Covid-19 Sentry

Contents

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

From Preprints

• Scientifically led response plan for future global open-source initiatives related to emergency intervention. -
  The modern era of interconnectedness and rapid technological advancements has ushered in a new paradigm of collaborative problem-solving. Open-source initiatives stand at the helm of this paradigm, driving a culture of shared innovation to tackle global challenges. The global response to the COVID-19 pandemic has magnified the pivotal role of open-source solutions, especially in times of emergency interventions. This guide is designed to assist governmental bodies and organizations in understanding, supporting, and leveraging open-source initiatives to effectively respond to future emergencies. It encapsulates valuable insights and actionable recommendations derived from a thorough examination of past open-source engagements, particularly during the COVID-19 pandemic.
  🖺 Full Text HTML: Scientifically led response plan for future global open-source initiatives related to emergency intervention.
• A Phase 2, randomized, double-blind, placebo-controlled multi-center trial sub-study for the clinical effects of paridiprubart treatment in hospitalized critically ill patients with COVID-19 ARDS -

  Background: Coronavirus disease 2019 (COVID-19) mortality is predominantly due to acute respiratory distress syndrome (ARDS). There are currently limited treatment options for ARDS, a life-threatening condition with different etiologies, secondary to inflammation-induced lung injury. Paridiprubart is a monoclonal antibody that inhibits Toll-like Receptor 4 (TLR4), a key player in ARDS pathophysiology. Methods: This was a prespecified sub-study of a randomized, double-blind, placebo-controlled, Phase 2 trial evaluating the efficacy and safety of paridiprubart in COVID-19 patients with ARDS receiving invasive mechanical ventilation and additional organ support. Efficacy outcomes were 28- and 60-day all-cause mortality, and improvement in COVID-19 severity and ventilation-free days at 28-days post-treatment. Results: Thirteen (13) and twenty (20) patients received paridiprubart and placebo, respectively. The groups were comparable for demographics and baseline parameters, except for higher kidney failure incidence and use of immune modulators and antivirals, and lower corticosteroids use in the paridiprubart group. Mortality at 28-days post-treatment was 7.7% (1/13) in the paridiprubart group versus 40.0% (8/20) for placebo (OR=0.125; 95% CI, 0.013-1.160; P=0.067; P[bootstrap]=0.011). 60-day mortality was 23.1% (3/13) in paridiprubart-treated patients and 45.0% (9/20) in placebo patients (OR=0.367; 95% CI, 0.077-1.749; P=0.208; P[bootstrap]=0.162). Mean survival time was 55.78 days for paridiprubart recipients compared to 41.44 days for placebo patients (HR=0.386; 95% CI, 0.077-1.436; P=0.156; P[bootstrap]=0.083). Although not statistically significant, results for other efficacy measures favored paridiprubart. Incidence of adverse events was similar in both groups. Conclusions: In COVID-19 patients with ARDS requiring invasive ventilation and organ support, paridiprubart was efficacious in preventing mortality and improving clinical outcomes, with no safety concerns.

  🖺 Full Text HTML: A Phase 2, randomized, double-blind, placebo-controlled multi-center trial sub-study for the clinical effects of paridiprubart treatment in hospitalized critically ill patients with COVID-19 ARDS
• Genomic evolution of SARS-CoV-2 variants of concern under in vitro neutralising selection pressure following two doses of the Pfizer-BioNTech BNT162b2 COVID-19 vaccine -
  Aims: To explore viral evolution during in vitro neutralisation using next generation sequencing, and to determine whether sera from individuals immunised with two doses of the Pfizer BioNTech vaccine (BNT162b2) are as effective at neutralising the SARSCoV2 variant of concern (VOC) Delta (B 1.617.2) compared to the earlier lineages Beta (B.1.351) and wildtype (lineage A.2.2) virus. Methods: Using a live virus SARSCoV2 neutralisation assay in Vero E6 cells we determined neutralising antibody titres (nAbT) in 14 participants (vaccine naive (n=2) and post second dose of BNT162b2 vaccination (n=12), median age 45 years [IQR 29 to 65], median time after second dose = 21 days [IQR 19 to 28] against three SARSCoV2 strains: wild-type, Beta and Delta. The determination of nAbT was performed by visual inspection of cytopathic effect (CPE) and inhouse quantitative reverse transcriptase real time quantitative polymerase chain reaction (RTqPCR) to confirm SARS-CoV-2 replication. A total of 110 representative samples including inoculum, neutralisation breakpoints at 72 hrs, negative and positive controls underwent genome sequencing using the Respiratory Viral Oligo Panel version 2 (RVOP) (Illumina Inc. (San Diego, United States of America)) viral enrichment and short read sequencing using (Illumina Inc. (San Diego, United States of America)),(Figure 1). Results: There was a significant reduction in nAbT observed against the Delta and Beta VOC compared with wildtype, 4.4 fold (p = >0.0006) and 2.3 fold (p = 0.0140), respectively (Figure 2). Neutralizing antibodies were not detected in one vaccinated immunosuppressed participant nor the vaccine naive participants (n=2). The highest nAbT against the SARS-CoV-2 variants investigated was obtained from a participant who was vaccinated following SARSCoV2 infection 12 months prior (Table S1). Limited consensus level mutations occurred in the SARS-CoV-2 genome of any lineage during in vitro neutralisation, however, consistent minority allele frequency variants (MFV) were detected in the SARS-CoV-2 polypeptide, spike (S) and membrane protein. Discussion: Significant reductions in nAbT post vaccination were identified, with Delta demonstrating a 4.4 fold reduction. The reduction in nAbT for the VOC Beta has been previously documented, however, limited data is available on vaccine evasion for the Delta VOC, the predominant strain currently circulating worldwide at the time. Studies in high incidence countries may not be applicable to low incidence settings such as Australia as nAbT may be significantly higher in vaccine recipients previously infected with SARSCoV2, as seen in our cohort. Monitoring viral evolution is critical to evaluate the impact of novel SARSCoV2 variants on vaccine effectiveness as mutational profiles in the sub-consensus genome could indicate increases in transmissibility, virulence or allow the development of antiviral resistance.
  🖺 Full Text HTML: Genomic evolution of SARS-CoV-2 variants of concern under in vitro neutralising selection pressure following two doses of the Pfizer-BioNTech BNT162b2 COVID-19 vaccine
• p38-MAPK is prerequisite for the synthesis of SARS-CoV-2 protein -
  The inhibition of p38 mitogen-activated protein kinase (p38-MAPK) by small molecule chemical inhibitors was previously shown to impair severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, however, mechanisms underlying antiviral activity remains unexplored. In this study, reduced growth of SARS-CoV-2 in p38- knockout Vero cells, together with enhanced viral yield in cells transfected with construct expressing p38, suggested that p38-MAPK is essential for the propagation of SARS-CoV-2. The SARS-CoV-2 was also shown to induce phosphorylation (activation) of p38, at time when transcription/translational activities are considered to be at the peak levels. Further, we demonstrated that p38 supports viral RNA/protein synthesis without affecting viral attachment, entry, and budding in the target cells. In addition, we demonstrated that long-term culture of SARS-CoV-2 in the presence of p38 inhibitor SB203580 does not easily select resistant viral mutants. In conclusion, we provide mechanistic insights on the regulation of SARS-CoV-2 replication by p38 MAPK.
  🖺 Full Text HTML: p38-MAPK is prerequisite for the synthesis of SARS-CoV-2 protein
• Comparative Analysis of SARS-CoV-2 Antigenicity across Assays and in Human and Animal Model Sera -
  The antigenic evolution of SARS-CoV-2 requires ongoing monitoring to judge the immune escape of newly arising variants. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human and animal sera. We compared 18 datasets generated using human, hamster, and mouse sera, and six different neutralization assays. Titer magnitude was lowest in human, intermediate in hamster, and highest in mouse sera. Fold change, immunodominance patterns and antigenic maps were similar among sera. Most assays yielded similar results, except for differences in fold change in cytopathic effect assays. Not enough data was available for conclusively judging mouse sera, but hamster sera were a consistent surrogate for human first-infection sera.
  🖺 Full Text HTML: Comparative Analysis of SARS-CoV-2 Antigenicity across Assays and in Human and Animal Model Sera
• Development of a mutant aerosolized ACE2 that neutralizes SARS-CoV-2 in vivo -
  The rapid evolution of variants of SARS-CoV-2 highlights the need for new therapies to prevent disease spread. SARS-CoV-2, like SARS-CoV-1, uses the human cell surface protein angiotensin-converting enzyme 2 (ACE2) as its native receptor. Here, we design and characterize a mutant ACE2 that enables rapid affinity purification of a dimeric protein by altering the active site to prevent autoproteolytic digestion of a C-terminal His10 epitope tag. In cultured cells, mutant ACE2 competitively inhibits lentiviral vectors pseudotyped with spike from multiple SARS-CoV-2 variants, as well as infectious SARS-CoV-2. Moreover, the protein can be nebulized and retains virus-binding properties. We developed a system for delivery of aerosolized ACE2 to K18-hACE2 mice and demonstrate protection by our modified ACE2 when delivered as a prophylactic agent. These results show proof-of-concept for an aerosolized delivery method to evaluate anti-SARS-CoV-2 agents in vivo and suggest a new tool in the ongoing fight against SARS-CoV-2 and other ACE2-dependent viruses.
  🖺 Full Text HTML: Development of a mutant aerosolized ACE2 that neutralizes SARS-CoV-2 in vivo
• SARS-CoV-2 Omicron BA.2.86: less neutralization evasion compared to XBB sub-variants -
  The continual emergence and circulation of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have caused a great challenge for the coronavirus disease 2019 (COVID-19) pandemic control. Recently, Omicron BA.2.86 was identified with more than 30 amino acid changes on the spike (S) protein, compared to Omicron BA.2 or XBB.1.5. The immune evasion potential of BA.2.86 is of great concern. In this study, we evaluated the neutralizing activities of sera collected from participants and mice. Participants were divided into five groups according to their vaccination (inactivated vaccine, protein subunit vaccine ZF2001 or ZF2202-A) and infection (Omicron BF.7/BA.5.2) status. ZF2202-A is ZF2001 vaccine's next-generation COVID-19 vaccine with updated bivalent Delta-BA.5 RBD-heterodimer immunogen. BALB/c mice were immunized with XBB.1.5 RBD-homodimer, BA.5-BA.2, Delta-XBB.1.5 or BQ.1.1-XBB.1.5 RBD-heterodimers protein vaccine candidates for evaluating the neutralizing responses. We found that Omicron BA.2.86 shows stronger immune evasion than BA.2 due to >30 additional mutations on S protein. Compared to XBB sub-variants, BA.2.86 does not display more resistance to the neutralizing responses induced by ZF2001-vaccination, BF.7/BA.5.2 breakthrough infection or a booster dose of ZF2202-A-vaccination. In addition, the mouse experiment results showed that BQ.1.1-XBB.1.5 RBD-heterodimer and XBB.1.5 RBD-homodimer induced high neutralizing responses against XBB sub-variants and BA.2.86, indicating that next-generation COVID-19 vaccine should be developed to enhance the protection efficacy against the circulating strains in the future.
  🖺 Full Text HTML: SARS-CoV-2 Omicron BA.2.86: less neutralization evasion compared to XBB sub-variants
• A supervised Bayesian factor model for the identification of multi-omics signatures -
  Motivation: Predictive biological signatures provide utility as biomarkers for disease diagnosis and prognosis, as well as prediction of responses to vaccination or therapy. These signatures are iden-tified from high-throughput profiling assays through a combination of dimensionality reduction and machine learning techniques. The genes, proteins, metabolites, and other biological analytes that compose signatures also generate hypotheses on the underlying mechanisms driving biological responses, thus improving biological understanding. Dimensionality reduction is a critical step in signature discovery to address the large number of analytes in omics datasets, especially for multi-omics profiling studies with tens of thousands of measurements. Latent factor models, which can account for the structural heterogeneity across diverse assays, effectively integrate multi-omics data and reduce dimensionality to a small number of factors that capture correlations and associations among measurements. These factors provide biologically interpretable features for predictive model-ing. However, multi-omics integration and predictive modeling are generally performed independent-ly in sequential steps, leading to suboptimal factor construction. Combining these steps can yield better multi-omics signatures that are more predictive while still being biologically meaningful. Results: We developed a supervised variational Bayesian factor model that extracts multi-omics signatures from high-throughput profiling datasets that can span multiple data types. Signature-based multiPle-omics intEgration via lAtent factoRs (SPEAR) adaptively determines factor rank, emphasis on factor structure, data relevance and feature sparsity. The method improves the recon-struction of underlying factors in synthetic examples and prediction accuracy of COVID-19 severity and breast cancer tumor subtypes. Availability: SPEAR is a publicly available R-package hosted at https://bitbucket.org/kleinstein/SPEAR.
  🖺 Full Text HTML: A supervised Bayesian factor model for the identification of multi-omics signatures
• Intracellular trafficking of furin enhances cellular intoxication by recombinant immunotoxins based on Pseudomonas exotoxin A -
  Furin is a mammalian serine protease with important roles in cellular homeostasis and disease. It cleaves and activates numerous endogenous and exogenous substrates, including the SARS-CoV-2 viral spike protein and protein toxins such as diphtheria toxin and Pseudomonas exotoxin A (PE). Recombinant immunotoxins (RITs) are toxin conjugates used as cancer therapeutics that connect tumor-directed antibodies with toxins for targeted cell killing. RITs based on PE have shown success in treating a variety of cancers, but often suffer from safety and efficacy concerns when used clinically. We have explored furin as a potential limiting factor in the intoxication pathway of PE-based RITs. Although the furin has widely recognized importance in RIT intoxication, its role is incompletely understood. Circumstantial evidence suggests that furin may act as a transporter for RITs in addition to its role of activation by cleavage. Here, we describe the creation of a CRISPR-engineered furin-deficient HEK293 cell line, {triangleup}Fur293. Using {triangleup}Fur293 and derivatives that express mutant forms of furin, we confirm the importance of furin in the PE RIT intoxication pathway and show that furin trafficking has a significant impact on RIT efficacy. Our data support the hypothesis that furin acts as a transporter during RIT intoxication, and suggest furin as a target to improve the effectiveness of RITs.
  🖺 Full Text HTML: Intracellular trafficking of furin enhances cellular intoxication by recombinant immunotoxins based on Pseudomonas exotoxin A
• ISARIC COVID-19 Clinical Data Report: 10 January 2023 -

  ISARIC (International Severe Acute Respiratory and emerging Infections Consortium) partnerships and outbreak preparedness initiatives enabled the rapid launch of standardised clinical data collection on COVID-19 in Jan 2020. Extensive global participation has resulted in a large, standardised collection of comprehensive clinical data from hundreds of sites across dozens of countries. Data are analysed regularly and reported publicly to inform patient care and public health response. This report, our 18th and final report, is a part of a series published over 3 years. Data have been entered for 945,317 individuals from 1807 partner institutions and networks across 76 countries. The comprehensive analyses detailed in this report includes hospitalised individuals of all ages for whom data collection occurred between 30 January 2020 and up to and including 10 January 2023, AND who have laboratory-confirmed SARS-COV-2 infection or clinically diagnosed COVID-19. For the 845,291 cases who meet eligibility criteria for this report, selected findings include: o Median age of 57 years, with an approximately equal (50/50) male:female sex distribution o 29% of the cohort are at least 70 years of age, whereas 6% are 0-19 years of age o The most common symptom combination in this hospitalised cohort is shortness of breath, cough, and history of fever, which has remained constant over time o The five most common symptoms at admission were shortness of breath, cough, history of fever, fatigue/malaise, and altered consciousness/confusion, which is unchanged from the previous reports o Age-associated differences in symptoms are evident, including the frequency of altered consciousness increasing with age, and fever, respiratory and constitutional symptoms being present mostly in those 40 years and above o 15% of patients with relevant data available (845,291) were admitted at some point during their illness into an intensive care unit (ICU), which has decreased from 19% during the 3 years of ISARIC reporting o Antibiotic agents were used in 37% of patients for whom relevant data are available (802,241), a significant reduction from our previous reports (80%) which reflects a shifting proportion of data contributed by different institutions; in ICU/HDU admitted patients with data available (64,669), 90% received antibiotics o Use of corticosteroids was reported in 25% of all patients for whom data were available (809,043); in ICU/HDU admitted patients with data available (64,713), 71% received corticosteroids o Outcomes are known for 762,728 patients and the overall estimated case fatality ratio (CFR) is 22% (95%CI 21.9-22), rising to 36% (95%CI 35.6-36.1) for patients who were admitted to ICU/HDU, demonstrating worse outcomes in those with the most severe disease We thank all the data contributors for their ongoing support.

  🖺 Full Text HTML: ISARIC COVID-19 Clinical Data Report: 10 January 2023
• ER-export and ARFRP1/AP-1-dependent delivery of SARS-CoV-2 Envelope to lysosomes controls late stages of viral replication -
  The beta-coronavirus SARS-CoV-2 is the causative agent of the global Covid-19 pandemic. Coronaviral Envelope (E) proteins are pentameric viroporins that play essential roles in assembly, release and pathogenesis. We developed an inert tagging strategy for SARS-CoV-2 E and find that it localises to the Golgi and to lysosomes. We identify sequences in E, conserved across Coronaviridae, responsible for ER-to-Golgi export, and relate this activity to interaction with COP-II via SEC24. Using proximity biotinylation, we identify host-cell factors that interact with E and identify an ARFRP1/AP-1 dependent pathway allowing Golgi-to-lysosome trafficking of E. We identify sequences in E that bind AP-1, are conserved across beta-coronaviruses and allow E to be trafficked from Golgi to lysosomes. We show that E acts to deacidify lysosomes and by developing a trans-complementation assay, we show that both lysosomal trafficking of E and its viroporin activity are necessary for efficient viral replication and release.
  🖺 Full Text HTML: ER-export and ARFRP1/AP-1-dependent delivery of SARS-CoV-2 Envelope to lysosomes controls late stages of viral replication
• Administration and Scoring Errors on The Woodcock Johnson IV Tests of Achievement:Before and During COVID-19 -
  Eighty Woodcock–Johnson IV Tests of Achievement protocols from 40 test administrators were examined to determine the types and frequencies of administration and scoring errors made. Non-critical errors (e.g., failure to record verbatim) were found on every protocol (M = 37.2). Critical (e.g., standard score, start point) errors were found on 98.8% of protocols (M = 15.3). Additionally, a series of paired samples t-test were conducted to determine differences in total, critical, and non-critical errors pre- and during-COVID-19. No statistic differences were found. Our findings add to a growing body of research that suggests that errors on norm-referenced tests of achievement are pervasive. However, the frequency of errors did not appear to be affected by COVID-19 stressors or social distancing requirements. Implications of these findings for training and practice are discussed. Suggestions for future research are also provided.
  🖺 Full Text HTML: Administration and Scoring Errors on The Woodcock Johnson IV Tests of Achievement:Before and During COVID-19
• A Comparison of Special Education Students’ Triennial Norm-Referenced Academic Achievement Before and During COVID-19 -
  Despite growing evidence for learning loss due to COVID-19, there is little research examining this phenomenon using norm-referenced tests (NRTs) or with special educations students. Using a repeated-measures design with 96 fourth through 12th grade students previously identified as eligible for special education services, the present study attempted to measure learning loss using W Difference Scores gathered from triennial evaluations using the Woodcock Johnson IV Tests of Achievement. Findings revealed that participants fell further behind proficiency expectations in the areas of decoding, spelling, and math calculation skills. Academic proficiency was found to differ markedly from normative expectations for typical same-age peers across tests, both prior to and during the COVID-19 pandemic. While academic proficiency was more like that of a clinical sample of students with learning disabilities, moderate to large differences in the sample means of most tests suggest that COVID-19 has had a negative impact on academic achievement.
  🖺 Full Text HTML: A Comparison of Special Education Students’ Triennial Norm-Referenced Academic Achievement Before and During COVID-19
• Recruitment, Consent and DNA Sample Acquisition in a U.S. Precision Health Cohort During the COVID-19 Pandemic -

  Aim: The Yale Generations Project (YGP) is a precision health cohort initiative that began enrollment in New Haven Connecticut USA in July 2019. In March 2020, after nine months of operation, pandemic restrictions prompted abrupt changes to staff availability as well as changes to the projects recruitment, consenting, and sample acquisition. This manuscript describes the successful addition of remote recruitment, consenting, and DNA sampling to YGP workflows during the initial 27-months of pandemic restrictions ending June 30, 2022. Methods: The initial YGP protocol established face-to-face workflow for recruiting, consenting and peripheral blood collection. A telemedicine consent protocol was initiated in April of 2020, and a remote saliva collection was established in October of 2020. De-identified data was extracted from YGP dataset and reported here. Results: At the completion of YGPs initial 36 months (9-months pre-pandemic and 27-months pandemic) YGP enrolled N=4949 volunteers. There were N=1,950 (216.7 per month) volunteers consented pre-pandemic and N=2,999 (111.1 per month) during pandemic. The peak consenting month was February 2020 with N=428. DNA sample acquisition peaked in the pre-pandemic month of February 2020 with N=291 peripheral blood draws, and in the pandemic period the peak DNA acquisition month was November 2020 with N=176 (N=68 peripheral blood draws and N=108 saliva samples). Conclusion: The YGP successfully transitioned from pre-pandemic recruiting, consenting and sample acquisition model that was exclusively face-to-face, to pandemic model that was predominantly remote. The added value of remote recruiting, consenting, and sampling has led to plans for an optimized hybrid model post-pandemic. Keywords: genomics, precision health, COVID-19, cohort

  🖺 Full Text HTML: Recruitment, Consent and DNA Sample Acquisition in a U.S. Precision Health Cohort During the COVID-19 Pandemic
• Analysis of Potential Risk Factors of COVID-19 Based on Variants: Omicron, Delta, and Alpha -

  The coronavirus disease 2019 (COVID-19) pandemic has changed which affects the risk of COVID-19 infection for specific subgroups. We focused on the subgroups based on the factors (sex, age, and vaccination) and COVID-19 strains (Alpha, Delta, and Omicron). Past studies focused on analyzing these factors based on one geographic region or one COVID-19 strain. Therefore, there is a need to understand these factors9 association with risk of COVID-19 infection through analyzing data from various geographic regions and strains. The association between COVID-19 strains and the factors was assessed through chi-square test and odds ratio tests. Sex, vaccination, age had a significant association with testing positive for the COVID-19 strains of interest in most geographies. The biggest difference was unvaccinated individuals have 3.14 higher odds of getting Alpha than vaccinated individuals in Canada. These findings provide insights into the groups that are more susceptible to contracting specific strains of COVID-19.

  🖺 Full Text HTML: Analysis of Potential Risk Factors of COVID-19 Based on Variants: Omicron, Delta, and Alpha

From Clinical Trials

• 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

• 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

• 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

• 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

• Cell Therapy With Treg Cells Obtained From Thymic Tissue (thyTreg) to Control the Immune Hyperactivation Associated With COVID-19 (THYTECH2) - Condition:   Systemic Inflammatory Response Syndrome
  Interventions:   Biological: Allogeneic thyTreg 5.000.000;   Biological: Allogeneic thyTreg 10.000.000
  Sponsors:   Hospital General Universitario Gregorio Marañon;   Instituto de Salud Carlos III
  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

• 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

• Stellate Ganglion Block With Lidocaine for the Treatment of COVID-19-Induced Parosmia - Condition:   Parosmia
  Interventions:   Procedure: Stellate Ganglion Block;   Other: Placebo
  Sponsor:   Lawson Health Research Institute
  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

• Amantadine Therapy for Cognitive Impairment in Long COVID - Conditions:   Long COVID;   Post-COVID19 Condition;   Post-Acute COVID19 Syndrome
  Intervention:   Drug: Amantadine
  Sponsor:   Ohio State University
  Not yet recruiting

From PubMed

• Pupillographic Analysis of COVID-19 Patients: Early and Late Results After Recovery - CONCLUSION: PDs were significantly larger in COVID-19 patients in all light intensities in the 1^(st) month after COVID-19. However, pupillary dilation was transient, and no significant difference was found in the 6^(th) month. We suggest that the transient pupillary dilation may be secondary to the autonomic nervous system dysfunction and/or optic nerve and visual pathways alterations following COVID-19.

• An In Silico Design of Peptides Targeting the S1/S2 Cleavage Site of the SARS-CoV-2 Spike Protein - SARS-CoV-2, responsible for the COVID-19 pandemic, invades host cells via its spike protein, which includes critical binding regions, such as the receptor-binding domain (RBD), the S1/S2 cleavage site, the S2 cleavage site, and heptad-repeat (HR) sections. Peptides targeting the RBD and HR1 inhibit binding to host ACE2 receptors and the formation of the fusion core. Other peptides target proteases, such as TMPRSS2 and cathepsin L, to prevent the cleavage of the S protein. However, research has…

• microRNA-185 Inhibits SARS-CoV-2 Infection through the Modulation of the Host’s Lipid Microenvironment - With the emergence of the novel betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), there has been an urgent need for the development of fast-acting antivirals, particularly in dealing with different variants of concern (VOC). SARS-CoV-2, like other RNA viruses, depends on host cell machinery to propagate and misregulate metabolic pathways to its advantage. Herein, we discovered that the immunometabolic microRNA-185 (miR-185) restricts SARS-CoV-2 propagation by…

• Protective versus Pathogenic Type I Interferon Responses during Virus Infections - Following virus infections, type I interferons are synthesized to induce the expression of antiviral molecules and interfere with virus replication. The importance of early antiviral type I IFN response against virus invasion has been emphasized during COVID-19 as well as in studies on the microbiome. Further, type I IFNs can directly act on various immune cells to enhance protective host immune responses to viral infections. However, accumulating data indicate that IFN responses can be harmful…

• Targeting SARS-CoV-2 Macrodomain-1 to Restore the Innate Immune Response Using In Silico Screening of Medicinal Compounds and Free Energy Calculation Approaches - Among the different drug targets of SARS-CoV-2, a multi-domain protein known as NSP3 is a critical element of the translational and replication machinery. The macrodomain-I, in particular, has been reported to have an essential role in the viral attack on the innate immune response. In this study, we explore natural medicinal compounds and identify potential inhibitors to target the SARS-CoV-2-NSP3 macrodomain-I. Computational modeling and simulation tools were utilized to investigate the…

• Mannose-Binding Lectins as Potent Antivirals against SARS-CoV-2 - The SARS-CoV-2 entry into host cells is mainly mediated by the interactions between the viral spike protein (S) and the ACE-2 cell receptor, which are highly glycosylated. Therefore, carbohydrate binding agents may represent potential candidates to abrogate virus infection. Here, we evaluated the in vitro anti-SARS-CoV-2 activity of two mannose-binding lectins isolated from the Brazilian plants Canavalia brasiliensis and Dioclea violacea (ConBR and DVL). These lectins inhibited SARS-CoV-2…

• Atovaquone and Pibrentasvir Inhibit the SARS-CoV-2 Endoribonuclease and Restrict Infection In Vitro but Not In Vivo - The emergence of SARS-CoV-1 in 2003 followed by MERS-CoV and now SARS-CoV-2 has proven the latent threat these viruses pose to humanity. While the SARS-CoV-2 pandemic has shifted to a stage of endemicity, the threat of new coronaviruses emerging from animal reservoirs remains. To address this issue, the global community must develop small molecule drugs targeting highly conserved structures in the coronavirus proteome. Here, we characterized existing drugs for their ability to inhibit the…

• Synthetic Frog-Derived-like Peptides: A New Weapon against Emerging and Potential Zoonotic Viruses - Given the emergence of the coronavirus disease 2019 (COVID-19), zoonoses have raised in the spotlight of the scientific community. Animals have a pivotal role not only for this infection, but also for many other recent emerging and re-emerging viral diseases, where they may represent both intermediate hosts and/or vectors for zoonoses diffusion. Today, roughly two-thirds of human infections are derived from animal origins; therefore, the search for new broad-spectrum antiviral molecules is…

• Natural Antibodies Produced in Vaccinated Patients and COVID-19 Convalescents Recognize and Hydrolyze Oligopeptides Corresponding to the S-Protein of SARS-CoV-2 - The S-protein is the major antigen of the SARS-CoV-2 virus, against which protective antibodies are generated. The S-protein gene was used in adenoviral vectors and mRNA vaccines against COVID-19. While the primary function of antibodies is to bind to antigens, catalytic antibodies can hydrolyze various substrates, including nucleic acids, proteins, oligopeptides, polysaccharides, and some other molecules. In this study, antibody fractions with affinity for RBD and S-protein (RBD-IgG and S-IgG)…

• Riding the Omicron BA.5 Wave: Improved Humoral Response after Vaccination with Bivalent Omicron BA.4-5-Adapted mRNA SARS-CoV-2 Vaccine in Chronic Hemodialysis Patients - Hemodialysis patients faced an excess morbidity and mortality during the COVID-19 pandemic. We evaluated the effect of second-generation mRNA vaccines against Omicron BA.4 and BA.5 variants of SARS-CoV-2 on humoral immunity. The study population comprised 66 adult hemodialysis patients who have encountered four SARS-CoV-2 antigen contacts through vaccination or infection. We assessed their humoral response using an anti-SARS-CoV-2 spike receptor binding domain IgG antibody assay (S-RBD-ab),…

• COVID-19 Bivalent Booster in Pregnancy: Maternal and Neonatal Antibody Response to Omicron BA.5, BQ.1, BF.7 and XBB.1.5 SARS-CoV-2 - Our study was to investigate the effects of bivalent COVID-19 booster vaccination during pregnancy on neutralizing antibody (Nab) levels in maternal blood (MB), transplacental transmission in umbilical cord blood (CB), and efficacy against Omicron SARS-CoV-2 subvariants including BA.5, BF.7, BQ.1, and XBB.1.5. We collected MB and CB from 11 pregnant participants during baby delivery and detected Nab inhibition by enzyme-linked immunosorbent assays (ELISA). Nab inhibition was 89-94% in MB and…

• Humoral Immunity in Immunosuppressed IBD Patients after the Third SARS-CoV-2 Vaccination: A Comparison with Healthy Control Subjects - CONCLUSION: Even after the third vaccination, immunosuppressed IBD patients exhibited diminished humoral immunity compared to healthy controls, especially those on anti-TNF therapy. Cases of penetrating infections led to considerably higher antibody levels in IBD patients under anti-TNF therapy compared to uninfected patients. Further investigation through prospective studies in immunosuppressed IBD patients is needed to determine whether this effectively safeguards against future infections or…

• Stand Up to Stand Out: Natural Dietary Polyphenols Curcumin, Resveratrol, and Gossypol as Potential Therapeutic Candidates against Severe Acute Respiratory Syndrome Coronavirus 2 Infection - The COVID-19 pandemic has stimulated collaborative drug discovery efforts in academia and the industry with the aim of developing therapies and vaccines that target SARS-CoV-2. Several novel therapies have been approved and deployed in the last three years. However, their clinical application has revealed limitations due to the rapid emergence of viral variants. Therefore, the development of next-generation SARS-CoV-2 therapeutic agents with a high potency and safety profile remains a high…

• Antiviral Effect of 5’-Arylchalcogeno-3-aminothymidine Derivatives in SARS-CoV-2 Infection - The understanding that zidovudine (ZDV or azidothymidine, AZT) inhibits the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 and that chalcogen atoms can increase the bioactivity and reduce the toxicity of AZT has directed our search for the discovery of novel potential anti-coronavirus compounds. Here, the antiviral activity of selenium and tellurium containing AZT derivatives in human type II pneumocytes cell model (Calu-3) and monkey kidney cells (Vero E6) infected with SARS-CoV-2, and their…

• Development of Masitinib Derivatives with Enhanced M^pro Ligand Efficiency and Reduced Cytotoxicity - Recently, a high-throughput screen of 1900 clinically used drugs identified masitinib, an orally bioavailable tyrosine kinase inhibitor, as a potential treatment for COVID-19. Masitinib acts as a broad-spectrum inhibitor for human coronaviruses, including SARS-CoV-2 and several of its variants. In this work, we rely on atomistic molecular dynamics simulations with advanced sampling methods to develop a deeper understanding of masitinib’s mechanism of M^(pro) inhibition. To improve the inhibitory…

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