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      Results of the Stop the Spread Ottawa (SSO) cohort study: a Canadian urban-based prospective evaluation of antibody responses and neutralisation efficiency to SARS-CoV-2 infection and vaccination

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          Abstract

          Background

          Predictors of COVID-19 vaccine immunogenicity and the influence of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require elucidation.

          Methods

          Stop the Spread Ottawa is a prospective cohort of individuals at-risk for or who have been infected with SARS-CoV-2, initially enrolled for 10 months beginning October 2020. This cohort was enriched for public-facing workers. This analysis focuses on safety and immunogenicity of the initial two doses of COVID-19 vaccine.

          Results

          Post-vaccination data with blood specimens were available for 930 participants. 22.8% were SARS-CoV2 infected prior to the first vaccine dose. Cohort characteristics include: median age 44 (IQR: 22–56), 66.6% women, 89.0% white, 83.2% employed. 38.1% reported two or more comorbidities and 30.8% reported immune compromising condition(s). Over 95% had detectable IgG levels against the spike and receptor binding domain (RBD) 3 months post second vaccine dose. By multivariable analysis, increasing age and high-level immune compromise predicted diminishing IgG spike and RBD titres at month 3 post second dose. IgG spike and RBD titres were higher immediately post vaccination in those with SARS-CoV-2 infection prior to first vaccination and spike titres were higher at 6 months in those with wider time intervals between dose 1 and 2. IgG spike and RBD titres and neutralisation were generally similar by sex, weight and whether receiving homogeneous or heterogeneous combinations of vaccines. Common symptoms post dose 1 vaccine included fatigue (64.7%), injection site pain (47.5%), headache (27.2%), fever/chills (26.2%) and body aches (25.3%). These symptoms were similar with subsequent doses.

          Conclusion

          The initial two COVID-19 vaccine doses are safe, well-tolerated and highly immunogenic across a broad spectrum of vaccine recipients including those working in public facing environments.

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          Most cited references21

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          Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

          Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
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            Population risk factors for severe disease and mortality in COVID-19: A global systematic review and meta-analysis

            Aim COVID-19 clinical presentation is heterogeneous, ranging from asymptomatic to severe cases. While there are a number of early publications relating to risk factors for COVID-19 infection, low sample size and heterogeneity in study design impacted consolidation of early findings. There is a pressing need to identify the factors which predispose patients to severe cases of COVID-19. For rapid and widespread risk stratification, these factors should be easily obtainable, inexpensive, and avoid invasive clinical procedures. The aim of our study is to fill this knowledge gap by systematically mapping all the available evidence on the association of various clinical, demographic, and lifestyle variables with the risk of specific adverse outcomes in patients with COVID-19. Methods The systematic review was conducted using standardized methodology, searching two electronic databases (PubMed and SCOPUS) for relevant literature published between 1st January 2020 and 9th July 2020. Included studies reported characteristics of patients with COVID-19 while reporting outcomes relating to disease severity. In the case of sufficient comparable data, meta-analyses were conducted to estimate risk of each variable. Results Seventy-six studies were identified, with a total of 17,860,001 patients across 14 countries. The studies were highly heterogeneous in terms of the sample under study, outcomes, and risk measures reported. A large number of risk factors were presented for COVID-19. Commonly reported variables for adverse outcome from COVID-19 comprised patient characteristics, including age >75 (OR: 2.65, 95% CI: 1.81–3.90), male sex (OR: 2.05, 95% CI: 1.39–3.04) and severe obesity (OR: 2.57, 95% CI: 1.31–5.05). Active cancer (OR: 1.46, 95% CI: 1.04–2.04) was associated with increased risk of severe outcome. A number of common symptoms and vital measures (respiratory rate and SpO2) also suggested elevated risk profiles. Conclusions Based on the findings of this study, a range of easily assessed parameters are valuable to predict elevated risk of severe illness and mortality as a result of COVID-19, including patient characteristics and detailed comorbidities, alongside the novel inclusion of real-time symptoms and vital measurements.
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              Aging and the Immune System: the Impact of Immunosenescence on Viral Infection, Immunity and Vaccine Immunogenicity

              Immunosenescence is characterized by a progressive deterioration of the immune system associated with aging. Multiple components of both innate and adaptive immune systems experience aging-related changes, such as alterations in the number of circulating monocytic and dendritic cells, reduced phagocytic activities of neutrophils, limited diversity in B/T cell repertoire, T cell exhaustion or inflation, and chronic production of inflammatory cytokines known as inflammaging. The elderly are less likely to benefit from vaccinations as preventative measures against infectious diseases due to the inability of the immune system to mount a successful defense. Therefore, aging is thought to decrease the efficacy and effectiveness of vaccines, suggesting aging-associated decline in the immunogenicity induced by vaccination. In this review, we discuss aging-associated changes in the innate and adaptive immunity and the impact of immunosenescence on viral infection and immunity. We further explore recent advances in strategies to enhance the immunogenicity of vaccines in the elderly. Better understanding of the molecular mechanisms underlying immunosenescence-related immune dysfunction will provide a crucial insight into the development of effective elderly-targeted vaccines and immunotherapies.
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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2023
                31 October 2023
                : 13
                : 10
                : e077714
                Affiliations
                [1 ]departmentDept of Medicine , Ringgold_6363University of Ottawa , Ottawa, Ontario, Canada
                [2 ]departmentSchool of Epidemiology and Public Health , Ringgold_12365University of Ottawa Faculty of Medicine , Ottawa, Ontario, Canada
                [3 ]departmentDepartment of Biochemistry , Ringgold_6363University of Ottawa , Ottawa, Ontario, Canada
                [4 ]departmentDepartment of Biochemistry Microbiology and Immunology , Ringgold_6363University of Ottawa , Ottawa, Ontario, Canada
                [5 ]departmentDepartment of Medicine , Ringgold_27337Ottawa Hospital , Ottawa, Ontario, Canada
                [6 ]departmentDepartment of Pathology and Laboratory Medicine , Ringgold_6363University of Ottawa , Ottawa, Ontario, Canada
                [7 ]departmentDivision of Infectious Diseases, Department of Medicine , Ringgold_27337Ottawa Hospital , Ottawa, Ontario, Canada
                [8 ]Ringgold_10055Ottawa Hospital Research Institute , Ottawa, Ontario, Canada
                [9 ]departmentChronic Disease Program , Ringgold_10055Ottawa Hospital Research Institute , Ottawa, Ontario, Canada
                [10 ]Coronavirus Variants Rapid Response Network , Ottawa, Ontario, Canada
                [11 ]departmentBiochemistry, Microbiology and Immunology , Ringgold_6363University of Ottawa , Ottawa, Ontario, Canada
                [12 ]departmentDivision of Infectious Diseases , Ottawa Hospital Research Institute Clinical Epidemiology Program , Ottawa,Canada, Ontario, Canada
                Author notes
                [Correspondence to ] Dr Curtis Cooper; ccooper@ 123456toh.ca
                Author information
                http://orcid.org/0000-0002-4209-1786
                http://orcid.org/0000-0001-5026-5531
                http://orcid.org/0000-0002-3368-3499
                Article
                bmjopen-2023-077714
                10.1136/bmjopen-2023-077714
                10619119
                37907304
                d84ad3d8-701f-41d9-8de0-0d01a4f5290e
                © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 14 July 2023
                : 03 October 2023
                Funding
                Funded by: COVID-Immunity Task Force (CITF);
                Funded by: CIHR;
                Award ID: 175622
                Award ID: 424425
                Award ID: 476885
                Funded by: Coronavirus Variants Rapid Response Network;
                Award ID: 156941
                Funded by: FundRef http://dx.doi.org/10.13039/100008572, University of Ottawa;
                Funded by: FundRef http://dx.doi.org/10.13039/501100000024, Canadian Institutes of Health Research;
                Funded by: CGS;
                Funded by: National Research Council of Canada's Pandemic Response Challenge Program;
                Categories
                Infectious Diseases
                1506
                2474
                1706
                Original research
                Custom metadata
                unlocked
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                Medicine
                covid-19,immunology,safety
                Medicine
                covid-19, immunology, safety

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