The continuing emergence of SARS-CoV-2 variants of concern (VOCs) presents a serious public health threat, exacerbating the effects of the COVID19 pandemic. Although millions of genomes have been deposited in public archives since the start of the pandemic, predicting SARS-CoV-2 clinical characteristics from the genome sequence remains challenging. In this study, we used a collection of over 29,000 high quality SARS-CoV-2 genomes to build machine learning models for predicting clinical detection cycle threshold (Ct) values, which correspond with viral load. After evaluating several machine learning methods and parameters, our best model was a random forest regressor that used 10-mer oligonucleotides as features and achieved an R2 score of 0.521 +/- 0.010 (95% confidence interval over 5 folds) and an RMSE of 5.7 +/- 0.034, demonstrating the ability of the models to detect the presence of a signal in the genomic data. In an attempt to predict Ct values for newly emerging variants, we predicted Ct values for Omicron variants using models trained on previous variants. We found that approximately 5% of the data in the model needed to be from the new variant in order to learn its Ct values. Finally, to understand how the model is working, we evaluated the top features and found that the model is using a multitude of k-mers from across the genome to make the predictions. However, when we looked at the top k-mers that occurred most frequently across the set of genomes, we observed a clustering of k-mers that span spike protein regions corresponding with key variations that are hallmarks of the VOCs including G339, K417, L452, N501, and P681, indicating that these sites are informative in the model and may impact the Ct values that are observed in clinical samples.
We isolated infectious SARS-CoV-2 from aerosol samples collected from hospital rooms of COVID19 patients. Isolated virus successfully replicated in cell cultures 14 months after collection, opening up prospects for retrospective analyses of samples stored during the previous waves of COVID-19.
Objectives: The Corona Virus Disease-2019 (COVID-19) pandemic has psychological consequences such as increased risk of depression, anxiety, and stress problems, exacerbating human health disparities. This study aimed to analyze depression and its causes in COVID-19-recovered patients in Bangladesh. Method: A cross-sectional study was conducted on COVID-19 recovered patients, who attended for follow-up after 14 days to 3 months at Dhaka Medical College Hospital (DMCH) and Dhaka North City Corporation Hospital (DNCCH), Dhaka, Bangladesh from 1st January to 31st December, 2021. Respondents were face-to-face interviewed with a semi-structured questionnaire after written agreement. The Patient Health Questionnaire (PHQ-9) was used to assess respondents9 depression, and data were analyzed using SPSS version-23, with p < 0.05 indicating statistical significance. Results: A total of 325 COVID-19 recovered patients aged from 15 to 65 years (mean 44.34 ±13.87 years) of age were included in this study, highest 23.1% of them belonged to 46-55 years, and majority (61.5%) of them were male. There were 69.5% of respondents had no signs of depression while 31% of them had with 26.7% being mildly depressed, 2.5% being extremely depressed, and 1.2% being severely depressed. Diabetes mellitus, hospitalization duration, social distancing, the social media post on COVID-19, loss of employment, family damage, and fear of re-infection were significantly associated with depression level of respondents. Conclusion: This study gives us a glimpse into the psychological health of COVID-19 recovered patients, and its findings highlight the imperative of alleviating their psychological anguish in Bangladesh.
During the COVID-19 pandemic, some countries, such as Australia, China, Iceland, New Zealand, Thailand, and Vietnam successfully implemented an elimination strategy, enacting strict border control and periods of lockdowns to end community transmission. Atlantic Canada and Canada9s territories implemented similar policies, and reported long periods with no community cases. In Newfoundland and Labrador (NL), Nova Scotia, and Prince Edward Island a median of 80% or more of daily reported cases were travel-related from July 1, 2020 to May 31, 2021. With increasing vaccination coverage, it may be appropriate to exit an elimination strategy, but most existing epidemiological frameworks are applicable only to situations where most cases occur in the community, and are not appropriate for regions that have implemented an elimination strategy. To inform the pandemic response in regions that are implementing an elimination strategy, we extend importation modelling to consider post-arrival travel restrictions, and pharmaceutical and non-pharmaceutical interventions in the local community. We find that shortly after the Omicron variant had begun spreading in Canada, the expected daily number of spillovers, infections spread to NL community members from travelers and their close contacts, was higher than any time previously in the pandemic. By December 24, 2021, the expected number of spillovers was 44% higher than the previous high, which occurred in late July 2021 shortly after travel restrictions were first relaxed. We develop a method to assess the characteristics of potential future community outbreaks in regions that are implementing an elimination strategy. We apply this method to predict the effect of variant and vaccination coverage on the size of hypothetical community outbreaks in Mount Pearl, a suburb of the St. John9s metropolitan area in NL. Our methodology can be used to evaluate alternative plans to relax public health restrictions when vaccine coverage is high in regions that have implemented an elimination strategy. This manuscript was submitted as part of a theme issue on “Modelling COVID-19 and Preparedness for Future Pandemics”.
Background: Long-term effectiveness of COVID-19 mRNA boosters in populations with different prior infection histories and clinical vulnerability profiles is inadequately understood. Methods: A national, matched, retrospective, target trial cohort study was conducted in Qatar to investigate effectiveness of a third mRNA (booster) dose, relative to a primary series of two doses, against SARS-CoV-2 omicron infection and against severe COVID-19. Associations were estimated using Cox proportional-hazards regression models. Results: Booster effectiveness relative to primary series was 41.1% (95% CI: 40.0-42.1%) against infection and 80.5% (95% CI: 55.7-91.4%) against severe, critical, or fatal COVID-19, over one-year follow-up after the booster. Among persons clinically vulnerable to severe COVID-19, effectiveness was 49.7% (95% CI: 47.8-51.6%) against infection and 84.2% (95% CI: 58.8-93.9%) against severe, critical, or fatal COVID-19. Effectiveness against infection was highest at 57.1% (95% CI: 55.9-58.3%) in the first month after the booster but waned thereafter and was modest at only 14.4% (95% CI: 7.3-20.9%) by the sixth month. In the seventh month and thereafter, coincident with BA.4/BA.5 and BA.2.75* subvariant incidence, effectiveness was progressively negative reaching -20.3% (95% CI: -55.0-29.0%) after one year of follow-up. Similar levels and patterns of protection were observed irrespective of prior infection status, clinical vulnerability, or type of vaccine (BNT162b2 versus mRNA-1273). Conclusions: Boosters reduced infection and severe COVID-19, particularly among those clinically vulnerable to severe COVID-19. However, protection against infection waned after the booster, and eventually suggested an imprinting effect of compromised protection relative to the primary series. However, imprinting effects are unlikely to negate the overall public health value of booster vaccinations.
COVID-19 Bivalent Booster Megastudy - Condition: Â COVID-19
Intervention:  Behavioral: COVID Booster text messages
Sponsor:  University of Pennsylvania
Enrolling by invitation
A Study on Utilization, Adherence, and Acceptability of Voluntary Routine COVID-19 Self-testing Among Students, Staff and Health Workers at Two Institutions in Mizoram, India. - Condition: Â COVID-19Â Pandemic
Intervention: Â Diagnostic Test: COVID-19 Self testing and related messaging
Sponsors:  PATH;  UNITAID;  Zoram Medical College;  Pacchunga University College;  ALERT India;  Government of Mizoram
Not yet recruiting
Using a Community-level Just-in-Time Adaptive Intervention to Address COVID-19 Testing Disparities - Condition: Â COVID-19
Interventions: Â Behavioral: Multi-Level Multi-Component Intervention (MLI); Â Behavioral: Community Just-In-Time Adaptive Intervention (Community JITAI)
Sponsors: Â The University of Texas Health Science Center, Houston; Â National Center for Advancing Translational Sciences (NCATS)
Active, not recruiting
Examining How a Facilitated Self-Sampling Intervention and Testing Navigation Intervention Influences COVID-19 Testing - Condition: Â COVID-19
Interventions: Â Behavioral: Facilitated Self-Sampling Intervention (FSSI); Â Behavioral: Testing Navigation Intervention (TNI).; Â Behavioral:Â Control
Sponsors: Â The University of Texas Health Science Center, Houston; Â National Center for Advancing Translational Sciences (NCATS)
Not yet recruiting
Assessing Performance of the Testing Done Simple Covid 19 Antigen Test - Condition: Â COVID-19
Intervention: Â Diagnostic Test: Testing Done Simple SARS CoV-2 Antigen Test
Sponsors:  Testing Done Simple;  Nao Medical Urgent Care
Recruiting
A Study to Evaluate EDP-235 in Non-hospitalized Adults With COVID-19 - Condition: Â COVID-19
Interventions: Â Drug:Â EDP-235; Â Drug:Â Placebo
Sponsor:  Enanta Pharmaceuticals, Inc
Recruiting
A Phase III of COVID-19 Vaccine EuCorVac-19 in Healthy Adults Aged 18 Years and Older - Condition: Â COVID-19
Interventions: Â Biological:Â EuCorVac-19; Â Biological:Â ChAdOx1
Sponsor:  EuBiologics Co.,Ltd
Recruiting
Study Evaluating GS-5245 in Participants With COVID-19 Who Have a High Risk of Developing Serious or Severe Illness - Condition: Â COVID-19
Interventions: Â Drug:Â GS-5245; Â Drug:Â GS-5245Â Placebo
Sponsor:  Gilead Sciences
Recruiting
The LAVA (Lateral Flow Antigen Validation and Applicability) 2 Study for COVID-19 - Condition: Â SARS-CoV-2Â Infection
Intervention:  Diagnostic Test: Innova Lateral Flow Test
Sponsor:  Alder Hey Children’s NHS Foundation Trust
Completed
Q-POC COVID-19 Clinical Evaluation - Condition: Â COVID-19
Interventions:  Diagnostic Test: RT-PCR Test;  Diagnostic Test: Real-time PCR Test
Sponsors:  QuantuMDx Group Ltd;  EDP Biotech;  Paragon Rx Clinical;  PathAI;  PRX Research and Development
Not yet recruiting
A Phase I/II Study of GLB-COV2-043 as a COVID-19 Vaccine Booster - Condition: Â COVID-19
Interventions:  Drug: GLB-COV2-043;  Drug: BNT162b2/COMIRNATY®
Sponsor:  GreenLight Biosciences, Inc.
Not yet recruiting
Enhancing Protection Against Influenza and COVID-19 for Pregnant Women and Medically at Risk Children - Conditions: Â Influenza; Â COVID-19
Intervention: Â Behavioral:Â Nudge
Sponsor:  University of Adelaide
Recruiting
Safety and Efficacy of Intranasal Administration of Avacc 10 Vaccine Against COVID-19 in Healthy Volunteers - Condition: Â COVID-19
Interventions:  Biological: Avacc 10;  Combination Product: Outer Membrane Vesicles (OMV) : OMV alone in vehicle;  Other: Placebo
Sponsors:  Intravacc B.V.;  Novotech (Australia) Pty Limited
Not yet recruiting
A Trial Evaluate the Immunogenicity and Safety of Recombinant COVID-19 Omicron-Delta Variant Vaccine (CHO Cell) - Condition: Â COVID-19
Interventions: Â Biological: Omicron-Delta Recombinant Novel Coronavirus Protein Vaccine (CHO cells); Â Biological: Recombinant Novel Coronavirus Protein Vaccine (CHO cells)
Sponsor:  Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
Recruiting
COVID-19 Antibody Responses in Cystic Fibrosis - Conditions:  COVID-19;  Cystic Fibrosis
Intervention:  Biological: Blood sample
Sponsors:  Hospices Civils de Lyon;  Queen’s University, Belfast
Recruiting
Evaluation of the anti-diabetic drug sitagliptin as a novel attenuate to SARS-CoV-2 evidence-based in silico: molecular docking and molecular dynamics - The current outbreak of COVID-19 cases worldwide has been responsible for a significant number of deaths, especially in hospitalized patients suffering from comorbidities, such as obesity, diabetes, hypertension. The disease not only has prompted an interest in the pathophysiology, but also it has propelled a massive race to find new anti-SARS-CoV-2 drugs. In this scenario, known drugs commonly used to treat other diseases have been suggested as alternative or complementary therapeutics. Herein…
In Silico and In Vitro studies of taiwan chingguan yihau (NRICM101) on TNF-α/IL-1β-induced human lung cells - COVID-19 pandemic has been a global outbreak of coronavirus (SARS-CoV-2 virus) since 2019. Taiwan Chingguan Yihau (NRICM101) is the first traditional Chinese medicine (TCM) classic herbal formula and is widely used for COVID-19 patients in Taiwan and more than 50 nations. This study is to investigate in silico target fishing for the components of NRICM101 and to explore whether NRICM101 inhibits cytokines-induced normal human lung cell injury in vitro. Our results showed that network prediction…
Comparison of RT-qPCR and RT-dPCR Platforms for the Trace Detection of SARS-CoV-2 RNA in Wastewater - We compared reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and RT digital PCR (RT-dPCR) platforms for the trace detection of SARS-CoV-2 RNA in low-prevalence COVID-19 locations in Queensland, Australia, using CDC N1 and CDC N2 assays. The assay limit of detection (ALOD), PCR inhibition rates, and performance characteristics of each assay, along with the positivity rates with the RT-qPCR and RT-dPCR platforms, were evaluated by seeding known concentrations of exogenous…
GLUCOSE AND MANNOSE ANALOGS INHIBIT KSHV REPLICATION BY BLOCKING N-GLYCOSYLATION AND INDUCING THE UNFOLDED PROTEIN RESPONSE - Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent for Kaposi’s sarcoma (KS), an HIV/AIDS-associated malignancy. Effective treatments against KS remain to be developed. The sugar analog 2-deoxy-d-glucose (2-DG) is an anti-cancer agent that is well-tolerated and safe in patients and was recently demonstrated to be a potent antiviral, including KSHV and SARS-Cov-2. Because 2-DG inhibits glycolysis and N-glycosylation, identifying its molecular targets is challenging. Here we…
Differential upregulation of AU-rich element-containing mRNAs in COVID-19 - CONCLUSIONS: Compared to the rest of the transcriptome, ARE-containing mRNAs are preferentially upregulated in response to viral infections at a global level. In the context of COVID-19, they are most upregulated in mild disease. Due to their large number, their levels measured by RNA-seq may provide a reliable indication of COVID-19 severity.
SARS-CoV-2 Spike protein suppresses CTL-mediated killing by inhibiting immune synapse assembly - CTL-mediated killing of virally infected or malignant cells is orchestrated at the immune synapse (IS). We hypothesized that SARS-CoV-2 may target lytic IS assembly to escape elimination. We show that human CD8+ T cells upregulate the expression of ACE2, the Spike receptor, during differentiation to CTLs. CTL preincubation with the Wuhan or Omicron Spike variants inhibits IS assembly and function, as shown by defective synaptic accumulation of TCRs and tyrosine phosphoproteins as well as…
Charge-Dependent Signal Changes for Label-Free Electrochemiluminescence Immunoassays - Label-free electrochemiluminescence (ECL) immunoassays (lf-ECLIA), based on biomarker-induced ECL signal changes, have attracted increasing attention due to the simple, rapid, and low-cost detection of biomarkers without secondary antibodies and complicated labeling procedures. However, the interaction rule and mechanism between analytical interfaces and biomarkers have rarely been explored. Herein, the interactions between biomarkers and analytical interfaces constructed by assembly of a…
Rational Development of Hypervalent Glycan Shield-Binding Nanoparticles with Broad-Spectrum Inhibition against Fatal Viruses Including SARS-CoV-2 Variants - Infectious virus diseases, particularly coronavirus disease 2019, have posed a severe threat to public health, whereas the developed therapeutic and prophylactic strategies are seriously challenged by viral evolution and mutation. Therefore, broad-spectrum inhibitors of viruses are highly demanded. Herein, an unprecedented antiviral strategy is reported, targeting the viral glycan shields with hypervalent mannose-binding nanoparticles. The nanoparticles exhibit a unique double-punch mechanism,…
DNA virus oncoprotein HPV18 E7 selectively antagonizes cGAS-STING-triggered innate immune activation - Cellular infections by DNA viruses trigger innate immune responses mediated by DNA sensors. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway has been identified as a DNA-sensing pathway that activates interferons in response to viral infection and, thus, mediates host defense against viruses. Previous studies have identified oncogenes E7 and E1A of the DNA tumor viruses, human papillomavirus 18 (HPV18) and adenovirus, respectively, as inhibitors of the…
Favipiravir Efficacy And Safety For The Treatment Of Severe Coronavirus Disease 2019: A Retrospective Study - CONCLUSIONS: In this study, Favipiravir showed better therapeutic responses in patients with severe COVID-19 infection, in terms of average duration of stay in the intensive care unit and was well tolerated in the younger age, but showed no mortality benefit. However, elevated levels of inflammatory markers, including increased ALT, AST, BUN, bilirubin, and creatinine, needs to be carefully examined.
Characteristics and source apportionment of PM2.5 under the dual influence of the Spring Festival and the COVID-19 pandemic in Yuncheng city - Based on the online and membrane sampling data of Yuncheng from January 1st to February 12th, 2020, the formation mechanism of haze under the dual influence of Spring Festival and COVID-19 (Corona Virus Disease) was analyzed. Atmospheric capacity, chemical composition, secondary transformation, source apportionment, backward trajectory, pollution space and enterprise distribution were studied. Low wind speed, high humidity and small atmospheric capacity inhibited the diffusion of air pollutants….
Active Ingredients of Reduning Injections Maintain High Potency against SARS-CoV-2 Variants - CONCLUSIONS: The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19.
Why Molnupiravir Fails in Hospitalized Patients - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has radically altered daily life. Effective antiviral therapies to combat COVID-19, especially severe disease, remain scarce. Molnupiravir is an antiviral that has shown clinical efficacy against mild-to-moderate COVID-19 but failed to provide benefit to hospitalized patients with severe disease. Here, we explained the mechanism behind the failure of molnupiravir in…
Ganoderma lucidum polysaccharides ameliorate lipopolysaccharide-induced acute pneumonia via inhibiting NRP1-mediated inflammation - CONTEXT: Ganoderma lucidum polysaccharides (GLP), from Ganoderma lucidum (Leyss. ex Fr.) Karst. (Ganodermataceae), are reported to have anti-inflammatory effects, including anti-neuroinflammation and anti-colitis. Nevertheless, the role of GLP in acute pneumonia is unknown.
The numerical solution of a mathematical model of the Covid-19 pandemic utilizing a meshless local discrete Galerkin method - It was in early December 2019 that the terrible news of the outbreak of new coronavirus disease (Covid-19) was reported by the world media, which appeared in Wuhan, China, and is rapidly spreading to other parts of China and several overseas countries. In the field of infectious diseases, modeling, evaluating, and predicting the rate of disease transmission are very important for epidemic prevention and control. Several preliminary mathematical models for Covid-19 are formulated by various…