We studied the virucidal efficacy of 0.4% povidone-iodine (PVP-I) nasal spray against SARS-CoV-2 in the patients’ nasopharynx at 3 minutes and 4 hours after PVP-I exposure. We used an open-label single-arm pilot study of adult patients with RT-PCR-confirmed COVID-19. All patients received three puffs of 0.4% PVP-I spray in each nostril. Nasopharyngeal (NP) swabs were collected before the PVP-I spray (baseline, left NP samples), and at 3 minutes (left and right NP samples) and 4 hours post-PVP-I spray (right NP samples). All swabs were tested by RT-PCR and cultured to measure the viable SARS-CoV-2 within 24 hours after collection. Fourteen patients were enrolled but viable SARS-CoV-2 was cultured from 12 patients (85.7%). The median viral titer at baseline was 3.5 log TCID 50 /mL (IQR 2.8-4.0 log TCID 50 /mL). At 3 minutes post-PVP-I spray via the left nostril, viral titers were reduced in 8 patients (66.7%). At 3 minutes post-PVP-I, the median viral titer was 3.4 log TCID 50 /mL (IQR 1.8-4.4 log TCID 50 /mL) ( P =0.162). At 4 hours post-PVP-I spray via the right nostril, 6 of 11 patients (54.5%) had either the same or minimal change in viral titers. The median viral titer 3 minutes post-PVP-I spray was 2.7 log TCID 50 /mL (IQR 2.0-3.9 log TCID 50 /mL). Four hours post-PVP-I spray the median titer was 2.8 log TCID 50 /mL (IQR 2.2-3.9 log TCID 50 /mL) ( P =0.704). No adverse effects of PVP-I nasal spray were detected. We concluded that 0.4% PVP-I nasal spray demonstrated minimal virucidal efficacy at 3 minutes post-exposure. At 4 hours post-exposure, the viral titer was unchanged from baseline. The poor virucidal activity of 0.4% PVP-I nasal spray is unlikely to reduce transmission of SARS-CoV-2 if used for prophylaxis.
COVID-19 has rapidly impacted societies on a global scale, with older people among the most affected. To care for older people living in their own homes, female family caregivers play a pivotal role. The current study aimed to explore the actions of female family caregivers and the challenges they faced in taking care of older people living at homes during the COVID-19 pandemic in Belu district, Indonesia. This qualitative study involved twenty female family caregivers, who were recruited using a combination of purposive and snowball sampling techniques. Findings were grouped into two main categories: (i) actions of female family caregivers in taking care of older adults during the COVID-19 pandemic. These included limiting both visitations of extended family members and older adults’ activities outside homes; explaining the virus to older adults and controlling their access to news, social media and smartphones; providing nutrition, supplement and maintaining daily diets; and (ii) challenges they faced in taking care of older adults included excessive fear of contracting COVID-19 and possibility of transmitting it to older people; feeling stressed; tired and overburdened. The study highlights the significant role family caregivers played to protect older people living at home. The findings can inform government to develop intervention programs that address and support the needs of both family caregivers and older people living at home.
Rationale: Neutrophils are important in the pathophysiology of COVID19 but the molecular changes contributing to altered neutrophil phenotypes following SARS-CoV-2 infection are not fully understood. Objectives: To use quantitative mass spectrometry-based proteomics to explore neutrophil phenotypes following acute SARS-CoV-2 infection and during recovery. Methods: Prospective observational study of hospitalised patients with PCR-confirmed SARS-CoV-2 infection (May 2020-December 2020). Patients were enrolled within 96 hours of admission, with longitudinal sampling up to 29 days. Control groups comprised non-COVID19 acute lower respiratory tract infection (LRTI) and age-matched non-infected controls. Neutrophils isolated from peripheral blood were processed for mass spectrometry. COVID19 severity and recovery were defined using the WHO ordinal scale. Measurements and Main Results: 84 COVID19 patients were included and compared to 91 LRTI patients and 42 controls. 5,800 neutrophil proteins were identified and 1,748 proteins were significantly different (q-value<0.05) in neutrophils from COVID19 patients compared to those of non-infected controls, including a robust interferon response at baseline, which was lost in severe patients one week after enrolment. Neutrophil changes associated with COVID19 disease severity and prolonged illness were characterized and candidate targets for modulation of neutrophil function were identified. Delayed recovery from COVID19 was associated with changes in metabolic and signalling proteins, complement, chemokine and leukotriene receptors, integrins and inhibitory receptors. Conclusions: SARS-CoV-2 infection results in the sustained presence of recirculating neutrophils with distinct metabolic profiles and altered capacities to respond to migratory signals and cues from other immune cells, pathogens or cytokines.
Abstract Introduction Health system resilience is the ability to prepare, manage, and learn from a sudden and unpredictable extreme change which impacts health systems. Health systems globally have recently been affected by a number of catastrophic events, including natural disasters, and infectious disease epidemics. Understanding health system resilience has never been more essential until emerging global pandemics. Therefore, the application of resilience-enhancing strategies with existing frameworks needs to be assessed to identify the management gaps and give valuable recommendations from the lessons learnt from the global pandemic. Methodology The systematic review will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews (PRISMA-SCR). Reporting data on health system building blocks and systematic searches on resilience enhancing strategies for the management of Public Health Emergencies of International Concerns (PHEIC) after the establishment of International Health Regulations (IHR) since managing PHEIC after the establishment of IHR in 2007 will be included. The search will be conducted in PubMed, Scopus, Web of Science, Google Scholar, and grey literature. A narrative synthesis will be performed to present the review findings. Discussion Health system resilience is key to coping with catastrophic events, such as the economic crisis and COVID-19 pandemic. The mapping of available literature towards the application of resilience-enhancing strategies with existing frameworks needs to be assessed to identify the management gaps and give valuable recommendations from the lessons learnt from the global pandemic to improve the level of preparedness and response to similar public health emergencies in the future. Conclusion A protocol for a global scoping review of health system resilience for pandemic management is described. This review will add to the body of knowledge about health systems enhancing research and policy formulation. Keywords: Health system resilience; Pandemi; Public health; Emergencies
Background: Nirmatrelvir/ritonavir is an effective therapy against SARS-CoV-2. Patients with end-stage renal disease (ESRD) are at high risk for severe COVID-19 and show impaired vaccine responses underlining the importance of antiviral therapy. However, use of nirmatrelvir/ritonavir is not recommended in these patients due to lack of clinical and pharmacokinetic data. Objective: To investigate pharmacokinetics and hepatic tolerance of nirmatrelvir/ritonavir in patients with ESRD and haemodialysis (HD). Patients and methods: Four patients diagnosed with SARS-CoV-2 infection received nirmatrelvir/ritonavir 150/100mg twice daily as recommended for renal impairment; HD ran in two- to three-day intervals. Plasma and serum samples were drawn before and after each HD during the 5-day treatment and for ensuing 3-5 days. Results: Median peak levels of nirmatrelvir obtained two hours after medication pre-HD in three patients were 7745ng/mL on day 3 and 6653ng/mL on day 5; median post-HD levels (C6h) declined to 5765ng/mL (74%) and 5521ng/mL (83%), on days 3 and 5 of treatment, respectively. Three days after end of treatment, median levels were 365ng/mL pre-HD and 30ng/mL post-HD. Measurements of the fourth patient, six hours after drug intake pre-HD showed nirmatrelvir-levels of 3704ng/mL on treatment day 3 which fell to 2308ng/mL post-HD, at one hour before intake of the next dose (Cmin). Conclusion: Use of nirmatrelvir/ritonavir in patients with ESRD results in high nirmatrelvir blood concentrations, which are still within the range known from patients without renal failure. No accumulation of nirmatrelvir took place and levels declined to zero within few days after end of treatment.
N95 respirators reduce risk of catching COVID-19 from an infected person both at near-field (e.g. < 6 feet) and far-field (e.g. > 6 feet). Air filtration is usually not effective at near-field, but emulating the far-field equivalent of N95 requires 95% reduction of particles (20x) from airborne particulate sources. A wide range of air change per hour (ACH) recommendations for air filtration exist ranging from 2 to 12 ACH (CDC, CDPH, etc.). Instead of inert airborne contaminant (e.g. salt water) which can be disruptive in occupied rooms, we describe a simpler procedure using an optical particle counter to track the decay of ambient aerosols (0.3 μm diameter) and measure ACH from exponential decay coefficients in a room and a whole house. Surface deposition in an unventilated room without ventilation or filtration was measured to be 0.6 ACH using ambient aerosols. ACH was also measured to be 3 to 17 using low-noise generating HEPA purifiers ($299-$999, reported CADR 114 to 1360 cfm) and Do-It-Yourself (DIY) air purifiers ($55-$160, 1“-5”, MERV 13-16, 1-filter box-fans and 4-filter Corsi-Rosenthal boxes). Using ACH and volume of room/house, estimated CADR per dollar varied 4x from below 80 cfm / $100 for tested HEPA purifiers at their highest speed (for maximum CADR) up to above 350 cfm / $100 run with tested DIY air purifiers running on their lowest speed (for reduced noise generation). Differences in CADR were observed in room versus house, and purifiers with higher airspeed had higher than expected CADR, possibly reflecting better mixing. Using 0.6 ACH as baseline for unventilated rooms, at least 12 ACH if not more is required for far-field protection equivalent to N95 respirators (95%), and this ACH can be achieved using either HEPA or DIY air filtration in a room or building and verified with ambient aerosols. This offers an independent, experimentally-derived interpretation of the 12 ACH recommended for airborne infection isolation rooms (AIIR) by CDC and WHO.
Genome sequences from evolving infectious pathogens allow quantification of case introductions and local transmission dynamics. We sequenced 11,357 SARS-CoV-2 genomes from Switzerland in 2020 - the 6th largest effort globally. Using a representative subset of these data, we estimated viral introductions to Switzerland and their persistence over the course of 2020. We contrast these estimates with simple null models representing the absence of certain public health measures. We show that Switzerland9s border closures de-coupled case introductions from incidence in neighboring countries. Under a simple model, we estimate an 86 - 98% reduction in introductions during Switzerland9s strictest border closures. Furthermore, the Swiss 2020 partial lockdown roughly halved the time for sampled introductions to die out. Finally, we quantified local transmission dynamics once introductions into Switzerland occurred, using a novel phylodynamic model. We find that transmission slowed 35 - 63% upon outbreak detection in summer 2020, but not in fall. This finding may indicate successful contact tracing over summer before overburdening in fall. The study highlights the added value of genome sequencing data for understanding transmission dynamics.
Background: An exploratory household transmission study was nested in SPECTRA, the phase 2/3 efficacy study of the adjuvanted recombinant protein-based COVID-19 vaccine SCB-2019. We compared occurrence of confirmed COVID-19 infections between households and household contacts of infected SPECTRA participants who were either placebo or SCB-2019 recipients. Methods: SPECTRA trial participants at eight study sites in the Philippines who developed rRT-PCR-confirmed COVID-19 were contacted by a study team blinded to assignment of index cases to vaccine or placebo groups to enroll in this household transmission study. Enrolled households and household contacts were monitored for three weeks using rRT-PCR and rapid antigen testing to detect new COVID-19 infections. Results: Observation of the households of 154 eligible COVID-19 index cases, 130 symptomatic and 24 asymptomatic at diagnosis, revealed household secondary attack rates for any COVID-19 infection of SCB-2019 index cases of 0.76% (90% CI: 0.15-3.90) compared with 5.88% (90% CI: 3.20-10.8) in placebo index case households, a relative risk reduction of 79% (90% CI: -28-97). The relative risk reduction of symptomatic COVID-19 was 84% (90% CI: 28-97) for household contacts of all COVID-19 infected index cases, and 80% (90% CI: 7-96) for household contacts of index cases with symptomatic COVID-19. Conclusions: In this prospective household contact study vaccination with SCB-2019 reduced SARS-CoV-2 transmission in households, so decreasing infections of household contacts, compared with placebo.
A Clinical Study to Evaluate the Efficacy and Safety of SIM0417 Orally Co-Administered With Ritonavir in Symptomatic Adult Participants With Mild to Moderate COVID-19 - Condition: COVID-19
Interventions: Drug: SIM0417; Drug: Placebo
Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Not yet recruiting
Self-management of Post COVID-19 Syndrome Using Wearable Biometric Technology - Condition: COVID-19
Intervention: Other: Self-management of post COVID-19 respiratory outcomes
Sponsor: University of Manitoba
Not yet recruiting
Clinical Study to Compare Efficacy and Safety of Casirivimab and Imdevimab Combination, Remdesivir and Favipravir in Hospitalized COVID-19 Patients - Condition: COVID-19
Interventions: Drug: Casirivimab and Imdevimab Drug Combination; Drug: Remdesivir; Drug: Favipiravir
Sponsor: Mansoura University Hospital
Completed
The Role of BCG Vaccine in the Clinical Evolution of COVID-19 and in the Efficacy of Anti-SARS-CoV-2 Vaccines - Condition: COVID-19
Interventions: Biological: BCG (Bacillus Calmette-Guérin) vaccine; Other: Placebo
Sponsors: Oswaldo Cruz Foundation; University of Sao Paulo; Federal University of Juiz de Fora
Recruiting
Cognitive Rehabilitation in Post-COVID-19 Condition - Condition: COVID-19
Intervention: Behavioral: Goal Management Training (GMT)
Sponsors: Lovisenberg Diakonale Hospital; University of Oslo; Icahn School of Medicine at Mount Sinai; University of Toronto; UiT The Arctic University of Norway; Oslo University Hospital
Not yet recruiting
Performance Evaluation of LumiraDx COVID-19 (SARS-CoV-2) Ag ULTRA Test (ASPIRE-2) - Condition: COVID-19
Interventions: Diagnostic Test: Nasal Swab; Diagnostic Test: Nasopharyngeal swab
Sponsor: LumiraDx UK Limited
Recruiting
Social Network Diffusion of COVID-19 Prevention for Diverse Criminal Legal Involved Communities - Condition: COVID-19
Interventions: Other: Education; Other: Motivational
Sponsor: University of Chicago
Not yet recruiting
A Study of Booster Immunization With COVID-19 Vaccine,Inactivated Co -Administration With Influenza Vaccine and Pneumococcal Polysaccharide Vaccine - Condition: COVID-19
Interventions: Biological: Adult group in immunogenicity and safety study of combined immunization; Biological: Elderly group in immunogenicity and safety study of combined immunization; Biological: Adult group in safety observation study of combined immunization; Biological: Elderly group in safety observation study of combined immunization
Sponsor: Sinovac Biotech Co., Ltd
Completed
EFFECTS OF INSPIRATORY MUSCLE TRAINING IN POST-COVID-19 PATIENTS - Condition: Covid19
Interventions: Other: TREATMENT GROUP (TG); Other: CONTROL GROUP (CG)
Sponsor: University Vila Velha
Completed
Evaluate the Safety and Efficacy of Allogeneic Umbilical Cord Mesenchymal Stem Cells in Patients With COVID-19 - Condition: COVID-19 Infection
Interventions: Biological: Allogeneic umbilical cord mesenchymal stem cells; Biological: Controlled normal saline
Sponsor: Ever Supreme Bio Technology Co., Ltd.
Active, not recruiting
Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome - Condition: Post-COVID-19 Syndrome
Interventions: Drug: Temelimab 54mg/kg; Drug: Placebo
Sponsor: GeNeuro SA
Not yet recruiting
The Effects of a Sublingual Sprayable Microemulsion of Vitamin D on Inflammatory Markers in COVID-19 Patients - Conditions: COVID-19; Vitamin D Deficiency
Intervention: Dietary Supplement: Vitamin D 25 (OH) 12000 IU in the form of a sublingual sprayable microemulsion
Sponsor: Pauls Stradins Clinical University Hospital
Completed
UNAIR Inactivated COVID-19 Vaccine Phase 3 - Conditions: COVID-19 Pandemic; COVID-19 Vaccines
Interventions: Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg; Biological: CoronaVac Biofarma COVID-19 Vaccine
Sponsors: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia
Recruiting
Hydrogen-Oxygen Generator With Nebulizer for Rehabilitation Treatment of COVID-19 - Conditions: COVID-19; AMS-H-03; Hydrogen-oxygen Gas
Interventions: Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03; Other: basic treatment
Sponsor: Shanghai Zhongshan Hospital
Recruiting
Huashi Baidu Granule in the Treatment of Pediatric Patients With Mild Coronavirus Disease 2019 - Condition: Coronavirus Disease 2019
Interventions: Drug: Huashi Baidu granule; Drug: compound pholcodine oral solution
Sponsor: Shanghai Children’s Medical Center
Completed
SARS-CoV-2 causes secretory diarrhea with an enterotoxin-like mechanism, which is reduced by diosmectite - CONCLUSIONS: SARS-CoV-2 induces calcium-dependent chloride secretion and oxidative stress without damaging intestinal epithelial structure. The effects are largely induced by the spike protein and are significantly reduced by diosmectite. SARS-CoV-2 should be added to the list of human enteric pathogens.
Quercetin against Emerging RNA Viral Diseases: Potential and Challenges for Translation - Because of higher adaptability and mutability, there is always a possibility for RNA viral disease outbreaks. There are no approved antivirals for the majority of RNA viruses including SARS-CoV-2, CHIKV, DENV, JEV, ZIKV, and EBOV. To treat these infections and to prepare for future epidemics there is a necessity to identify effective therapeutic strategies with broad-spectrum actions against RNA viruses. Unregulated inflammation is the major cause of the severity associated with these viral…
A nanomaterial targeting the spike protein captures SARS-CoV-2 variants and promotes viral elimination - The global emergency caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic can only be solved with effective and widespread preventive and therapeutic strategies, and both are still insufficient. Here, we describe an ultrathin two-dimensional CuInP(2)S(6) (CIPS) nanosheet as a new agent against SARS-CoV-2 infection. CIPS exhibits an extremely high and selective binding capacity (dissociation constant (K(D)) < 1 pM) for the receptor binding domain of the spike…
Honghua extract mediated potent inhibition of COVID-19 host cell pathways - Honghua (Carthami flos) and Xihonghua (Croci stigma) have been used in anti-COVID-19 as Traditional Chinese Medicine, but the mechanism is unclear. In this study, we applied network pharmacology by analysis of active compounds and compound-targets networks, enzyme kinetics assay, signaling pathway analysis and investigated the potential mechanisms of anti-COVID-19. We found that both herbs act on signaling including kinases, response to inflammation and virus. Moreover, crocin likely has an…
Association between antidepressant use and ED or hospital visits in outpatients with SARS-CoV-2 - Antidepressants have previously been associated with better outcomes in patients hospitalized with COVID-19, but their effect on clinical deterioration among ambulatory patients has not been fully explored. The objective of this study was to assess whether antidepressant exposure was associated with reduced emergency department (ED) or hospital visits among ambulatory patients with SARS-CoV-2 infection. This retrospective cohort study included adult patients (N = 25 034) with a positive…
Aptamers targeting SARS-COV-2: a promising tool to fight against COVID-19 - SARS-CoV-2, the causative agent of COVID-19, remains among the main causes of global mortality. Although antigen/antibody-based immunoassays and neutralizing antibodies targeting SARS-CoV-2 have been successfully developed over the past 2 years, they are often inefficient and unreliable for emerging SARS-CoV-2 variants. Novel approaches against SARS-CoV-2 and its variants are therefore urgently needed. Aptamers have been developed for the detection and inhibition of several different viruses…
Evaluation of the active constituents of Nilavembu Kudineer for viral replication inhibition against SARS-CoV-2: An approach to targeting RNA-dependent RNA polymerase (RdRp) - The World Health Organization has declared the novel coronavirus (COVID-19) outbreak a global pandemic and emerging threat to people in the 21st century. SARS-CoV-2 constitutes RNA-Dependent RNA Polymerase (RdRp) viral proteins, a critical target in the viral replication process. No FDA-approved drug is currently available, and there is a high demand for therapeutic strategies against COVID-19. In search of the anti-COVID-19 compound from traditional medicine, we evaluated the active moieties…
Hesperetin as an anti-SARS-CoV-2 agent can inhibit COVID-19-associated cancer progression by suppressing intracellular signaling pathways - Hesperetin, an aglycone metabolite of hesperidin with high bioavailability, recently gained attention due to its anti-COVID-19 and anti-cancer properties. Multiple studies revealed that cancer patients are prone to experience a severe form of COVID-19 and higher mortality risk. In addition, studies suggested that COVID-19 can potentially lead to cancer progression through multiple mechanisms. This study proposes that hesperetin not only can be used as an anti-COVID-19 agent but also can reduce…
SARS-CoV-2 Papain-Like Protease: Structure, Function and Inhibition - Emerging variants of SARS-CoV-2 and potential novel epidemic coronaviruses underline the importance of investigating various viral proteins as potential drug targets. The papain-like protease of coronaviruses has been less explored than other viral proteins; however, its substantive role in viral replication and impact on the host immune response make it a suitable target to study. This review article focuses on the structure and function of the papain-like protease (PLpro) of SARS-CoV-2,…
Phytochemical drug discovery for COVID-19 using high-resolution computational docking and machine learning assisted binder prediction - The COVID-19 pandemic has resulted in millions of deaths around the world. Multiple vaccines are in use, but there are many underserved locations that do not have adequate access to them. Variants may emerge that are highly resistant to existing vaccines, and therefore cheap and readily obtainable therapeutics are needed. Phytochemicals, or plant chemicals, can possibly be such therapeutics. Phytochemicals can be used in a polypharmacological approach, where multiple viral proteins are inhibited…
CADD Studies in the Discovery of Potential ARI (Aldose Reductase Inhibitors) Agents for the Treatment of Diabetic Complications - The lack of currently available drugs for the treatment of diabetes complications has stimulated our interest in finding new Aldose Reductase inhibitors (ARIs) with more beneficial biological properties. One metabolic method by the use of aldose reductase inhibitors in the first step of the polyol pathway. to control excess glucose flux in diabetic tissues. Computer-aided drug discovery (CADD) plays a key role in finding and optimizing potential lead substances. AR inhibitors (ARI) have been…
Wearing the face mask affects our social attention over space - Recent studies suggest that covering the face inhibits the recognition of identity and emotional expressions. However, it might also make the eyes more salient, since they are a reliable index to orient our social and spatial attention. This study investigates (1) whether the pervasive interaction with people with face masks fostered by the COVID-19 pandemic modulates the processing of spatial information essential to shift attention according to other’s eye-gaze direction (i.e., gaze-cueing…
Anti-human ACE2 antibody neutralizes and inhibits virus production of SARS-CoV-2 variants of concern - The global pandemic caused by SARS-CoV-2 is a major public health problem. Virus entry occurs via binding to ACE2. Five SARS-CoV-2 variants of concern (VOCs) were reported so far, all having immune escape characteristics. Infection with the current VOC Omicron were noticed in immunized and recovered individuals, therefore development of new treatments against VOC infections are urgently needed. Most approved mAbs treatments against SARS-CoV-2 are directed against the spike protein of the…
Identification of potent inhibitors of SARS-CoV-2 infection by combined pharmacological evaluation and cellular network prioritization - Pharmacologically active compounds with known biological targets were evaluated for inhibition of SARS-CoV-2 infection in cell and tissue models to help identify potent classes of active small molecules and to better understand host-virus interactions. We evaluated 6710 clinical and preclinical compounds targeting 2183 host proteins by immunocytofluorescence-based screening to identify SARS-CoV-2 infection inhibitors. Computationally integrating relationships between small molecule structure,…
NOTCH signaling in COVID-19: a central hub controlling genes, proteins, and cells that mediate SARS-CoV-2 entry, the inflammatory response, and lung regeneration - In the lungs of infected individuals, the downstream molecular signaling pathways induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are incompletely understood. Here, we describe and examine predictions of a model in which NOTCH may represent a central signaling axis in lung infection in Coronavirus Disease 2019 (COVID-19). A pathway involving NOTCH signaling, furin, ADAM17, and ACE2 may be capable of increasing SARS-CoV-2 viral entry and infection. NOTCH signaling can also…