scholarly journals Contribution of endogenous and exogenous antibodies to clearance of SARS-CoV-2 during convalescent plasma therapy

2021 ◽  
Author(s):  
Maddalena Marconato ◽  
Irene A. Abela ◽  
Anthony Hauser ◽  
Magdalena Schwarzmüller ◽  
Rheliana Katzensteiner ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Early Stage ◽  
Antibody Therapy ◽  
Viral Clearance ◽  
Therapeutic Effects ◽  
Efficacy Evaluation ◽  
Plasma Therapy ◽  
Early Stages ◽  
Rapid Clearance ◽  
The Impact

AbstractNeutralizing antibodies are considered a key correlate of protection by current SARS-CoV-2 vaccines. The ability of antibody-based therapies, including convalescent plasma, to affect established disease remains to be elucidated. Only few monoclonal therapies and only when used at a very early stage of infection have shown efficacy. Here, we conducted a proof-of-principle study of convalescent plasma therapy in a phase I trial in 30 COVID-19 patients including immunocompromised individuals hospitalized early after onset of symptoms. A comprehensive longitudinal monitoring of the virologic, serologic, and disease status of recipients in conjunction with detailed post-hoc seroprofiling of transfused convalescent plasma, allowed deciphering of parameters on which plasma therapy efficacy depends. Plasma therapy was safe and had a significant effect on viral clearance depending on neutralizing and spike SARS-CoV-2 antibody levels in the supplied convalescent plasma. Endogenous immunity had strong effects on virus control. Lack of endogenous neutralizing activity at baseline was associated with a higher risk of systemic viremia. The onset of endogenous neutralization had a noticeable effect on viral clearance but, importantly, even after adjusting for their endogenous neutralization status recipients benefitted from therapy with high neutralizing antibody containing plasma.In summary, our data demonstrate a clear impact of exogenous antibody therapy on the rapid clearance of viremia in the early stages of infection and provide directions for improved efficacy evaluation of current and future SARS-CoV-2 therapies beyond antibody-based interventions. Incorporating an assessment of the endogenous immune response and its dynamic interplay with viral production is critical for determining therapeutic effects.One Sentence SummaryThis study demonstrates the impact of exogenous antibody therapy by convalescent plasma containing high neutralizing titers on the rapid clearance of viremia in the early stages of SARS-CoV-2 infection.

Review Article on Convalescent Plasma Therapy For COVID-19

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1750-1754
Author(s):  
Chahak Goyal
Keyword(s):  
Neutralizing Antibodies ◽  
Survival Rates ◽  
Antibody Therapy ◽  
Scientific Data ◽  
Emerging Infections ◽  
Plasma Therapy ◽  
The Us ◽  
Duration Of Infection ◽  
Novel Coronavirus ◽  
Further Development

In December 2019, China witnessed a novel coronavirus (COVID 19) in Wuhan which eventually became a pandemic on March 11, 2020. No specific drugs, vaccines have been approved yet for its treatment as it is a novel virus, though convalescent plasma is expected to increase the survival rates and also it is easily available. Studies have shown that in every epidemic, medical professionals often use plasma because it is the only available option at that time. This passive antibody therapy has been used  since the 1890s to treat emerging infections and diseases like measles, Ebola, H1N1 flu, polio, etc. Researchers at John Hopkins University were specially the first ones to get approval from the FDA for the clinical trials as in some cases of emergency, they tried plasma therapy and got success. After China and the US and several other countries showed relative improvement rates with convalescent plasma therapy, INDIA has therefore also given the go-ahead for framing a protocol to conduct a clinical trial for the same. Plasma collected from recovered COVID patients has neutralizing antibodies which are expected to reduce the duration of infection. According to the scientific data, Convalescent Plasma Therapy in COVID 19 seems effective, safe and reduces death rates. Further development of improved plasma, vaccines and other therapeutic agents depends on the quick generation of data on pathogenesis and immune response of SARS- COV-2

scholarly journals Comprehensive mapping of binding hot spots of SARS-CoV-2 RBD-specific neutralizing antibodies for tracking immune escape variants

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Chunyan Yi ◽  
Xiaoyu Sun ◽  
Yixiao Lin ◽  
Chenjian Gu ◽  
Longfei Ding ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Early Stage ◽  
Neutralizing Antibody ◽  
Additive Effect ◽  
Escape Mutation ◽  
Prospective Surveillance ◽  
Antibody Recognition ◽  
Antigenic Sites ◽  
The Impact

Abstract Background The receptor-binding domain (RBD) variants of SARS-CoV-2 could impair antibody-mediated neutralization of the virus by host immunity; thus, prospective surveillance of antibody escape mutants and understanding the evolution of RBD are urgently needed. Methods Using the single B cell cloning technology, we isolated and characterized 93 RBD-specific antibodies from the memory B cells of four COVID-19 convalescent individuals in the early stage of the pandemic. Then, global RBD alanine scanning with a panel of 19 selected neutralizing antibodies (NAbs), including several broadly reactive NAbs, was performed. Furthermore, we assessed the impact of single natural mutation or co-mutations of concern at key positions of RBD on the neutralization escape and ACE2 binding function by recombinant proteins and pseudoviruses. Results Thirty-three amino acid positions within four independent antigenic sites (1 to 4) of RBD were identified as valuable indicators of antigenic changes in the RBD. The comprehensive escape mutation map not only confirms the widely circulating strains carrying important immune escape RBD mutations such as K417N, E484K, and L452R, but also facilitates the discovery of new immune escape-enabling mutations such as F486L, N450K, F490S, and R346S. Of note, these escape mutations could not affect the ACE2 binding affinity of RBD, among which L452R even enhanced binding. Furthermore, we showed that RBD co-mutations K417N, E484K, and N501Y present in B.1.351 appear more resistant to NAbs and human convalescent plasma from the early stage of the pandemic, possibly due to an additive effect. Conversely, double mutations E484Q and L452R present in B.1.617.1 variant show partial antibody evasion with no evidence for an additive effect. Conclusions Our study provides a global view of the determinants for neutralizing antibody recognition, antigenic conservation, and RBD conformation. The in-depth escape maps may have value for prospective surveillance of SARS-CoV-2 immune escape variants. Special attention should be paid to the accumulation of co-mutations at distinct major antigenic sites. Finally, the new broadly reactive NAbs described here represent new potential opportunities for the prevention and treatment of COVID-19.

Neutralizing antibodies to interferon beta-1b multiple sclerosis: a clinico-radiographic paradox in the BEYOND trial

2011 ◽  
Vol 18 (2) ◽  
pp. 181-195 ◽  
Author(s):  
Douglas S Goodin ◽  
Hans-Peter Hartung ◽  
Paul O’Connor ◽  
Massimo Filippi ◽  
Barry Arnason ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Interferon Beta ◽  
Negative Impact ◽  
Therapeutic Effects ◽  
Radiographic Outcomes ◽  
Baseline Factors ◽  
Clinical Measures ◽  
The Impact ◽  
To Receive ◽  
The Relationship

Background: The frequency and impact of neutralizing antibodies (NAbs) to interferon beta-1b (IFNβ-1b) on clinical and radiographic outcomes is controversial. Objective: To assess NAb impact in the BEYOND study. Methods: 2244 patients were randomized (2:2:1) to receive IFNβ-1b, either 250 or 500 µg, or glatiramer acetate, 20 mg, and observed for 2–3.5 years. NAb titers were determined every 6 months. A titer ≥20 NU/ml was considered NAb positive. Efficacy was compared between NAb-positive and NAb-negative patients, using comprehensive statistical analyses, taking into account the delayed appearance of NAbs, the time-dependent changes in the relapse rate, spontaneous reversions to NAb-negative status, NAb-titer level, and also adjusting for baseline factors. Results: In the IFNβ-1b 250 µg group, NAb-positive titers were detected (≥ once) in 319 patients (37.0%); of these, 112 (35.1%) reverted to NAb-negative status. In the IFNβ-1b 500 µg group, 340 patients (40.7%) became NAb-positive and 119 (35.0%) reverted to NAb-negative status. In both IFNβ groups, especially the 250 µg arm, NAb-positive status was not associated with a convincing impact on any clinical outcome measure by any statistical analysis. By contrast, in both IFNβ groups, NAbs were associated with a very consistent deleterious impact on most MRI outcomes. Conclusion: There was a notable dissociation between the impact of NAbs on MRI and clinical outcomes. On MRI measures, the impact was consistent and convincing, whereas on clinical measures a negative impact of NAbs was not found. The basis for this clinico-radiographic paradox is unknown but it suggests that the relationship between NAbs and the therapeutic effects of IFNβ-1b is complex.

scholarly journals Anticipating EGFR Targeting in Early Stages of Lung Cancer: Leave No Stone Unturned

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2685
Author(s):  
Lorenzo Belluomini ◽  
Silvia Teresa Riva ◽  
Michele Simbolo ◽  
Riccardo Nocini ◽  
Ilaria Trestini ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Early Stage ◽  
Target Therapy ◽  
Complete Response ◽  
Early Stage Lung Cancer ◽  
Early Stages ◽  
Resected Nsclc ◽  
Egfr Mutant ◽  
The Impact

 Background: The current treatment landscape of early stage lung cancer is rapidly evolving, particularly in EGFR mutant non-small cell lung cancer (NSCLC), where target therapy is moving to early stages. In the current review, we collected the available data exploring the impact of EGFR targeting in both neoadjuvant and adjuvant settings, underlying lights and shadows and discussing the existing open issues. Methods: We performed a comprehensive search using PubMed and the proceedings of major international meetings to identify neoadjuvant/adjuvant trials with EGFR tyrosine kinase inhibitors (TKIs) in NSCLC. Results: Limited data are available so far about the activity/efficacy of neoadjuvant TKIs in EGFR mutant NSCLC, with only modest downstaging and pathological complete response rates reported. Differently, the ADAURA trial already proposed osimertinib as a potential new standard of care in resected NSCLC harboring an activating EGFR mutation. Conclusion: Anticipating targeted therapy to early stage EGFR mutant NSCLC presents great opportunities but also meaningful challenges in the current therapeutic/diagnostic pathway of lung cancer care. Appropriate endpoint(s) selection for clinical trials, disease progression management, patients’ and treatment selection, as well as need to address the feasibility of molecular profiling anticipation, represent crucial issues to face before innovation can move to early stages. 

KAJIAN DAMPAK KEBIJAKAN PENUTUPAN LOKALISASI TELEJU OLEH PEMERINTAH KOTA PEKANBARU

2017 ◽  
Vol 15 (2) ◽  
pp. 78
Author(s):  
M. Zainuddin
Keyword(s):  
Social Order ◽  
Qualitative Method ◽  
Negative Impact ◽  
Early Stage ◽  
Policy Research ◽  
Research Approach ◽  
Policy Content ◽  
The Government ◽  
Closure Policy ◽  
The Impact

This research to analyze the impact of closure policy Teleju brothel by Pekanbaru govermentin 2010. Guidelines for works are Pekanbaru Local Regulations No. 12 of 2008 on Social Order-liness. Closure this brothel inflicts positive and negative impact for society.The research wasconducted to obtain early stage formula for the government to take action against the prostitu-tion activities. This research uses policy research approach with a qualitative method, becausein prostitution activities and prohibition by goverment is an assessment that needs to be done byanalyzing documents and unstructured interview.The results showed that after the closing of the Teleju brothel have an impact on the deploy-ment of a prostitution and affect the economy of the surrounding residents. Government seeksto tackle prostitution in Pekanbaru by moving the brothel, conduct regular raids and providetraining. The effort is considered to be less than the maximum because the handling is not basedon the root of the problem and not programmed properly. There are several causes of failure ofgovernment to overcome the prostitution problem in Pekanbaru, including: policy content isless focus on the prostitution problem, the government did not proceeds with data, lack of finan-cial support, contra productive programs between local government with the police and TNI,and the policy object is difficult to be given understanding.

HBOT Application at Cases of Gingival Inflammation

2019 ◽  
Author(s):  
Ilma Robo
Keyword(s):  
Root Resorption ◽  
Periodontal Diseases ◽  
Therapeutic Effects ◽  
Clinical Effects ◽  
Gingival Inflammation ◽  
Beneficial Effects ◽  
New Therapeutic Approaches ◽  
Short Period ◽  
Mechanical Therapy ◽  
The Impact

The treatment of periodontal diseases, mainly of their origin, with the most common clinical manifestation in form of gingival inflammation, is manifold and powerful, including: mechanical therapy, antibiotic, antiseptic and various approaches to treatment, which are recommended to be used within a short period of time. New therapeutic approaches have been proven as alternative treatment to conventional therapy, or in combination with conventional therapies, to reduce the number of periodontopathic pathogens in gingival sulcus. HBOT has a detrimental effect on periodontal microorganisms, as well as beneficial effects on the healing of periodontal tissue, increasing oxygen pressure in gingival pockets. Our study is aimed at reviewing the current published literature on hyperbaric oxygen therapy and focuses on role of HBOT as a therapeutic measure for the individual with periodontal disease in general and for the impact on the recovery of gingival inflammation. HBOT and periodontal treatment together, reduce up to 99% of the gram-negative anaerobic load of subgingival flora. HBOT, significantly reduces subgingival anaerobic flora. Clinical effects in 2-year follow-up of treated patients are sensitive. Reduction of gingival hemorrhage indexes, depth of peritoneum, plaque index, occurs in cases of combination of HBOT and detraction. Reduced load persists up to 2 months after therapy. The significant increase in connective tissue removal starts at the end of 2nd week, to achieve the maximum in week 3-6 of application. HBOT used for re-implantation, stimulates the healing of periodontal membrane, pulp, prevents root resorption, healing of periodontal lining tissues. HBOT, significantly reduces the hemorrhage index with 1.2 value difference, 0.7mm probe depth, reduces gingival fluid by 2. HGH exposure is increased by gingival blood flow, with a difference of 2 in measured value. The therapeutic effects of HBOT in the value of the evaluation index can be saved up to 1-year post treatment.

Fluoxetine Protects against Dendritic Spine Loss in Middle-aged APPswe/PSEN1dE9 Double Transgenic Alzheimer’s Disease Mice

2020 ◽  
Vol 17 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Jing Ma ◽  
Yuan Gao ◽  
Wei Tang ◽  
Wei Huang ◽  
Yong Tang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Early Stage ◽  
Learning Ability ◽  
Middle Aged ◽  
Protein Levels ◽  
Spine Pathology ◽  
The Impact

Background: Studies have suggested that cognitive impairment in Alzheimer’s disease (AD) is associated with dendritic spine loss, especially in the hippocampus. Fluoxetine (FLX) has been shown to improve cognition in the early stage of AD and to be associated with diminishing synapse degeneration in the hippocampus. However, little is known about whether FLX affects the pathogenesis of AD in the middle-tolate stage and whether its effects are correlated with the amelioration of hippocampal dendritic dysfunction. Previously, it has been observed that FLX improves the spatial learning ability of middleaged APP/PS1 mice. Objective: In the present study, we further characterized the impact of FLX on dendritic spines in the hippocampus of middle-aged APP/PS1 mice. Results: It has been found that the numbers of dendritic spines in dentate gyrus (DG), CA1 and CA2/3 of hippocampus were significantly increased by FLX. Meanwhile, FLX effectively attenuated hyperphosphorylation of tau at Ser396 and elevated protein levels of postsynaptic density 95 (PSD-95) and synapsin-1 (SYN-1) in the hippocampus. Conclusion: These results indicated that the enhanced learning ability observed in FLX-treated middle-aged APP/PS1 mice might be associated with remarkable mitigation of hippocampal dendritic spine pathology by FLX and suggested that FLX might be explored as a new strategy for therapy of AD in the middle-to-late stage.

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