OBJECTIVES Three years following the start of the COVID-19 pandemic, the World Health Organization (WHO) declared COVID-19 a global health emergency of international concern. As immunity levels in the population acquired through past infections and vaccinations have been decreasing, booster vaccinations have become necessary to control new outbreaks. This study aimed to determine the most suitable vaccination strategy to control the COVID-19 surge. METHODS A mathematical model was developed to simultaneously consider the immunity levels induced by vaccines and infections, and employed to analyze the possibility of future resurgence and control using vaccines and antivirals. RESULTS As of May 11, 2023, a peak in resurgence is predicted to occur around mid-October of the same year if the current epidemic trend continues without additional vaccinations. In the best scenario, the peak number of severely hospitalized patients can be reduced by 43% (480) compared to the scenario without vaccine intervention (849). Depending on the outbreak trends and vaccination strategies, the best timing for vaccination in terms of minimizing the said peak varies from May to August 2023. CONCLUSIONS Our results indicate that if the epidemic continues, the best timing for vaccinations must be earlier than specified by the current plan in Korea. Further monitoring of outbreak trends is crucial for determining the optimal timing of vaccinations to manage future surges.
Background: Social determinants of health are non-medical factors that influence health outcomes (SDOH). There is a wealth of SDOH information available via electronic health records, clinical reports, and social media, usually in free text format, which poses a significant challenge and necessitates the use of natural language processing (NLP) techniques to extract key information. Objective: The objective of this research is to advance the automatic extraction of SDOH from clinical texts. Setting and Data: The case reports of COVID-19 patients from the published literature are curated to create a corpus. A portion of the data is annotated by experts to create gold labels, and active learning is used for corpus re-annotation. Methods: A named entity recognition (NER) framework is developed and tested to extract SDOH along with a few prominent clinical entities (diseases, treatments, diagnosis) from the free texts. Results: The proposed NER implementation achieves an accuracy (F1-score) of 92.98% on our test set and generalizes well on benchmark data. A careful analysis of case examples demonstrates the superiority of the proposed approach in correctly classifying the named entities. Conclusions: NLP can be used to extract key information, such as SDOH from free texts. A more accurate understanding of SDOH is needed to further improve healthcare outcomes.
Background: Although rapid screening for and diagnosis of COVID-19 are still urgently needed, most current testing methods are either long, costly, and/or poorly specific. The objective of the present study was to determine whether or not artificial-intelligence-enhanced real-time MS breath analysis is a reliable, safe, rapid means of screening ambulatory patients for COVID-19. Methods: In two prospective, open, interventional studies in a single university hospital, we used real-time, proton transfer reaction time-of-flight mass spectrometry to perform a metabolomic analysis of exhaled breath from adults requiring screening for COVID-19. Artificial intelligence and machine learning techniques were used to build mathematical models based on breath analysis data either alone or combined with patient metadata. Results: We obtained breath samples from 173 participants, of whom 67 had proven COVID-19. After using machine learning algorithms to process breath analysis data and further enhancing the model using patient metadata, our method was able to differentiate between COVID-19-positive and -negative participants with a sensitivity of 98%, a specificity of 74%, a negative predictive value of 98%, a positive predictive value of 72%, and an area under the receiver operating characteristic curve of 0.961. The predictive performance was similar for asymptomatic, weakly symptomatic and symptomatic participants and was not biased by the COVID-19 vaccination status. Conclusions: Real-time, non-invasive, artificial-intelligence-enhanced mass spectrometry breath analysis might be a reliable, safe, rapid, cost-effective, high-throughput method for COVID-19 screening.
Objectives: In this retrospective cohort study, we aimed to investigate symptom severity change following COVID-19 vaccination among post COVID-19 condition (PCC) patients on Bonaire. Methods: Symptomatic cases who tested positive for SARS-CoV-2 between the start of the pandemic and 1 October 2021, were unrecovered on the interview day, and unvaccinated prior to infection were identified from the national case registry. Patients were interviewed by telephone between 15 November and 4 December 2021 about sociodemographic factors, pre-pandemic health, COVID-19 symptoms and vaccination status. We compared symptom severity change between the acute and post-acute disease phase (>4 weeks after disease onset) of 14 symptoms on a five-point Likert scale for 36 PCC patients having received at least one dose of the BNT162 (BioNTech/Pfizer) vaccine and 11 patients who remained unvaccinated, using separate multiple linear regression models. Results: Most common post-acute symptoms included fatigue (81%), reduced physical endurance (79%), and reduced muscle strength (64%). Post-infection vaccination was significantly associated with reduced severity of heart palpitations, after adjusting for acute phase severity and duration of illness (β 0.60, 95% CI 0.18, 1.02). We did not find a statistically significant association with symptom severity change for other, more prevalent symptoms. Conclusions: Larger prospective studies are needed to confirm our observation in a small study population that post-infection COVID-19 vaccination was associated with reduced severity of heart palpitations among those with this symptom self-attributed to SARS-CoV-2 infection.
Objectives: Growing evidence has highlighted the global mental health impacts of the COVID-19 pandemic and lockdown, particularly in societies with pre-existing socioeconomic adversities and public health concerns. Despite the sudden and prolonged nature of many psychosocial stressors during the pandemic, recent studies have shown that communities utilized several coping mechanisms to buffer the mental health consequences of COVID-related stress. This paper examines the extent to which coping resources and social support buffered against the mental health effects of COVID-19 psychosocial stress among adults in South Africa. Materials & Methods: Adult participants (n=117) completed an online survey during the second and third waves of the COVID-19 pandemic in South Africa (January-July 2021), which assessed experiences of stress, coping resources, social support, and four mental health outcomes: depression, anxiety, post-traumatic stress disorder, and bipolar disorder. Moderation analyses examined the potential buffering role of coping resources and social support against the mental health effects of COVID-19 stress. Results: Adults reported elevated rates of psychiatric symptoms. Coping resources buffered against the poor mental health effects of COVID-19 psychosocial stress, whereas perceived social support did not significantly moderate the association between COVID-19 stress and adult mental health. Discussion: These results suggest that adults in our sample utilized a variety of coping resources to protect their mental health against psychosocial stress experienced during the COVID-19 lockdown and pandemic in South Africa. Additionally, existing mental health conditions and strained social relationships may have attenuated the potential stress-buffering effect of perceived social support on adult mental health.
Estimates of Covid-19 excess mortality are often considered to reflect the true death toll of the pandemic. As such, information on excess mortality is urgently needed to better understand the impact of the pandemic and prepare for future crises. This study estimated Covid-19 excess mortality at the provincial, regional, and national levels in China and investigated its associated regional disparities. The analyses were based on population and death rates data published by the national and provincial bureaus of statistics in China. The results suggest that excess deaths in China were over 1 million during each year of the pandemic, totaling to over 4 million by the end of 2022, at an excess death rate of 15.4%. This rate was likely comparable to that of the Organization for Economic Cooperation and Development (OECD), but higher than the US rate. Striking disparities were discovered among the 31 provinces with excess death rates ranging from negative rates in two eastern provinces to over 30% in three inland provinces. Rates in western China were over twice as high as those in eastern China. Variations with each individual regions were the largest in the central region and the smallest in the Northeast, which was the hardest hit with excess death rate of over 23%. The regional disparities in excess mortality rates seem to reflect pre-existing regional inequalities in socio-economic development in China. Such findings suggest that China has far to go to mitigate regional inequalities, achieve sustainability, and prepare for the next major crises.
Background There is evidence of pre-established vulnerability in individuals that increases the risk of their progression to severe disease or death, though the mechanisms that cause this are still not fully understood. Previous research has demonstrated that a urinary peptide classifier (COV50) predicts disease progression and death from SARS-CoV-2 at an early stage, indicating that the outcome prediction may be partly due to already present vulnerabilities. The aim of this study is to examine the ability of COV50 to predict future non-COVID-19-related mortality, and evaluate whether the pre-established vulnerability can be generic and explained on a molecular level by urinary peptides. Methods Urinary proteomic data from 9193 patients (1719 patients sampled at intensive care unit (ICU) admission and 7474 patients with other diseases (non-ICU)) were extracted from the Human Urinary Proteome Database. The previously developed COV50 classifier, a urinary proteomics biomarker panel consisting of 50 peptides, was applied to all datasets. The association of COV50 scoring with mortality was evaluated. Results In the ICU group, an increase in the COV50 score of one unit resulted in a 20% higher relative risk of death (adj. HR 1.2 [95% CI 1.17-1.24]). The same increase in COV50 in non-ICU patients resulted in a higher relative risk of 61% (adj. HR 1.61 [95% CI 1.47-1.76]), in line with adjusted meta-analytic HR estimate of 1.55. The most notable and significant changes associated with future fatal events were reductions of specific collagen fragments, most of collagen alpha I(I). Conclusion The COV50 classifier is predictive of death in the absence of SARS-CoV-2 infection, suggesting that it detects pre-existing vulnerability. Prediction is based mainly on collagen fragments, possibly reflecting disturbances in the integrity of the extracellular matrix. These data may serve as basis for proteomics guided intervention aiming towards manipulating/improving collagen turnover, thereby reducing the risk of death.
Probiotic and Colchicine in COVID-19 - Condition: COVID-19
Interventions: Drug: Colchicine 0.5 MG; Dietary Supplement: Probiotic Formula; Other: Standard protocol
Sponsor: Ain Shams University
Completed
Influence of Manual Diaphragm Release on Pulmonary Functions in Women With COVID-19 - Condition: COVID-19 Pneumonia
Interventions: Other: manual therapy; Other: breathing exercise and prone position alone
Sponsor: Cairo University
Completed
Study Evaluating SHEN26 Capsule in Patients With Mild to Moderate COVID-19 - Condition: COVID-19
Interventions: Drug: SHEN26 capsule; Drug: SHEN26 placebo
Sponsor: Shenzhen Kexing Pharmaceutical Co., Ltd.
Recruiting
A Clinical Trial of Recombinant COVID-19 Bivalent (XBB+Prototype) Protein Vaccine (Sf9 Cell) in Booster Vaccination - Condition: COVID-19
Interventions: Biological: Recombinant COVID-19 Bivalent (XBB+Prototype) Protein Vaccine (Sf9 Cell) (WSK-V101C); Biological: Recombinant COVID-19 vaccine(Sf9 Cell) (WSK-V101)
Sponsor: WestVac Biopharma Co., Ltd.
Not yet recruiting
A Phase Ⅲ Clinical Trial of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell) in Booster Vaccination - Condition: COVID-19
Interventions: Biological: High dose of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell); Biological: Low dose of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell); Biological: control group; Biological: Placebo group
Sponsor: WestVac Biopharma Co., Ltd.
Not yet recruiting
Impact Of Sensory Re-Education Paradigm On Sensation And Quality Of Life In Patients Post-Covid 19 Polyneuropathy - Condition: Post-COVID-19 Syndrome
Interventions: Other: sensory re-education training; Other: traditional treatment
Sponsor: Cairo University
Not yet recruiting
A Study to Investigate the Safety, Immunogenicity of a Bivalent mRNA Vaccine RQ3025 as a Booster Dose in Healthy Adults - Condition: COVID-19
Interventions: Biological: RQ3013; Biological: RQ3025
Sponsors: Affiliated Hospital of Yunnan University; Yunnan University; Kunming Medical University
Recruiting
A Study to Evaluate the Safety and Efficacy of COVID-19 Convalescent Plasma (CCP) Transfusion to Prevent COVID-19 in Adult Recipients Following Hematopoietic Stem Cell Transplantation - Conditions: COVID-19; Hematopoietic Stem Cell Transplantation
Intervention: Biological: COVID Convalescent Plasma
Sponsor: Institute of Hematology & Blood Diseases Hospital
Recruiting
Cupping Therapy on Immune System in Post Covid -19 - Condition: Covid-19 Patients
Interventions: Combination Product: Cupping therapy with convential medical treatment; Drug: Convential medical treatment
Sponsor: Cairo University
Completed
Evaluating the Efficacy of Remdesivir for Long COVID Following a Confirmed COVID-19 Infection. - Conditions: SARS-CoV-2 Infection; COVID-19
Intervention: Drug: Remdesivir
Sponsors: University of Derby; University of Exeter; Peninsula Clinical Trials Unit; University Hospitals of Derby and Burton NHS Foundation Trust
Not yet recruiting
Immunogenicity and Safety Study of SARS-CoV-2 DNA Vaccine (ICCOV) - Condition: COVID-19
Intervention: Biological: SARS-CoV-2 DNA Vaccine (ICCOV)
Sponsors: Immuno Cure 3 Limited; The University of Hong Kong
Recruiting
Phase 3 Study of S-217622 in Prevention of Symptomatic SARS-CoV-2 Infection - Condition: SARS-CoV-2 Infection
Interventions: Drug: S-217622; Drug: Placebo
Sponsor: Shionogi
Recruiting
LIAISON NES Flu A/B & COVID-19 Clinical Agreement - Conditions: Influenza A; Influenza Type B; Coronavirus Disease 2019
Intervention: Diagnostic Test: LIAISON NES FLU A/B & COVID-19
Sponsor: DiaSorin Molecular LLC
Not yet recruiting
NC Testing in LC & POTS: A Pilot Study - Conditions: Postural Orthostatic Tachycardia Syndrome; Post Acute Sequelae of SARS CoV 2 Infection
Intervention: Other: IV normal saline (1 Litre)
Sponsor: University of Calgary
Not yet recruiting
To Investigate Efficacy, Pharmacodynamics, and Safety of BC 007 in Participants With Long COVID - Condition: Long Covid
Intervention: Drug: BC 007 or matching placebo
Sponsor: Berlin Cures GmbH
Recruiting
Reconsideration of interferon treatment for viral diseases: Lessons from SARS, MERS, and COVID-19 - Periodic pandemics of coronavirus (CoV)-related pneumonia have been a major challenging issue since the outbreak of severe acute respiratory syndrome (SARS) in 2002 and Middle East respiratory syndrome (MERS) in 2012. The ongoing pandemic of CoV disease (COVID-19) poses a substantial threat to public health. As for the treatment options, only limited antiviral agents have been approved hitherto, and clinicians mainly focus on currently available drugs including the conventional antiviral…
Two Novel Adenovirus Vectors Mediated Differential Antibody Responses via Interferon-α and Natural Killer Cells - Recombinant adenovirus vectors have been widely used in vaccine development. To overcome the preexisting immunity of human adenovirus type 5 (Ad5) in populations, a range of chimpanzee or rare human adenovirus vectors have been generated. However, these novel adenovirus vectors mediate the diverse immune responses in the hosts. In this study, we explored the immune mechanism of differential antibody responses to SARS-CoV-2 S protein in mice immunized by our previously developed two novel simian…
SARS-CoV-2 nsp13 Restricts Episomal DNA Transcription without Affecting Chromosomal DNA - Nonstructural protein 13 (nsp13), the helicase of SARS-CoV-2, has been shown to possess multiple functions that are essential for viral replication, and is considered an attractive target for the development of novel antivirals. We were initially interested in the interplay between nsp13 and interferon (IFN) signaling, and found that nsp13 inhibited reporter signal in an IFN-β promoter assay. Surprisingly, the ectopic expression of different components of the RIG-I/MDA5 pathway, which were used…
SARS-CoV-2 hijacks p38β/MAPK11 to promote virus replication - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, drastically modifies infected cells to optimize virus replication. One such modification is the activation of the host p38 mitogen-activated protein kinase (MAPK) pathway, which plays a major role in inflammatory cytokine production, a hallmark of severe COVID-19. We previously demonstrated that inhibition of p38/MAPK activity in SARS-CoV-2-infected cells reduced…
Accelerating drug target inhibitor discovery with a deep generative foundation model - Inhibitor discovery for emerging drug-target proteins is challenging, especially when target structure or active molecules are unknown. Here, we experimentally validate the broad utility of a deep generative framework trained at-scale on protein sequences, small molecules, and their mutual interactions-unbiased toward any specific target. We performed a protein sequence-conditioned sampling on the generative foundation model to design small-molecule inhibitors for two dissimilar targets: the…
ARF6 is a host factor for SARS-CoV-2 infection in vitro - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged beta-coronavirus that enter cells via two routes, direct fusion at the plasma membrane or endocytosis followed by fusion with the late endosome/lysosome. While the viral receptor, ACE2, multiple entry factors and the mechanism of fusion of the virus at the plasma membrane have been investigated extensively, viral entry via the endocytic pathway is less understood. By using a human hepatocarcinoma cell line, Huh-7,…
Irreversible Inactivation of SARS-CoV-2 by Lectin Engagement with Two Glycan Clusters on the Spike Protein - Host cell infection by SARS-CoV-2, similar to that by HIV-1, is driven by a conformationally metastable and highly glycosylated surface entry protein complex, and infection by these viruses has been shown to be inhibited by the mannose-specific lectins cyanovirin-N (CV-N) and griffithsin (GRFT). We discovered in this study that CV-N not only inhibits SARS-CoV-2 infection but also leads to irreversibly inactivated pseudovirus particles. The irreversibility effect was revealed by the observation…
Viral evasion of the interferon response at a glance - Re-emerging and new viral pathogens have caused significant morbidity and mortality around the world, as evidenced by the recent monkeypox, Ebola and Zika virus outbreaks and the ongoing COVID-19 pandemic. Successful viral infection relies on tactical viral strategies to derail or antagonize host innate immune defenses, in particular the production of type I interferons (IFNs) by infected cells. Viruses can thwart intracellular sensing systems that elicit IFN gene expression (that is, RIG-I-like…
Preventing Occludin Tight-Junction Disruption via Inhibition of microRNA-193b-5p Attenuates Viral Load and Influenza-induced Lung Injury - Virus-induced lung injury is associated with loss of pulmonary epithelial-endothelial tight junction integrity. While the alveolar-capillary membrane may be an indirect target of injury; viruses may interact directly and/or indirectly with miRs to augment their replication potential and evade the host antiviral defense system. Here we expose how the influenza virus (H1N1) capitalizes on host-derived interferon-induced, microRNA (miR)-193b-5p to target occludin and compromise antiviral defenses….
The impact of COVID-19 on the intention of third-child in China: an empirical analysis based on survey data - BACKGROUND: Against the grim background of declining intention to have children, the ravages of COVID-19 have pushed China and the world into a more complex social environment. To adapt to the new situation, the Chinese government implemented the three-child policy in 2021.
Activity of nsp14 Exonuclease from SARS-CoV-2 towards RNAs with Modified 3’-Termini - The COVID-19 pandemic has shown the urgent need for new treatments for coronavirus infections. Nucleoside analogs were successfully used to inhibit replication of some viruses through the incorporation into the growing DNA or RNA chain. However, the replicative machinery of coronaviruses contains nsp14, a non-structural protein with a 3’→5’-exonuclease activity that removes misincorporated and modified nucleotides from the 3’ end of the growing RNA chain. Here, we studied the efficiency of…
Effective inhibition of HCoV-OC43 and SARS-CoV-2 by phytochemicals in vitro and in vivo - Several coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human coronavirus OC43 (HCoV-OC43) can cause respiratory infections in humans. To address the need for reliable anti-coronavirus therapeutics, we screened 16 active phytochemicals selected from medicinal plants used in traditional applications for respiratory-related illnesses. An initial screen was completed using HCoV-OC43. The phytochemicals lycorine (LYC), capsaicin (CAP), rottlerin (RTL),…
Generation of host-directed and virus-specific antivirals using targeted protein degradation promoted by small molecules and viral RNA mimics - Targeted protein degradation (TPD), as exemplified by proteolysis-targeting chimera (PROTAC), is an emerging drug discovery platform. PROTAC molecules, which typically contain a target protein ligand linked to an E3 ligase ligand, recruit a target protein to the E3 ligase to induce its ubiquitination and degradation. Here, we applied PROTAC approaches to develop broad-spectrum antivirals targeting key host factors for many viruses and virus-specific antivirals targeting unique viral proteins….
A broad-spectrum macrocyclic peptide inhibitor of the SARS-CoV-2 spike protein - The ongoing COVID-19 pandemic has had great societal and health consequences. Despite the availability of vaccines, infection rates remain high due to immune evasive Omicron sublineages. Broad-spectrum antivirals are needed to safeguard against emerging variants and future pandemics. We used messenger RNA (mRNA) display under a reprogrammed genetic code to find a spike-targeting macrocyclic peptide that inhibits SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Wuhan strain infection…
Specific nasopharyngeal Corynebacterium strains serve as gatekeepers against SARS-CoV-2 infection - The SARS-CoV-2 virus is still causing a worldwide problem. The virus settles primarily on the nasal mucosa, and the infection and its course depend on individual susceptibility. Our aim was to investigate the nasopharynx composition’s role in the individual susceptibility. During the first phase of SARS-CoV-2 pandemic, nasopharyngeal microbiome samples of close contact unvaccinated patients were investigated by 16S rRNA analysis and by culturing. The whole genome of cultured Corynebacteria was…