Covid-19 Sentry

Contents

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

From Preprints

• Social Sharing of Emotion During the Collective Crisis of COVID-19 -
  We collected data from two sources—social media and online questionnaires—to investigate the emotional consequences of social sharing during the COVID-19 pandemic. Study 1 tracked and analysed emotionality of tweets posted over the course of a month in the crisis period and found that users who tweeted more frequently about COVID-19 expressed decreasing negative sentiment over time. Study 2 focused on immediate consequences of sharing COVID-related events and found a selective attenuating effect of sharing on participants’ negative feelings about their personal experience. Participants generally perceived their feelings about an event to have improved when that event was shared but perceived relatively less improvement when the shared event was a news story (especially one shared in-person) than when it was a personal experience. Overall, both studies suggested that social sharing is linked with emotional recovery and therefore appears to be an adaptive response to a persistent collective crisis.
  🖺 Full Text HTML: Social Sharing of Emotion During the Collective Crisis of COVID-19
• Neutralization of SARS-CoV-2 BQ.1.1 and XBB.1.5 by Breakthrough Infection Sera from Previous and Current Waves in China -
  SARS-CoV-2 is continuing to evolve and diversify, with an array of various Omicron sub-lineages, including BA.5, BA.2.75, BN.1, BF.7, BQ.1, BQ.1.1, XBB and XBB.1.5, now circulating globally at recent time. In this study, we evaluated the neutralization sensitivity of a comprehensive panel of Omicron subvariants to sera from different clinical cohorts, including individuals who received homologous or heterologous booster vaccinations, vaccinated people who had Delta or BA.2 breakthrough infection in previous waves, and patients who had BA.5 or BF.7 breakthrough infection in the current wave in China. All the Omicron subvariants exhibited substantial neutralization evasion, with BQ.1, BQ.1.1, XBB.1, and XBB.1.5 being the strongest escaped subvariants. Sera from Omicron breakthrough infection, especially the recent BA.5 or BF.7 breakthrough infection, exhibited higher neutralizing activity against all Omicron sub-lineages, indicating the chance of BA.5 and BF.7 being entirely replaced by BQ or XBB subvariants in China in a short-term might be low. We also demonstrated that the BQ and XBB subvariants were the most resistant viruses to monoclonal antibodies. Continuing to monitor the immune escape of SARS-CoV-2 emerging variants and developing novel broad-spectrum vaccines and antibodies are still crucial.
  🖺 Full Text HTML: Neutralization of SARS-CoV-2 BQ.1.1 and XBB.1.5 by Breakthrough Infection Sera from Previous and Current Waves in China
• Host genetics and COVID-19 severity: increasing the accuracy of latest severity scores by Boolean quantum features -
  The impact of common and rare variants in COVID-19 host genetics is widely studied in [16]. Here, common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. Firstly, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score, the so called IPGS, which offers a very simple description of the contribution of host genetics in COVID-19 severity. IPGS leads to an accuracy of 55-60% on different cohorts and, after a logistic regression with in input both IPGS and the age, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using the information on the host organs involved in the disease. We generalized the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features”, inspired by the Quantum Mechanics. The organs’ coefficients were set via the application of the genetic algorithm Pygad and, after that, we defined two new Integrated PolyGenic Score (IPGS1 and IPGS2). By applying a logistic regression with both IPGS2 (or indifferently IPGS1) and age as input, we reach an accuracy of 84-86%, thus improving the results previously shown in [16] by a factor of 10%.
  🖺 Full Text HTML: Host genetics and COVID-19 severity: increasing the accuracy of latest severity scores by Boolean quantum features
• A Bayesian inference method to estimate transmission trees with multiple introductions; applied to SARS-CoV-2 in Dutch mink farms. -
  Knowledge of who infected whom during an outbreak of an infectious disease is important to determine risk factors for transmission and to design effective control measures. Both whole-genome sequencing of pathogens and epidemiological data provide useful information about the transmission events and underlying processes. Existing models to infer transmission trees usually assume that the pathogen is introduced only once from outside into the population of interest. However, this is not always true. For instance, SARS-CoV-2 is suggested to be introduced multiple times in mink farms in the Netherlands from the SARS-CoV-2 pandemic among humans. Here, we developed a Bayesian inference method combining whole-genome sequencing data and epidemiological data, allowing for multiple introductions of the pathogen in the population. Our method does not a priori split the outbreak into multiple phylogenetic clusters, nor does it break the dependency between the processes of mutation, within-host dynamics, transmission, and observation. We implemented our method as an additional feature in the R-package phybreak. On simulated data, our method identifies the number of introductions with high accuracy. Moreover, when a single introduction was simulated, our method produces similar estimates of parameters and transmission trees as the existing package. When applied to data from a SARS-CoV-2 outbreak in Dutch mink farms, the method provides strong evidence for 13 introductions, which is 20 percent of all infected farms. Using the new feature of the phybreak package, transmission routes of a more complex class of infectious disease outbreaks can be inferred which will aid infection control in future outbreaks.
  🖺 Full Text HTML: A Bayesian inference method to estimate transmission trees with multiple introductions; applied to SARS-CoV-2 in Dutch mink farms.
• Macrodomain Mac1 of SARS-CoV-2 Nonstructural Protein 3 Hydrolyzes Diverse ADP-ribosylated Substrates -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that resulted in more than 6-million deaths worldwide. The virus encodes several non-structural proteins (Nsps) that contain elements capable of disrupting cellular processes. Among these Nsp proteins, Nsp3 contains macrodomains, e.g., Mac1, Mac2, Mac3, with potential effects on host cells. Mac1 has been shown to increase SARS-CoV-2 virulence and disrupt ADP-ribosylation pathways in mammalian cells. ADP-ribosylation results from the transfer of the ADP-ribose moiety of NAD+ to various acceptors, e.g., proteins, DNA, RNA, contributing on a cell’s biological processes. ADP-ribosylation is the mechanism of action of bacterial toxins, e.g., Pseudomonas toxins, diphtheria toxin that disrupt protein biosynthetic and signaling pathways. On the other hand, some viral macrodomains cleavage ADP-ribose-acceptor bond, generating free ADP-ribose. By this reaction, the macrodomain-containing proteins interfere ADP-ribose homeostasis in host cells. Here, we examined potential hydrolytic activities of SARS-CoV-2 Mac1, 2, and 3 on substrates containing ADP-ribose. Mac1 cleaved alpha-NAD+, but not beta-NAD+, consistent with stereospecificity at the C-1-bond. In contrast to ARH1 and ARH3, Mac1 did not require Mg2+ for optimal activity. Mac1 also hydrolyzed O-acetyl-ADP-ribose and ADP-ribose-1-phosphate, but not Mac2 and Mac3. However, Mac1 did not cleave alpha-ADP-ribose-(arginine) and ADP-ribose-(serine)-histone H3 peptide, suggesting that Mac1 hydrolyzes ADP-ribose attached to O- and N-linked functional groups, with specificity at the catalytic site in the ADP-ribose moiety. We conclude that SARS-CoV-2 Mac1 may exert anti-viral activity by reversing host-mediated ADP-ribosylation. New insights on Nsp3 activities may shed light on potential SARS-CoV-2 therapeutic targets.
  🖺 Full Text HTML: Macrodomain Mac1 of SARS-CoV-2 Nonstructural Protein 3 Hydrolyzes Diverse ADP-ribosylated Substrates
• Predicting COVID-19 case status from self-reported symptoms and behaviors using data from a massive online survey -

  With the varying availability of RT-PCR testing for COVID-19 across time and location, there is a need for alternative methods of predicting COVID-19 case status. In this study, multiple machine learning (ML) models were trained and assessed for their ability to accurately predict the COVID-19 case status using US COVID-19 Trends and Impact Survey (CTIS) data. The CTIS includes information on testing, symptoms, demographics, behaviors, and vaccination status. The best performing model was XGBoost, which achieved an F1 score of ≈ 94% in predicting whether an individual was COVID-19 positive or negative. This is a notable improvement on existing models for predicting COVID-19 case status and demonstrates the potential for ML methods to provide policy-relevant estimates.

  🖺 Full Text HTML: Predicting COVID-19 case status from self-reported symptoms and behaviors using data from a massive online survey
• Longitudinal changes in IgG-type SARS-CoV-2 antibody titers after COVID-19 vaccination and, prominent increase in antibody titers when infected after vaccination -

  【Objective】 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers level and duration of elevated levels are considered important indicators for confirming the efficacy of coronavirus disease 2019 (COVID-19) vaccines. The objective of this study was to demonstrate the changes in antibody titers after the second and third doses of the COVID-19 vaccine, and to determine the antibody titers in cases of spontaneous infection with SARS-CoV-2 after vaccination. 【Materials and Methods】 From June 2021 to February 2023, IgG-type SARS-CoV-2 antibody titers were measured in 127 participants, including 74 outpatients and 53 staffs, at the Osaka Dental University Hospital (65 males and 62 females, mean age 52.3 years). 【Results】 Consistent with previous reports, the SARS-CoV-2 antibody titer decreased with time, not only after the second dose, but also after the third dose of the vaccine if there is no spontaneous COVID-19 infection. We also confirmed that the third booster vaccination was effective in increasing the antibody titer. Sixteen cases of natural infections were observed after administering two or more doses of the vaccine. Eleven of these patients had post-infection antibody titers exceeding 40,000 AU/mL, and some cases continued to maintain antibody titers in the tens of thousands of AU/mL even after more than 6 months had passed since infection. 【Conclusion】 The rise in and duration of antibody titers against SARS-CoV-2 are considered important indicators for confirming the efficacy of novel COVID-19 vaccines. A longitudinal follow-up of antibody titers after vaccination in larger studies is warranted.

  🖺 Full Text HTML: Longitudinal changes in IgG-type SARS-CoV-2 antibody titers after COVID-19 vaccination and, prominent increase in antibody titers when infected after vaccination
• Rapid prototyping of models for COVID-19 outbreak detection in workplaces -

  Early case detection is critical to preventing onward transmission of COVID-19 by enabling prompt isolation of index infections, and identification and quarantining of contacts. Timeliness and completeness of ascertainment depend on the surveillance strategy employed. We use rapid prototype modelling to quickly investigate the effectiveness of testing strategies, to aid decision making. Models are developed with a focus on providing relevant results to policy makers, and these models are continually updated and improved as new questions are posed. The implementation of testing strategies in high risk settings in Australia was supported using models to explore the effects of test frequency and sensitivity on outbreak detection. An exponential growth model is firstly used to demonstrate how outbreak detection changes with varying growth rate, test frequency and sensitivity. From this model we see that low sensitivity tests can be compensated for by high frequency testing. This model is then updated to an Agent Based Model, which was used to test the robustness of the results from the exponential model, and to extend it to include intermittent workplace scheduling. These models help our fundamental understanding of disease detectability through routine surveillance in workplaces and evaluate the impact of testing strategies and workplace characteristics on the effectiveness of surveillance. This analysis highlights the risks of particular work patterns while also identifying key testing strategies to best improve outbreak detection in high risk workplaces.

  🖺 Full Text HTML: Rapid prototyping of models for COVID-19 outbreak detection in workplaces
• Addressing a climate emergency amidst the COVID-19 pandemic: A mixed-methods study on a hospital evacuation during the 2021 European floods -

  Introduction: In July 2021, several European countries were affected by severe floods with water levels of the river Meuse reaching a record high. VieCuri Medical Center (Venlo, the Netherlands) is a hospital located directly adjacent to this river, and in response to the flood threat it was decided to completely evacuate the hospital. The aim of this study was to explore the decision-making process of this emergent evacuation. Methods: A mixed-method approach was used. Qualitative data were collected through semi-structured interviews with 11 key participants closely involved in the evacuation. Quantitative data on the patients that were admitted at the time of the evacuation decision were collected, and included 30-day mortality, 7-day readmission rates and Charlson Comorbidity Index. Results: Three themes were constructed from the interviews: risk-assessment, COVID-19 experience and collaboration. Participants highlighted the role of previous experiences from the COVID-19 pandemic. The use of a national patient coordination center enabled to rapidly assess capacity of potential destination hospitals. Furthermore, the hospital preparedness for evacuation could be improved by a thorough analysis of locoregional hazards and preparing for loss of regional healthcare capacity. Findings unrelated to decision-making included the inefficiency of large-scale ambulance dispatches and the expansion of business continuity plans. No patients died unanticipated during this hospital evacuation or within 30 days. Conclusion: Experiences of the COVID-19 pandemic and the availability of a national patient coordination center were found to be decisive in performing this evacuation. This allowed for the swift identification of available capacity in appropriate destination hospitals.

  🖺 Full Text HTML: Addressing a climate emergency amidst the COVID-19 pandemic: A mixed-methods study on a hospital evacuation during the 2021 European floods
• Dogs and cats are less susceptible to the omicron variant of concern of SARS-CoV-2 - a field study -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic of unprecedented extent. Beside humans, a number of animal species can be infected, however, in some species differing susceptibilities were observed depending on the virus variant. Here, we serologically investigated cats and dogs living in households with human COVID-19 patients. The study was conducted during the transition period from delta as the dominating variant of concern (VOC) to omicron (BA.1/BA.2) to investigate the frequency of virus transmission of both VOCs from infected owners to their pets. The animal sera were tested by surrogate virus neutralization tests (sVNT) using either the original receptor-binding domain (RBD), enabling the detection of antibodies against the delta variant, or an omicron-specific RBD. Of the 290 canine samples, 20 tested positive by sVNT, but there were marked differences between the sampling time, and, related thereto, the virus variants, the dogs had contact to. While in November 2021 infected owners led to 50% seropositive dogs (18/36), only 0.8% (2/254) of animals with household contacts to SARS-CoV-2 between December 2021 and April 2022 tested positive. In all cases, the positive reaction was recorded against the original RBD. For cats, a similar pattern was seen, as in November 2021 38.1% (16/42) tested positive and between December 2021 and March 2022 only 5.0% (10/199). The markedly reduced ratio of seropositive animals during the period of omicron circulation suggests a considerably lower susceptibility of dogs and cats to this VOC. To examine the effect of BA.2, BA.4 and BA.5 omicron subvariants, sera taken in the second and third quarter of 2022 from randomly selected cats were investigated. 2.3% (11/372) tested seropositive and all of them showed a stronger reaction against the original RBD, further supporting the assumption of a lower susceptibility of companion animals to the omicron VOC.
  🖺 Full Text HTML: Dogs and cats are less susceptible to the omicron variant of concern of SARS-CoV-2 - a field study
• Understanding the Impact of Social Engagement Activities, Health Protocol Maintenance, and Social Interaction on Depression During Covid-19 Pandemic Among Older Americans -

  Objectives: Depression is a critical public health concern among older Americans. However, little is known about how older adults social engagement activities, health protocol maintenance, and social interaction (both physically and virtually) potentially contribute to their feelings of depression. Methods: Data were collected from the Covid-19 supplement to the National Health and Aging Trend Study (NHATS) and core longitudinal follow-up study. A total of 3,181 Medicare-eligible older adults between June and December 2020 were examined how self-reported depression is related to social engagement activities, health protocols, social interaction with friends and family (F&F), and doctors using multiple logistic regression. Results: This study reveals that the lack of social engagement activities, such as birthday parties and long-term care visits significantly contributes to older adults depression (OR: 1.34, 90% CI: 1.07-1.68, p=0.012, and OR: 1.28, 90% CI: 1.01-1.65, p=0.053 respectively). Subsequently, health protocols compliance with washing hands and wearing masks in public places were more likely 2.36 times and 3.44 times higher symptoms of depression for the older adults than those who were not maintaining those protocols (OR: 2.36, 90% CI: 1.24-4.57, p=0.009, OR: 3.44, 90% CI: 1.97-6.17, p<0.001 respectively). Furthermore, the lack of virtual social interaction via phone and text message with F&F is significantly related to depression whereas email or video call are not significantly related to depression for older adults. During Covid-19 pandemic, in-person visits with doctors significantly reduced patients depression on the other hand email communication significantly increased. However other virtual interactions with doctors did not significantly associate with patients depression. Conclusion: The lack of social engagement, maintaining health protocols, and lacking virtual interactions over the phone significantly increase depression symptoms for older adults during the Covid-19 pandemic. Therefore, it would be beneficial to take initiative to engage older adults in a variety of social activities to make them feel more connected to their community. The older population should be contacted by phone during the Covid-19 pandemic with encouraging messages and informed of the importance of maintaining health protocols.

  🖺 Full Text HTML: Understanding the Impact of Social Engagement Activities, Health Protocol Maintenance, and Social Interaction on Depression During Covid-19 Pandemic Among Older Americans
• Serosurvey of SARS-COV-2 at a large public university -

  Arizona State University (ASU) is one the largest universities in the United States, with more than 79,000 students attending in-person classes. We conducted a seroprevalence study from September 13-17, 2021 to estimate the number of people in our community with SARS-CoV-2-specific antibodies due to previous exposure to SARS-CoV-2 and/or vaccination. Participants provided their age, gender, race, status (student or employee), and general COVID-19 health-related information like previous exposure and vaccination status. The seroprevalence of the anti-receptor binding domain (RBD) antibody was 90% by a lateral flow assay and 88% by a semi-quantitative chemiluminescent immunoassay. The seroprevalence for anti-nucleocapsid (NC) was 20%. In addition, individuals with previous natural COVID infection plus vaccination had higher anti-RBD antibody levels compared to those who had vaccination only or infection only. Individuals who had a breakthrough infection had the highest anti-RBD antibody levels. Accurate estimates of the cumulative incidence of SARS-CoV-2 infection can inform the development of university risk mitigation protocols such as encouraging booster shots, extending mask mandates, or reverting to online classes. It could help us to have clear guidance to take action at the first sign of the next surge as well, especially since there is a surge of COVID subvariant infections.

  🖺 Full Text HTML: Serosurvey of SARS-COV-2 at a large public university
• Impact of Immune Evasion, Waning and Boosting on Dynamics of Population Mixing Between a Vaccinated Majority and Unvaccinated Minority -

  Background: We previously demonstrated that when vaccines prevent infection, the dynamics of mixing between vaccinated and unvaccinated sub-populations is such that use of imperfect vaccines markedly decreases risk for vaccinated people, and for the population overall. Risks to vaccinated people accrue disproportionately from contact with unvaccinated people. In the context of the emergence of Omicron SARS-CoV-2 and evolving understanding of SARS-CoV-2 epidemiology, we updated our analysis to evaluate whether our earlier conclusions remained valid. Methods: We modified a previously published Susceptible-Infectious-Recovered (SIR) compartmental model of SARS-CoV-2 with two connected sub-populations: vaccinated and unvaccinated, with non-random mixing between groups. Our expanded model incorporates diminished vaccine efficacy for preventing infection with the emergence of Omicron SARS-CoV-2 variants, waning immunity, the impact of prior immune experience on infectivity, hybrid effects of infection in previously vaccinated individuals, and booster vaccination. We evaluated the dynamics of an epidemic within each subgroup and in the overall population over a 10-year time horizon. Results: Even with vaccine efficacy as low as 20%, and in the presence of waning immunity, the incidence of COVID-19 in the vaccinated subpopulation was lower than that among the unvaccinated population across the full 10-year time horizon. The cumulative risk of infection was 3-4 fold higher among unvaccinated people than among vaccinated people, and unvaccinated people contributed to infection risk among vaccinated individuals at twice the rate that would have been expected based on the frequency of contacts. These findings were robust across a range of assumptions around the rate of waning immunity, the impact of hybrid immunity, frequency of boosting, and the impact of prior infection on infectivity in unvaccinated people. Interpretation: Although the emergence of the Omicron variants of SARS-CoV-2 has diminished the protective effects of vaccination against infection with SARS-CoV-2, updating our earlier model to incorporate loss of immunity, diminished vaccine efficacy and a longer time horizon, does not qualitatively change our earlier conclusions. Vaccination against SARS-CoV-2 continues to diminish the risk of infection among vaccinated people and in the population as a whole. By contrast, the risk of infection among vaccinated people accrues disproportionately from contact with unvaccinated people.

  🖺 Full Text HTML: Impact of Immune Evasion, Waning and Boosting on Dynamics of Population Mixing Between a Vaccinated Majority and Unvaccinated Minority
• Olfactory Dysfunction in the COVID-19 Era: An Umbrella Review Focused on Neuroimaging, Management, and Follow-up -

  Purpose: The coronavirus disease 2019 (COVID-19) is surrounded the world and is associated with multiorgan damage. Olfactory dysfunction is a common manifestation in COVID-19 patients, and in some cases, presents before the coryza signs. We conducted this umbrella review to provide a practical guide on managing, imaging findings, and follow-up of COVID-19 patients with olfactory dysfunction (OD). Methods: A comprehensive search was performed in PubMed, Embase, Scopus, and Web of Science databases from December 2019 until the end of July 2022. Systematic reviews and meta-analyses addressing management and imaging findings of the olfactory manifestations of COVID-19 were included in the study. The quality assessment of included articles was carried out using the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool. Results: A total of 23 systematic reviews were reviewed in this umbrella review. The number of included studies varied between 2 to 155 articles. Several demographic variables were not adequately reported across all the included systematic reviews, including age, gender, preexisting comorbidities, or whether participants had been hospitalized or admitted to the intensive care unit (ICU) due to COVID‐19. Conclusion: It seems that the coronavirus can infect olfactory system structures that play roles in the transmission and interpretation of smell sense. Based on studies, a large proportion of patients experienced OD following COVID-19 infection, and the majority of OD was resolved spontaneously. The possibility of long-lasting OD was higher in young adults with moderate clinical manifestation. Olfactory training (OT) was the most effective therapy. Intranasal corticosteroids (ICS) are also recommended.

  🖺 Full Text HTML: Olfactory Dysfunction in the COVID-19 Era: An Umbrella Review Focused on Neuroimaging, Management, and Follow-up
• Underlying driving forces of the SARS-CoV-2 evolution: immune evasion and ACE2 binding affinity -
  The evolution of SARS-CoV-2 is characterized by the emergence of new variants with a sheer number of mutations compared to their predecessors, which conferred resistance to pre-existing antibodies and/or increased transmissibility. The recently emerged Omicron subvariants also exhibit a strong tendency for immune evasion, suggesting adaptive evolution. However, previous studies have been limited to specific lineages or subsets of mutations, the overall evolutionary trajectory of SARS-CoV-2 and the underlying driving forces are still not fully understood. In this study, we analyzed the mutations present in all open-access SARS-CoV-2 genomes (until November 2022) and correlated the mutation’s incidence and fitness change with its impact on immune evasion and ACE2 binding affinity. Our results showed that the Omicron lineage had an accelerated mutation rate in the RBD region, while the mutation incidence in other genomic regions did not change dramatically over time. Moreover, mutations in the RBD region (but not in any other genomic regions) exhibited a lineage-specific pattern and tended to become more aggregated over time, and the mutation incidence was positively correlated with the strength of antibody pressure on the specific position. Additionally, the incidence of mutation was also positively correlated with changes in ACE2 binding affinity, but with a lower correlation coefficient than with immune evasion. In contrast, the mutation’s effect on fitness was more closely correlated with changes in ACE2 binding affinity than immune evasion. In conclusion, our results suggest that immune evasion and ACE2 binding affinity play significant and diverse roles in the evolution of SARS-CoV-2.
  🖺 Full Text HTML: Underlying driving forces of the SARS-CoV-2 evolution: immune evasion and ACE2 binding affinity

From Clinical Trials

• Phase Ⅰ Clinical Trial of a Candidate COVID-19 Vaccine - Condition:   COVID-19
  Intervention:   Biological: Recombinant COVID-19 Vaccine (chimpanzee adenovirus vector) for Inhalation
  Sponsors:   Wuhan BravoVax Co., Ltd.;   National University Hospital, Singapore;   Shanghai BravoBio Co., Ltd.
  Not yet recruiting

• Plitidepsin Versus Control in Immunocompromised Adult Participants With Symptomatic COVID-19 Requiring Hospital Care - Condition:   COVID-19
  Intervention:   Drug: Plitidepsin
  Sponsor:   PharmaMar
  Not yet recruiting

• Evaluation of Corfluvec Vaccine for the Prevention of COVID-19 in Healthy Volunteers - Condition:   COVID-19
  Interventions:   Biological: Corfluvec component 1 low dose;   Biological: Corfluvec component 2 low dose;   Biological: Corfluvec component 1 high dose;   Biological: Corfluvec component 2 high dose;   Biological: Corfluvec low dose;   Biological: Corfluvec high dose;   Biological: Placebo
  Sponsors:   Tatyana Zubkova;   MDP-CRO, LLC;   St. Petersburg State Pavlov Medical University
  Active, not recruiting

• COVID-19 Self-testing Study - Condition:   COVID-19
  Intervention:   Behavioral: SMARTest mobile app for COVID-19 self-testing
  Sponsor:   Columbia University
  Recruiting

• A Study of Efficacy and Safety of Azvudine vs. Nirmatrelvir-Ritonavir in the Treatment of COVID-19 Infection - Condition:   COVID-19
  Interventions:   Drug: Azvudine;   Drug: Nirmatrelvir-Ritonavir
  Sponsors:   Shandong Provincial Hospital;   Central hospital Affiliated to Shandong First Medical University;   The Second Affiliated Hospital of Shandong First Medical University;   The Affiliated Hospital Of Southwest Medical University;   Gansu Provincial Hospital
  Not yet recruiting

• Tetrandrine Tablets Used in Hospitalized Adults With COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Tetrandrine
  Sponsor:   Peking University Third Hospital
  Not yet recruiting

• INFLUENCE OF HIGH FREQUENCY CHEST WALL OSCILLATION IN HOSPITALIZED PATIENTS WITH COVID-19 - Condition:   COVID-19
  Intervention:   Device: HIGH FREQUENCY CHEST WALL OSCILLATION
  Sponsor:   Cairo University
  Not yet recruiting

• A Study To Assess The Efficacy and Safety of HH-120 Nasal Spray for the Treatment of Mild COVID-19 - Condition:   COVID-19
  Interventions:   Drug: HH-120 nasal spray;   Drug: Placebo Comparator
  Sponsor:   Huahui Health
  Recruiting

• Study of Flonoltinib Maleate Tablets in the Treatment of Severe Novel Coronavirus (COVID-19) Infection - Condition:   COVID-19
  Interventions:   Drug: VV116+SOC;   Drug: SOC
  Sponsor:   Chengdu Zenitar Biomedical Technology Co., Ltd
  Recruiting

• Pirfenidone in Adult Hospitalized Patients With COVID-19 - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: Pirfenidone Oral Product;   Drug: Pirfenidone placebo
  Sponsor:   Capital Medical University
  Active, not recruiting

• The Difference Between Non-invasive High-frequency Oscillatory Ventilation and Non-invasive Continuous Airway Pressure Ventilation in COVID-19 With Acute Hypoxemia - Conditions:   COVID-19 Pneumonia;   Non-invasive Ventilation
  Interventions:   Device: Non-invasive high-frequency oscillatory ventilation;   Device: Non-invasive continuous positive airway pressure ventilation
  Sponsor:   Guangzhou Institute of Respiratory Disease
  Not yet recruiting

• COVID-19 Molecular OTC At Home Test - Condition:   COVID-19 Pandemic
  Intervention:   Diagnostic Test: Diagnostic Test: IN Vitro
  Sponsor:   3EO Health
  Not yet recruiting

• Randomized-controlled Trial of Immunoadsorption (IA) in Patients With Chronic Fatigue Syndrome (CFS) Including Patients With Post-COVID-19 CFS (PACS-CFS) - Condition:   ME/CSF Including CFS Related to Post-acute COVID-19 Syndrome (PACS)
  Intervention:   Device: Immunoadsorption
  Sponsor:   Charite University, Berlin, Germany
  Not yet recruiting

• Phase II/III Immunogenicity and Safety Study of the AVX/COVID-12 Vaccine Against COVID-19 Applied as a Booster. - Condition:   SARS-CoV-2 Infection
  Interventions:   Biological: AVX-COVID/12;   Biological: ChAdOx-1-S[recombinant]
  Sponsors:   Laboratorio Avi-Mex, S.A. de C.V.;   National Council of Science and Technology, Mexico;   Instituto Nacional de Enfermedades Respiratorias
  Recruiting

• Brain-Training Treatment for Long COVID in Older Adults - Condition:   Post-Acute COVID-19 Syndrome
  Intervention:   Other: NeuroFlex (computerized gamified tasks)
  Sponsor:   UConn Health
  Not yet recruiting

From PubMed

• COVID-19: Understanding the impact of anti-hypertensive drugs and hydroxychloroquine on the ACE1 and ACE2 in lung and adipose tissue in SHR and WKY rats - Hypertensive individuals taking anti-hypertensive drugs from renin-angiotensin system inhibitors may exhibit a more severe evolution of the disease when contracting the SARS-CoV-2 virus (COVID-19 disease) due to potential increases in ACE2 expression. The study investigated ACE1 and ACE2 axes and hydroxychloroquine in the lungs and adipose tissue of male and female normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHRs). SHRs were treated with losartan (10 mg/kg/day) or…

• Detection of IgM, IgG, IgA and neutralizing antibody responses to SARS-CoV-2 infection and mRNA vaccination - Introduction. One correlate of immunity for coronavirus disease 2019 (COVID-19) is the laboratory detection of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. These tests are widely implemented for clinical, public health, or research uses.Hypothesis/Gap Statement. Antibody responses by all classes of immunoglobulins may form from infection and vaccination, but few studies have performed direct head-to-head comparisons between these groups.Aim. The objective of this…

• Inhibition of SARS-CoV-2 nucleocapsid protein-RNA interaction by guanosine oligomeric RNA - The interaction of the β-coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein with genomic RNA is initiated by specific RNA regions and subsequently induces the formation of a continuous polymer with characteristic structural units for viral formation. We hypothesized that oligomeric RNAs, whose sequences are absent in the 29.9-kb genome sequence of SARS-CoV-2, might affect RNA-N protein interactions. We identified two such hexameric RNAs, In-1…

• LY6E protects mice from pathogenic effects of murine coronavirus and SARS-CoV-2 - LY6E is an antiviral protein that inhibits coronavirus entry. Its expression in immune cells allows mice to control murine coronavirus infection. However, it is not known which immune cell subsets mediate this control or whether LY6E protects mice from SARS-CoV-2. In this study, we used tissue-specific Cre recombinase expression to ablate Ly6e in distinct immune compartments or in all epiblast-derived cells, and bone marrow chimeras to target Ly6e in a subset of radioresistant cells. Mice…

• Vitamin D and estrogen steroid hormones and their immunogenetic roles in Infectious respiratory (TB and COVID-19) diseases - The role of steroid hormones against infectious diseases has been extensively studied. From immunomodulatory action to direct inhibition of microorganism growth, hormones D3 (VD3) and 17β-estradiol (E2), and the genetic pathways modulated by them, are key targets for a better understanding pathogenesis of infectious respiratory diseases (IRD) such as tuberculosis (TB) and the coronavirus disease-19 (COVID-19). Currently, the world faces two major public health problems, the outbreak of COVID-19,…

• Cell-autonomous requirement for ACE2 across organs in lethal mouse SARS-CoV-2 infection - Angiotensin-converting enzyme 2 (ACE2) is the cell-surface receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). While its central role in Coronavirus Disease 2019 (COVID-19) pathogenesis is indisputable, there remains significant debate regarding the role of this transmembrane carboxypeptidase in the disease course. These include the role of soluble versus membrane-bound ACE2, as well as ACE2-independent mechanisms that may contribute to viral spread. Testing these roles…

• DDX3X Is Hijacked by Snakehead Vesiculovirus Phosphoprotein To Facilitate Virus Replication via Stabilization of the Phosphoprotein - Asp-Glu-Ala-Asp (DEAD) box helicase 3 X-linked (DDX3X) plays important regulatory roles in the replication of many viruses. However, the role of DDX3X in rhabdovirus replication has seldomly been investigated. In this study, snakehead vesiculovirus (SHVV), a kind of fish rhabdovirus, was used to study the role of DDX3X in rhabdovirus replication. DDX3X was identified as an interacting partner of SHVV phosphoprotein (P). The expression level of DDX3X was increased at an early stage of SHVV…

• CRISPR-Cas13d effectively targets SARS-CoV-2 variants, including Delta and Omicron, and inhibits viral infection - The recent pandemic of variants of concern (VOC) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need for innovative anti-SARS-CoV-2 approaches in addition to vaccines and antiviral therapeutics. Here, we demonstrate that a CRISPR-Cas13-based strategy against SARS-CoV-2 can effectively degrade viral RNA. First, we conducted a cytological infection experiment, screened CRISPR-associated RNAs (crRNAs) targeting conserved regions of viruses, and used an in vitro…

• An Intelligent ABM-based Framework for Developing Pandemic-Resilient Urban Spaces in Post-COVID Smart Cities - As of August 2022, the COVID-19 pandemic has accounted for over six million deaths globally. The urban population has been severely affected by this viral pandemic and the ensuing lockdowns, resulting in increased poverty and inequality, slowed economic growth, and a general decline in quality of life. This paper proposes a framework to evaluate the effects of the pandemic by combining agent-based simulations-based on Susceptible-Infectious-Recovered (SIR) model-with a hybrid neural network. A…

• Severe acute respiratory syndrome coronavirus 2 may cause liver injury via Na⁺/H⁺ exchanger - The liver has many significant functions, such as detoxification, the urea cycle, gluconeogenesis, and protein synthesis. Systemic diseases, hypoxia, infections, drugs, and toxins can easily affect the liver, which is extremely sensitive to injury. Systemic infection of severe acute respiratory syndrome coronavirus 2 can cause liver damage. The primary regulator of intracellular pH in the liver is the Na^(+)/H(+) exchanger (NHE). Physiologically, NHE protects hepatocytes from apoptosis by…

• Age-adjusted impact of prior COVID-19 on SARS-CoV-2 mRNA vaccine response - More people with a history of prior infection are receiving SARS-CoV-2 vaccines. Understanding the level of protection granted by ‘hybrid immunity’, the combined response of infection- and vaccine-induced immunity, may impact vaccination strategies through tailored dosing. A total of 36 infected (‘prior infection’) and 33 SARS-CoV-2 ‘naïve’ individuals participated. Participants provided sera six months after completing a round of BNT162b2 vaccination, to be processed for anti-spike antibody…

• The possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19-Results from a pragmatic randomized clinical trial - CONCLUSION: The results revealed in this exploratory study suggest a possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19. It is proposed that the two agents possibly acting in synergy, interfere the SARS-CoV-2 replication, and thus help a speedy recovery in the early-stage of COVID-19. Further research is highly encouraged.

• Enantioselective inhibition of the SARS-CoV-2 main protease with rhenium(i) picolinic acid complexes - Infections of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have triggered a global pandemic with millions of deaths worldwide. Herein, the synthesis of functionalized Re(i) tricarbonyl complexes as inhibitors of the SARS-CoV-2 main protease, also referred to as the 3-chymotrypsin-like protease (3CL^(pro)), is presented. The metal complexes were found to inhibit the activity of the enzyme with IC(50) values in the low micromolar range. Mass spectrometry revealed that the metal…

• Studies of cytotoxicity effects, SARS-CoV-2 main protease inhibition, and in silico interactions of synthetic chalcones - SARS-CoV-2 main protease (Mpro) plays an essential role in proteolysis cleavage that promotes coronavirus replication. Thus, attenuating the activity of this enzyme represents a strategy to develop antiviral agents. We report inhibitory effects against Mpro of 40 synthetic chalcones, and cytotoxicity activities, hemolysis, and in silico interactions of active compounds. Seven of them bearing a (E)-3-(furan-2-yl)-1-arylprop-2-en-1-one skeleton (10, 28, and 35-39) showed enzyme inhibition with…

• Nucleolin mediates SARS-CoV-2 replication and viral-induced apoptosis of host cells - Host-oriented antiviral therapeutics are promising treatment options to combat COVID-19 and its emerging variants. However, relatively little is known about the cellular proteins hijacked by SARS-CoV-2 for its replication. Here we show that SARS-CoV-2 induces expression and cytoplasmic translocation of the nucleolar protein, nucleolin (NCL). NCL interacts with SARS-CoV-2 viral proteins and co-localizes with N-protein in the nucleolus and in stress granules. Knockdown of NCL decreases the stress…

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