Covid-19 Sentry

Contents

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

From Preprints

• The benefits of voluntary plasma donations: safety, price, and supply resilience -
  This article summarizes data on blood and blood component VNRD compared to remunerated donations, in the context of safety for patients and donors, price of products, and supply resiliency. This is particularly relevant given the ongoing debate on the proposal for a regulation on substances of human origin (SoHO). Data indicated that when donors are remunerated and therefore donate very frequently, the safety of the patients receiving these donations and the donors themselves is at risk. Moreover, when donations were VNRD compared to remunerated, PDMP prices increased less between 2018 and 2023 and were therefore more cost-effective for patients and healthcare systems. Lastly, the supply of plasma was found to be more resilient during the COVID-19 pandemic when donors were non-remunerated compared to when they were remunerated. In addition, once countries implement remuneration, it cannot be reversed without risking the supply. We strongly urge policy makers to rely on empirical evidence as a basis for decision-making regarding the proposal for a regulation on SoHO.
  🖺 Full Text HTML: The benefits of voluntary plasma donations: safety, price, and supply resilience
• Influenza Hospitalisations in England during the 2022/23 Season: do different data sources drive divergence in modelled waves? A comparison of surveillance and administrative data. -

  Background Seasonal influenza places a substantial burden annually on healthcare services. Policies during the COVID-19 pandemic limited the transmission of seasonal influenza, making the timing and magnitude of a potential resurgence difficult to ascertain and important to forecast its impact. Methods We have developed a hierarchical generalised additive model (GAM) for the short-term forecasting of hospital admissions with a positive test for the influenza virus sub-regionally across England. The model incorporates a multi-level structure of spatio-temporal splines, weekly cycles in admissions, and spatial correlation. Using multiple performance metrics including interval score, coverage, bias, and median absolute error, the predictive performance is evaluated for the 2022/2023 seasonal wave. Performance is measured against autoregressive integrated moving average (ARIMA) and Prophet time series models. Results Across the epidemic phases the hierarchical GAM shows improved performance, at all geographic scales relative to the ARIMA and Prophet models. Temporally, the hierarchical GAM has overall an improved performance at 7 and 14 day time horizons. The performance of the GAM is most sensitive to the flexibility of the smoothing function that measures the national epidemic trend. Conclusions This study introduces an approach to short-term forecasting of hospital admissions for the influenza virus using hierarchical, spatial, and temporal components. The methodology was designed for the real time forecasting of epidemics. This modelling framework was used across the 2022/2023 winter for healthcare operational planning by the UK Health Security Agency and the National Health Service in England.

  🖺 Full Text HTML: Influenza Hospitalisations in England during the 2022/23 Season: do different data sources drive divergence in modelled waves? A comparison of surveillance and administrative data.
• Impact of natural disasters on HIV risk behaviors, seroprevalence, and virological supression in a hyperendemic fishing village in Uganda -

  Background: Understanding the impact of natural disasters on the HIV epidemic in populations with high HIV burden is critical for the effective delivery of HIV control efforts. We assessed HIV risk behaviors, seroprevalence, and viral suppression in a high-HIV prevalence Lake Victoria fishing community before and after COVID-19 emergence/lockdown and a severe lake flooding event, both of which occurred in 2020. Methods: We used data from the largest Lake Victoria fishing community in the Rakai Community Cohort Study, an open population-based HIV surveillance cohort in south-central Uganda, collected prior to (September-December 2018) and after (October-December 2021) COVID-19 emergence/lockdown and a severe flooding event, to evaluate the impact of natural disasters on the key population-level HIV outcomes listed above. Households impacted by flooding were identified using drone data and through consultation with village community health workers. The entire study population was subject to extensive COVID-19-related lockdowns in the first half of 2020. Differences in HIV-related outcomes before and after COVID, and between residents of flooded and non-flooded households, were assessed using a difference-in-difference statistical modeling approach. Findings: 1,226 people participated in the pre- and post-COVID surveys, of whom 506 (41%) were affected by flooding and 513 (41%) were female. HIV seroprevalence in the initial period was 37% in flooded and 36.8% in non-flooded households. Following the COVID-19 pandemic/lockdown, we observed a decline in HIV-associated risk behaviors. Transactional sex declined from 29.4% to 24.8% (p=0.011), and inconsistent condom use with non-marital partners declined from 41.6% to 37% (p=0.021) in the pre- and post-COVID periods. ART coverage increased from 91.6% to 97.2% (p<0.001). There was 17% decline in transactional sex (aPR=0.83, 95% CI: 0.75-0.92) and 28% decline in the overall HIV risk score (aPR=0.83, 95% CI: 0.75-0.92) among HIV-seronegatives and 5% increase in ART coverage between the pre- and post-COVID periods. We observed no statistically significant differences in changes of HIV risk behavior, seroprevalence, or viral suppression outcomes comparing those affected by floods to those not affected by floods in the periods before and after COVID in difference-in-difference analyses. Interpretation: Despite a high background burden of HIV, the COVID-19 pandemic, and severe flooding, we observed no adverse impact on HIV risk behaviors, seroprevalence, or virologic outcomes. This may be attributed to innovative HIV programming during the period and or population resilience. Understanding exactly what HIV programs and personal/community-level strategies worked to maintain good public health outcomes despite extreme environmental and pandemic conditions may help improve HIV epidemic control during future natural disaster events.

  🖺 Full Text HTML: Impact of natural disasters on HIV risk behaviors, seroprevalence, and virological supression in a hyperendemic fishing village in Uganda
• SARS-CoV-2 lineage-specific disease symptoms and disease severity in Sao Caetano do Sul city, Brazil -

  Background: The city of Sao Caetano do Sul, Brazil, established a web-based platform to provide primary care to suspected COVID-19 patients, integrating clinical and demographic data and sample metadata. Here we describe lineage-specific spatiotemporal dynamics of infections, clinical symptoms, and disease severity during the first year of the epidemic. Methods: We selected and sequenced 879 PCR+ swab samples (8% of all reported cases), obtaining a spatially and temporally representative set of sequences. Daily lineage-specific prevalence was estimating using a moving-window approach, allowing inference of cumulative cases and symptom probability stratified by lineage using integrated data from the platform. Results: Most infections were caused by B.1.1.28 (41.3%), followed by Gamma (31.7%), Zeta (9.6%) and B1.1.33 (9.0%). Gamma and Zeta were associated with larger prevalence of dyspnoea (respectively 81.3% and 78.5%) and persistent fever (84.7% and 61.1%) compared to B.1.1.28 and B.1.1.33. Ageusia, anosmia, and coryza were respectively 18.9%, 20.3% and 17.8% less commonly caused by Gamma, while altered mental status was 108.9% more common in Zeta. Case incidence was spatially heterogeneous and larger in poorer and younger districts. Discussion: Our study demonstrates that Gamma was associated with more severe disease, emphasising the role of its increased disease severity in the heightened mortality levels in Brazil.

  🖺 Full Text HTML: SARS-CoV-2 lineage-specific disease symptoms and disease severity in Sao Caetano do Sul city, Brazil
• Commentary on the Strategic Interventions for Agriculture, Climate Change, and Food Security Proposed by the National Science and Technology Commission at the 9th Biennial Conference on Science and Technology -
  Agriculture in Sri Lanka occupies 45.46% of the land and consumes over 80% of the country’s freshwater resources. Rice farming is the most prominent agricultural practice, with 1.8 million families engaged in it. The tea plantation sector produces tea annually, contributing to 285,877 metric tons of export volume. Tea exports contribute nearly 38% of the total agricultural products, with a target of $2,044 million in income by 2025. Climate change and natural resources significantly impact agriculture, with irregular rainfall patterns, temperature variation, and drought causing significant challenges. The proposed interventions under the food crops, plantation, and export crops sectors include enhancing certified seed production, promoting value-added products, and developing training and awareness programs for low-carbon lifestyles. Food security is another area where climate change impacts the agricultural sector, with nearly 26% of the population affected by food security by 2050 due to the COVID-19 pandemic and the conflict between Russia and Ukraine. To address this issue, the proposed strategic interventions aim to achieve SDG 1, SDG 2, and SDG 13, the recommendations of the Paris Agreement on Climate Change, and the actions of the Milan Urban Food Policy Fund. However, more concerns can be put forward to minimize or eliminate diseases in agricultural sectors due to climate change and minimize food waste or loss.
  🖺 Full Text HTML: Commentary on the Strategic Interventions for Agriculture, Climate Change, and Food Security Proposed by the National Science and Technology Commission at the 9th Biennial Conference on Science and Technology
• Caveolin-1 mediates neuroinflammation and cognitive impairment in SARS-CoV-2 infection -
  Leukocyte infiltration of the CNS can contribute to neuroinflammation and cognitive impairment. Brain endothelial cells regulate adhesion, activation, and diapedesis of T cells across the blood-brain barrier (BBB) in inflammatory diseases. The integral membrane protein Caveolin-1 (Cav-1) critically regulates BBB permeability, but its influence on T cell CNS infiltration in respiratory viral infections is unknown. In this study, we sought to determine the role of Cav-1 at the BBB in neuroinflammation in a COVID-19 mouse model. We used mice genetically deficient in Cav-1 to test the role of this protein in T cell infiltration and cognitive impairment. We found that SARS-CoV-2 infection upregulated brain endothelial Cav-1. Moreover, SARS-CoV-2 infection increased brain endothelial cell vascular cell adhesion molecule-1 (VCAM-1) and CD3+ T cell infiltration of the hippocampus, a region important for short term learning and memory. Concordantly, we observed learning and memory deficits. Importantly, genetic deficiency in Cav-1 attenuated brain endothelial VCAM-1 expression and T cell infiltration in the hippocampus of mice with SARS-CoV-2 infection. Moreover, Cav-1 KO mice were protected from the learning and memory deficits caused by SARS-CoV-2 infection. These results indicate the importance of BBB permeability in COVID-19 neuroinflammation and suggest potential therapeutic value of targeting Cav-1 to improve disease outcomes.
  🖺 Full Text HTML: Caveolin-1 mediates neuroinflammation and cognitive impairment in SARS-CoV-2 infection
• Th2 and Th17-Associated Immunopathology Following SARS-CoV-2 Breakthrough Infection in Spike-vaccinated ACE2-humanized Mice -
  Vaccines have demonstrated remarkable effectiveness in protecting against COVID-19; however, concerns regarding vaccine-associated enhanced respiratory diseases (VAERD) following breakthrough infections have emerged. Spike protein subunit vaccines for SARS-CoV-2 induce VAERD in hamsters, where aluminum adjuvants promote a Th2-biased immune response, leading to increased type 2 pulmonary inflammation in animals with breakthrough infections. To gain a deeper understanding of the potential risks and the underlying mechanisms of VAERD, we immunized ACE2-humanized mice with SARS-CoV-2 Spike protein adjuvanted with aluminum and CpG-ODN. Subsequently, we exposed them to increasing doses of SARS-CoV-2 to establish a breakthrough infection. The vaccine elicited robust neutralizing antibody responses, reduced viral titers, and enhanced host survival. However, following a breakthrough infection, vaccinated animals exhibited severe pulmonary immunopathology, characterized by a significant perivascular infiltration of eosinophils and CD4+ T cells, along with increased expression of Th2/Th17 cytokines. Intracellular flow cytometric analysis revealed a systemic Th17 inflammatory response, particularly pronounced in the lungs. Our data demonstrate that aluminum/CpG adjuvants induce strong antibody and Th1-associated immunity against COVID-19 but also prime a robust Th2/Th17 inflammatory response, which may contribute to the rapid onset of T cell-mediated pulmonary immunopathology following a breakthrough infection. These findings underscore the necessity for further research to unravel the complexities of VAERD in COVID-19 and to enhance vaccine formulations for broad protection and maximum safety.
  🖺 Full Text HTML: Th2 and Th17-Associated Immunopathology Following SARS-CoV-2 Breakthrough Infection in Spike-vaccinated ACE2-humanized Mice
• The Risk of Mpox (Monkeypox) Importation and Subsequent Outbreak Potential in Mainland China: A Retrospective Statistical Modelling Study -

  The 2022 mpox outbreak has spread rapidly across multiple countries in the non-endemic region, mainly among men who have sex with men (MSM), while China only has limited recorded importation and no local outbreak. We constructed probabilistic models to simulate the risk of mpox importation in mainland China, with the help of reported monkeypox cases during this multi-country outbreak and the international air-travel data. And we further evaluated the mpox outbreak potential given that undetected mpox infections were introduced into men who have sex with men, considering different transmissibility, population immunity and population activity. We found that the reduced international air-travel volume and stringent border entry policy decreased about 94% and 69% mpox importations respectively. Once a mpox case is introduced into active MSM population with almost no population immunity, the risk of triggering local transmission is estimated at 42%, and would rise to >95% with over six cases. Our study demonstrates the key role of the reduced international air-travel volume and stringent border entry policy during the COVID-19 pandemic on reducing mpox importations, and the subsequent risk of triggering local outbreaks among MSM.

  🖺 Full Text HTML: The Risk of Mpox (Monkeypox) Importation and Subsequent Outbreak Potential in Mainland China: A Retrospective Statistical Modelling Study
• Association between common adverse events after COVID-19 vaccination and anti-SARS-CoV-2 antibody concentrations in a population-based prospective cohort study in the Netherlands -

  INTRODUCTION: Adverse events (AE) such as pain at injection site or fever are common after COVID-19 vaccination. We aimed to describe determinants of AE after COVID-19 vaccination and investigate the association between AE and pre- and post-vaccination antibody concentrations. METHODS: Participants of an ongoing prospective cohort study (VASCO) completed a questionnaire on AE within two months after COVID-19 vaccination and provided 6-monthly serum samples. Data from May 2021 to November 2022 were included. Logistic regression analyses were performed to investigate determinants of AE after mRNA vaccination, including pre-vaccination Ig antibody concentrations against the receptor binding domain. Multivariable linear regression was performed in SARS-CoV-2 naive participants to assess the association between AE and log-transformed antibody concentrations 3-8 weeks after mRNA vaccination. RESULTS: 47,947 AE questionnaires were completed by 28,032 participants. In 42% and 34% of questionnaires, injection site and systemic AE were reported, respectively. In 2.2% of questionnaires, participants sought medical attention due to AE. AE were reported significantly more frequently by women, younger participants (<60 years), participants with medical risk conditions and Spikevax recipients (versus Comirnaty). Higher pre-vaccination antibody concentrations were associated with higher incidence of systemic AE after the second and third dose, but not with injection site AE or AE for which medical attention was sought. Any AE after the third dose was associated with higher post-vaccination antibody concentrations (geometric mean concentration ratio: 1.38, 95%CI 1.23-1.54). CONCLUSION: Our study suggests that high pre-vaccination antibody levels induce AE, and that experiencing AE may be a marker for a good antibody response to vaccination.

  🖺 Full Text HTML: Association between common adverse events after COVID-19 vaccination and anti-SARS-CoV-2 antibody concentrations in a population-based prospective cohort study in the Netherlands
• COVID-19 cases associated with testing policies in 34 highly democratic countries, 2020-2022 -

  COVID-19 testing policies varied in time from testing only the symptomatic, testing the symptomatic and persons at higher risk of severe disease, on-demand testing for people who wanted one, and two periods of government-imposed mass testing in Slovakia. Using Poisson regression, this study examines the associations of COVID-19 cases during the times that the noted policies were in effect in 34 countries rated highest on democracy scores. Statistically corrected for other risk factors, increases in negative tests were associated with subsequent surges in cases when on-demand testing was promoted, particularly when coupled with poor contact tracing. Mass testing in Slovakia was associated with reduced spread of the virus for short periods but was deemed unsustainable. The data support the hypothesis that on-demand testing resulted in the unanticipated consequence of increased travel and increased exposure of travelers to the virus.

  🖺 Full Text HTML: COVID-19 cases associated with testing policies in 34 highly democratic countries, 2020-2022
• KCL TEST: an open-source inspired asymptomatic SARS-CoV-2 surveillance programme in an academic institution -

  Objectives: To establish a SARS-CoV-2 PCR testing programme in an academic institution to analyze saliva samples collected from asymptomatic staff and students. Design: PCR to detect SARS-CoV-2 RNA in saliva self-collected by asymptomatic students and staff members from King′s College London, and their household contacts. Standards for diagnostics testing set by the DHSC (UK) were followed to develop an automated saliva PCR service for SARS-CoV-2 detection. Prospective study that run from December 2020 until July 2022. Setting: Testing took place in an academic institution including 18 different locations in London (UK). Participants: There were no selection criteria; asymptomatic participants were encouraged to test regularly (twice weekly when on campus). Main outcome measures: Number of tests, number of participants and positive rate. Results: 158,277 PCR tests were carried out on saliva, of which 2,989 were positive (1.89%), collected by 20,186 participants. Between 10-30% of campus footfall were tested. The positive rate was equivalent to that reported by the Office for National Statistics (UK), except for the period encompassing the delta variant; this wave was nearly absent in our cohort. We employed non-commercial reagents and an open source-inspired automated pipeline for sample processing. This rapidly developed service was awarded UKAS accreditation under the ISO15189 standard. Conclusions: Including academic institutions in pandemic preparedness is a critical consideration, considering the experience in developing, validating, and implementing economic and scalable testing solutions. Given the joint ventures in hospital pathology departments across the UK and the move to centralised, automated, commercial tests, focusing on academic centres that can carry out research and development to test for novel and re-emerging pathogens should be a top priority.

  🖺 Full Text HTML: KCL TEST: an open-source inspired asymptomatic SARS-CoV-2 surveillance programme in an academic institution
• XAV-19 a Glyco-Humanized polyclonal antibody targeting SARS-CoV-2 accelerates the recovery of mild to moderate COVID-19 patients and keeps its neutralizing activity against Omicron and its subvariants. -

  Background: XAV-19 is a glyco-humanized swine polyclonal antibody targeting SARS-CoV-2. The safety and clinical efficacy of XAV-19 was investigated in patients with a WHO score of 2 to 4 in the WHO 7-point ordinal scale. The activity of XAV-19 against Omicron and its subvariants was assessed in vitro. Methods: A phase II/III, multicentric randomized double-blind placebo-controlled, clinical trial was conducted to evaluate the safety and clinical efficacy of XAV-19 in inpatients with COVID-19 requiring or not oxygen therapy and outpatients not requiring oxygen (EUROXAV trial, NCT04928430). Most patients were not vaccinated. The primary endpoint was the proportion of patients with an aggravation of COVID-19 within 8 days after treatment. Binding and neutralization of Omicron or its subvariants by XAV-19 was investigated by ELISA or with a whole virus neutralization assay. Results: Patients received either 150mg of XAV-19 (N=139) or placebo (N=140). Low enrolment forced the premature trial termination. XAV-19 was well tolerated. No difference in the primary endpoint, nor in the proportion with an improvement at day 8 (secondary endpoint) was observed between the 2 groups. For patients not requiring oxygen therapy, XAV-19 reduced the time to improvement significantly (7 days vs 14 days p=0.0159). Neutralizing activity against Omicron and BA.2, BA2.12.1, BA.4/5 and BQ1.1 subvariants was shown in vitro. Conclusions: XAV-19 did not reduce the aggravation in COVID-19 patients. While it did not bring any benefit to patients requiring oxygen, it reduced the time to improvement for patients not requiring oxygen (WHO score 2 or 3). These preliminary clinical data might indicate a therapeutic potential for patients with mild to moderate COVID-19 requiring supplementation with anti-SARS-CoV-2 neutralizing antibodies.

  🖺 Full Text HTML: XAV-19 a Glyco-Humanized polyclonal antibody targeting SARS-CoV-2 accelerates the recovery of mild to moderate COVID-19 patients and keeps its neutralizing activity against Omicron and its subvariants.
• Excess deaths in China during SARS-CoV-2 viral waves in 2022-2023 -

  Background The extent to which the Omicron variant of SARS-CoV-2 raised death rates in China during its viral wave of December 2022-January 2023 remains undocumented. Methods We worked with an established national survey organization to survey 8,004 adults in all 31 administrative areas of China to ask about deaths in families since January 2020. We examined age-specific death rates, focusing on deaths above age 60 years, and at 15-59 years. We compared these to the United Nations (UN) estimates of age-specific mortality in 2019. Findings The survey participants were broadly similar to the 2020 census and other national surveys in age, sex, region, and smoking status, but had lower SARS-CoV-2 vaccination rates and higher education levels. There were no differences between reporting of deaths during the Omicron period versus earlier. The survey captured 456 deaths, of which 329 occurred at ages 60+ years and 212 were women. At ages 60+ years, death rates per 1000 rose 242% (95%CI 128-398%) during December 2022-January 2023. Deaths at ages 15-59 years did not rise appreciably. The UN estimates approximately 675,000 deaths per month at ages 60+ years in 2019. If rates doubled nationally as in our survey, China had approximately 1.35 million excess deaths over the two months. Interpretation China experienced a sharp but short increase in excess deaths among its elderly during the Omicron wave. If death registry data corroborate our estimates of substantial excess deaths in China, the worldwide estimates of excess deaths to 2023 may need upward adjustment.

  🖺 Full Text HTML: Excess deaths in China during SARS-CoV-2 viral waves in 2022-2023
• Mobilising Immigrant-Origin Voters into Survey Participation: the Effect of In-person Canvassing Versus Postal Reminders on Response Rates in a Longitudinal Election Survey -
  This paper experimentally analyses the effects of in-person canvassing and postal reminders on the mobilization of non-respondents for a telephone panel survey in Germany. We compare the response rates among randomly selected individuals who were visited by canvassers and those reminded by an invitation letter. We further conduct multivariate analyses to control for different contexts in the survey area, characteristics of canvassers and information about (non-)respondents available from the sampling frame. The sample was drawn from the population registry of the city of Duisburg, Germany, and fieldwork started during the peak of the COVID-19 pandemic with most shops and restaurants being closed. Target persons in the sample were eligible voters from the two largest immigrant-origin groups in Germany who had not responded to an initial postal invitation to the survey. In-person canvassing significantly increases the probability of reacting to the survey invitation (18.3 % diff., 95 % c.i., 16.2 – 20.3 %) and to participate in the first wave of a three-wave longitudinal telephone survey (2.1 % diff., 95 % c.i., 0.7 – 3.5 %). Within the canvassed group, direct personal contact to a target person has a significantly higher effect on participation rates (14.0 % diff., 95 % c.i., 18.2 – 9.7). As a collateral plus, the fieldwork documentation helped the research team to gain more knowledge about non-respondents. However, panel attrition rises among those being canvassed (17.9 % diff., 95 % c.i., 9.7 – 26.0 %) and the cost per successfully mobilized individual is by far lower with postal reminders.
  🖺 Full Text HTML: Mobilising Immigrant-Origin Voters into Survey Participation: the Effect of In-person Canvassing Versus Postal Reminders on Response Rates in a Longitudinal Election Survey
• Comprehensive analysis of nasal IgA antibodies induced by intranasal administration of the SARS-CoV-2 spike protein -
  Intranasal vaccination is an attractive strategy for preventing COVID-19 disease as it stimulates the production of multimeric secretory immunoglobulin A (IgAs), the predominant antibody isotype in the mucosal immune system, at the target site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry. Currently, the evaluation of intranasal vaccine efficacy is based on the measurement of polyclonal antibody titers in nasal lavage fluid. However, how individual multimeric secretory IgA protects the mucosa from SARS-CoV-2 infection remains to be elucidated. To understand the precise contribution and molecular nature of multimeric secretory IgAs induced by intranasal vaccines, we developed 99 monoclonal IgAs from nasal mucosa and 114 monoclonal IgAs or IgGs from nonmucosal tissues of mice that were intranasally immunized with the SARS-CoV-2 spike protein. The nonmucosal IgAs exhibited shared origins and both common and unique somatic mutations with the related nasal IgA clones, indicating that the antigen-specific plasma cells in the nonmucosal tissues originated from B cells stimulated at the nasal mucosa. Comparing the spike protein binding reactivity, angiotensin-converting enzyme-2-blocking and SARS-CoV-2 virus neutralization of monomeric and multimeric IgA pairs recognizing different epitopes showed that even nonneutralizing monomeric IgA, which represents 70% of the nasal IgA repertoire, can protect against SARS-CoV-2 infection when expressed as multimeric secretory IgAs. Our investigation is the first to demonstrate the function of nasal IgAs at the monoclonal level, showing that nasal immunization can provide effective immunity against SARS-CoV-2 by inducing multimeric secretory IgAs at the target site of virus infection.
  🖺 Full Text HTML: Comprehensive analysis of nasal IgA antibodies induced by intranasal administration of the SARS-CoV-2 spike protein

From Clinical Trials

• Immunogenicity of Concomitant Administration of COVID-19 Vaccines With Influenza Vaccines - Conditions: COVID-19; Influenza; Vaccine Reaction; Contaminant Injected
  Interventions: Biological: Omicron-containing COVID-19 vaccine; Biological: influenza vaccine
  Sponsors: Catholic Kwandong University; Korea University Guro Hospital
  Recruiting

• Narrative Intervention for Long COVID-19 (NICO) - Conditions: Long COVID; Long Covid19
  Interventions: Behavioral: Narrative Intervention for Long COVID-19 (NICO)
  Sponsors: University of Colorado, Denver
  Active, not recruiting

• Inspiratory Muscle Training in People With Long COVID- A Pilot Investigation. - Conditions: Long COVID
  Interventions: Device: PrO2
  Sponsors: University of Bath; Swansea University
  Not yet recruiting

• Home-Based Respiratory Muscle Strength Training Program for Individuals With Post-COVID-19 Persistent Dyspnea - Conditions: Post-COVID-19 Syndrome; Dyspnea
  Interventions: Device: Respiratory Muscle Strength Trainers
  Sponsors: University of South Florida
  Not yet recruiting

• Inspiratory Muscle Strength Training in Post-Covid Syndrome - Conditions: Cardiovascular Abnormalities; Post-COVID-19 Syndrome; Physical Exercise
  Interventions: Other: Inspiratory muscle strength training
  Sponsors: D’Or Institute for Research and Education
  Recruiting

• Rural Tailored Communication to Promote SARS-CoV-2 Antibody Testing in Saliva - Conditions: SARS-CoV2 Infection
  Interventions: Behavioral: General SARS-CoV-2 Communication; Behavioral: Rural-Targeted SARS-CoV-2 Communication
  Sponsors: Michigan State University; National Cancer Institute (NCI); Johns Hopkins University
  Recruiting

• Cognitive Rehabilitation Therapy for COVID-19 - Conditions: Post-Acute COVID-19 Syndrome
  Interventions: Behavioral: Compensatory Cognitive Training for COVID-19; Behavioral: Holistic Cognitive Education
  Sponsors: VA Office of Research and Development
  Not yet recruiting

• COVID Rehabilitation - Conditions: Rehabilitation; Post-Acute COVID-19 Syndrome; Post-Infectious Disorders
  Interventions: Behavioral: One day course; Behavioral: Individual follow-ups
  Sponsors: University Hospital of North Norway; University of Bergen; Oslo University Hospital; Norwegian University of Science and Technology
  Not yet recruiting

• Phase 3 Open-Label Controlled Trial of Convalescent Plasma in Early COVID-19 Infection - Conditions: Covid19
  Interventions: Drug: Convalescent Plasma; Other: Standard of Care
  Sponsors: Larkin Community Hospital
  Withdrawn

• Food Effects of GST-HG171 Tablets Combined With Ritonavir in Healthy Chinese Participants - Conditions: COVID-19 Respiratory Infection
  Interventions: Drug: GST-HG171/ritonavir; Drug: ritonavir
  Sponsors: Fujian Akeylink Biotechnology Co., Ltd.
  Active, not recruiting

• Improving Post COVID-19 Syndrome With Hyperbaric Oxygen Treatments - Conditions: Post COVID-19 Condition; Post-COVID-19 Syndrome; Post-COVID Syndrome; COVID-19; Fatigue; Fatigue Syndrome, Chronic
  Interventions: Device: Monoplace Hyperbaric Chamber (Class III medical device).
  Sponsors: Sunnybrook Health Sciences Centre
  Not yet recruiting

• Education of Medical Staff to Post Acute Covid susTained sYmptoms - Conditions: Post-acute COVID-19 Syndrome
  Interventions: Other: Training in the management of functional disorders; Other: Reimbursement of 3 long consultations
  Sponsors: Assistance Publique - Hôpitaux de Paris; ANRS, Emerging Infectious Diseases
  Not yet recruiting

• Pharmacist Management of Paxlovid eVisits - Conditions: COVID-19; Quality of Care
  Interventions: Other: Pharmacist Care; Other: AFM Pool Care
  Sponsors: Kaiser Permanente
  Not yet recruiting

• tDCS in the Management of Post-COVID Disorders - Conditions: Long COVID
  Interventions: Device: Transcranial Direct Current Stimulation (tDCS); Behavioral: Motor Training; Behavioral: Cognitive Training
  Sponsors: Universidade Federal de Pernambuco; São Paulo State University
  Recruiting

• Equity Evaluation of Fact Boxes on Informed COVID-19 and Influenza Vaccination Decisions - Study Protocol - Conditions: COVID-19; Influenza
  Interventions: Other: Fact box
  Sponsors: Harding Center for Risk Literacy
  Not yet recruiting

From PubMed

• The SARS-CoV-2 protein ORF3c is a mitochondrial modulator of innate immunity - The SARS-CoV-2 genome encodes a multitude of accessory proteins. Using comparative genomic approaches, an additional accessory protein, ORF3c, has been predicted to be encoded within the ORF3a sgmRNA. Expression of ORF3c during infection has been confirmed independently by ribosome profiling. Despite ORF3c also being present in the 2002-2003 SARS-CoV, its function has remained unexplored. Here we show that ORF3c localizes to mitochondria, where it inhibits innate immunity by restricting IFN-β…

• Synthesis, evaluation, and mechanism of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones as potent reversible SARS-CoV-2 entry inhibitors - A class of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones were designed and synthesized via Michael addition, cyclization, aldol condensation, and deprotonation to inhibit the human transmembrane protease serine 2 (TMPRSS2) and Furin, which are involved in priming the SARS-CoV-2 Spike for virus entry. The most potent inhibitor 2f (81) was found to efficiently inhibit the replication of various SARS-CoV-2 delta and omicron variants in VeroE6 and Calu-3 cells, with EC(50) range of…

• Antiviral Effects of Micafungin against Pteropine Orthoreovirus, an Emerging Zoonotic Virus Carried by Bats - Bat-borne emerging zoonotic viruses cause major outbreaks, such as the Ebola virus, Nipah virus, and/or beta coronavirus. Pteropine orthoreovirus (PRV), whose spillover event occurred from fruits bats to humans, causes respiratory syndrome in humans widely in South East Asia. Repurposing approved drugs against PRV is an effective tool to confront future PRV pandemics. We screened 2,943 compounds in an FDA-approved drug library and identified eight hit compounds that reduce viral cytopathic…

• Cellular assays for dynamic quantification of deubiquitinase activity and inhibition - Deubiquitinases (DUBs) are proteolytic enzymes that catalyze the removal of ubiquitin from protein substrates. The critical role of DUBs in regulating protein ubiquitination makes them attractive drug targets in oncology, neurodegenerative disease, and antiviral development. Biochemical assays for quantifying DUB activity have enabled characterization of substrate preferences and discovery of small molecule inhibitors. However, assessing the efficacy of these inhibitors in cellular contexts to…

• Transporter modulation of molnupiravir and its metabolite β-D-N4-hydroxycytidine across the blood-brain barrier in a rat - CONCLUSIONS: In summary, molnupiravir rapidly transforms into NHC and crosses the BBB and reaches the brain at approximately 0.3-0.8% of the blood‒brain ratio. The maximum concentration of NHC in the blood and brain is above the average half maximal inhibitory concentration (IC50) of the drug required to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, suggesting a therapeutic effect. The penetration of NHC is modulated by NBMPR. These findings provide constructive…

• Evaluation and Mechanistic Investigation of Human Milk Oligosaccharide against SARS-CoV-2 - Four human milk oligosaccharides (HMOs), 3’-sialyllactose (3’-SL), 6’-sialyllactose (6’-SL), 2’-fucosyllactose (2’-FL), and 3-fucosyllactose (3-FL), were assessed for their possible antiviral activity against the SARS-CoV-2 spike receptor binding domain (RBD) in vitro. Among them, only 2’-FL/3-FL exhibited obvious antibinding activity against direct binding and trans-binding in competitive immunocytochemistry and enzyme-linked immunosorbent assays. The antiviral effects of 2’-FL/3-FL were…

• Explore intersection genes of oxymatrine and COVID-19 with lung cancer as potential therapeutic targets based on network pharmacology - Introduction. Oxymatrine is a natural quinazine alkaloid extracted from Sophora flavescens and has many medicinal values. Oxymatrine showed protective effects, viral inhibition and effects against lung cancer.Hypothesis/Gap Statement. Individuals with lung cancer exhibit heightened vulnerability to COVID-19 infection due to compromised immune function. In conjunction with COVID-19, it is hypothesized that oxymatrine may exert potent pharmacological effects on lung cancer patients.Aim. The…

• Discovery of Nanosota-2, -3, and -4 as super potent and broad-spectrum therapeutic nanobody candidates against COVID-19 - Nanobodies are single-domain antibodies derived from camelid animals. Here, we discovered three anti-SARS-CoV-2 nanobodies, namely, Nanosota-2, -3, and -4, from an alpaca immunized with SARS-CoV spike protein. We further characterized the antiviral activities of these Fc-tag-fused nanobodies. Notably, Nanosota-2 inhibits the prototypic SARS-CoV-2 strain in vitro (with an IC(50) of 2 pM) and in mice (at a dosage of 4 mg/kg or administered 18 hours post-challenge). These potency metrics are the…

• SARS-COV-2 protein NSP9 promotes cytokine production by targeting TBK1 - SARS-COV-2 infection-induced excessive or uncontrolled cytokine storm may cause injury of host tissue or even death. However, the mechanism by which SARS-COV-2 causes the cytokine storm is unknown. Here, we demonstrated that SARS-COV-2 protein NSP9 promoted cytokine production by interacting with and activating TANK-binding kinase-1 (TBK1). With an rVSV-NSP9 virus infection model, we discovered that an NSP9-induced cytokine storm exacerbated tissue damage and death in mice. Mechanistically, NSP9…

• Enhanced binding and inhibition of SARS-CoV-2 by a plant-derived ACE2 protein containing a fused mu tailpiece - Infectious diseases such as Coronavirus disease 2019 (COVID-19) and Middle East respiratory syndrome (MERS) present an increasingly persistent crisis in many parts of the world. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The angiotensin-converting enzyme 2 (ACE2) is a crucial cellular receptor for SARS-CoV-2 infection. Inhibition of the interaction between SARS-CoV-2 and ACE2 has been proposed as a target for the prevention and treatment of COVID-19. We…

• Dysregulation of intracellular redox homeostasis by the SARS-CoV-2 ORF6 protein - SARS-CoV-2 has evolved several strategies to overcome host cell defenses by inducing cell injury to favour its replication. Many viruses have been reported to modulate the intracellular redox balance, affecting the Nuclear factor erythroid 2-Related Factor 2 (NRF2) signaling pathway. Although antioxidant modulation by SARS-CoV-2 infection has already been described, the viral factors involved in modulating the NRF2 pathway are still elusive. Given the antagonistic activity of ORF6 on several…

• Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections - Several drug screening campaigns identified Calpeptin as a drug candidate against SARS-CoV-2. Initially reported to target the viral main protease (M^(pro)), its moderate activity in M^(pro) inhibition assays hints at a second target. Indeed, we show that Calpeptin is an extremely potent cysteine cathepsin inhibitor, a finding additionally supported by X-ray crystallography. Cell infection assays proved Calpeptin’s efficacy against SARS-CoV-2. Treatment of SARS-CoV-2-infected Golden Syrian…

• Red Blood Cell-Derived Extracellular Vesicles Display Endogenous Antiviral Effects and Enhance the Efficacy of Antiviral Oligonucleotide Therapy - The COVID-19 pandemic has resulted in a large number of fatalities and, at present, lacks a readily available curative treatment for patients. Here, we demonstrate that unmodified red blood cell-derived extracellular vesicles (RBCEVs) can inhibit SARS-CoV-2 infection in a phosphatidylserine (PS) dependent manner. Using T cell immunoglobulin mucin domain-1 (TIM-1) as an example, we demonstrate that PS receptors on cells can significantly increase the adsorption and infection of authentic and…

• SIRT-1 is required for release of enveloped enteroviruses - Enterovirus D68 (EV-D68) is a re-emerging enterovirus that causes acute respiratory illness in infants and has recently been linked to Acute Flaccid Myelitis. Here, we show that the histone deacetylase, SIRT-1, is essential for autophagy and EV-D68 infection. Knockdown of SIRT-1 inhibits autophagy and reduces EV-D68 extracellular titers. The proviral activity of SIRT-1 does not require its deacetylase activity or functional autophagy. SIRT-1’s proviral activity is, we demonstrate, mediated…

• Inhaled nitric oxide: can it serve as a savior for COVID-19 and related respiratory and cardiovascular diseases? - Nitric oxide (NO), as an important gaseous medium, plays a pivotal role in the human body, such as maintaining vascular homeostasis, regulating immune-inflammatory responses, inhibiting platelet aggregation, and inhibiting leukocyte adhesion. In recent years, the rapid prevalence of coronavirus disease 2019 (COVID-19) has greatly affected the daily lives and physical and mental health of people all over the world, and the therapeutic efficacy and resuscitation strategies for critically ill…

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