Purpose: A subset of patients with post-COVID-19 condition (PCC) fulfill the clinical criteria of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). To establish the diagnosis of ME/CFS for clinical and research purposes, comprehensive scores have to be evaluated. Methods: We developed the Munich Berlin Symptom Questionnaires (MBSQs) and supplementary scoring sheets (SSSs) to allow for a rapid evaluation of common ME/CFS case definitions. The MBSQs were applied to young patients with chronic fatigue and post-exertional malaise (PEM) who presented to the MRI Chronic Fatigue Center for Young People (MCFC). Trials were retrospectively registered (NCT05778006, NCT05638724). Results: Using the MBSQs and SSSs, we report on ten patients aged 11 to 25 years diagnosed with ME/CFS after asymptomatic SARS-CoV-2 infection or mild to moderate COVID-19. Results from their MBSQs and from well-established patient-reported outcome measures indicated severe impairments of daily activities and health-related quality of life. Conclusions: ME/CFS can follow SARS-CoV-2 infection in patients younger than 18 years, rendering structured diagnostic approaches most relevant for pediatric PCC clinics. The MBSQs and SSSs represent novel diagnostic tools that can facilitate the diagnosis of ME/CFS in children, adolescents, and adults with PCC and other post-viral syndromes.
Background: Subvariants of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) omicron XBB-lineage have the potential to escape immunity provided by prior infection or vaccination. For Covid-19 immunizations beginning in the Fall 2023, the U.S. FDA has recommended updating to a monovalent omicron XBB.1.5-containing vaccine. Methods: In this ongoing, phase 2/3 study participants were randomized 1:1 to receive 50-µg doses of mRNA-1273.815 monovalent (50-µg omicron XBB.1.5 spike mRNA) or mRNA-1273.231 bivalent (25-µg omicron XBB.1.5 and 25-µg omicron BA.4/BA.5 spike mRNAs)vaccines, administered as 5th doses, to adults who previously received a primary series and 3rd dose of an original mRNA coronavirus disease 2019 (Covid-19) vaccine, and a 4th dose of a bivalent (omicron BA.4/BA.5 and original SARS-CoV-2) vaccine. Interim safety and immunogenicity data 15 days post-vaccination are presented. Results: In April 2023, participants received mRNA-1273.815 (n=50) and mRNA-1273.231 (n=51). The median intervals from the prior dose of BA.4/BA.5-containing bivalent vaccine were 8.2 and 8.3 months for the mRNA-1273.815 and mRNA-1273.231 groups, respectively. Both vaccines increased neutralizing antibody (nAb) geometric mean titers against all variants tested at day 15 post-booster nAb compared to pre-booster levels. Geometric mean fold-rises from pre-booster titers after the monovalent booster were higher against XBB.1.5, XBB.1.16 and SARS-CoV-2 (D614G) than those of the bivalent booster and were comparable against BA.4/BA.5 and BQ1.1 variants for both vaccines. The monovalent vaccine also elicited nAb responses against omicron XBB.2.3.2, EG.5.1, and FL.1.5.1 that were similar to those seen for XBB.1.5 in a subset (n=20) of participants. The occurrence of solicited adverse reactions and unsolicited adverse events were overall similar to those previously reported for the original mRNA-1273 50-µg and omicron BA.4/BA.5-containing bivalent mRNA-1273 vaccines. Conclusion: In this interim analysis, XBB.1.5-containing monovalent and bivalent vaccines elicited potent neutralizing responses against variants of the omicron XBB-lineage (XBB.1.5, XBB.1.6, XBB.2.3.2) as well as more recent (EG.5.1, FL.1.5.1) variants. The safety profile of the XBB.1.5-containing vaccine was consistent with those of prior vaccines. These results support the Covid-19 vaccine update in 2023-2024 to a monovalent XBB.1.5-containing vaccine.
Purpose: To examine the associations between vision impairment (VI) and COVID19 testing and vaccination services in older US adults. Methods: This cross-sectional study assessed data from adults aged 65 years or older who participated in the National Health and Aging Trends Study (year 2021), a nationally representative sample of Medicare beneficiaries. Exposure: Distance VI (<20/40), near VI (<20/40), contrast sensitivity impairment (CSI) (<1.55 logCS), and any VI (distance, near, or CSI). Outcomes: Self-reported COVID-19 testing and vaccination. Results: Of 2,822 older adults, the majority were female (weighted; 55%) and White (82%), and 32% had any VI. In fully-adjusted regression analyses, older adults with any VI had similar COVID19 vaccination rates to adults without any VI (OR:0.77, 95% CI:0.54, 1.09), but had lower odds of COVID19 testing (OR:0.82, 95% CI:0.68, 0.97). Older adults with distance (OR:0.47, 95% CI:0.22, 0.99) and near (OR:0.68, 95% CI:0.47, 0.99) VI were less likely to be vaccinated for COVID19, while those with CSI were less likely to test for COVID19 (OR:0.76, 95% CI:0.61, 0.95), as compared to peers without respective impairments. The remaining associations were not significant (p>.05). Conclusions and Relevance: These findings highlight inequities in the COVID19 pandemic response for people with vision disability and emphasize the need for equitable prioritization of accessibility of healthcare services for all Americans.
Background Ethnic minorities living in high-income countries have been disproportionately affected by COVID-19 in terms of infection rates and hospitalisations; however, less is known about long COVID in this population. Our aim was to examine the risk of long COVID and associated symptoms among ethnic minorities. Methods and Findings A Danish nationwide register-based cohort study of individuals diagnosed with COVID-19 aged ≥18 years (n=2 334 271) between January 2020 and August 2022. We calculated the risk of long COVID diagnosis and long COVID symptoms among ethnic minorities compared with native Danes using multivariable Cox proportional hazard regression and logistic regression, respectively. Ethnic minorities from North Africa (adjusted hazard ratio [aHR] 1.41; 95% CI 1.12–1.79), Middle East (aHR 1.38; 95% CI 1.24–1.55), Eastern Europe (aHR 1.35; 95% CI 1.22–1.49), and Asia (aHR 1.23; 95% CI 1.09–1.40) had significantly greater risk of long COVID diagnosis than native Danes in both unadjusted and adjusted models. In the analysis by largest countries of origin, the greater risks of long COVID diagnosis were found in Iraqis (aHR 1.56; 95% CI 1.30– 1.88), Turks (aHR 1.42; 95% CI 1.24–1.63), and Somalis (aHR 1.42; 95% CI 1.07–1.91) after adjustment for confounders. Significant factor associated with an increased risk of long COVID diagnosis was COVID-19 hospitalisation. Furthermore, the odds of reporting cardiopulmonary symptoms (including dyspnoea, cough, and chest pain) and any long COVID symptoms were higher among North African, Middle Eastern, Eastern European, and Asian than among native Danes in both unadjusted and adjusted models. Conclusions Belonging to an ethnic minority group was significantly associated with an increased risk of long COVID indicating the need to better understand long COVID drivers and address care and treatment strategies in this population.
Background: The COVID-19 pandemic is a respiratory illness that has spread to over 210 countries and killed over 6 million people. There is no specific treatment for COVID-19, but vaccines have been developed that can help prevent severe illness and death. A number of studies have investigated the effect of vaccination on disease severity and outcome, and the findings indicate that vaccination is linked to a significant reduction in the risk of hospitalization, intensive care unit admission, and death from the disease. However, there is a scarcity of evidence in Africa in general, and no similar study has been conducted in Ethiopia yet. Therefore, the study aimed to assess the effect of vaccination on COVID-19 disease severity and need for Intensive Care Unit (ICU) admission among hospitalized patients at a private specialty clinic in Ethiopia. Methods: A retrospective cohort study was conducted among 126 patients with COVID-19, 41 vaccinated and 85 unvaccinated, who were hospitalized between September 2021 and May 2022. Data was summarized using frequency (percentage) and median (interquartile range). To compare the characteristics of the two groups, Chi-square/ Fisher9s Exact and Mann Whitney U tests at p-value of ≤ 0.05 were used. To identify the effect of vaccination on COVID-19 disease severity, Marginal Structural Model (MSM) with inverse probability weighting (IPW) approach using robust poisson regression model was fitted and adjusted relative risk (ARR) and 95% CI for ARR were used for interpreting the result. Results: The cohort included groups that were fairly comparable in terms of their sociodemographic and clinical characteristics. More than half of the participants were older than 60 years (52.4%), were males (56.3%) and had one or more comorbid illness (52.4%). At admission 85 (67.5%) had severe disease and 11 (8.7%) progressed after hospitalization and required ICU admission, of which three unvaccinated cases died. From the final model, vaccination was found to be associated with a 62% decreased risk of developing severe COVID-19 disease if infected, compared to not getting vaccinated (ARR=0.38, 95% CI=0.23-0.65, p<0.0001). Conclusions: The study9s findings support previous reports that vaccinated people are less likely to develop severe COVID-19 disease if infected with the virus, emphasizing the importance of continuing efforts to promote COVID-19 vaccination not only to safeguard individuals but also to confer community-level immunity.
Introduction: The MMR vaccine has been shown by several studies over the years to have a potent effect on heterologous immunity. The reduction in mortality and respiratory and gastrointestinal diseases in childhood has been consolidated with recent studies demonstrating a better evolution of COVID-19 with the use of this vaccine. Stimulation of innate immunity by the MMR vaccine can be very useful, both used alone or in association with other vaccines, especially those for COVID-19. Objectives: To evaluate the decrease in the incidence of infection or severity of COVID-19 with the use of the MMR vaccine before and after the use of specific vaccines against COVID-19. Methods: This extension analysis followed 120 volunteers healthcare professionals aged 18 to 60 who received the MMR vaccine before the specific COVID-19 vaccine and 73 volunteers who used the MMR vaccine after the COVID-19 vaccine. Visits to the Research Center were carried out at an average interval of 4 weeks for 12 weeks. The diagnosis of COVID-19 was performed using the RT-PCR technique for the SARS-CoV-2 virus. Results: The most used vaccine against COVID-19 was Coronavac in 59.1%. A total of 44 cases of COVID-19 were diagnosed (20% of the sample), the vast majority of which were mild cases (70.5%). There was no difference in the incidence and severity of COVID-19 in health professionals who used the MMR vaccine before or after the specific vaccine against the SARS-CoV-2 virus (Coronavirus or AstraZeneca). Conclusion: The incidence and severity of COVID-19 does not differ with the use of the MMR vaccine before or after the specific vaccine against COVID-19.
OBJECTIVES: To analyze the symptoms and severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (pwMS) on immunotherapy using data from the COVID-19 in multiple sclerosis (MS) Global Data Sharing Initiative dataset provided by PhysioNet. METHODS: The open-access COVID-19 in MS Global Data Sharing Initiative dataset was obtained through credentialed access using PhysioNet. The variables analyzed included body mass index (BMI), symptoms of COVID-19, age, current use of disease-modifying therapy (DMT), efficacy of DMT, comorbidities, hospitalization status, and type of MS. A linear regression analysis was completed. Data analysis and visualization were completed using STATA v1.5, R-Studio v1.1.447, Python v3.8, and its associated libraries, including NumPy, Pandas, and Matplotlib. RESULTS: A total of 1141 participants were included in the analysis. 904 women and 237 men were diagnosed with MS. Among the pwMS included in the study; 208 (19.54%) had a suspected infection with COVID-19 and only 49 (5.25%) were confirmed. Any COVID-19 symptom was present in 360 individuals. The commonly reported DMT agents included dimethyl fumarate (12.71%) and fingolimod (10.17%). 101 in total (8.85%) reported not using any DMT. Factors associated with hospitalization and/or admission to the ICU included having any comorbidity (p = 0.01), neuromuscular disorder (p = 0.046), hypertension (p = 0.005), chronic kidney disease (p < 0.001), and immunodeficiency (p = 0.003). The type of MS, the duration of the disease, and high-efficacy DMT therapy did not have a statistically significant influence on hospitalization. CONCLUSION: This study underscores the importance of comorbidities, especially neuromuscular disorders, hypertension, chronic kidney disease (CKD), and immunodeficiencies, as possible prognostic indicators for worse outcomes of COVID-19 in pwMS. On the contrary, the type of MS, the duration of the disease, and the efficacy of disease-modifying therapy did not significantly affect the severity of the symptoms of COVID-19 in this cohort.
Abstract Background ADAM17 are emerging as an important role in the severe outcomes of COVID-19. This study aims to characterize causal relationship between ADAM17 and COVID-19. Methods Using mendelian randomization analyses, we examined the causal effects for circulating ADAM17 on COVID-19 outcomes using summary statistics from large genome wide association studies of ADAM17 (up to 35 559 individuals) from the Icelandic Cancer Project and deCODE genetics, critical COVID-19 (cases:13 769; controls:1 072 442), hospitalized COVID-19 (cases:32 519; controls: 2 062 805) and SARS-CoV-2 infection (cases:122 616; controls:2 475 240) from the COVID-19 Host Genetics Initiative. Results Mendelian randomization analyses demonstrated that 1 standard deviation increase of genetically determined circulating ADAM17 at extracellular domain were associated with increasing risk of developing critical COVID-19 (odds ratio [OR]=1.26, 95% CI 1.03-1.55). Multivariable MR analysis suggested a direct causal role of circulating ADAM17 at extracellular domain on the risk of critical COVID-19 (OR=1.09; 95% CI 1.01-1.17), accounting for body mass index. Casual effects for the cytoplasmic domain of ADAM17 on COVID-19 were not observed. Conclusion Our results suggest that the increased circulating ADAM17 at extracellular domain are associated with a high risk of critical COVID-19 strengthening that of ADAM17 may contribute to the risk stratification and a therapeutic option for severe COVID-19.
Introduction The widespread use of antigen-detection rapid diagnostic tests (Ag-RDTs) has revolutionized SARS-CoV-2 (COVID-19) testing, particularly through the option of self-testing. The full extent of Ag-RDT utilization for self-testing, however, remains largely unexplored. To inform the development of WHO guidance on COVID-19 self-testing, we conducted a cross-sectional survey to gather the views and experiences of policy makers, researchers, and implementers worldwide. Methods The survey was shared through professional networks via email and social media, encouraging onward sharing. We used closed and open-ended questions related to policy and program information concerning the regulation, availability, target population, indications, implementation, benefits, and challenges of COVID-19 self-testing (C19ST). We defined self-testing as tests performed and interpreted by an untrained individual, often at home. Descriptive summaries, cross-tabulations, and proportions were used to calculate outcomes at the global level and by WHO region and World Bank income classifications. Results Between 01 and 11 February 2022, 844 individuals from 139 countries responded to the survey, with 45% reporting affiliation with governments and 47% operating at the national level. 504 respondents from 101 countries reported policies supporting C19ST for a range of use cases, including symptomatic and asymptomatic populations. More respondents from low-and-middle-income countries (LMICs) than high-income countries (HICs) reported a lack of an C19ST policy (61 vs 11 countries) and low population-level reach of C19ST. Respondents with C19ST experience perceived that the tests were mostly acceptable to target populations, provided significant benefits, and highlighted several key challenges to be addressed for increased success. Reported costs varied widely, ranging from specific programmes enabling free access to certain users and others with high costs via the private sector. Conclusion Based on the survey responses, systems for the regulatory review, policy development and implementation of C19STappeared to be much more common in HIC when compared to LIC in early 2022, though most respondents indicated self-testing was available to some extent (101 out of 139 countries) in their country. Addressing such global inequities is critical for ensuring access to innovative and impactful interventions in the context of a public health emergency of international concern. The challenges and opportunities highlighted by survey respondents could be valuable to consider as future testing strategies are being set for outbreak-prone diseases.
Background. Loneliness is a serious public health problem and became even more visible during the COVID-19 pandemic. Yet it is unknown which aspects of social networks are most important. Here, we evaluated social network structure and function and associations with moderate and severe social and emotional loneliness in older adults. Methods. This cross-sectional study includes online questionnaire data (SaNAE cohort, August-November 2020), in independently living Dutch adults aged 40 years and older. For the separate outcomes social and emotional loneliness, associations with structural network aspects (e.g., network diversity - having various types of relationships, and density - having network members who know each other), and functional network aspects (informational, emotional, and practical social support) were assessed and risk estimates were adjusted for the number of contacts, age, educational level, level of urbanization and chronic conditions. Multivariable logistic regression analyses were stratified by sex. Results. Of 3,396 participants (55% men; mean age 65 years), 18% were socially lonely which was associated with a less diverse and less dense network, living alone, feeling less connected to friends, not having a club membership, and fewer emotional supporters (men only) or informational supporters (women only). 28% were emotionally lonely, which was associated with being socially lonely, and more exclusively online (versus in-person) contacts (men only), and fewer emotional supporters (women only). Conclusion. Network structure and function beyond the mere number of contacts is key in loneliness, and in particular, the types of relationships are important. Public health strategies should be sex-tailored and promote network diversity and density, club membership, informational and emotional support, and in-person contact.
Predicting an individual9s risk of infectious disease is a critical technology in infectious disease response. During the COVID-19 pandemic, identifying and isolating individuals at high risk of infection was an essential task for epidemic control. We introduce a new machine learning model that predicts the risk of COVID-19 infection using only individuals9 mobile cell tower location information. This model distinguishes the cell tower location information of an individual into residential and non-residential areas and calculates whether the cell tower locations overlapped with other individuals. It then generates various variables from the information of overlapping and predicts the possibility of COVID-19 infection using a machine learning algorithm. The predictive model we developed showed performance comparable to models using individual9s clinical information. This predictive model, which can be used to predict infections of diseases with asymptomatic infections such as COVID-19, has the advantage of supplementing the limitations of existing infectious disease prediction models that use symptoms and other information.
THE EFFECT OF ARGININE AND GLUTAMINE ON COVID-19 PATIENTS OUTCOME: A RANDOMIZED CLINICAL TRIAL - Condition: Â COVID-19
Intervention:  Dietary Supplement: Neomune
Sponsors:  Universitas Sriwijaya;  M. Djamil General Hospital
Completed
Study of Obeldesivir in Children and Adolescents With COVID-19 - Condition: Â COVID-19
Intervention: Â Drug:Â Obeldesivir
Sponsor:  Gilead Sciences
Not yet recruiting
A Pilot Clinical Evaluation of Astepro® Nasal Spray for Management of Early SARS-CoV-2 Infection - Condition:  COVID-19
Interventions:  Drug: Experimental: Primary Cohort;  Other: Placebo Comparator: Primary Cohort - Placebo
Sponsor:  University of Chicago
Active, not recruiting
Immunogenicity and Safety of AdCLD-CoV19-1 OMI as a Booster: A COVID-19 Preventive Vaccine in Healthy Volunteers - Conditions: Â COVID-19; Â Vaccines
Interventions: Â Biological:Â AdCLD-CoV19-1Â OMI; Â Biological: Comirnaty Bivalent 0.1mg/mL (tozinameran and riltozinameran)
Sponsor:  Cellid Co., Ltd.
Not yet recruiting
Using Text Messages to Boost COVID-19 Vaccine Booking Rate - Conditions:  Vaccination Hesitancy;  COVID-19
Interventions: Â Behavioral: Behavioural science-informed text messages; Â Behavioral:Â Control
Sponsors:  The Behavioural Insights Team;  Public Health England;  Department of Health and Social Care;  NHS England and NHS Improvement
Completed
Ivermectin to Prevent SARS-CoV-2 (COVID-19) Hospitalisation in Subjects Over 50 - Conditions: Â COVID-19; Â SARS-CoV-2
Interventions: Â Drug:Â Ivermectin; Â Drug:Â Placebo
Sponsor:  Insud Pharma
Terminated
Digital Health Literacy on COVID-19 for All: Co-creation and Evaluation of Interventions for Ethnic Minorities and Chinese People With Chronic Illnesses in Hong Kong - Conditions:  Digital Health Literacy;  COVID-19
Intervention:  Behavioral: Digital health literacy intervention
Sponsor:  The Hong Kong Polytechnic University
Not yet recruiting
Methylprednisolone in Patients With Cognitive Deficits in Post-COVID-19 Syndrome (PCS) - Condition: Â Post-COVID-19Â Syndrome
Intervention: Â Drug:Â Methylprednisolone
Sponsor:  Charite University, Berlin, Germany
Not yet recruiting
COVID-19 Vaccination Hesitancy in Adults With Sickle Cell Disease - Conditions:  Sickle Cell Disease;  COVID-19 Vaccine;  Vaccine Hesitancy
Intervention: Â Behavioral: SCD-specific COVID-19 vaccination information (SCVI) video
Sponsors:  Duke University;  American Society of Hematology
Not yet recruiting
A Study to Learn About New COVD-19 RNA Vaccine Candidates for New Varients in Healthy Individuals - Conditions: Â SARS-CoV-2Â Infection; Â COVID-19
Intervention:  Biological: BNT162b2 (Omi XBB.1.5)
Sponsors:  BioNTech SE;  Pfizer
Not yet recruiting
Leveraging Community Health Workers to Combat COVID-19 and Mental Health Misinformation in Haiti, Malawi, and Rwanda - Conditions:  Mental Health;  COVID-19;  Misinformation
Interventions: Â Behavioral: Card-Sorting Activity (Pre-intervention design); Â Behavioral: SMS Crafting (Pre-intervention design); Â Behavioral:Â SMSÂ Messaging
Sponsors:  Harvard Medical School (HMS and HSDM);  Partners in Health
Active, not recruiting
Effect of Pulmonary Rehabilitation Among Post-COVID-19 Patients in a Tertiary Care Hospital in Bangladesh - Condition:  Pulmonary Pathology
Intervention:  Behavioral: Pulmonary Rehabilitation
Sponsor: Â Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
Active, not recruiting
Pulmonary Artery Pressure in COVID-19 Survivors - Condition:  Pulmonary Hypertension Secondary
Intervention: Â Diagnostic Test: right heart catheterization (RHC).
Sponsor:  Mansoura University Hospital
Enrolling by invitation
Preliminary Efficacy of a Technology-based Physical Activity Intervention for Older Korean Adults During the COVID-19 Pandemic - Conditions:  Cardiovascular Health;  Physical Function
Intervention:  Behavioral: Golden Circle
Sponsor:  University of Illinois at Urbana-Champaign
Completed
Study of LAU-7b for the Treatment of Long COVID in Adults - Condition:  Long COVID
Interventions:  Drug: LAU-7b for 3 cycles;  Drug: LAU-7b for 1 cycle, then placebo;  Other: Placebo for 3 cycles
Sponsor:  Laurent Pharmaceuticals Inc.
Not yet recruiting
The contribution of Australian fathers in getting food on the table among families with young children - CONCLUSIONS: The findings suggest the need to consider father-specific strategies to overcome time barriers and opportunities to enhance their capabilities for healthy home food provisioning.
Design, synthesis, and greener pasture biological assessment of a novel nucleoside: 1-(α-D-ribofuranosyl)-6,7-difluoro-2-methyl-4-quinazolinone as an inhibitor of COVID-19 and Alzheimer’s disease - Synthesis of a new fluorinated nucleoside of 6,7-difluoro-2-methyl-4-quinazolinone was described. 2-Amino-4,5-difluorobenzoic acid 1 reacts with (CH(3)CO)(2)O followed by ammonia to form (1H)-6,7-difluoro-2-methyl-4-quinazolinone 3a. Ribosylation of a silylated 4 with l-O-acety1-2,3-5-tri-O-benzoyl-α-D-ribofuranose 5 forms a protected nucleoside 6 then unprotected from 6 to give a free nucleoside 7. Greener pasture biological docking of the cystine protease of COVID-19 [M^(pro), code 7BQY, PDB]…
Reducing airborne transmission of SARS-CoV-2 by an upper-room ultraviolet germicidal irradiation system in a hospital isolation environment - Upper-room ultraviolet germicidal irradiation (UVGI) technology can potentially inhibit the transmission of airborne disease pathogens. There is a lack of quantitative evaluation of the performance of the upper-room UVGI for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) airborne transmission under the combined effects of ventilation and UV irradiation. Therefore, this study aimed to explore the performance of the upper-room UVGI system for reducing SARS-CoV-2 virus transmission in…
Dexamethasone attenuates interferon-related cytokine hyperresponsiveness in COVID-19 patients - CONCLUSION: We describe the anti-inflammatory impact of dexamethasone on the pathways contributing to cytokine hyperresponsiveness observed in severe manifestations of COVID-19, including type I/II IFN signaling. Dexamethasone could have adverse effects in COVID-19 patients with mild symptoms by inhibiting IFN responses in early stages of the disease, whereas it exhibits beneficial effects in patients with severe clinical phenotypes by efficiently diminishing cytokine hyperresponsiveness.
Investigation of Iminosugars as Antiviral Agents against SARS-CoV-2 Main Protease: Inhibitor Design and Optimization, Molecular Docking, and Molecular Dynamics Studies to Explore Potential Inhibitory Effect of 1-Deoxynojirmycin Series - CONCLUSION: The present findings confer opportunities for compounds 17a, 7, and 8 that could be developed as new therapeutic agents against COVID-19. These compounds are suggested on the basis of pharmacokinetic parameters as well as therapeutic importance and hence could be tested in-vitro.
A complement atlas identifies interleukin-6-dependent alternative pathway dysregulation as a key druggable feature of COVID-19 - Improvements in COVID-19 treatments, especially for the critically ill, require deeper understanding of the mechanisms driving disease pathology. The complement system is not only a crucial component of innate host defense but can also contribute to tissue injury. Although all complement pathways have been implicated in COVID-19 pathogenesis, the upstream drivers and downstream effects on tissue injury remain poorly defined. We demonstrate that complement activation is primarily mediated by the…
The S1’-S3’ Pocket of the SARS-CoV-2 Main Protease Is Critical for Substrate Selectivity and Can Be Targeted with Covalent Inhibitors - The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a well-characterized target for antiviral drug discovery. To date, most antiviral drug discovery efforts have focused on the S4-S1’ pocket of Mpro; however, it is still unclear whether the S1’-S3’ pocket per se can serve as a new site for drug discovery. In this study, the S1’-S3’ pocket of Mpro was found to differentially recognize viral peptidyl substrates; for instance, S3’ in Mpro strongly favors Phe…
Cyclotheonellazoles D-I, Potent Elastase Inhibitory Thiazole-Containing Cyclic Peptides from Theonella sp. (2131) - Six new thiazole-containing cyclic peptides, the cyclotheonellazoles D-I (1-6), were isolated from the Australian marine sponge Theonella sp. (2131) with their structures assigned by comprehensive 1D and 2D NMR spectroscopic and MS spectrometric analyses, Marfey’s derivatization studies, and comparison with time-dependent density functional theory (TDDFT) calculated ECD data. The Type 2 azole-homologated peptides herein comprise up to five nonproteinogenic amino acids, including the protease…
Assessment of efficacy and safety of endoscopic lung volume reduction with one-way valves in patients with a very low FEV1 - CONCLUSION: Our study highlights the potential efficacy of one-way valves, even in patients with very low FEV(1), as these patients experienced significant improvements in FEV(1), 6MWD and quality of life. No death was reported, suggesting a good safety profile, even in these high-risk patients.
Prevalence of oral complications in the course of severe SARS-CoV-2 infection under mechanical non-invasive ventilation - CONCLUSIONS: COVID-19 hospitalised patients with severe symptoms crossing with poor oral health-related conditions. This may exacerbate a response for COVID infection, and play a role in cytokine storm. For Covid-19 management, to inhibit extraoral/intraoral complications, it is recommended to adjust oral hygiene procedures, including antibacterial, protective, moisturising agents after individual oral health assessment.
The Possible Mechanisms of Cu and Zn in the Treatment and Prevention of HIV and COVID-19 Viral Infection - Due to their unique properties and their potential therapeutic and prophylactic applications, heavy metals have attracted the interest of many researchers, especially during the outbreak of COVID-19. Indeed, zinc (Zn) and copper (Cu) have been widely used during viral infections. Zn has been reported to prevent excessive inflammatory response and cytokine storm, improve the response of the virus to Type I interferon (IFN-1), and enhance the production of IFN-a to counteract the antagonistic…
SARS-CoV-2 nucleocapsid protein inhibits the PKR-mediated integrated stress response through RNA-binding domain N2b - The nucleocapsid protein N of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enwraps and condenses the viral genome for packaging but is also an antagonist of the innate antiviral defense. It suppresses the integrated stress response (ISR), purportedly by interacting with stress granule (SG) assembly factors G3BP1 and 2, and inhibits type I interferon responses. To elucidate its mode of action, we systematically deleted and over-expressed distinct regions and domains. We show that…
A Mixture of Essential Oils from Three Cretan Aromatic Plants Inhibits SARS-CoV-2 Proliferation: A Proof-of-Concept Intervention Study in Ambulatory Patients - INTRODUCTION: The need for effective therapeutic regimens for non-critically ill patients during the COVID-19 pandemic remained largely unmet. Previous work has shown that a combination of three aromatic plants’ essential oils (CAPeo) (Thymbra capitata (L.) Cav., Origanum dictamnus L., Salvia fruticose Mill.) has remarkable in vitro antiviral activity. Given its properties, it was urgent to explore its potential in treating mild COVID-19 patients in primary care settings.
Peptide foldamer-based inhibitors of the SARS-CoV-2 S protein-human ACE2 interaction - The entry of the SARS-CoV-2 virus into a human host cell begins with the interaction between the viral spike protein (S protein) and human angiotensin-converting enzyme 2 (hACE2). Therefore, a possible strategy for the treatment of this infection is based on inhibiting the interaction of the two abovementioned proteins. Compounds that bind to the SARS-CoV-2 S protein at the interface with the alpha-1/alpha-2 helices of ACE2 PD Subdomain I are of particular interest. We present a stepwise…
CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis - Aberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection, yet the underlying mechanism remains obscure. Here we show that serum levels of SARS-CoV-2 envelope (E) protein are associated with coagulation disorders of COVID-19 patients, and intravenous administration of the E protein is able to potentiate thrombosis in mice. Through protein pull-down and mass spectrometry, we find that CD36, a transmembrane glycoprotein, directly binds with E protein and…