Background: Protection against SARS-CoV-2 symptomatic infection and severe COVID-19 of previous infection, mRNA two-dose vaccination, mRNA three-dose vaccination, and hybrid immunity of previous infection and vaccination were investigated in Qatar for the Alpha, Beta, and Delta variants. Methods: Six national, matched, test-negative, case-control studies were conducted between January 18-December 18, 2021 on a sample of 239,120 PCR-positive tests and 6,103,365 PCR-negative tests. Results: Effectiveness of previous infection against Alpha, Beta, and Delta reinfection was 89.5% (95% CI: 85.5-92.3%), 87.9% (95% CI: 85.4-89.9%), and 90.0% (95% CI: 86.7-92.5%), respectively. Effectiveness of two-dose BNT162b2 vaccination against Alpha, Beta, and Delta infection was 90.5% (95% CI, 83.9-94.4%), 80.5% (95% CI: 79.0-82.0%), and 58.1% (95% CI: 54.6-61.3%), respectively. Effectiveness of three-dose BNT162b2 vaccination against Delta infection was 91.7% (95% CI: 87.1-94.7%). Effectiveness of hybrid immunity of previous infection and two-dose BNT162b2 vaccination was 97.4% (95% CI: 95.4-98.5%) against Beta infection and 94.5% (95% CI: 92.8-95.8%) against Delta infection. Effectiveness of previous infection and three-dose BNT162b2 vaccination was 98.1% (95% CI: 85.7-99.7%) against Delta infection. All five forms of immunity had >90% protection against severe, critical, or fatal COVID-19 regardless of variant. Similar effectiveness estimates were observed for mRNA-1273. Conclusions: All forms of natural and vaccine immunity prior to Omicron introduction provided strong protection against infection and severe COVID-19. Hybrid immunity conferred the strongest protection and its level was consistent with previous-infection immunity and vaccine immunity acting independently of each other.
Background: The COVID-19 pandemic has highlighted the role of infectious disease forecasting in informing public policy. However, significant barriers remain for effectively linking infectious disease forecasts to public health decision making, including a lack of model validation. Forecasting model performance and accuracy should be evaluated retrospectively to understand under which conditions models were reliable and could be improved in the future. Methods: Using archived forecasts from the California Department of Public Health9s California COVID Assessment Tool (https://calcat.covid19.ca.gov/cacovidmodels/), we compared how well different forecasting models predicted COVID-19 hospitalization census across California counties and regions during periods of Alpha, Delta, and Omicron variant predominance. Results: Based on mean absolute error estimates, forecasting models had variable performance across counties and through time. When accounting for model availability across counties and dates, some individual models performed consistently better than the ensemble model, but model rankings still differed across counties. Local transmission trends, variant prevalence, and county population size were informative predictors for determining which model performed best for a given county based on a random forest classification analysis. Overall, the ensemble model performed worse in less populous counties, in part because of fewer model contributors in these locations. Conclusions: Ensemble model predictions could be improved by incorporating geographic heterogeneity in model coverage and performance. Consistency in model reporting and improved model validation can strengthen the role of infectious disease forecasting in real-time public health decision making.
SARS-CoV-2 in infected patient mainly display pulmonary and oronasal tropism however, the presence of the virus has also been demonstrated in stools of patients and consequently in wastewater treatment plant effluents, questioning the potential risk of environmental contamination (such as seawater contamination) through inadequately treated wastewater spill-over into surface or coastal waters. The environmental detection of RNA alone does not substantiate risk of infection, and evidence of an effective transmission is not clear where empirical observations are lacking. Therefore, here, we decided to experimentally evaluate the persistence and infectious capacity of the Porcine epidemic diarrhea virus (PEDv), considered as a coronavirus representative model and SARS-CoV-2 surrogate, in the coastal environment of France. Coastal seawater was collected, sterile-filtered, and inoculated with PEDv before incubation for 0–4 weeks at four temperatures representative of those measured along the French coasts throughout the year (4, 8, 15, and 24°C). The decay rate of PEDv was determined using mathematical modeling and was then used to determine the half-life of the virus along the French coast in accordance with temperatures from 2000 to 2021. We experimentally observed an inverse correlation between seawater temperature and the persistence of infectious viruses in seawater and confirm that the risk of transmission of infectious viruses from contaminated stool in wastewater to seawater during recreational practices is very limited. The present work represents a good model to assess the risk of transmission of not only SARS-CoV-2 but may also be used to model the risk of other coronaviruses, specifically enteric coronaviruses.
It is widely acknowledged that vaccinating at maximal effort in the face of an ongoing epidemic is the best strategy to minimise infections and deaths from the disease. Despite this, no one has proved that this is guaranteed to be true if the disease follows multi-group SIR (Susceptible-Infected-Recovered) dynamics. This paper provides a novel proof of this principle for the existing SIR framework, showing that the total number of deaths or infections from an epidemic is decreasing in vaccination effort. Furthermore, it presents a novel model for vaccination which assumes that vaccines are distributed randomly to the unvaccinated population and suggests, using COVID-19 data, that this more accurately captures vaccination dynamics than the model commonly found in the literature. However, as the novel model provides a strictly larger set of possible vaccination policies, the results presented in this paper hold for both models.
The COVID-19 pandemic further exacerbated disruptions to elective care services in the UK, leading to longer waits for treatment and a growing elective surgery backlog. There have been growing calls for the creation of surgical hubs to help reduce this backlog. Surgical hubs aim to increase surgical capacity by providing quicker access to procedures, as well as facilitate infection control by segregating patients and staff from emergency care. This rapid review aimed to assess the effectiveness, efficiency, and acceptability of surgical hubs in supporting planned care activity, to inform the implementation of these hubs in Wales. The review identified evidence available up until January 2023. Twelve primary studies were included, eight of which used comparative methods. Most of the studies were conducted during the COVID-19 pandemic and described surgical hubs designed mainly to mitigate the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Outcome measures reported included clinical, performance, economic, and patient reported outcomes across a variety of different surgical disciplines. Most of the studies did not describe surgical hubs based on their structure, i.e., standalone, integrated, or ring-fenced hubs. The evidence relating to the impact of surgical hubs on clinical outcomes appeared to be heterogenous and limited. Included studies did not appear to control for the impact of the COVID-19 pandemic on outcomes. Evidence of the impact of surgical hubs on performance outcomes such as efficiency, utilisation/usage, volume of surgeries/treatments, performance, cancellations, and time from diagnosis to treatment is limited. Evidence relating to the economic impact of surgical hubs is also limited, however there is evidence to suggest that total average costs are lower in surgical hubs when compared to general hospitals. Evidence relating to the impact of surgical hubs on patient reported outcomes is limited but indicates there may be a positive effect on patient satisfaction and compliance. Considerable variation in the types of surgical hubs reviewed, surgical disciplines, along with the small number of comparative studies, as well as methodological limitations across included studies, could limit the applicability of these findings.
Background: Whether COVID-19 has had a disproportionate impact on mortality among persons with diagnosed HIV (PWDH) in United States is unclear. Through our macro-scale analysis, we seek to better understand how COVID-19 and subsequent behavioral changes affected mortality among PWDH. Methods: We obtained mortality and population size data for the years 2018-2020 from the National HIV Surveillance System (NHSS) for the PWDH population aged ≥13 years in the United States, and from publicly available data for the general population. We computed mortality rates and excess mortality for both the general and PWDH populations. Stratifications by age, race/ethnicity, and sex-at birth were considered. For each group, we determined whether the 2020 mortality rates and mortality risk ratio showed a statistically significant change from 2018-2019. Results: Mortality rates increased in 2020 from 2018-2019 across the general population in all groups. Among PWDH, mortality rates either increased, or showed no statistically significant change. The mortality risk ratio between PWDH and the general population decreased 7.7% in 2020. Approximately 1550 excess deaths occurred among PWDH in 2020, with Black, Hispanic/Latino and PWDH above 55 and older representing the majority of excess deaths. Conclusions: While mortality rates among PWDH increased in 2020 relative to 2018-2019, the increases were smaller than those observed in the general population. This suggests that COVID-19 and resulting behavioral changes among PWDH did not result in disproportionate mortality among PWDH. These findings suggest that COVID-19, and any associated indirect effects, do not represent a proportionally greater risk for PWDH compared to the general population.
Effectiveness and Safety of Quinine Sulfate as add-on Therapy for COVID-19 in Hospitalized Adults in Indonesia ( DEAL-COVID19 ) - Condition: COVID-19
Interventions: Drug: Standard of Care + Quinine Sulfate; Drug: Standard of Care
Sponsors: Universitas Padjadjaran; National Research and Innovation Agency of Indonesia; Prodia Diacro Laboratories P.T.
Recruiting
Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Exosomes in Treating Chronic Cough After COVID-19 - Condition: Long COVID-19 Syndrome
Intervention: Biological: MSC-derived exosomes
Sponsors: Huazhong University of Science and Technology; REGEN-αGEEK (SHENZHEN) MEDICAL TECHNOLOGY CO., LTD.
Recruiting
Efficacy and Safety of Nirmatrelvir/Ritonavir for Treating Omicron Variant of COVID-19 - Condition: Omicron Variant of COVID-19
Intervention: Drug: Nirmatrelvir/Ritonavir
Sponsor: Xiangao Jiang
Completed
A Study of mRNA-1283.222 Injection Compared With mRNA-1273.222 Injection in Participants ≥12 Years of Age to Prevent COVID-19 - Condition: COVID-19
Interventions: Biological: mRNA-1283.222; Biological: mRNA-1273.222
Sponsor: ModernaTX, Inc.
Recruiting
To Evaluate the Safety and Efficacy of Meplazumab in Treatment of COVID-19 Sequelae - Condition: COVID-19
Interventions: Biological: Meplazumab for injection; Other: Normal saline
Sponsor: Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd
Recruiting
Evaluation of the RD-X19 Treatment Device in Individuals With Mild COVID-19 - Condition: COVID-19
Interventions: Device: RD-X19; Device: Sham
Sponsor: EmitBio Inc.
Recruiting
Clinical Study for the Efficacy and Safety of Ropeginterferon Alfa-2b in Adult COVID-19 Patients With Comorbidities - Condition: COVID-19
Interventions: Drug: Ropeginterferon alfa-2b; Procedure: SOC
Sponsor: National Taiwan University Hospital
Not yet recruiting
Assessment of Immunogenicity, Safety and Reactogenicity of a Booster Dose of Various COVID-19 Vaccine Platforms in Individuals Primed With Several Regimes. - Condition: COVID-19
Interventions: Biological: SCB-2019/Clover; Biological: AstraZeneca/Fiocruz; Biological: Pfizer/Wyeth
Sponsors: D’Or Institute for Research and Education; Bill and Melinda Gates Foundation
Active, not recruiting
Postoperative Sugammadex After COVID-19 - Conditions: General Anesthesia; COVID-19
Interventions: Drug: Sugammadex Sodium; Drug: neostigmine 50µg/kg + glycopyrollate 0.01mg/kg
Sponsor: Korea University Ansan Hospital
Not yet recruiting
A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study to Determine the Safety and Effectiveness of Azeliragon in the Treatment of Patients Hospitalized for Coronavirus Disease 2019 (COVID-19) - Condition: COVID-19
Interventions: Drug: Azeliragon; Drug: Placebo
Sponsor: Salim S. Hayek
Recruiting
Cognitive-behavioral Therapy for Mental Disorder in COVID-19 Survivors - Condition: Post Acute COVID-19 Syndrome
Intervention: Behavioral: mindfulness-based stress reduction (MBSR) and cognitive behavioral therapy (CBT)
Sponsor: Azienda Socio Sanitaria Territoriale di Lecco
Recruiting
Efficacy of Lactobacillus Paracasei PS23 for Patients With Post-COVID-19 Syndrome - Condition: Post-COVID-19 Syndrome
Intervention: Dietary Supplement: PS23 heat-treated
Sponsors: Mackay Memorial Hospital; Bened Biomedical Co., Ltd.
Recruiting
Exploring the Effect of Video Interventions on Intentions for Continued COVID-19 Vaccination - Conditions: Vaccine Refusal; COVID-19
Interventions: Behavioral: Informational Video; Behavioral: Altruistic Video; Behavioral: Individualistic Video
Sponsor: Sir Mortimer B. Davis - Jewish General Hospital
Not yet recruiting
Effect of Telerehabilitation Practice in Long COVID-19 Patients - Conditions: Long COVID-19; Long COVID; Post COVID-19 Condition; Post-COVID-19 Syndrome; Post-COVID Syndrome
Interventions: Behavioral: Telerehabilitation; Behavioral: Standard rehabilitation care
Sponsor: Indonesia University
Recruiting
Rehabilitation Treatment of Patients With COVID-19 - Conditions: Rehabilitation; Pneumonia, Viral; COVID-19; Quality of Life
Interventions: Other: exercises; Other: massage
Sponsors: I.M. Sechenov First Moscow State Medical University; MEDSI Clinical Hospital 1, ICU
Completed
Antiviral activities of hemp cannabinoids - Hemp is an understudied source of pharmacologically active compounds and many unique plant secondary metabolites including more than 100 cannabinoids. After years of legal restriction, research on hemp has recently demonstrated antiviral activities in silico, in vitro, and in vivo for cannabidiol (CBD), Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), and several other cannabinoids against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), human…
Prospecting native and analogous peptides with anti-SARS-CoV-2 potential derived from the trypsin inhibitor purified from tamarind seeds - The study aimed to prospect in silico native and analogous peptides with anti-SARS-CoV-2 potential derived from the trypsin inhibitor purified from tamarind seeds (TTIp). From the most stable theoretical model of TTIp (TTIp 56/287), in silico cleavage was performed for the theoretical identification of native peptides and generation of analogous peptides. The anti-SARS-CoV-2 potential was investigated through molecular dynamics (MD) simulation between the peptides and binding sites of…
Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19 - Rhinoviruses and allergens, such as house dust mite are major agents responsible for asthma exacerbations. The influence of pre-existing airway inflammation on the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely unknown. We analyse mechanisms of response to viral infection in experimental in vivo rhinovirus infection in healthy controls and patients with asthma, and in in vitro experiments with house dust mite, rhinovirus and SARS-CoV-2 in human primary…
Kv1.3 blockade by ShK186 modulates CD4+ effector memory T-cell activity of patients with Granulomatosis with polyangiitis - CONCLUSIONS: Modulation of cellular effector function by ShK-186 may constitute a novel treatment strategy for GPA with high specificity and less harmful side effects.
Kinetics and ability of binding antibody and surrogate virus neutralization tests to predict neutralizing antibodies against the SARS-CoV-2 Omicron variant following BNT162b2 booster administration - CONCLUSIONS: This study showed a significant drop in humoral immunity 6 months after booster administration. Anti-RBD IgG and Omicron sVNT assays were highly correlated and could predict neutralizing activity with moderate performance.
MHC class I links with severe pathogenicity in C57BL/6N mice infected with SARS-CoV-2/BMA8 - CONCLUSIONS: Taken together, our work shows that host MHC molecules play a crucial role in the pathogenicity differences of SARS-CoV-2/BMA8 infection. This provides a more profound insight into the pathogenesis of SARS-CoV-2, and contributes enlightenment and guidance for controlling the virus spread.
Discovery and structural characterization of monkeypox virus methyltransferase VP39 inhibitors reveal similarities to SARS-CoV-2 nsp14 methyltransferase - Monkeypox is a disease with pandemic potential. It is caused by the monkeypox virus (MPXV), a double-stranded DNA virus from the Poxviridae family, that replicates in the cytoplasm and must encode for its own RNA processing machinery including the capping machinery. Here, we present crystal structures of its 2’-O-RNA methyltransferase (MTase) VP39 in complex with the pan-MTase inhibitor sinefungin and a series of inhibitors that were discovered based on it. A comparison of this 2’-O-RNA MTase…
Synthesis of SARS-CoV-2 Mpro inhibitors bearing a cinnamic ester warhead with in vitro activity against human coronaviruses - COVID-19 now ranks among the most devastating global pandemics in history. The causative virus, SARS-CoV-2, is a new human coronavirus (hCoV) that spreads among humans and animals. Great efforts have been made to develop therapeutic agents to treat COVID-19, and among the available viral molecular targets, the cysteine protease SARS-CoV-2 M^(pro) is considered the most appealing one due to its essential role in viral replication. However, the inhibition of M^(pro) activity is an interesting…
Diosmetin alleviates acute lung injury caused by lipopolysaccharide by targeting barrier function - Acute lung injury (ALI) is an acute and devastating disease caused by systemic inflammation e.g. patients infected with bacteria and viruses such as SARS-CoV-2 have an unacceptably high mortality rate. It has been well documented that endothelial cell damage and repair play a central role in the pathogenesis of ALI because of its barrier function. Nevertheless, the leading compounds that effectively accelerate endothelial cell repair and improve barrier dysfunction in ALI are largely unknown. In…
Molecular Networking Accelerated Discovery of Biflavonoid Alkaloids from Cephalotaxus sinensis - Four undescribed biflavonoid alkaloids, sinenbiflavones A-D, were isolated from Cephalotaxus sinensis using a MS/MS-based molecular networking guided strategy. Their structures were elucidated by series of spectroscopic methods (HRESIMS, UV, IR, 1D, and 2D NMR). Sinenbiflavones A-D are the first examples of amentoflavone-type (C-3’-C-8’’) biflavonoid alkaloids. Meanwhile, sinenbiflavones B and D are the unique C-6-methylated amentoflavone-type biflavonoid alkaloids. Sinenbiflavone D showed weak…
Integrin β1 is a key determinant of the expression of angiotensin-converting enzyme 2 (ACE2) in the kidney epithelial cells - The expression of the angiotensin-converting enzyme 2 (ACE2) is altered in multiple chronic kidney diseases like hypertension and renal fibrosis, where the signaling from the basal membrane proteins is critical for the development and progression of the various pathologies. Integrins are heterodimeric cell surface receptors that have important roles in the progression of these chronic kidney diseases by altering various cell signaling pathways in response to changes in the basement membrane…
Myeloperoxidase Inhibition in Heart Failure With Preserved or Mildly Reduced Ejection Fraction: SATELLITE Trial Results - CONCLUSIONS: AZD4831 inhibited myeloperoxidase and was well tolerated in patients with HF and LVEF ≥40%. Efficacy findings were exploratory due to early termination but warrant further clinical investigation of AZD4831.
Awareness raising and dealing with methanol poisoning based on effective strategies - Intoxication with methanol most commonly occurs as a consequence of ingesting, inhaling, or coming into contact with formulations that include methanol as a base. Clinical manifestations of methanol poisoning include suppression of the central nervous system, gastrointestinal symptoms, and decompensated metabolic acidosis, which is associated with impaired vision and either early or late blindness within 0.5-4 h after ingestion. After ingestion, methanol concentrations in the blood that are…
Ferrocenoyl-substituted quinolinone and coumarin as organometallic inhibitors of SARS-CoV-2 3CLpro main protease - The 3-chymotrypsin-like protease 3CLpro from SARS-CoV-2 is a potential target for antiviral drug development. In this work, three organometallic ferrocene-modified quinolinones and coumarins were compared to their benzoic acid ester analogues with regard to inhibition of 3CLpro using a HPLC-based assay with a 15mer model peptide as the substrate. In contrast to FRET-based assays, this allows direct identification of interference of buffer constituents with the inhibitors, as demonstrated by the…
Transcription factor Dmrt1 triggers the SPRY1-NF-κB pathway to maintain testicular immune homeostasis and male fertility - Bacterial or viral infections, such as Brucella, mumps virus, herpes simplex virus, and Zika virus, destroy immune homeostasis of the testes, leading to spermatogenesis disorder and infertility. Of note, recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells, leading to male reproductive dysfunction. Due to the many side effects associated with antibiotic therapy, finding alternative treatments for inflammatory injury remains critical. Here, we found…