibition, Structure-Activity Relationships, Antiviral Activity, and X-ray Structure Determination - The main protease (M^(pro), 3CL^(pro)) of SARS-CoV-2 is an attractive target in coronaviruses because of its crucial involvement in viral replication and transcription. Here, we report on the design, synthesis, and structure-activity relationships of novel small-molecule thioesters as SARS-CoV-2 M^(pro) inhibitors. Compounds 3w and 3x exhibited excellent SARS-CoV-2 M^(pro) inhibition with k(inac)/K(i) of 58,700 M^(-1) s^(-1) (K(i) = 0.0141 μM) and 27,200 M^(-1) s^(-1) (K(i) = 0.0332 μM),…

• Metalloproteinase-Dependent and TMPRSS2-Independent Cell Surface Entry Pathway of SARS-CoV-2 Requires the Furin Cleavage Site and the S2 Domain of Spike Protein - The ongoing global vaccination program to prevent SARS-CoV-2 infection, the causative agent of COVID-19, has had significant success. However, recently, virus variants that can evade the immunity in a host achieved through vaccination have emerged. Consequently, new therapeutic agents that can efficiently prevent infection from these new variants, and hence COVID-19 spread, are urgently required. To achieve this, extensive characterization of virus-host cell interactions to identify effective…

• The Burden of Hypercoagulability in COVID-19 - The novel coronavirus disease 2019 (COVID-19) infection has widespread impact on multiple organ systems, including damage to endothelial cells. Various studies have found evidence for direct mechanisms by which interaction between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and endothelial cells lead to extensive damage to the latter, and indirect mechanisms, such as excessively elevated cytokines, can also result in the same outcome. Damage to the endothelium results in release…

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