Covid-19 Sentry

Contents

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

From Preprints

• Following pandemic guidelines is associated with better wellbeing -
  Background: In response to the Covid-19 pandemic, most countries implemented physical distancing measures. Many mental health experts warned that through increasing social isolation and anxiety, these measures could negatively affect psychosocial wellbeing. However, socially aligning with others by adhering to these measures may also be beneficial for wellbeing. Methods: We examined these two contrasting hypotheses using cross-national survey data (N=

6675. collected fortnightly from participants in 115 countries over 3 months at the beginning of the pandemic. In addition to providing demographic data, participants completed a standardised wellbeing scale, and reported how much they, and others in their social circle and country, were adhering to the distancing measures. Results: We found that being a woman, having lower educational attainment, living alone and being vulnerable to Covid-19 were risk factors for poorer wellbeing. Being young (18-25) was also associated with lower wellbeing, but longitudinal analyses showed that young participants’ wellbeing improved over 3 months. In contrast to widespread views that physical distancing measures negatively affect wellbeing, results showed that following these guidelines was positively associated with wellbeing, even for people in demographic risk groups or those highly vulnerable to Covid-19. Conclusions: These findings provide an important counterpart to the idea that pandemic containment measures such as physical distancing negatively impacted wellbeing unequivocally. Despite the overall burden of the pandemic on psychosocial wellbeing, social alignment with others can still contribute to positive wellbeing. The pandemic has manifested our propensity to adapt to challenges, particularly highlighting how social alignment can forge resilience.
      🖺 Full Text HTML: Following pandemic guidelines is associated with better wellbeing

• LGBTQ+ mental health during the COVID-19 pandemic: Testing mechanisms and moderators of risk -
  The COVID-19 pandemic has created tremendous, and unequal, burdens on mental and physical health throughout the United States. Prior work suggests that LGBTQ+ individuals have experienced disproportionate harms due to the COVID-19 pandemic, but potential mechanisms underlying these disparities remain unclear. In a large (N = 893) sample of U.S. LGBTQ+ adults, we examined four theoretically derived risk factors as potential contributors to depression, anxiety, and suicidal ideation during the summer of 2020. Stressors and disruptions due to the COVID-19 pandemic were common, with over 25% of participants experiencing changes in their living situation, 40% reporting interruptions in health care access, and high levels stress due to social isolation, financial concerns, and increased mental health symptoms. We found that social disconnection, disruptions in health care, financial strain, and efforts to avoid disclosing one’s sexual orientation or gender identity at home were each associated with poorer mental health, with the largest effects evident for identity disclosure avoidance. Transgender and gender diverse adults reported poorer mental health overall, but gender identity did not moderate the effects of other tested risk factors. Results highlight the importance of considering LGBTQ+ mental health in the context of minority-specific stress processes, in addition to more general social determinants of health.
  🖺 Full Text HTML: LGBTQ+ mental health during the COVID-19 pandemic: Testing mechanisms and moderators of risk
• Structures of SARS-CoV-2 B.1.351 neutralizing antibodies provide insights into cocktail design against concerning variants -
  The spread of the SARS-CoV-2 variants could seriously dampen the global effort to tackle the COVID-19 pandemic. Recently, we investigated the humoral antibody responses of SARS-CoV-2 convalescent patients and vaccinees towards circulating variants, and identified a panel of monoclonal antibodies (mAbs) that could efficiently neutralize the B.1.351 (Beta) variant. Here we investigate how these mAbs target the B.1.351 spike protein using cryo-electron microscopy. In particular, we show that two superpotent mAbs, BD-812 and BD-836, have non-overlapping epitopes on the receptor-binding domain (RBD) of spike. Both block the interaction between RBD and the ACE2 receptor; and importantly, both remain fully efficacious towards the B.1.617.1 (Kappa) and B.1.617.2 (Delta) variants. The BD-812/BD-836 pair could thus serve as an ideal antibody cocktail against the SARS-CoV-2 VOCs.
  🖺 Full Text HTML: Structures of SARS-CoV-2 B.1.351 neutralizing antibodies provide insights into cocktail design against concerning variants
• Evolutionary dynamics of indels in SARS-CoV-2 spike glycoprotein -
  SARS-CoV-2, responsible for the current COVID-19 pandemic that claimed over 4.2 million lives, belongs to a class of enveloped viruses that undergo quick evolutionary adjustments under selection pressure. Numerous variants have emerged in SARS-CoV-2 that are currently posing a serious challenge to the global vaccination effort and COVID-19 management. The evolutionary dynamics of this virus are only beginning to be explored. In this work, we have analysed 1.79 million spike glycoprotein sequences of SARS-CoV-2 and found that the virus is fine-tuning the spike with numerous amino acid insertions and deletions (indels). Indels seem to have a selective advantage as the proportions of sequences with indels were steadily increasing over time, currently at over 89%, with similar trends across countries/variants. There were as many as 420 unique indel positions and 447 unique combinations of indels. Despite their high frequency, indels resulted in only minimal alteration, including both gain and loss, of N-glycosylation sites. As indels and point mutations are positively correlated and sequences with indels have significantly more point mutations, they have implications in the context of evolutionary dynamics of the SARS-CoV-2 spike glycoprotein.
  🖺 Full Text HTML: Evolutionary dynamics of indels in SARS-CoV-2 spike glycoprotein
• Comparable neutralization of SARS-CoV-2 Delta AY.1 and Delta in individuals sera vaccinated with BBV152 -
  The recent emergence of the SARS-CoV-2 Variant of Concern B.1.617.2 (Delta) variant and its high transmissibility has led to the second wave in India. BBV152 a whole-virion inactivated SARS-CoV-2 vaccine used for mass immunization in India, showed a 65.2% protection against the Delta variant in a double-blind, randomized, multicentre, phase 3 clinical trial. Subsequently, Delta has been further mutated to Delta AY.1, AY.2, and AY.3. Of these, AY.1 variant was first detected in India in April 2021 and subsequently from twenty other countries as well. Here, we have evaluated the IgG antibody titer and neutralizing potential of sera of COVID-19 naive individuals full doses of BBV152 vaccine, COVID-19 recovered cases with full dose vaccines and breakthrough cases post-immunization BBV152 vaccines against Delta, Delta AY.1 and B.1.617.3. A reduction in neutralizing activity was observed with the COVID-19 naive individuals full vaccinated (1.3, 1.5, 1.9-fold), COVID-19 recovered cases with full BBV152 immunization (2.5, 3.5, 3.8-fold) and breakthrough cases post-immunization (1.9, 2.8, 3.5-fold) against Delta, Delta AY.1 and B.1.617.3 respectively compared to B.1 variant. A minor reduction was observed in the neutralizing antibody titer in COVID- 19 recovered cases full BBV152 vaccinated and post immunized infected cases compared to COVID-19 naive vaccinated individuals. However, with the observed high titers, the sera of individuals belonging to all the aforementioned groups they would still neutralize the Delta, Delta AY.1 and B.1.617.3 variants effectively.
  🖺 Full Text HTML: Comparable neutralization of SARS-CoV-2 Delta AY.1 and Delta in individuals sera vaccinated with BBV152
• Spike protein multiorgan tropism suppressed by antibodies targeting SARS-CoV-2 -
  While there is clinical evidence of severe acute respiratory syndrome coronavirus 2 multiorgan tropism in severely infected coronavirus 19 patients, it is unclear if there is differential multiorgan biodistribution and organ uptake in healthy young individuals, a group that usually has asymptomatic to moderate coronavirus 19 symptoms. In addition, for antibody therapies and vaccines that target the spike protein, it is unclear if these reduce severe acute respiratory syndrome coronavirus 2 or spike protein multiorgan tropism equally. We used fluorescently labeled spike protein near infrared fluorescence to study viral behavior, using an in vivo dynamic imaging system, in young mice. We found a spike protein body-wide biodistribution followed by a slow regional elimination, except for the liver, which showed an accumulation. Spike protein uptake was highest for the lungs, and this was followed by kidney, heart and liver, but, unlike the choroid plexus, it was not detected in the brain parenchyma or cerebrospinal fluid. Thus, the brain vascular barriers were effective in restricting the entry of spike protein into brain parenchyma in young healthy mice. While both anti-angiotensin converting enzyme 2 and anti-spike protein antibodies suppressed spike protein biodistribution and organ uptake, anti-spike protein antibody was more effective. By extension, our data support the efficacy of these antibodies on severe acute respiratory syndrome coronavirus 2 biodistribution kinetics and multiorgan tropism that could determine coronavirus 19 organ-specific outcomes.
  🖺 Full Text HTML: Spike protein multiorgan tropism suppressed by antibodies targeting SARS-CoV-2
• Multi-layered transcriptomic analyses reveal an immunological overlap between COVID-19 and hemophagocytic lymphohistiocytosis associated with disease severity -
  Clinical and hyperinflammatory overlap between COVID-19 and hemophagocytic lymphohistiocytosis (HLH) has been reported. However, the underlying mechanisms are unclear. Here we show that COVID-19 and HLH have an overlap of signaling pathways and gene signatures commonly dysregulated, which were defined by investigating the transcriptomes of 1253 subjects (controls, COVID-19, and HLH patients) using microarray, bulk RNA-sequencing (RNAseq), and single-cell RNAseq (scRNAseq). COVID-19 and HLH share pathways involved in cytokine and chemokine signaling as well as neutrophil- mediated immune responses that associate with COVID-19 severity. These genes are dysregulated at protein level across several COVID-19 studies and form an interconnected network with differentially expressed plasma proteins which converge to neutrophil hyperactivation in COVID-19 patients admitted to intensive care unit. scRNAseq analysis indicated that these genes are specifically upregulated across different leukocyte populations, including lymphocyte subsets and immature neutrophils. Artificial intelligence modeling confirmed the strong association of these genes with COVID-19 severity. Thus, our work indicates putative therapeutic pathways for intervention.
  🖺 Full Text HTML: Multi-layered transcriptomic analyses reveal an immunological overlap between COVID-19 and hemophagocytic lymphohistiocytosis associated with disease severity
• Specialized interferon ligand action in COVID19 -

  The impacts of IFN signaling on COVID19 pathology are multiple, with protective and harmful effects being documented. We report here a multi-omics investigation of IFN signaling in hospitalized COVID19 patients, defining the biosignatures associated with varying levels of 12 different IFN ligands. Previously we showed that seroconversion associates with decreased production of select IFN ligands (Galbraith et al, 2021). We show now that the antiviral transcriptional response in circulating immune cells is strongly associated with a specific subset of ligands, most prominently IFNA2 and IFNG. In contrast, proteomics signatures indicative of endothelial damage associate with levels of IFNB and IFNA6. Differential IFN ligand production is linked to distinct constellations of circulating immune cells. Lastly, IFN ligands associate differentially with activation of the kynurenine pathway, dysregulated fatty acid metabolism, and altered central carbon metabolism. Altogether, these results reveal specialized IFN ligand action in COVID19, with potential diagnostic and therapeutic implications.

  🖺 Full Text HTML: Specialized interferon ligand action in COVID19
• COVID-19 vaccine response in people with multiple sclerosis -

  Objective: To investigate the effect of disease modifying therapies on serological response to SARS-CoV2 vaccines in people with multiple sclerosis Methods: 473 people with multiple sclerosis from 5 centres provided one or more dried blood spot samples and a questionnaire about COVID-19 and vaccine history. Information about disease and drug history was extracted from their medical records. Dried blood spots were eluted and tested for antibodies to SARS-CoV2 receptor binding domain. Seropositivity was expressed according to validated cut-off indices. Antibody titers were partitioned into tertiles using data from people on no disease modifying therapy as a reference. We calculated the odds ratio of seroconversion (Univariate logistic regression) and compared quantitative vaccine response (Kruskal Wallis) following SARS-CoV2 vaccine according to disease modifying therapy. We used regression modelling to explore the effect of factors including vaccine timing, treatment duration, age, vaccine type and lymphocyte count on vaccine response. Results: Compared to no disease modifying therapy, the use of anti-CD20 monoclonal antibodies (odds ratio 0.03; 95% confidence interval 0.01-0.06, p<0.001) and fingolimod (odds ratio 0.41; 95% confidence interval 0.01-0.12) were associated with lower seroconversion following SARS-CoV2 vaccine. All other drug groups did not differ significantly from the untreated cohort. Both time since last anti-CD20 treatment and total time on treatment were significantly related with serological response to vaccination. Vaccine type significantly predicted seroconversion, but not in those on anti-CD20 medications. Interpretation: Some disease modifying therapies carry a risk of attenuated response to SARS- CoV2 vaccination in people with MS. We provide recommendations for the practical management of this patient group.

  🖺 Full Text HTML: COVID-19 vaccine response in people with multiple sclerosis
• Wastewater based surveillance system to detect SARS-CoV-2 genetic material for countries with on-site sanitation facilities: an experience from Bangladesh -

  The presence of SARS-CoV-2 genetic materials in wastewater has become a matter of grave for many countries of the world. Wastewater based epidemiology, in this context, emerged as an important tool in developed countries where proper sewage system is available. Due to the recent shift in the spread of the infection from urban to rural areas, it is now equally important to develop a similar mechanism for rural areas as well. Considering the urgency of the issue a study was conducted in 14 districts of Bangladesh and a total of 238 sewage samples were collected in two different periods from December 2020 to January 2021. We are the first to propose a surveillance system for both urban and rural areas where a proper sewage system is absent. Based on RT-PCR analysis of the water samples, in more than 92% of cases, we found the presence of the SARS-COV-2 gene (ORF1ab, N, and Internal Control-IC). The trend of Ct value varies for different study locations. The spread of genetic material for on-site (m = - 0.0386) sanitation system was found more prominent than that of off-site sewage system (m = 0.0105); which indicated the shift of genetic material from urban to rural areas. Wastewater samples were also measured for physicochemical parameters, including pH (6.30 - 12.50) and temperature (22.10 - 32.60)C. The highest viral titer of 1975 copy/mL in sewage sample was observed in a sample collected from the isolation ward of the SARS-COV-2 hospital. Additionally, a correlation was found between bacterial load and SARS-CoV-2 genetic materials. The results indicated the association of increased Ct values with decreasing number of patients and vice versa. The findings reported in this paper contributed to the field of wastewater-based epidemiology dealing with SARS-COV-2 surveillance for developing countries where proper sewage system is absent and highlighting some of the challenges associated with this approach in such settings. Keywords: On-site Sanitation, Off- site Sanitation, SARS-CoV-2, Genetic Materials, Developing Countries, Rural Wastewater-Based Surveillance System.

  🖺 Full Text HTML: Wastewater based surveillance system to detect SARS-CoV-2 genetic material for countries with on-site sanitation facilities: an experience from Bangladesh
• ‘I don’t feel like I’m learning how to be a doctor’: early insights regarding the impact of Covid-19 on UK medical student professional identity -

  Phenomenon Professional identity development is recognised as a core goal of medical education alongside knowledge and skill acquisition. Identity is a complex entity that can be conceptualised as externally influenced, but individually constructed. Integration from legitimate bystander to “old timer” of the medical community of practice provides a backdrop for individual negotiation of professional identity. During Covid-19, the medical community of practice and education experienced significant disruption. We sought to investigate how these disruptions impacted professional identity development by examining conflicts between students9 identities highlighted by the pressures of the pandemic. Approach A mixed-methods survey was distributed to medical students in the UK. The survey was active from 2nd May to 15th June 2020, during the height of the first wave of the Covid-19 pandemic in the UK. Operating within the paradigm of constructivism, we conducted a reflexive thematic analysis of qualitative responses. Analysis was focused around the disruption to medical education, actions taken by medical students during this disruption, and the tension between student actions where they existed in conflict. Findings Three themes were constructed to describe the identities that participants felt were in conflict during the first wave of the Covid-19 pandemic: Status and role as a future doctor; status and role as a student; and status and role as a member of the wider community. Students noted that lack of clinical exposure was detrimental to their education, implicitly recognising that many aspects of professional identity formation are forged in the clinical environment. Participants were keen to volunteer clinically but struggled to balance this with academic work. Participants worried about the risk to their families and the wider community, and wanted to ensure that their skills would add value to the clinical environment. Volunteers felt frustrated when they were unable to perform tasks which aligned with their identities future doctors, with the exception of participants who worked as interim FY1s (FiY1s), which aligned well with the roles of FY1s. Insights As hypothesised, the participants in this study experienced disruptions to their professional identity development during the first wave of the Covid-19 pandemic in 2020. This work provides early evidence, collected at the beginning of the pandemic, that the effects of disruptions to professional identity development were wide-reaching, often negative, and represent an important topic for future exploration. Given that the pandemic has highlighted areas of identity tension, these findings have the potential to provide insight into how medical training can better nurture professional identity development during and beyond international crises.

  🖺 Full Text HTML: ‘I don’t feel like I’m learning how to be a doctor’: early insights regarding the impact of Covid-19 on UK medical student professional identity
• Dominance of Alpha and Iota variants in SARS-CoV-2 vaccine breakthrough infections in New York City -

  The efficacy of COVID-19 mRNA vaccines is high, but breakthrough infections still occur. We compared the SARS- CoV-2 genomes of 76 breakthrough cases after full vaccination with BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), or JNJ-78436735 (Janssen) to unvaccinated controls (February-April 2021) in metropolitan New York, including their phylogenetic relationship, distribution of variants, and full spike mutation profiles. Their median age was 48 years; seven required hospitalization and one died. Most breakthrough infections (57/76) occurred with B.1.1.7 (Alpha) or B.1.526 (Iota). Among the 7 hospitalized cases, 4 were infected with B.1.1.7, including 1 death. Both unmatched and matched statistical analyses considering age, sex, vaccine type, and study month as covariates supported the null hypothesis of equal variant distributions between vaccinated and unvaccinated in chi-squared and McNemar tests (p>0.1) highlighting a high vaccine efficacy against B.1.1.7 and B.1.526. There was no clear association among breakthroughs between type of vaccine received and variant. In the vaccinated group, spike mutations in the N-terminal domain and receptor-binding domain that have been associated with immune evasion were overrepresented. The evolving dynamic of SARS-CoV-2 variants requires broad genomic analyses of breakthrough infections to provide real-life information on immune escape mediated by circulating variants and their spike mutations.

  🖺 Full Text HTML: Dominance of Alpha and Iota variants in SARS-CoV-2 vaccine breakthrough infections in New York City
• TREATMENTS, RESOURCE UTILIZATION, AND OUTCOMES OF COVID-19 PATIENTS PRESENTING TO EMERGENCY DEPARTMENTS ACROSS PANDEMIC WAVES: AN OBSERVATIONAL STUDY BY THE CANADIAN COVID-19 EMERGENCY DEPARTMENT RAPID RESPONSE NETWORK (CCEDRRN) -

  Background: Treatment strategies for coronavirus disease 2019 (COVID-19) evolved between pandemic waves. Our objective was to compare treatments, acute care resource utilization, and outcomes of COVID-19 patients presenting to Emergency Departments across two pandemic waves. Methods: This observational study enrolled consecutive eligible COVID-19 patients presenting to 46 Emergency Departments participating in the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) between March 1 and December 31, 2020. We collected data by retrospective chart review. Our primary outcome was in-hospital mortality. We used logistic regression modeling to assess the impact of pandemic wave on outcomes. Results: We enrolled 9,967 patients in 8 provinces, 3,336 from the first and 6,631 from the second wave. Patients in the second wave were younger, fewer met criteria for severe COVID-19, and more were discharged from the Emergency Department. Adjusted for patient characteristics and disease severity, steroid use increased (odds ratio [OR] 8.0; 95% confidence interval [CI] 6.4 — 10.0), while the use of invasive mechanical ventilation decreased (OR 0.5; 95%CI 0.4 — 0.6) in the second wave. After adjusting for differences in patient characteristics and disease severity, the odds of hospitalization (OR 0.7; 95%CI 0.6 — 0.8) and critical care admission (OR 0.6; 95%CI 0.4 — 0.7) decreased, while mortality remained unchanged (OR 1.0; 95%CI 0.7-1.4). Interpretation: In patients presenting to Canadian acute care facilities, rapid uptake of steroid therapy was evident. Mortality was stable despite lower critical care utilization in the second wave.

  🖺 Full Text HTML: TREATMENTS, RESOURCE UTILIZATION, AND OUTCOMES OF COVID-19 PATIENTS PRESENTING TO EMERGENCY DEPARTMENTS ACROSS PANDEMIC WAVES: AN OBSERVATIONAL STUDY BY THE CANADIAN COVID-19 EMERGENCY DEPARTMENT RAPID RESPONSE NETWORK (CCEDRRN)
• The association between statin and COVID-19 adverse outcomes: National COVID-19 cohort in South Korea -

  Background: There currently exists limited and conflicting clinical data on the use of statins amongst COVID-19 patients. Given the both paucity and lack of consensus among data on statin9s efficacy and safety amongst COVID-19 patients, the current guideline is to continue statin in COVID-19 patients, who have previously been treated with statins. The aim of this paper was to compare hospitalized patients with COVID-19 who did and did not receive statins, in terms of COVID-19 outcomes. Methods: We conducted population-based retrospective study using South Korea9s nationwide healthcare database as of May 15 2020. We identified 4,349 patients hospitalized with COVID-19 and aged 40 years or older. The cohort entry was defined as the date of hospitalization. Statin users were individuals with inpatient and outpatient prescription records of statins in the 240 days before cohort entry, and non-users were those without such records during this period. Our primary outcome was a composite endpoint of all-cause death, intensive care unit (ICU) admission, mechanical ventilation use and cardiovascular outcomes (myocardial infarction (MI), transient cerebral ischemic attacks (TIA) or stroke). We conducted inverse probability of treatment weighting (IPTW)-adjusted logistic regression analysis to estimate odds ratio (OR) and corresponding 95% confidence intervals (CI), to compare outcomes between statin users and non-users. Findings: 1,115 patients were statin users (mean age = 65.9 years; 60% female), and 3,234 were non-users (mean age = 58.3 years; 64% female). Statin use was not associated with increased risk of the primary outcome (IPTW OR 0.82; 95% CI: 0.60-1.11). Subgroup analysis showed a protective role of statins, for individuals with hypertension (IPTW OR 0.40; 95% CI: 0.23-0.69, p for interaction: 0.0087). Interpretation: Given that statins are not detrimental and that it may be beneficial amongst hypertensive patients and relatively cheap, we would encourage further investigation into statin for the prevention and treatment of COVID-19.

  🖺 Full Text HTML: The association between statin and COVID-19 adverse outcomes: National COVID-19 cohort in South Korea
• Decline in pneumococcal disease in young children during the COVID-19 pandemic associated with suppression of seasonal respiratory viruses, despite persistent pneumococcal carriage: A prospective cohort study -

  Background: Invasive pneumococcal disease (IPD) declined during the COVID-19 pandemic. Previous studies hypothesized that this was due to reduced pneumococcal transmission resulting from non-pharmacological interventions. We used multiple ongoing cohort surveillance projects in children <5 years to test this hypothesis. Methods: The first SARS-CoV-2 cases were detected in February-2020, resulting in a full lockdown, followed by several partial restrictions. Data from ongoing surveillance projects captured the incidence dynamics of community-acquired alveolar pneumonia (CAAP), non-alveolar lower respiratory infections necessitating chest X-rays (NA-LRI), nasopharyngeal pneumococcal carriage in non-respiratory visits, nasopharyngeal respiratory virus detection (by PCR), and nationwide invasive pneumococcal disease (IPD). Monthly rates (January-2020 through February-2021 vs. mean monthly rates 2016-2019 [expected rates]) adjusted for age and ethnicity, were compared. Findings: CAAP and bacteremic pneumococcal pneumonia were strongly reduced (incidence rate ratios, [IRRs] 0.07 and 0.19, respectively); NA-LRI and non-pneumonia IPD were also reduced, with a lesser magnitude (IRRs, 0.46 and 0.42, respectively). In contrast, pneumococcal carriage prevalence was only slightly reduced and density of colonization and pneumococcal serotype distributions were similar to previous years. The pneumococcus-associated disease decline was temporally associated with a full suppression of RSV, influenza viruses, and hMPV, often implicated as co-pathogens with pneumococcus. In contrast, adenovirus, rhinovirus, and parainfluenza activities were within or above expected levels. Interpretation: Reductions in pneumococcal and pneumococcus-associated diseases occurring during the COVID-19 pandemic were not predominantly related to reduced pneumococcal transmission and carriage but were strongly associated with the complete disappearance of specific respiratory viruses. Funding: Partially funded by Pfizer, Inc.

  🖺 Full Text HTML: Decline in pneumococcal disease in young children during the COVID-19 pandemic associated with suppression of seasonal respiratory viruses, despite persistent pneumococcal carriage: A prospective cohort study

From Clinical Trials

• Phase II/III Study of AZD2816, for the Prevention of COVID-19 in Adults - Conditions:   COVID-19;   SARS-CoV-2
  Interventions:   Biological: AZD1222;   Biological: AZD2816
  Sponsor:   AstraZeneca
  Recruiting

• Clinical Trial For Early SARS-CoV-2 (COVID-19) Treatment - Condition:   Covid19
  Interventions:   Drug: Hydroxychloroquine;   Drug: Favipiravir;   Drug: Favipiravir + Hydroxychloroquine;   Drug: Placebo
  Sponsor:   Health Institutes of Turkey
  Completed

• Echinacea Drug for Covid-19 - Condition:   Covid19
  Intervention:   Drug: ECHINACEA ARKOPHARMA
  Sponsors:  
  Jesús R. Requena;   IDIS;   SALUD;   Laboratoires Arkopharma
  Recruiting

• Effects of Respiratory Muscle Training in Patients With Post COVID-19 - Condition:   Covid19
  Interventions:   Other: Exercise training group;   Other: Control training group
  Sponsor:   Gazi University
  Completed

• SOLIDARITY Finland Long COVID-19 - Condition:   Covid19
  Intervention:   Drug: Remdesivir
  Sponsors:  
  Clinical Urology and Epidemiology Working Group;   University of Helsinki;   World Health Organization;   Helsinki University Central Hospital;   Hyvinkää Hospital;   Kanta-Häme Central Hospital;   Kuopio University Hospital;   Oulu University Hospital;   Porvoo Hospital;   Seinajoki Central Hospital;   Mikkeli Central Hospital;   Tampere University Hospital
  Recruiting

• Vaccination for Recovered Inpatients With COVID-19 (VATICO) - Condition:   Covid19
  Interventions:   Biological: Moderna mRNA-1273 COVID-19 vaccine;   Biological: Pfizer BNT162b2 COVID-19 vaccine
  Sponsors:   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Minnesota;   National Institute of Allergy and Infectious Diseases (NIAID);   University of Copenhagen;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Medical Research Council
  Not yet recruiting

• COVID-19 and Lung Ultrasound Utility - Condition:   Covid19
  Intervention:   Device: Device: Butterfly iQ
  Sponsor:  
  Rocket Doctor Inc.
  Recruiting

• Efficacy of Canrenone as add-on Treatment in Moderate to Severe ARDS in COVID-19 - Condition:   COVID-19 Acute Respiratory Distress Syndrome
  Intervention:  
  Drug: Potassium Canrenoate
  Sponsors:   Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico;   University of Milan;   IRCCS Azienda Ospedaliero-Universitaria di Bologna
  Not yet recruiting

• Saliva-based COVID-19 DNA Aptamer Test - Condition:   Covid19
  Intervention:   Device: AptameX
  Sponsors:   Achiko AG;   Udayana University
  Recruiting

• Evaluation of the RD-X19 Treatment Device in Individuals With Mild to Moderate COVID-19 - Condition:   COVID19
  Interventions:   Device: RD-X19;   Device: Sham
  Sponsor:  
  EmitBio Inc.
  Recruiting

• Evaluation of The Efficacy of Triazavirin Versus Oseltamivir in Egyptian Patients Infected With COVID-19 - Condition:   Covid19
  Intervention:   Drug: standard treatment COVID-19 + Triazavirin
  Sponsor:   Ain Shams University
  Recruiting

• The Efficacy of Nigella Sativa Versus VitaminD3 as Supplement Therapy in Coronavirus Disease 2019 (COVID-19) - Condition:   Covid19
  Intervention:   Dietary Supplement: Nigella Sativa capsule twice daily
  Sponsor:   Ain Shams University
  Recruiting

• Effect of Cyproheptadine on Ventilatory Support-free Days in Critically Ill Patients With COVID-19 - Condition:   COVID-19 Pneumonia
  Intervention:   Drug: Cyproheptadine
  Sponsor:  
  Hospital de Clinicas de Porto Alegre
  Not yet recruiting

• Intervention to Promote COVID-19 Vaccination - Conditions:   Covid19;   Vaccination
  Intervention:   Behavioral: Health System Vaccination Text Messages
  Sponsors:   University of Massachusetts, Worcester;   National Institute on Minority Health and Health Disparities (NIMHD)
  Not yet recruiting

• Effects of COVID-19 on Cavernous Smooth Muscle - Conditions:   Erectile Dysfunction Due to Diseases Classified Elsewhere;   Covid19
  Intervention:  
  Diagnostic Test: corpus cavernosum electromyography
  Sponsor:   Ankara Yildirim Beyazıt University
  Completed

From PubMed

• Multi-omic profiling of plasma reveals molecular alterations in children with COVID-19 - Rationale: Children usually develop less severe symptoms responding to Coronavirus Disease 2019 (COVID-19) than adults. However, little is known about the molecular alterations and pathogenesis of COVID-19 in children. Methods: We conducted plasma proteomic and metabolomic profilings of the blood samples of a cohort containing 18 COVID-19-children with mild symptoms and 12 healthy children, which were enrolled from hospital admissions and outpatients, respectively. Statistical analyses were…

• Mutations in SARS-CoV-2 ORF8 Altered the Bonding Network With Interferon Regulatory Factor 3 to Evade Host Immune System - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been continuously mutating since its first emergence in early 2020. These alterations have led this virus to gain significant difference in infectivity, pathogenicity, and host immune evasion. We previously found that the open-reading frame 8 (ORF8) of SARS-CoV-2 can inhibit interferon production by decreasing the nuclear translocation of interferon regulatory factor 3 (IRF3). Since several mutations in ORF8 have been observed,…

• Discovery and evolution of 12N-substituted aloperine derivatives as anti-SARS-CoV-2 agents through targeting late entry stage - So far, there is still no specific drug against COVID-19. Taking compound 1 with anti-EBOV activity as the lead, fifty- four 12N-substituted aloperine derivatives were synthesized and evaluated for the anti-SARS-CoV-2 activities using pseudotyped virus model. Among them, 8a exhibited the most potential effects against both pseudotyped and authentic SARS-CoV-2, as well as SARS-CoV and MERS-CoV, indicating a broad-spectrum anti-coronavirus profile. The mechanism study disclosed that 8a might block…

• Safety of inhaled ivermectin as a repurposed direct drug for treatment of COVID-19: A preclinical tolerance study - CONCLUSION: The safety of inhaledivermectin-HP-β-CD formulation is dose-dependent. Nevertheless, use of low doses(0.05 and 0.1 mg/kg) could be considered as a possible therapeutic regimen in COVID-19 cases.

• Flavonoids in Ampelopsis grossedentata as covalent inhibitors of SARS-CoV-2 3CL(pro): Inhibition potentials, covalent binding sites and inhibitory mechanisms - Coronavirus 3C-like protease (3CL^(pro)) is a crucial target for treating coronavirus diseases including COVID-19. Our preliminary screening showed that Ampelopsis grossedentata extract (AGE) displayed potent SARS-CoV-2-3CL^(pro) inhibitory activity, but the key constituents with SARS-CoV-2-3CL^(pro) inhibitory effect and their mechanisms were unrevealed. Herein, a practical strategy via integrating bioactivity-guided fractionation and purification, mass spectrometry-based peptide profiling and…

• Synthetic and computational efforts towards the development of peptidomimetics and small-molecule SARS-CoV 3CLpro inhibitors - Severe Acute Respiratory Syndrome (SARS) is a severe febrile respiratory disease caused by the beta genus of human coronavirus, known as SARS-CoV. Last year, 2019-n-CoV (COVID-19) was a global threat for everyone caused by the outbreak of SARS-CoV-2. 3CLpro, chymotrypsin-like protease, is a major cysteine protease that substantially contributes throughout the viral life cycle of SARS-CoV and SARS-CoV-2. It is a prospective target for the development of SARS-CoV inhibitors by applying a…

• Computational identification of repurposed drugs against viruses causing epidemics and pandemics via drug-target network analysis - Viral epidemics and pandemics are considered public health emergencies. However, traditional and novel antiviral discovery approaches are unable to mitigate them in a timely manner. Notably, drug repurposing emerged as an alternative strategy to provide antiviral solutions in a timely and cost-effective manner. In the literature, many FDA-approved drugs have been repurposed to inhibit viruses, while a few among them have also entered clinical trials. Using experimental data, we identified…

• Sialic acid-conjugate modified doxorubicin nanoplatform for treating neutrophil-related inflammation - Neutrophils, the most abundant leukocytes in human peripheral blood, are important effector cells that mediate the inflammatory response. During neutrophil dysfunction, excessive activation and uncontrolled infiltration are the core processes in the progression of inflammation-related diseases, including severe coronavirus disease-19 (COVID-19), sepsis, etc. Herein, we used sialic acid-modified liposomal doxorubicin (DOX-SAL) to selectively target inflammatory neutrophils in the peripheral blood…

• A synthetic nanobody targeting RBD protects hamsters from SARS-CoV-2 infection - SARS-CoV-2, the causative agent of COVID-19¹, features a receptor-binding domain (RBD) for binding to the host cell ACE2 protein^(1-6). Neutralizing antibodies that block RBD-ACE2 interaction are candidates for the development of targeted therapeutics^(7-17). Llama-derived single-domain antibodies (nanobodies, ~15 kDa) offer advantages in bioavailability, amenability, and production and storage owing to their small sizes and high stability. Here, we report the rapid selection of 99 synthetic…

• A 34-Year-Old Woman from Brazil with Pulmonary Lymphangioleiomyomatosis Diagnosed by Raised Serum Vascular Endothelial Growth Factor-D (VEGF-D) Levels and Lung Cysts on Computed Tomography Imaging Presenting with COVID-19 Pneumonia - BACKGROUND There is growing concern about the clinical course of certain diseases in patients who are simultaneously infected by SARS-CoV-2. This report is of a 34-year-old woman from Brazil with a recent diagnosis of pulmonary lymphangioleiomyomatosis (LAM) diagnosed by raised serum VEGF-D levels and the finding of lung cysts on computed tomography (CT) imaging, who presented with COVID-19 pneumonia. CASE REPORT Five months after the diagnosis of pulmonary LAM, which was based on the presence…

• Targeting COVID-19 (SARS-CoV-2) main protease through active phytocompounds of ayurvedic medicinal plants - Emblica officinalis (Amla), Phyllanthus niruri Linn. (Bhumi Amla) and Tinospora cordifolia (Giloy) - A molecular docking and simulation study - Coronavirus Disease-2019 (COVID-19), a viral disease caused by severe acute respiratory syndrome coronavirus-2 (SARS- CoV-2) was declared a global pandemic by WHO in 2020. In this scenario, SARS-CoV-2 main protease (COVID-19 M^(pro)), an enzyme mainly involved in viral replication and transcription is identified as a crucial target for drug discovery. Traditionally used medicinal plants contain a large amount of bioactives and pave a new path to develop drugs and medications for COVID-19. The…

• Potent antiviral activity of Agrimonia pilosa, Galla rhois, and their components against SARS-CoV-2 - Agrimonia pilosa (AP), Galla rhois (RG), and their mixture (APRG64) strongly inhibited SARS-CoV-2 by interfering with multiple steps of the viral life cycle including viral entry and replication. Furthermore, among 12 components identified in APRG64, three displayed strong antiviral activity, ursolic acid (1), quercetin (7), and 1,2,3,4,6-penta-O- galloyl-β-d-glucose (12). Molecular docking analysis showed these components to bind potently to the spike receptor- binding-domain (RBD) of the…

• Facile synthesis, antimicrobial and antiviral evaluation of novel substituted phenyl 1,3-thiazolidin-4-one sulfonyl derivatives - A series of novel substituted phenyl 1, 3-thiazolidin-4-one sulfonyl derivatives 5 (a-t) were synthesized and screened for their in-vitro anti-microbial and anti-viral activity. The result of the anti-microbial assay demonstrated compounds 5d, 5f, 5g, 5h, 5i, 5j showed prominent inhibitory activity against all the tested Gram-positive and Gram-negative bacterial strains, while compounds 5g, 5j, 5o, 5p, 5q showed significant activity against the entire set of fungal strains as compared to…

• Synthetic Peptides That Antagonize the Angiotensin-Converting Enzyme-2 (ACE-2) Interaction with SARS-CoV-2 Receptor Binding Spike Protein - The SARS-CoV-2 viral spike protein S receptor-binding domain (S-RBD) binds ACE2 on host cells to initiate molecular events, resulting in intracellular release of the viral genome. Therefore, antagonists of this interaction could allow a modality for therapeutic intervention. Peptides can inhibit the S-RBD:ACE2 interaction by interacting with the protein- protein interface. In this study, protein contact atlas data and molecular dynamics simulations were used to locate interaction hotspots on the…

• Quantum simulations of SARS-CoV-2 main protease M(pro) enable high-quality scoring of diverse ligands - The COVID-19 pandemic has led to unprecedented efforts to identify drugs that can reduce its associated morbidity/mortality rate. Computational chemistry approaches hold the potential for triaging potential candidates far more quickly than their experimental counterparts. These methods have been widely used to search for small molecules that can inhibit critical proteins involved in the SARS-CoV-2 replication cycle. An important target is the SARS-CoV-2 main protease Mpro, an enzyme that cleaves…

From Patent Search

• Camellia nitidissima C.W.Chi Caffeine and Chlorogenic acid composition for anti-SARS-CoV-2 and preparation method and application thereof - - link

• A Novel Method COVID -19 infection using Deep Learning Based System - - link

• A SYSTEM AND METHOD FOR COVID- 19 DIAGNOSIS USING DETECTION RESULTS FROM CHEST X- RAY IMAGES - - link

• Advanced Machine Learning System combating COVID-19 virus Detection, Spread, Prevention and Medical Assistance. - - link

• 一种包装重组流感病毒的重组载体和重组流感病毒及其构建方法和应用 - 本发明提供了一种包装重组流感病毒的重组载体和重组流感病毒及其构建方法和应用，涉及生物医药技术领域。本发明利用A型流感病毒八个基因片段为骨架包装出带有新型冠状病毒SARS‑CoV‑2表面刺突蛋白受体结合域（SARS‑CoV‑2_RBD）片段的重组流感病毒，此重组流感病毒可在复制过程中表达具有生物学活性和免疫原性的刺突蛋白受体结合区域RBD。本发明所述重组流感病毒rgH1N1（PR8）‑PA‑RBD可作为重组病毒类药物，用于2019新型冠状病毒肺炎（COVID‑19）的预防；也可作为体外SARS‑COV‑2 RBD等相关抗原表达和体内递呈系统。 - link

• Differential detection kit for common SARS-CoV-2 variants in COVID-19 patients - - link

• 新型冠状病毒B.1.525尼日利亚突变株RBD的基因及其应用 - 本发明属于生物技术领域，具体涉及新型冠状病毒B.1.525尼日利亚突变株RBD的基因及其应用。本发明的新型冠状病毒B.1.525尼日利亚突变株RBD的基因，其核苷酸序列如SEQ ID NO.1或SEQ ID NO.6所示。本发明通过优化野生型新型冠状病毒B.1.525尼日利亚突变株RBD的基因序列，并结合筛选确定了相对最佳序列，优化后序列产生的克隆表达效率比野生型新型冠状病毒B.1.525尼日利亚突变株RBD序列表达效率大幅提高，从而，本发明的新型冠状病毒B.1.525尼日利亚突变株RBD的基因可以用于制备新型冠状病毒疫苗。 - link

• 一种新型冠状病毒的mRNA疫苗 - 本发明公开了一种新型冠状病毒的mRNA疫苗。本发明提供的疫苗，其活性成分为mRNA，如序列表的序列6所示。本发明还保护TF‑RBD蛋白，如序列表的序列2所示。本发明的发明人通过一系列序列设计和序列优化得到了特异DNA分子，进一步构建了特异重组质粒，将特异重组质粒进行体外转录，可以得到多聚化TF‑RBD mRNA。进一步的，发明人制备了负载TF‑RBD mRNA的脂质纳米粒。本发明对于新型冠状病毒的防控具有重大的应用推广价值。 - link

• 新型冠状病毒B．1．1．7英国突变株RBD的基因及其应用 - 本发明属于生物技术领域，具体涉及新型冠状病毒B．1．1．7英国突变株RBD的基因及其应用。本发明的新型冠状病毒B．1．1．7英国突变株RBD的基因，其核苷酸序列如SEQ ID NO.1或SEQ ID NO.6所示。本发明通过优化野生型新型冠状病毒B．1．1．7英国突变株RBD的基因序列，并结合筛选确定了相对最佳序列，优化后序列产生的克隆表达效率比野生型新型冠状病毒B．1．1．7英国突变株RBD序列表达效率大幅提高，从而，本发明的新型冠状病毒B．1．1．7英国突变株RBD的基因更有利于用于制备新型冠状病毒疫苗。 - link

• SARS-CoV-2 anti-viral therapeutic - - link