Travel destinations, particularly large resorts in otherwise small communities, risk infectious disease outbreaks from an influx of visitors who may import infections during peak seasons. The COVID-19 pandemic highlighted this risk in the context of global travel and has raised questions about appropriate interventions to curb the potential spread of infectious disease at tourist destinations. In Colorado, the initial outbreaks of SARS-CoV-2 in the state occurred in ski communities, leading to large economic losses from closures and visitor restrictions. In this study, we modeled SARS-CoV-2 transmission during the 2020-21 season in a ski region of Colorado to determine optimal combinations of intervention strategies that would keep the region below a predetermined threshold of SARS-CoV-2 infection density. This analysis used an age-stratified, deterministic SEIR compartmental model of disease transmission, calibrated to cellphone-based mobility data, to simulate infection trajectories during the winter ski season. Under three national infection levels corresponding to high, medium, and low viral importation risk, we estimated the potential impact of interventions including policy and behavior changes, visitor restriction strategies, and case investigation/contact tracing, in order to quantify the relative and absolute impacts of these interventions in the context of the COVID-19 pandemic. Our results suggest that, in the context of low viral importation risk, case investigation/contact tracing and policy and behavior changes may be sufficient to stay below predetermined infection thresholds without visitor restrictions. However, if viral importation risk is high, visitor restrictions and/or screening for infected visitors would be needed to avoid lockdown-like control scenarios and large outbreaks in tourist communities. These findings provide important guidance to tourist destinations for balancing policy impact in future infectious disease outbreaks.
Wastewater surveillance of severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2) has proven a practical complement to clinical data for assessing community-scale infection trends. Clinical assays, such as the CDC–promulgated N1, N2, and N3 have been used to detect and quantify viral RNA in wastewater but, to date, have not included estimates of reliability of true positive or true negative. Bayes Theorem was applied to estimate Type I and Type II error rates for detections of the virus in wastewater. Conditional probabilities of true positive or true negative were investigated when one assay was used, or multiple assays were run concurrently. Cumulative probability analysis was used to assess the likelihood of true SARS–CoV–2 detection using multiple samples. Results demonstrate highly reliable positive (>0.86 for priors >0.25) and negative (>0.80 for priors = 0.50) results using a single assay. Using N1 and N2 concurrently caused greater reliability (>0.99 for priors <0.05) when results concurred but generated potentially counterintuitive interpretations when results were discordant. Regional wastewater surveillance data was investigated as a means of setting prior probabilities. Probability of true detection with a single marker was investigated using cumulative probability across all combinations of positive and negative results for a set of three samples. Findings using a low (0.11) and uniformed (0.50) initial prior resulted in high probabilities of detection (>0.95) even when a set of samples included one or two negative results, demonstrating the influence of high sensitivity and specificity values. Analyses presented here provide a practical framework for understanding analytical results generated by wastewater surveillance programs.
The CLARITY trial (Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY Disease) investigates the effectiveness of angiotensin receptor blockers in addition to standard care compared to placebo (in Indian sites) with standard care in reducing the duration and severity of lung failure in patients with COVID-19. The CLARITY trial is a multi-centre, randomised controlled Bayesian adaptive trial with regular planned analyses where pre- specified decision rules will be assessed to determine whether the trial should be stopped due to sufficient evidence of treatment effectiveness or futility. Here we describe the statistical analysis plan for the trial, and define the pre- specified decision rules, including those that could lead to the trial being halted. The primary outcome is clinical status on a 7-point ordinal scale adapted from the WHO Clinical Progression scale assessed at Day 14. The primary analysis will follow the intention-to-treat principle. A Bayesian adaptive trial design was selected because there is considerable uncertainty about the extent of potential benefit of this treatment.
Background Although effective vaccines have been developed against COVID-19, the level of neutralizing antibodies (Nabs) induced after vaccination in the real world is still unknown. To evaluate the level and persistence of NAbs induced by two inactivated COVID-19 vaccines in China. Methods and findings Serum samples were collected from 1,335 people aged 18 and over who were vaccinated with COVID-19 inactivated vaccine in Peking University People9s Hospital from January 19 to June 23, 2021, for detection of COVID-19 antibodies. The WHO standard of SARS-CoV-2 NAbs was detected. The coefficients of variation between the detection results and the true values of the NAbs detected by the WHO standard were all lower than the WHO international standard 3% after the dilution of the original and the dilution of the theoretical concentrations of 500 IU/mL, 250 IU/mL, 125 IU/mL, 72.5 IU/mL, 36.25 IU/mL and 18.125 IU/mL. On day 11-70, the positive rate of NAbs against COVID-19 was 82% to 100%; From day 71 to 332, the positive rate of NAbs decreased to 27%. The level of NAbs was significantly higher at 3-8 Weeks than at 0-3 Weeks. There was a high linear correlation between NAbs and IgG antibodies in 1335 vaccinated patients. NAbs levels were decreased in 31 of 38 people (81.6%) at two time points after the second dose of vaccine. There was no significant difference in age between the group with increased and decreased neutralizing antibody levels (x2 =-0.034, P>0.05). The positive rate of NAbs in the two-dose vaccine group (77.3%) was significantly higher than that in the one-dose group (18.1%), with statistical difference (x2=312.590, P<0.001). A total of 206 people who were 11-70 days after receiving the second dose were tested and divided into three groups: 18-40 years old, 41-60 years old and >60 years old. The positive rates of NAbs in three groups (18-40 years old, 41-60 years old and >60 years old) were 95.14%, 78.43% and 81.8%, respectively. The positive rate of NAbs was significantly higher in 18-40 years old than in 41-60 years old (x2=12.547, P <0.01). The titer of NAbs in 18-40 years old group was significantly higher than that in 41-60 years old group (t=-0.222, P <0.01). The positive rate of NAbs in male group (89.32%) was lower than in female (91.26%), but there was no significant difference (x2=0.222, P >0.05). Conclusions The positive rate of NAbs was the highest from 10 to 70 days after the second dose of vaccine, and the positive rate gradually decreased as time went by. There was a high linear correlation between COVID-19 NAbs and IgM/IgG antibodies in vaccinators, suggesting that in cases where NAbs cannot be detected, IgM/IgG antibodies can be detected instead. The level of NAbs produced after vaccination was affected by age, but not by gender. The highest levels of NAbs were produced between shots 21 to 56 days apart, suggesting that 21 to 56 days between shots is suitable for vaccination.
Background: As at end of July 2021, the COVID-19 pandemic has been less severe in sub-Saharan Africa than elsewhere. In Malawi, there have been two subsequent epidemic waves. We therefore aimed to describe the dynamics of SARS-CoV-2 exposure in Malawi. Methods: We measured the seroprevalence of anti-SARS-CoV-2 antibodies among randomly selected blood donor sera in Malawi from January 2020 to February 2021. In a subset, we also assesed in vitro neutralisation against the original variant (D614G WT) and the Beta variant. Findings: A total of 3586 samples were selected from the blood donor database, of which 2685 (74.9%) were male and 3132 (87.3%) were aged 20-49 years. Of the total, 469 (13.1%) were seropositive. Seropositivity was highest in October 2020 (15.7%) and February 2021 (49.7%) reflecting the two epidemic waves. Unlike the first wave, both urban and rural areas had high seropositivity by February 2021, Balaka (rural, 37.5%), Blantyre (urban, 54.8%), Lilongwe (urban, 54.5%) and Mzuzu (urban, 57.5%). First wave sera showed potent in vitro neutralisation activity against the original variant (78%[7/9]) but not the Beta variant (22% [2/9]). Second wave sera potently neutralised the Beta variant (73% [8/11]). Interpretation: The findings confirm extensive SARS-CoV-2 exposure in Malawi over two epidemic waves with likely poor cross-protection to reinfection from the first on the second wave. Since prior exposure augments COVID-19 vaccine immunity, prioritising administration of the first dose in high SARS-CoV-2 exposure settings could maximise the benefit of the limited available vaccines in Malawi and the region.
Background: The SARS-CoV-2 Delta variant (B.1.617.2), initially identified in India, has become predominant in several countries, including Portugal. Few studies have compared the effectiveness of mRNA vaccines against Delta versus Alpha variant of concern (VOC) and estimated variant-specific viral loads in vaccine infection breakthroughs cases. In the context of Delta dominance, this information is critical to inform decision-makers regarding the planning of restrictions and vaccination roll-out. Methods: We developed a case-case study to compare mRNA vaccines9 effectiveness against Delta (B.1.617.2) versus Alpha (B.1.1.7) variants. We used RT-PCR positive cases notified to the National Surveillance System between 17th of May and 4th of July 2021 (week 20 to 26) and information about demographics and vaccination status through the electronic vaccination register. Whole-genome sequencing (WGS) or spike (S) gene target failure (SGTF) data were used to classify SARS-CoV-2 variants. The odds of vaccinated individuals to become infected (odds of vaccine infection breakthrough) in Delta cases compared to Alpha SARS-CoV-2 cases was estimated by conditional logistic regression adjusted for age group, sex, and matched by the week of diagnosis. As a surrogate of viral load, mean RT-PCR Ct values were stratified and compared between vaccine status and VOC. Results: Of the 2 097 SARS-CoV-2 RT- PCR positive cases included in the analysis, 966 (46.1%) were classified with WGS and 1131 (53.9%) with SGTF. Individuals infected with the Delta variant were more frequently vaccinated 162 (12%) than individuals infected with the Alpha variant 38 (5%). We report a statistically significant higher odds of vaccine infection breakthrough for partial (OR=1.70; CI95% 1.18 to 2.47) and complete vaccination (OR=1.96; CI95% 1.22 to 3.14) in the Delta cases when compared to the Alpha cases, suggesting lower mRNA vaccine effectiveness against Delta cases. On our secondary analysis, we observed lower mean Ct values for the Delta VOC cases versus Alpha, regardless the vaccination status. Additionally, the Delta variant cases revealed a Ct-value mean increase of 2.24 (CI95% 0.85 to 3.64) between unvaccinated and fully vaccinated breakthrough cases contrasting with 4.49 (CI95% 2.07 to 6.91) in the Alpha VOC, suggesting a lower impact of vaccine on viral load of Delta cases. Conclusions: We found significantly higher odds of vaccine infection breakthrough in Delta cases when compared to Alpha cases, suggesting lower effectiveness of the mRNA vaccines in preventing infection with the Delta variant. Additionally, the vaccine breakthrough cases are estimated to be of higher mean Ct values, suggesting higher infectiousness with the Delta variant infection. These findings can help decision-makers weigh on the application or lifting of control measures and adjusting vaccine roll-out depending on the predominance of the Delta variant and the coverage of partial and complete mRNA vaccination.
Background: Immune protection following either vaccination or infection with SARS-CoV-2 decreases over time. Objective: To determine the kinetics of SARS-CoV-2 IgG antibodies following administration of two doses of BNT162b2 vaccine, or SARS-CoV-2 infection in unvaccinated individuals. Methods: Antibody titers were measured between January 31, 2021, and July 31, 2021 in two mutually exclusive groups: i) vaccinated individuals who received two doses of BNT162b2 vaccine and had no history of previous infection with COVID-19 and ii) SARS-CoV-2 convalescents who had not received the vaccine. Results: A total of 2,653 individuals fully vaccinated by two doses of vaccine during the study period and 4,361 convalescent patients were included. Higher SARS-CoV-2 IgG antibody titers were observed in vaccinated individuals (median 1581 AU/mL IQR [533.8-5644.6]) after the second vaccination, than in convalescent individuals (median 355.3 AU/mL IQR [141.2-998.7]; p<0.001). In vaccinated subjects, antibody titers decreased by up to 40% each subsequent month while in convalescents they decreased by less than 5% per month. Six months after BNT162b2 vaccination 16.1% subjects had antibody levels below the seropositivity threshold of <50 AU/mL, while only 10.8% of convalescent patients were below <50 AU/mL threshold after 9 months from SARS-CoV-2 infection. Conclusions: This study demonstrates individuals who received the Pfizer-BioNTech mRNA vaccine have different kinetics of antibody levels compared to patients who had been infected with the SARS-CoV-2 virus, with higher initial levels but a much faster exponential decrease in the first group.
Introduction: COVID-19 vaccination is recommended for people living with HIV (PLWH), among whom social inequities and co-morbidities may drive risks of COVID-19 infection and outcome severity. Among a provincial (British Columbia) sample, we determined the prevalence of COVID-19 vaccine intention by HIV status and assessed socio- demographic, vaccine hesitancy, and psychological predictors of vaccine intention. Methods: Individuals (25-69y) recruited from province-wide research cohorts completed an online survey examining COVID-19 impacts (August/2020-March/2021). Among women and gender diverse participants, we compared intention to receive a recommended COVID-19 vaccine (Very likely/Likely vs Neutral/Unlikely/Very Unlikely) by self-reported HIV status. Logistic regression models assessed the independent effect of HIV status and other factors on vaccine intention. Results: Of 5,588 participants, 69 (1.2%) were PLWH, of whom 79.7% were on antiretroviral therapy. Intention to vaccinate was significantly lower among PLWH compared to participants not living with HIV (65.2% vs 79.6%; OR: 0.44; 95%CI: 0.32-0.60). However, this association was attenuated after adjustment for social disparities (aOR:0.85; 95%CI: 0.48-1.55). Among PLWH, those with greater vaccine confidence, positive attitudes towards the COVID-19 vaccine, and more strongly influenced by direct and indirect social norms to vaccinate had significantly higher odds of vaccine intention. Discussion: Tailored messaging is needed to build vaccine confidence, address questions about vaccine benefits, and support informed vaccination decision-making to promote COVID-19 vaccine uptake among women and gender diverse PLWH.
Whole-genome sequencing of viral isolates is critical for informing transmission patterns and ongoing evolution of pathogens, especially during a pandemic. However, when genomes have low variability in the early stages of a pandemic, the impact of technical and/or sequencing errors increases. We quantitatively assessed inter-laboratory differences in consensus genome assemblies of 72 matched SARS-CoV-2-positive specimens sequenced at different laboratories in Sydney, Australia. Raw sequence data were assembled using two different bioinformatics pipelines in parallel, and resulting consensus genomes were compared to detect laboratory-specific differences. Matched genome sequences were predominantly concordant, with a median pairwise identity of 99.997%. Identified differences were predominantly driven by ambiguous site content. Ignoring these produced differences in only 2.3% (5/216) of pairwise comparisons, each differing by a single nucleotide. Matched samples were assigned the same Pango lineage in 98.2% (212/216) of pairwise comparisons, and were mostly assigned to the same phylogenetic clade. However, epidemiological inference based only on single nucleotide variant distances may lead to significant differences in the number of defined clusters if variant allele frequency thresholds for consensus genome generation differ between laboratories. These results underscore the need for a unified, best-practices approach to bioinformatics between laboratories working on a common outbreak problem.
COVID-19 has affected all countries. Its containment represents a unique challenge for India due to a large population (>1.38 billion) across a wide range of population densities. Assessment of the COVID-19 disease burden is required to put the disease impact into context and support future pandemic policy development. Here, we present the national-level burden of COVID-19 in India in 2020 that accounts for differences across urban and rural regions and across age groups. Disability-adjusted life years (DALY) due to COVID-19 were estimated in the Indian population in 2020, comprised of years of life lost (YLL) and years lived with disability (YLD). Scenario analyses were conducted to account for excess deaths not recorded in the official data and for reported COVID-19 deaths. The direct impact of COVID-19 in 2020 in India was responsible for 14,106,060 (95% uncertainty interval [UI] 14,030,129-14,213,231) DALYs, consisting of 99.2% (95% UI 98.47-99.64%) YLLs and 0.80% (95% UI 0.36-1.53) YLDs. DALYs were higher in urban (56%; 95% UI 56-57%) than rural areas (44%; 95% UI 43.4-43.6) and in males (64%) than females (36%). In absolute terms, the highest DALYs occurred in the 51-60-year-old age group (28%) but the highest DALYs per 100,000 persons were estimated for the 71-80 year old age group (5,481; 95% UI 5,464-5,500 years). There were 4,823,791 (95% UI 4,760,908-4,924,307) DALYs after considering reported COVID-19 deaths only. The DALY estimations have direct and immediate implications not only for public policy in India, but also internationally given that India represents one sixth of the global population.
Importance: Vaccines against SARS-CoV-2 are highly effective in the general population; however, their efficacy may be diminished in maintenance dialysis patients, a population particularly vulnerable to COVID-19 infection and morbidity. Objective: We assessed vaccine response in a national sample of maintenance dialysis patients and identified predictors of response. Design: Retrospective cohort study Setting: 130 Dialysis Clinic, Inc (DCI) facilities Participants: Maintenance dialysis patients without known prior COVID-19 or a positive baseline antibody titer Exposure(s): Vaccine type and clinical characteristics Main Outcome(s): Using a semi-quantitative assay for antibodies against SARS-CoV-2 spike antigen, vaccine response was defined as at least one titer ≥1 U/L between 14 and 74 days after completion of a SARS-CoV-2 vaccine series. Regression analysis was used to identify characteristics associated with response. Results: Among 1528 patients, 437 received BNT162b2/Pfizer vaccine, 766 received mRNA-1273/Moderna, and 325 received Ad26.COV2.S/Janssen. Serologic response differed significantly by vaccine type: 381/437 (87%) among BNT162b2/Pfizer recipients, 736/766 (96%) among mRNA-1273/Moderna recipients, and 119/325 (37%) among Ad26.COV2.S/Janssen recipients. Vaccine type, older age, immune-modulating medication, history of transplantation, and lower serum albumin were associated with vaccine non-response. Conclusions and Relevance: Serologic response to mRNA vaccines is robust among maintenance dialysis patients. Future research should evaluate durability of this response, correlation between seroresponse and protection from COVID-19, and the role of the AD26.COV2.S/Janssen vaccine in this vulnerable population.
Background: Coronavirus disease COVID-19 has spread worldwide extremely rapidly. Although many individuals have been infected and have cleared the virus, developing virus-specific antibodies and effector/memory T cells, an important question still to be answered is what levels of T cell and antibody responses are sufficient to protect from the infection. Methods: In 5,340 Moscow residents, we evaluated the anti-SARS-CoV-2 IgM/IgG titers and the frequencies of the T cells specific to the nucleocapsid, membrane, and spike proteins of SARS-CoV-2, using IFNy; ELISpot, and we also evaluated the fractions of virus-specific CD4+ and CD8+ T cells using intracellular staining of IFNy; and IL2 followed by flow cytometry. Furthermore, we analyzed the post-inclusion COVID-19 rates as a function of the assessed antibody and T cell responses using the Kaplan-Meyer estimator method. Results: We showed that T cell and antibody responses are closely interconnected and commonly are induced concurrently. Individuals positive for both antibody and T cell immunities demonstrated the highest levels of protectivity against the SARS-CoV-2 infection, indistinguishably from individuals with antibody response only. Meanwhile, individuals with T cell response only demonstrated slightly higher protectivity than individuals without both types of immunity, as measured from N-protein-specific or CD4+IL2+ T cells. However, these individuals were characterized by higher IgG titers than individuals without any immunity, although the titers were below the seropositivity cut-off. Conclusions: The results of the study indicated the advantage of serology testing over the analysis of T cell responses for the prediction of SARS-CoV-2 infection rates on a populational level.
As global vaccination campaigns against SARS-CoV-2 proceed, there is emerging interest in the longevity of immune protection, especially with regard to increasingly infectious virus variants. Neutralizing antibodies (Nabs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are promising correlates of protective immunity and have been successfully used for prevention and therapy. To assess neutralizing capacity, we developed a bead-based multiplex ACE2 RBD competition assay as a large scalable, time-, cost-, and material-saving alternative to infectious live-virus neutralization tests. By mimicking the interaction between ACE2 and RBD, this assay detects the presence of Nabs against SARS-CoV2 in serum. Using this multiplex approach allows the simultaneous analysis of Nabs against all SARS-CoV-2 variants of concern and variants of interest in a single well. Following validation, we analyzed 325 serum samples from 186 COVID-19 patients of varying severity. Neutralization capacity was reduced for all variants examined compared to wild-type, especially for those displaying the E484K mutation. The neutralizing immune response itself, while highly individualistic, positively correlates with IgG levels. Neutralization capacity also correlated with disease severity up to WHO grade 7, after which it reduced.
Although clinical trials and real-world studies have affirmed the effectiveness and safety of the FDA-authorized COVID-19 vaccines, reports of breakthrough infections and persistent emergence of new variants highlight the need to vigilantly monitor the effectiveness of these vaccines. Here we compare the effectiveness of two full-length Spike protein-encoding mRNA vaccines from Moderna (mRNA-1273) and Pfizer/BioNTech (BNT162b2) in the Mayo Clinic Health System over time from January to July 2021, during which either the Alpha or Delta variant was highly prevalent. We defined cohorts of vaccinated and unvaccinated individuals from Minnesota (n = 25,589 each) matched on age, sex, race, history of prior SARS-CoV-2 PCR testing, and date of full vaccination. Both vaccines were highly effective during this study period against SARS-CoV-2 infection (mRNA-1273: 86%, 95%CI: 81-90.6%; BNT162b2: 76%, 95%CI: 69-81%) and COVID-19 associated hospitalization (mRNA-1273: 91.6%, 95% CI: 81-97%; BNT162b2: 85%, 95% CI: 73-93%). In July, vaccine effectiveness against hospitalization has remained high (mRNA-1273: 81%, 95% CI: 33-96.3%; BNT162b2: 75%, 95% CI: 24-93.9%), but effectiveness against infection was lower for both vaccines (mRNA-1273: 76%, 95% CI: 58-87%; BNT162b2: 42%, 95% CI: 13-62%), with a more pronounced reduction for BNT162b2. Notably, the Delta variant prevalence in Minnesota increased from 0.7% in May to over 70% in July whereas the Alpha variant prevalence decreased from 85% to 13% over the same time period. Comparing rates of infection between matched individuals fully vaccinated with mRNA-1273 versus BNT162b2 across Mayo Clinic Health System sites in multiple states (Minnesota, Wisconsin, Arizona, Florida, and Iowa), mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2 (IRR = 0.50, 95% CI: 0.39-0.64). In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2 (IRR: 0.39, 95% CI: 0.24-0.62). Our observational study highlights that while both mRNA COVID-19 vaccines strongly protect against infection and severe disease, further evaluation of mechanisms underlying differences in their effectiveness such as dosing regimens and vaccine composition are warranted.
Pulmonary Rehabilitation Post-COVID-19 - Condition: COVID-19
Intervention: Other: Exercise program (virtual/remote)
Sponsors: University of Manitoba; Health Sciences Centre Foundation, Manitoba; Health Sciences Centre, Winnipeg, Manitoba
Not yet recruiting
A Study of PF-07321332/Ritonavir in Non-hospitalized Low-Risk Adult Participants With COVID-19 - Condition: COVID-19
Interventions: Drug: PF-07321332; Drug: Ritonavir; Drug: Placebo
Sponsor: Pfizer
Not yet recruiting
Mix and Match Heterologous Prime-Boost Study Using Approved COVID-19 Vaccines in Mozambique - Condition: Covid19
Interventions: Biological: BBIBP-CorV - Inactivated SARS-CoV-2 vaccine (Vero cell); Biological: AZD1222 (replication-deficient Ad type 5 vector expressing full-length spike protein)
Sponsors: International Vaccine Institute; The Coalition for Epidemic Preparedness Innovations (CEPI); Instituto Nacional de Saúde (INS), Mozambique; University of Antananarivo; International Centre for Diarrhoeal Disease Research, Bangladesh; Harvard University; Heidelberg University
Not yet recruiting
Targeting de Novo Pyrimidine Biosynthesis by Leflunomide for the Treatment of COVID-19 Virus Disease - Condition: COVID-19
Intervention: Drug: leflunomide
Sponsor:
Ashford and St. Peter’s Hospitals NHS Trust
Active, not recruiting
COVID-19 Methylene Blue Antiviral Treatment - Condition: Covid19
Interventions: Drug: Methylene Blue; Drug: Saline nasal spray
Sponsors: Irkutsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences; Irkutsk State Medical University
Recruiting
Phase I/II Clinical Trial of Recombinant COVID-19 Vaccine (Sf9 Cells) in Children and Adolescents - Condition: COVID-19
Interventions: Biological: Recombinant COVID-19 vaccine (Sf9 cells); Other: Placebo control
Sponsors: WestVac Biopharma Co., Ltd.; West China Hospital
Not yet recruiting
To Evaluate Efficacy & Safety of Proxalutamide in Hospitalized Covid-19 Subjects - Condition: Covid19
Interventions: Drug: GT0918; Drug: Standard of care; Drug: Matching placebo
Sponsors: Suzhou Kintor Pharmaceutical Inc,; IQVIA Biotech
Not yet recruiting
Double Blind Randomized Clinical Trial of Use of Colchicine Added to Standard Treatment in Hospitalized With Covid-19 - Condition: COVID-19 Infection
Intervention: Drug: Colchcine
Sponsor:
Asociacion Instituto Biodonostia
Active, not recruiting
Relaxation Exercise in Patients With COVID-19 - Condition: Covid19
Intervention: Other: Relaxation technique
Sponsor: Beni- Suef University
Completed
Philippine Trial to Determine Efficacy and Safety of Favipiravir for COVID-19 - Condition: Covid19
Interventions: Combination Product: Favipiravir + Standard of Care; Procedure: Standard of Care
Sponsors: University of the Philippines; Department of Health, Philippines
Recruiting
Combination of Dietary Supplements Curcumin, Quercetin and Vitamin D for Early Symptoms of COVID-19 - Condition: Covid19
Interventions: Drug: Standard of care; Dietary Supplement: combination of curcumin, quercetin and Vitamin D
Sponsor: Ayub Teaching Hospital
Not yet recruiting
Evaluation of the Effects of Bradykinin Antagonists on Pulmonary Manifestations of COVID-19 Infections (AntagoBrad- Cov Study). - Condition: Covid19
Interventions: Drug: C1 Inhibitor Human; Drug: Icatibant Injection; Other: Placebo
Sponsor: GCS Ramsay Santé pour l’Enseignement et la Recherche
Completed
A Study to Evaluate the Safety and Efficacy of Artemisinin- a Herbal Supplement on COVID-19 Subjects - Condition: Covid19
Interventions: Dietary Supplement: Artemisinin; Drug: Dexamethasone
Sponsors: Mateon Therapeutics; Windlas Biotech Private Limited
Completed
Clinical Trial to Assess the Efficacy and Safety of Inhaled AQ001S in the Management of Acute COVID-19 Symptoms - Condition: Covid19
Intervention: Drug: Drug, inhalation
Sponsor:
Aquilon Pharmaceuticals S.A.
Not yet recruiting
Local and General Immune Response After Coronavirus Disease (COVID-19) Vaccination in Volunteers - Condition: Covid19
Intervention: Procedure: Blood and nasal fluid sampling before and after COVID-19 vaccination
Sponsors: University Hospital, Ghent; University Ghent; Vlaams Instituut voor Biotechnologie
Active, not recruiting
Challenges of short substrate analogues as SARS-CoV-2 main protease inhibitors - Specific anti-coronaviral drugs complementing available vaccines are urgently needed to fight the COVID-19 pandemic. Given its high conservation across the betacoronavirus genus and dissimilarity to human proteases, the SARS-CoV-2 main protease (M^(pro)) is an attractive drug target. SARS-CoV-2 M^(pro) inhibitors have been developed at unprecedented speed, most of them being substrate-derived peptidomimetics with cysteine-modifying warheads. In this study, M^(pro) has proven resistant towards…
Evaluation of a Visually-Read Rapid Antigen Test Kit (SGA V-Chek) for Detection of SARS-CoV-2 Virus - Although the reverse transcriptase polymerase chain reaction (RT-PCR) method has been accepted as the reference method in the detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA, it requires special laboratory conditions, complicated and expensive laboratory instruments, competent laboratory staff and long testing duration. Antigen testing methods such as enzyme immunoassay, fluorescent antibody and visually-read immunochromatographic rapid antigen detection (RAD) tests…
OFF-State-Specific Inhibition of the Proprotein Convertase Furin - The pro-protein convertase furin is a highly specific serine protease involved in the proteolytic maturation of many proteins in the secretory pathway. It also activates surface proteins of many viruses including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furin inhibitors effectively suppress viral replication and thus are promising antiviral therapeutics with broad application potential. Polybasic substrate-like ligands typically trigger conformational changes shifting…
Vitamin D3 and its hydroxyderivatives as promising drugs against COVID-19: a computational study - The epidemiologic correlation between the poor prognosis of SARS-CoV-2 infection and vitamin D deficiency has been observed worldwide, however, their molecular mechanisms are not fully understood. In this study, we used combined molecular docking, molecular dynamics simulations and binding free energy analyses to investigate the potentials of vitamin D3 and its hydroxyderivatives as TMPRSS2 inhibitor and to inhibit the SARS-CoV-2 receptor binding domain (RBD) binding to angiotensin-converting…
Probing the Allosteric Inhibition Mechanism of a Spike Protein Using Molecular Dynamics Simulations and Active Compound Identifications - The receptor recognition of the novel coronavirus SARS-CoV-2 relies on the “down-to-up” conformational change in the receptor-binding domain (RBD) of the spike (S) protein. Therefore, understanding the process of this change at the molecular level facilitates the design of therapeutic agents. With the help of coarse-grained molecular dynamic simulations, we provide evidence showing that the conformational dynamics of the S protein are globally cooperative. Importantly, an allosteric path was…
Phase 1 study in healthy participants of the safety, pharmacokinetics, and pharmacodynamics of enpatoran (M5049), a dual antagonist of toll-like receptors 7 and 8 - This study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple oral doses of enpatoran (formerly named M5049), a new toll-like receptor (TLR) 7 and 8 dual antagonist, and the effect of food on a single dose in healthy participants. In this single phase 1, randomized (3:1), double-blind, placebo- controlled study, 96 participants received single and multiple ascending oral doses of enpatoran. Participants in single-dose cohorts received one…
MicroRNA-28-3p inhibits angiotensin-converting enzyme 2 ectodomain shedding in 293T cells treated with the spike protein of severe acute respiratory syndrome coronavirus 2 by targeting A disintegrin and metalloproteinase 17 - Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is the virus that causes coronavirus disease 2019. Angiotensin‑converting enzyme 2 (ACE2) is the SARS‑CoV binding site and is ubiquitously expressed in endothelial cells of several organs, with the highest levels in the cardiovascular system, kidney and lungs. A disintegrin and metalloproteinase 17 (ADAM17) is involved in ectodomain shedding of ACE2. In the present study, reverse‑transcription‑quantitative PCR, transfection, TUNNEL…
Rational Design of Hybrid SARS-CoV-2 Main Protease Inhibitors Guided by the Superimposed Cocrystal Structures with the Peptidomimetic Inhibitors GC-376, Telaprevir, and Boceprevir - SARS-CoV-2 main protease (M^(pro)) is a cysteine protease that mediates the cleavage of viral polyproteins and is a validated antiviral drug target. M^(pro) is highly conserved among all seven human coronaviruses, with certain M^(pro) inhibitors having broad-spectrum antiviral activity. In this study, we designed two hybrid inhibitors UAWJ9-36-1 and UAWJ9-36-3 based on the superimposed X-ray crystal structures of SARS-CoV-2 M^(pro) with GC-376, telaprevir, and boceprevir. Both UAWJ9-36-1 and…
Poliovirus Vaccination Induces a Humoral Immune Response That Cross Reacts With SARS-CoV-2 - Background: Millions have been exposed to SARS-CoV-2, but the severity of resultant infections has varied among adults and children, with adults presenting more serious symptomatic cases. Children may possess an immunity that adults lack, possibly from childhood vaccinations. This retrospective study suggests immunization against the poliovirus may provide an immunity to SARS-CoV-2. Methods: Publicly available data were analyzed for possible correlations between national median ages and…
Downregulation of CD45 Signaling in COVID-19 Patients Is Reversed by C24D, a Novel CD45 Targeting Peptide - CD45, the predominant transmembrane tyrosine phosphatase in leukocytes, is required for the efficient induction of T cell receptor signaling and activation. We recently reported that the CD45-intracellular signals in peripheral blood mononuclear cells (PBMCs) of triple negative breast cancer (TNBC) patients are inhibited. We also reported that C24D, an immune modulating therapeutic peptide, binds to CD45 on immune-suppressed cells and resets the functionality of the immune system via the CD45…
Morphological cell profiling of SARS-CoV-2 infection identifies drug repurposing candidates for COVID-19 - The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated disease COVID-19, requires therapeutic interventions that can be rapidly identified and translated to clinical care. Traditional drug discovery methods have a >90% failure rate and can take 10 to 15 y from target identification to clinical use. In contrast, drug repurposing can significantly accelerate translation. We developed a quantitative high-throughput screen to identify efficacious…
An overview of the preclinical discovery and development of remdesivir for the treatment of coronavirus disease 2019 (COVID-19) - INTRODUCTION: Remdesivir (RDV) is an inhibitor of the viral RNA-dependent RNA polymerases that are active in some RNA viruses, including the Ebola virus and zoonotic coronaviruses. When severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was identified as the etiologic agent of the coronavirus disease 2019 (COVID-19), several investigations have assessed the potential activity of RDV in inhibiting viral replication, giving rise to hope for an effective treatment.
Efficient inactivation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in human apheresis platelet concentrates with amotosalen and ultraviolet A light - CONCLUSION: SARS-CoV-2 was efficiently inactivated in platelet concentrates by amotosalen/UVA treatment. These results are in line with previous inactivation data for SARS-CoV-2 in plasma as well as MERS-CoV and SARS-CoV-1 in platelets and plasma, demonstrating efficient inactivation of human coronaviruses.
Osteopathic interventions via telehealth in a pediatric population: a retrospective case series - CONCLUSIONS: In our small retrospective case series, osteopathic interventions via telehealth resulted in decreased average pain scores following treatment while minimizing risk of viral exposure and transmission. Further study is needed to determine if such treatment methods could be effective on a larger scale when distance or illness preclude an in-person OMT visit.
Deconstructing the Treatment Effect of Remdesivir in the Adaptive COVID-19 Treatment Trial-1: Implications for Critical Care Resource Utilization - CONCLUSIONS: Remdesivir speeds time to recovery by preventing worsening to clinical states that would extend the course of hospitalization and increase intensive respiratory support, thereby reducing the overall demand for hospital care.
SARS-COV-2 BINDING PROTEINS - - link
자외선살균등 - 본 발명은 사람의 의복이나 사용한 마스크 등에 부착하여 있다 호흡기로 유입되어 감염을 유발할 수 있는 COVID-19와 같은 유해균류를 간편하게 살균하기 위한 휴대용 자와선살균등에 관한 것이다. 반감기가 길고 인체에 유해한 오존을 발생하지 않으면서 탁월한 살균능력이 있는 250~265nm(최적은 253.7nm) 파장의 자외선을 발광하는 자외선램프를 본 발명의 막대형의 자외선살균등 광원으로 사용하고 비광원부를 손으로 잡고 의복이나 사용한 마스크 등 유해균류가 부착되었을 것으로 의심되는 곳에 자외선을 조사하여 간편하게 유해균류를 살균하므로써 감염을 예방하기 위한 휴대용 자외선살균등에 관함 것이다. - link
A Protein chip and kit for detecting SARS-CoV-2 N protein and its preparation method - - link
Protein chip and kit for detecting the SARS-CoV-2 S antigen - - link
Cabina de desinfección de doble carga exterior - - link
A Novel Method COVID -19 infection using Deep Learning Based System - - link
一种新冠病毒疫苗的表达载体及其构建方法、应用和疫苗 - 本发明适用于生物技术领域，提供了一种新冠病毒疫苗的表达载体及其构建方法、应用和疫苗，该表达载体的构建方法包括以下步骤：将表达新冠病毒S蛋白与NP蛋白的核苷酸序列使用2A肽进行连接，合成融合基因；在融合基因的两端分别包含两个酶切位点，并装载到质粒，得到重组质粒；对重组质粒进行双酶切，切胶回收目的基因片段；对原始的质粒进行双酶切，切胶回收载体片段；将目的基因片段和载体片段进行连接，得到所述表达载体。本发明实施例通过同时表达冠状病毒S蛋白受体结合区与NP蛋白，使该表达载体感染的细胞不但可以诱导抗体反应还能诱导T细胞反应，从而有效诱导体液免疫和细胞免疫，为受试者提供更强的免疫保护。 - link
EMPUNADURA DE RAQUETA O PALA PARA JUEGO DE PELOTA CON DISPENSADOR LIQUIDO POR CAPILARIDAD INSERTADO - - link
A SYSTEM AND METHOD FOR COVID- 19 DIAGNOSIS USING DETECTION RESULTS FROM CHEST X- RAY IMAGES - - link
Ein System (2000) zum computergestützten Nachverfolgen einer von einer Person (1) durchzuführenden Testprozedur, insbesondere für einen Virusnachweistest, bevorzugt zur Durchführung eines SARS-CoV-2 Tests, wobei das System (2000) umfasst: