Background Hospital-at-home (HaH) care has been proposed as an alternative to inpatient care for patients with COVID-19. Previous reports were hospital-led and involved patients triaged at the hospitals. To reduce the burden on hospitals, we constructed a novel HaH care model organised by a team of local primary care clinics. Methods We conducted a multi-center retrospective cohort study of the COVID-19 patients who received our HaH care from Jan 1st to Mar 31st, 2022. Patients who were not able to be triaged for the need for hospitalization by the Health Center solely responsible for the management of COVID-19 patients in Osaka City were included. The primary outcome was receiving medical care beyond the HaH care defined as a composite outcome of any medical consultation, hospitalization, or death within 30 days from the initial treatment. Results Of 382 eligible patients, 34 (9%) were triaged for hospitalization immediately after the initial visit. Of the remaining 348 patients followed up, 37 (11%) developed the primary outcome, while none died. Obesity, fever, and gastrointestinal symptoms at baseline were independently associated with an increased risk of needing medical care beyond the HaH care. A further 129 (37%) patients were managed online alone without home visit, and 170 (50%) required only one home visit in addition to online treatment. Conclusions The HaH care model with a team of primary care clinics was able to triage patients with COVID-19 who needed immediate hospitalization without involving hospitals, and treated most of the remaining patients at home.
Background The COVID-19 pandemic has had a significant impact on delivery of NHS care. We have developed the OpenSAFELY Service Restoration Observatory (SRO) to describe this impact on primary care activity and monitor its recovery. Objectives To develop key measures of primary care activity and describe the trends in these measures throughout the COVID-19 pandemic. Methods With the approval of NHS England we developed an open source software framework for data management and analysis to describe trends and variation in clinical activity across primary care electronic health record (EHR) data on 48 million adults. We developed SNOMED-CT codelists for key measures of primary care clinical activity selected by a expert clinical advisory group and conducted a population cohort-based study to describe trends and variation in these measures January 2019-December 2021, and pragmatically classified their level of recovery one year into the pandemic using the percentage change in the median practice level rate. Results We produced 11 measures reflective of clinical activity in general practice. A substantial drop in activity was observed in all measures at the outset of the COVID-19 pandemic. By April 2021, the median rate had recovered to within 15% of the median rate in April 2019 in six measures. The remaining measures showed a sustained drop, ranging from a 18.5% reduction in medication reviews to a 42.0% reduction in blood pressure monitoring. Three measures continued to show a sustained drop by December 2021. Conclusions The COVID-19 pandemic was associated with a substantial change in primary care activity across the measures we developed, with recovery in most measures. We delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. We will continue to expand the set of key measures to be routinely monitored using our publicly available NHS OpenSAFELY SRO dashboards with near real-time data.
Despite recognition of the diversity of the Asian American population, the mortality impact of the COVID-19 pandemic has been limited to estimates for non-Hispanic Asian Americans in aggregate. This study provides estimates of life expectancy at birth before (2019) and during the pandemic, along with a broad set of demographic, health-related, and socioeconomic risk factors for COVID-19, for the six largest Asian American subgroups: Asian Indians, Chinese, Filipino, Japanese, Korean, and Vietnamese. Our study places these estimates in the context of the broader U.S. population by including the corresponding estimates for non-Hispanic Whites, non-Hispanic Blacks, Hispanics, and non-Hispanic Native Americans. We use data on age-specific all-cause mortality from CDC WONDER and population estimates from the 2015-2019 American Community Survey to construct life tables for each Asian subgroup by year. While losses in life expectancy during the second year of the pandemic diminished significantly among all racial/ethnic and Asian subgroups, these improvements do not compensate for the large increases in death rates in 2020. All major Asian subgroups except Japanese experienced greater losses of life in 2019-2020 as well as cumulatively (2019-2021) than Whites, with Vietnamese, Filipinos, and other South/Southeast Asians having suffered the largest declines in life expectancy among non-Hispanic Asians. Vietnamese and other Southeast Asians experienced the greatest cumulative losses across all racial/ethnic groups except Native Americans. Our findings underscore the heterogeneity of loss in life expectancy within the Asian American population while identifying some of the risk factors that likely underlie this large variation.
Introduction The Omicron variant of the SARS-CoV-2 virus is described as more contagious than previous variants. We sought to assess risk to healthcare workers (HCWs) caring for patients with COVID-19 in surgical/obstetrical settings, and the perception of risk amongst this group. Methods From January to April, 2022, reverse transcription polymerase chain reaction was used to detect the presence of SARS-CoV-2 viral RNA in patient, environmental (floor, equipment, passive air) samples, and HCWs masks (inside surface) during urgent surgery or obstetrical delivery for patients with SARS-CoV-2 infection. The primary outcome was the proportion of HCWs masks testing positive. Results were compared with our previous cross-sectional study involving obstetrical/surgical patients with earlier variants (2020/21). HCWs completed a risk perception electronic questionnaire. Results 11 patients were included: 3 vaginal births and 8 surgeries. 5/108 samples (5%) tested positive (SARS-CoV-2 Omicron) viral RNA: 2/5 endotracheal tubes, 1/22 floor samples, 1/4 patient masks and 1 nasal probe. No samples from the HCWs masks (0/35), surgical equipment (0/10) and air samples (0/11) tested positive. No significant differences were found between the Omicron and 2020/21 patient groups positivity rates (Mann-Whitney U test, p = 0.838) or the level of viral load from the naso-pharyngeal swabs (p = 0.405). Nurses had a higher risk perception than physicians (p = 0.0377). Conclusion No significant difference in contamination rates were found between SARS-CoV-2 Omicron BA.1 and previous variants in surgical/obstetrical settings. This is reassuring as no HCW mask was positive and no HCW tested positive for COVID-19 post-exposure.
Importance: The origin of highly divergent “cryptic” SARS-CoV-2 Spike sequences, which appear in wastewater but not clinical samples, is unknown. These wastewater sequences have harbored many of the same variants that later emerged in Omicron. If these enigmatic sequences are human-derived and transmissible, they could both be a source of future variants and a valuable tool for forecasting sequences that should be incorporated into vaccines and therapeutics. Objective: To determine whether enigmatic SARS-CoV-2 lineages detected in wastewater have a human or non-human (i.e., animal) source. Design: On January 11, 2022, an unusual Spike sequence was detected in municipal wastewater from a metropolitan area. Over the next four months, more focused wastewater sampling resolved the source of this variant. Setting: This study was performed in Wisconsin, United States, which has a comprehensive program for detecting SARS-CoV-2 in wastewater. Participants: Composite wastewater samples were used for this study; therefore, no individuals participated. Main Outcome(s) and Measure(s): The primary outcome was to determine the host(s) responsible for shedding this variant in wastewater. Both human and non-human hosts were plausible candidates at the study9s outset. Results: The presence of the cryptic virus was narrowed from a municipal wastewater sample (catchment area >100,000 people) to an indoor wastewater sample from a single facility (catchment area ~30 people), indicating the human origin of this virus. Extraordinarily high concentrations of viral RNA (~520,000,000 genome copies / L and ~1,600,000,000 genome copies / L in June and August 2022, respectively) were detected in the indoor wastewater sample. The virus sequence harbored a combination of fixed nucleotide substitutions previously observed only in Pango lineage B.1.234, a variant that circulated at low levels in Wisconsin from October 2020 to February 2021. Conclusions and Relevance: High levels of persistent SARS-CoV-2 shedding from the gastrointestinal tract of an infected individual likely explain the presence of evolutionarily advanced, “cryptic variants” observed in some wastewater samples.
This cross-sectional study investigated health management, well-being, and pandemic-related perspectives in Shanghainese adults ≥50 years during early and strict COVID-19 control measures. A self-report survey was administered via Wenjuanxing between March-April/2020. Items from the Somatic Symptom Scale, Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 were administered, as well as pandemic-specific questions. 1181 primarily married, retired females participated; Many had hypertension (n=521, 44.1%), coronary artery disease (CAD; n=201, 17.8%) and diabetes (n=171, 14.5%). While most respondents (n=868; 73.5%) were strictly following control measures (including limiting visits with children; n=390, 33.0%) and perceived they could tolerate that beyond 6 months (n=555;47.0%), they were optimistic about the future if control measures were continued (n=969;82.0%), and perceived impact would be temporary (n=646;64.7%). 52 of those with any condition (8.2%) and 19 of those without a condition (3.5%) reported the pandemic was impacting their health. Somatic symptoms were high (29.4+/-7.1/36), with Sleep & Cognitive symptoms highest. 24.4% and 18.9% of respondents had elevated depressive and anxious symptoms, respectively; greater distress was associated with lower income (p=0.018), having hypertension (p=0.001) and CAD (p<0.001), more negative perceptions of global COVID-19 control (p=0.004), COVID-19 spread (p≤0.001), impact on life and health (p<0.001), compliance with control measures (p<0.001), and shorter time control measures could be tolerated (p<0.001) in adjusted analyses. In the initial COVID-19 outbreak, most older adults were optimistic and resilient with regard to the epidemic and control measures. However, the distress of older adults is not trivial, particularly in those with health issues.
Objective To verify the impact (effect) of the COVID-19 pandemic on the rates of reporting of interpersonal violence against children aged 0-11 years old in Salvador, Bahia, from 2020 to 2021. Methods The study used two epidemiological approaches: a) temporal aggregation and b) an individual cross section, based on cases of interpersonal violence against children reported in SINAN from 2009 to 2021. Annual rates of reporting of interpersonal violence against children (per 10,000) and percentages were calculated according to different strata of each variable of interest. The temporal trend was analyzed using the simple linear regression method (R2=0.6955) applied to the rates from 2014 to 2019, the period in which they showed the most consistency. Results The rates of reporting of violence against children showed a large variation, with a mean of 4.7/10,000. In 2021, the rate was 7/10,000 (a 45.8% increase on the previous year). Regression analysis indicated a mean reduction of 0.337/10,000 a year, and expected rates of 4.62 and 4.28/10,000, respectively, for 2020 and 2021. Conclusion The occurrence of COVID-19 and, particularly, the increase in the number of reported cases of interpersonal violence against children in the second year of the pandemic in Bahia suggest that these events may be directly or indirectly related. More robust studies are needed to confirm this relationship.
Near-term probabilistic forecasts for infectious diseases such as COVID-19 and influenza play an important role in public health communication and policymaking. From 2013-2019, the FluSight challenge run by the Centers for Disease Control and Prevention invited researchers to develop and submit forecasts using influenza-like illness (ILI) as a measure of influenza burden. Here we examine how several statistical models and an autoregressive neural network model perform for forecasting ILI during the COVID-19 pandemic, where historical patterns of ILI were highly disrupted. We find that the autoregressive neural network model which forecasted ILI well pre-COVID still performs well for some locations and forecast horizons, but its performance is highly variable, and performs poorly in many cases. We found that a simple exponential smoothing statistical model is in the top half of ranked models we evaluated nearly 75% of the time. Our results suggest that even simple statistical models may perform as well as or better than more complex machine learning models for forecasting ILI during the COVID-19 pandemic. We also created an ensemble model from the limited set of time series forecast models we created here. The limited ensemble model was rarely the best or the worst performing model compared to the rest of the models assessed, confirming previous observations from other infectious disease forecasting efforts on the less variable and generally favorable performance of ensemble forecasts. Our results support previous findings that no single modeling approach outperforms all other models across all locations, time points, and forecast horizons, and that ensemble forecasting consortia such as the COVID-19 Forecast Hub and FluSight continue to serve valuable roles in collecting, aggregating, and ensembling forecasts using fundamentally disparate modeling strategies.
Objective: To investigate temporal trends, severe outcomes, and rebound among systemic autoimmune rheumatic disease (SARD) patients according to outpatient SARS-CoV-2 treatment. Methods: We performed a retrospective cohort study investigating outpatient SARS-CoV-2 treatments among SARD patients at Mass General Brigham (23/Jan/2022-30/May/2022). We identified SARS-CoV-2 infection by positive PCR or antigen test (index date=first positive test) and SARDs using diagnosis codes and immunomodulator prescription. Outpatient treatments were confirmed by medical record review. The primary outcome was hospitalization or death within 30 days following the index date. COVID-19 rebound was defined as documentation of negative then newly-positive SARS-CoV-2 tests. The association of any vs. no outpatient treatment with hospitalization/death was assessed using multivariable logistic regression. Results: We analyzed 704 SARD patients with COVID-19 (mean age 58.4 years, 76% female, 49% with rheumatoid arthritis). Treatment as outpatient increased over calendar time (p<0.001). A total of 426(61%) received outpatient treatment: 307(44%) with nirmatrelvir/ritonavir, 105(15%) with monoclonal antibodies, 5(0.7%) with molnupiravir, 3(0.4%) with outpatient remdesivir, and 6(0.9%) with combinations. There were 9/426 (2.1%) hospitalizations/deaths among those treated as outpatient compared to 49/278 (17.6%) among those with no outpatient treatment (adjusted odds ratio [aOR] 0.12, 0.05 to 0.25). 25/318 (8%) of patients who received oral outpatient treatment had documented COVID-19 rebound. Conclusion: Outpatient treatment was strongly associated with lower odds of severe COVID-19 compared to no outpatient treatment. At least 8% of SARD patients experienced COVID-19 rebound. These findings highlight the importance of outpatient COVID-19 treatment for SARD patients and the need for further research on rebound.
Background: Wrist-worn devices can keep track of a persons daily health status, including those likely to become infected with the SARS-CoV-2 virus. Technological solutions using mobile devices are being developed to predict the time course of COVID-19. Objective: In this proof-of-concept study, we use heart rate data to detect the first sign of infection in people who have been diagnosed with COVID-19 and to monitor the time-course of the illness. Methods: The heart-rate data were analysed using a multiplicative cascade driven by a Gaussian process. This provides two parameters, mean and standard deviation, which when combined with similar parameters estimated from control series, provide a Health Index. Results: For 90% of 31 cases, the Health Index tracked COVID-19 infection with the virus and subsequent recovery. The first sign of COVID-19 was detected on average nine days before symptoms were reported. Conclusions: Early detection of COVID-19 may lead to a reduction in the spread of the virus. The Heath Indexs potential use for the early detection of complications arising from Long COVID would be an important innovation.
Safety and Efficacy of Medications COVID-19 - Condition: Severe Covid-19
Intervention: Drug: Oral bedtime melatonin
Sponsor: Hospital San Carlos, Madrid
Completed
Use of Multiple Doses of Convalescent Plasma in Mechanically Intubated Patients With COVID-19 - Condition: COVID-19
Intervention: Biological: Multiple doses of anti-SARS-CoV-2 Convalescent Plasma
Sponsors: Hospital Regional Dr. Rafael Estévez; Complejo Hospitalario Dr. Arnulfo Arias Madrid; Hospital Santo Tomas; Hospital Punta Pacífica, Pacífica Salud; Insituto Conmemorativo Gorgas de Estudios para la Salud; Sociedad Panameña de Hematología; Institute of Scientific Research and High Technology Services (INDICASAT AIP); University of Panama; Sistema Nacional de Investigación de Panamá
Completed
Open Multicenter Study for Assessment of Efficacy and Safety of Molnupiravir in Adult Patients With COVID-19 - Condition: COVID-19
Interventions: Drug: Molnupiravir (Esperavir); Drug: Standard of care
Sponsor: Promomed, LLC
Completed
Open Multicentre Study of the Safety and Efficacy Against COVID-19 of Nirmatrelvir/Ritonavir in the Adult Population - Condition: COVID-19
Interventions: Drug: nirmatrelvir/ritonavir; Drug: Standard of care
Sponsors: Promomed, LLC; Sponsor GmbH
Completed
Effects of Respiratory Muscle Training in Individuals With Long-term Post-COVID-19 Symptoms - Conditions: Covid19; Post-acute COVID-19 Syndrome
Interventions: Other: Inspiratory + expiratory muscle training group; Other: Inspiratory + expiratory muscle training sham group; Other: Exercise training program
Sponsors: Universidad Complutense de Madrid; Colegio Profesional de Fisioterapeutas de la Comunidad de Madrid
Recruiting
Recombinant COVID-19 Vaccine (CHO Cell, NVSI-06-09) Phase III Clinical Trial - Conditions: COVID-19; Coronavirus Infections
Interventions: Biological: LIBP-Rec-Vaccine; Biological: BIBP-Rec-Vaccine; Biological: placebo
Sponsors: National Vaccine and Serum Institute, China; China National Biotec Group Company Limited; Lanzhou Institute of Biological Products Co., Ltd; Beijing Institute of Biological Products Co Ltd.
Not yet recruiting
Boost Intentions and Facilitate Action to Promote COVID-19 Booster Take-up - Conditions: COVID-19; Vaccines
Interventions: Behavioral: Eligibility reminder; Behavioral: Link to a narrow set of vaccine venues; Behavioral: Link to a broad set of vaccine venues; Behavioral: Doctors’ recommendation and value of vaccine
Sponsor: University of California, Los Angeles
Not yet recruiting
Effects of Prompt to Bundle COVID-19 Booster and Flu Shot - Conditions: COVID-19; Vaccines
Interventions: Behavioral: Reminder to boost protection against COVID-19; Behavioral: Flu Tag Along; Behavioral: COVID-19 Booster & Flu Bundle
Sponsor: University of California, Los Angeles
Not yet recruiting
Information Provision and Consistency Framing to Increase COVID-19 Booster Uptake - Conditions: COVID-19; Vaccines
Interventions: Behavioral: Reminder that facilitates action; Behavioral: Consistency framing; Behavioral: Information provision about the uniqueness of the bivalent booster; Behavioral: Information provision about bivalent booster eligibility; Behavioral: Information provision about the severity of COVID-19 symptoms
Sponsor: University of California, Los Angeles
Not yet recruiting
OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients: a Randomized Factorial Controlled Strategy Trial - Conditions: COVID-19; Immunodeficiency
Interventions: Drug: Paxlovid 5 days; Drug: Paxlovid 10 days; Drug: Tixagevimab and Cilgavimab
Sponsors: ANRS, Emerging Infectious Diseases; University Hospital, Geneva
Not yet recruiting
A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Combined Modified RNA Vaccine Candidates Against COVID-19 and Influenza - Conditions: Influenza, Human; COVID-19
Interventions: Biological: bivalent BNT162b2 (original/Omi BA.4/BA.5); Biological: qIRV (22/23); Biological: QIV
Sponsors: BioNTech SE; Pfizer
Not yet recruiting
Study to Evaluate Safety, Tolerability, Efficacy and Pharmacokinetics of ASC10 in Mild to Moderate COVID-19 Patients - Condition: SARS CoV 2 Infection
Interventions: Drug: ASC10; Drug: Placebo
Sponsor: Ascletis Pharmaceuticals Co., Ltd.
Not yet recruiting
COVID-19 MP Biomedicals SARS-CoV-2 Ag OTC: Clinical Evaluation - Conditions: SARS-CoV2 Infection; COVID-19
Interventions: Device: iCura COVID-19 Antigen Rapid Home Test; Device: RT-PCR Test
Sponsors: MP Biomedicals, LLC; EDP Biotech
Completed
COVID-19 MP Biomedicals Rapid SARS-CoV-2 Antigen Test Usability - Conditions: Sars-CoV-2 Infection; COVID-19
Intervention: Device: Rapid SARS-CoV-2 Antigen Test
Sponsors: MP Biomedicals, LLC; EDP Biotech
Completed
Nitric Oxide Nasal Spray (NONS) To Treat and Prevent the Exacerbation of Infection in Individuals With Mild COVID-19 - Condition: SARS-CoV-2 Infection
Intervention: Drug: Nitric Oxide
Sponsors: Sanotize Research and Development corp.; Glenmark Pharmaceuticals Ltd. India
Completed
Antiviral drug design based on structural insights into the N-terminal domain and C-terminal domain of the SARS-CoV-2 nucleocapsid protein - Nucleocapsid (N) protein plays crucial roles in the life cycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including the formation of ribonucleoprotein (RNP) complex with the viral RNA. Here we reported the crystal structures of the N-terminal domain (NTD) and C-terminal domain (CTD) of the N protein and an NTD-RNA complex. Our structures reveal a unique tetramer organization of NTD and identify a distinct RNA binding mode in the NTD-RNA complex, which could contribute to…
SARS-CoV-2 drives NLRP3 inflammasome activation in human microglia through spike protein - Coronavirus disease-2019 (COVID-19) is primarily a respiratory disease, however, an increasing number of reports indicate that SARS-CoV-2 infection can also cause severe neurological manifestations, including precipitating cases of probable Parkinson’s disease. As microglial NLRP3 inflammasome activation is a major driver of neurodegeneration, here we interrogated whether SARS-CoV-2 can promote microglial NLRP3 inflammasome activation. Using SARS-CoV-2 infection of transgenic mice expressing…
BC-11 is a covalent TMPRSS2 fragment inhibitor that impedes SARS-CoV-2 host cell entry - Host cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is facilitated via priming of its spike glycoprotein by the human transmembrane protease serine 2 (TMPRSS2). Although camostat and nafamostat are two highly potent covalent TMPRSS2 inhibitors, they nevertheless did not hold promise in COVID-19 clinical trials, presumably due to their short plasma half-lives. Herein, we report an integrative chemogenomics approach based on computational modeling and in vitro enzymatic…
High-Throughput Assay for Identifying Diverse Antagonists of the Binding Interaction between the ACE2 Receptor and the Dynamic Spike Proteins of SARS-CoV-2 - SARS-CoV-2, a coronavirus strain that started a worldwide pandemic in early 2020, attaches to human cells by binding its spike (S) glycoprotein to a host receptor protein angiotensin-converting enzyme 2 (ACE2). Blocking the interaction between the S protein and ACE2 has emerged as an important strategy for preventing viral infection. We systematically developed and optimized an AlphaLISA assay to investigate binding events between ACE2 and the ectodomain of the SARS-CoV-2 S protein (S-614G:…
25-Hydroxycholesterol Mediates Cholesterol Metabolism to Restrict Porcine Deltacoronavirus Infection via Suppression of Transforming Growth Factor β1 - Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus in pigs, is one of the major pathogens for lethal watery diarrhea in piglets and poses a threat to public health because of its potential for interspecies transmission to humans. 25-Hydroxycholesterol (25HC), a derivative of cholesterol, exhibits multiple potential modulating host responses to pathogens, including viruses and bacteria, as well as pathogen-induced inflammation, while its antiviral effect on PDCoV and how…
Generation of Angiotensin-Converting Enzyme 2/Transmembrane Protease Serine 2-Double-Positive Human Induced Pluripotent Stem Cell-Derived Spheroids for Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Drug Evaluation - We newly generated two human induced pluripotent stem cell (hiPSC)-derived spheroid lines, termed Spheroids_(4M)^(ACE2-TMPRSS2) and Spheroids_(15M63)^(ACE2-TMPRSS2), both of which express angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), which are critical for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Both spheroids were highly susceptible to SARS-CoV-2 infection, and two representative anti-SARS-CoV-2 agents, remdesivir and 5h…
Enhanced Inactivation of Pseudoparticles Containing SARS-CoV-2 S Protein Using Magnetic Nanoparticles and an Alternating Magnetic Field - Severe acute respiratory syndrome coronavirus 2’s (SARS-CoV-2) rapid global spread has posed a significant threat to human health, and similar outbreaks could occur in the future. Developing effective virus inactivation technologies is critical to preventing and overcoming pandemics. The infection of SARS-CoV-2 depends on the binding of the spike glycoprotein (S) receptor binding domain (RBD) to the host cellular surface receptor angiotensin-converting enzyme 2 (ACE2). If this interaction is…
Inosine: a broad-spectrum anti-inflammatory against SARS-CoV-2 infection-induced acute lung injury via suppressing TBK1 phosphorylation - SARS-CoV-2-induced cytokine storms constitute the primary cause of COVID-19 progression, severity, criticality, and death. Glucocorticoid and anti-cytokine therapies have been frequently administered to treat COVID-19 but have had limited clinical efficacy in severe and critical cases. Nevertheless, the weaknesses of these treatment modalities have prompted the development of anti-inflammatory therapy against this infection. We found that the broad-spectrum anti-inflammatory agent inosine…
In vitro effect of Withania somnifera, AYUSH-64, and remdesivir on the activity of CYP-450 enzymes: Implications for possible herb-drug interactions in the management of COVID-19 - Ayurvedic medicines Withania somnifera Dunal (ashwagandha) and AYUSH-64 have been used for the prevention and management of COVID-19 in India. The present study explores the effect of Ashwagandha and AYUSH-64 on important human CYP enzymes (CYP3A4, CYP2C8, and CYP2D6) to assess their interaction with remdesivir, a drug used for COVID-19 management during the second wave. The study also implies possible herb-drug interactions as ashwagandha and AYUSH-64 are being used for managing various…
Use of natural cysteine protease inhibitors in limiting SARS-Co-2 fusion into human respiratory cells - Specific antibodies that humans acquire as a result of disease or after vaccination are needed to effectively suppress infection with a specific variant of SARS CoV-2 virus. The S protein of the D614G variant of coronavirus is used as an antigen in known vaccines to date. It is known that COVID-19 disease resulting from infection with this coronavirus can often be very dangerous to the health and lives of patients. In contrast, vaccines produce antibodies against an older version of the protein…
Evaluation of 1,4-naphthoquinone derivatives as antibacterial agents: activity and mechanistic studies - The diverse and large-scale application of disinfectants posed potential health risks and caused ecological damage during the 2019-nCoV pandemic, thereby increasing the demands for the development of disinfectants based on natural products, with low health risks and low aquatic toxicity. In the present study, a few natural naphthoquinones and their derivatives bearing the 1,4-naphthoquinone skeleton were synthesized, and their antibacterial activity against selected bacterial strains was…
Effect of stimulated platelets in COVID-19 thrombosis: Role of alpha7 nicotinic acetylcholine receptor - Since early 2020, SARS-CoV-2-induced infection resulted in global pandemics with high morbidity, especially in the adult population. COVID-19 is a highly prothrombotic condition associated with subsequent multiorgan failure and lethal outcomes. The exact mechanism of the prothrombotic state is not well understood and might be multifactorial. Nevertheless, platelets are attributed to play a crucial role in COVID-19-associated thrombosis. To date, platelets’ role was defined primarily in…
Factors influencing the SARS-CoV-2 infection and vaccination induced immune response in rheumatoid arthritis - CONCLUSION: Our study showed that the SARS-CoV-2-specific antibody levels were substantially reduced in RA patients treated with TNF-α-inhibitors (N=51) and IL-6-inhibitor (N=15). In addition, anti-CD20 therapy (N=4) inhibited both SARS-CoV-2-induced humoral and cellular immune responses. Furthermore, the magnitude of humoral and cellular immune response was dependent on the age and decreased over time. The RNA vaccines and ChAdOx1s vaccine effectively increased the level of anti-S antibodies.
Impairment of antiviral immune response and disruption of cellular functions by SARS-CoV-2 ORF7a and ORF7b - SARS-CoV-2, the causative agent of the present COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome, and some have been implicated in facilitating infection and pathogenesis through their interaction with cellular components. Among these proteins, accessory protein ORF7a and ORF7b functions are poorly understood. In this study, A549 cells were transduced to express ORF7a and ORF7b, respectively, to explore more in depth the role of each accessory protein in the…
Common NLRP3 inflammasome inhibitors and Covid-19: Divide and conquer - Severe SARS-CoV-2 infection causes systemic inflammation, cytokine storm, and hypercytokinemia due to activation of the release of pro-inflammatory cytokines that have been associated with case-fatality rate. The immune overreaction and cytokine storm in the infection caused by SARS-CoV-2 may be linked to NLRP3 inflammasome activation which has supreme importance in human innate immune response mainly against viral infections. In SARS-CoV-2 infection, NLRP3 inflammasome activation results in the…