Covid-19 Sentry

Contents

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

From Preprints

• Malariology (A Continuing Education Activity) -
  Malariology is the scientific study of Malaria. Malaria is a life-threatening disease caused by parasites that are transmitted to people through the bites of infected female Anopheles mosquitoes. It is preventable and curable. Malaria can be caused by several species of Plasmodium parasites, each of which has a complex life cycle. Malaria parasites are transmitted to human hosts by female mosquitoes of the genus Anopheles. Numerous physiological, behavioral, and ecological characteristics determine how effective various Anopheles species are as vectors of malaria. They cause illness, abnormal function, or damage in their human hosts. “Uncomplicated” malaria entails a series of recurring episodes of chills, intense fever, and sweating and sometimes includes other symptoms such as headache, malaise, fatigue, body aches, nausea, and vomiting. In some cases, and especially in groups such as children and pregnant women, the disease can progress to “severe malaria,” including complications such as cerebral malaria/coma, seizures, severe anemia, respiratory distress, kidney and liver failure, cardiovascular collapse, and shock. Long-term impacts include death, disability, and significant socioeconomic burden on societies where the disease is prevalent. A better understanding of the biological processes underlying the progression of infection to disease is urgently needed to reduce the morbidity and mortality of malaria. Over the past several years, the completion of several genome projects related to malaria has marked the beginning of a new era of malaria research. The National Institute of Allergy and Infectious Diseases NIAID-supported researchers have sequenced the genomes of 16 Anopheline mosquito species, including the Anopheles gambiae mosquito, a major malaria vector, and more than 100 isolates of both Plasmodium falciparum, the deadliest malaria parasite, and Plasmodium vivax, the most widespread malaria parasite. Plasmodium ovale is a species of parasitic protozoon (plural: protozoan) that causes tertian malaria in humans. Like the other malaria parasites of primates, this parasite is only transmitted via the bites of infected Anopheles mosquitoes. The interaction between the Plasmodium parasite and host immune system during infection strikes a tenuous balance. The relationship can elicit protective immunity or trigger harmful immune responses. The complex nature of both the malaria parasite and the human immune response has made it difficult to unravel the mechanisms of protection or pathology in humans. An improved understanding of the immunology of malaria is likely to provide key insights into ways to enhance human immunity while reducing disease burdens. Analytical data is critical to both developing novel vaccines and drugs and implementing effective control and prevention programs. Understanding malaria on a population level and determining the biological, behavioral, and environmental factors that influence malaria epidemiology and transmission are especially important as the global community strengthens anti-malaria efforts. As the COVID-19 pandemic spreads rapidly around the globe, there is an urgent need to aggressively tackle the novel coronavirus while ensuring that other killer diseases, such as malaria, are not neglected. The WHO Global Malaria Programme is leading a cross-partner effort to mitigate the negative impact of the coronavirus in malaria-affected countries and, where possible, contribute towards a successful COVID-19 response; The Global Technical Strategy for Malaria 2016-2030 (GTS) & Immunisation Agenda 2030 (IA2030) are aimed at calls for all malaria-endemic countries to accelerate efforts towards elimination and attainment of malaria-free status. Also in combating re-establishment in Malaria free countries. Along with the Roll Back Malaria (RBM), US President’s Malaria Initiative (PMI), Action and Investment to defeat Malaria 2016-2030 (AIM) and various other malaria fighters ambitious targets of reducing malaria case incidence and mortality rates globally by at least 90% by 2030.
  🖺 Full Text HTML: Malariology (A Continuing Education Activity)
• Identification of small molecules with virus growth enhancement properties -
  The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused the pandemic disease known as coronavirus disease 2019 (COVID-19). COVID-19 vaccines were developed at record speed and were authorized approximately a year after the original outbreak. This fast response saved the lives of countless individuals and reduced the disease burden of many more. The experience has served as a reminder of the necessity to implement solid vaccine development platforms and fast production pipelines. Manufacturing vaccines for enveloped viruses, including some SARS-CoV-2 vaccines, often relies on the production of large quantities of viruses in vitro. Thus, speeding up or increasing virus production would expedite vaccine development. With this objective in mind, we established a high throughput screening (HTS) to identify small molecules that enhance or speed up host-virus membrane fusion. Among the HTS hits, we identified that ethynylestradiol augments SARS-CoV-2 fusion activity in both the absence and presence of TMPRSS2. Furthermore, we confirmed that ethynylestradiol can boost the growth of not only SARS-CoV-2 but also Influenza A virus in vitro. A small molecule with these characteristics could be implemented to improve vaccines production.
  🖺 Full Text HTML: Identification of small molecules with virus growth enhancement properties
• Precise identification of cell states altered indisease with healthy single-cell references -
  Single cell genomics is a powerful tool to distinguish altered cell states in disease tissue samples, through joint analysis with healthy reference datasets. Collections of data from healthy individuals are being integrated in cell atlases that provide a comprehensive view of cellular phenotypes in a tissue. However, it remains unclear whether atlas datasets are suitable references for disease-state identification, or whether matched control samples should be employed, to minimise false discoveries driven by biological and technical confounders. Here we quantitatively compare the use of atlas and control datasets as references for identification of disease-associated cell states, on simulations and real disease scRNA-seq datasets. We find that reliance on a single type of reference dataset introduces false positives. Conversely, using an atlas dataset as reference for latent space learning followed by differential analysis against a matched control dataset leads to precise identification of disease-associated cell states. We show that, when an atlas dataset is available, it is possible to reduce the number of control samples without increasing the rate of false discoveries. Using a cell atlas of blood cells from 12 studies to contextualise data from a case-control COVID-19 cohort, we sensitively detect cell states associated with infection, and distinguish heterogeneous pathological cell states associated with distinct clinical severities. Our analysis provides guiding principles for design of disease cohort studies and efficient use of cell atlases within the Human Cell Atlas.
  🖺 Full Text HTML: Precise identification of cell states altered indisease with healthy single-cell references
• An intranasal self-amplifying RNA SARS-CoV-2 vaccine produces durable respiratory and systemic immunity -
  While mRNA vaccines have been highly effective over the past 2 years in combating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), waning of vaccine-induced antibody responses and lack of induction of respiratory tract immunity contribute to ongoing infection and transmission. However, intranasally (i.n.) administered vaccines may induce mucosal immunity at the site of respiratory virus infection and may thus boost protection. In this work, we present an i.n. administered SARS-CoV-2 self-amplifying RNA (saRNA) vaccine, delivered by a nanostructured lipid carrier (NLC), which induces both potent respiratory mucosal and systemic immune responses. Following prime-boost immunization in C57BL/6 mice, i.n. vaccination induces serum neutralizing antibody titers, bone marrow resident IgG-secreting cells, and robust systemic polyfunctional T cells, similar to intramuscular (i.m.) vaccination. The intranasal vaccine additionally induces key SARS-CoV-2-reactive lung-resident polyfunctional memory and lung-homing T cell populations. As a booster following i.m. administration, the i.n. vaccine also elicits robust mucosal and systemic immunity, exceeding an i.m. booster, durable for at least 4 months. The potent mucosal and systemic immunogenicity of this i.n. saRNA vaccine may be key for combating SARS-CoV-2 and other respiratory pathogens.
  🖺 Full Text HTML: An intranasal self-amplifying RNA SARS-CoV-2 vaccine produces durable respiratory and systemic immunity
• Evasive spike variants elucidate the preservation of T cell immune response to the SARS-CoV-2 omicron variant -
  The Omicron variants boast the highest infectivity rates among all SARS-CoV-2 variants. Despite their lower disease severity, they can reinfect COVID-19 patients and infect vaccinated individuals as well. The high number of mutations in these variants render them resistant to antibodies that otherwise neutralize the spike protein of the original SARS-CoV-2 spike protein. Recent research has shown that despite its strong immune evasion, Omicron still induces strong T Cell responses similar to the original variant. This work investigates the molecular basis for this observation using the neural network tools NetMHCpan-4.1 and NetMHCiipan-4.0. The antigens presented through the MHC Class I and Class II pathways from all the notable SARS-CoV-2 variants were compared across numerous high frequency HLAs. All variants were observed to have equivalent T cell antigenicity. A novel positive control system was engineered in the form of spike variants that did evade T Cell responses, unlike Omicron. These evasive spike proteins were used to statistically confirm that the Omicron variants did not exhibit lower antigenicity in the MHC pathways. These results suggest that T Cell immunity mounts a strong defense against COVID-19 which is difficult for SARS-CoV-2 to overcome through mere evolution.
  🖺 Full Text HTML: Evasive spike variants elucidate the preservation of T cell immune response to the SARS-CoV-2 omicron variant
• Assessing the Effect of Selective Serotonin Reuptake Inhibitors in the Prevention of Post-Acute Sequelae of COVID-19 -

  Importance: Post-acute sequelae of COVID-19 (PASC) produce significant morbidity, prompting evaluation of interventions that might lower risk. Selective serotonin reuptake inhibitors (SSRIs) potentially could modulate risk of PASC via their central hypothesized immunomodulatory, and/or antiplatelet properties and therefore have been hypothesized to be of potential benefit in patients with PASC, although clinical data are lacking. Objectives: The main objective was to evaluate whether SSRIs with agonist activity at the sigma-1 receptor lower the risk of PASC, since agonism at this receptor may serve as a mechanism by which SSRIs attenuate an inflammatory response. A secondary objective was to determine whether potential benefit could be traced to sigma-1 agonism by evaluating the risk of PASC among recipients of SSRIs that are not S1R agonists. Design: Retrospective study leveraging real-world clinical data within the National COVID Cohort Collaborative (N3C), a large centralized multi-institutional de-identified EHR database. Presumed PASC was defined based on a computable PASC phenotype trained on the U09.9 ICD-10 diagnosis code to more comprehensively identify patients likely to have the condition, since the ICD code has come into wide-spread use only recently. Setting: Population-based study at US medical centers. Participants: Adults (≥ 18 years of age) with a confirmed COVID-19 diagnosis date between October 1, 2021 and April 7, 2022 and at least one follow up visit 45 days post-diagnosis. Of the 17 933 patients identified, 2021 were exposed at baseline to a S1R agonist SSRI, 1328 to a non-S1R agonist SSRI, and 14 584 to neither. Exposures: Exposure at baseline (at or prior to COVID-19 diagnosis) to an SSRI with documented or presumed agonist activity at the S1R (fluvoxamine, fluoxetine, escitalopram, or citalopram), an SSRI without agonist activity at S1R (sertraline, an antagonist, or paroxetine, which does not appreciably bind to the S1R), or none of these agents. Main Outcome and Measurement: Development of PASC based on a previously validated XGBoost-trained algorithm. Using inverse probability weighting and Poisson regression, relative risk (RR) of PASC was assessed. Results: A 26% reduction in the RR of PASC (0.74 [95% CI, 0.63-0.88]; P = 5 x 10-4) was seen among patients who received an S1R agonist SSRI compared to SSRI unexposed patients and a 25% reduction in the RR of PASC was seen among those receiving an SSRI without S1R agonist activity (0.75 [95% CI, 0.62 - 0.90]; P = 0.003) compared to SSRI unexposed patients. Conclusions and Relevance: SSRIs with and without reported agonist activity at the S1R were associated with a significant decrease in the risk of PASC. Future prospective studies are warranted.

  🖺 Full Text HTML: Assessing the Effect of Selective Serotonin Reuptake Inhibitors in the Prevention of Post-Acute Sequelae of COVID-19
• Galectin approach to lower covid transmission - Drug Development for clinical use -

  Background: SARS-CoV-2 vaccines play an important role in reducing disease severity, hospitalization, and death, although they failed to prevent the transmission of SARS-CoV-2 variants. Therefore, an effective antiviral such as a Galectin-3 (Gal-3) antagonist might have the potential to prevent viral transmission. ProLectin-M (PL-M), a Gal-3 antagonist, has been shown to have anti-SARS-CoV-2 activity in previous studies. Aim: The present study aimed to further evaluate the antiviral effect of PL-M tablets in 34 subjects with COVID-19 disease, in addition to determining the antiviral mechanisms of PL-M by NMR studies. Methods: The efficacy of PL-M was evaluated in a randomized, double-blind, placebo-controlled clinical study in patients with mild to moderately severe COVID-19. Primary endpoints included changes in absolute RT-PCR Ct values of the nucleocapsid and open reading frame (ORF) genes from baseline to days 3 and 7. The incidence of adverse events, changes in blood biochemistry, inflammatory biomarkers, and levels of antibodies against COVID-19 were also evaluated as part of the safety evaluation. In vitro 1H-15N HSQC NMR spectroscopy studies were also performed to determine the interactions of PL-M with Gal-3 and the S1 spike protein of SARS-CoV-2. Results: PL-M treatment significantly (p = 0.001) increased RT-PCR cycle counts for N and ORF genes on days 3 (Ct values 32.09 and 30.69 +/- 3.38, respectively) and 7 (Ct values 34.91 +/- 0.39 and 34.85 +/- 0.61, respectively) compared to placebo. All subjects were RT-PCR negative for both genes in the PL-M treatment group from day 3 onwards. The Ct values in the placebo group were consistently less than 29 (target cycle count 29) for both genes until day 7, and no placebo subjects were negative by RT-PCR. 1H-15N HSQC NMR spectroscopy revealed that PL-M specifically binds Gal-3 in the same way as the structurally similar NTD of the SARS-CoV-2 S1 subunit. Conclusion: PL-M is safe and effective for clinical use in reducing viral load and promoting rapid viral clearance in COVID-19 patients by inhibiting SARS-CoV-2 entry into cells through inhibition of Gal-3. Keywords: Galectin-3, ProLectin-M, SARS-CoV-2, Clinical Trial, NMR, Spike protein.

  🖺 Full Text HTML: Galectin approach to lower covid transmission - Drug Development for clinical use
• The role of cholesterol metabolism in predicting clinical outcome of patients with severe COVID-19 -

  Transcriptomic analysis conducted by us previously revealed upregulation of genes involved in low-density lipoprotein particle receptor (LDLR) activity pathway in lethal COVID-19. Last data suggested the possible role of extracellular vesicles and exomeres in COVID-19 pathogenesis. The aim of the present study was to retro-spectively evaluate parameters of cholesterol metabolism as possible predictors of fatal outcome of COVID-19. Blood from 39 patients with severe COVID-19 (the main cohort) were collected at the time of admission to the intensive care unit (ICU) (T1) and 7 days after admission to the ICU (T2). After 30 days patients were divided into two subgroups according to outcome-21 non-survivors and 18 survivors. 28 patients (13 non-survivors and 15 survivors) with severe COVID-19 were included as the replication cohort. The study demonstrated that plasma low- and high-density lipoprotein cholesterol levels (LDL-C and HDL-C) were decreased and CCL20/MIP3?, IL-10, IL-15, IL-27 concentrations were increased in non-survivors compared to controls in T1. STAB1 gene expression was higher in non-survivors than in survivors (p=0.017) in T2. The conjoint fraction of exomeres and LDL particles measured by dynamic light scattering (DLS) was decreased in non-survivors com-pared to survivors in both the main and replication cohorts. We first showed that change of exomeres fraction may be critical in fatal outcome of COVID-19.

  🖺 Full Text HTML: The role of cholesterol metabolism in predicting clinical outcome of patients with severe COVID-19
• Helminth exposure protects against murine SARS-CoV-2 infection through macrophage dependent T cell activation -
  Helminth endemic regions report lower COVID-19 morbidity and mortality. Here, we show that lung remodeling from a prior infection with a lung migrating helminth, Nippostrongylus brasiliensis, enhances viral clearance and survival of human-ACE2 transgenic mice challenged with SARS-CoV-2 (SCV2). This protection is associated with a lymphocytic infiltrate including an increased accumulation of pulmonary SCV2-specific CD8+ T cells and anti-CD8 antibody depletion abrogated the N. brasiliensis-mediated reduction in viral loads. Pulmonary macrophages with a type-2 transcriptional signature persist in the lungs of N. brasiliensis exposed mice after clearance of the parasite and establish a primed environment for increased antigen presentation. Accordingly, depletion of macrophages ablated the augmented viral clearance and accumulation of CD8+ T cells driven by prior N. brasiliensis infection. Together, these findings support the concept that lung migrating helminths can limit disease severity during SCV2 infection through macrophage-dependent enhancement of anti-viral CD8+ T cell responses.
  🖺 Full Text HTML: Helminth exposure protects against murine SARS-CoV-2 infection through macrophage dependent T cell activation
• Assessing the accuracy of California county level COVID-19 hospitalization forecasts to inform public policy decision making -

  The COVID-19 pandemic has highlighted the role of infectious disease forecasting in informing public policy. However, significant barriers remain for effectively linking infectious disease forecasts to public health decision making, including a lack of model validation. Forecasting model performance and accuracy should be evaluated retrospectively to understand under which conditions models were reliable and could be improved in the future. Using archived forecasts from the California Department of Public Health9s California COVID Assessment Tool (https://calcat.covid19.ca.gov/cacovidmodels/), we compared how well different forecasting models predicted COVID-19 hospitalization census across California counties and regions during periods of Alpha, Delta, and Omicron variant predominance. Based on mean absolute error estimates, forecasting models had variable performance across counties and through time. When accounting for model availability across counties and dates, some individual models performed consistently better than the ensemble model, but model rankings still differed across counties. Local transmission trends, variant prevalence, and county population size were informative predictors for determining which model performed best for a given county based on a random forest classification analysis. Overall, the ensemble model performed worse in less populous counties, in part because of fewer model contributors in these locations. Ensemble model predictions could be improved by incorporating geographic heterogeneity in model coverage and performance. Consistency in model reporting and improved model validation can strengthen the role of infectious disease forecasting in real-time public health decision making.

  🖺 Full Text HTML: Assessing the accuracy of California county level COVID-19 hospitalization forecasts to inform public policy decision making
• Use of home pulse oximetry to enhance remote COVID-19 monitoring: Evaluating a single centre experience. -

  Introduction Telehealth and remote monitoring of patients with mild COVID19 infection have developed rapidly in response to the pandemic. Many healthcare systems have embraced telehealth for remote clinical monitoring and pulse oximetry for enhanced monitoring. Methods The experience of a large healthcare centre9s COVID Virtual Ward was reviewed retrospectively with a particular focus on evaluating the effectiveness, safety and utility of finger pulse oximetry within the home. Data from a 2 month period in early 2022 during a BA1 Omicron wave was retrospectively reviewed. 551 high risk patients were issued with pulse oximeters for monitoring oxygen saturations within their home. All patients received daily clinical review via telephone by a nurse or doctor. The group was highly vaccinated with only 6.4 percent of the cohort unvaccinated. Oximeters were promptly delivered via courier service across a vast geographical area. Results Pulse oximetry was well utilised by almost all patients. Only 2.7 percent of the cohort demonstrated resting oxygen saturations of less than 94 percent during their Virtual Ward admission. 91 percent of patients reporting dyspnoea were able to be safely managed without escalation to an emergency department due to reassuring clinical and oximetry assessment. Home oxygen saturations correlated well with saturations recorded within the ED, with no patients found to have lower saturations compared with home saturations. Discussion Within a high risk population experiencing COVID19 infection, pulse oximetry was a useful tool in clinical assessment, correlated well with hospital based pulse oximetry and allowed a substantial reduction in COVID19 related ED presentations.

  🖺 Full Text HTML: Use of home pulse oximetry to enhance remote COVID-19 monitoring: Evaluating a single centre experience.
• The interface between SARS-CoV-2 and non-communicable diseases (NCDs) in a high HIV/TB burden district level hospital setting, Cape Town, South Africa -

  Background COVID-19 experiences on noncommunicable diseases (NCDs) from district-level hospital settings during waves I and II are scarcely documented. The aim of this study is to investigate the NCDs associated with COVID-19 severity and mortality in a district-level hospital with a high HIV/TB burden. Methods This was a retrospective observational study that compared COVID-19 waves I and II at Khayelitsha District Hospital in Cape Town, South Africa. COVID-19 adult patients with a confirmed SARS-CoV-2 polymerase chain reaction (PCR) or positive antigen test were included. In order to compare the inter wave period, clinical and laboratory parameters on hospital admission of noncommunicable diseases, the Student t-test or Mann-Whitney U for continuous data and the X2 test or Fishers9 Exact test for categorical data were used. The role of the NCD subpopulation on COVID-19 mortality was determined using latent class analysis (LCA). Findings Among 560 patients admitted with COVID-19, patients admitted during wave II were significantly older than those admitted during wave I. The most prevalent comorbidity patterns were hypertension (87%), diabetes mellitus (65%), HIV/AIDS (30%), obesity (19%), Chronic Kidney Disease (CKD) (13%), Congestive Cardiac Failure (CCF) (8.8%), Chronic Obstructive Pulmonary Disease (COPD) (3%), cerebrovascular accidents (CVA)/stroke (3%), with similar prevalence in both waves except HIV status [(23% vs 34% waves II and I, respectively), p = 0.022], obesity [(52% vs 2.5%, waves II and I, respectively), p <0.001], previous stroke [(1% vs 4.1%, waves II and I, respectively), p = 0.046]. In terms of clinical and laboratory findings, our study found that wave I patients had higher haemoglobin and HIV viral loads. Wave II, on the other hand, had statistically significant higher chest radiography abnormalities, fraction of inspired oxygen (FiO2), and uraemia. The adjusted odds ratio for death vs discharge between waves I and II was similar (0.94, 95%CI: 0.84-1.05). Wave I had a longer average survival time (8.0 vs 6.1 days) and a shorter average length of stay among patients discharged alive (9.2 vs 10.7 days). LCA revealed that the cardiovascular phenotype had the highest mortality, followed by diabetes and CKD phenotypes. Only Diabetes and hypertension phenotypes had the lowest mortality. Conclusion Even though clinical and laboratory characteristics differed significantly between the two waves, mortality remained constant. According to LCA, the cardiovascular, diabetes, and CKD phenotypes had the highest death probability.

  🖺 Full Text HTML: The interface between SARS-CoV-2 and non-communicable diseases (NCDs) in a high HIV/TB burden district level hospital setting, Cape Town, South Africa
• Neurologic sequalae of COVID-19 are determined by immunologic imprinting from previous Coronaviruses. -

  Coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global public health emergency. Although SARS-CoV-2 is primarily a respiratory pathogen, extra-respiratory organs, including the central nervous system (CNS), can also be affected. Neurologic symptoms have been observed not only during acute SARS-CoV-2 infection, but also at distance from respiratory disease, also known as long-COVID or neurological post-acute sequelae of COVID-19 (neuroPASC). The pathogenesis of neuroPASC is not well understood, but hypotheses include SARS-CoV-2-induced immune dysfunctions, hormonal dysregulations, and persistence of SARS-CoV-2 reservoirs. In this study, we used a high throughput systems serology approach to dissect the humoral response to SARS-CoV-2 (and other common Coronaviruses - 229E, HKU1, NL63, OC43) in the serum and cerebrospinal fluid (CSF) from 112 infected individuals who developed or did not develop neuroPASC. Unique SARS-CoV-2 humoral profiles were observed in the CSF of neuroPASC. All antibody isotypes (IgA, IgM, IgA) and subclasses (IgA1-2; IgG1-4) were detected in serum, whereas CSF was characterized by focused IgG1 (and absence of IgM). These data argue in favor of compartmentalized brain-specific responses against SARS-CoV-2 through selective transfer of antibodies from the serum to the CSF across the blood-brain-barrier, rather than intrathecal synthesis, where more diversity in antibody classes/subclasses would be expected. Moreover, compared to individuals who did not develop post-acute neurological complications following infection (n=94), those with neuroPASC (n=18) exhibited attenuated systemic antibody responses against SARS-CoV-2, characterized by decreased capacity to activate antibody-dependent complement deposition (ADCD), NK cell activation (ADNKA) and to bind Fcγ receptors. However, surprisingly, neuroPASC showed significantly expanded antibody responses to other common Coronaviruses, including 229E, HKU1, NL63, and OC43. This biased humoral activation across coronaviruses was particularly enriched in neuroPASC individuals with poor outcome, suggesting an original antigenic sin (or immunologic imprinting), where pre-existing immune responses against related viruses shape the response to current infection, as a key prognostic biomarker of neuroPASC disease. Overall, these findings point to a pathogenic role for compromised anti-SARS-CoV-2 responses in the CSF, likely resulting in incomplete virus clearance from the brain and persistent neuroinflammation, in the development of post-acute neurologic complications of SARS-CoV-2 infection.

  🖺 Full Text HTML: Neurologic sequalae of COVID-19 are determined by immunologic imprinting from previous Coronaviruses.
• Characterizing responsiveness to the COVID-19 pandemic in the United States and Canada using mobility data -

  Background: Mobile phone-derived human mobility data are a proxy for disease transmission risk and have proven useful during the COVID-19 pandemic for forecasting cases and evaluating interventions. We propose a novel metric using mobility data to characterize responsiveness to rising case rates. Methods: We examined weekly reported COVID-19 incidence and retail and recreation mobility from Google Community Mobility Reports for 50 U.S. states and nine Canadian provinces from December 2020 to November 2021. For each jurisdiction, we calculated the responsiveness of mobility to COVID-19 incidence when cases were rising. Responsiveness across countries was summarized using subgroup meta-analysis. We also calculated the correlation between the responsiveness metric and the reported COVID-19 death rate during the study period. Findings: Responsiveness in Canadian provinces (β = -1.45; 95% CI: -2.45, -0.44) was approximately five times greater than in U.S. states (β = -0.30; 95% CI: -0.38, -0.21). Greater responsiveness was moderately correlated with a lower reported COVID-19 death rate during the study period (Spearman9s ρ = 0.51), whereas average mobility was only weakly correlated the COVID-19 death rate (Spearman9s ρ = 0.20). Interpretation: Our study used a novel mobility-derived metric to reveal a near-universal phenomenon of reductions in mobility subsequent to rising COVID-19 incidence across 59 states and provinces of the U.S. and Canada, while also highlighting the different public health approaches taken by the two countries. Funding: This study received no funding.

  🖺 Full Text HTML: Characterizing responsiveness to the COVID-19 pandemic in the United States and Canada using mobility data
• Comparison of the reactogenicity and immunogenicity between two-dose mRNA COVID-19 vaccine and inactivated followed by an mRNA vaccine in children aged 5 - 11 years -

  Objective: To compare the reactogenicity and immunogenicity between the two-dose mRNA COVID-19 vaccine regimen and one or two doses of inactivated vaccine followed by an mRNA vaccine regimen in healthy children between 5-11 years of age. Methods: A prospective cohort study was performed at King Chulalongkorn Memorial Hospital in Thailand between March to June 2022. Healthy children between 5-11 years of age were enrolled and received the two-dose mRNA COVID-19 vaccine (BNT162b2) regimen or the inactivated (CoronaVac) vaccine followed by the BNT162b2 vaccine regimen. In addition, healthy children who received two doses of BBIBP-CorV between 1-3 months prior were enrolled to receive a heterologous BNT162b2 as a third dose (booster). Reactogenicity was assessed by a self-reported online questionnaire. Immunogenicity analysis was performed to determine binding and surrogate neutralizing antibodies to SARS-CoV-2 wild-type and Omicron variants. Results: Overall, 166 eligible children were enrolled. Local and systemic AE which occurred within 7 days after vaccination were mild to moderate and well-tolerated. At one-month, post-two or post-three doses, children vaccinated with two-dose BNT162b2, CoronaVac/BNT162b2, and two-dose BBIBP-CorV followed by BNT162b2 elicited similar levels of anti-receptor-binding domain (RBD) IgG. However, the two-dose BNT162b2 and two-dose BBIBP-CorV followed by BNT162b2 groups elicited higher neutralizing activities against Omicron BA.2 variant than the CoronaVac/BNT162b2 group. Conclusion: The heterologous, CoronaVac vaccine followed by the BNT162b2 vaccine, regimen elicited lower neutralizing activities against the emerging Omicron BA.2 variant than the two-dose mRNA regimen. A third dose (booster) mRNA vaccine should be prioritized for this group.

  🖺 Full Text HTML: Comparison of the reactogenicity and immunogenicity between two-dose mRNA COVID-19 vaccine and inactivated followed by an mRNA vaccine in children aged 5 - 11 years

From Clinical Trials

• COVID-19 Bivalent Booster Megastudy - Condition:   COVID-19
  Intervention:   Behavioral: COVID Booster text messages
  Sponsor:   University of Pennsylvania
  Enrolling by invitation

• Using a Community-level Just-in-Time Adaptive Intervention to Address COVID-19 Testing Disparities - Condition:   COVID-19
  Interventions:   Behavioral: Multi-Level Multi-Component Intervention (MLI);   Behavioral: Community Just-In-Time Adaptive Intervention (Community JITAI)
  Sponsors:   The University of Texas Health Science Center, Houston;   National Center for Advancing Translational Sciences (NCATS)
  Active, not recruiting

• Examining How a Facilitated Self-Sampling Intervention and Testing Navigation Intervention Influences COVID-19 Testing - Condition:   COVID-19
  Interventions:   Behavioral: Facilitated Self-Sampling Intervention (FSSI);   Behavioral: Testing Navigation Intervention (TNI).;   Behavioral: Control
  Sponsors:   The University of Texas Health Science Center, Houston;   National Center for Advancing Translational Sciences (NCATS)
  Not yet recruiting

• Assessing Performance of the Testing Done Simple Covid 19 Antigen Test - Condition:   COVID-19
  Intervention:   Diagnostic Test: Testing Done Simple SARS CoV-2 Antigen Test
  Sponsors:   Testing Done Simple;   Nao Medical Urgent Care
  Recruiting

• 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 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.
  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

• A Phase 1, Randomised, Double-blinded, Placebo-controlled, Dose-escalation Study to Evaluate the Safety and Immunogenicity of RH109 as Booster - Condition:   COVID-19 Pandemic
  Interventions:   Biological: Lyophilized COVID-19 mRNA Vaccine;   Drug: Sodium chloride
  Sponsors:   Wuhan Recogen Biotechnology Co., Ltd.;   Shenzhen Rhegen Biotechnology Co., Ltd.;   Wuhan Rhegen Biotechnology Co., Ltd.
  Not yet recruiting

• Role of Tele-physical Therapy in Patients With Type 2 Diabetes Mellitus Following COVID-19 Infection. - Conditions:   Type 2 Diabetes Mellitus;   COVID-19
  Interventions:   Other: Tele physical therapy;   Other: Patient educationa and Conventional exercises
  Sponsor:   Prince Sattam Bin Abdulaziz University
  Completed

From PubMed

• Design, Synthesis, and Biological Evaluation of Novel Ruxolitinib and Baricitinib Analogues for Potential Use Against COVID-19 - The coronavirus pandemic known as COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), threatens public health worldwide. Approval of COVID-19 vaccines and antiviral drugs have greatly reduced the severe cases and mortality rate. However, the continues mutations of viruses are challenging the efficacies of vaccines and antiviral drugs. Drug repurposing campaign has identified two JAK1/2 inhibitors ruxolitinib and baricitinib as potential antiviral drugs. Ruxolitinib…

• SARS-CoV-2 at the Human-Animal Interface: Implication for Global Public Health from an African Perspective - The coronavirus disease 2019 (COVID-19) pandemic has become the most far-reaching public health crisis of modern times. Several efforts are underway to unravel its root cause as well as to proffer adequate preventive or inhibitive measures. Zoonotic spillover of the causative virus from an animal reservoir to the human population is being studied as the most likely event leading to the pandemic. Consequently, it is important to consider viral evolution and the process of spread within zoonotic…

• A Short 5’triphosphate RNA nCoV-L Induces a Broad-Spectrum Antiviral Response by Activating RIG-I - Small molecular nucleic acid drugs produce antiviral effects by activating pattern recognition receptors (PRRs). In this study, a small molecular nucleotide containing 5’triphosphoric acid (5’PPP) and possessing a double-stranded structure was designed and named nCoV-L. nCoV-L was found to specifically activate RIG-I, induce interferon responses, and inhibit duplication of four RNA viruses (Human enterovirus 71, Human poliovirus 1, Human coxsackievirus B5 and Influenza A virus) in cells. In…

• Canine Coronavirus Activates Aryl Hydrocarbon Receptor during In Vitro Infection - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that interacts with substrates, including microbial metabolites. Recent advances reveal that AhR is involved in the host response to coronaviruses (CoVs) infection. Particularly, AhR antagonists decrease the expression of angiotensin-converting enzyme 2 (ACE2) via AhR up-regulation, resulting in suppression of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in mammalian cells. Herein, we report…

• An ACE2-Based Decoy Inhibitor Effectively Neutralizes SARS-CoV-2 Omicron BA.5 Variant - The recently circulating SARS-CoV-2 Omicron BA.5 is rampaging the world with elevated transmissibility compared to the original SARS-CoV-2 strain. Immune escape of BA.5 was observed after treatment with many monoclonal antibodies, calling for broad-spectrum, immune-escape-evading therapeutics. In retrospect, we previously reported Kansetin as an ACE2 mimetic and a protein antagonist against SARS-CoV-2, which proved potent neutralization bioactivity on the Reference, Alpha, Beta, Delta, and…

• Immunogenicity of an mRNA-Based COVID-19 Vaccine among Adolescents with Obesity or Liver Transplants - There are limited data regarding the immunogenicity of mRNA-based SARS-CoV-2 vaccine BNT162b2 among immunosuppressed or obese adolescents. We evaluated the humoral immune response in adolescents with obesity and adolescent liver transplant recipients (LTRs) after receiving two BNT162b2 doses. Sixty-eight participants (44 males; mean age 14.9 ± 1.7 years), comprising 12 LTRs, 24 obese, and 32 healthy adolescents, were enrolled. Immunogenicity was evaluated by anti-SARS-CoV-2 spike protein…

• In Silico Approach for the Evaluation of the Potential Antiviral Activity of Extra Virgin Olive Oil (EVOO) Bioactive Constituents Oleuropein and Oleocanthal on Spike Therapeutic Drug Target of SARS-CoV-2 - Since there is an urgent need for novel treatments to combat the current coronavirus disease 2019 (COVID-19) pandemic, in silico molecular docking studies were implemented as an attempt to explore the ability of selected bioactive constituents of extra virgin olive oil (EVOO) to act as potent SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) antiviral compounds, aiming to explore their ability to interact with SARS-CoV-2 Spike key therapeutic target protein. Our results suggest that…

• Identification of Doxorubicin as Repurposing Inhibitory Drug for MERS-CoV PLpro - Middle East respiratory syndrome coronavirus (MERS-CoV), belonging to the betacoronavirus genus can cause severe respiratory illnesses, accompanied by pneumonia, multiorgan failure, and ultimately death. CoVs have the ability to transgress species barriers and spread swiftly into new host species, with human-to-human transmission causing epidemic diseases. Despite the severe public health threat of MERS-CoV, there are currently no vaccines or drugs available for its treatment. MERS-CoV…

• Impact of TMPRSS2 Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2 - As a cellular protease, transmembrane serine protease 2 (TMPRSS2) plays roles in various physiological and pathological processes, including cancer and viral entry, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we conducted expression, mutation, and prognostic analyses for the TMPRSS2 gene in pan-cancers as well as in COVID-19-infected lung tissues. The results indicate that TMPRSS2 expression was highest in prostate cancer. A high expression of TMPRSS2 was…

• Homology Modeling and Molecular Dynamics-Driven Search for Natural Inhibitors That Universally Target Receptor-Binding Domain of Spike Glycoprotein in SARS-CoV-2 Variants - The rapid spread of SARS-CoV-2 required immediate actions to control the transmission of the virus and minimize its impact on humanity. An extensive mutation rate of this viral genome contributes to the virus’ ability to quickly adapt to environmental changes, impacts transmissibility and antigenicity, and may facilitate immune escape. Therefore, it is of great interest for researchers working in vaccine development and drug design to consider the impact of mutations on virus-drug interactions….

• Lentinus edodes Polysaccharides Alleviate Acute Lung Injury by Inhibiting Oxidative Stress and Inflammation - Acute lung injury (ALI) is a kind of lung disease with acute dyspnea, pulmonary inflammation, respiratory distress, and non-cardiogenic pulmonary edema, accompanied by the mid- and end-stage characteristics of COVID-19, clinically. It is imperative to find non-toxic natural substances on preventing ALI and its complications. The animal experiments demonstrated that Lentinus edodes polysaccharides (PLE) had a potential role in alleviating ALI by inhibiting oxidative stress and inflammation, which…

• Ultra-Large-Scale Screening of Natural Compounds and Free Energy Calculations Revealed Potential Inhibitors for the Receptor-Binding Domain (RBD) of SARS-CoV-2 - The emergence of immune-evading variants of SARS-CoV-2 further aggravated the ongoing pandemic. Despite the deployments of various vaccines, the acquired mutations are capable of escaping both natural and vaccine-induced immune responses. Therefore, further investigation is needed to design a decisive pharmacological treatment that could efficiently block the entry of this virus into cells. Hence, the current study used structure-based methods to target the RBD of the recombinant variant…

• Broad Antiviral Effects of Echinacea purpurea against SARS-CoV-2 Variants of Concern and Potential Mechanism of Action - SARS-CoV-2 variants of concern (VOCs) represent an alarming threat as they show altered biological behavior and may escape vaccination effectiveness. Broad-spectrum antivirals could play an important role to control infections. The activity of Echinacea purpurea (Echinaforce^(®) extract, EF) against (i) VOCs B1.1.7 (alpha), B.1.351.1 (beta), P.1 (gamma), B1.617.2 (delta), AV.1 (Scottish), B1.525 (eta), and B.1.1.529.BA1 (omicron); (ii) SARS-CoV-2 spike (S) protein-pseudotyped viral particles and…

• Glycyrrhizin Inhibits SARS-CoV-2 Entry into Cells by Targeting ACE2 - Coronavirus Disease 2019 (COVID-19) is a highly infectious and pathogenic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early in this epidemic, the herbal formulas used in traditional Chinese medicine (TCM) were widely used for the treatment of COVID-19 in China. According to Venn diagram analysis, we found that Glycyrrhizae Radix et Rhizoma is a frequent herb in TCM formulas against COVID-19. The extract of Glycyrrhizae Radix et Rhizoma exhibits an…

• The Expression Levels of SARS-CoV-2 Infection-Mediating Molecules Promoted by Interferon-γ and Tumor Necrosis Factor-α Are Downregulated by Hydrogen Sulfide - Autoimmune thyroid diseases (AITDs), which include Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), have a higher prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the literature. The effects of AITD-associated cytokines on SARS-CoV-2 infection-mediating molecule levels might be involved in the pathogenesis of susceptibility. We speculated that hydrogen sulfide (H(2)S) might attenuate this process since H(2)S has antiviral effects. Using…

From Patent Search