Covid-19 Sentry

Contents

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

From Preprints

• Mutual information networks reveal evolutionary relationships within the influenza A virus polymerase -
  The influenza A (IAV) RNA polymerase is an essential driver of IAV evolution. Mutations that the polymerase introduces into viral genome segments during replication are the ultimate source of genetic variation, including within the three subunits of the IAV polymerase (PB2, PB1, and PA). Evolutionary analysis of the IAV polymerase is complicated, because changes in mutation rate, replication speed, and drug resistance involve epistatic interactions among its subunits. In order to study the evolution of the human seasonal H3N2 polymerase since the 1968 pandemic, we identified pairwise evolutionary relationships among ~7000 H3N2 polymerase sequences using mutual information (MI), which measures the information gained about the identity of one residue when a second residue is known. To account for uneven sampling of viral sequences over time, we developed a weighted MI metric (wMI) and demonstrate that wMI outperforms raw MI through simulations using a well-sampled SARS-CoV-2 dataset. We then constructed wMI networks of the H3N2 polymerase to extend the inherently pairwise wMI statistic to encompass relationships among larger groups of residues. We included HA in the wMI network to distinguish between functional wMI relationships within the polymerase and those potentially due to hitchhiking on antigenic changes in HA. The wMI networks reveal coevolutionary relationships among residues with roles in replication and encapsidation. Inclusion of HA highlighted polymerase-only subgraphs containing residues with roles in the enzymatic functions of the polymerase and host adaptability. This work provides insight into the factors that drive and constrain the rapid evolution of influenza viruses.
  🖺 Full Text HTML: Mutual information networks reveal evolutionary relationships within the influenza A virus polymerase
• CD4+ and CD8+ T cell and antibody correlates of protection against Delta vaccine breakthrough infection: A nested case-control study within the PITCH study -

  T cell correlates of protection against SARS-CoV-2 infection after vaccination (9vaccine breakthrough9) are incompletely defined, especially the specific contributions of CD4+ and CD8+ T cells. We studied 279 volunteers in the Protective Immunity from T Cells in Healthcare Workers (PITCH) UK study, including 32 cases (with SARS-CoV-2 positive testing after two vaccine doses during the Delta-dominant era) and 247 controls (no positive test nor anti-nucleocapsid seroconversion during this period). 28 days after second vaccination, before all breakthroughs occurred, cases had lower ancestral S- and RBD-specific immunoglobulin G titres and S1- and S2-specific T cell interferon gamma (IFNγ) responses compared with controls. In a subset of matched cases and controls, cases had lower CD4+ and CD8+ IFNγ and tumour necrosis factor responses to Delta S peptides with reduced CD8+ responses to Delta versus ancestral peptides compared with controls. Our findings support a protective role for T cells against Delta breakthrough infection.

  🖺 Full Text HTML: CD4+ and CD8+ T cell and antibody correlates of protection against Delta vaccine breakthrough infection: A nested case-control study within the PITCH study
• Lives and Livelihood, Not Quite a Trade-Off: A Cross-Country Analysis of the Short-Term Impact of COVID-19 Mortality on Real GDP -

  Introduction. A supposed lives-livelihood trade-off (LLTO) has been at the centre stage of the COVID-19 pandemic, where policymakers often attempt to balance the health cost of COVID-19, including deaths, and the economic cost of lockdowns. Methodology. This paper uses country-level panel (longitudinal) data on real GDP, stringency of non-pharmaceutical interventions (NPIs), economic policy support, COVID-19 deaths, and vaccination to quantify the short-run LLTO. Beyond descriptive analysis, adjustments were made — (1) two-stage least squares instrumental variables in a cross-sectional setting using pre-pandemic institutional quality as the excluded instrument, and (2) two-way fixed effects in a panel data setting. Findings. Real GDP is negatively associated with COVID-19 deaths, as does more stringent containment measures. However, the offsetting positive association of real GDP with economic policy support is substantial. A historical decomposition of average real GDP that the positive attribution of fiscal support roughly equates the negative attribution of lockdown stringency and COVID-19 mortality. Conclusion. Cross-country empirical evidence suggests no direct tradeoff between the economy, and public health. A change in policy thinking from a LLTO paradigm to a 9no trade-off9 entails economic policy treating public health goals as invariant in supporting incomes through adequate, direct, and timely means.

  🖺 Full Text HTML: Lives and Livelihood, Not Quite a Trade-Off: A Cross-Country Analysis of the Short-Term Impact of COVID-19 Mortality on Real GDP
• Evaluation of SARS-CoV-2 isolation in cell culture from nasal/nasopharyngeal swabs or saliva specimens of patients with COVID-19 -
  It has been revealed that SARS-CoV-2 can be efficiently isolated from clinical specimens such as nasal/nasopharyngeal swabs or saliva in cultured cells. In this study, we examined the efficiency of viral isolation including SARS-CoV-2 mutant strains between nasal/nasopharyngeal swab or saliva specimens. Furthermore, we also examined the comparison of viral isolation rates by sample species using simulated specimens for COVID-19. As a result, it was found that the isolation efficiency of SARS-CoV-2 in the saliva specimens was significantly lower than that in the nasal/nasopharyngeal swab specimens. In order to determine which component of saliva is responsible for the lower isolation rate of saliva specimens, we tested the abilities of lactoferrin, amylase, cathelicidin, and mucin, which are considered to be abundant in saliva, to inhibit the infection of SARS-CoV-2 pseudotyped viruses (SARS-CoV-2pv). Lactoferrin and amylase were found to inhibit SARS-CoV-2pv infection. In conclusion, even if the same number of viral genome copies was detected by the real-time RT-PCR test, infection of SARS-CoV-2 present in saliva is thought to be inhibited by inhibitory factors such as lactoferrin and amylase, compared to nasal/nasopharyngeal swab specimens.
  🖺 Full Text HTML: Evaluation of SARS-CoV-2 isolation in cell culture from nasal/nasopharyngeal swabs or saliva specimens of patients with COVID-19
• A burns and COVID-19 shared stress responding gene network deciphers CD1C-CD141- DCs as the key cellular components in septic prognosis -
  Differential body responses to various stresses, infectious or noninfectious, govern clinical outcomes ranging from asymptoma to death. However, the common molecular and cellular nature of the stress responsome across different stimuli is not described. In this study, we compared the expression behaviors between burns and COVID-19 infection by choosing the transcriptome of peripheral blood from related patients as the analytic target since the blood cells reflect the systemic landscape of immune homeostasis. We identified an immune co-stimulator (CD86)-centered network, named stress-response core (SRC), which coordinated multiple immune processes and was robust in membership and highly related to the clinical traits in both burns and COVID-19. An independent whole blood single-cell RNA sequencing of COVID-19 patients demonstrated that the monocyte-dendritic cell (Mono-DC) wing was the major cellular source of the SRC, among which the higher expression of the SRC in the monocyte was associated with the asymptomatic COVID-19 patients, while the quantity-restricted and function-defected CD1C-CD141- DCs were recognized as the key signature which linked to bad consequences in COVID-19. Specifically, the proportion of the CD1C-CD141- DCs and their SRC expression levels were step-wise reduced along with worse clinic conditions while the sub-cluster of CD1C-CD141- DCs of the critical COVID-19 patients was characterized of IFN signaling quiescence, high mitochondrial metabolism and immune-communication inactivation. Thus, our study identified an expression-synchronized and function-focused gene network which was decreased under burns and COVID-19 stress and argued the CD1C-CD141- DC as the prognosis-related cell population which might serve as a new target of diagnosis and therapy.
  🖺 Full Text HTML: A burns and COVID-19 shared stress responding gene network deciphers CD1C-CD141- DCs as the key cellular components in septic prognosis
• CHARACTERISTICS OF ACUTE PSYCHIATRIC DISORDERS IN PATIENTS WITH COVID-19 IN A THIRD-LEVEL HOSPITAL IN PERU -

  Objective: To describe the sociodemographic and clinical characteristics of acute psychiatric disorders in COVID-19 patients in an emergency department at a national reference psychiatry and mental health hospital. Methods: A descriptive observational study was performed. Data were collected from medical records of patients admitted by emergency according to the International Classification of Diseases (ICD-11). The group of patients with a first acute psychiatric episode vs. patients with more than one acute psychiatric episode were compared. Results: 110 patients were included; 61.8% corresponded to the female sex and the mean age was 36 years. 49.1% corresponded to schizophrenia, followed by acute polymorphic psychotic disorder (13.6%), bipolar disorder (10%), and depressive episodes (7.3%). Psychotic disorders and depressive episodes occurred in a higher percentage in the group with a first episode, 42.4% (p< 0.001), and 15.2% (p< 0.001), respectively. The episodes of schizophrenia were higher in the group of patients with previous episodes (63.6%). Conclusions: A higher frequency of cases of acute psychotic disorder and depressive disorders was found as the first episode in patients with COVID-19 infection; however, within the group with previous episodes, greater predominance of patients with acute disorders due to schizophrenia was found.

  🖺 Full Text HTML: CHARACTERISTICS OF ACUTE PSYCHIATRIC DISORDERS IN PATIENTS WITH COVID-19 IN A THIRD-LEVEL HOSPITAL IN PERU
• Effectiveness of SARS-CoV-2 Vaccines against Omicron Infection and Severe Events: A Systematic Review and Meta-Analysis of Test-Negative Design Studies -

  Background: Evaluating vaccine effectiveness (VE) of a full vaccine series and booster doses against COVID-19 is important for health decision-making. Methods: We systematically searched papers that evaluated VE of SARS-CoV-2 vaccines on PubMed, Web of Science, Cochrane Library, Google Scholar, Embase, Scopus, and preprint servers (bioRxiv and medRxiv) published from November 26th, 2021 to June 27th, 2022 (for full doses and first booster), and to January 8th, 2023 (for the second booster). The pooled VE against Omicron-associated symptomatic or any infection as well as severe events are estimated in a meta-analysis framework. Results: From 2,552 citations identified, a total of 42 were included. The vaccination of the first booster provided stronger protection against Omicron than the full doses alone, shown by the VE estimates of 53.1% (95% CI: 48.0-57.8) vs. 28.6% (95% CI: 18.5-37.4) against infection and 82.5% (95% CI: 77.8-86.2) vs. 57.3% (95% CI: 48.5-64.7) against severe disease. The second booster offered strong protection among adults within 60 days of vaccination against infection (VE=53.1%, 95% CI: 48.0-57.8) and severe disease (VE=87.3% (95% CI: 75.5-93.4), comparable to the first booster with corresponding VE estimates of 59.9% against infection and 84.8% against severe disease. The VEs of the booster doses against severe disease among adults sustained beyond 60 days, 77.6% (95% CI: 69.4-83.6) for the first and 85.9% (95% CI: 80.3-89.9) for the second booster. The VE against infection was less sustainable regardless of dose type. Pure mRNA vaccines provided comparable protection to partial mRNA vaccines, but both provided higher protection than non-mRNA vaccination. Conclusion: One or two booster doses of current SARS-CoV-2 vaccines provide considerable protection against Omicron infection and substantial and sustainable protection against Omicron-induced severe clinical outcomes.

  🖺 Full Text HTML: Effectiveness of SARS-CoV-2 Vaccines against Omicron Infection and Severe Events: A Systematic Review and Meta-Analysis of Test-Negative Design Studies
• Composite Deep Network with Feature Weighting for Improved Delineation of COVID Infection in Lung CT -

  An early effective screening and grading of COVID-19 has become imperative towards optimizing the limited available resources of the medical facilities. An automated segmentation of the infected volumes in lung CT is expected to significantly aid in the diagnosis and care of patients. However, an accurate demarcation of lesions remains problematic due to their irregular structure and location(s) within the lung. A novel deep learning architecture, Composite Deep network with Feature Weighting (CDNetFW), is proposed for efficient delineation of infected regions from lung CT images. Initially a coarser-segmentation is performed directly at shallower levels, thereby facilitating discovery of robust and discriminatory characteristics in the hidden layers. The novel feature weighting module helps prioritise relevant feature maps to be probed, along with those regions containing crucial information within these maps. This is followed by estimating the severity of the disease. The deep network CDNetFW has been shown to outperform several state-of-the-art architectures in the COVID-19 lesion segmentation task, as measured by experimental results on CT slices from publicly available datasets, especially when it comes to defining structures involving complex geometries.

  🖺 Full Text HTML: Composite Deep Network with Feature Weighting for Improved Delineation of COVID Infection in Lung CT
• Inflammasome activation and pulmonary viral loads define two distinct clinical outcomes in COVID-19 -

  COVID-19 has affected more than half a billion people worldwide, with more than 6.3 million deaths, but the pathophysiological mechanisms involved in lethal cases and the host determinants that determine the different clinical outcomes are still unclear. In this study, we assessed lung autopsies of 47 COVID-19 patients and examined the inflammatory profiles, viral loads, and inflammasome activation. Additionally, we correlated these factors with the patients clinical and histopathological conditions. Robust inflammasome activation, mediated by macrophages and endothelial cells, was detected in the lungs of lethal cases of SARS-CoV-2. An analysis of gene expression allowed for the classification of COVID-19 patients into two different clusters. Cluster 1 died with higher viral loads and exhibited a reduced inflammatory profile than Cluster 2. Illness time, mechanical ventilation time, pulmonary fibrosis, respiratory functions, histopathological status, thrombosis, viral loads and inflammasome activation significantly differed between the two clusters. Our data demonstrated two distinct profiles in lethal cases of COVID-19, thus indicating that the balance of viral replication and inflammasome-mediated pulmonary inflammation led to different clinical outcomes. We provide important information to understand clinical variations in severe COVID-19, a process that is critical for decisions between immune-mediated or antiviral-mediated therapies for the treatment of critical cases of COVID-19.

  🖺 Full Text HTML: Inflammasome activation and pulmonary viral loads define two distinct clinical outcomes in COVID-19
• Integrative modelling of reported case numbers and seroprevalence reveals time-dependent test efficiency and infection rates -

  Mathematical models have been widely used during the ongoing SARS-CoV-2 pandemic for data interpretation, forecasting, and policy making. However, most models are based on officially reported case numbers, which depend on test availability and test strategies. The time dependence of these factors renders interpretation difficult and might even result in estimation biases. Here, we present a computational modelling framework that allows for the integration of reported case numbers with seroprevalence estimates obtained from representative population cohorts. To account for the time dependence of infection and testing rates, we embed flexible splines in an epidemiological model. The parameters of these splines are estimated, along with the other parameters, from the available data using a Bayesian approach. The application of this approach to the official case numbers reported for Munich (Germany) and the seroprevalence reported by the prospective COVID-19 Cohort Munich (KoCo19) provides first estimates for the time dependence of the under-reporting factor. Furthermore, we estimate how the effectiveness of non-pharmaceutical interventions and of the testing strategy evolves over time. Overall, our results show that the integration of temporally highly resolved and representative data is beneficial for accurate epidemiological analyses.

  🖺 Full Text HTML: Integrative modelling of reported case numbers and seroprevalence reveals time-dependent test efficiency and infection rates
• Being cut off from social identity resources has shaped loneliness during the COVID-19 pandemic: A longitudinal interview study with medically vulnerable older adults from the United Kingdom -
  Older adulthood is often a time of identity change arising from physical decline and social isolation which can increase loneliness. These effects are thought to be exacerbated by public health threats such as COVID-19 which disproportionately restrict older adults, though research has yet to fully explore how this occurs. We used a Qualitative Longitudinal Research (QLR) interview approach to follow nine vulnerable older adults (Mage=79.4) for fourteen months through 2019 and 2020 in order to understand their unfolding experiences of pandemic-related isolation. A theoretically guided thematic analysis found that participants initially experienced “Threatened Social Contact” due to age-related vulnerabilities which reduced their ability to manage “Being Categorised as a Vulnerable Older Person”. Consequently, participants experienced a “Restriction in Ability to Gain or Maintain Identities” leading to “Undermining of Reciprocal Support” and “Wellbeing hindered by Loneliness-Related Fears”. Findings highlighted that COVID-19 exacerbates existing negative age-related categorisations, contributing to a loss of reciprocal support in older adulthood. More generally, interventions to ameliorate loneliness among older adults would benefit from explicitly addressing ageism as well as enhancing group-based connectedness.
  🖺 Full Text HTML: Being cut off from social identity resources has shaped loneliness during the COVID-19 pandemic: A longitudinal interview study with medically vulnerable older adults from the United Kingdom
• Using Managers’ Expectations for Ex-ante Policy Evaluation: Evidence from the COVID-19 Crisis -
  Evaluation of the impacts of government policies during an economic crisis is often delayed until the outcomes are realized. Policies can be better guided if they can be evaluated amid a crisis, before the realization of outcomes. This study examines whether survey data on the expectations of small business managers can help evaluate two high-stake subsidies for firms amid the COVID-19 crisis in Japan, namely, Subsidy Program for Sustaining Businesses (SPSB) and Employment Adjustment Subsidy (EAS). We evaluate the accuracy of managers’ expectations, estimate the impact of subsidies on the expected firm survival, and compare it with the estimated impact on realized survival. We find that the managers’ expectations on their future sales, survival rate, and the possibility of receiving these subsidies predict the realized outcomes, although they were highly pessimistic about their survival rates. We find that the estimated impacts of the SPSB on the expected survival rates have the same sign as the estimated impact on the realized survival rates, but the size is more than twice because of the pessimism on survival. The estimated impacts of the EAS are both insignificant. Therefore, although its impact may be overestimated, managers’ expectations are useful for selecting an effective policy.
  🖺 Full Text HTML: Using Managers’ Expectations for Ex-ante Policy Evaluation: Evidence from the COVID-19 Crisis
• Estimates of protection against SARS-CoV-2 infection and severe COVID-19 in Germany before the 2022/2023 winter season - the IMMUNEBRIDGE project -

  Despite the need to generate valid and reliable estimates of protection against SARS-CoV-2 infection and severe course of COVID-19 for the German population in summer 2022, there was a lack of systematically collected population-based data allowing for the assessment of the protection level in real-time. In the IMMUNEBRIDGE project, we harmonised data and biosamples for nine population-/hospital-based studies (total number of participants n=33,637) to provide estimates for protection levels against SARS-CoV-2 infection and severe COVID-19 between June and November 2022. Based on evidence synthesis, we formed a combined endpoint of protection levels based on the number of self-reported infections/vaccinations in combination with nucleocapsid/spike antibody responses (“confirmed exposures”). Four confirmed exposures represented the highest protection level, and no exposure represented the lowest. Most participants were seropositive against the spike antigen; 37% of the participants ≥79 years had less than four confirmed exposures (highest level of protection) and 5% less than three. In the subgroup of participants with comorbidities, 46-56% had less than four confirmed exposures. We found major heterogeneity across federal states, with 4%-28% of participants having less than three confirmed exposures. Using serological analyses, literature synthesis and infection dynamics during the survey period, we observed moderate to high levels of protection against severe COVID-19, whereas the protection against SARS-CoV-2 infection was low across all age groups. We found relevant protection gaps in the oldest age group and amongst individuals with comorbidities, indicating a need for additional protective measures in these groups.

  🖺 Full Text HTML: Estimates of protection against SARS-CoV-2 infection and severe COVID-19 in Germany before the 2022/2023 winter season - the IMMUNEBRIDGE project
• Construction of Fosmid-based SARS-CoV-2 replicons for antiviral drug screening and replication analyses in biosafety level 2 facilities -
  The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has necessitated the global development of countermeasures since its outbreak. However, current therapeutics and vaccines to stop the pandemic are insufficient and this is mainly because of the emergence of resistant variants, which requires the urgent development of new countermeasures, such as antiviral drugs. Replicons, self-replicating RNAs that do not produce virions, are a promising system for this purpose because they safely recreate viral replication, enabling antiviral screening in biosafety level (BSL)-2 facilities. We herein constructed three pCC2Fos-based RNA replicons lacking some open reading frames (ORF) of SARS-CoV-2: the Dorf2-8, {Delta}orf2.4, and {Delta}orf2 replicons, and validated their replication in Huh-7 cells. The functionalities of the {Delta}orf2-8 and {Delta}orf2.4 replicons for antiviral drug screening were also confirmed. We conducted puromycin selection following the construction of the {Delta}orf2.4-puro replicon by inserting a puromycin-resistant gene into the {Delta}orf2.4 replicon. We observed the more sustained replication of the {Delta}orf2.4-puro replicon by puromycin pressure. The present results will contribute to the establishment of a safe and useful replicon system for analyzing SARS-CoV-2 replication mechanisms as well as the development of novel antiviral drugs in BSL-2 facilities.
  🖺 Full Text HTML: Construction of Fosmid-based SARS-CoV-2 replicons for antiviral drug screening and replication analyses in biosafety level 2 facilities
• Factors associated with adverse outcomes among patients hospitalized at a COVID-19 treatment center run by Médecins sans Frontières in Herat, Afghanistan -

  Background Though many studies on COVID have been published to date, data on COVID-19 epidemiology, symptoms, risk factors and severity in low- and middle-income countries (LMICS), such as Afghanistan are sparse. Objective To describe clinical characteristics, severity, and outcomes of patients hospitalized in the MSF COVID-19 treatment center (CTC) in Herat, Afghanistan and to assess risk factors associated with severe outcomes. Methods 1113 patients were included in this observational study between June 2020 and April 2022. Descriptive analysis was performed on clinical characteristics, complications, and outcomes of patients. Univariate description by Cox regression to identify risk factors for an adverse outcome was performed. Adverse outcome was defined as death or transfer to a level 3 intensive care located at another health facility. Finally, factors identified were included in a multivariate Cox survival analysis. Results A total of 165 patients (14.8%) suffered from a severe disease course, with a median time of 6 days (interquartile range: 2-11 days) from admission to adverse outcome. In our multivariate model, we identified male gender, age over 50, high O2 flow administered during admission, lymphopenia, anemia and O2 saturation <=93% during the first three days of admission as predictors for a severe disease course (p<0.05). Conclusion Our analysis concluded in a relatively low rate of adverse outcomes of 14.8%. This is possibly related to the fact, that the resources at an MSF-led facility are higher, in terms of human resources as well as supply of drugs and biomedical equipment, including oxygen therapy devices, compared to local hospitals. Predictors for severe disease outcomes were found to be comparable to other settings.

  🖺 Full Text HTML: Factors associated with adverse outcomes among patients hospitalized at a COVID-19 treatment center run by Médecins sans Frontières in Herat, Afghanistan

From Clinical Trials

• MG Granules Improve COVID-19 Efficacy and Safety of Convalescent Exercise Tolerance - Condition:   COVID-19
  Intervention:   Drug: Manzi Guben granules
  Sponsors:   Second Affiliated Hospital, School of Medicine, Zhejiang University;   The First Affiliated Hospital of Zhejiang Chinese Medical University;   Hangzhou Hospital of Traditional Chinese Medicine;   Suzhou Hospital of Traditional Chinese Medicine
  Not yet recruiting

• Effects of Pilates in Patients With Post- -COVID-19 Syndrome: Controlled and Randomized Clinical Trial - Condition:   COVID-19
  Intervention:   Procedure: Pilates Exercises
  Sponsor:   Michele de Aguiar Zacaria
  Recruiting

• Heterologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine in Children 12-17 Years of Age - Condition:   COVID-19
  Intervention:   Biological: SARS-CoV-2 subunit protein recombinant vaccine
  Sponsors:   PT Bio Farma;   Faculty of Medicine Universitas Padjadjaran
  Not yet recruiting

• Improving Adherence to COVID-19 Prevention Behaviours: Test of Persuasive Messages - Condition:   COVID-19
  Intervention:   Behavioral: Persuasive Appeal
  Sponsor:   University of Calgary
  Completed

• Incidence of COVID-19 Following Vaccination in Botswana Against SARS CoV 2 - Condition:   COVID-19
  Intervention:   Drug: AZD 1222
  Sponsors:   Botswana Harvard AIDS Institute Partnership;   AstraZeneca;   Botswana Ministry of Health
  Completed

• Study Evaluating GS-5245 in Nonhospitalized Participants With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: GS-5245;   Drug: GS-5245 Placebo
  Sponsor:   Gilead Sciences
  Not yet recruiting

• A Study To Assess The Efficacy and Safety of HH-120 Nasal Spray for the Treatment of Mild COVID-19 - Condition:   COVID-19
  Interventions:   Drug: HH-120 nasal spray;   Drug: Placebo Comparator
  Sponsor:   Huahui Health
  Recruiting

• Study for Efficacy and Safety Assessment of the Drug RADAMIN®VIRO for COVID-19 Postexposure Prophylaxis - Condition:   COVID-19
  Interventions:   Drug: Double-Stranded RNA sodium salt;   Drug: Placebo
  Sponsor:   Promomed, LLC
  Completed

• Study of Flonoltinib Maleate Tablets in the Treatment of Severe Novel Coronavirus (COVID-19) Infection - Condition:   COVID-19
  Interventions:   Drug: VV116+SOC;   Drug: SOC
  Sponsor:   Chengdu Zenitar Biomedical Technology Co., Ltd
  Recruiting

• Study to Access the Efficacy and Safety of STI-1558 in Adult Subjects With Mild or Moderate (COVID-19) - Condition:   COVID-19
  Interventions:   Drug: STI-1558;   Drug: STI-1558 placebo
  Sponsor:   Zhejiang ACEA Pharmaceutical Co. Ltd.
  Not yet recruiting

• Pirfenidone in Adult Hospitalized Patients With COVID-19 - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: Pirfenidone Oral Product;   Drug: Pirfenidone placebo
  Sponsor:   Capital Medical University
  Active, not recruiting

• Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cells in the Treatment of Long COVID-19 - Condition:   Long COVID-19
  Intervention:   Biological: UC-MSCs
  Sponsor:   Shanghai East Hospital
  Not yet recruiting

• CONFIDENCE: a Multicomponent Clinic-based Intervention to Promote COVID-19 Vaccine Intention and Uptake Among Diverse Youth and Adolescents - Condition:   COVID-19 Vaccination
  Intervention:   Behavioral: CONFIDENCE
  Sponsors:   University of Massachusetts, Worcester;   Merck Sharp & Dohme LLC;   Baystate Health
  Not yet recruiting

• Cognitive Rehabilitation for People With Cognitive Covid19 - Condition:   Long Covid19
  Intervention:   Behavioral: Cognitive rehabilitation
  Sponsors:   University College, London;   Bangor University;   St George’s University Hospitals NHS Foundation Trust;   University of Brighton;   University Hospital Southampton NHS Foundation Trust;   Greater Manchester Mental Health NHS Foundation Trust
  Not yet recruiting

• MGC Health COVID-19 & Flu A+B Home Multi Test Usability Study - Conditions:   COVID-19;   Influenza A;   Influenza B
  Interventions:   Diagnostic Test: MGC Health COVID-19 & Flu A+B Home Multi Test;   Diagnostic Test: MGC Health COVID-19 & Flu A+B Home Multi Test (2 to 13 y/o)
  Sponsors:   Medical Group Care, LLC;   CSSi Life Sciences
  Recruiting

From PubMed

• Effect of DPP4/CD26 expression on SARS‑CoV‑2 susceptibility, immune response, adenosine (derivatives m⁶₂A and CD) regulations on patients with cancer and healthy individuals - The worldwide COVID‑19 pandemic was brought on by a new coronavirus (SARS Cov‑2). A marker/receptor called Dipeptidyl peptidase 4/CD26(DPP4/CD26) may be crucial in determining susceptibility to tumors and coronaviruses. However, the regulation of DPP4 in COVID‑invaded cancer patients and its role on small molecule compounds remain unclear. The present study used the Human Protein Atlas, Monaco, and Schmiedel databases to analyze the expression of DPP4 in human tissues and immune cells. The…

• P2X7 purinergic receptor: A potential target in heart diseases (Review) - The P2X7 purinergic receptor (P2X7R) is a non‑selective cation channel activated by high levels of adenosine triphosphate that are commonly present in serious conditions. Activation of this purinergic receptor is closely related to the development of various disease states including inflammatory and neurodegenerative disorders, orthopedic diseases and types of cancer. Accumulating evidence has shown that the P2X7R plays a crucial role in the development of various heart diseases. For example,…

• The OM-85 bacterial lysate: a new tool against SARS-CoV-2? - The emergence of SARS-CoV-2, a novel coronavirus, caused the global Coronavirus disease of 2019 (COVID-19) pandemic. Because SARS-CoV-2 mutates rapidly, vaccines that induce immune responses against viral components critical for target cell infection strongly mitigate but do not abrogate viral spread, and disease rates remain high worldwide. Complementary treatments are therefore needed to reduce the frequency and/or severity of SARS-CoV-2 infections. OM-85, a standardized lysate of 21 bacterial…

• Renin-Angiotensin-Aldosterone Axis Inhibition Improves Outcome of Diabetic Patients with Chronic Hypertension and COVID-19: An Iranian Perspective - CONCLUSIONS: The current study suggests that ACE inhibitors and ARBs are associated with decreased mortality, ICU admission, and better ICU survival in the diabetic subgroup of hypertensive patients.

• Nanoscale Interaction Mechanisms of Antiviral Activity - Nanomaterials have now found applications across all segments of society including but not limited to energy, environment, defense, agriculture, purification, food medicine, diagnostics, and others. The pandemic and the vulnerability of humankind to emerging viruses and other infectious diseases has renewed interest in nanoparticles as a potential new class of antivirals. In fact, a growing body of evidence in the literature suggests nanoparticles may have activity against multiple viruses…

• Novel Investigational Anti-SARS-CoV-2 Agent Ensitrelvir “S-217622”: A Very Promising Potential Universal Broad-Spectrum Antiviral at the Therapeutic Frontline of Coronavirus Species - Lately, nitrogenous heterocyclic antivirals, such as nucleoside-like compounds, oxadiazoles, thiadiazoles, triazoles, quinolines, and isoquinolines, topped the therapeutic scene as promising agents of choice for the treatment of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and their accompanying ailment, the coronavirus disease 2019 (COVID-19). At the same time, the continuous emergence of new strains of SARS-CoV-2, like the Omicron variant and its multiple…

• High SARS-CoV-2 tropism and activation of immune cells in the testes of non-vaccinated deceased COVID-19 patients - CONCLUSIONS: Our findings indicate that high angiotensin II levels and activation of mast cells and macrophages may be critical for testicular pathogenesis. Importantly, our findings suggest that patients who become critically ill may exhibit severe alterations and harbor the active virus in the testes.

• Effect of chitooligosaccharide on the inhibition of SARS-CoV-2 main protease - CONCLUSION: This study provides the theoretical basis to develop targeted Mpro inhibitors for the screening and application of anti-novel coronavirus drugs.

• Novel dithiocarbamates selectively inhibit 3CL protease of SARS-CoV-2 and other coronaviruses - Since end of 2019, the global and unprecedented outbreak caused by the coronavirus SARS-CoV-2 led to dramatic numbers of infections and deaths worldwide. SARS-CoV-2 produces two large viral polyproteins which are cleaved by two cysteine proteases encoded by the virus, the 3CL protease (3CL^(pro)) and the papain-like protease, to generate non-structural proteins essential for the virus life cycle. Both proteases are recognized as promising drug targets for the development of anti-coronavirus…

• Screen for Modulation of Nucleocapsid Protein Condensation Identifies Small Molecules with Anti-Coronavirus Activity - Biomolecular condensates formed by liquid-liquid phase separation have been implicated in multiple diseases. Modulation of condensate dynamics by small molecules has therapeutic potential, but so far, few condensate modulators have been disclosed. The SARS-CoV-2 nucleocapsid (N) protein forms phase-separated condensates that are hypothesized to play critical roles in viral replication, transcription, and packaging, suggesting that N condensation modulators might have anti-coronavirus activity…

• Synthesis, X-ray crystal structure, Hirshfeld surface analysis and computational investigation into the potential inhibitory action of novel 6-(p-tolyl)-2-((p-tolyl)thio)methyl-7H-[1.2.4]triazolo[5,1-b][1,3,4]thiadiazine inhibits the main protease of COVID-19 - In recent times, the novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now become a worldwide pandemic. With over 71 million confirmed cases, even though the effectiveness and side effects of the specific drugs and vaccines approved for this disease are still limited. Scientists and researchers from all across the world are working to find a vaccine and a cure for COVID-19 by using large-scale drug discovery and analysis….

• The effect of vitamin C supplementation on favipiravir-induced oxidative stress and proinflammatory damage in livers and kidneys of rats - Favipiravir (FPV), an effective antiviral agent, is a drug used to treat influenza and COVID-19 by inhibiting the RNA-dependent RNA polymerase (RdRp) of RNA viruses. FPV has the potential to increase oxidative stress and organ damage. The purpose of this study was to demonstrate the oxidative stress and inflammation caused by FPV in the liver and kidneys of rats, as well as to investigate the curative effects of vitamin C (VitC). A total of 40 Sprague-Dawley male rats were randomly and equally…

• Supporting and inhibiting factors of accepting COVID-19 booster vaccination in the elderly in north Jakarta, Indonesia - CONCLUSIONS: Most of the elderly displayed positive attitudes concerning booster shots, but it was discovered that some barriers need to be removed.

• Comparison of the mucosal and systemic antibody responses in Covid-19 recovered patients with one dose of mRNA vaccine and unexposed subjects with three doses of mRNA vaccines - CONCLUSION: The booster benefited all subjects to obtain neutralizing antibody (NAb) against omicron BA.1 variant in plasma while only the Covid-19 recovered subjects had an extra enrichment in nasal NAb against omicron BA.1 variant.

• The development and validation of the pandemic medication-assisted treatment questionnaire for the assessment of pandemic crises impact on medication management and administration for patients with opioid use disorders - Pandemic and the globally applied restriction measures mainly affect vulnerable population groups, such as patients with opioid use disorders. Towards inhibiting SARS-Cov-2 spread, the medication-assisted treatment (MAT) programs follow strategies targeting the reduction of in-person psychosocial interventions and an increase of take-home doses. However, there is no available instrument to examine the impact of such modifications on diverse health aspects of patients under MAT. The aim of this…

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