Purinergic signaling modulates immune function and is involved in the immunopathogenesis of several viral infections. This study aimed to investigate alterations in purinergic pathways in COVID-19 patients. Lower plasma ATP and adenosine levels were identified in mild and severe COVID-19 patients associated with proinflammatory cytokine profiles compared to healthy controls. Mild COVID-19 patients presented lower frequencies of CD4+CD25+CD39+ (activated/memory Treg) and CD4+CD25+CD39+CD73+ T cells, and increased frequencies of high differentiated (CD27-CD28-) CD8+T cells compared to health controls. Severe COVID-19 patients also showed higher frequencies of CD4+CD39+, CD4+CD25-CD39+ (memory T effector cell), high differentiated CD8+ T cells (CD27-CD28-) and diminished frequencies of CD4+CD73+, CD4+CD25+CD39+ mTreg, CD4+CD25+CD39+CD73+, CD8+CD73+ and low-differentiated CD8+ T cells (CD27+CD28+) in the blood in relation to mild COVID-19 patients and controls. Moreover, severe COVID-19 patients presented higher expression of PD-1 on low-differentiated CD8+ T cells. Both severe and mild COVID-19 patients presented higher frequencies of CD4+Annexin-V+ and CD8+Annexin-V+ T cells, showing increased T cell apoptosis. Plasma samples collected from severe COVID-19 patients were able to decrease the expression of CD73 on CD4+ and CD8+ T cells of a healthy donor. Interestingly, the in vitro incubation of PBMC from severe COVID-19 patients with adenosine reduced the NF-kB activation in T cells and monocytes. Together, these data add new knowledge regarding the immunopathology of COVID-19 through purinergic regulation, especially concerning adenosine deficiency.
We present a novel methodology for the stable rate estimation of hospitalization and death related to the Corona Virus Disease 2019 (COVID-19) using publicly available reports from various distinct communities. These rates are then used to estimate underreported infections on the corresponding areas by making use of reported daily hospitalizations and deaths. The impact of underreporting infections on vaccination strategies is estimated under different disease- transmission scenarios using a Susceptible-Exposed-Infective-Removed-like (SEIR) epidemiological model.
BACKGROUND: Academic research on the disproportionate impact of COVID-19 among Native Americans has largely been restricted to particular indigenous groups or reservations. OBJECTIVE: We estimate COVID-19 mortality for Native Americans relative to other racial/ethnic groups and explore how state-level mortality is associated with known risk factors. METHODS: We use the Standard Mortality Ratio (SMR), adjusted for age and county, to estimate COVID-19 mortality by racial/ethnic groups for the U.S. and 10 selected states. The prevalence of risk factors is derived from the American Community Survey and the Behavioral Risk Factor Surveillance System. RESULTS: The SMR for Native Americans greatly exceeds those for Black and Latino populations and varies enormously across states. There is a strong correlation between the share of Native Americans living on a reservation and the SMR. The SMR for Native Americans is also highly correlated with the income-poverty ratio and the prevalence of multigenerational families, crowded housing, frontline worker status, and health insurance (excluding the Indian Health Service). Risk factors associated with socioeconomic status and co-morbidities are generally more prevalent for Native Americans living on homelands, a proxy for reservation status, than for those living elsewhere. CONCLUSIONS: Most risk factors for COVID-19 are disproportionately high among Native Americans, particularly for those living on homelands. Reservation life appears to increase the risk of COVID-19 mortality. CONTRIBUTION: We assemble and analyze a broader set of COVID-19-related risk factors for Native Americans than previous studies, a critical step toward understanding the exceptionally high COVID-19 death rates in this population.
Background It has been proven that inactivated COVID-19 vaccines are safe and effective in general population with intact immunity. However, their safety and immunogenicity have not been demonstrated in people living with HIV (PLWH). Methods 42 HIV-1 infected individuals who were stable on cART and 28 healthy individuals were enrolled in this study. Two doses of an inactivated COVID-19 vaccine (BIBP-CorV) were given 4 weeks apart. The safety and reactogenicity of the vaccine were evaluated by observing clinical adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and surrogate neutralization assays. Cell-mediated immune responses and vaccine induced T cell activation were measured by flow cytometry. Findings All the HIV-1 infected participants had a CD4+ T cell count of above 200 cells/μL both at baseline and 4 weeks after vaccination. No solicited adverse reaction was observed among all participants. Similar binding antibody, neutralizing antibody and S protein specific T cell responses were elicited in PLWH and healthy individuals. Further analyses showed that PLWH with low baseline CD4+/CD8+ T cell ratios (<0.6) generated lower antibody responses after vaccination than PLWH with medium (0.6~1.0) or high (≥1.0) baseline CD4+/CD8+ T cell ratios (P<0.01). The CD3+, CD4+ and CD8+ T cell counts of PLWH decreased significantly after vaccination, but it did not lead to any adverse clinical manifestation. Moreover, we found that the general burden of HIV-1 among the PLWH cohort decreased significantly (P=0.0192) after vaccination. And the alteration of HIV-1 viral load was not significantly associated with the vaccine induced CD4+ T cell activation. Interpretation Our data demonstrate that the inactivated COVID-19 vaccine is safe and immunogenic in PLWH who are stable on cART with unsuppressed CD4 counts. Funding This work was funded by the National Natural Science Foundation of China (Grant No. 81971559, 82041010).
Background/Objectives The aim of this study was to evaluate the association between obesity and hospitalization in mild COVID-19 adult outpatients in Brazil. Subjects/Methods Adults with signs and symptoms suggestive of acute SARS- CoV-2 infection who sought two hospitals (one public and one private) emergency department were prospectively enrolled. Patients with confirmed COVID-19 at inclusion were followed by phone calls at day (D) D7, D14 and D28. Multivariable logistic regression models were employed to explore the association between obesity and other potential predictors for hospitalization. Results A total of 1,050 participants were screened, 310 were diagnosed with COVID-19 by RT-PCR. Median age was 37.4 (IQR 29.8-45.0) years, and 186 (60.0%) were female. Duration of symptoms was 3.0 (IQR 2.0-5.0) days, and 10.0 (IQR 8.0-12.0) was the median number of symptoms at inclusion. A total of 98 (31.6%) were obese, and 243 (78.4%) had no previous medical conditions. Twenty three participants (23/310, 7.4%) required hospitalization during the period. After adjusting, obesity (BMI≥30.0 kg/m2) (OR=2.69, 95%CI 1.63-4.83, P<0.001) and older age (OR=1.05, 95%CI 1.01-1.09, P<0.001), were significantly associated with higher risks of hospitalization. Conclusions Obesity, followed by aging, was the main factor associated with hospital admission for COVID-19 in a young population in a low- middle income country. Our findings highlighted the need for actions to promote additional protection for obese population, such as vaccination, and to encourage lifestyle changes.
Objective: To evaluate COVID-19 lateral flow testing (LFT) among asymptomatic university students. Study design: Mixed methods evaluation of LFT among University of Bristol students. Methods: i) An analysis of testing uptake and exploration of demographic variations in uptake using logistic regression; ii) an online student survey about views on university testing; and iii) qualitative interviews to explore participants9 experiences of testing and subsequent behaviour, analysed using a thematic approach. Results: 12,391 LFTs were conducted on 8025/36,054 (22.3%) students. Only one in 10 students had the recommended two tests. There were striking demographic disparities in uptake with those from ethnic minority groups having lower uptake (e.g. 3% of Chinese students were tested vs. 30.7% of White students), and variations by level and year of study (ranging from 5.3% to 33.7%), place of residence (29.0% to 35.6%) and faculty (15.2% to 32.8%). Differences persisted in multivariable analyses. A total of 436 students completed the online survey, and twenty in-depth interviews were conducted. Barriers to engagement with testing included a lack of awareness, knowledge and understanding, and concerns about the accuracy and safety. Students understood limitations of LFTs but requested further information about test accuracy. Tests were used to inform behavioural decisions, often in combination with other information, such as the potential for exposure to the virus and perceptions of vulnerability. Conclusions: The low uptake of testing brings into question the role of mass LFT in university settings. Innovative strategies may be needed to increase LFT uptake among students.
Randomized Study to Evaluate Intranasal Dose of STI-2099 (COVI-DROPS™) in Outpatient Adults With Mild COVID-19 Infection - Condition: COVID-19
Interventions: Biological: COVI-DROPS; Drug: Placebo
Sponsor: Sorrento Therapeutics, Inc.
Not yet recruiting
Evaluating Safety, Tolerability, and Potential Efficacy of Intranasal AD17002 in Adults With Mild COVID-19 - Condition: Covid19
Interventions: Biological: AD17002; Biological: Placebo (Formulation buffer)
Sponsor: Advagene Biopharma Co. Ltd.
Not yet recruiting
Lymphatic Osteopathic Manipulative Medicine to Enhance Coronavirus (COVID-19) Vaccination Efficacy - Condition: COVID-19
Interventions: Other: Lymphatic OMM; Other: Light Touch
Sponsor: Rowan University
Not yet recruiting
Efficacy and Safety of Ergoferon for COVID-19 Prevention During Vaccination Against SARS-CoV-2 - Condition: Immunization Against COVID-19
Interventions: Drug: Ergoferon; Drug: Placebo
Sponsor: Materia Medica Holding
Recruiting
Efficacy of Home Inspiratory Muscle Training in Post-covid-19 Patients: a Randomized Clinical Trial - Condition: Covid19
Intervention: Device: Inspiratory muscle training
Sponsor:
Universidade Federal do Rio Grande do Norte
Recruiting
A Ph 2 Trial With an Oral Tableted COVID-19 Vaccine - Condition: COVID-19
Interventions: Drug: VXA-CoV2-1.1-S; Other: Placebo Tablets
Sponsor: Vaxart
Recruiting
Impact of Nudges on Downloads of COVID-19 Exposure Notification Smartphone Apps: A Randomized Trial - Condition: COVID-19
Interventions: Behavioral: Self-Benefit/Social Norm; Behavioral: Self- Benefit/No Social Norm; Behavioral: Other Benefit/Social Norm; Behavioral: Other Benefit/No Social Norm
Sponsors: University of Pennsylvania; Pennsylvania Department of Health
Completed
Safety and Immunogenicity of SARS-CoV-2 Protein Subunit Recombinant Vaccine - Condition: Covid19
Interventions: Biological: SARS-CoV-2 Protein Subunit Recombinant Vaccine; Biological: SARS-CoV-2 Inactivated Vaccine
Sponsors: PT Bio Farma; Fakultas Kedokteran Universitas Indonesia; National Institute of Health Research and Development, Ministry of Health Republic of Indonesia
Not yet recruiting
A Safety and Tolerability Study of BDB-001 in Mild, Moderate COVID-19 Patients - Condition: COVID-19
Intervention: Drug: BDB-001 injection
Sponsors:
Staidson (Beijing) Biopharmaceuticals Co., Ltd; Beijing Defengrui Biotechnology Co. Ltd
Completed
Acetylsalicylic Acid in COVID-19 (ASA-SARS) - Conditions: SARS-CoV2 Infection; Covid19
Interventions: Drug: Low-dose acetylsalicylic acid; Drug: Placebo
Sponsors: Barcelona Institute for Global Health; Hospital Universitario de Torrejón,Madrid; Hospital Universitario Infanta Leonor; Fundació Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau; Hospital del Mar; Hopsital Central de Maputo, Mozambique
Not yet recruiting
Pulmonary Function in Patients Recovering From COVID19 Infection : a Pilot Study - Condition: COVID-19
Intervention: Diagnostic Test: diaphragm ultrasonography
Sponsor: University Hospital, Limoges
Not yet recruiting
Safety and Immunogenicity Study of Booster Vaccination With Medium-dosage or High-dosage SARS-CoV-2 Inactivated Vaccine for Prevention of COVID-19 - Condition: COVID-19
Interventions: Biological: High-dosage SARS-CoV-2 vaccine; Biological: Medium-dosage SARS-CoV-2 vaccine
Sponsor: Sinovac Biotech Co., Ltd
Not yet recruiting
Evaluation of the Efficacy of Probiotics to Reduce the Occurrence of Long COVID - Condition: COVID-19
Interventions: Dietary Supplement: Probiotics; Dietary Supplement: Placebo
Sponsors: Centre de recherche du Centre hospitalier universitaire de Sherbrooke; Lallemand Health Solutions
Not yet recruiting
Telerehabilitation in COVID-19 Survivors - Conditions: COVID-19; Telerehabilitation
Interventions: Other: telerehabilitation; Other: home exercise program; Other: informed program
Sponsor: Bandırma Onyedi Eylül University
Recruiting
Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cells,NVSI-06-08) and Inactivated COVID-19 Vaccine (Vero Cells) in Population Aged 18 Years and Above - Conditions: COVID-19 Pneumonia; Coronavirus Infections
Interventions: Biological: Recombinant COVID-19 Vaccine (CHO cell,NVSI-06-08); Biological: COVID-19 vaccine (Vero cells); Biological: 3 doses Recombinant COVID-19 Vaccine (CHO cell,NVSI-06-08)
Sponsors: National Vaccine and Serum Institute, China; China National Biotec Group Company Limited; Lanzhou Institute of Biological Products Co., Ltd
Not yet recruiting
The Role of Traditional Chinese Medicine in COVID-19: Theory, Initial Clinical Evidence, Potential Mechanisms, and Implications - CONCLUSION: While there is initial support for the use of Traditional Chinese Medicine for COVID-19, conclusions cannot be drawn to support its use as a replacement for conventional COVID-19 treatment, given the lack of high-quality evidence from strictly-designed randomized controlled trials. However, there is initial evidence suggesting that TCM may serve as an effective adjunct to conventional treatments in alleviating COVID-19 symptoms. More research is needed to confirm the efficacy and…
Structure and Dynamics of RNA Guanine Quadruplexes in SARS-CoV-2 Genome. Original Strategies against Emerging Viruses - Guanine quadruplex (G4) structures in the viral genome have a key role in modulating viruses’ biological activity. While several DNA G4 structures have been experimentally resolved, RNA G4s are definitely less explored. We report the first calculated G4 structure of the RG-1 RNA sequence of SARS-CoV-2 genome, obtained by using a multiscale approach combining quantum and classical molecular modeling and corroborated by the excellent agreement between the corresponding calculated and experimental…
Acetylation of H3K27 activated lncRNA NEAT1 and promoted hepatic lipid accumulation in non-alcoholic fatty liver disease via regulating miR-212-5p/GRIA3 - Non-alcoholic fatty liver disease (NAFLD) was a world-wide health burden. H3K27 acetylation, long non-coding RNA (lncRNA), and miRNA were all implicated in NAFLD regulation, yet the detailed regulatory mechanism was not well understood. LncRNA NEAT1, miR-212-5p, and GRIA3 expression were detected both in high fatty acid-treated hepatocytes cells and NAFLD patients. Lipid droplets were stained and analyzed by oil red O staining. Expression of fatty acid synthase (FASN), acetyl-CoA carboxylase…
Sweet Drugs for Bad Bugs: A Glycomimetic Strategy against the DC-SIGN-Mediated Dissemination of SARS-CoV-2 - The C-type lectin receptor DC-SIGN is a pattern recognition receptor expressed on macrophages and dendritic cells. It has been identified as a promiscuous entry receptor for many pathogens, including epidemic and pandemic viruses such as SARS-CoV-2, Ebola virus, and HIV-1. In the context of the recent SARS-CoV-2 pandemic, DC-SIGN-mediated virus dissemination and stimulation of innate immune responses has been implicated as a potential factor in the development of severe COVID-19. Inhibition of…
Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 Replication by Hypertonic Saline Solution in Lung and Kidney Epithelial Cells - An unprecedented global health crisis has been caused by a new virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We performed experiments to test if a hypertonic saline solution was capable of inhibiting virus replication. Our data show that 1.2% NaCl inhibited virus replication by 90%, achieving 100% of inhibition at 1.5% in the nonhuman primate kidney cell line Vero, and 1.1% of NaCl was sufficient to inhibit the virus replication by 88% in human epithelial lung cell…
Characterization of Phytochemicals in Ulva intestinalis L. and Their Action Against SARS-CoV-2 Spike Glycoprotein Receptor-Binding Domain - Coronavirus disease-2019 (COVID-19) has caused a severe impact on almost all aspects of human life and economic development. Numerous studies are being conducted to find novel therapeutic strategies to overcome COVID-19 pandemic in a much effective way. Ulva intestinalis L. (Ui), a marine microalga, known for its antiviral property, was considered for this study to determine the antiviral efficacy against severe acute respiratory syndrome-associated Coronavirus-2 (SARS-CoV-2). The algal sample…
Evidence of SARS-CoV-2-Specific Memory B Cells Six Months After Vaccination With the BNT162b2 mRNA Vaccine - SARS-CoV-2 mRNA vaccines have demonstrated high efficacy and immunogenicity, but limited information is currently available on memory B cell generation and long-term persistence. Here, we investigated spike-specific memory B cells and humoral responses in 145 subjects, up to 6 months after the BNT162b2 vaccine (Comirnaty) administration. Spike-specific antibodies peaked 7 days after the second dose and significant antibody titers and ACE2/RBD binding inhibiting activity were still observed after…
ORF3a Protein of Severe Acute Respiratory Syndrome Coronavirus 2 Inhibits Interferon-Activated Janus Kinase/Signal Transducer and Activator of Transcription Signaling via Elevating Suppressor of Cytokine Signaling 1 - Coronavirus disease 2019 (COVID-19) has caused a crisis to global public health since its outbreak at the end of 2019. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of COVID-19, appears to efficiently evade the host immune responses, including interferon (IFN) signaling. Several SARS-CoV-2 viral proteins are believed to involve in the inhibition of IFN signaling. In this study, we discovered that ORF3a, an accessory protein of SARS-CoV-2, inhibited IFN-activated…
Integrin activation is an essential component of SARS-CoV-2 infection - SARS-CoV-2 infection depends on binding its spike (S) protein to angiotensin-converting enzyme 2 (ACE2). The S protein expresses an RGD motif, suggesting that integrins may be co-receptors. Here, we UV-inactivated SARS-CoV-2 and fluorescently labeled the envelope membrane with octadecyl rhodamine B (R18) to explore the role of integrin activation in mediating cell entry and productive infection. We used flow cytometry and confocal microscopy to show that SARS- CoV-2^(R18) particles engage…
Investigating Lipid-Modulating Agents for Prevention or Treatment of COVID-19: JACC State-of-the-Art Review - Coronavirus disease-2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multiorgan manifestations. Lipid-modulating agents may be useful in treating patients with COVID-19. These agents may inhibit viral entry by lipid raft disruption or ameliorate the inflammatory response and endothelial activation. In addition, dyslipidemia with lower high-density lipoprotein cholesterol and higher triglyceride levels portend worse outcomes in patients with COVID-19. Upon a…
Possible Benefits of Zinc supplement in CVD and COVID-19 Comorbidity - As far as comorbidity is concerned, cardiovascular diseases (CVD) appear to be accounted for the highest prevalence, severity, and fatality among COVID 19 patients. A wide array of causal links connecting CVD and COVID-19 baffle the overall prognosis as well as the efficacy of the given therapeutic interventions. At the centre of this puzzle lies ACE2 that works as a receptor for the SARS-CoV-2, and functional expression of which is also needed to minimize vasoconstriction otherwise would lead…
Nasal delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the disease COVID-19 can lead to serious symptoms, such as severe pneumonia, in the elderly and those with underlying medical conditions. While vaccines are now available, they do not work for everyone and therapeutic drugs are still needed, particularly for treating life- threatening conditions. Here, we showed nasal delivery of a new, unmodified camelid single-domain antibody (VHH), termed K-874A, effectively inhibited…
Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19 - [Figure: see text].
Therapeutic strategies for Covid-19 based on molecular docking and dynamic studies to the ACE-2 receptors, Furin, and viral spike proteins - SARS-CoV-2 is a pandemic virus that caused infections and deaths in many world countries, including the Middle East. The virus-infected human cells by binding via ACE-2 receptor through the Spike protein of the virus with Furin’s help causing cell membrane fusion leading to Covid-19-cell entry. No registered drugs or vaccines are triggering this pandemic viral disease yet. Our present work is based on molecular docking and dynamics simulation that performed to spike protein-ACE-2 interface…
Surface Glycan Modification of Cellular Nanosponges to Promote SARS-CoV-2 Inhibition - Cellular binding and entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are mediated by its spike glycoprotein (S protein), which binds with not only the human angiotensin-converting enzyme 2 (ACE2) receptor but also glycosaminoglycans such as heparin. Cell membrane-coated nanoparticles (“cellular nanosponges”) mimic the host cells to attract and neutralize SARS-CoV-2 through natural cellular receptors, leading to a broad-spectrum antiviral strategy. Herein, we show that…