Covid-19 Sentry

Contents

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

From Preprints

• Hierarchical assembly of single-stranded RNA -
  Single-stranded RNA (ssRNA) plays a major role in the flow of genetic information–most notably in the form of messenger RNA (mRNA)–and in the regulation of biological processes. The highly dynamic nature of chains of unpaired nucleobases challenges structural characterizations of ssRNA by experiments or molecular dynamics (MD) simulations alike. Here we use hierarchical chain growth (HCG) to construct ensembles of ssRNA chains. HCG assembles the structures of protein and nucleic acid chains from fragment libraries created by MD simulations. Applied to homo- and heteropolymeric ssRNAs of different lengths, we find that HCG produces structural ensembles that overall are in good agreement with diverse experiments including nuclear magnetic resonance (NMR), small-angle X-ray scattering (SAXS), and single-molecule Forster resonance energy transfer (FRET). The agreement can be further improved by ensemble refinement using Bayesian inference of ensembles (BioEn). HCG can also be used to assemble RNA structures that combine base-paired and unpaired regions, as illustrated for the 5’ untranslated region (UTR) of SARS-CoV-2 mRNA.
  🖺 Full Text HTML: Hierarchical assembly of single-stranded RNA
• Intestinal microbiota programming of alveolar macrophages influences severity of respiratory viral infection -
  Investigating the influence of intestinal microbiota composition on respiratory viral infection (RVI) revealed that segmented filamentous bacteria (SFB), naturally acquired or exogenously administered, protected mice against influenza virus (IAV) infection, as assessed by viral titers, histopathology, and clinical disease features. Such protection, which also applied to RSV and SARS-CoV-2, was independent of interferon and adaptive immunity but required basally resident alveolar macrophages (AM), which, in SFB-negative mice, were quickly depleted as RVI progressed. Examination of AM from SFB-colonized mice revealed that they were intrinsically altered to resist IAV-induced depletion and inflammatory signaling. Yet, AM from SFB-colonized mice were not quiescent. Rather, they directly disabled IAV via enhanced complement production and phagocytosis. Transplant of SFB-transformed AM into SFB-free hosts recapitulated SFB-mediated protection against IAV mechanistically linking intestinal microbiota, AM phenotype, and RVI severity.
  🖺 Full Text HTML: Intestinal microbiota programming of alveolar macrophages influences severity of respiratory viral infection
• TMPRSS2 activation of Omicron lineage Spike glycoproteins is regulated by TMPRSS2 cleavage of ACE2 -
  Continued high levels spread of SARS-CoV-2 globally enabled accumulation of changes within the Spike glycoprotein, leading to resistance to neutralising antibodies and concomitant changes to entry requirements that increased viral transmission fitness. Herein, we demonstrate a significant change in ACE2 and TMPRSS2 use by primary SARS-CoV-2 isolates that occurred upon arrival of Omicron lineages. Mechanistically we show this shift to be a function of two distinct ACE2 pools based on cleavage or non-cleavage of ACE2 by TMPRSS2 activity. In engineered cells overexpressing ACE2 and TMPRSS2, ACE2 was cleaved by TMPRSS2 and this led to either augmentation or progressive attenuation of pre-Omicron and Omicron lineages, respectfully. In contrast, TMPRSS2 resistant ACE2 restored infectivity across all Omicron lineages through enabling ACE2 binding that facilitated TMPRSS2 spike activation. Therefore, our data support the tropism shift of Omicron lineages to be a function of evolution towards the use of uncleaved pools of ACE2 with the latter consistent with its role as a chaperone for many tissue specific amino acid transport proteins.
  🖺 Full Text HTML: TMPRSS2 activation of Omicron lineage Spike glycoproteins is regulated by TMPRSS2 cleavage of ACE2
• Healthcare system barriers impacting the care of Canadians with myalgic encephalomyelitis: a scoping review -

  Background: Myalgic encephalomyelitis (ME, also known as chronic fatigue syndrome or ME/CFS) is a debilitating, complex, multi-system illness. Developing a comprehensive understanding of the multiple and interconnected barriers to optimal care will help advance strategies and care models to improve quality of life for people living with ME in Canada. Objectives: To: (1) identify and systematically map the available evidence; (2) investigate the design and conduct of research; (3) identify and categorize key characteristics; and (4) identify and analyze knowledge gaps related to healthcare system barriers for people living with ME in Canada. Methods: The protocol was preregistered in July 2022. Peer-reviewed and grey literature was searched, and patient partners retrieved additional records. Eligible records were Canadian, included people with ME/CFS and included data or synthesis relevant to healthcare system barriers. Results: In total, 1821 records were identified, 406 were reviewed in full, and 21 were included. Healthcare system barriers arose from an underlying lack of consensus and research on ME and ME care; the impact of long-standing stigma, disbelief, and sexism; inadequate or inconsistent healthcare provider education and training on ME; and the heterogeneity of care coordinated by family physicians. Conclusions: People living with ME in Canada face significant barriers to care, though this has received relatively limited attention. This synthesis, which points to several areas for future research, can be used as a starting point for researchers, healthcare providers and decision-makers who are new to the area or encountering ME more frequently due to the COVID-19 pandemic.

  🖺 Full Text HTML: Healthcare system barriers impacting the care of Canadians with myalgic encephalomyelitis: a scoping review
• Spatio-temporal surveillance and early detection of SARS-CoV-2 variants of concern: a retrospective analysis -

  The SARS-CoV-2 pandemic has been characterized by the repeated emergence of genetically distinct virus variants of increased transmissibility and immune evasion compared to pre-existing lineages. In many countries, their containment required the intervention of public health authorities and the imposition of control measures. While the primary role of testing is to identify infection, target treatment, and limit spread (through isolation and contact tracing), a secondary benefit is in terms of surveillance and the early detection of new variants. Here we study the spatial invasion and early spread of the Alpha, Delta, and Omicron (BA.1 and BA.2) variants in England from September 2020 to February 2022 using the random neighbourhood covering (RaNCover) method. This is a statistical technique for the detection of aberrations in spatial point processes, which we tailored here to community PCR (polymerase-chain-reaction) test data where the TaqPath kit provides a proxy measure of the switch between variants. Retrospectively, RaNCover detected the earliest signals associated with the four novel variants that led to large infection waves in England. With suitable data our method therefore has the potential to rapidly detect outbreaks of future SARS-CoV-2 variants, thus helping to inform targeted public health interventions.

  🖺 Full Text HTML: Spatio-temporal surveillance and early detection of SARS-CoV-2 variants of concern: a retrospective analysis
• Human origin ascertained for SARS-CoV-2 Omicron-like spike sequences detected in wastewater: a targeted surveillance study of a cryptic lineage in an urban sewershed -

  Summary Background: The origin of novel SARS-CoV-2 spike sequences found in wastewater, without corresponding detection in clinical specimens, remains unclear. We sought to determine the origin of one such “cryptic” wastewater lineage by tracking and characterizing its persistence and genomic evolution over time. Methods: We first detected a cryptic lineage in Wisconsin municipal wastewater in January 2022. By systematically sampling wastewater from targeted sub-sewershed lines and maintenance holes using compositing autosamplers, we traced this lineage (labeled WI-CL-001) to its source at a single commercial building. There we detected WI-CL-001 at concentrations as high as 2.7 x 109 genome copies per liter (gc/L) via RT-dPCR. In addition to using metagenomic 12s rRNA sequencing to determine the virus9s host species, we also sequenced SARS-CoV-2 spike receptor binding domains (RBDs), and where possible, whole viral genomes to identify and characterize the evolution of this lineage over the 13 consecutive months that it was detectable. Findings: The vast majority of 12s rRNAs sequenced from wastewater leaving the identified source building were human. Additionally, we generated over 100 viral RBD and whole genome sequences from wastewater samples containing the cryptic lineage collected between January 2022 and January 2023. These sequences contained a combination of fixed nucleotide substitutions characteristic of Pango lineage B.1.234, which circulated in humans in Wisconsin at low levels from October 2020 to February 2021. Despite this, mutations in the spike gene, and elsewhere, resembled those subsequently found in Omicron variants. Interpretation: We propose that prolonged detection of WI-CL-001 in wastewater represents persistent shedding of SARS-CoV-2 from a single human initially infected by an ancestral B.1.234 virus. The accumulation of convergent “Omicron-like” mutations in WI-CL-0019s ancestral B.1.234 genome likely reflects persistent infection and extensive within-host evolution. Funding: The Rockefeller Foundation, Wisconsin Department of Health Services, Centers for Disease Control and Prevention (CDC), National Institute on Drug Abuse (NIDA), and the Center for Research on Influenza Pathogenesis and Transmission. Research in context Evidence before this study: To identify other studies that characterized unusual wastewater-specific SARS-CoV-2 lineages, we conducted a PubMed search using the keywords “cryptic SARS-CoV-2 lineages” or “novel SARS-CoV-2 lineages” in addition to “wastewater” on May 9, 2023. From the 18 papers retrieved, only two reported wastewater-specific cryptic lineages. These lineages were identified by members of our author team in wastewater from California, Missouri, and New York City. None of these could be definitively traced to a specific source. A third study in Nevada identified a unique recombinant variant (designated Pango lineage XL) in wastewater, which was also discovered in two clinical specimens from the same community. However, it was unclear whether the clinical specimens collected were from the same individual(s) responsible for the virus detected in the wastewater. To our knowledge, no prior study has successfully traced novel SARS-CoV-2 lineages detected in wastewater back to a specific location. How and where cryptic lineages are introduced into wastewater is not known. The added value of this study: This study documents the presence and likely source of a novel and highly divergent cryptic SARS-CoV-2 lineage detected in Wisconsin wastewater for 13 months. In contrast to previously reported cryptic lineages, we successfully traced the lineage (WI-CL-001) to a single commercial building with approximately 30 employees. The exceptionally high viral RNA concentrations at the source building facilitated the tracing effort and allowed for the sequencing of WI-CL-0019s whole genome, expanding our view of the lineage9s mutational landscape beyond the spike gene. Implications of all the available evidence: WI-CL-0019s persistence in wastewater, its heavily mutated Omicron-like genotype, and its identified point source at a human-occupied commercial building all support the hypothesis that cryptic wastewater lineages can arise from persistently infected humans. Because cryptic wastewater lineages have some amino acid changes that subsequently emerge in circulating viruses, increased global monitoring of such lineages could help forecast variants that may arise in the future.

  🖺 Full Text HTML: Human origin ascertained for SARS-CoV-2 Omicron-like spike sequences detected in wastewater: a targeted surveillance study of a cryptic lineage in an urban sewershed
• Occupational Health Management in New Work - a Protocol for a Mixed-Method Study: Project BGM4NewWork -

  Background: The world of work is undergoing profound changes towards agile, flexible, democratic, and digital forms of work, so called New Work (NW). The COVID-19 pandemic accelerated these changes and confronted the working world with new challenges. Effects on employee health are ambivalent and remain unclear. Moreover, there is a lack of evidence as to whether existing occupational health management (OHM) measures meet the needs of employees working in new forms of work. Methods/Design: This prospective mixed-method project will include four substudies to identify different NW forms, resulting health risk, benefits and protective factors in subgroups, and derive target group-specific OHM services. In the four substudies, the following methods will be used: (1) a scoping review, semi-standardized interviews, and an online survey, (2) a systematic review, an online survey, an expert workshop and qualitative interviews, (3) workplace observations, and (4) expert workshops. Recommendations for action will be derived from the findings of all substudies and summarized in a checklist for OHM in NW settings. Conclusion: Findings will expand the state of knowledge about NW settings and associated health effects. The development of an evidence-based checklist for target group-specific identification of NW settings and associated health risks, benefits and protective factors can be used as a basis for action regarding OHM in companies. The findings can provide guidance on how future OHM services should be designed to meet the needs of employees.

  🖺 Full Text HTML: Occupational Health Management in New Work - a Protocol for a Mixed-Method Study: Project BGM4NewWork
• Targeted MRM-analysis of plasma proteins in frozen whole blood samples from patients with COVID-19 -

  The COVID-19 pandemic has exposed a number of key challenges that need to be urgently addressed. In particular, rapid identification and validation of prognostic markers is required. Mass spectrometric studies of blood plasma proteomics provide a deep understanding of the relationship between the severe course of infection and activation of specific pathophysiological pathways. Analysis of plasma proteins in whole blood may also be relevant for the pandemic as it requires minimal sample preparation. Here, for the first time, frozen whole blood samples were used to analyze 189 plasma proteins using multiple reaction monitoring (MRM) mass spectrometry and stable isotope-labeled peptide standards (SIS). A total of 128 samples (FRCC, Russia) from patients with mild (n=40), moderate (n=36) and severe (n=19) COVID-19 infection and healthy controls (n=33) were analyzed. Levels of 114 proteins were quantified and compared. Significant differences between all of the groups were revealed for 61 proteins. Changes in the levels of 30 reproducible COVID-19 markers (SERPING1, CRP, C9, ORM1, APOA1, SAA1/SAA2, LBP, AFM, IGFALS, etc.) were consistent with studies performed with serum/plasma samples. Levels of 70 proteins correlated between whole blood and plasma samples. The best-performing classifier built with 13 significantly different proteins achieved the best combination of ROC-AUC (0.93-0.95) and accuracy (0.87-0.93) metrics and distinguished patients from controls, as well as patients by severity and risk of mortality. Overall, the results support the use of frozen whole blood for MRM analysis of plasma proteins and assessment of the status of patients with COVID-19.

  🖺 Full Text HTML: Targeted MRM-analysis of plasma proteins in frozen whole blood samples from patients with COVID-19
• Enhancing social inclusion through the implementation of evidence-based digital health interventions for mental health and alcohol other drug use problems in the wake of COVID-19: A study protocol -

  At any one time, over 900 million people globally experience a mental disorder (including alcohol/other drug use disorders, Whiteford et al., 2013), and this is increasing by about 3% each year (ABS, 2018). Adding to these challenges, the COVID-19 pandemic presents clear risks for a substantial decline in global mental health. Preliminary evidence points towards an overall rise in symptoms of anxiety and coping responses to stress (Holmes et al., 2020), including increased drug and alcohol use amongst the general population. The greatest mental health impacts of the COVID-19 pandemic will be felt, however, by those who are already most marginalised and people with pre-existing mental health and substance use disorders, who have a higher susceptibility to stress than the general population (Yao et al., 2020). eCliPSE is an online clinical portal developed by CI Professor Frances Kay-Lambkin in partnership with the research team and the NSW Ministry of Health to facilitate access to evidence-based ehealth treatments for mental health and alcohol/other drug [AOD] use problems. However, since the testing of eCliPSE in 2017, uptake of this tool via clinician referral has been low, and no clear models existed for digital treatment integration into health services (Batterham et al., 2015). There are very few examples in the available literature of successful implementation of digital interventions in clinical services, and many failures (Mohr et al., 2017). In response to this, our team has developed an evidence-informed Integrated Translation and Engagement Model (ITEM) to drive the uptake of digital therapeutics into mental health and alcohol/other drug services across NSW. Based on the latest evidence for effective implementation, a consideration of individual, social, environmental, and structural factors, the ITEM synthesises diverse theoretical approaches into a coherent, integrated model. The pandemic has highlighted (and exacerbated) social inequities in relation to the prevalence of mental illness, as well as treatment options. Technology has the potential to respond to this challenge, but Australia lags behind the rest of the world in implementing sustainable, effective digital tools into health service delivery. Additionally, no tool currently exists for the evaluation of dual diagnosis capability of digital programs.

  🖺 Full Text HTML: Enhancing social inclusion through the implementation of evidence-based digital health interventions for mental health and alcohol other drug use problems in the wake of COVID-19: A study protocol
• When police pull back: Neighborhood-level effects of de-policing on violent and property crime -
  Many U.S. cities witnessed both de-policing and increased crime in 2020, yet it remains unclear whether the former contributed to the latter. Indeed, much of what is known about the effects of proactive policing on crime comes from studies that evaluate highly focused interventions atypical of day-to-day policing, use cities as the unit of analysis, or cannot rule out endogeneity. This study addresses each of these issues, thereby advancing the evidence base concerning the effects of policing on crime. Leveraging two exogenous shocks presented by the onset of COVID-19 and social unrest following the murder of George Floyd, we evaluated the effects of sudden and sustained reductions in high-discretion policing on crime at the neighborhood level in Denver. Multilevel models accounting for trends in prior police activity, neighborhood structure, seasonality, and population mobility revealed mixed results. On one hand, large-scale reductions in stops and drug-related arrests were associated with significant increases in violent and property crimes, respectively. On the other hand, fewer disorder arrests did not affect crime. These results were not universal across neighborhoods. We discuss the implications of these findings in light of debates concerning the appropriate role of policing in the 21st century.
  🖺 Full Text HTML: When police pull back: Neighborhood-level effects of de-policing on violent and property crime
• Statistical analysis of three data sources for Covid-19 monitoring in Rhineland-Palatinate, Germany -

  In Rhineland-Palatinate, Germany, a system of three data sources has been established to track the Covid-19 pandemic. These sources are the number of Covid-19-related hospitalizations, the Covid-19 genecopies in wastewater, and the prevalence derived from a cohort study. This paper presents an extensive comparison of these parameters. It is investigated whether wastewater data and a cohort study can be valid surrogate parameters for the number of hospitalizations and thus serve as predictors for coming Covid-19 waves. We observe that this is possible in general for the cohort study prevalence, while the wastewater data suffer from a too large variability to make quantitative predictions by a purely data-driven approach. However, the wastewater data as well as the cohort study prevalence are able to detect hospitalizations waves in a qualitative manner. Furthermore, a detailed comparison of different normalization techniques of wastewater data is provided.

  🖺 Full Text HTML: Statistical analysis of three data sources for Covid-19 monitoring in Rhineland-Palatinate, Germany
• Who Is the Most Stressed During COVID-19 Isolation? Data From 27 Countries -
  ****************** ***************************** ****************** ************************ ***** This is old, not peer-reviewed version of the manuscript. For published version, please visit: https://doi.org/10.1111/aphw.12234 *********************************************** ****************** ************** *********** **** To limit the rapid spread of COVID-19, countries have asked their citizens to stay at home. As a result, demographic and cultural factors related to home life became especially relevant to predicting population well-being during isolation. This pre-registered worldwide study analyses the relationship between the number of adults and children in a household, marital status, age, gender, individualism-collectivism and perceived stress. We used the COVIDiSTRESS Global Survey data of 54,245 online participants from 27 countries. The data was collected worldwide between March 30 and April 6, 2020. Our results provide evidence that higher levels of stress are associated with younger age, being a woman, being single, staying with more children, and living in collectivistic cultures. We discuss our findings by emphasizing the need for the public health to focus on both physical and psychological well-being of these groups, as they may be especially susceptible to experiencing elevated levels of stress.
  🖺 Full Text HTML: Who Is the Most Stressed During COVID-19 Isolation? Data From 27 Countries
• In COVID-19 health messaging, loss framing increases anxiety with little-to-no concomitant benefits: Experimental evidence from 84 countries -
  The COVID-19 pandemic (and its aftermath) highlights a critical need to communicate health information effectively to the global public. Given that subtle differences in information framing can have meaningful effects on behavior, behavioral science research highlights a pressing question: Is it more effective to frame COVID-19 health messages in terms of potential losses (e.g., “If you do not practice these steps, you can endanger yourself and others”) or potential gains (e.g., “If you practice these steps, you can protect yourself and others”)? Collecting data in 48 languages from 15,929 participants in 84 countries, we experimentally tested the effects of message framing on COVID-19-related judgments, intentions, and feelings. Loss- (vs. gain-) framed messages increased self-reported anxiety among participants cross-nationally with little-to-no impact on policy attitudes, behavioral intentions, or information seeking relevant to pandemic risks. These results were consistent across 84 countries, three variations of the message framing wording, and 560 data processing and analytic choices. Thus, results provide an empirical answer to a global communication question and highlight the emotional toll of loss-framed messages. Critically, this work demonstrates the importance of considering unintended affective consequences when evaluating nudge-style interventions.
  🖺 Full Text HTML: In COVID-19 health messaging, loss framing increases anxiety with little-to-no concomitant benefits: Experimental evidence from 84 countries
• A Global Experiment on Motivating Social Distancing during the COVID-19 Pandemic -
  Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e. a controlling message) compared to no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly-internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared to the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly-internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing: Controlled motivation was associated with more defiance and less long-term behavioral intentions to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges.
  🖺 Full Text HTML: A Global Experiment on Motivating Social Distancing during the COVID-19 Pandemic
• A global test of brief reappraisal interventions on emotions during the COVID-19 pandemic -
  The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion regulation strategy which modifies how one thinks about a situation. Participants from 87 countries/regions (N = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vs. both control conditions) had consistent effects in reducing negative emotions and increasing positive emotions across different measures. Reconstrual and repurposing had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world to build resilience during the pandemic and beyond.
  🖺 Full Text HTML: A global test of brief reappraisal interventions on emotions during the COVID-19 pandemic

From Clinical Trials

• SA55 Injection: a Potential Therapy for the Prevention and Treatment of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: SA55 Injection;   Other: Placebo for SA55 injection
  Sponsor:   Sinovac Life Sciences Co., Ltd.
  Recruiting

• A Study to Assess the Safety, Tolerability and Preliminary Efficacy of HH-120 for the Treatment of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: HH-120;   Drug: placebo
  Sponsor:   Huahui Health
  Completed

• Psychosomatic, Physical Activity or Both for Post-covid19 Syndrom - Condition:   Post-COVID-19 Syndrome
  Interventions:   Behavioral: Exercise Therapy;   Behavioral: Psychotherapy
  Sponsors:   Hannover Medical School;   Health Insurance Audi BKK;   occupational health service Volkswagen AG;   Helmholtz Centre for Infection Research
  Not yet recruiting

• A Study to Investigate the Prevention of COVID-19 withVYD222 in Adults With Immune Compromise and in Participants Aged 12 Years or Older Who Are at Risk of Exposure to SARS-CoV-2 - Conditions:   COVID-19;   SARS-CoV-2
  Interventions:   Drug: VYD222;   Drug: Normal saline
  Sponsor:   Invivyd, Inc.
  Recruiting

• ACTIV-6: COVID-19 Study of Repurposed Medications - Arm G (Metformin) - Condition:   Covid19
  Interventions:   Other: Placebo;   Drug: Metformin
  Sponsors:   Susanna Naggie, MD;   National Center for Advancing Translational Sciences (NCATS);   Vanderbilt University Medical Center
  Recruiting

• Omicron BA.4/5-Delta COVID-19 Vaccine Phase I Clinical Trial - Condition:   COVID-19
  Interventions:   Biological: Omicron BA.4/5-Delta strain recombinant novel coronavirus protein vaccine (CHO cells);   Biological: Placebo
  Sponsors:   Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.;   Hunan Provincial Center for Disease Control and Prevention
  Not yet recruiting

• Reducing COVID-19 Vaccine Hesitancy Among Hispanic Parents - Conditions:   Vaccine-Preventable Diseases;   COVID-19 Pandemic;   Health-Related Behavior;   Health Knowledge, Attitudes, Practice;   Narration
  Interventions:   Behavioral: Baseline surveys;   Behavioral: Digital Storytelling Intervention;   Behavioral: Information Control Intervention
  Sponsors:   Arizona State University;   Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  Not yet recruiting

• Evaluation of Safety and Immunogenicity of a SARS-CoV-2(Severe Acute Respiratory Syndrome Coronavirus 2) Booster Vaccine (LEM-mR203) - Conditions:   COVID-19 Infection;   COVID-19 Vaccine Adverse Reaction
  Interventions:   Biological: LEM-mR203;   Biological: Placebo
  Sponsor:   Lemonex
  Not yet recruiting

• Non-pharmacological and TCM-based Treatment for Long COVID Symptoms - Condition:   Long Covid19
  Intervention:   Behavioral: Acupuncture and TCM-based lifestyle management
  Sponsor:   The Hong Kong Polytechnic University
  Not yet recruiting

• SA55 Novel Coronavirus Broad-spectrum Neutralizing Antibody Nasal Spray in Health People - Condition:   COVID-19
  Intervention:   Drug: SA55 nasal spray
  Sponsor:   Sinovac Life Sciences Co., Ltd.
  Recruiting

• A Bioequivalence Trial of Fasting Single Oral STI-1558 Capsule in Healthy Chinese Subjects - Condition:   COVID-19
  Intervention:   Drug: STI-1558
  Sponsor:   Zhejiang ACEA Pharmaceutical Co. Ltd.
  Not yet recruiting

• A Study to Determine the Tolerability of Intranasal LMN-301 - Condition:   COVID-19
  Intervention:   Biological: LMN-301
  Sponsor:   Lumen Bioscience, Inc.
  Not yet recruiting

• Mind Body Intervention for Long COVID - Conditions:   Long COVID;   Post-Acute Sequelae of COVID-19;   COVID Long-Haul
  Intervention:   Behavioral: Mind Body Intervention #1
  Sponsor:   Beth Israel Deaconess Medical Center
  Not yet recruiting

• Safety of Simultaneous mRNA COVID-19 Vaccine With Other Childhood Vaccines in Young Children - Conditions:   Fever After Vaccination;   Fever;   Seizures Fever
  Interventions:   Biological: Pfizer-BioNTech COVID-19 Vaccine;   Biological: Routine Childhood Vaccinations
  Sponsors:   Duke University;   Kaiser Permanente;   Columbia University;   Children’s Hospital Medical Center, Cincinnati;   Centers for Disease Control and Prevention
  Not yet recruiting

• SA55 Injection Phase II Study in the Treatment of Mild/Moderate COVID-19 Patients - Condition:   Infection of Upper Respiratory Tract Caused by 2019-nCoV
  Intervention:   Drug: SA55 Injection
  Sponsor:   Sinovac Life Sciences Co., Ltd.
  Recruiting

From PubMed

• TGF-β1 reduces the differentiation of porcine IgA-producing plasma cells by inducing IgM⁺ B cells apoptosis via Bax/Bcl2-Caspase3 pathway - Transforming growth factor β1 (TGF-β1) performs a critical role in maintaining homeostasis of intestinal mucosa regulation and controls the survival, proliferation, and differentiation of many immune cells. In this study, we discovered that the infection of porcine epidemic diarrhea virus (PEDV), a coronavirus, upregulated TGF-β1 expression via activating Tregs. Besides, recombinant porcine TGF-β1 decreased the percentage of CD21^(+) B cells within the lymphocyte population in vitro. We further…

• Therapeutic benefits of prophetic medicine remedies in treating hematological diseases (A review article) - Hematological disorders are common medical ailments constituting an important cause of morbidity and mortality worldwide, which may be managed efficiently using different prophetic medicine remedies as adjuvants to current therapeutics. Prophetic medicine includes the body of knowledge about medicine that has been derived from the deeds, customs (sunnah), ahadith (sayings), actions, and agreements of Prophet Muhammad, peace be upon him. This review article aims at exploring the magnitude of…

• The binding mechanism of failed, in processing and succeed inhibitors target SARS-CoV-2 main protease - Since the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several variants have caused a persistent pandemic. Consequently, it is crucial to develop new potential anti-SARS-CoV-2 drugs with specificity. To minimize potential failures and preserve valuable clinical resources for the development of other useful drugs, researchers must enhance their understanding of the interactions between drugs and SARS-CoV-2. While numerous crystal structures of the SARS-CoV-2 main…

• Chromone-embedded peptidomimetics and furopyrimidines as highly potent SARS-CoV-2 infection inhibitors: docking and MD simulation study - CONCLUSIONS: The study investigated the inhibition of viral replication using chromone derivatives, finding high inhibitory effects in the peptidomimetic family compared to other studies.

• A viral RNA-dependent RNA polymerase inhibitor VV116 broadly inhibits human coronaviruses and has synergistic potency with 3CLpro inhibitor nirmatrelvir - During the ongoing pandemic, providing treatment consisting of effective, low-cost oral antiviral drugs at an early stage of SARS-CoV-2 infection has been a priority for controlling COVID-19. Although Paxlovid and molnupiravir have received emergency approval from the FDA, some side effect concerns have emerged, and the possible oral agents are still limited, resulting in optimized drug development becoming an urgent requirement. An oral remdesivir derivative, VV116, has been reported to have…

• Identification of γ-Fagarine as a novel antiviral agent against respiratory virus (hMPV) infection - Human metapneumovirus (hMPV) causes significant upper and lower respiratory disease in all age groups worldwide. However, there is no licensed drugs or vaccine available against hMPV. γ-Fagarine, an alkaloida isolated from the root of zanthoxylum, has been reported to be effective in the treatment of cancer, inflammatory diseases and antivirals. However, little is known about the inhibitory effect of γ-Fagarine against respiratory virus infection and the mechanism. In this study, we aim to…

• Structural basis for translation inhibition by MERS-CoV Nsp1 reveals a conserved mechanism for betacoronaviruses - All betacoronaviruses (β-CoVs) encode non-structural protein 1 (Nsp1), an essential pathogenicity factor that potently restricts host gene expression. Among the β-CoV family, MERS-CoV is the most distantly related member to SARS-CoV-2, and the mechanism for host translation inhibition by MERS-CoV Nsp1 remains controversial. Herein, we show that MERS-CoV Nsp1 directly interacts with the 40S ribosomal subunit. Using cryogenic electron microscopy (cryo-EM), we report a 2.6-Å structure of the…

• Simultaneous Targeting of IL-1-Signaling and IL-6-Trans-Signaling Preserves Human Pulmonary Endothelial Barrier Function During a Cytokine Storm - CONCLUSIONS: These findings strongly suggest a major role for both IL-6 trans-signaling and IL-1β signaling in the pathological increase in permeability of the human lung microvasculature and reveal combinatorial strategies that enable the gradual control of pulmonary endothelial barrier function in response to a cytokine storm.

• SARS-CoV-2 protein NSP2 enhances microRNA-mediated translational repression - Viruses use microRNAs (miRNAs) to impair the host antiviral response and facilitate viral infection by expressing their own miRNAs or co-opting cellular miRNAs. miRNAs inhibit translation initiation of their target mRNAs by recruiting the GIGYF2/4EHP translation repressor complex to the mRNA 5´-cap structure. We recently reported that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encoded non-structural protein 2 (NSP2) interacts with GIGYF2. This interaction is critical for…

• De novo design of a stapled peptide targeting SARS-CoV-2 spike protein receptor-binding domain - Although effective vaccines have been developed against SARS-CoV-2, many regions in the world still have low rates of vaccination and new variants with mutations in the viral spike protein have reduced the effectiveness of most available vaccines and treatments. There is an urgent need for a drug to cure this disease and prevent infection. The SARS-CoV-2 virus enters the host cell through protein-protein interaction between the virus’s spike protein and the host’s angiotensin converting enzyme…

• Assessment of safety and intranasal neutralizing antibodies of HPMC-based human anti-SARS-CoV-2 IgG1 nasal spray in healthy volunteers - An HPMC-based nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (nasal antibody spray or NAS) was developed to strengthen COVID-19 management. NAS exhibited potent broadly neutralizing activities against SARS-CoV-2 with PVNT(50) values ranging from 0.0035 to 3.1997 μg/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, ancestral, Delta, Omicron BA.1, BA.2, BA.4/5, and BA.2.75. Biocompatibility assessment showed no potential…

• Responses of patients with cancer to mRNA vaccines depend on the time interval between vaccination and last treatment - CONCLUSION: Accordingly, our data support that timing of mRNA-based therapy is critical and we suggest that at least a 6-months or 12-months waiting interval should be observed before mRNA vaccination in systemically treated patients.

• Discovery of a Druggable, Cryptic Pocket in SARS-CoV-2 nsp16 Using Allosteric Inhibitors - A collaborative, open-science team undertook discovery of novel small molecule inhibitors of the SARS-CoV-2 nsp16-nsp10 2’-O-methyltransferase using a high throughput screening approach with the potential to reveal new inhibition strategies. This screen yielded compound 5a, a ligand possessing an electron-deficient double bond, as an inhibitor of SARS-CoV-2 nsp16 activity. Surprisingly, X-ray crystal structures revealed that 5a covalently binds within a previously unrecognized cryptic pocket…

• Cinnamaldehyde inhibits cytokine storms induced by the ORF3a protein of SARS-CoV-2 via ROS-elimination in activated T cells - Cytokine storms are the cause of complications in patients with severe COVID-19, and it becomes the target of therapy. Several natural compounds were selected to screen the inhibitory effect on T-cell proliferation by Fluorescence-Activated Cell Sorting (FACS) and cytokine production by enzyme-linked immunosorbent assay (ELISA). Open reading frame 3a (ORF3a) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulates the specific T-cell activation model in vivo and in vitro. The…

• How does the Immunological System Change during the SARS-COV-2 Attack? A Clue for the New Immunotherapy Discovery - The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) is one of the biggest unsolved global problems of the 21st century for which there has been no definitive cure yet. Like other respiratory viruses, SARS-COV-2 triggers the host immunity dramatically, causing dysfunction in the immune system, both innate and adaptive, which is a common feature of COVID-19 patients. Evidence shows that in the early stages of COVID-19, the immune system is suppressed…

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