Vaccines against SARS-CoV-2, the virus that causes COVID-19, showed high efficacy against symptomatic illness caused by the ancestral strain. Yet recent variants such as Omicron and its sublineages substantially escape vaccine-induced neutralizing antibodies. In response, bivalent mRNA booster vaccines updated to better match the BA.4-5 lineages have been made available. Yet the reactogenicity of these vaccines might negatively impact willingness to receive the booster immunization. While serious side effects following vaccination are rare, mRNA vaccines frequently lead to mild adverse events such as injection site pain, lymphadenopathy, myalgia, and fever. Over-the-counter analgesics might mitigate some of these mild adverse events, but animal models of SARS-CoV-2 infection have shown that non-steroidal anti-inflammatory drugs (NSAIDs) substantially reduce antiviral antibody responses, which are the best correlates of protection against COVID-19. It remains unknown whether these same inhibitory effects are seen in humans after mRNA vaccination. We surveyed 6,010 individuals who received COVID-19 vaccines regarding analgesic use and correlated these results with Spike-specific antibody levels. We found no negative impact of analgesic use on antibody levels, and in fact observed slightly elevated concentrations of anti-Spike antibodies in individuals who used painkillers. Logistic regression analyses demonstrated a higher proportion of those experiencing fatigue and muscle aches between NSAID users and those not taking pain medication, suggesting that the elevated antibody levels were likely associated with inflammation and mild adverse events rather than analgesic use per se. Together, our results suggest no detriment to painkiller use to alleviate symptoms after vaccination against COVID-19.
Objective: To examine the scientific literature on mask-use as source control to protect others from respiratory infections before and after the onset of the COVID-19 pandemic. Design: Systematic review. Methods: We examined primary research on mask usage as a means of source control to protect others by reducing the spread of respiratory diseases and contrasted the literature published before the onset of the COVID-19 pandemic with that published afterward. Articles were obtained through a search of PubMed and a review of article references. March 1, 2020 was selected as the cutoff date to distinguish between the pre-COVID-19 and post-COVID-19 periods. Results: 195 articles met our inclusion criteria. The sample included 55 articles on source control published before the start of the COVID-19 pandemic, and 140 articles published after the pandemic began, representing a 154.5% increase. The percentage of randomized control trials (RCT) and cluster RCTs declined by 94.9% (p<0.001), representing only 1.4% of the post-pandemic literature. The percentage of studies conducted on human subjects declined by 48.8% (p<0.001), and the percentage of studies in healthcare facilities declined by 64.5% (p=0.019). One in 5 post-pandemic studies (21.4%) were conducted in real world settings; 1 in 10 post-pandemic studies (10.0%) were done with computer modeling. Study authors were significantly more supportive of masks as source control in the post-pandemic literature. Conclusions: The quality of evidence in the published literature on masks as source control is lower after the start of the COVID-19 pandemic, with notable shifts in methodologies, research subjects, setting, and author tone.
Virus-specific antibodies are important determinants of protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While regarded as the gold standard for detecting functional antibodies, conventional virus neutralisation tests (VNT) or pseudotyped virus neutralisation tests (pVNT) require biosafety level 2 or 3 facilities. Alternatively, the virus-free surrogate virus neutralisation test (sVNT) quantifies inhibitory antibodies that prevent the spike protein from binding to its receptor, human angiotensin-converting enzyme 2 (hACE2). We evaluated secreted nanoluciferase (NLuc)-tagged spike (S) protein fragments as diagnostic antigens in the sVNT in the framework of a vaccination study. First, spike fragments of different lengths were tested for their suitability as diagnostic antigens in a capture enzyme immunoassay (EIA) using unprocessed culture supernatants of transfected cells, identifying the receptor binding domain (RBD) of S as the optimal construct. The sensitivity of the in-house sVNT relying on the NLuc-labelled RBD equalled or surpassed a commercial sVNT (cPass, GenScript Diagnostics) and an in-house pVNT four weeks after the first vaccination (98% vs. 94% and 72%, respectively), reaching 100% in all assays four weeks after the second and third vaccinations. Additionally, serum reactivity with spike constructs of Omicron BA.1 was tested. Compared with a capture EIA, the in-house sVNT and pVNT displayed superior discrimination between wild-type- and variant-specific reactivity of sera. Differences in reactivity were most pronounced after the first and second vaccinations, whereas the third vaccination resulted in robust, cross-reactive detection of Omicron constructs. In conclusion, assays utilising NLuc-labelled protein fragments permit the quantification and functional assessment of SARS-CoV-2-specific antibodies and the detection of variant-specific differences in reactivity. Potential applications include monitoring therapy and vaccine efficacy and follow-up of prolonged disease courses in high-risk groups. Designed as straightforward, highly flexible modular systems, these tests can be readily adapted to further emerging viral variants.
We assessed Urban Scaling Theory using time-series data by quantifying allometric scaling relationships of coronavirus disease (COVID-19) cases, deaths, and demographic cohorts within and across three major variant waves of the pandemic (first, delta, omicron). Results indicate that with county-level population size in the United States, the burden of cases disproportionately impacted larger-sized counties. In contrast, the burden of deaths disproportionately impacted smaller counties, which may be partially due to a higher proportion of older adults who live in smaller counties. Future infectious disease burden across populations might be attenuated by applying Urban Scaling Theory to epidemiological efforts through identifying disease allometry and concomitant allocation of medical interventions.
The COVID-19 pandemic has presented a significant challenge to societal mental health. Yet, it remains unknown which factors influence the mental adaptation from lockdown to subsequent relaxation periods, particularly for vulnerable groups. This study used smartphone-based monitoring to explore how 74 individuals with major depression (MDD) and 77 healthy controls (HCs) responded to the transition from lockdown to relaxation during the first wave of the COVID-19 pandemic (March 21 to November 01, 2020) regarding interpersonal interactions, COVID-19-related fear (fear of participants9 own health, the health of close relatives, and the pandemics9 economic impact), and the feeling of isolation. Furthermore, we investigated the effect of a diagnosis of MDD and the experience of childhood maltreatment (CM) on adaptive functioning. During the transition from lockdown to relaxation, we observed an increase in direct contacts and a decrease in indirect contacts and self-perceived isolation in the study population. The diagnosis of MDD and the experience of CM moderated a maintenance of COVID-19-related fear: HCs and participants without the experience of CM showed a decrease in fear, while fear of participants with MDD and with an experience of CM did not change significantly. The finding that elevated COVID-19-related fear was sustained in vulnerable groups after lockdown measures were lifted could help guide psychosocial prevention efforts in future pandemic emergencies.
Background The COVID-19 pandemic amplified the risk environment for people who inject drugs (PWID), making continued access to harm reduction services imperative. Research has shown that some harm reduction service providers were able to continue to provide services throughout the pandemic. Most of these studies, however, focused on staff perspectives, not those of PWID. Our study examines changes in perceptions of access to harm reduction services among PWID participating in a longitudinal study conducted through the University of Illinois-Chicago9s Community Outreach Intervention Project field sites during the COVID-19 pandemic. Methods Responses to a COVID-19 module added to the parent study survey that assessed the impact of COVID-19 on PWID participating in an ongoing longitudinal study were analyzed to understand how study participants’ self-reported access to harm reduction services changed throughout the pandemic. Mixed effects logistic regression was used to examine difficulty in syringe access as an outcome of COVID-19 phase. Results Most participants reported that access to syringes and naloxone remained the same as prior to the pandemic. Participants had significantly higher odds of reporting difficulty in accessing syringes earlier in the pandemic. Conclusions The lack of perceived changes in harm reduction access by PWID and the decrease in those reporting difficulty accessing syringes as the pandemic progressed suggests the efficacy of adaptations to harm reduction service provision (e.g., window and mobile service) during the pandemic. Further research is needed to understand how the COVID-19 pandemic may have impacted PWIDs’ engagement with harm reduction services.
Pharmacist Management of Paxlovid eVisits - Conditions: COVID-19; Quality of Care
Interventions: Other: Pharmacist Care; Other: AFM Pool Care
Sponsors: Kaiser Permanente
Not yet recruiting
Equity Evaluation of Fact Boxes on Informed COVID-19 and Influenza Vaccination Decisions - Study Protocol - Conditions: COVID-19; Influenza
Interventions: Other: Fact box
Sponsors: Harding Center for Risk Literacy
Not yet recruiting
tDCS in the Management of Post-COVID Disorders - Conditions: Long COVID
Interventions: Device: Transcranial Direct Current Stimulation (tDCS); Behavioral: Motor Training; Behavioral: Cognitive Training
Sponsors: Universidade Federal de Pernambuco; SĂŁo Paulo State University
Recruiting
Early Awake Alterning Prone Positioning Combined With Non-invasive Oxygen Therapy in Patients With COVID-19. - Conditions: COVID-19 Pneumonia
Interventions: Other: Prone position; Other: Standard treatment
Sponsors: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Terminated
Effects of a Home-Based Exercise Intervention in Subjects With Long COVID - Conditions: Long COVID-19; Post-COVID-19 Syndrome
Interventions: Other: home-based concurrent exercise
Sponsors: University of Vienna
Recruiting
ACTIVATE in Public Housing - Conditions: Pneumonia; Influenza; Varicella Zoster; Meningitis; COVID-19; Vaccine Hesitancy
Interventions: Behavioral: Increasing Willingness and Uptake of Influenza, Pneumonia, Meningitis, HZV, and COVID-19 Vaccination
Sponsors: Charles Drew University of Medicine and Science
Not yet recruiting
Study of the Vector Vaccine GamCovidVac-M (Altered Antigenic Composition) - Conditions: COVID-19
Interventions: Biological: GamCovidVac-M vector vaccine for the prevention of COVID-19 with altered antigenic composition
Sponsors: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
Not yet recruiting
Study of the Vector Vaccine GamCovidVac for the Prevention of COVID-19 With Altered Antigenic Profile With Participation of Adult Volunteers - Conditions: COVID-19
Interventions: Biological: GamCovidVac vector vaccine for the prevention of COVID-19 (with altered antigenic profile)
Sponsors: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
Not yet recruiting
Effects of Cacao FLAvonoids in LOng Covid Patients (FLALOC) - Conditions: Long Covid19; Fatigue Syndrome, Chronic
Interventions: Dietary Supplement: Flavonoids
Sponsors: Guillermo Ceballos Reyes; Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado
Recruiting
Exercise Interventions in Post-acute Sequelae of Covid-19 - Conditions: COVID-19
Interventions: Behavioral: Exercise
Sponsors: University of Virginia
Not yet recruiting
The Efficacy of the 2023-2024 Updated COVID-19 Vaccines Against COVID-19 Infection - Conditions: COVID-19; Vaccine-Preventable Diseases; SARS CoV 2 Infection; Upper Respiratory Tract Infection; Upper Respiratory Disease
Interventions: Biological: Novavax COVID-19 vaccine (2023-2024 formula XBB containing); Biological: Pfizer COVID-19 mRNA vaccine (2023-2024 formula XBB containing)
Sponsors: Sarang K. Yoon, DO, MOH; Westat; Novavax
Not yet recruiting
Clinical Trial to Evaluate the Safety of RQ-01 in SARS-CoV-2 Positive Subjects - Conditions: COVID-19; Infectious Disease; Symptomatic COVID-19 Infection Laboratory-Confirmed; SARS CoV 2 Infection
Interventions: Combination Product: RQ-001; Other: Placebo
Sponsors: Red Queen Therapeutics, Inc.; PPD
Recruiting
Motivational Interviewing for Vaccine Uptake in Latinx Adults - Conditions: Vaccine Hesitancy
Interventions: Other: EHR alert; Behavioral: Motivational Interviewing; Behavioral: Warm hand off to nurse
Sponsors: Boston College; East Boston Neighborhood Health Center; Harvard School of Public Health (HSPH); Boston Children’s Hospital; National Institute of Nursing Research (NINR)
Not yet recruiting
Study of “Sputnik Lite” for the Prevention of COVID-19 With Altered Antigenic Composition. - Conditions: COVID-19
Interventions: Biological: “Sputnik Lite” vaccine for the prevention of COVID-19 with altered antigenic composition
Sponsors: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
Not yet recruiting
Study Will Assess the Safety, Neutralizing Activity and Efficacy of AZD3152 in Adults With Conditions Increasing Risk of Inadequate Protective Immune Response After Vaccination and Thus Are at High Risk of Developing Severe COVID-19 - Conditions: COVID-19, SARS-CoV-2
Interventions: Biological: Biological: AZD3152; Biological: Biological: Placebo
Sponsors: AstraZeneca
Not yet recruiting
Exploration of phenolic acid derivatives as inhibitors of SARS-CoV-2 main protease and receptor binding domain: potential candidates for anti-SARS-CoV-2 therapy - Severe acute respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the etiological virus of Coronavirus Disease 2019 (COVID-19) which has been a public health concern due to its high morbidity and high mortality. Hence, the search for drugs that incapacitate the virus via inhibition of vital proteins in its life cycle is ongoing due to the paucity of drugs in clinical use against the virus. Consequently, this study was aimed at evaluating the potentials of natural phenolics against the Main…
The Apolipoprotein E neutralizing antibody inhibits SARS-CoV-2 infection by blocking cellular entry of lipoviral particles - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent for coronavirus disease 2019 (COVID-19). Although vaccines have helped to prevent uncontrolled viral spreading, our understanding of the fundamental biology of SARS-CoV-2 infection remains insufficient, which hinders effective therapeutic development. Here, we found that Apolipoprotein E (ApoE), a lipid binding protein, is hijacked by SARS-CoV-2 for infection. Preincubation of SARS-CoV-2 with a neutralizing antibody…
Unnatural Endotype B PPAPs as Novel Compounds with Activity against Mycobacterium tuberculosis - Pre-SARS-CoV-2, tuberculosis was the leading cause of death by a single pathogen. Repetitive exposure of Mycobacterium tuberculosis(Mtb) supported the development of multidrug- and extensively drug-resistant strains, demanding novel drugs. Hyperforin, a natural type A polyprenylated polycyclic acylphloroglucinol from St. John’s wort, exhibits antidepressant and antibacterial effects also against Mtb. Yet, Hyperforin’s instability limits the utility in clinical practice. Here, we present photo-…
In vitro reconstitution of SARS-CoV-2 Nsp1-induced mRNA cleavage reveals the key roles of the N-terminal domain of Nsp1 and the RRM domain of eIF3g - SARS CoV-2 nonstructural protein 1 (Nsp1) is the major pathogenesis factor that inhibits host translation using a dual strategy of impairing initiation and inducing endonucleolytic cleavage of cellular mRNAs. To investigate the mechanism of cleavage, we reconstituted it in vitro on β-globin, EMCV IRES, and CrPV IRES mRNAs that use unrelated initiation mechanisms. In all instances, cleavage required Nsp1 and only canonical translational components (40S subunits and initiation factors), arguing…
Lipid droplets in Zika neuroinfection: Potential targets for intervention? - Lipid droplets (LD) are evolutionarily conserved lipid-enriched organelles with a diverse array of cell- and stimulus-regulated proteins. Accumulating evidence demonstrates that intracellular pathogens exploit LD as energy sources, replication sites, and part of the mechanisms of immune evasion. Nevertheless, LD can also favor the host as part of the immune and inflammatory response to pathogens. The functions of LD in the central nervous system have gained great interest due to their presence…
Tetherin antagonism by SARS-CoV-2 ORF3a and spike protein enhances virus release - The antiviral restriction factor, tetherin, blocks the release of several different families of enveloped viruses, including the Coronaviridae. Tetherin is an interferon-induced protein that forms parallel homodimers between the host cell and viral particles, linking viruses to the surface of infected cells and inhibiting their release. We demonstrate that SARS-CoV-2 infection causes tetherin downregulation and that tetherin depletion from cells enhances SARS-CoV-2 viral titres. We investigate…
Characterization of pre-existing anti-PEG and anti-AGAL antibodies towards PRX-102 in patients with Fabry disease - Polyethylene glycol (PEG)ylated drugs are used for medical treatment, since PEGylation either decreases drug clearance or/and shields the protein from undesirable immunogenicity. PEGylation was implemented in a new enzyme replacement therapy for Fabry disease (FD), pegunigalsidase-alfa (PRX-102). However, exposure to PEG via life-style products and vaccination can result in the formation of anti-PEG antibodies. We demonstrate the de novo formation of functional anti-PEG antibodies in a healthy…
W254 in furin functions as a molecular gate promoting anti-viral drug binding: Elucidation of putative drug tunneling and docking by non-equilibrium molecular dynamics - Furins are serine endoproteases that process precursor proteins into their biologically active forms, and they play essential roles in normal metabolism and disease presentation, including promoting expression of bacterial virulence factors and viral pathogenesis. Thus, furins represent vital targets for development of antimicrobial and antiviral therapeutics. Recent experimental evidence indicated that dichlorophenyl (DCP)-pyridine “BOS” drugs (e.g., BOS-318) competitively inhibit human furin…
The N-terminal peptide of the main protease of SARS-CoV-2, targeting dimer interface, inhibits its proteolytic activity - The main protease (Mpro) of SARS-CoV-2 cleaves 11 sites of viral polypeptide chains and generates essential non-structural proteins for viral replication. Mpro is an important drug target against COVID-19. In this study, we developed a real-time fluorometric turn-on assay system to evaluate Mpro proteolytic activity for a substrate peptide between NSP4 and NSP5. It produced reproducible and reliable results suitable for HTS inhibitor assays. Thus far, most inhibitors against Mpro target the…
Antcin-B, a phytosterol-like compound from Taiwanofungus camphoratus inhibits SARS-CoV-2 3-chymotrypsin-like protease (3CLPro) activity in silico and in vitro - Despite the remarkable development of highly effective vaccines, including mRNA-based vaccines, within a limited timeframe, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not been entirely eradicated. Thus, it is crucial to identify new effective anti-3CL^(Pro) compounds, pivotal for the replication of SARS-CoV-2. Here, we identified an antcin-B phytosterol-like compound from Taiwanofungus camphoratus that targets 3CL^(Pro) activity….
Designing peptides predicted to bind to the omicron variant better than ACE2 via computational protein design and molecular dynamics - Brought about by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease (COVID-19) pandemic has resulted in large numbers of worldwide deaths and cases. Several SARS-CoV-2 variants have evolved, and Omicron (B.1.1.529) was one of the important variants of concern. It gets inside human cells by using its S1 subunit’s receptor-binding domain (SARS-CoV-2-RBD) to bind to Angiotensin-converting enzyme 2 receptor’s peptidase domain (ACE2-PD). Using peptides to inhibit…
Porcine deltacoronavirus accessory protein NS6 harnesses VPS35-mediated retrograde trafficking to facilitate efficient viral infection - Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus with the potential to infect humans. Accessory protein NS6, encoded by PDCoV, is a key factor required for optimal viral replication. However, the precise mechanism(s) used by PDCoV NS6 to function remains largely unclear. The retromer is an evolutionarily highly conserved protein complex that plays an important role in normal cellular biological processes and viral replication. In this study, we identified VPS35,…
Natto extract inhibits infection caused by the Aujeszky’s disease virus in mice - Aujeszky’s disease virus (ADV), also known as Suid alphaherpesvirus 1, which mainly infects swine, causes life-threatening neurological disorders. This disease is a serious global risk factor for economic losses in the swine industry. The development of new anti-ADV drugs is highly anticipated and required. Natto, a traditional Japanese fermented food made from soybeans, is a well-known health food. In our previous study, we confirmed that natto has the potential to inhibit viral infections by…
Molecular docking analysis of novel quercetin derivatives for combating SARS-CoV-2 - Quercetin belongs to the flavonoid family, which is one of the most frequent types of plant phenolics. This flavonoid compound is a natural substance having a number of pharmacological effects, including anticancer and antioxidant capabilities, as well as being a strong inhibitor of various toxicologically important enzymes. We discuss the potential of newly recently synthesized quercetin-based derivatives to inhibit SARS-CoV-2 protein. ADMET analysis indicated that all of the studied compounds…
Native SEC and Reversed-Phase LC-MS Reveal Impact of Fab Glycosylation of Anti-SARS-COV-2 Antibodies on Binding to the Receptor Binding Domain - The binding affinity of monoclonal antibodies (mAbs) for their intended therapeutic targets is often affected by chemical and post-translational modifications in the antigen binding (Fab) domains. A new two-dimensional analytical approach is described here utilizing native size exclusion chromatography (SEC) to separate populations of antibodies and bound antibody-antigen complexes for subsequent characterization of these modifications by reversed-phase (RP) liquid chromatography-mass…