New variants of SARS-CoV-2, vaccine immune response and the Brazilian reality

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly pathogenic β-coronavirus, is the etiologic agent of coronavirus disease 2019 (COVID-19), which gave rise to a difficult to control pandemic, especially in Brazil. Approximately 4,000 mutations have been identified in SARS-CoV-2, with the majority being redundant without having any biological effect on the virus. The aim of the present study was to objectively understand how new SARS-CoV-2 variants can affect vaccine response, in addition to highlighting the current situation in Brazil in the face of the pandemic and considering epidemiological and immunological aspects of COVID-19. The main protective correlate investigated in most vaccines is the neutralizing antibody titer induced by immunizing agents, observed in the pre-clinical phase in animals, whose action is to block the binding of the spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor, preventing infection. Up to the second half of 2021, the variants that are of greatest concern worldwide and require molecular surveillance are Alpha variant (or B.1.1.7 lineage), Beta (or B.1.351 lineage), Gamma (or P1 lineage) and Delta (or B.1.617.2 lineage). Brazil finds itself in a highly unfavorable scenario, with the circulation of variants of concern, mainly Gamma and Delta, with high fatality rates for COVID-19 and low vaccination rate. Given the still latent situation of the COVID-19 pandemic in Brazil, the lack of global planning for action strategies for non-pharmacological prevention measures, there is an imminent risk of the emergence of new variants due to the finding of susceptible hosts and the high proliferative rate of SARS-CoV-2. It is urgent to increase the genotyping of positive samples isolated from infected individuals, the speed of vaccination of the entire population and the unification of non pharmacological preventive measures throughout the country.

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DNA-Directed Patterning for Versatile Validation and Characterization of a Lipid-Based Nanoparticle Model of SARS-CoV-2

10.26434/chemrxiv.14208455 ◽

2021 ◽

Author(s):

Molly Kozminsky ◽

Thomas Carey ◽

Lydia L. Sohn

Keyword(s):

High Throughput ◽

Glass Substrate ◽

Rapid Development ◽

Neutralizing Antibody ◽

S Protein ◽

Biological Relevance ◽

The Face ◽

Great Control ◽

Tetraspanin Cd63

Lipid-based nanoparticles have risen to the forefront of the COVID-19 pandemic—from encapsulation of vaccine components to modeling the virus, itself. Their rapid development in the face of the volatile nature of the pandemic requires high-throughput, highly flexible methods for characterization. DNA-directed patterning is a versatile method to immobilize and segregate lipid-based nanoparticles for subsequent analysis. DNA-directed patterning selectively conjugates oligonucleotides onto a glass substrate and then hybridizes them to complementary oligonucleotides tagged to the liposomes, thereby patterning them with great control and precision. The power of this method is demonstrated by characterizing a novel recapitulative lipid-based nanoparticle model of SARS-CoV-2 —S-liposomes— which present the SARS-CoV-2 spike (S) protein on their surfaces. Patterning of a mixture of S-liposomes and liposomes that display the tetraspanin CD63 into discrete regions of a substrate is used to show that ACE2 specifically binds to S-liposomes. Importantly, DNA-directed patterning of S-liposomes is used to verify the performance of a commercially available neutralizing antibody against the S protein. Ultimately, the introduction of S-liposomes to ACE2-expressing cells demonstrates the biological relevance of DNA-directed patterning. Overall, DNA-directed patterning enables a wide variety of custom assays for the characterization of any lipid-based nanoparticle.

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Apathy and Ignorance: False Prophets of Autism and the Anti-Vaccine Movement

Viruses, Plagues, and History ◽

10.1093/oso/9780190056780.003.0019 ◽

2020 ◽

pp. 389-398

Author(s):

Michael B. A. Oldstone

Keyword(s):

Public Health ◽

Health Workers ◽

Vaccination Rate ◽

Personal Beliefs ◽

The United Kingdom ◽

False Reporting ◽

The Face ◽

Public Health Workers ◽

The Impact ◽

The Brain

This chapter highlights the story of autism, the widespread acceptance of its incorrect cause, and the impact on use of vaccines, all stemming directly from deliberate, false reporting. The basic conflict is twofold. First, involvement of a scientific method that must be reproducible, be reliable, and possess substantial proof is in conflict with common/personal beliefs. Second, doctors, scientists, and public health workers, despite their mandate to listen to parents and patients concerning their opinions, must base medical conclusions on evidence that validates the outcome of each patient’s health issue. It is in this milieu that autism and the anti-vaccine groups still do battle. In 1998, Lancet, a usually respectable and reputable English journal, published Dr. Andrew Wakefield’s opinion that the measles, mumps, rubella (German measles) vaccine injected into the arms of children caused inflammation, leading to harmful chemicals entering the bloodstream through the gut (intestine). These factors, he said, traveled to the brain, where the harmful chemicals/toxins caused autism. In the face of this “fake news” about the source of autism and measles, the vaccination rate for measles dropped in the United Kingdom and Ireland.

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423. Implementation of a Hierarchy of Controls in a Mobile Health Unit to Safely Care for Inpatients with COVID-19 during Healthcare System Surge

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.623 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S312-S312

Author(s):

Paige Reason ◽

Jerome A Leis ◽

Claudia Cocco ◽

Lynfa Stroud ◽

Michelle Hladunewich ◽

...

Keyword(s):

Mobile Health ◽

Healthcare Workers ◽

Patient Characteristics ◽

Vaccination Rate ◽

Health Unit ◽

Term Care ◽

Mandatory Education ◽

Pandemic Planning ◽

Alpha Variant ◽

Mobile Health Unit

Abstract Background In April 2021, Sunnybrook Health Sciences Centre opened a Mobile Health Unit (MHU, i.e. medical tents) under the direction of the Ontario Ministry of Health and Long Term Care in response to a surge in hospitalized patients with COVID-19 during wave three of the pandemic. Providing care to patients in non-conventional spaces is not new, however, experience in safely caring for COVID-19 patients in these settings is lacking. Our aim is to describe the implementation of our MHU and associated outcomes of these COVID-19 patients. Methods A multidisciplinary clinical and operations team was created to plan, execute and operate a safe environment for COVID-19 patients and healthcare workers within the MHU. Patient selection was restricted to patients with COVID-19 who were clinically recovering from severe COVID-19 pneumonia. Ventilation was optimized with air flow directed away from patient areas, velocity reduced to below 0.25 meters per second, and air exchanges of 24-28 per hour. All healthcare workers working in the MHU were offered COVID-19 vaccine and required to complete mandatory education if they declined (vaccination rate of 87% was achieved among dedicated staff). Universal masking and eye protection was used throughout the MHU with designated areas for donning and doffing personal protective equipment. Results In total, 32 patients with COVID-19 were managed in the MHU between 26 April and 21 May, 2021. Table 1 provides the summary of patient characteristics. All patients had a median of one-day of transmission-based precautions remaining in their course and were infected with Alpha variant with exception of one patient with the Gamma variant. Among those patients with genotyping available, all were infected with SARS-CoV-2 carrying the N501Y mutation. Four of the 32 patients required transfer to the main hospital for medical indication while the others were discharged home or to rehabilitation. None of the healthcare workers who worked within the MHU developed COVID-19 infection. Conclusion We safely cared for patients recovering from COVID-19 infection in an MHU to support system healthcare capacity. Our experience, including the specific hierarchy of controls implemented, may be helpful for future pandemic planning. Disclosures All Authors: No reported disclosures

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SARS-CoV-2 Pandemic Preventive Methods Efficacy - A Simulation Case Study

10.1101/2021.10.17.21265111 ◽

2021 ◽

Author(s):

Malak Saad ◽

Emad M Boctor

Keyword(s):

Decision Tree ◽

Screening Test ◽

Vaccination Rate ◽

Decision Makers ◽

Screening Tests ◽

Sample Population ◽

Virus Spread ◽

Health Target ◽

The Face ◽

Preventive Methods

The world has been facing the SARS-CoV-2, a.k.a. COVID-19, pandemic with different preventive methods including social distancing, face masking, screening tests (a.k.a. active surveillance), and vaccination. There are many publications and studies on the efficacy of each of these preventive methods for the last couple of years. Not all methods are readily available in each country and not all methods are accepted by all people in each society. In this study, we explore the interaction of the three preventive methods: face masking, vaccinations, and screening tests. We study a confined space to represent schools, businesses, or healthcare facilities and we model the spread of the COVID-19 virus for a 60-day period among a sample population while varying the percentage of people adopting one or more of the three preventive methods. To interpret the simulation results, we define a (Health Goal) target, for example achieving <5% infection rate, i.e., protecting 95% or more of the sample population. We then construct a (Decision Tree) that depicts all valid combinations that achieve this goal. Multiple scenarios are derived from the decision tree to guide decision makers in drawing effective policies to contain the virus spread. We demonstrate a ramping vaccination rate scenario, a removal of the face-masking mandate scenario, and a cost-minimizing goal scenario. The study highlights the efficacy of combining the three prevention methods to constrain the virus spread among the sample population. For example, results show that a combination of 0% vaccination rate, 6% daily screening test rate, and 80% face masking rate will achieve the target ≥95 protection rate, which can represent a scenario in which vaccination is not yet readily available. As the vaccination rate ramps up to 80% among the sample population, the screening test rate can be 0%, while the face masking rate can be as low as 5% to still achieve the health target. Many other scenarios are derived from this study to meet the defined health target, which represents the flexibility afforded to policy and decision makers when trying to adopt a combination of these preventive methods to contain virus spread. The study also reveals the higher efficiency of either the vaccination or screening test over face masking under the assumed virus transmissibility rates in the study.

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Stability and Stabilization of Ecosystem for Epidemic Virus Transmission Under Neumann Boundary Value Via Impulse Control

10.20944/preprints202102.0197.v1 ◽

2021 ◽

Cited By ~ 1

Author(s):

Ruofeng Rao

Keyword(s):

Impulse Control ◽

Virus Transmission ◽

Neumann Boundary ◽

Reaction Diffusion ◽

Control Technique ◽

Prevention Measures ◽

Unique Existence ◽

Globally Exponential Stability ◽

The Face ◽

The Stability

In this paper, by using the variational method, a sufficient condition for the unique existence of the stationary solution of the reaction-diffusion ecosystem is obtained, which directly leads to the global asymptotic stability of the unique equilibrium point. Besides, employing impulse control technique derives the globally exponential stability criterion of delayed feedback ecosystem.And numerical examples illuminate the effectiveness of impulse control, which has a certain enlightening effect on the actual epidemic prevention work . That is, in the face of the epidemic situation, taking a certain frequency of positive and effective epidemic prevention measures is conducive to the stability and control of the epidemic situation. particularly, the newly-obtained theorems quantifies this feasible step.

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COVID-19 deaths and hospitalizations averted by rapid vaccination rollout in the United States

10.1101/2021.07.07.21260156 ◽

2021 ◽

Author(s):

Seyed Moghadas ◽

Pratha Sah ◽

Meagan C Fitzpatrick ◽

Affan Shoukat ◽

Abhishek Pandey ◽

...

Keyword(s):

Randomized Clinical Trials ◽

Immune Escape ◽

Vaccine Coverage ◽

Vaccination Campaign ◽

Population Level ◽

The United States ◽

Country Level ◽

The Us ◽

The Face ◽

Alpha Variant

Importance: Randomized clinical trials have shown that the COVID-19 vaccines currently approved in the US are highly efficacious. However, more evidence is needed to understand the population-level impact of the US vaccination rollout in the face of the changing landscape of COVID-19 pandemic in the US, including variants with higher transmissibility and immune escape. Objective: To quantify the population-level impact of the US vaccination campaign in averting cases, hospitalizations and deaths from December 12, 2020 to June 28, 2021. Design: Age-stratified agent-based model which included transmission dynamics of the Alpha, Gamma and Delta variants in addition to the original Wuhan-1 variant. Setting: Our model was calibrated to COVID-19 outbreak and vaccine rollout in the US. Model predictions were made at the country level. Participants: Simulated age-stratified population representing US demographics. Main Outcomes and Measures: Cases, hospitalizations and deaths averted by vaccination against COVID-19 in the US, compared to the counterfactuals of no vaccination and vaccination administered at half the actual pace. Results: The swift vaccine rollout in the US curbed a potential resurgence of cases in April 2021, which would have been otherwise fuelled by the Alpha variant. Compared to the scenario without vaccines, we estimated that the actual vaccination program averted more than 26 million cases, 1.2 million hospitalizations and saved 279,000 lives. A vaccination campaign with half the actual rollout rate would have led to an additional 460,000 hospitalizations and 121,000 deaths. Conclusions and Relevance: The COVID-19 vaccination campaign in the US has had an extraordinary impact on reducing disease burden despite the emergence of highly transmissible variants. These findings highlight that the pace of vaccination was essential for mitigating COVID-19 in the US, and underscore the urgent need to close the vaccine coverage gaps in communities across the country.

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Quantitative Restoration of Immune Defense in Old Animals Determined by Naive Antigen-Specific CD8 T cell Numbers

10.1101/2021.08.09.453882 ◽

2021 ◽

Author(s):

Jennifer Uhrlaub ◽

Mladen Jergović ◽

Christine M. Bradshaw ◽

Sandip Sonar ◽

Christoper P. Coplen ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cd8 T Cells ◽

Neutralizing Antibody ◽

Immune Defense ◽

Cell Numbers ◽

Specific Effector ◽

The Face ◽

Old Mice

Many older humans and animals exhibit reduced immune responses to infection and vaccination, and this often directly correlates to the numbers and frequency of naive T (Tn) cells. We found such a correlation between reduced numbers of blood CD8+ Tn cells and severe clinical outcomes of WNV in both humans naturally exposed to, and mice experimentally infected with, West Nile virus (WNV). To examine possible causality, we sought to increase the number of CD8 Tn cells by treating C57BL/6 mice with IL-7 complexes (IL-7C, anti-IL-7 mAb bound to IL-7), shown previously to efficiently increase peripheral T cell numbers by homeostatic proliferation. T cells underwent robust expansion following IL-7C administration to old mice increasing the number of total T cells (>four-fold) and NS4b:H-2Db-restricted antigen-specific CD8 T cells (two-fold). This improved the numbers of NS4b-specific CD8 T cells detected at the peak of the response against WNV, but not survival in the face of WNV challenge. IL-7C treated old animals also showed no improvement in WNV-specific effector immunity (neutralizing antibody and in vivo T cell cytotoxicity). To test quantitative limits to which CD8 Tn cell restoration could improve protective immunity, we transferred graded doses of Ag-specific precursors into old mice, and showed that injection of 5,400 (but not of 1,800 or 600) adult naive WNV-specific CD8 T cells significantly increased survival after WNV. These results set quantitative limits to the level of Tn reconstitution necessary to improve immune defense in older organisms, and are discussed in light of targets of immune reconstitution.

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Fast and long-lasting immune response to S-trimer COVID-19 vaccine adjuvanted by PIKA

Molecular Biomedicine ◽

10.1186/s43556-021-00054-z ◽

2021 ◽

Vol 2 (1) ◽

Author(s):

Yuan Liu ◽

Lianpan Dai ◽

Xiaoli Feng ◽

Ran Gao ◽

Nan Zhang ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Vaccine Candidate ◽

Neutralizing Antibody ◽

Protein Vaccine ◽

Humoral Immune ◽

Humoral Immune Responses ◽

The Face ◽

Potential Vaccine ◽

High Level

AbstractIn the face of the emerging variants of SARS-CoV-2, there is an urgent need to develop a vaccine that can induce fast, effective, long-lasting and broad protective immunity against SARS-CoV-2. Here, we developed a trimeric SARS-CoV-2 S protein vaccine candidate adjuvanted by PIKA, which can induce robust cellular and humoral immune responses. The results showed a high level of neutralizing antibodies induced by the vaccine was maintained for at least 400 days. In the study of non-human primates, PIKA adjuvanted S-trimer induced high SARS-CoV-2 neutralization titers and protected from virus replication in the lung following SARS-CoV-2 challenge. In addition, the long-term neutralizing antibody response induced by S-trimer vaccine adjuvanted by PIKA could neutralize multiple SARS-CoV-2 variants and there is no obvious different among the SARS- CoV-2 variants of interest or concern, including B.1.351, B.1.1.7, P.1, B.1.617.1 and B.1.617.2 variants. These data support the utility of S-trimer protein adjuvanted by PIKA as a potential vaccine candidate against SARS-CoV-2 infection.

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Single-dose SARS-CoV-2 vaccine in a prospective cohort of COVID-19 patients

10.1101/2021.05.25.21257797 ◽

2021 ◽

Author(s):

Marit J. van Gils ◽

Hugo D.G. Willegen ◽

Elke Wynberg ◽

Alvin X. Han ◽

Karlijn van der Straten ◽

...

Keyword(s):

Single Dose ◽

Prospective Cohort ◽

Serum Antibody ◽

Neutralizing Antibody ◽

Credible Interval ◽

Time Interval ◽

Vaccine Response ◽

Vaccine Strategy ◽

Igg Antibody ◽

Antibody Titers

Background The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose sparing strategies, particularly single vaccine dosing of individuals with prior SARS-CoV-2 infection. Methods We evaluated SARS-CoV-2 specific antibody responses following a single-dose of BNT162b2 (Pfizer-BioNTech) mRNA vaccine in 155 previously SARS-CoV-2-infected individuals participating in a population-based prospective cohort study of COVID-19 patients. Participants varied widely in age, comorbidities, COVID-19 severity and time since infection, ranging from 1 to 15 months. Serum antibody titers were determined at time of vaccination and one week after vaccination. Responses were compared to those in SARS-CoV-2-naive health care workers after two BNT162b2 mRNA vaccine doses. Results Within one week of vaccination, IgG antibody levels to virus spike and RBD proteins increased 27 to 29-fold and neutralizing antibody titers increased 12-fold, exceeding titers of fully vaccinated SARS-CoV-2-naive controls (95% credible interval (CrI): 0.56 to 0.67 v. control 95% CrI: -0.16 to -0.02). Pre-vaccination neutralizing antibody titers had the largest positive mean effect size on titers following vaccination (95% CrI (0.16 to 0.45)). COVID-19 severity, the presence of comorbidities and the time interval between infection and vaccination had no discernible impact on vaccine response. Conclusion A single dose of BNT162b2 mRNA vaccine up to 15 months after SARS-CoV-2 infection provides neutralizing titers exceeding two vaccine doses in previously uninfected individuals. These findings support wide implementation of a single-dose mRNA vaccine strategy after prior SARS-CoV-2 infection.

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Ticket Inspectors in Action: Body-worn Camera Analysis of Aggressive and Non-aggressive Passenger Encounters

10.31234/osf.io/jcazp ◽

2019 ◽

Author(s):

Camilla Bank Friis ◽

Lasse Suonperä Liebst ◽

Richard Philpot ◽

Marie Rosenkrantz Lindegaard

Keyword(s):

Risk Factors ◽

Workplace Aggression ◽

Organizational Level ◽

Occupational Hazard ◽

Prevention Measures ◽

Face To Face ◽

Factors Associated ◽

The Face ◽

Interactional Analysis ◽

The Individual

AbstractObjective: Workplace aggression is a harmful occupational hazard, which has been associated with individual and organizational level risk factors. By comparison, little is known about the face-to-face interactional dynamics that shape employee victimizations. To address this gap, we provide an interactional analysis of how ticket inspector actions are asso-ciated with the risk of passenger aggression. Method: Data was a video sample of 123 ticket fining events from public buses recorded by occupational body-worn cameras. We systemati-cally coded the inspector and passenger actions in each fining event. The individual and inter-actional risk factors associated with passenger aggression were estimated with a logistic re-gression model. Results: Our empirical analysis suggests that aggressive fining events unfold as “character contests,” in which the actions of the inspectors are associated with the aggres-sive outcome. Conclusions: These findings are in line with situational approaches to violence highlighting that aggressive incidents often develop as an interplay between victim and of-fender actions. We propose focusing on the behavioral actions of employees for prevention measures of workplace aggression.

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