Background. Several studies assessed the effect of pre-morbid exposure to proton pump inhibitors (PPIs) on disease course in adult COVID-19 patients with somewhat inconsistent results. Methods. This population-based matched cohort study embraced first COVID-19 episodes in adults diagnosed up to August 15 2021 in Croatia. Considering over-the- counter (OTC) availability of PPIs, patients were classified based on exposure to PPIs and burden of PPI-requiring conditions as “non-users” (no issued prescriptions, no recorded treatment-requiring conditions between January 1 2019 and COVID-19 diagnosis), “possible users” (no issued prescriptions, recorded treatment-requiring conditions; OTC use possible) and “users” (different intensity of issued prescriptions over 12 months prior to diagnosis, at least one within 3 months). Subsets were mutually exactly matched in respect to a range of pre-COVID-19 characteristics. The contrast between “users” and “possible users” was considered the most informative for the effect of PPIs that is separate of the effect of PPI-requiring conditions. Results. Among 433609 COVID-19 patients, 332389 were PPI “non- users”, 18170 were “possible users”, and 55098 were “users”. Users and possible users were matched 41195 to 17334 and 33272 to 16434 in the primary and sensitivity analyses. There was no relevant difference between “users” and “possible users” regarding COVID-19-related mortality [RR=0.93 (95%CI 0.85-1.02; RD= -0.34% (-0.73, 0.03) in primary and RR=0.88 (0.78-0.98); RD=-0.45 (-0.80, -0.11) in sensitivity analysis] or COVID-19-related hospitalizations [RR=1.04 (0.97-1.13); RD=0.29% (-0.16, 0.73) in primary and RR=1.05 (0.97-1.15); RD=0.32% (-0.12, 0.75) in sensitivity analysis]. Conclusions. Pre-morbid exposure to PPIs does not affect the risk of death or hospitalization in adult COVID-19 patients.
The SARS-CoV-2 Omicron (B.1.1.529) variant first emerged as the BA.1 sub-lineage, with extensive escape from neutralizing immunity elicited by previous infection with other variants, vaccines, or combinations of both. Two new sub-lineages, BA.4 and BA.5, are now emerging in South Africa with changes relative to BA.1, including L452R and F486V mutations in the spike receptor binding domain. We isolated live BA.4 and BA.5 viruses and tested them against neutralizing immunity elicited to BA.1 infection in participants who were Omicron/BA.1 infected but unvaccinated (n=24) and participants vaccinated with Pfizer BNT162b2 or Johnson and Johnson Ad26.CoV.2S with breakthrough Omicron/BA.1 infection (n=15). In unvaccinated individuals, FRNT50, the inverse of the dilution for 50% neutralization, declined from 275 for BA.1 to 36 for BA.4 and 37 for BA.5, a 7.6 and 7.5-fold drop, respectively. In vaccinated BA.1 breakthroughs, FRNT50 declined from 507 for BA.1 to 158 for BA.4 (3.2-fold) and 198 for BA.5 (2.6-fold). Absolute BA.4 and BA.5 neutralization levels were about 5-fold higher in this group versus unvaccinated BA.1 infected participants. The observed escape of BA.4 and BA.5 from BA.1 elicited immunity is more moderate than of BA.1 against previous immunity. However, the low absolute neutralization levels for BA.4 and BA.5, particularly in the unvaccinated group, are unlikely to protect well against symptomatic infection. This may indicate that, based on neutralization escape, BA.4 and BA.5 have potential to result in a new infection wave.
The COVID-19 pandemic has shed light on the fractures of healthcare systems around the world, particularly in relation to the healthcare workforce. Frontline staff, in particular, have been exposed to unprecedented strain and delivering care during the pandemic has impacted their safety, mental health and wellbeing. The aim of this paper was to explore the experiences of HCWs delivering care in the UK during the COVID-19 pandemic to understand their wellbeing needs, experiences and strategies used to maintain wellbeing (at individual and organizational levels). We analysed 94 telephone interviews with HCWs and 2000 tweets about HCWs mental health taking place during the first year of the COVID-19 pandemic. Results were grouped under six themes: redeployment; wellbeing support and coping strategies; mental health effects; organisational support; social network and public support. These findings demonstrate a need for open conversations, where staff9s wellbeing needs and strategies can be shared and encouraged, rather than implementing solely top-down psychological interventions. At the macro level, findings also highlighted the impact on HCWs9 wellbeing of public and government support, as well as the need for ensuring protection through PPE, testing, and/or vaccines for frontline workers.
Background Despite the potential widespread global use of the ChAdOx1-S booster, to date there are no published data on the real-world effectiveness. VE studies have found one and two doses of the ChAdOx1-S vaccine to be highly effective, and clinical trial data have demonstrated enhanced immunity following a ChAdOx1-S booster. In England, some individuals received a ChAdOx1-S booster where vaccination with mRNA vaccines was clinically contraindicated. Methods The demographic characteristics of those who received a ChAdOx1-S booster were compared to those who received a BNT162b2 booster. A test-negative case control design was used to estimate vaccine effectiveness of the ChAdOx1-S booster against symptomatic disease and hospitalisation in England. Findings Those who received a ChAdOx1-S booster were more likely to be female (adjusted odds ratio (OR) 1.67 (1.64-1.71)), in a clinical risk group (adjusted OR 1.58 (1.54-1.63)), in the CEV group (adjusted OR 1.84 (1.79-1.89)) or severely immunosuppressed (adjusted OR 2.05 (1.96-2.13)). Protection against symptomatic disease in those aged 65 years and older peaked at 66.1% (16.6 to 86.3%) and 68.5% (65.7 to 71.2%) amongst those who received the ChAdOx1-S and BNT162b2 booster vaccines, respectively. Protection waned to 44.5% (22.4 to 60.2%) and 54.1% (50.5 to 57.5%) after 5-9 weeks. Protection against hospitalisation following Omicron infection peaked at 82.3% (64.2 to 91.3%) after receiving a ChAdOx1-S booster, as compared to 90.9% (88.7 to 92.7%) for those who received a BNT162b2 booster. Interpretation Differences in the population boosted with ChAdOx1-S in England renders direct comparison of vaccine effectiveness by manufacturer challenging. Nonetheless, this study supports the use of the ChAdOx1-S booster for protection against severe disease with COVID-19 in settings that have not yet offered booster doses and suggests that those who received ChAdOx1-S as a booster in England do not require re-vaccination ahead of others.
This work presents a methodology to recreate the observed dynamics of emerging infectious diseases and to generate short-term forecasts for their evolution based on superspreading events occurring on key calendar dates. The method is illustrated by the COVID-19 pandemic dynamics in Mexico and Peru up to January 31, 2022. We also produce scenarios obtained through the estimation of a time-dependent contact rate, with the main assumption that the dynamic of the disease is determined by the mobility and social activity of the population during holidays and other important calendar dates. First, historical changes in the effective contact rate on predetermined dates are estimated. Then, this information is used to forecast scenarios under the assumption that the trends of the effective contact rate observed in the past will be similar on the same but future key calendar dates. All other conditions are assumed to remain constant in the time scale of the projections. One of the main features of the methodology is that it avoids the necessity of fixing values of the dynamic parameters for the whole prediction period. Results show that considering the key dates as reference information is useful to recreate the different outbreaks, slow or fast-growing, that an epidemic can present and, in most cases, make good short-term predictions.
Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we performed longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identified transcriptional and proteomic signatures of COVID-19 severity, and found distinct temporal molecular profiles in patients with severe disease. Supervised learning revealed that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. Notably, we show that both the levels and trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, are the strongest predictors of clinical outcome. Strikingly, we observed that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4, providing a potential explanation for the prolonged elevation of thrombotic risk following COVID-19.
Anti-CD20 antibodies react with CD20 expressed not only on malignant B cells but also on normal B cells. It has been reported that patients treated with anti-CD20 antibodies had an insufficient response to two-dose mRNA SARS-CoV-2 vaccination. To investigate the efficacy of a third dose in these patients, we investigated serum IgG antibody titers for S1 protein after third vaccination in 22 patients treated with anti-CD20 antibody who failed two-dose vaccination. Results showed that overall, 50% of patients seroconverted. Although no patient who received the third dose within 1 year of the last anti-CD20 antibody administration showed an increase in S1 antibody titer, 69% of patients who received the third dose more than 1 year after the last anti-CD20 antibody administration seroconverted. Our data show that a third dose of vaccination is effective in improving seroconversion rate in patients treated with anti-CD20 antibody who failed standard two-dose vaccination.
Background: Wastewater-based epidemiology is a promising approach but robust epidemiological models to relate wastewater to community prevalence are lacking. Assessments of SARS-CoV-2 infection rates have relied primarily on convenience sampling, which does not provide reliable estimates of community prevalence because of inherent biases. Methods: From August 2020 to February 2021, we conducted a serial stratified randomized samplings to estimate the prevalence of anti-SARS-CoV-2 antibodies in 3,717 participants, and weekly sampling of community wastewater for SARS- CoV-2 concentrations in Jefferson County, KY. With the use of a Susceptible, Infected, Recovered (SIR)-type model, we obtained longitudinal estimates of prevalence and compared these with wastewater concentration, using regression analysis. Findings: Model analysis revealed significant temporal differences in epidemic peaks; the average incidence rate based on serological sampling in some areas was up to 50% higher than health department rates based on convenience sampling. The model-estimated average prevalence rates correlated well with wastewater (correlation=0.63). In regression analysis, a weekly unit increase in wastewater concentration of SARS-CoV-2 corresponded to an average increase of between 1-1.3 cases of SARS-CoV-2 infection per 100K residents. Interpretation: Publicly available health department incidence rates vastly underestimate true community incidence and wastewater has a high potential to provide robust estimates of community spread of infection. Funding: This work was supported by contracts from the Centers for Disease Control and Louisville-Jefferson County Metro Government, and grants from the James Graham Brown Foundation, the Owsley Brown II Family Foundation, Jewish Heritage Fund and the Center for Predictive Medicine for Biodefense and Emerging Infectious Disease.
This study aims to investigate the health-related quality of life and coping strategies among COVID-19 survivors in Bangladesh. Methods: This is a cross-sectional study of 2198 adult, male was 72.38% (n=1591) and female 27.6% (n=607), COVID-19 survivors living in Bangladesh. Data were collected from previously diagnosed COVID-19 participants (confirmed by an RT-PCR test) via door-to-door interviews in the eight different divisions in Bangladesh. For data collection, Bengali translated Brief COPE inventory and WHO Brief Quality of Life (WHO-QOLBREF) questionnaires were used. The data collection period was from June 2020 to March 2021. Results: Males 72.38% (1591) were more affected by COVID-19 than females 27.62% (607). Age showed significant correlations with physical, psychological and social relationships; whereas, gender showed only significant correlation with physical health (p<0.001). Marital status, occupation, living area, and co-morbidities showed significant co-relation with all four domains of QoL (p<0.001). Education and affected family members showed significant correlation with physical and social relationship (p<0.001). However, smoking habit showed significant correlations with both social relationship and environment (p<0.001). Age and marital status showed a significant correlation with avoidant coping strategy (p<0.001); whereas gender and co- morbidities showed significant correlation with problem focused coping strategies (p<0.001). Educational qualification, occupation and living area showed significant correlation with all three coping strategies (p<0.001). Conclusion: Survivors of COVID-19 showed mixed types of coping strategies; however, the predominant coping strategy was avoidant coping, followed by problem focused coping, with emotion focused coping reported as the least prevalent. Marital status, occupation, living area and co-morbidities showed a greater effect on QoL in all participants.
Background Solid organ transplant recipients have attenuated immune responses to SARS-CoV-2 vaccines. In this study, we report on immune responses to 3rd- (V3) and 4th- (V4) doses of heterologous and homologous vaccines in a kidney transplant population. Methods 724 kidney transplant recipients were prospectively screened for serological responses following 3 primary doses of a SARS-CoV2 vaccine. 322 patients were sampled post-V4 for anti-spike (anti-S), with 69 undergoing assessment of SARS-CoV-2 T-cell responses. All vaccine doses were received post-transplant, only mRNA vaccines were used for V3 and V4 dosing. All participants had serological testing performed post-V2 and at least once prior to their 1st dose of vaccine. Results 586/724 (80.9%) patients were infection-naive post-V3; 141/2586 (24.1%) remained seronegative at 31 (21-51) days post-V3. Timing of vaccination in relation to transplantation, OR: 0.28 (0.15-0.54), p=0.0001; immunosuppression burden, OR: 0.22 (0.13-0.37), p<0.0001, and a diagnosis of diabetes, OR: 0.49 (0.32-0.75), p=0.001, remained independent risk factors for non-seroconversion. Seropositive patients post-V3 had greater anti-S if primed with BNT162b2 compared with ChAdOx1, p=0.001. Post-V4, 45/239 (18.8%) infection-naive patients remained seronegative. De novo seroconversion post-V4 occurred in 15/60 (25.0%) patients who were seronegative post-V3. There was no difference in anti-S post-V4 by vaccine combination, p=0.50. Anti-S post-V4 were sequentially greater in those seroconverting post V2- compared with V3- , and V3- compared with V4-, at 1561 (567-5211), 379 (101-851) and 19 (9.7-48) BAU/ml respectively. T-cell responses were poor, with only 11/54 (20.4%) infection-naive patients having detectable T-cell responses post-V4, with no difference seen by vaccine type. Conclusion A significant proportion of transplant recipients remain seronegative following 3- and 4- doses of SARS-CoV-2 vaccines, with poor T-cell responses, and are likely to have inadequate protection against infection.
Objectives: To investigate how differential access to key interventions to reduce sexually transmitted infections (STI), HIV, and their sequelae changed during the COVID-19 pandemic. Methods: British participants (18-59y) completed a cross-sectional web survey one year (March to April 2021) after the initial lockdown in Britain. Quota-based sampling and weighting resulted in a quasi-representative population sample. We compared Natsal-COVID data with Natsal-3, a household-based probability sample cross-sectional survey (16-74y) conducted in 2010-12. Reported unmet need for condoms because of the pandemic and uptake of chlamydia testing/HIV testing/cervical cancer screening were analysed among sexually-experienced participants (18-44y) (n=2869, Natsal-COVID; n=8551, Natsal-3). Odds ratios adjusted for age (aOR) and other potential confounders (AOR) describe associations with demographic and behavioural factors. Results: In 2021, 6.9% of women and 16.2% of men reported unmet need for condoms because of the pandemic. This was more likely among participants: aged 18-24 years, of Black or Black British ethnicity, and reporting same-sex sex (past five years) or one or more new relationships (past year). Chlamydia and HIV testing were more commonly reported by younger participants, those reporting condomless sex with new sexual partners, and men reporting same-sex partners; a very similar distribution to 10 years previously (Natsal-3). However, there were differences during the pandemic, including stronger associations with chlamydia testing for men reporting same-sex partners; with HIV testing for women reporting new sexual partners; and with cervical screening among smokers. Conclusions: Our study suggests differential access to key primary and secondary STI/HIV prevention interventions continued during the first year of the COVID-19 pandemic. However, the available evidence does not suggest substantial changes in inequalities in since 2010-12. While the pandemic might not have exacerbated inequalities in access to primary and secondary prevention, it is clear that large inequalities persisted, typically among those at greatest STI/HIV risk.
Background: The outbreak of Coronavirus disease, which originated in Wuhan, China in 2019, has affected the lives of billions of people globally. Throughout 2020, the reproduction number of COVID-19 was widely used by decision- makers to explain their strategies to control the pandemic. Methods: In this work, we deduce and analyze both initial and effective reproduction numbers for 12 diverse world regions between February and December of 2020. We consider mobility reductions, mask wearing and compliance with masks, mask efficacy values alongside other non-pharmaceutical interventions (NPIs) in each region to get further insights in how each of the above factored into each region9s SARS- COV-2 transmission dynamic. Results: We quantify in each region the following reductions in the observed effective reproduction numbers of the pandemic: i) reduction due to decrease in mobility (as captured in Google mobility reports);
The COVAX program aims to provide global equitable access to life-saving vaccines. However, vaccine protectionism by wealthy nations has limited progress towards vaccine sharing goals. For example, as of April 2022 only ~20% of the population in Africa has received at least one COVID-19 vaccine dose. Here we use a two-nation coupled epidemic model to evaluate optimal vaccine-sharing policies given a selfish objective: in which countries with vaccine stockpiles aim to minimize fatalities in their own populations. Despite the selfish objective, we find it is often optimal for a donor nation to share a significant fraction of its vaccine stockpile. Mechanistically, sharing a vaccine stockpile reduces the intensity of outbreaks in the recipient nation, in turn reducing travel-associated incidence in the donor nation. This effect is intensified as vaccination rates decrease and epidemic coupling increases. Despite acting selfishly, vaccine sharing by a donor nation significantly reduces transmission and fatalities in the recipient nation. Moreover, we find that there are hybrid sharing policies that have a negligible effect on fatalities in the donor nation compared to the optimal policy while significantly reducing fatalities in the recipient nation. Altogether, these findings provide a rationale for nations with extensive vaccine stockpiles to share with other nations.
Clinical Performance Evaluation of the Bio-Self™ COVID-19 Antigen Home Test - Condition: COVID-19
Interventions: Device: Bio-Self COVID-19 Antigen Home Test; Device: Standard of Care COVID-19 Test; Diagnostic Test: RT-PCR Test
Sponsors: BioTeke USA, LLC; CSSi Life Sciences
Not yet recruiting
Immunogenicity and Safety of Fractional Booster Dose of COVID-19 Vaccines Available for Use in Pakistan/Brazil: A Phase 4 Dose-optimizing Trial - Condition: COVID-19
Interventions: Biological: Sinovac; Biological: AZD1222; Biological: BNT162b2
Sponsors: Albert B. Sabin Vaccine Institute; Aga Khan University; Oswaldo Cruz Foundation; Stanford University
Not yet recruiting
A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine as a Booster Dose in Population Aged 12-17 Years - Conditions: COVID-19; SARS-CoV-2 Infection
Interventions: Biological: SCTV01E; Biological: mRNA-1273
Sponsor: Sinocelltech Ltd.
Not yet recruiting
A First-In-Human Phase 1b Study of AmnioPul-02 in COVID-19 - Condition: COVID-19
Intervention: Drug: AmnioPul-02
Sponsor: Amniotics AB
Not yet recruiting
A Study of COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Older Adults. - Condition: COVID-19
Interventions: Biological: 20 μg dose of SYS6006; Biological: 30 μg dose of SYS6006; Biological: 50 μg dose of SYS6006; Drug: Placebo
Sponsor:
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Recruiting
Safety, Reactogenicity, and Immunogenicity Study of a Lyophilized COVID-19 mRNA Vaccine - Condition: Covid19
Interventions: Biological: A Lyophilized COVID-19 mRNA Vaccine; Biological: Placebo
Sponsor: Jiangsu Rec-Biotechnology Co., Ltd.
Not yet recruiting
A Study of COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Adults Aged 18 -59 Years. - Condition: COVID-19
Interventions: Biological: 20 μg dose of SYS6006; Biological: 30 μg dose of SYS6006; Biological: 50 μg dose of SYS6006; Drug: Placebo
Sponsor:
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Recruiting
Phase 2b/3 Trial of NuSepin® in COVID-19 Pneumonia Patients - Condition: COVID-19 Pneumonia
Interventions: Drug: NuSepin® 0.2 mg/kg; Drug: NuSepin® 0.4 mg/kg; Drug: Placebo
Sponsor: Shaperon
Recruiting
Aerobic Exercise and Covid-19 Survivors With Post-Intensive Care Syndrome (Pics) - Conditions: COVID-19; Post Intensive Care Syndrome
Interventions:
Other: Aerobic Exercise Training; Other: Home Plan
Sponsor: Riphah International University
Not yet recruiting
Efficacy and Safety of JT001 (VV116) Compared With Paxlovid - Condition: COVID-19
Interventions: Drug: JT001; Drug: Paxlovid
Sponsor:
Vigonvita Life Sciences
Recruiting
Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles as Early Goal Directed Therapy for COVID-19 Moderate-to-Severe Acute Respiratory Distress Syndrome (ARDS): A Phase III Clinical Trial - Condition: COVID-19 Acute Respiratory Distress Syndrome
Intervention: Drug: EXOFLO
Sponsor: Direct Biologics, LLC
Not yet recruiting
Use of Continuous Glucose Monitors in Coronavirus Disease 2019 ICU and Potential Inpatient Settings - Conditions: Covid19; Diabetes Mellitus
Intervention: Device: continuous glucose monitoring
Sponsor: Tanureet K Arora
Completed
Phase Ⅱ Clinical Trial of SARS-CoV-2 mRNA Vaccine - Condition: SARS-CoV-2
Interventions: Biological: SARS-CoV-2 (LVRNA009) 50μg group; Biological: SARS-CoV-2 (LVRNA009) 100μg group; Other: Placebo
Sponsors: AIM Vaccine Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention
Active, not recruiting
Sample Collection for Evaluation of the Panbio™ COVID-19/ Flu A&B Rapid Panel. - Conditions: COVID-19; Influenza A; Influenza Type B
Intervention: Diagnostic Test: Nasal and Nasopharyngeal Sampling of the Panbio™ COVID-19/ Flu A&B Rapid Panel
Sponsor: Abbott Rapid Dx
Recruiting
Pilot Trial on Immunosuppression Modulation to Increase SARS-CoV-2 Vaccine Response in Kidney Transplant Recipients - Condition: COVID-19
Interventions: Other: Immunosuppression reduction; Other: No immunosuppression reduction
Sponsor: Medical University of Vienna
Active, not recruiting
Interleukin 6 inhibition in severe COVID-19: Another piece of the puzzle - No abstract
Nafamostat mesylate monotherapy in patients with moderate COVID-19 : A single-center retrospective study - Coronavirus disease 2019 (COVID-19) expanded dramatically all over the world. Nafamostat mesylate inhibits the intracellular entry of novel severe acute respiratory syndrome coronavirus 2 and it has been thought as the therapeutic potential of treatment for patients with COVID-19. In the present study, patients with moderate COVID-19 who were admitted to our hospital were retrospectively analyzed. 31 patients received nafamostat mesylate monotherapy and 33 patients received conservative…
A method for the generation of pseudovirus particles bearing SARS coronavirus spike protein in high yields - The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has threatened human health and the global economy. Development of additional vaccines and therapeutics is urgently required, but such development with live virus must be conducted with biosafety level 3 confinement. Pseudotyped viruses have been widely adopted for studies of virus entry and pharmaceutical development to overcome this restriction. Here we describe a modified protocol to generate vesicular…
Xuanfei Baidu decoction attenuates intestinal disorders by modulating NF-κB pathway, regulating T cell immunity and improving intestinal flora - CONCLUSIONS: Our data indicate that XFBD treatment attenuated intestinal disorders associated with inhibiting inflammation, remodeling of intestinal immunity, and improving intestinal flora. These findings provide a scientific basis for the clinical use of XFBD and offer a potential therapeutic approach for the treatment of COVID-19 patients with intestinal symptoms.
Regulation of IFNα-induced expression of the short ACE2 isoform by ULK1 - The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to hijack angiotensin converting enzyme 2 (ACE2) for entry into mammalian cells. A short isoform of ACE2, termed deltaACE2 (dACE2), has recently been identified. In contrast to ACE2, the short dACE2 isoform lacks the ability to bind the spike protein of SARS-CoV-2. Several studies have proposed that expression of ACE2 and/or dACE2 is induced by interferons (IFNs). Here, we report that drug-targeted…
Promising therapeutic approach for SARS-CoV-2 infection by using a rutin-based combination therapy - The development of new therapeutic approaches for SARS-CoV-2 infection is of particular current importance. The combination therapy proposed here is based on already proven, safe compounds. The natural compound rutin, one of the six therapy components, has the potential to inhibit both viral and host cell targets. In addition, this therapy involves the use of acetylsalicylic acid, vitamin C and vitamin D 3 , which should be administered together with calcium and magnesium. The importance of each…
Phosphate-regulated expression of the SARS-CoV-2 receptor-binding domain in the diatom Phaeodactylum tricornutum for pandemic diagnostics - The worldwide COVID-19 pandemic caused by the SARS-CoV-2 betacoronavirus has highlighted the need for a synthetic biology approach to create reliable and scalable sources of viral antigen for uses in diagnostics, therapeutics and basic biomedical research. Here, we adapt plasmid-based systems in the eukaryotic microalgae Phaeodactylum tricornutum to develop an inducible overexpression system for SARS-CoV-2 proteins. Limiting phosphate and iron in growth media induced expression of the…
Inhibitory mechanism of Ambroxol and Bromhexine Hydrochlorides as potent blockers of molecular interaction between SARS-CoV-2 spike protein and human angiotensin-converting Enzyme-2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects the host cells through interaction of its spike protein with human angiotensin-converting enzyme 2 (hACE-2). High binding affinity between the viral spike protein and host cells hACE-2 receptor has been reported to enhance the viral infection. Thus, the disruption of this molecular interaction will lead to reduction in viral infectivity. This study, therefore, aimed to analyze the inhibitory potentials of two mucolytic drugs;…
A raising dawn of pentoxifylline in management of inflammatory disorders in Covid-19 - The existing pandemic viral infection caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) leads to coronavirus disease 2019 (Covid-19). SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as an entry-point into affected cells and down-regulation of ACE2 by this virus triggers the release of pro-inflammatory cytokines and up- regulation of angiotensin II. These changes may lead to hypercytokinemia and the development of cytokine storm with the development of acute…
The determination of haemagglutinin influenza antibodies in the Polish population in the epidemic season 2020/2021 during the SARS-CoV-2 pandemic - The aim of the study was to prove the level of antibodies against haemagglutinin in the sera of people from seven age groups in the epidemic season 2020/2021 in Poland to determine the differentiation of the antibody level and the protection rate depending on age. The level of anti-haemagglutinin antibodies was established by haemagglutinin inhibition test (HAI). A total of 700 randomly selected sera from people belonging to 7 different age groups were tested. The results confirmed the presence…
Harnessing Natural Products by a Pharmacophore-Oriented Semisynthesis Approach for the Discovery of Potential Anti- SARS-CoV-2 Agents - Natural products possessing unique scaffolds may have antiviral activity but their complex structures hinder facile synthesis. A pharmacophore-oriented semisynthesis approach was applied to (-)-maoelactone A ( 1 ) and oridonin ( 2 ) for the discovery of anti-SARS-CoV-2 agents. The Wolff rearrangement/lactonization cascade (WRLC) reaction was developed to construct the unprecedented maoelactone-type scaffold during semisynthesis of 1 . Further mechanistic study suggested a concerted mechanism for…
Inflammasome activation in infected macrophages drives COVID-19 pathology - Severe COVID-19 is characterized by persistent lung inflammation, inflammatory cytokine production, viral RNA, and sustained interferon (IFN) response all of which are recapitulated and required for pathology in the SARS-CoV-2 infected MISTRG6-hACE2 humanized mouse model of COVID-19 with a human immune system^(1-20). Blocking either viral replication with Remdesivir^(21-23) or the downstream IFN stimulated cascade with anti-IFNAR2 in vivo in the chronic stages of disease attenuated the…
Recent advances in passive immunotherapies for COVID-19: The Evidence-Based approaches and clinical trials - In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing a global pandemic called COVID-19. Currently, there is no definitive treatment for this emerging disease. Global efforts resulted in developing multiple platforms of COVID-19 vaccines, but their efficacy in humans should be wholly investigated in the long-term clinical and epidemiological follow-ups. Despite the international efforts, COVID-19 vaccination accompanies challenges, including financial and…
Mutations in the SARS-CoV-2 RNA dependent RNA polymerase confer resistance to remdesivir by distinct mechanisms - The nucleoside analog remdesivir (RDV) is a Food and Drug Administration (FDA)-approved antiviral for treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Thus, it is critical to understand factors that promote or prevent RDV resistance. We passaged SARS-CoV-2 in the presence of increasing concentrations of GS-441524, the parent nucleoside of RDV. After 13 passages, we isolated three viral lineages with phenotypic resistance as defined by increases in…
A multifunctional colorimetric sensor array for bacterial identification and real-time bacterial elimination to prevent bacterial contamination - Effective identification and real-time inactivation of pathogenic microorganisms is of great importance for preventing their infection and spread in public health, especially considering the huge threat of coronavirus disease 2019 (COVID-19). Herein, a novel multifunctional colorimetric sensor array with 3,3’,5,5’-tetramethylbenzidine (TMB) as a single probe has been constructed. TMB can be efficiently oxidized to generate oxidized TMB (oxTMB) by HAuCl(4), which displays four characteristic…