Purpose: The effect of vasopressors on mortality of critically ill patients with COVID-19 has not been studied extensively. Methods: A systematic search of PubMed, Scopus, and clinicaltrials.gov was conducted for relevant articles until January 2022. Eligibility criteria were randomized controlled and non-randomized trials. The primary outcome was all-cause mortality at 28 days or 30 days. The quality of studies was assessed using the MINORS tool. Paired meta- analysis was used to estimate the pooled risk ratios along with their 95% Confidence Interval. Results: In total, 33 studies were included. Twenty-one studies with a total population of 7900 individuals provided data on mortality. Patients who received vasopressors were statistically significantly more likely to die compared to those who did not receive vasopressor therapy [RR (95%CI): 4.26 (3.15, 5.76); p<0.001]. This result remained statistically significant regardless of the in-hospital setting. In-hospital and 30-day mortality were statistically significantly higher in patients who received vasopressors [RR (95%CI): 4.60 (2.47, 8.55); p<0.001 and RR (95%CI): 2.97 (1.72, 5.14); p<0.001, respectively]. Four studies provided data on specific vasopressors; the highest mortality rate was observed in patients treated with vasopressin or epinephrine, while patients receiving angiotensin-II as a sole or second-line vasopressor agent had the lowest mortality rate. Also, analysis of 10 studies with a total population of 3519 individuals revealed that patients who received vasopressors were statistically significantly more likely to experience acute kidney injury [RR (95%CI): 3.17 (2.21, 4.54); p<0.001]. Conclusion: Vasopressors have detrimental effect on survival of critically ill patients with COVID-19.
Objective: To assess myocarditis and pericarditis reporting rate as adverse drug reactions (ADRs) for the messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccines authorized in Europe. Methods: Data on myocarditis and pericarditis related to mRNA COVID-19 vaccines (period: January 1, 2021 - February 11, 2022) were collected from the EudraVigilance database and combined with the European Centre for Disease Prevention and Control9s (ECDC) vaccination tracker database. The reporting rate was expressed as 1 million individual vaccinated-days with a corresponding 95% confidence interval (CI), and an observed-to-expected (OE) analysis was performed to check if there was an excess risk for myocarditis or pericarditis following mRNA COVID-19 vaccination. Results: The reporting rate of myocarditis per 1 million individual vaccinated-days in the study period was 17.27 (95% CI, 16.34-18.26) for the CX-024414 vaccine and 8.44 (95% CI, 8.18-8.70) for TOZINAMERAN vaccine. The reporting rate for pericarditis per 1 million individual vaccinated-days in the study period was 9.76 (95% CI, 9.06-10.51) for the CX-024414 vaccine and 5.79 (95% CI, 5.56-6.01) for TOZINAMERAN vaccine. The OE analysis showed that both vaccines produced a myocarditis standardized morbidity ratio (SMR) greater than 1, with the CX-024414 vaccine having a greater SMR than TOZINAMERAN. The SMR for pericarditis was greater than 1 when considering the lowest background incidence, but smaller than 1 when considering the highest background incidence. Conclusions: Our results suggest an excess risk of myocarditis following the first dose of mRNA COVID-19 vaccine, but the relationship between pericarditis and mRNA COVID-19 vaccine remains unclear.
We assessed the association between self-reported mask use during non-household interactions and COVID-19 infection during three pandemic periods. Odds of infection for those who did not always compared to those who always wore a mask was 66% higher during pre-Delta, 53% higher during Delta, declining to 16% higher during Omicron.
It has been previously reported that chronic infection with human cytomegalovirus (CMV) may contribute to poor vaccine responses against de novo antigens in older adults. We assessed effects of CMV serostatus on antibody quantity and quality, as well as cellular memory responses, after 2 and 3 SARS-CoV-2 mRNA vaccine doses, in older adults in congregate living facilities. CMV serostatus did not affect anti-Spike and anti-RBD IgG antibody levels, nor neutralization capacity against wildtype or beta variants of SARS-CoV-2. CMV seropositivity altered T cell expression of senescence-associated markers and increased TEMRA cell numbers, as has been previously reported; however, this did not impact the Spike-specific CD4+ T cell memory responses. CMV seropositive individuals did not have a higher incidence of COVID-19, though prior infection influenced humoral immunity. Therefore, CMV seropositivity may alter T cell composition but does not impede humoral or cellular memory responses after SARS-CoV-2 mRNA vaccination in older adults.
Background. Variant-adaptated vaccines against coronavirus disease 2019 (COVID-19) as boosters are needed to increase a broader protection against SARS CoV-2 variants. New adjuvanted recombinant protein vaccines as heterologous boosters could maximize the response. Methods. In this randomized, single-blinded, multicenter trial, adults who had received two doses of Pfizer-BioNTech mRNA vaccine (BNT162b2) 3 to7 months before were randomly assigned to receive a boost of BNT162b2, Sanofi/GSK SARS-CoV-2 adjuvanted recombinant protein MV D614 (monovalent parental formulation) or SARS-CoV-2 adjuvanted recombinant protein MV B.1.351 vaccine (monovalent Beta formulation). The primary endpoint was the percentage of subjects with a ≥ 10-fold increase in neutralizing antibody titers for the Wuhan (D614) and B.1.351 (Beta) SARS-CoV-2 viral strains between day 0 and day 15. Findings. The percentages of participants whose neutralizing antibody titers against the Wuhan (D614) SARS-CoV-2 strain increased by a factor ≥10 between day 0 and day 15 was 55.3% (95% CI 43.4-66.7) in MV D614 group (n=76), 76.1% (64.5-85.4) in MV B.1.351 (Beta) group (n=71) and 63.2% (51.3-73.9) in BNT162b2 group (n=76). These percentages were 44.7% (33.3-56.6), 84.5% (74.0-92.0) and 51.3% (39.6-63.0) for the B.1.351 (Beta) viral strain, respectively. Higher neutralizing antibodies rates against Delta and Omicron BA.1 variants were also elicited after Sanofi/GSK MV Beta vaccine compared to the other vaccines. Comparable reactogenicity profile was observed with the three vaccines. Interpretation. Heterologous boosting with the Sanofi/GSK Beta formulation vaccine resulted in a higher neutralizing antibody response against Beta variant but also the original strain and Delta and Omicron BA.1 variants, compared with mRNA BNT162b2 vaccine or the Sanofi/GSK MVD614 formulation. New vaccines containing Beta spike protein may represent an interesting strategy for broader protection against SARS CoV-2 variants.
Importance: While much of the attention on the COVID-19 pandemic was directed at the daily counts of cases and those with serious disease overwhelming health services, increasingly, reports have appeared of people who experience debilitating symptoms after the initial infection. This is popularly known as long COVID. Objective: To estimate by country and territory of the number of patients affected by long COVID in 2020 and 2021, the severity of their symptoms and expected pattern of recovery Design: We jointly analyzed ten ongoing cohort studies in ten countries for the occurrence of three major symptom clusters of long COVID among representative COVID cases. The defining symptoms of the three clusters (fatigue, cognitive problems, and shortness of breath) are explicitly mentioned in the WHO clinical case definition. For incidence of long COVID, we adopted the minimum duration after infection of three months from the WHO case definition. We pooled data from the contributing studies, two large medical record databases in the United States, and findings from 44 published studies using a Bayesian meta-regression tool. We separately estimated occurrence and pattern of recovery in patients with milder acute infections and those hospitalized. We estimated the incidence and prevalence of long COVID globally and by country in 2020 and 2021 as well as the severity-weighted prevalence using disability weights from the Global Burden of Disease study. Results: Analyses are based on detailed information for 1906 community infections and 10526 hospitalized patients from the ten collaborating cohorts, three of which included children. We added published data on 37262 community infections and 9540 hospitalized patients as well as ICD-coded medical record data concerning 1.3 million infections. Globally, in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8-312.9) people suffered from any of the three symptom clusters of long COVID. This corresponds to 3.69% (1.38-7.96) of all infections. The fatigue, respiratory, and cognitive clusters occurred in 51.0% (16.9-92.4), 60.4% (18.9-89.1), and 35.4% (9.4-75.1) of long COVID cases, respectively. Those with milder acute COVID-19 cases had a quicker estimated recovery (median duration 3.99 months [IQR 3.84-4.20]) than those admitted for the acute infection (median duration 8.84 months [IQR 8.10-9.78]). At twelve months, 15.1% (10.3-21.1) continued to experience long COVID symptoms. Conclusions and relevance: The occurrence of debilitating ongoing symptoms of COVID-19 is common. Knowing how many people are affected, and for how long, is important to plan for rehabilitative services and support to return to social activities, places of learning, and the workplace when symptoms start to wane.
Background: The SARS-CoV-2 Omicron variant is currently the dominant variant globally. This 3rd interim analysis of a living systematic review summarizes evidence on COVID-19 vaccine effectiveness (VE) and duration of protection against Omicron. Methods: We systematically searched the COVID-19 literature for controlled studies evaluating the effectiveness of COVID-19 vaccines approved in the European Union up to 14/01/2022, complemented by hand-searches of websites and metasearch engines up to 11/02/2022. We considered the following comparisons: full primary immunization vs. no vaccination; booster immunization vs. no vaccination; booster vs. primary immunization. VE against any confirmed SARS-CoV-2 infection, symptomatic, and severe COVID-19 (i.e. COVID-19-related hospitalization, ICU-admission, or death) was indicated providing estimate ranges. Meta-analysis was not performed due to high study heterogeneity. Risk of bias was assessed with ROBINS-I, certainty of evidence evaluated using GRADE. Results: We identified 26 studies, including 430 to 2.2 million participants. VE against any confirmed SARS-CoV-2 infection compared to no vaccination ranged between 0-62% after full primary immunization, and between 34-66% after a booster dose. VE-range for booster vs. primary immunization was 34-54.6%. Against symptomatic COVID-19, VE ranged between 6-76% after full primary immunization, and between 19-73.9% after booster immunization, if compared to no vaccination. When comparing booster vs. primary immunization VE ranged between 56-69%. VE against severe COVID-19 compared to no vaccination ranged between 3-84% after full primary immunization, and between 12-100% after a booster dose. One study compared booster vs. primary immunization (VE 100%, 95% CI 71.4-100). VE was characterized by a moderate to strong decline within three to six months for SARS- CoV-2 infections and symptomatic COVID-19. Against severe COVID-19 protection remained robust at least for up to six months. Waning immunity was more profound after primary than booster immunization. Risk of bias was moderate to critical across studies and outcomes. GRADE-certainty was very low for all outcomes. Author9s conclusions: Under the Omicron variant, effectiveness of EU-licensed COVID-19 vaccines in preventing any SARS-CoV-2 infection or mild disease is low and only short-lasting after primary immunization, but can be improved by booster vaccination. VE against severe COVID-19 remains high and is long-lasting, especially after receiving the booster vaccination.
Abstract With the advent of the COVID-19 pandemic, in-person social interactions and opportunities for accessing resources that sustain health and well-being have drastically reduced. We therefore designed the pan-Canadian population-based prospective COVID-19: HEalth and Social Inequities across Neighbourhoods (COHESION) cohort to provide deeper understanding of how the COVID-19 pandemic context affects mental health and well-being, key determinants of health, and health inequities. This paper presents the design of the two-phase COHESION Study, and descriptive results from the first phase conducted between May 2020 and September 2021. During that period, the COHESION research platform collected monthly data linked to COVID-19 such as infection and vaccination status, perceptions and attitudes regarding pandemic-related measures, and information on participants’ physical and mental health, well-being, sleep, loneliness, resilience, substances use, living conditions, social interactions, activities, and mobility. The 1,268 people enrolled in the Phase 1 COHESION Study are for the most part from Ontario (47%) and Quebec (33%), aged 48 ± 16 years [mean± standard deviation (SD)], and mainly women (78%), White (85%), with a university degree (63%), and living in large urban centers (70%). According to the 298 ± 68 (mean ± SD) prospective questionnaires completed each month in average, the first year of follow-up reveals significant temporal variations in standardized indexes of well-being, loneliness, anxiety, depression, and psychological distress. The COHESION Study will allow identifying trajectories of mental health and well-being while investigating their determinants and how these may vary by subgroup, over time, and across different provinces in Canada, in the unique context of the COVID-19 pandemic.
Unlike mRNA vaccines based only on the Spike protein, inactivated SARS-CoV-2 vaccines should induce a diversified T cell response recognizing distinct structural proteins. Here we performed a comparative analysis of SARS- CoV-2 specific T cells in healthy individuals following vaccination with inactivated SARS-CoV-2 or mRNA vaccines. Relative to Spike mRNA vaccination, inactivated vaccines elicited a lower magnitude of Spike-specific T cells, but the combined Membrane, Nucleoprotein and Spike specific T cell response was quantitatively comparable to the sole Spike T cell response induced by mRNA vaccines, and they efficiently tolerate the mutations characterizing the Omicron lineage. However, this multi-protein specific T cell response was not mediated by a coordinated CD4 and CD8 T cell expansion but by selected priming of CD4 T cells. These findings can help in defining the role of CD4 and CD8 T cells in the efficacy of the different vaccines to control severe COVID-19 after Omicron infection.
Covid-19 has caused more than 1 million deaths in the US, including at least 1,433 deaths among children and young people (CYP) aged 0-19 years. Deaths among US CYP are rare in general, and so we argue here that the mortality burden of Covid-19 in CYP is best understood in the context of all other causes of CYP death. Using publicly available data from the National Center for Health Statistics, and comparing to mortality in 2019, the immediate pre-pandemic period, we find that Covid-19 is a leading cause of death in CYP aged 0-19 years in the US, ranking #9 among all causes of deaths, #5 in disease related causes of deaths (excluding accidents, assault and suicide), and #1 in deaths caused by infectious / respiratory diseases. Due to the impact of mitigations such as social distancing and our comparison of a single disease (Covid-19) to groups of causes such as deaths from pneumonia and influenza, these rankings are likely conservative lower bounds. Our findings underscore the importance of continued vaccination campaigns for CYP over 5 years of age in the US and for effective Covid-19 vaccines for under 5 year olds.
Background: Omicron variant strain dominated since the beginning of 2022. Its infectivity was supposes to be higher than Delta variant strain or strains in past. Object: We estimated prevalence of omicron variant strain, particularly bA.2 variant and COVID-19 vaccine effectiveness of the third dose in Japan as well as controlling for waning of second dose of vaccine, other mutated strains, the Olympic Games, and countermeasures. Method: The effective reproduction number R(t) was regressed on shares of omicron variant strain and bA.2 and vaccine coverage of the third dose, as well as along with data of temperature, humidity, mobility, share of the other mutated strains, and an Olympic Games and countermeasures. The study period was February, 2020 through February 21, 2022, as of March 15, 2022. Results : Estimation results indicated that waning of the second dose vaccine e with 150 days prior was the most appropriate specification. Moreover, bA.2 of omicron variant strain has higher infectively than other variant strain or traditional strain. Discussion: Because of data limitation since emerging bA.2, the estimated its infectively will change over time.
The COVID-19 Pandemic has prompted innovation and research to further understand not only SARS-CoV-2, but other respiratory viruses as well. Since the start of the pandemic there has been a lack in influenza collection and surveillance. In October 2021 the Life Sciences Testing Center at Northeastern University implemented the TaqPath™ COVID-19, Flu A, Flu B combo kit to test for multiple respiratory diseases among the University’s population. During this time the SARS- CoV-2 variant of concern, Omicron B.1.1.529, became the dominant strain in the greater Boston area. During this time an inverse correlation in the detection of positive SARS-CoV-2 and Influenza A was observed. More data is needed to determine if this observed inverse correlation on positivity rate is linked to public health measures or biological mechanism within the immune system.
A Safety and Efficacy Study of Hymecromone Tablets for the Treatment of Patients With COVID-19. - Condition: COVID-19
Interventions: Drug: Hymecromone tablets; Other: Placebo
Sponsor: Shanghai Zhongshan Hospital
Recruiting
Study on Sequential Immunization of Omicron Inactivated COVID-19 Vaccine and Prototype Inactivated COVID-19 Vaccine in Population Aged 18 Years Old and Above - Condition: COVID-19
Interventions: Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated; Biological: COVID-19 Vaccine (Vero Cell), Inactivated
Sponsors:
China National Biotec Group Company Limited; Beijing Institute of Biological Products Co Ltd.; Hunan Provincial Center for Disease Control and Prevention
Recruiting
A Phase Ia, Dose-finding Study to Assess the Safety and Immunogenicity of a COVID-19 Vaccine Booster in Healthy Adults - Condition: COVID-19
Intervention: Biological: Prime-2-CoV_Beta
Sponsors:
University Hospital Tuebingen; FGK Clinical Research GmbH; VisMederi srl; Staburo GmbH; Viedoc Technologies AB
Not yet recruiting
A Study to Learn About the Study Medicine (Called Nirmatrelvir/Ritonavir) in Pregnant Women With Mild or Moderate COVID-19. - Condition: COVID-19
Interventions: Drug: nirmatrelvir; Drug: ritonavir
Sponsor: Pfizer
Not yet recruiting
Evaluation of COVID-19 Vaccines Given as a Booster in Healthy Adults in Indonesia (MIACoV Indonesia) - Condition: COVID-19
Interventions: Biological: Pfizer-BioNTech Standard dose; Biological: AstraZeneca Standard dose; Biological: Pfizer-BioNTech Fractional dose; Biological: AstraZeneca Fractional dose; Biological: Moderna Standard dose; Biological: Moderna Fractional dose
Sponsors: Murdoch Childrens Research Institute; Universitas Padjadjaran (UNPAD); Universitas Indonesia (UI); Health Development Policy Agency, Ministry of Health Republic of Indonesia; Coalition for Epidemic Preparedness Innovations; The Peter Doherty Institute for Infection and Immunity
Not yet recruiting
A Study to Evaluate the Efficacy and Safety of DXP604 in Patients With Mild to Moderate COVID-19 - Condition: COVID-19
Intervention: Biological: DXP604
Sponsor:
Wuhan Institute of Biological Products Co., Ltd
Not yet recruiting
Sequential Immunization of Two Doses of Inactivated COVID-19 Vaccine (Omicron) in Vaccinated Population Aged 18 Years and Above - Condition: COVID-19
Interventions: Biological: BIBP Omicron Inactivated COVID-19 vaccine (Vero Cell); Biological: WIBP Omicron Inactivated COVID-19 vaccine (Vero Cell); Biological: COVID-19 Vaccine (Vero Cell), Inactivated
Sponsors: China National Biotec Group Company Limited; Beijing Institute of Biological Products Co Ltd.; Wuhan Institute of Biological Products Co., Ltd; The University of Hong Kong
Not yet recruiting
Immunogenicity and Safety of Booster Immunization of COVID-19 Vaccine (Vero Cell), Inactivated (Omicron Variant) in Healthy People Aged 18 Years and Above - Condition: COVID-19
Interventions: Biological: COVID-19 Vaccine (Vero cell), Inactivated (Omicron variant); Biological: COVID-19 Vaccine (Vero cell), Inactivated (CZ strain)
Sponsor:
Sinovac Research and Development Co., Ltd.
Not yet recruiting
A Randomized, Open-label, Dose-ranging Study in Adults and Pediatric Individuals ≥ 12 Years of Age to Assess the Safety, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of AZD7442, for Pre-exposure Prophylaxis of COVID-19 - Condition: Coronavirus Disease 2019 (COVID-19)
Intervention: Biological: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061])
Sponsor: AstraZeneca
Not yet recruiting
Inhaled Interferon α2b Treatment in Mild-to-moderate COVID-19 Infected Children - Conditions: COVID-19; Children
Interventions: Drug: Inhaled Interferon α2b; Other: Standard of Care
Sponsors: Children’s Hospital of Fudan University; RenJi Hospital; Shanghai Children’s Hospital; Shanghai Children’s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine
Recruiting
INTEGrating Ag-RDTs for COVID in MNCH,HIV and TB Services in Cameroon and Kenya:A Cluster Randomized Trial of Two Models - Condition: COVID-19
Intervention: Diagnostic Test: Test all
Sponsors:
Elizabeth Glaser Pediatric AIDS Foundation; UNITAID; Kenya Ministry of Health; Ministry of Public Health, Cameroon
Not yet recruiting
Pulmonary Rehabilitation Program With Pulsed Electromagnetic Field Therapy in Patients With Post-covid Sequelae. - Condition: COVID-19
Interventions: Device: Pulsed ectromagnetid field therapy; Other: Pulmonary rehabilitation program (PRP)
Sponsor: University of Malaga
Not yet recruiting
Paxlovid in the Treatment of COVID-19 Patients With Uremia - Conditions: COVID-19; Uremia
Interventions: Drug: Paxlovid; Drug: standard-of-care
Sponsor: Ruijin Hospital
Not yet recruiting
Telemedically Assisted Sampling of COVID-19 Patients - Is the Sampling Quality Sufficient - Conditions: Telemedicine; Pharynx; COVID-19
Intervention: Diagnostic Test: telemedically guided oropharyngeal + nasal (OP+N) self-sampling (GSS) and nasopharyngeal (NP) or OP+N sampling performed by health care professionals (HCP)
Sponsor: Teststation Praxis Dr. med Bielecki
Active, not recruiting
Improving Pediatric COVID-19 Vaccine Uptake Using an mHealth Tool - Conditions: COVID-19 Vaccines; Telemedicine; Vaccine Hesitancy; Pediatric ALL
Interventions: Behavioral: COVID-19 Vaccine Uptake App; Other: General Health App
Sponsors:
University of Arkansas; National Institutes of Health (NIH); University of Nebraska; University of Montana
Not yet recruiting
Retraction: Jiang, H.; Mei, Y.-F. SARS-CoV-2 Spike Impairs DNA Damage Repair and Inhibits V(D)J Recombination In Vitro. Viruses 2021, 13, 2056 - The published article […].
Palmitoylethanolamide (PEA) Inhibits SARS-CoV-2 Entry by Interacting with S Protein and ACE-2 Receptor - Lipids play a crucial role in the entry and egress of viruses, regardless of whether they are naked or enveloped. Recent evidence shows that lipid involvement in viral infection goes much further. During replication, many viruses rearrange internal lipid membranes to create niches where they replicate and assemble. Because of the close connection between lipids and inflammation, the derangement of lipid metabolism also results in the production of inflammatory stimuli. Due to its pivotal…
Infectious Bronchitis Virus Nsp14 Degrades JAK1 to Inhibit the JAK-STAT Signaling Pathway in HD11 Cells - Coronaviruses (CoVs) are RNA viruses that can infect a wide range of animals, including humans, and cause severe respiratory and gastrointestinal disease. The Gammacoronavirus avian infectious bronchitis virus (IBV) causes acute and contagious diseases in chickens, leading to severe economic losses. Nonstructural protein 14 (Nsp14) is a nonstructural protein encoded by the CoV genome. This protein has a regulatory role in viral virulence and replication. However, the function and mechanism of…
SARS-CoV-2 Envelope (E) Protein Binds and Activates TLR2 Pathway: A Novel Molecular Target for COVID-19 Interventions - This paper presents a molecular characterization of the interaction between the SARS-CoV-2 envelope (E) protein and TLR2. We demonstrated that the E protein, both as a recombinant soluble protein and as a native membrane protein associated with SARS-CoV-2 viral particles, interacts physically with the TLR2 receptor in a specific and dose-dependent manner. Furthermore, we showed that the specific interaction with the TLR2 pathway activates the NF-κB transcription factor and stimulates the…
A Unique Robust Dual-Promoter-Driven and Dual-Reporter-Expressing SARS-CoV-2 Replicon: Construction and Characterization - The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, SARS2) remains a great global health threat and demands identification of more effective and SARS2-targeted antiviral drugs, even with successful development of anti-SARS2 vaccines. Viral replicons have proven to be a rapid, safe, and readily scalable platform for high-throughput screening, identification, and evaluation of antiviral drugs against positive-stranded RNA viruses. In the study, we report a unique robust HIV long…
Comparison of Six Serological Immunoassays for the Detection of SARS-CoV-2 Neutralizing Antibody Levels in the Vaccinated Population - Neutralizing antibody (NAb) detection is critical for evaluating herd immunity and monitoring the efficacy of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, quantitative SARS-CoV-2 antibody levels after vaccination were measured by chemiluminescent immunoassays, enzyme immunoassays, and surrogate virus neutralization tests (sVNTs), as well as plaque reduction neutralization tests (PRNT). Sequential blood samples were collected before and 1 and 3…
A Broad Antiviral Strategy: Inhibitors of Human DHODH Pave the Way for Host-Targeting Antivirals against Emerging and Re-Emerging Viruses - New strategies to rapidly develop broad-spectrum antiviral therapies are urgently required for emerging and re-emerging viruses. Host-targeting antivirals (HTAs) that target the universal host factors necessary for viral replication are the most promising approach, with broad-spectrum, foresighted function, and low resistance. We and others recently identified that host dihydroorotate dehydrogenase (DHODH) is one of the universal host factors essential for the replication of many…
Probenecid Inhibits Respiratory Syncytial Virus (RSV) Replication - RNA viruses like SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV) are dependent on host genes for replication. We investigated if probenecid, an FDA-approved and safe urate-lowering drug that inhibits organic anion transporters (OATs) has prophylactic or therapeutic efficacy to inhibit RSV replication in three epithelial cell lines used in RSV studies, i.e., Vero E6 cells, HEp-2 cells, and in primary normal human bronchoepithelial (NHBE) cells, and in BALB/c mice. The studies…
Targeting of Silver Cations, Silver-Cystine Complexes, Ag Nanoclusters, and Nanoparticles towards SARS-CoV-2 RNA and Recombinant Virion Proteins - Background: Nanosilver possesses antiviral, antibacterial, anti-inflammatory, anti-angiogenesis, antiplatelet, and anticancer properties. The development of disinfectants, inactivated vaccines, and combined etiotropic and immunomodulation therapy against respiratory viral infections, including COVID-19, remains urgent. Aim: Our goal was to determine the SARS-CoV-2 molecular targets (genomic RNA and the structural virion proteins S and N) for silver- containing nanomaterials. Methods: SARS-CoV-2…
Montelukast Inhibits HCoV-OC43 Infection as a Viral Inactivator - Coronaviruses (CoVs) consist of a large group of RNA viruses causing various diseases in humans and in lots of animals. Human coronavirus (HCoV) OC43, the prototype of beta-coronavirus discovered in the 1960s, has been circulating in humans for long time, and infection with other emerging strains of beta-coronavirus (SARS-CoV, SARS-CoV-2, and MERS-CoV) can lead to severe illness and death. In this study, we found that montelukast, a leukotriene receptor antagonist, potently inhibited the…
Antimicrobial Biomaterial on Sutures, Bandages and Face Masks with Potential for Infection Control - Antimicrobial resistance (AMR) is a challenge for the survival of the human race. The steady rise of resistant microorganisms against the common antimicrobials results in increased morbidity and mortality rates. Iodine and a plethora of plant secondary metabolites inhibit microbial proliferation. Antiseptic iodophors and many phytochemicals are unaffected by AMR. Surgical site and wound infections can be prevented or treated by utilizing such compounds on sutures and bandages. Coating surgical…
Inclusion of a Phytomedicinal Flavonoid in Biocompatible Surface-Modified Chylomicron Mimic Nanovesicles with Improved Oral Bioavailability and Virucidal Activity: Molecular Modeling and Pharmacodynamic Studies - Morin hydrate (MH) is a widely-used Asian phytomedicinal flavonoid with a wide range of reported therapeutic activities. However, MH has limited oral bioavailability due to its low aqueous solubility and intestinal permeability, which in turn hinders its potential antiviral activity. The study reported herein was designed to encapsulate MH in polyethyleneglycolated (PEGylated) chylomicrons (PCMs) and to boost its antiviral activity and biological availability for oral administration using a rat…
Methylene Blue Is a Nonspecific Protein-Protein Interaction Inhibitor with Potential for Repurposing as an Antiviral for COVID-19 - We have previously identified methylene blue, a tricyclic phenothiazine dye approved for clinical use for the treatment of methemoglobinemia and for other medical applications as a small-molecule inhibitor of the protein-protein interaction (PPI) between the spike protein of the SARS-CoV-2 coronavirus and ACE2, the first critical step of the attachment and entry of this coronavirus responsible for the COVID-19 pandemic. Here, we show that methylene blue concentration dependently inhibits this…
Inhibition of Human Respiratory Influenza A Virus and Human Betacoronavirus-1 by the Blend of Double-Standardized Extracts of Aronia melanocarpa (Michx.) Elliot and Sambucus nigra L - Viral and bacterial diseases are among the greatest concerns of humankind since ancient times. Despite tremendous pharmacological progress, there is still a need to search for new drugs that could treat or support the healing processes. A rich source of bioactive compounds with antiviral potency include plants such as black chokeberry and elderberry. The aim of this study was to assess the in vitro antiviral ability of an originally designed double- standardized blend of extracts from Aronia…
Integrin/TGF-β1 Inhibitor GLPG-0187 Blocks SARS-CoV-2 Delta and Omicron Pseudovirus Infection of Airway Epithelial Cells In Vitro, Which Could Attenuate Disease Severity - As COVID-19 continues to pose major risk for vulnerable populations, including the elderly, immunocompromised, patients with cancer, and those with contraindications to vaccination, novel treatment strategies are urgently needed. SARS-CoV-2 infects target cells via RGD-binding integrins, either independently or as a co-receptor with surface receptor angiotensin-converting enzyme 2 (ACE2). We used pan-integrin inhibitor GLPG-0187 to demonstrate the blockade of SARS- CoV-2 pseudovirus infection of…