Responding to a rapidly evolving pandemic like COVID-19 is challenging, and involves anticipating novel variants, vaccine uptake, and behavioral adaptations. Human judgment systems can complement computational models by providing valuable real-time forecasts. We report findings from a study conducted on Metaculus, a community forecasting platform, in partnership with the Virginia Department of Health, involving six rounds of forecasting during the Omicron BA.1 wave in the United States from November 2021 to March 2022. We received 8355 probabilistic predictions from 129 unique users across 60 questions pertaining to cases, hospitalizations, vaccine uptake, and peak/trough activity. We observed that the case forecasts performed on par with national multi-model ensembles and the vaccine uptake forecasts were more robust and accurate compared to baseline models. We also identified qualitative shifts in Omicron BA.1 wave prognosis during the surge phase, demonstrating rapid adaptation of such systems. Finally, we found that community estimates of variant characteristics such as growth rate and timing of dominance were in line with the scientific consensus. The observed accuracy, timeliness, and scope of such systems demonstrates the value of incorporating them into pandemic policymaking workflows.
Cancer patients are at high risk of severe COVID-19 with high morbidity and mortality. Further, impaired humoral response renders SARS-CoV-2 vaccines less effective and treatment options are scarce. Randomized trials using convalescent plasma are missing for high-risk patients. Here, we performed a multicenter trial (https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE) in hospitalized patients with severe COVID-19 within four risk groups (1, cancer; 2, immunosuppression; 3, lab-based risk factors; 4, advanced age) randomized to standard of care (CONTROL) or standard of care plus convalescent/vaccinated anti-SARS-CoV-2 plasma (PLASMA). For the four groups combined, PLASMA did not improve clinically compared to CONTROL (HR 1.29; p=0.205). However, cancer patients experienced shortened median time to improvement (HR 2.50, p=0.003) and superior survival in PLASMA vs. CONTROL (HR 0.28; p=0.042). Neutralizing antibody activity increased in PLASMA but not in CONTROL cancer patients (p=0.001). Taken together, convalescent/vaccinated plasma may improve COVID-19 outcome in cancer patients unable to intrinsically generate an adequate immune response.
Background: The prolonged presence of infectious severe acute respiratory syndrome coronavirus (SARS-CoV-2) in deceased coronavirus disease 2019 (COVID-19) patients has been reported. However, infectious virus titers have not been determined. Such information is important for public health, death investigation, and handling corpses. Aim: The aim of this study was to assess the level of SARS-CoV-2 infectivity in COVID-19 corpses. Methods: We collected 11 nasopharyngeal swabs and 19 lung tissue specimens from 11 autopsy cases with COVID-19 in 2021. We then investigated the viral genomic copy number by real-time reverse transcription-polymerase chain reaction and infectious titers by cell culture and virus isolation. Results: Infectious virus was present in 6 of 11 (55%) cases, 4 of 11 (36%) nasopharyngeal swabs, and 9 of 19 (47%) lung specimens. The virus titers ranged from 6.00E + 01 plaque-forming units (PFU)/mL to 2.09E + 06 PFU/g. In all cases in which an infectious virus was found, the time from death to discovery was within 1 day and the longest postmortem interval was 13 days. Conclusion: COVID-19 corpses may have high titers of infectious virus after a long postmortem interval (up to 13 days). Therefore, appropriate infection control measures must be taken when handling corpses.
Multi-model and multi-team ensemble forecasts have become widely used to generate reliable short-term predictions of infectious disease spread. Notably, various public health agencies have used them to leverage academic disease modelling during the COVID-19 pandemic. However, ensemble forecasts are difficult to interpret and require extensive effort from numerous participating groups as well as a coordination team. In other fields, resource usage has been reduced by training simplified models that reproduce some of the observed behaviour of more complex models. Here we used observations of the behaviour of the European COVID-19 Forecast Hub ensemble combined with our own forecasting experience to identify a set of properties present in current ensemble forecasts. We then developed a parsimonious forecast model intending to mirror these properties. We assess forecasts generated from this model in real time over six months (the 15th of January 2022 to the 19th o July 2022) and for multiple European countries. We focused on forecasts of cases one to four weeks ahead and compared them to those by the European forecast hub ensemble. We find that the surrogate model behaves qualitatively similarly to the ensemble in many instances, though with increased uncertainty and poorer performance around periods of peak incidence (as measured by the Weighted Interval Score). The performance differences, however, seem to be partially due to a subset of time points, and the proposed model appears better probabilistically calibrated than the ensemble. We conclude that our simplified forecast model may have captured some of the dynamics of the hub ensemble, but more work is needed to understand the implicit epidemiological model that it represents.
The infection fatality rate (IFR) of COVID-19 among non-elderly people in the absence of vaccination or prior infection is important to estimate accurately, since 94% of the global population is younger than 70 years and 86% is younger than 60 years. In systematic searches in SeroTracker and PubMed (protocol: https://osf.io/xvupr), we identified 40 eligible national seroprevalence studies covering 38 countries with pre-vaccination seroprevalence data. For 29 countries (24 high-income, 5 others), publicly available age-stratified COVID-19 death data and age-stratified seroprevalence information were available and were included in the primary analysis. The IFRs had a median of 0.035% (interquartile range (IQR) 0.013 - 0.056%) for the 0-59 years old population, and 0.095% (IQR 0.036 - 0.125%,) for the 0-69 years old. The median IFR was 0.0003% at 0-19 years, 0.003% at 20-29 years, 0.011% at 30-39 years, 0.035% at 40-49 years, 0.129% at 50-59 years, and 0.501% at 60-69 years. Including data from another 9 countries with imputed age distribution of COVID-19 deaths yielded median IFR of 0.025-0.032% for 0-59 years and 0.063-0.082% for 0-69 years. Meta-regression analyses also suggested global IFR of 0.03% and 0.07%, respectively in these age groups. The current analysis suggests a much lower pre-vaccination IFR in non-elderly populations than previously suggested. Large differences did exist between countries and may reflect differences in comorbidities and other factors. These estimates provide a baseline from which to fathom further IFR declines with the widespread use of vaccination, prior infections, and evolution of new variants.
Background: There is uncertainty about the mortality impact of the COVID-19 pandemic in Africa because of poor ascertainment of cases and limited national civil vital registration. We analysed excess mortality from 1st January 2020-5th May 2022 in a Health and Demographic Surveillance Study in Coastal Kenya where the SARS-CoV-2 seroprevalence reached 75% among adults in March 2022 despite vaccine uptake of only 17%. Methods: We modelled expected mortality in 2020-2022 among a population of 306,000 from baseline surveillance data between 2010-2019. We calculated excess mortality as the ratio of observed/expected deaths in 5 age strata for each month and for each national wave of the pandemic. We estimated cumulative mortality risks as the total number of excess deaths in the pandemic per 100,000 population. We investigated observed deaths using verbal autopsy. Findings: We observed 16,236 deaths among 3,410,800 person years between 1st January 2010 and 5th May 2022. Across 5 waves of COVID-19 cases during 1st April 2020-16th April 2022, population excess mortality was 4.1% (95% PI -0.2%, 7.9%). Mortality was elevated among those aged ≥65 years at 14.3% (95% PI 7.4%, 21.6%); excess deaths coincided with wave 2 (wild-type), wave 4 (Delta) and wave 5 (Omicron BA1). Among children aged 1-14 years there was negative excess mortality of -20.3% (95% PI -29.8%, -8.1%). Verbal autopsy data showed a transient reduction in deaths from acute respiratory infections in 2020 at all ages. For comparison with other studies, cumulative excess mortality risk for January 2020-December 2021, age-standardized to the Kenyan population, was 47.5/100,000. Interpretation: Net excess mortality during the pandemic was substantially lower in Coastal Kenya than in many high income countries. However, adults, aged ≥65 years, experienced substantial excess mortality suggesting that targeted COVID-19 vaccination of older persons may limit further COVID-19 deaths by protecting the residual pool of naive individuals.
A Study to Learn About a Repeat 5-Day Treatment With the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With Return of COVID-19 Symptoms and SARS-CoV-2 Positivity After Finishing Treatment With Nirmatrelvir/Ritonavir - Condition: COVID-19
Interventions: Drug: nirmatrelvir; Drug: ritonavir; Drug: placebo for nirmatrelvir
Sponsor: Pfizer
Not yet recruiting
Recombinant Omicron-Delta COVID-19 Vaccine (CHO Cell) - Condition: COVID-19
Interventions: Biological: Recombinant Omicron-Delta COVID-19 Vaccine (CHO Cell); Biological: Inactivated COVID-19 vaccine (Vero Cell)
Sponsors: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; First Affiliated Hospital Bengbu Medical College
Active, not recruiting
A Phase III Study to Evaluate Immunogenicity and Safety of COVID-19 Vaccine EuCorVac-19 in Healthy Adults - Condition: COVID-19
Interventions: Biological: EuCorVac-19; Biological: ChAdOx1
Sponsor: EuBiologics Co.,Ltd
Recruiting
Study Evaluating Diltiazem in Combination With Standard Treatment in the Management of Patients Hospitalized With COVID-19 Pneumonia - Condition: COVID-19
Intervention: Drug: DILTIAZEM TEVA 60 mg or placebo
Sponsors: Hospices Civils de Lyon; Signia Therapeutics
Not yet recruiting
VAX-MOM COVID-19: Increasing Maternal COVID-19 Vaccination - Conditions: Immunization; Infection; Pregnancy Related; COVID-19
Interventions: Behavioral: VAX-MOM COVID-19 Intervention; Other: Standard of Care
Sponsors: University of Rochester; Centers for Disease Control and Prevention; University of California, Los Angeles
Not yet recruiting
COVID-19 Simulation Education on Nursing Students - Conditions: COVID-19 Pandemic; Simulation of Physical Illness
Interventions: Behavioral: Simulation training; Other: Control Group
Sponsor: Mehmet Akif Ersoy University
Completed
COVID-19 Booster Dose Reminder/Recall for Adolescents - Condition: COVID-19 Vaccines
Intervention: Behavioral: Reminder/Recall Sent Via Preferred Method of Communication
Sponsor: Marshfield Clinic Research Foundation
Active, not recruiting
Safety and Immunogenicity of AdCLD-CoV19-1 OMI as a Booster: A SARS-CoV-2 (COVID-19) Preventive Vaccine - Conditions: COVID-19; Vaccines
Interventions: Biological: AdCLD-CoV19-1 OMI (Part A); Biological: AdCLD-CoV19-1 OMI (Part B); Other: Placebo (Part B)
Sponsor: Cellid Co., Ltd.
Active, not recruiting
The Effect of Different Masks Used by Pregnant Women on Vital Signs and Non Stress Test During The COVID-19 - Conditions: Covid-19; Pregnant; Fetus; Mask
Intervention: Behavioral: Single surgical mask group, Double surgical mask group, N95 mask group
Sponsor: Bozok University
Completed
Personalized Computerized Training Program for Cognitive Dysfunction After COVID-19 - Conditions: Post-Acute COVID-19; Long COVID
Intervention: Device: CogniFit’s CCT Post COVID-19
Sponsor: Universidad Antonio de Nebrija
Completed
Understanding the Impact of Death Conditions Linked to the COVID-19 Crisis on the Grieving Process in Bereaved Families - Condition: Psychological Disorder
Intervention: Other: Qualitative research interview
Sponsor: Assistance Publique - Hôpitaux de Paris
Not yet recruiting
Efficacy of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) in People With Post Covid-19 Condition. - Conditions: Emotional Disorder; Post COVID-19 Condition; Anxiety Disorders; Depressive Disorder
Intervention: Behavioral: Unified Protocol for Transdiagnostic Treatment of Emotional Disorders
Sponsor: Instituto de Investigación Sanitaria Aragón
Not yet recruiting
Sequential Enhanced Safety Study of a Novel Coronavirus Messenger RNA (mRNA) Vaccine in Adults Aged 18 Years and Older. - Condition: Corona Virus Disease 2019(COVID-19)
Intervention: Biological: 0.3ml of mRNA vaccine
Sponsor: Yu Qin
Enrolling by invitation
Impact of Teeth Brushing in Ventilated COVID-19 Patients. - Conditions: Microbial Colonization; COVID-19 Respiratory Infection; Dysbiosis; VAP - Ventilator Associated Pneumonia; HAI
Intervention: Procedure: Oral Procedure
Sponsor: University Hospital in Krakow
Completed
Physiology of Long COVID and the Impact of Cardiopulmonary Rehabilitation on Quality-of-Life and Functional Capacity - Condition: Post-acute Sequelae of SARS-CoV-2 Infection
Intervention: Behavioral: Exercise
Sponsor: University of Colorado, Denver
Not yet recruiting
Intradermal Testing With COVID-19 mRNA Vaccines Predicts Tolerance - CONCLUSION: Sensitization to SARS-CoV-2 mRNA vaccines can be detected with intradermal testing. Significantly more individuals were sensitized to mRNA vaccines in the post-vaccination cohort. A two-step 10-90%-vaccination protocol can be safely administered upon negative skin testing.
Inhibition of the SARS-CoV-2 helicase at single-nucleotide resolution - The genome of SARS-CoV-2 encodes for a helicase called nsp13 that is essential for viral replication and highly conserved across related viruses, making it an attractive antiviral target. Here we use nanopore tweezers, a high-resolution single-molecule technique, to gain detailed insight into how nsp13 turns ATP-hydrolysis into directed motion along nucleic acid strands. We measured nsp13 both as it translocates along single-stranded DNA or unwinds short DNA duplexes. Our data confirm that nsp13…
Prophylactic treatment of Glycyrrhiza glabra mitigates COVID-19 pathology through inhibition of pro-inflammatory cytokines in the hamster model and NETosis - Severe coronavirus disease (COVID-19) is accompanied by acute respiratory distress syndrome and pulmonary pathology, and is presented mostly with an inflammatory cytokine release, a dysregulated immune response, a skewed neutrophil/lymphocyte ratio, and a hypercoagulable state. Though vaccinations have proved effective in reducing the COVID-19-related mortality, the limitation of the use of vaccine against immunocompromised individuals, those with comorbidity, and emerging variants remains a…
3’UTR of SARS-CoV-2 spike gene hijack host miR-296 or miR-520h to disturb cell proliferation and cytokine signaling - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has becoming globally public health threat. Recently studies were focus on SARS-CoV-2 RNA to design vaccine and drugs. It was demonstrated that virus RNA could play as sponge to host noncoding RNAs to regulate cellular processes. Bioinformatic research predicted a series of motif on SARS-CoV-2 genome where are targets of human miRNAs. In this study, we used dual-luciferase reporter assays to validate the interaction between 3’UTR of…
Synthesis and Evaluation of a Silver Nanoparticle/Polyurethane Composite That Exhibits Antiviral Activity against SARS-CoV-2 - In this proof-of-concept study, we aim to produce a polyurethane (PU)-based composite that can reduce the amount of viable SARS-CoV-2 virus in contact with the surface of the polymeric film without further interventions such as manual cleaning. Current protocols for maintaining the hygiene of commonly used touchpoints (door handles, light switches, shop counters) typically rely on repeated washing with antimicrobial products. Since the start of the SARS-CoV-2 pandemic, frequent and costly…
Antibacterial, Antifungal and Antiviral Polymeric Food Packaging in Post-COVID-19 Era - Consumers are now more concerned about food safety and hygiene following the COVID-19 pandemic. Antimicrobial packaging has attracted increased interest by reducing contamination of food surfaces to deliver quality and safe food while maintaining shelf life. Active packaging materials to reduce contamination or inhibit viral activity in packaged foods and on packaging surfaces are mostly prepared using solvent casting, but very few materials demonstrate antiviral activity on foods of animal…
Mulberrofuran G, a Mulberry Component, Prevents SARS-CoV-2 Infection by Blocking the Interaction between SARS-CoV-2 Spike Protein S1 Receptor-Binding Domain and Human Angiotensin-Converting Enzyme 2 Receptor - Despite the recent development of RNA replication-targeted COVID-19 drugs by global pharmaceutical companies, their prescription in clinical practice is limited by certain factors, including drug interaction, reproductive toxicity, and drug resistance. COVID-19 drugs with multiple targets for the SARS-CoV-2 life cycle may lead to a successful reduction in drug resistance as well as enhanced therapeutic efficacy, and natural products are a potential source of molecules with therapeutic effects…
Garcinia cambogia Phenolics as Potent Anti-COVID-19 Agents: Phytochemical Profiling, Biological Activities, and Molecular Docking - COVID-19 is a disease caused by the coronavirus SARS-CoV-2 and became a pandemic in a critically short time. Phenolic secondary metabolites attracted much attention from the pharmaceutical industries for their easily accessible natural sources and proven antiviral activity. In our mission, a metabolomics study of the Garcinia cambogia Roxb. fruit rind was performed using LC-HRESIMS to investigate its chemical profile, especially the polar aspects, followed by a detailed phytochemical analysis,…
The Discovery of Small Allosteric and Active Site Inhibitors of the SARS-CoV-2 Main Protease via Structure-Based Virtual Screening and Biological Evaluation - The main protease enzyme (M^(pro)) of SARS-CoV-2 is one of the most promising targets for COVID-19 treatment. Accordingly, in this work, a structure-based virtual screening of 3.8 million ligand libraries was carried out. After rigorous filtering, docking, and post screening assessments, 78 compounds were selected for biological evaluation, 3 of which showed promising inhibition of the M^(pro) enzyme. The obtained hits (CB03, GR04, and GR20) had reasonable potencies with K(i) values in the…
In Silico Evaluation of Natural Flavonoids as a Potential Inhibitor of Coronavirus Disease - The recent coronavirus disease (COVID-19) outbreak in Wuhan, China, has led to millions of infections and the death of approximately one million people. No targeted therapeutics are currently available, and only a few efficient treatment options are accessible. Many researchers are investigating active compounds from natural plant sources that may inhibit COVID-19 proliferation. Flavonoids are generally present in our diet, as well as traditional medicines and are effective against various…
Design, Synthesis and In Vitro Evaluation of Spirooxindole-Based Phenylsulfonyl Moiety as a Candidate Anti-SAR-CoV-2 and MERS-CoV-2 with the Implementation of Combination Studies - The search for an effective anti-viral to inhibit COVID-19 is a challenge for the specialized scientific research community. This work investigated the anti-coronavirus activity for spirooxindole-based phenylsulfone cycloadducts in a single and combination protocols. The newly designed anti-SARS-CoV-2 therapeutics spirooxindoles synthesized by [3 + 2] cycloaddition reactions represent an efficient approach. One-pot multicomponent reactions between phenyl vinyl sulfone, substituted isatins, and…
Antiviral Drugs Screening for Swine Acute Diarrhea Syndrome Coronavirus - Coronaviruses as possible cross-species viruses have caused several epidemics. The ongoing emergency of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has posed severe threats to the global economy and public health, which has generated great concerns about zoonotic viruses. Swine acute diarrhea syndrome coronavirus (SADS-CoV), an alpha-coronavirus, was responsible for mass piglet deaths, resulting in unprecedented economic losses, and no approved drugs or vaccines are currently…
Examining the Relationship between Paternal Mental Health and Informal Support Networks: Reflections on the Impact of the COVID-19 Pandemic - Paternal mental health remains an under-researched area in the UK. Consequently, father-focused formal and informal support provisions fail to address the complex emotional and psychological wellbeing needs of fathers. Drawing on data from twenty semi-structured interviews with fathers in the York area, this study seeks to better understand how access to and participation in informal support networks is influenced by gendered perceptions and the impact hegemonic perceptions of masculinity have…
NSP4 and ORF9b of SARS-CoV-2 Induce Pro-Inflammatory Mitochondrial DNA Release in Inner Membrane-Derived Vesicles - Circulating cell-free mitochondrial DNA (cf-mtDNA) has been found in the plasma of severely ill COVID-19 patients and is now known as a strong predictor of mortality. However, the underlying mechanism of mtDNA release is unexplored. Here, we show a novel mechanism of SARS-CoV-2-mediated pro-inflammatory/pro-apoptotic mtDNA release and a rational therapeutic stem cell-based approach to mitigate these effects. We systematically screened the effects of 29 SARS-CoV-2 proteins on mitochondrial damage…
Could Endogenous Glucocorticoids Influence SARS-CoV-2 Infectivity? - Endogenous glucocorticoids and their synthetic analogues, such as dexamethasone, stimulate receptor-mediated signal transduction mechanisms on target cells. Some of these mechanisms result in beneficial outcomes whereas others are deleterious in the settings of pathogen infections and immunological disorders. Here, we review recent studies by several groups, including our group, showing that glucocorticoids can directly interact with protein components on SARS-CoV-2, the causative agent of…