Viral infections can have profound and durable functional impacts on the immune system. There is an urgent need to characterize the long-term immune effects of SARS-CoV-2 infection given the persistence of symptoms in some individuals and the continued threat of novel variants including the recent rapid acceleration in infections. As the majority of COVID-19 patients experienced mild disease, here we use systems immunology approaches to comparatively assess the post-infection immune status (mean: 151 [5th - 95th percentile: 58 - 235] days after diagnosis) and subsequent innate and adaptive responses to seasonal influenza vaccination (as an “immune challenge”) in 33 previously healthy individuals after recovery from mild, non-hospitalized COVID-19, as compared to 40 age- and sex- matched healthy controls with no history of COVID-19. Sex-specific, temporally stable shifts in signatures of metabolism, T-cell activation, and innate immune/inflammatory processes suggest that mild COVID-19 can establish new post-infection immunological set-points. COVID-19-recovered males had an increase in CD71hi B-cells (including influenza-specific subsets) before vaccination and more robust innate, influenza-specific plasmablast, and antibody responses after vaccination compared to healthy males. Intriguingly, by day 1 post-vaccination in COVID-19-recovered subjects, the expression of numerous innate defense/immune receptor genes (e.g., Toll-like receptors) in monocytes increased and moved away from their post-COVID-19 repressed state toward the pre-vaccination baseline of healthy controls, and these changes tended to persist to day 28 in females, hinting that the acute inflammatory responses induced by vaccination could partly reset the immune states established by prior mild COVID-19. Our study reveals sex-dimorphic immune imprints and in vivo functional impacts of mild COVID-19 in humans, suggesting that prior COVID-19 could change future responses to vaccination and in turn, vaccines could help reset the immune system after COVID-19, both in an antigen-agnostic manner.
The newly found Omicron SARS-CoV-2 variant of concern has rapidly spread worldwide. Omicron carries numerous mutations in key regions and is associated with increased transmissibility and immune escape. The variant has recently been divided into four subvariants with substantial genomic differences, in particular between Omicron BA.1 and BA.2. With the surge of Omicron subvariants BA.1 and BA.2, a large number of reinfections from earlier cases has been observed, raising the question of whether BA.2 specifically can escape the natural immunity acquired shortly after a BA.1 infection. To investigate this, we selected a subset of samples from more than 1,8 million cases of infections in the period from November 22, 2021, until February 11, 2022. Here, individuals with two positive samples, more than 20 and less than 60 days apart, were selected. From a total of 187 reinfection cases, we identified 47 instances of BA.2 reinfections shortly after a BA.1 infection, mostly in young unvaccinated individuals with mild disease not resulting in hospitalization or death. In conclusion, we provide evidence that Omicron BA.2 reinfections do occur shortly after BA.1 infections but are rare.
Henipavirus infection (NiV), a fatal disease transmitted by bats has caused human death and disease in India and Bangladesh. With an average case fatality rate of more than 70%, NiV has the potential to cause widespread outbreaks that can have a devastating impact on human health. Spillover of NiV from bats to humans is influenced by several factors mainly human behaviour and human interaction with bats. Climatic conditions and habitat destruction influence the shedding of the virus and the transmission of the disease to humans. Limited research has been conducted on the factors driving these spillover events. As the world has recently witnessed the devastating impact of the COVID-19 global pandemic, a forewarning of spillover events will enable the adoption of adequate measures to prevent and control future outbreaks. Our study maps the likely changing distribution of NiV reservoir Pteropus medius bat species using future climate and landuse change predictions. We use existing data to predict which districts within India and Bangladesh have increased risk of spillover of NiV in the future. We use Species Distribution Modelling to predict the likely change in the distribution of P. medius under different future scenarios and the concurrent increase in the risk of NiV spillover events. We focus on the influence of anthropogenic changes in different socioeconomic scenarios to predict future spillover events. We consider climate and social goals set by the International Panel on Climate Change (IPPC) to create accurate predictions of regions at risk of NiV spillovers. We find that the risk of NiV spillover events in India and Bangladesh will likely increase. More districts are predicted to be at risk of NiV spillovers under the high population growth and persistent environmental degradation scenario than under moderate population growth and medium challenges to achieve climate goals. This highlights the significance of population growth and climate change when considering disease outbreaks and public health. Our findings will enable the authorities in the predicted spillover regions to take public health measures to prevent and control NiV outbreaks.
We model Covid-19 vaccine uptake as a reinforcement learning dynamic between two populations: the vaccine adopters, and the vaccine hesitant. Using data available from the Center for Disease Control (CDC), we calculate a payoff matrix governing the dynamic interaction between these two groups and show they are playing a Hawk-Dove evolutionary game with an internal evolutionarily stable Nash equilibrium (the asymptotic percentage of vaccinated in the population). We then ask whether vaccine adoption can be improved by implementing dynamic incentive schedules that reward/punish the vaccine hesitant, and if so, what schedules are optimal and how effective are they likely to be? When is the optimal time to start an incentive program, and how large should the incentives be? By using a tailored replicator dynamic reinforcement learning model together with optimal control theory, we show that well designed and timed incentive programs can improve vaccine uptake by shifting the Nash equilibrium upward in large populations, but only so much, and incentive sizes above a certain threshold show diminishing returns.
Background: The adoption of remote methods of care has been accelerated by the COVID-19 pandemic, but concerns exist relating to the potential impact on health disparities. This evaluation explores the implementation of COVID-19 remote home monitoring services across England, focussing on patients experiences and engagement with the service. Methods: The study was a rapid, multi-site, mixed methods evaluation. Data were collected between January and June 2021. We conducted qualitative interviews with staff service leads, and patients and carers receiving the service. We conducted quantitative surveys with staff delivering the service, and patients and carers receiving the service across 28 sites in England, UK. Qualitative data were analysed using thematic analysis and quantitative data were analysed using univariate and multivariate methods. Findings: Many sites designed their service to be inclusive to the needs of their local population. Strategies included widening eligibility criteria, prioritising vulnerable groups, and creating referral pathways. Many sites also adapted their services according to patient needs, including providing information in different languages or more accessible formats, offering translation services, offering non-digital options, or providing face-to-face assessments. Despite these adaptions, disparities were reported across patient groups (e.g. age, health status, ethnicity, level of education) in their experience of and engagement with the service. Interpretation: Services must determine how best to design and implement remote monitoring services to be of value to all populations. National guidance should play a role in supporting services to best serve the needs of their populations, and patients and staff must play an active role in service design.
Without any realistic prospect of comprehensive global vaccine coverage and lasting immunity, control of pandemics such as COVID-19 will require implementation of large-scale, rapid identification and isolation of infectious individuals to limit further transmission. Here, we describe an automated, high-throughput integrated screening platform, incorporating saliva-based loop-mediated isothermal amplification (LAMP) technology, that is designed for population-scale sensitive detection of infectious carriers of SARS-CoV-2 RNA. Central to this surveillance system is the Sentinel testing instrument, which is capable of reporting results within 25 minutes of saliva sample collection with a throughput of up to 3,840 results per hour. It incorporates continuous flow loading of samples at random intervals to cost-effectively adjust for fluctuations in testing demand. Independent validation of our saliva-based RT- LAMP technology on an automated LAMP instrument coined the Sentinel, found 98.7% sensitivity, 97.6% specificity, and 98% efficiency against a RT-PCR comparator assay, confirming its suitability for surveillance screening. This Sentinel surveillance system offers a feasible and scalable approach to complement vaccination, to curb the spread of COVID-19 variants, and control future pandemics to save lives.
While it is well established that the rate of COVID-19 infections can be suppressed by social distancing, environmental effects may also affect it. We consider the hypothesis that natural Ultra-Violet (UV) light is reducing COVID-19 infections by enhancing human immunity through increasing levels of Vitamin-D and Nitric Oxide or by suppressing the virus itself. We focus on the United Kingdom (UK), by examining daily COVID-19 infections (F) and UV Index (UVI) data from 23 March 2020 to 10 March 2021. We find an intriguing empirical anti-correlation between log10(F) and log10(UVI) with a correlation coefficient of -0.934 from 11 May 2020 (when the first UK lockdown ended) to 10 March
Wastewater surveillance for SARS-CoV-2 is being used worldwide to understand COVID-19 infection trends in a community. We found the emergence and rapid timeline for dominance of the Omicron variant was accurately reflected in wastewater when measured with droplet digital (dd)PCR. We were able to distinguish Omicron from the circulating Delta variant because Omicron has a mutation in the N1 probe binding region that diminished the fluorescent signal within individual droplets. The ddPCR platform may be advantageous for wastewater surveillance since analysis of the data can segregate fluorescent signals from different individual templates. In contrast, platforms such as qPCR that rely solely on the intensity of fluorescence for quantification would not distinguish a subset of variants with mutations affecting the reaction and could underestimate SARS-CoV-2 concentrations. The proportion of Omicron in wastewater was tightly correlated to clinical cases in five cities and provided a higher resolution timeline of appearance and dominance (>75%) than sequenced clinical samples, which were limited in less populated areas. Taken together, this work demonstrates wastewater is a reliable metric for tracking SARS-CoV-2 at a population level.
A recent MMWR reported that the effectiveness of a 3rd dose of SARS-CoV-2 mRNA vaccine waned quickly in the Omicron-predominant period. Similarly, a substantial decline of immune responses induced by a 3rd dose of inactivated vaccines was also observed in our study. In response to the fast waning immune response and the great threat of Omicron variant of concern (VOC) to frontline healthcare workers (HCWs), 38 HCWs who were in our previous cohort investigating responses to the first three doses of inactivated vaccines participated in the current study and volunteered to receive a 4th homologous booster. Here, we demonstrated that the 4th dose is safe and capable of recalling waned immune responses 6 months after the 3rd dose. However, a greater suppression on the induction of overall Neutralizing antibodies (NAbs) and NAbs targeting the receptor-binding domain (RBD) was found in participants with stronger immune responses after the 3rd dose. As a result, a stepwise elevation of RBD-NAbs from the 1st to the 3rd vaccination achieved a “turning point”. The peak RBD-NAbs level induced by the 4th dose was inferior to the peak of the 3rd dose. Accompanied with reduced induction of RBD-NAbs, the immune system shifted responses to the nucleocapsid protein (NP) and the N-terminal domain (NTD) of the spike protein. Although NTD directed antibodies are capable of neutralization, they only compensated the loss of RBD-NAbs to ancestral SARS-CoV-2 virus but not to the Omicron variant due to a substantial conformational change of Omicron NTD. This longitudinal clinical study monitored the immune response of the same cohort for every doses, shaping a relationship between the trajectory of immune focus and the dynamics of the neutralizing potency against the evolving virus. Our data reveal that immune responses could not be endlessly elevated, while suppression of heightened immune responses focusing on one subunit together with a shift of immune responses to other subunits would occur after repeated vaccination. Thus, an updated vaccine with more diverse epitopes capable of inducing NAbs against VOCs would be a future direction for boosters.
Objectives: To assess total antibody levels against Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS CoV-2) spike protein up to 12 months after Coronavirus Disease (COVID-19) infection in non-vaccinated individuals and the possible predictors of antibody persistence. Methods: This is a prospective multi-centre longitudinal cohort study. Participants The study included SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) positive and negative participants in South-Eastern Norway from February to December 2020. Possible predictors of SARS-CoV-2 total antibody persistence was assessed. The SARS-CoV-2 total antibody levels against spike protein were measured three to five months after PCR in 391 PCR-positive and 703 PCR-negative participants; 212 PCR-positive participants were included in follow- up measurements at 10 to 12 months. The participants completed a questionnaire including information about symptoms, comorbidities, allergies, body mass index (BMI), and hospitalisation. Primary outcome The SARS-CoV-2 total antibody levels against spike protein three to five and 10 to 12 months after PCR positive tests. Results: SARS-CoV-2 total antibodies against spike protein were present in 366 (94%) non-vaccinated PCR-positive participants after three to five months, compared with nine (1%) PCR-negative participants. After 10 to 12 months, antibodies were present in 204 (96%) non-vaccinated PCR-positive participants. Of the PCR-positive participants, 369 (94%) were not hospitalised. The mean age of the PCR-positive participants was 48 years (SD 15, range 20-85) and 50% of them were male. BMI ≥ 25 kg/m 2 was positively associated with decreased antibody levels (OR 2.34, 95% CI 1.06 to 5.42). Participants with higher age and self-reported initial fever with chills or sweating were less likely to have decreased antibody levels (age: OR 0.97, 95% CI 0.94 to 0.99; fever: OR 0.33, 95% CI 0.13 to 0.75). Conclusion Our results indicate that the level of SARS- CoV-2 total antibodies against spike protein persists for the vast majority of non-vaccinated PCR-positive persons at least 10 to 12 months after mild COVID-19.
The COVID-19 pandemic was accompanied by varying movement restriction measures across populations worldwide. These restrictions altered daily activities at all levels, including food access and intake, as well as psychological feelings during lockdown. The main objective of the present study was to evaluate health, and nutrition behaviors during confinement during the first wave of the COVID-19 pandemic in Panama. We conducted a cross-sectional study using an online survey for data collection; a total of 1,561 surveys were validated. The majority of respondents were women (74.2%) between 18 and 49 years old. Among the respondents, 83.3% indicated a university education level, and 49.9% reported a monthly family income equal to or less than 1,000 USD. In addition, more than 50% self-reported overweight or obesity. Responses were analyzed using k-means algorithms to identify food intake patterns; we found three patterns: a healthy food intake pattern, a non-healthy food intake pattern and a mixed food intake pattern. The respondents with healthy food intake and non-healthy food intake patterns reported better socioeconomic conditions. Individuals classified as having mixed food intake patterns had lower incomes, less education and higher unemployment rates. Regarding emotions, we found that women experienced more negative emotions, such as fear, worry and anxiety, during the lockdown period. Taken together, these results suggest that the mobility restriction measures imposed during the COVID-19 pandemic affected food intake patterns by exacerbating existing inequalities. We believe that directing resources towards strategies with the greatest positive impacts on public health remains key, especially in critical situations such as the COVID-19 pandemic.
Objective In Japan, healthcare workers (HCWs) are vaccinated against contagious viruses (measles, rubella, chickenpox, mumps, and hepatitis B) to prevent nosocomial infection. However, some do not produce sufficient antibodies after vaccination (low responders). Whether these low responders to conventional vaccines (live attenuated viruses or inactivated viruses) can produce adequate antibodies to mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains to be elucidated. Methods We conducted a prospective cohort study of 50 HCWs who received two doses of mRNA BNT162b2 vaccine 3 weeks apart. SARS-CoV-2 anti-spike antibodies were measured 11 times, from before the first BNT162b2 vaccination to 5 months after the second vaccination. The antibody titers of low responders and normal responders were compared. In addition, SARS-CoV-2 neutralizing antibody activity was measured twice in low responders, 1 week to 1 month, and 5 months after the second vaccination. Results After vaccination, SARS-CoV-2 anti- spike antibody was detectable in the samples from low and normal responders at each timepoint. The median SARS-CoV-2 anti-spike antibody titer was higher in low responders than in normal responders 1 week after receiving the second dose of BNT162b2 vaccine (3721.0 vs 2251.5, P=0.029). Low responders had SARS-CoV-2 neutralizing antibody activity 1 week to 1 month, and 5 months after the second vaccination, which exceeded the positive threshold 5 months after the second vaccination. Conclusion After BNT162b2 vaccination, low responders acquired adequate SARS-CoV-2 anti-spike and SARS- CoV-2 neutralizing antibodies to prevent SARS-CoV-2. These results suggest that vaccination with mRNA vaccine against SARS-CoV-2 should also be recommended for low responders to conventional vaccines.
Objective The severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) has caused a pandemic claiming more than 4 million lives worldwide. Overwhelming Coronavirus-Disease-2019 (COVID-19) respiratory failure placed tremendous demands on healthcare systems increasing the death toll. Cost-effective prognostic tools to characterize COVID-19 patients9 likely to progress to severe hypoxemic respiratory failure are still needed. Design We conducted a retrospective cohort study to develop a model utilizing demographic and clinical data collected in the first 12-hours admission to explore associations with severe hypoxemic respiratory failure in unvaccinated and hospitalized COVID-19 patients. Setting University based healthcare system including 6 hospitals located in the Galveston, Brazoria and Harris counties of Texas. Participants Adult patients diagnosed with COVID-19 and admitted to one of six hospitals between March 19th and June 31st, 2020. Primary outcome The primary outcome was defined as reaching a WHO ordinal scale between 6-9 at any time during admission, which corresponded to severe hypoxemic respiratory failure requiring high-flow oxygen supplementation or mechanical ventilation. Results We included 329 participants in the model cohort and 62 (18.8%) met the primary outcome. Our multivariable regression model found that lactate dehydrogenase (OR 2.36), qSOFA score (OR: 2.26), and neutrophil to lymphocyte ratio (OR:1.15) were significant predictors of severe disease. The final model showed an area under curve (AUC) of 0.84. The sensitivity analysis and point of influence analysis did not reveal inconsistencies. Conclusions Our study suggests that a combination of accessible demographic and clinical information collected on admission may predict the progression to severe COVID-19 among adult patients with mild and moderate disease. This model requires external validation prior to its use.
Genome sequencing proved to be an excellent tool to monitor the molecular epidemiology of the disease caused by SARS-CoV-2, i.e., coronavirus disease (COVID-19). Some reports of infected, vaccinated individuals have aroused great interest because they are primarily being infected with circulating variants of concern (VOCs). To investigate the cases of infected, vaccinated individuals in Salvador, Bahia, Brazil, we performed genomic monitoring to estimate the magnitude of the different VOCs in these cases. Nasopharyngeal swabs from infected (symptomatic and asymptomatic), fully vaccinated individuals (n=29) who were of varying age and had RT-qPCR Ct values of ≤30 were subjected to viral sequencing using Nanopore technology. Our analysis revealed that the Omicron variant was found in 99% of cases and that only one case was due to the Delta variant. Infected, fully vaccinated patients have a favorable clinical prognosis; however, within the community, they become viral carriers with the aggravating factor of viral dissemination of VOCs not neutralized by the vaccines.
Evaluation of Full Versus Fractional Doses of COVID-19 Vaccines Given as a Booster in Adults in Australia - Mongolia, Indonesia, Australia Coronavirus (MIACoV). - Condition: COVID-19
Interventions: Biological: Tozinameran - Standard dose; Biological: Tozinameran - fractional dose; Biological: Elasomeran - standard dose; Biological: Elasomeran - fractional dose
Sponsors: Murdoch Childrens Research Institute; Coalition for Epidemic Preparedness Innovations; PATH; The Peter Doherty Institute for Infection and Immunity
Not yet recruiting
Zofin to Treat COVID-19 Long Haulers - Condition: COVID-19
Interventions: Drug: Zofin; Other: Placebo
Sponsors:
Organicell Regenerative Medicine; Proxima Clinical Research, Inc.
Not yet recruiting
Pulmonary Rehabilitation Implemented With VR for Post-COVID-19 Patients - Condition: COVID-19
Intervention: Procedure: Pulmonary Rehabilitation Program
Sponsor: The Opole University of Technology
Recruiting
Pulmonary Rehabilitation Implemented With Virtual Reality for Post-COVID-19 Patients - Condition: COVID-19
Intervention: Procedure: Pulmonary rehabilitation
Sponsor:
The Opole University of Technology
Not yet recruiting
Fourth COVID-19 Vaccine Dose- mRNA1273 - Condition: COVID-19 Pandemic
Intervention: Biological: mRNA1273 vaccine
Sponsor: Sheba Medical Center
Active, not recruiting
HEART Rate Variability Biofeedback in LOng COVID-19 (HEARTLOC) - Condition: COVID-19
Intervention: Behavioral: Heart Rate Variability Biofeedback (HRV-B)
Sponsors: University of Leeds; University of Manchester; Leeds Comunity Healthcare NHS Trust
Recruiting
Anti-inflammatory Drug Algorithm for COVID-19 Home Treatment - Condition: COVID-19
Interventions: Drug: Recommended treatment schedule; Drug: Usual care
Sponsors: Mario Negri Institute for Pharmacological Research; Family physicians
Not yet recruiting
Fourth BNT162b2 COVID-19 Vaccine Dose - Condition: COVID-19 Pandemic
Intervention: Biological: BNT162b2 vaccine
Sponsor: Sheba Medical Center
Active, not recruiting
Effects of Aerobic Exercise in Patients With Post COVID-19 - Condition: COVID-19
Interventions: Other: High-intensity interval aerobic exercise training; Other: Control Group
Sponsor: Gazi University
Not yet recruiting
A Phase II Study of the Immunogenicity and Safety of SCTV01C in Population Aged ≥12 Years and Previously Vaccinated With Inactivated COVID-19 Vaccine - Conditions: COVID-19; SARS-CoV2 Infection
Interventions: Biological: SCTV01C; Biological: Comirnaty
Sponsor: Sinocelltech Ltd.
Not yet recruiting
A Phase II Clinical Trial to Evaluate the Immunogenicity and Safety of SCTV01E in Population Aged ≥18 Years Previously Fully Vaccinated With mRNA COVID-19 Vaccine - Conditions: COVID-19; Sars-CoV-2 Infection
Interventions: Biological: SCTV01E; Biological: Comirnaty
Sponsor: Sinocelltech Ltd.
Not yet recruiting
A Phase II Clinical Trial to Evaluate the Immunogenicity and Safety of SCTV01C and SCTV01E in Population Aged ≥12 Years Previously Fully Vaccinated With Inactivated COVID-19 Vaccine - Conditions: COVID-19; SARS-CoV-2 Infection
Interventions: Biological: SCTV01C; Biological: SCTV01E; Biological: Sinopharm inactivated COVID-19 vaccine
Sponsor: Sinocelltech Ltd.
Not yet recruiting
A Phase II Clinical Trial to Evaluate the Immunogenicity and Safety of SCTV01C in Population Aged ≥18 Years and Previously Fully Vaccinated With Either Inactivated or mRNA COVID-19 Vaccine or Previously Diagnosed With COVID-19 - Conditions: COVID-19; SARS-CoV-2 Infection
Interventions: Biological: SCTV01C; Biological: Sinopharm inactivated COVID-19 vaccine; Biological: Comirnaty
Sponsor: Sinocelltech Ltd.
Not yet recruiting
Immunogenicity and Safety of the SpikoGen COVID-19 Vaccine in Children Aged 5 to <12 Years and 12 to <18 Years Compared With Adults Aged 18 to 40 Years - Condition: COVID-19
Interventions: Biological: Low-dose SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant; Biological: SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant
Sponsors:
Cinnagen; Vaxine Pty Ltd
Not yet recruiting
Safety and Immunogenicity of COVI-VAC as a Booster Dose in Adults Previously Vaccinated Against COVID-19 - Conditions: COVID-19; SARS-CoV-2
Intervention: Biological: COVI-VAC
Sponsor:
Codagenix, Inc
Not yet recruiting
Nucleosides and emerging viruses: a new story - With several US Food and Drug Administration (FDA)-approved drugs and high barriers to resistance, nucleoside and nucleotide analogs remain the cornerstone of antiviral therapies for not only herpesviruses, but also HIV and hepatitis viruses (B and C); however, with the exception of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which vaccines have been developed at unprecedented speed, there are no vaccines or small antivirals yet available for (re)emerging viruses, which are…
Synthesis and In Vitro Study of Artemisinin/Synthetic Peroxide Based Hybrid Compounds against SARS-CoV-2 and Cancer - The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause life-threatening diseases in millions of people worldwide, in particular, in patients with cancer, and there is an urgent need for antiviral agents against this infection. While in vitro activities of artemisinins against SARS-CoV-2 and cancer have recently been demonstrated, no study of artemisinin and/or synthetic peroxide-based hybrid compounds active against both cancer and SARS-CoV-2 has been reported yet….
Decoupling SARS-CoV-2 ORF6 localization and interferon antagonism - Like many pathogenic viruses, SARS-CoV-2 must overcome interferon (IFN)-mediated host defenses for infection establishment. To achieve this, SARS-CoV-2 deploys overlapping mechanisms to antagonize IFN production and signaling. The strongest IFN antagonist is the accessory protein ORF6, which localizes to multiple membranous compartments, including the nuclear envelope, where it directly binds nuclear pore components Nup98-Rae1 to inhibit nuclear translocation of activated STAT1/IRF3…
Engineered Extracellular vesicles antagonize SARS-CoV-2 infection by inhibiting mTOR signaling - Effective treatment approaches for patients with COVID-19 remain limited and are neither curative nor widely applicable. Activated specialized tissue effector extracellular vesicles (ASTEX) derived from genetically-enhanced skin fibroblasts, exert disease-modifying bioactivity in vivo in models of heart disease. Here we report that ASTEX antagonizes SARS-CoV-2 infection and its pathogenic sequelae: In human lung epithelial cells exposed to SARS-CoV-2, ASTEX is cytoprotective and antiviral…
Shedding Light on the Synthesis, Crystal Structure, Characterization, and Computational Study of Optoelectronic Properties and Bioactivity of Imine derivatives - Two imine compounds named as (E)-2-(((3,4-dichlorophenyl)imino)methyl)phenol (DC2H) and (E)-4-(((2,4-dimethylphenyl)imino)methyl)phenol (DM4H) are synthesized, and their crystal structures are verified using the single-crystal X-ray diffraction (XRD) technique. The crystal structures of the compounds are compared with the closely related crystal structures using the Cambridge Structural Database (CSD). The crystal packing in terms of intermolecular interactions is fully explored by Hirshfeld…
A Computer-Aided Approach for the Discovery of D-Peptides as Inhibitors of SARS-CoV-2 Main Protease - The SARS-CoV-2 main protease, also known as 3-chymotrypsin-like protease (3CL^(pro)), is a cysteine protease responsible for the cleavage of viral polyproteins pp1a and pp1ab, at least, at eleven conserved sites, which leads to the formation of mature nonstructural proteins essential for the replication of the virus. Due to its essential role, numerous studies have been conducted so far, which have confirmed 3CL^(pro) as an attractive drug target to combat Covid-19 and have reported a vast…
Phytochemicals of Euphorbia hirta L. and Their Inhibitory Potential Against SARS-CoV-2 Main Protease - Euphorbia hirta L. is a medicinal plant widely used in the Philippines and across tropical Asia against various diseases, including respiratory disorders. In this study, the phytochemical components of E. hirta were investigated in silico for their potential to inhibit the severe acute respiratory syndrome-coronavirus-2 main protease (SARS-CoV-2 Mpro), a coronavirus disease 2019 (COVID-19) drug target that plays a critical role in the infection process of SARS- CoV-2. Phytochemical mining in…
Molecular Docking and Dynamics Studies to Explore Effective Inhibitory Peptides Against the Spike Receptor Binding Domain of SARS-CoV-2 - The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic due to the high transmission and mortality rate of this virus. The world health and economic sectors have been severely affected by this deadly virus, exacerbated by the lack of sufficient efficient vaccines. The design of effective drug candidates and their rapid development is necessary to combat this virus. In this study, we selected 23 antimicrobial peptides from the literature and predicted…
Targeting SARS-CoV-2 Proteases for COVID-19 Antiviral Development - The emergence of severe acute respiratory syndrome (SARS-CoV-2) in 2019 marked the third occurrence of a highly pathogenic coronavirus in the human population since 2003. As the death toll surpasses 5 million globally and economic losses continue, designing drugs that could curtail infection and disease progression is critical. In the US, three highly effective Food and Drug Administration (FDA)-authorized vaccines are currently available, and Remdesivir is approved for the treatment of…
Corrigendum: Inhibition of SARS-CoV-2 by Targeting Conserved Viral RNA Structures and Sequences - [This corrects the article DOI: 10.3389/fchem.2021.802766.].
Perspectives on nano-nutraceuticals to manage pre and post COVID-19 infections - Optimized therapeutic bio-compounds supported by bio-acceptable nanosystems (i.e., precise nanomedicine) have ability to promote health via maintaining body structure, organ function, and controlling chronic and acute effects. Therefore, nano-nutraceuticals (designed to neutralize virus, inhibit virus bindings with receptors, and support immunity) utilization can manage COVID-19 pre/post-infection effects. To explore these approaches well, our mini-review explores optimized bio-active compounds,…
Antiviral drug discovery by targeting the SARS-CoV-2 polyprotein processing by inhibition of the main protease - The spread of SARS-CoV-2, the causative agent for COVID-19, has led to a global and deadly pandemic. To date, few drugs have been approved for treating SARS-CoV-2 infections. In this study, a structure-based approach was adopted using the SARS-CoV-2 main protease (M^(pro)) and a carefully selected dataset of 37,060 compounds comprising M^(pro) and antiviral protein-specific libraries. The compounds passed two-step docking filtration, starting with standard precision (SP) followed by extra…
Human/SARS-CoV-2 Genome-Scale Metabolic Modeling to Discover Potential Antiviral Targets for COVID-19 - BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused a substantial increase in mortality and economic and social disruption. The absence of US Food and Drug Administration-approved drugs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need for new therapeutic drugs to combat COVID-19.
Angiogenic Role of Mesothelium-Derived Chemokine CXCL1 During Unfavorable Peritoneal Tissue Remodeling in Patients Receiving Peritoneal Dialysis as Renal Replacement Therapy - Peritoneal dialysis (PD) is a valuable ‘home treatment’ option, even more so during the ongoing Coronavirus pandemic. However, the long-term use of PD is limited by unfavourable tissue remodelling in the peritoneal membrane, which is associated with inflammation-induced angiogenesis. This appears to be driven primarily through vascular endothelial growth factor (VEGF), while the involvement of other angiogenic signaling pathways is still poorly understood. Here, we have identified the crucial…
INSIGHTS INTO THE BIOLOGICAL IMPACT OF COVID-19 AND ITS VACCINES ON HUMAN HEALTH - COVID-19 (coronavirus disease-2019) is a contagious illness that has been declared a global epidemic by the World Health Organization (WHO). The coronavirus causes diseases ranging in severity from the common cold to severe respiratory diseases and death. Coronaviruses primarily affect blood pressure by attaching to the angiotensin converting enzyme 2 (ACE 2) receptor. This virus has an impact on multiple organ systems, including the central nervous system, immune system, cardiovascular system,…
SOCIAL NAVIGATION SYSTEM FOR MOBILE ROBOTS IN THE EMERGENCY DEPARTMENT TECHNOLOGY - The emergency department (ED) is a safety-critical environment in which healthcare workers (HCWs) are overburdened, overworked, and have limited resources, especially during the COVID-19 pandemic. One way to address this problem is to explore the use of robots that can support clinical teams, e.g., to deliver materials or restock supplies. However, due to EDs being overcrowded, and the cognitive overload HCWs experience, robots need to understand various levels of patient acuity so they avoid disrupting care delivery. In this invention, we introduce the Safety-Critical Deep Q-Network (SafeDQN) system, a new acuity-aware navigation system for mobile robots. SafeDQN is based on two insights about care in EDs: high-acuity patients tend to have more HCWs in attendance and those HCWs tend to move more quickly. We compared SafeDQN to three classic navigation methods, and show that it generates the safest, quickest path for mobile robots when navigating in a simulated ED environment. We hope this work encourages future exploration of social robots that work in safety-critical, human-centered environments, and ultimately help to improve patient outcomes and save lives. Figure 1. - link
A SYSTEM BASED ON DEEP LEARNING FOR ANALYZING DELAYED ENHANCEMENT MAGNETIC RESONANCE IMAGING TO IDENTIFY COVID 19 AND METHOD THEREOF - The present invention discloses a system based on deep learning for analyzing delayed enhancement magnetic resonance imaging to identify COVID 19 and method thereof. The method and system include, but not limited to, a processing unit adapted to process the data based on deep learning data modelling in the magnetic resonance imaging associated with the digital image scanning system for diagnosis COVID 19 with the spatial resolution that each frame is deposited is 256 * 256, and being creating that level and vertical resolution respectively are 256 pixels (pixel), the read/write address that the read/write address of each image element, which is controlled by processing unit and forms circuit and finishes; And the data that will be stored in memory are input to a real-time microcontroller, it is characterized in that: analyze and compare by the Multi-source Information Fusion analytical system by using the real-time microcontroller to deliver the D/A changer then, digital signal is become analogue signal output. - link
一种特异性结合新型冠状病毒S蛋白的抗体及其应用 - 本发明涉及一种特异性结合新型冠状病毒S蛋白的抗体及其应用，属于生物技术领域。本发明提供了一种抗原，所述抗原包括氨基酸序列如SEQ ID NO.1所示的多肽，氨基酸序列如SEQ ID NO.2所示的多肽，与SEQ ID NO.1所示氨基酸序列具有80%以上同源性，且具有诱发针对SARS‑CoV‑2 S蛋白免疫反应功能的衍生多肽，和/或，与SEQ ID NO.2所示氨基酸序列具有80%以上同源性，且具有诱发针对SARS‑CoV‑2 S蛋白免疫反应功能的衍生多肽；使用所述抗原对动物进行免疫可获得能够与SARS‑CoV‑2 S蛋白特异性结合的多克隆抗体。 - link
检测SARS-CoV-2变异株的组合物、试剂盒、方法及其用途 - 本发明属于分子生物学检测领域；涉及SARS‑CoV‑2奥密克戎（Omicron）变异株的检测。本发明提供了包含所述组合物的试剂盒，所述组合物的用途，以及用于检测SARS‑CoV‑2变异株并分型的方法。通过检测SARS‑CoV‑2变异株S基因上的4个不同的特征功能变异位点，对奥密克戎变异株进行分型，从而在单管反应体系中同时实现SARS‑CoV‑2病毒及奥密克戎变异株分型的检测。本发明的组合物，结合荧光探针熔解曲线法，其成本低，通量高。并且操作简便，结果读取过程通过熔解峰Tm值即可以判定。检测全过程均在单管封闭条件下进行，避免了由于样本间交叉引起的假阳性和环境污染。 - link
一种用于检测病毒的试剂盒 - 本发明提供了一种用于检测病毒的试剂盒，包括裂解病毒的试剂和病毒的免疫层析检测装置，通过在试纸条上设置连接标记区域和检测区域的缓冲过渡区域，以及在卡壳盖上设置三条压住试纸条的压条，减缓样本的流速，提高样本在试纸条上的层析和过滤效果，并搭配裂解病毒的试剂，暴露出更多的抗原或者抗原位点，从而大幅提高待测物的检测灵敏度，特别是针对新型冠状病毒的裂解，可以明显提高样本中的病毒抗原浓度，从而采用特定结构的免疫荧光测试条，提高检测的最低阀值，防止漏检。 - link
一种用于检测病毒的试剂和试剂盒 - 本发明提供了一种用于检测病毒的试剂和试剂盒，包括裂解病毒的试剂和试纸条，通过在试纸条上设置连接标记区域和检测区域的缓冲过渡区域，减缓样本的流速，提高样本在试纸条上的层析和过滤效果，并搭配裂解病毒的试剂裂解病毒，暴露出更多的抗原或者抗原位点，从而提高检测的灵敏度。在样本中病毒量特别低的时候，希望能够获得阳性结果，就希望获得更多的抗原片段或者病毒片段，采用本发明提供的裂解液对样本进行裂解，可以明显提高样本中的病毒抗原浓度，从而采用免疫荧光测试条，提高检测的最低阀值，防止漏检，特别适用于针对新型冠状病毒的裂解。 - link
一种结合冠状病毒双特异性抗体的抗药抗体及其制备方法和应用 - 本发明公开了一种结合冠状病毒双特异性抗体的抗药抗体及其制备方法和应用。所述抗药抗体包含重链可变区和轻链可变区，所述重链可变区包含HCDR1、HCDR2和HCDR3，所述轻链可变区包含LCDR1、LCDR2和LCDR3，其中各功能区的序列详见本发明。本发明筛选得到的抗药抗体具有较高的结合亲和力和特异性。 - link
FOLDABLE KIDS NEST - The objective of the present invention is to provide a bird’s nest bag which allows a kid to sleep or sit inside. According to the embodiment of the present invention, the bird nest bag is used to isolate kids below 2 years, who are affected by COVID-19. The netted portion of the bag allows a clear visibility to check on the user by the medical assistants, during emergency situations. The children below two years of age can be isolated in the bags for a shorter duration. (Refer Fig. 1) - link
IDENTIFICATION AND ALARM SYSTEM FOR FACIAL CORONA MASK USING CNN BASED IMAGE PROCESSING - tThe covid-19 epidemic is the world’s largest wake-up call for people to pay attention to their own and society’s health. One thing to keep in mind is that there is a segment of the population that has been exposed to the covid-19 virus and has generated antibodies without developing any significant illnesses and is continuing to be healthy. This indicates that a significant section of the population, even excluding the elderly, lacks the necessary bodily immunity to combat a Viral infection. As terrible as covid-19 is on a global scale, developing personal health standards and preventative measures for any pathogenic virus as a community would have spared many lives. In’this work, a camera is combined with an image processing system to recognise facial masks, which may be improved in a variety of ways. First and foremost, this method is meant to identify masks on a single person’s face. While this method is efficient in identifying someone has a mask, it does not ensure that they will wear it all of the time. The most effective update for this task is to install a camera with a wide field of view so that many individuals can be seen in the frame, and the faces of those who aren’t wearing markings can be identified, as well as the number of people and the timing. - link
一种腺病毒载体重组新冠病毒B.1.429变异株疫苗及其应用 - 本发明公开了一种以人5型复制缺陷型腺病毒为载体的新冠变异株疫苗。所述疫苗以E1、E3联合缺失的复制缺陷型人5型腺病毒为载体，基因组中整合有经优化设计的新型冠状病毒B.1.429变异株抗原基因（Ad5‑nCoV‑B.1.429）。该疫苗在宿主细胞中可以有效表达保护性抗原蛋白。使用该疫苗单次免疫即可激发针对新冠野生株以及B.1.351、B.1.617.2变异株的抗体反应。与2019野生型新型冠状病毒疫苗联用，疫苗加强免疫后可以激发强烈且广谱的新冠病毒变异株中和抗体反应。无论用作单独免疫，还是同新冠野生株疫苗联用作异型加强免疫时，该疫苗均能激发较为广谱的中和抗体反应，具有一定的应用优势，可作为疫苗候选株，用于应对持续蔓延的新冠变异株疫情。 - link