Population-representative estimates of SARS-CoV-2 infection prevalence and antibody levels in specific geographic areas at different time points are needed to optimise policy responses. However, even population-wide surveys are potentially impacted by biases arising from differences in participation rates across key groups. Here, we use spatio-temporal regression and post-stratification models to UKs national COVID-19 Infection Survey (CIS) to obtain representative estimates of PCR positivity (6,496,052 tests) and antibody prevalence (1,941,333 tests) for different regions, ages and ethnicities (7-December-2020 to 4-May-2022). Not accounting for vaccination status through post-stratification led to small underestimation of PCR positivity, but more substantial overestimations of antibody levels in the population (up to 21%), particularly in groups with low vaccine uptake in the general population. There was marked variation in the relative contribution of different areas and age-groups to each wave. Future analyses of infectious disease surveys should take into account major drivers of outcomes of interest that may also influence participation, with vaccination being an important factor to consider.
Bivalent COVID-19 vaccines were introduced in 2022 but knowledge of how their effectiveness against severe COVID-19 outcomes is sustained over time is currently limited. In Finnish register-based cohort analyses, we compared the risk of severe COVID-19 outcomes among those who received bivalent vaccination (exposed) between 1 September 2022 and 31 January 2023 to those who did not (unexposed). Among elderly aged 65-120 years, bivalent vaccination reduced the risk of hospitalisation and death due to COVID-19. Among the elderly the hazard ratios comparing exposed and unexposed ranged from 0.36 to 0.43 during the first 14-30 days since bivalent vaccination but signs of waning were observed as soon as two months after vaccination. Among the chronically ill aged 18-64 years bivalent vaccination did not reduce the risk of severe COVID-19 outcomes. These results are crucial for further developing COVID-19 vaccination programme worldwide.
Objective: To assess the real-world effectiveness of molnupiravir (MOL) in reducing the need for hospitalization in at-risk, non-hospitalized patients with confirmed COVID-19. Methods: A single-center, non-randomized, observational retrospective study of non-hospitalized patients with confirmed COVID-19 treated at the Clinic for Infectious and Tropical Diseases, University Clinical Center in Belgrade, Serbia. Results: Between December 15th, 2021, and February 15th, 2022, 320 patients were eligible for inclusion in the study. Of these, 165 received treatment with molnupiravir (51.6%), while both groups were similar in gender and age distribution. The treatment group had a higher proportion of vaccination (75.2% vs. 51%, p<0.001) but was similar to the control group in terms of multiple comorbidity predomination (65.5% vs. 65.2%, p 0.956). The majority of patients who received MOL did not require hospitalization (92.7 vs. 24.5%, p<0.001) and needed oxygen supplementation less frequently than those in the control group (0.6% vs. 31%, p<0.001). During the follow-up period of 12.12 +/- 3.5 days, none of the patients on MOL were admitted to the Intensive Care Unit (vs. 10.3%, p<0.001). Molnupiravir significantly reduced the risk of hospitalization by 97.9% (HR 0.021, p<0.001). Conclussion: Our study has proven the effectiveness of molnupiravir in preventing hospitalization in a population at risk for developing severe forms of COVID-19. Keywords: Molnupiravir; COVID-19;
Background: Systematic screening is a potential tool for reducing the prevalence of tuberculosis and counteracting COVID-related disruptions in care. Repeated community-wide screening can also measure changes in the prevalence of tuberculosis over time. Methods: We conducted serial, cross-sectional tuberculosis case-finding campaigns in one community in Kampala, Uganda, in 2019 and 2021. Both campaigns sought sputum for tuberculosis testing (Xpert MTB/RIF Ultra) from all adolescents and adults. We estimated the prevalence of tuberculosis among screening participants in each campaign and compared characteristics of people with tuberculosis across campaigns. We simultaneously enrolled and characterized community residents who were diagnosed with tuberculosis through routine care and assessed trends in facility-based diagnosis. Results: We successfully screened 12,033 community residents (35% of the estimated adult/adolescent population) in 2019 and 11,595 (33%) in 2021. In 2019, 0.94% (95% CI 0.77-1.13%) of participants tested Xpert-positive (including trace). This proportion fell to 0.52% (95%CI 0.40-0.67%) in 2021; the prevalence ratio was 0.55 [95%CI: 0.40-0.75]). There was no change in the age (median 26 vs 26), sex (56% vs 59% female), or prevalence of chronic cough (49% vs 54%) among those testing positive. By contrast, the rate of routine facility-based diagnosis remained steady in the eight months before each campaign (210 [95%CI 155-279] vs. 240 [95%CI 181-312] per 100,000 per year). Conclusions: Following an intensive initial case-finding campaign in an urban Ugandan community in 2019, the burden of prevalent tuberculosis as measured by systematic screening had decreased by 45% in 2021, despite the intervening COVID-19 pandemic.
Background: To investigate the etiology and clinical characteristics of community-acquired pneumonia (CAP) among children requiring bronchoalveolar lavage (BAL) and analyze the impact of the coronavirus disease 2019 (COVID-19) pandemic on the pathogen spectrum and clinical manifestations. Methods: Children <14 years old hospitalized with CAP requiring BLA were enrolled between February 2019 to January 2020 and August 2021 to July 2022. Multiplex reverse transcription polymerase chain reaction (mRT-PCR) was used for pathogen detection. The demographic and clinical characteristics were compared between different pathogen-type infection groups, and before and during the COVID-19 pandemic. Results: Pathogen was detected in 91.66% (1363/1487) children. Mycoplasma pneumoniae, adenovirus and human rhinovirus were the most frequently detected pathogens. The frequency of detection of virus infections and co-infections was decreased during the pandemic, but the detection of atypical bacterial infections was increased. The clinical manifestations and the results of CT scans and fiberoptic bronchoscopy showed a significant difference between different types of pathogen infection, and lung inflammation was reduced during the COVID-19 pandemic compared with before the pandemic. Conclusions: M. pneumoniae infection might be the greatest pediatric disease burden leading to CAP in northern China. Wearing masks and social distancing in public places during the COVID-19 pandemic effectively reduced the transmission of respiratory viruses, but it did not reduce the infection rate of M. pneumoniae. In addition, these interventions significantly reduced lung inflammation in children compared with before the pandemic.
The wastewater-based epidemiology (WBE) of SARS-CoV-2 is a quick and cost-effective method of tracking virus transmission. However, few studies reported on campus or in academic or residential settings worldwide. In this study, we demonstrated the WBE approach to detect, monitor, and evaluate genomic variants of SARS-CoV-2 fragments in a sewage treatment plant (STP) located on the campus of CSIR National Chemical Laboratory, Pune, India. Herein we describe the early warning capability of WBE, with viral load rise in campus sewage water up to 14 days before its clinical detection. This was supported further by a significant correlation between SARS-CoV-2 RNA concentration and clinically reported COVID-19 cases on campus. Additionally, we comprehended the probable targets missed by the quantitative qRT-PCR using amplicon-based sequencing due to low viral load. The analysis revealed the presence of signature mutations of the Omicron (S:N679K, S:N764K, S:D796Y, N:P13L, ORF1a:T3255I, ORF1a:K856R, ORF1a:P3395H, and N:S413R) before the lineage was first detected globally. Further, we used Lineage decomposition (LCS) tool to detect the Variant of Concern (VOC)/Variant of Interest (VOI) signals upto a month earlier in sewage water samples. The analysis also indicated the transition of lineage from Delta to Omicron in late Decemeber,2021. This is the first study in India highlighting the use of on-campus STP to evaluate the local spread of SARS-CoV-2, which could aid in preventing COVID-19 in academic institutes/universities. This study proves the usefulness of WBE as an early warning system for detecting, tracking and tracing VOCs using the sequencing approach. The current study could aid in taking critical decisions to tackle the pandemic scenario on campus.
Background: Oral nirmatrelvir/ritonavir is a treatment for COVID-19, but whether treatment during the acute phase reduces the risk of developing Long COVID is unknown. Methods: Using the Covid Citizen Science (CCS) online cohort, we surveyed individuals who reported their first SARS-CoV-2 positive test between March and August 2022 regarding Long COVID symptoms. We excluded those who were pregnant, unvaccinated, hospitalized for COVID-19, or received other antiviral therapy. The primary exposure was oral nirmatrelvir/ritonavir. The primary outcome was the presence of any Long COVID symptoms reported on cross-sectional surveys in November and December 2022. We used propensity-score models and inverse probability of treatment weighting to adjust for differences in treatment propensity. Our secondary question was whether symptom or test positivity rebound were associated with Long COVID. Results: 4684 individuals met the eligibility criteria, of whom 988 (21.1%) were treated and 3696 (78.9%) were untreated; 353/988 (35.7%) treated and 1258/3696 (34.0%) untreated responded to the survey. Median age was 55 years and 66% were female. We did not identify an association between nirmatrelvir/ritonavir treatment and Long COVID symptoms (OR 1.15; 95%CI 0.80-1.64). Among n=666 treated with nirmatrelvir/ritonavir who responded who responded to questions about rebound, rebound symptoms or test positivity were not associated with Long COVID symptoms (OR 1.34; 95%CI 0.74-2.41; p=0.33). Conclusions: Within this cohort, treatment with nirmatrelvir/ritonavir among vaccinated, non-hospitalized individuals was not associated with lower prevalence of Long COVID symptoms or severity of Long COVID. Experiencing rebound symptoms or test positivity is not strongly associated with developing Long COVID.
Background Observational research studies have shown that even after the acute phase, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect patients, and increase the risk of cardiovascular, mental, metabolic, and other disorders. However, the spectrum of diseases for individuals with a genetic predisposition to COVID-19 remains unclear. Methods We leveraged individual-level data from UK Biobank to implement a phenome-wide association study to explore the relationships between COVID-19 and 1061 diseases. Then, the inverse-variance weighted (IVW) method was adopted with summary-level data from global consortiums as sensitivity analyses combined with other MR methods with different model assumptions to identify robust associations. Findings The PheWAS found severe respiratory, hospitalized, and susceptibility COVID-19 had detrimental effects on 36, 37, and 51 kinds of diseases, separately. The IVW test found severe respiratory COVID-19 had detrimental effects on breast cancer [OR 95% CI: 1.065 (1.000-1.133) ], pan-cancer [OR 95% CI: 1.002 (1.000-1.004) ], and Alzheimer9s disease [OR 95% CI: 1.042 (1.005-1.081) ], etc. Hospitalized COVID-19 had detrimental effects on ischemic stroke (IS) [OR 95%CI: 1.049 (1.001-1.100) ], breast cancer [OR 95%CI: 1.139 (1.011-1.283) ], and pan-cancer [OR 95%CI: 1.003 (1.000-1.006) ], etc. Susceptibility COVID-19 had detrimental effects on deep vein thrombosis (DVT) of lower extremities [OR 95%CI: 2.392 (1.167-4.902) ], venous thromboembolism [OR 95%CI: 1.962 (1.115-3.453) ], pulmonary heart disease/diseases of pulmonary circulation [OR 95%CI: 1.767 (1.142-2.733) ], IS (large artery atherosclerosis) [OR 95%CI: 1.405 (1.025-1.927) ], myocardial infarction [OR 95%CI: 1.235 (1.012-1.509) ], heart failure [OR 95%CI: 1.140 (1.009-1.287) ], etc. Interpretation This study describes the extensive link between genetically determined COVID-19 and a broad range of diseases, especially those of the circulatory system, neuropsychiatric system, neoplasms, immune system, and digestive systems. Early detection and management of post-COVID-19 conditions could be tremendously beneficial to public health.
Exercise Training Six-Months After Discharge in Post-COVID-19 Syndrome - Condition: COVID-19 Pneumonia
Intervention: Other: Aerobic exercise and strength training
Sponsor: Ukbe Sirayder
Completed
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm C (Fluticasone) - Condition: Covid19
Interventions: Drug: Fluticasone; Other: Placebo
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Completed
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm A (Ivmermectin 400) - Condition: Covid19
Interventions: Drug: Ivermectin; Other: Placebo
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Completed
Counter-Regulatory Hormonal and Stress Systems in Patients With COVID-19 - Condition: COVID-19
Intervention: Diagnostic Test: Blood sampling
Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Completed
Exploratory Efficacy of N-Acetylcysteine in Patients With History of COVID-19 - Condition: COVID-19
Interventions: Drug: N-Acetylcysteine; Drug: Placebo
Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Active, not recruiting
A Specific miRNA Encoded by SARS-CoV-2 as a Diagnostic Tool to Predict Disease Severity in COVID-19 Patients - Condition: COVID-19
Intervention: Diagnostic Test: miRNA analysis in plasma
Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Completed
Telerehabilitation in the Post-COVID-19 Patient (TRIALS) - Condition: Post-COVID-19 Syndrome
Intervention: Other: Telerehabilitation program
Sponsor: Istituto Auxologico Italiano
Recruiting
Effect of Selected Types of Breathing Exercises on Different Outcome Measures in Covid-19 Patients - Condition: COVID-19
Intervention: Other: breathing exercise
Sponsor: Basma Mosaad Abd-elrahman Abushady
Completed
Application and Research of Mesenchymal Stem Cells in Alleviating Severe Development of COVID-19 Infection - Condition: COVID-19
Interventions: Biological: Umbilical cord mesenchymal stem cells implantation; Other: Comparator
Sponsor: Hebei Medical University
Recruiting
Immunogenicity and Reactogenicity of the Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine - Conditions: Vaccine Reaction; COVID-19
Interventions: Biological: Comirnaty® BNT162b2 /Omicron BA.4-5 vaccine (Pfizer-BioNTech); Biological: VidPrevtyn® Beta vaccine (Sanofi/GSK)
Sponsors: Assistance Publique - Hôpitaux de Paris; IREIVAC/COVIREIVAC Network
Not yet recruiting
Study of WPV01 Compared With Placebo in Patients With Mild/Moderate COVID-19 Infection - Condition: COVID-19 Infection
Interventions: Drug: WPV01; Drug: Placebo
Sponsor: Westlake Pharmaceuticals (Hangzhou) Co., Ltd.
Not yet recruiting
ARVAC-A New Recombinant Coronavirus Disease 2019 (COVID-19) - Condition: COVID-19 Vaccine
Interventions: Biological: Gamma Variant RBD-based ARVAC-CG vaccine; Biological: Omicron Variant RBD-based ARVAC-CG vaccine; Biological: Bivalent RBD-based ARVAC-CG vaccine; Other: Placebo
Sponsors: Mónica Edith Lombardo; Universidad Nacional de San Martín (UNSAM); National Council of Scientific and Technical Research, Argentina; Laboratorio Pablo Cassará S.R.L.
Recruiting
A Study of HH-120 Nasal Spray in Close Contacts of Those Diagnosed With COVID-19 - Conditions: COVID-19; SARS-CoV-2 Infection
Intervention: Drug: HH-120 Nasal Spray
Sponsor: Beijing Ditan Hospital
Completed
Mitigating Mental and Social Health Outcomes of COVID-19: A Counseling Approach - Conditions: Social Determinants of Health; Mental Health Issue; COVID-19
Interventions: Other: Individual Counseling; Other: Group Counseling; Other: Resources
Sponsors: New Mexico State University; National Institutes of Health (NIH)
Not yet recruiting
A Phase 1/2 Study to Assess the Safety and Immunogenicity of JCXH-221, an mRNA-based Broadly Protective COVID-19 Vaccine - Conditions: COVID-19; Infectious Disease
Interventions: Biological: JCXH-221; Biological: Active Comparator; Other: Placebo
Sponsors: Immorna Biotherapeutics, Inc.; ICON plc
Not yet recruiting
Vitamin C promotes ACE2 degradation and protects against SARS-CoV-2 infection - ACE2 is a major receptor for cellular entry of SARS-CoV-2. Despite advances in targeting ACE2 to inhibit SARS-CoV-2 binding, strategies to flexibly and sufficiently reduce ACE2 levels for the prevention of SARS-CoV-2 infection have not been explored. Here, we reveal vitamin C (VitC) administration as a potent strategy to prevent SARS-CoV-2 infection. VitC reduces ACE2 protein levels in a dose-dependent manner, while even a partial reduction in ACE2 levels can greatly inhibit SARS-CoV-2…
Low hanging fruit for combatting SARS-CoV-2? - Entry of SARS-CoV-2 into human respiratory cells, mediated by the spike protein, is absolutely dependent on the cellular receptor ACE2 (angiotensin-converting enzyme-2). This makes ACE2 an attractive target for therapeutic intervention in COVID-19. In this issue, Zuo et al. discover that vitamin C, an essential nutrient and common dietary supplement, can target ACE2 for ubiquitin-dependent degradation, resulting in the inhibition of SARS-CoV-2 infection (Zuo et al, 2023). The study identifies…
Comparison of Anakinra and Tocilizumab in Anticytokine Therapy in the Treatment of Coronavirus Disease-2019 - CONCLUSION: We observed the positive effects of the use of tocilizumab on clinical improvement in the early period; mechanical ventilation requirement was delayed and at a lower rate. Anakinra treatment did not change mortality and PaO(2)/FiO(2) rates. Mechanical ventilation requirements occurred earlier in the patients who were not receiving any anticytokine therapy. Studies with larger patient populations are needed to demonstrate the potential efficacy of anticytokine therapy.
Transcriptome and metabolome profiling unveils the mechanisms of naphthalene acetic acid in promoting cordycepin synthesis in Cordyceps militaris - Cordycepin, an important active substance in Cordyceps militaris, possesses antiviral and other beneficial activities. In addition, it has been reported to effectively promote the comprehensive treatment of COVID-19 and thus has become a research hotspot. The addition of naphthalene acetic acid (NAA) is known to significantly improve the yield of cordycepin; however, its related molecular mechanism remains unclear. We conducted a preliminary study on C. militaris with different concentrations of…
Determining the Optimal SARS-CoV-2 mRNA Vaccine Dosing Interval for Maximum Immunogenicity - CONCLUSION: Increased mRNA vaccine dosing intervals longer than 38 days result in higher levels of anti-spike antibodies and ACE-2 inhibition when assessed six months after the first COVID-19 vaccine.
In vitro metabolic characterization of the SARS-CoV-2 papain-like protease inhibitors GRL0617 and HY-17542 - The SARS-CoV-2 pandemic requires a new therapeutic target for viral infection, and papain-like protease (Plpro) has been suggested as a druggable target. This in-vitro study was conducted to examine the drug metabolism of the GRL0617 and HY-17542, Plpro inhibitors. Metabolism of these inhibitors was studied to predict the pharmacokinetics in human liver microsomes. The hepatic cytochrome P450 (CYP) isoforms responsible for their metabolism were identified using recombinant enzymes. The drug-drug…
Polypropylene Modified with Ag-Based Semiconductors as a Potential Material against SARS-CoV-2 and Other Pathogens - The worldwide outbreak of the coronavirus pandemic (COVID-19) and other emerging infections are difficult and sometimes impossible to treat, making them one of the major public health problems of our time. It is noteworthy that Ag-based semiconductors can help orchestrate several strategies to fight this serious societal issue. In this work, we present the synthesis of α-Ag(2)WO(4), β-Ag(2)MoO(4), and Ag(2)CrO(4) and their immobilization in polypropylene in the amounts of 0.5, 1.0, and 3.0 wt %,…
Hemolytic uremic syndrome in the setting of COVID-19 successfully treated with complement inhibition therapy: An instructive case report of a previously healthy toddler and review of literature - CONCLUSION: Although reports of HUS in the setting of COVID-19 continue to pour in, the questions of exact mechanism and similarities to MIS-C remain. Our case for the first time accentuates the use of complement blockade as a valuable treatment option in this scenario. We sincerely believe that reporting on HUS as a complication of COVID-19 in children will give rise to improved diagnosis and treatment, as well as better understanding of both of these intricating diseases.
Pharmacokinetics and Pharmacodynamics of Imatinib for Optimal Drug Repurposing from Cancer to COVID-19 - CONCLUSION: COVID-19 patients exhibit higher total imatinib exposure compared to cancer patients, attributed to differences in plasma protein concentrations. Higher imatinib exposure in COVID-19 patients did not associate with improved clinical outcomes. Total C(trough) and AUC(ave) inversely associated with some PD-outcomes, which may be biased by disease course, variability in metabolic rate and protein binding. Therefore, additional PKPD analyses into unbound imatinib and its main metabolite…
Establishment of angiotensin-converting enzyme 2 and cluster of differentiation 147 dual target cell membrane chromatography based on SNAP-tag technology for screening anti severe acute respiratory syndrome coronavirus 2 active components - Patients have different responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and these may be life-threatening for critically ill patients. Screening components that act on host cell receptors, especially multi-receptor components, is challenging. The in-line combination of dual-targeted cell membrane chromatography and a liquid chromatography-mass spectroscopy (LC-MS) system for analyzing angiotensin-converting enzyme 2 (ACE2) and cluster of differentiation 147…
Design and characterization of novel SARS-CoV-2 fusion inhibitors with N-terminally extended HR2 peptides - Development of potent and broad-spectrum antivirals against SARS-CoV-2 remains one of top priorities, especially in the case of that current vaccines cannot effectively prevent viral transmission. We previously generated a group of fusion-inhibitory lipopeptides, with one formulation being evaluated under clinical trials. In this study, we dedicated to characterize the extended N-terminal motif (residues 1161-1168) of the so-called spike (S) heptad repeat 2 (HR2) region. Alanine scanning…
Pinosrtobin from plants and propolis against human coronavirus HCoV-OC43 by modulating host AHR/CYP1A1 pathway and lipid metabolism - Coronaviruses, as enveloped positive-strand RNA viruses, manipulate host lipid compositions to enable robust viral replication. Temporal modulation of the host lipid metabolism is a potential novel strategy against coronaviruses. Here, the dihydroxyflavone pinostrobin (PSB) was identified through bioassay that inhibited the increment of human coronavirus OC43 (HCoV-OC43) in human ileocecal colorectal adenocarcinoma cells. Lipid metabolomic studies showed that PSB interfered with linoleic acid…
Global loss of cellular m6A RNA methylation following infection with different SARS-CoV-2 variants - Host-viral interactions during SARS-CoV-2 infection are needed to understand COVID-19 pathogenesis and may help to guide the design of novel antiviral therapeutics. N6-methyladenosine modification (m6A), one of the most abundant cellular RNA modifications, regulates key processes in RNA metabolism during a stress response. Gene expression profiles observed post-infection with different SARS-CoV-2 variants show changes in the expression of genes related to RNA catabolism, including m6A readers…
Dual mechanism: Epigenetic inhibitor apabetalone reduces SARS-CoV-2 Delta and Omicron variant spike binding and attenuates SARS-CoV-2 RNA induced inflammation - The SARS-CoV-2 virus initiates infection via interactions between the viral spike protein and the ACE2 receptors on host cells. Variants of concern have mutations in the spike protein that enhance ACE2 binding affinity, leading to increased virulence and transmission. Viral RNAs released after entry into host cells trigger interferon-I (IFN-I) mediated inflammatory responses for viral clearance and resolution of infection. However, overreactive host IFN-I responses and pro-inflammatory signals…
Immune evasion of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); molecular approaches - In December 2019, a new betacoronavirus, known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), caused an outbreak at the Wuhan seafood market in China. The disease was further named coronavirus disease 2019 (COVID-19). In March 2020, the World Health Organization (WHO) announced the disease to be a pandemic, as more cases were reported globally. SARS-CoV-2, like many other viruses, employs diverse strategies to elude the host immune response and/or counter immune responses. The…