Article

BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting

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Abstract

Background: As mass vaccination campaigns against coronavirus disease 2019 (Covid-19) commence worldwide, vaccine effectiveness needs to be assessed for a range of outcomes across diverse populations in a noncontrolled setting. In this study, data from Israel's largest health care organization were used to evaluate the effectiveness of the BNT162b2 mRNA vaccine. Methods: All persons who were newly vaccinated during the period from December 20, 2020, to February 1, 2021, were matched to unvaccinated controls in a 1:1 ratio according to demographic and clinical characteristics. Study outcomes included documented infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), symptomatic Covid-19, Covid-19-related hospitalization, severe illness, and death. We estimated vaccine effectiveness for each outcome as one minus the risk ratio, using the Kaplan-Meier estimator. Results: Each study group included 596,618 persons. Estimated vaccine effectiveness for the study outcomes at days 14 through 20 after the first dose and at 7 or more days after the second dose was as follows: for documented infection, 46% (95% confidence interval [CI], 40 to 51) and 92% (95% CI, 88 to 95); for symptomatic Covid-19, 57% (95% CI, 50 to 63) and 94% (95% CI, 87 to 98); for hospitalization, 74% (95% CI, 56 to 86) and 87% (95% CI, 55 to 100); and for severe disease, 62% (95% CI, 39 to 80) and 92% (95% CI, 75 to 100), respectively. Estimated effectiveness in preventing death from Covid-19 was 72% (95% CI, 19 to 100) for days 14 through 20 after the first dose. Estimated effectiveness in specific subpopulations assessed for documented infection and symptomatic Covid-19 was consistent across age groups, with potentially slightly lower effectiveness in persons with multiple coexisting conditions. Conclusions: This study in a nationwide mass vaccination setting suggests that the BNT162b2 mRNA vaccine is effective for a wide range of Covid-19-related outcomes, a finding consistent with that of the randomized trial.

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... Since the study was conducted during the vaccine rollout, participants were enrolled at varying stages of their vaccination process. We assumed that vaccines reach their full effect 7 days after receiving a second dose (Dagan et al., 2021;Haas et al., 2021;Goldberg et al., 2021). Cases were therefore considered vaccinated if their symptom onset (or if unknown, the date of their first positive PCR test) occurred ≥ 7 days after the second dose. ...
... We show, consistent with previous studies (Munitz et al., 2021;Pritchard et al., 2021), that BNT162b2 vaccination is highly effective against infection by the Alpha variant. In general population studies, vaccine effectiveness for symptomatic infections ranged from 57% 14 days after the first dose (Dagan et al., 2021) to 89% (Dagan et al., 2021), and 97% 7 days after the second dose (Haas et al., 2021). For asymptomatic infections, vaccine effectiveness against infection was 79% 10 days after the first dose (Tande et al., 2022) and 94% 14 days after the second dose (SE, 2021). ...
... We show, consistent with previous studies (Munitz et al., 2021;Pritchard et al., 2021), that BNT162b2 vaccination is highly effective against infection by the Alpha variant. In general population studies, vaccine effectiveness for symptomatic infections ranged from 57% 14 days after the first dose (Dagan et al., 2021) to 89% (Dagan et al., 2021), and 97% 7 days after the second dose (Haas et al., 2021). For asymptomatic infections, vaccine effectiveness against infection was 79% 10 days after the first dose (Tande et al., 2022) and 94% 14 days after the second dose (SE, 2021). ...
Thesis
Among the methods for the quantitative study of infectious diseases transmission in host populations, molecular epidemiology that reconstructs pathogen phylogenies by using pathogen genetic sequences and mathematical modelling of infectious diseases that fits mechanistic models of disease transmission to epidemiological data such as case counts are of particular interest to epidemiologists. These two approaches rely on different data sources whose availability depends on the setting. They also rely on different concepts and models leading to complementary pictures of disease transmission. The main objective of this thesis is to better understand how viral infectious diseases such as rabies and COVID-19 circulate in host populations using respectively geolocated and timestamped viral genetic sequences and detailed epidemiological data at the individual level. The first part of this thesis focuses on rabies, a neglected tropical zoonosis, that is estimated to cause 59,000 human deaths per year mostly among rural and poor populations in Africa and Asia. Its causing agent, rabies virus (RABV), mainly circulates in domestic dog populations. Despite being a vaccine-preventable disease in both humans and dogs, rabies remains poorly studied and its circulation in dogs poorly understood. First, we reviewed from the literature all mathematical models and molecular epidemiology studies on dog rabies circulation to synthesize the contribution of both approaches to the understanding of rabies dynamics in dogs. Then, we described RABV spread in Cambodia, one of the most affected countries worldwide, using RABV genomes isolated from dogs and Bayesian continuous phylogeography methods. We used Cambodia as a model of endemic circulation of RABV and exemplified how phylogeography can help characterize circulation in such context. We found that introductions from foreign countries are not necessary to sustain transmission in Cambodia. However, these results are conditional on the sampling of the RABV genomes. To further understand how sampling affects Bayesian phylogeography methods, we performed a simulation study where we evaluated the performances of three Bayesian discrete phylogeography algorithms under increasing levels of bias, and tested whether alternative sampling strategies, and integration of incidence data improve the performances of the algorithms under biased sampling conditions. The second part of this thesis concentrates on SARS-CoV-2 transmission at one of the smallest population scale, households. This setting is particularly suitable to detailed follow-up of household members after introduction of a case, and thus, enables to evaluate how susceptibility and infectivity vary between individuals. First, we estimated BNT162b2 vaccine effectiveness against infection and against transmission if infected during the Alpha wave in Israel using a mathematical model of SARS-CoV-2 transmission in partially vaccinated households. We further explored how model misspecification in a context of differing contact patterns between adults and children would impact estimates of relative infectivity and susceptibility of children compared to adults. Overall, this thesis explores how molecular epidemiology and modelling contribute to the understanding of infectious diseases transmission at the population level and highlights the need for data integration.
... With the outbreak of the disease in Israel, as in other parts of the world, the organ transplant activity was initially suspended, this was due to overall uncertainty and lack of knowledge and data regarding all aspects of management of the disease: clinical (risk of transmission from donor to recipient, risk related to immunosuppression, etc.) and operational (hospital resources and personnel shortage) [16,17]. The impact on organ transplantation varied with respect to organ type with preferential deferral of kidney transplant candidates who were stable on renal replacement therapy [15,[18][19][20]. ...
... The high efficacy of the mRNA-based BNT162b2 vaccine against SARS-CoV-2 [16] and the clever and fast coronavirus national immunization program launched by the Israeli authorities on 20 December 2020 has changed dramatically the dynamics of the epidemic in a relatively short period of time. In fact, by 24 February, 85% of individuals older than 60 years were already vaccinated with two doses. ...
Article
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Coronavirus disease 2019 (COVID-19) has affected tens of millions of people globally since it was declared a pandemic by the World Health Organization on 11 March 2020. Since its outbreak in December 2019, the ongoing coronavirus COVID-19 pandemic has led to global social, economic and healthcare crises affecting millions of people and causing the death of hundreds of thousands of people worldwide. As with other fields of healthcare, the pandemic with its heavy workload imposed on hospital services and personnel significantly affected solid organ transplantation. Concerns for potential exposure to the virus and its related severe acute respiratory syndrome coronavirus type 2 (SARS-CoV2) have profoundly altered the process of organ donation and recovery, acceptance of organ offers, management of potential recipients and living donors, and above all transplanted and immunosuppressed patients. All those issues required prompt implementation of new practice measures and guidelines as well as continuous adaptations to the fluid and rapidly changing situation. Herein we describe a single transplant center experience with kidney transplantation during the COVID-19 pandemic; we review the national and institutional measures and restrictions undertaken in different phases of the ongoing event as well as the outcomes.
... 4 Las vacunas contra la COVID-19 comúnmente aplicadas en todo el mundo son de las marcas comerciales: Pfizer-BioNTech, Moderna ® , Johnson & Johnson ® y Astra Zeneca ® . 5 Con el surgimiento de esta emergencia sanitaria se han presentado dos escenarios clínicos en cuanto a enfermedades autoinmunitarias: uno inducido propiamente por el SARS-CoV-2 y el otro post-vacunación. Los estudios recientes sugieren que la miocarditis, trombocitopenia trombótica inmunitaria, vasculitis por IgA, entre otras enfermedades autoinmunitarias, pueden desencadenarse por las vacunas contra la COVID-19 en pacientes predispuestos. ...
... Los estudios recientes sugieren que la miocarditis, trombocitopenia trombótica inmunitaria, vasculitis por IgA, entre otras enfermedades autoinmunitarias, pueden desencadenarse por las vacunas contra la COVID-19 en pacientes predispuestos. 4,5 Los mecanismos para adquirir autoinmunidad luego de la infección por SARS-CoV-2 incluyen: "mimetismo molecular" y "activación de espectadores"; es decir, la infección conduce a la activación del antígeno. 3,6 La aparición de enfermedades autoinmunitarias pueden originarse por diversos factores, mediante un estado de hiperestimulación del sistema inmunitario, donde los virus representan un factor de riesgo para adquirir autoinmunidad. ...
... Safe and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have provided significant protection from the coronavirus disease 2019 (COVID-19) [1][2][3][4]. Nonetheless, the emergence of successive variants and variable time intervals since vaccination and SARS-CoV-2 infection have been accompanied by breakthrough COVID-19 severe enough to require hospitalization [5][6][7]. The successive appearance of viral mutations, waxing and waning disease-and vaccine-derived immunity, improved therapeutics, and variably effective and sustainable public health measures make assessments of differential vaccine efficacy against each SARS-CoV-2 variant particularly challenging [7,8]. ...
... p-value < 0.05 was considered significant (marked in bold).2 This was assessed using the World Health Organization COVID-19 Clinical Progression Scale[21]. ...
Article
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Evidence suggests that monovalent vaccine formulations are less effective against the Omicron SARS-CoV-2 than against previous variants. In this retrospective cohort study of hospitalized adults with PCR-confirmed COVID-19 during the Delta (October–November 2021) and Omicron (January–April 2022) variant predominant periods in Slovenia, we assessed the association between primary vaccination against SARS-CoV-2 and progression to critically severe disease (mechanical ventilation or death). Compared with the 529 patients hospitalized for acute COVID-19 during the Delta period (median age 65 years; 58.4% men), the 407 patients hospitalized during the Omicron period (median age 75 years; 50.6% men) were older, more often resided in long-term care facilities, and had higher Charlson comorbidity index scores. After adjusting for age, sex, the Charlson comorbidity index, the presence of immunocompromising conditions, and vaccination status, the patients admitted during the Omicron period had comparable odds of progressing to critically severe disease to those admitted during the Delta period. The 334/936 (35.7%) patients completing at least primary vaccination had lower odds of progression to critically severe disease and shorter hospital stay than unvaccinated patients; however, the protective effect of vaccination was less pronounced during the Omicron than during the Delta period. Although the Omicron variant appeared to better evade immunity induced by monovalent vaccines than the Delta variant, vaccination against SARS-CoV-2 remained an effective intervention to decrease morbidity and mortality in COVID-19 patients infected with the Omicron variant.
... In the early stages of the COVID- 19 also approved use of a few Vaccines across the world. It has been estimated that vaccines prevent infection by 60-92% [7,8], hospitalizations by 87-94% [7,9 and deaths by 72%-100% [7,10] after 7-28 days of receiving the second dose of the vaccines for Alpha, Beta, or Delta variant of concern (VOC). ...
... In the early stages of the COVID- 19 also approved use of a few Vaccines across the world. It has been estimated that vaccines prevent infection by 60-92% [7,8], hospitalizations by 87-94% [7,9 and deaths by 72%-100% [7,10] after 7-28 days of receiving the second dose of the vaccines for Alpha, Beta, or Delta variant of concern (VOC). ...
Article
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Objectives We compared the global reported cumulative case-fatality ratio (rCFR) and excess mortality between top-20 countries with COVID-19 vaccination rates, the rest of the world and Sub-Saharan Africa (SSA) before and after commencement of vaccination programmes. Methods We performed time series model to understand the trend of rCFR over time and performed generalized linear mixed model to understand role of vaccination on rCFR. Results By 31 December 2022, on average 260.3 doses of COVID-19 vaccines per 100 people had been administered in the top-20 vaccinated countries, compared to 152.1 doses in the rest of the world, and 51.2 in SSA. The mean rCFR of COVID-19 had dropped by 69.0% in the top in the top-20 vaccinated countries, 26.5% in the rest of the world and 7.6% in SSA. The excess mortality had dropped by 48.7% in top vaccinated countries compared to 62.5% in the rest of the world and 60.7% in SSA. In a generalized linear mixed model, reported number of vaccine doses administered doses (/100 population) (Odds ratio:0.64) was associated with a steeper reduction of the country's COVID-19 rCFR. Conclusions Vaccine equity and faster roll-out across the
... The current study demonstrated a significant reduction in post-vaccination COVID-19 incidents and severe disease after the second dose of the three vaccines. Thus, the present study results lend further credence to the findings of several studies [28,[31][32][33] that showed the critical role of vaccine completion in reducing infection and COVID-19-related severe disease. The confirmed COVID-19 infections detected after vaccine completion were 57/1500 (3%), and none of the cases was associated with severe symptoms in this study cohort. ...
... The COVID-19 vaccines' effectiveness demonstrated in this study was coupled with a low risk of adverse events. The adverse events of the three types of vaccines assessed in the current study are comparable to those reported in several studies [28][29][30][31][32][33]. Serious vaccine adverse events, severe allergic reaction/anaphylaxis, Guillain-Barré syndrome, thrombosis, thrombocytopenia, seizures, and myocarditis observed in this study were rare as they occurred in 10 (0.66%) participants, all of whom had comorbidities. ...
Article
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To date, the effectiveness of COVID-19 vaccines and booster doses has yet to be evaluated in longitudinal head-to-head studies. This single-center longitudinal study assessed the effectiveness of ChAdOx1 nCoV-19, BNT162b2, and mRNA-1273 vaccines and assessed two BNT162b2 boosters in 1550 participants, of whom 26% had comorbidities. In addition, the SARS-CoV-2 antibody dynamics was monitored. A group of 1500 unvaccinated subjects was included as the controls. The study’s endpoint was the development of virologically-proven COVID-19 cases after vaccine completion, while the secondary endpoint was hospitalizations due to severe COVID-19. Overall, 23 (4.6%), 16 (3%), and 18 (3.8%) participants vaccinated with ChAdOx1 nCoV-19, BNT162b2, and mRNA-1273, respectively, developed COVID-19 after vaccine completion, with an effectiveness of 89%, 92%, and 90%. Ten COVID-19 cases were reported in participants with comorbidities, three of whom were hospitalized. No hospitalizations occurred after boosters. SARS-CoV-2 antibody levels peaked 2–4 weeks after the second vaccine dose but declined after a mean of 28.50 ± 3.48 weeks. Booster doses significantly enhanced antibody responses. Antibody titers ≤ 154 U/mL were associated with a higher risk of COVID-19 emergence. Thus, COVID-19 vaccines effectively reduced COVID-19 and prevented severe disease. The vaccine-induced SARS-CoV-2 antibody responses declined after 28–32 weeks. Booster doses induced significant maintained responses. SARS-CoV-2 antibody levels may help determine the timing and need for vaccine booster doses.
... • Those with Covid-19 symptoms were prevented from obtaining a vaccine. As explained in (Reeder, 2021) this always leads to an overestimate of vaccine efficacy and was also a feature of the other major observational study in Israel (Dagan et al., 2021) and which also reported high efficacy rates for the Pfizer vaccine. ...
... We have provided many other examples 13 where we have been directly affected by this. While re-investigating the flaws in (Haas et al., 2021) we discovered that other major observational studies making similar claims of efficacy for the Pfizer and other vaccines such as (Dagan et al., 2021;Pilishvili et al., 2021) also had blatant statistical flaws which were revealed in reports that never managed to get published, such as (Reeder, 2021). None of this should come as a surprise to those who have examined in detail the full Pfizer phase 3 trial data which, contrary to showing 95% efficacy, may reveal zero or negative efficacy 14 . ...
Preprint
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In May 2021 The Lancet published a study of the Pfizer covid vaccine on the population of Israel, claiming to show it was 95% effective. On 17 May 2021 we submitted a rapid response 250-word letter explaining why the study was flawed and how the 95% claim was exaggerated. After an initial response saying they would ask the authors for a response to our letter we heard nothing until 20 months later. On 8 January 2023 The Lancet sent an email apologising for never having got back to us about the letter, saying that they had asked the lead author Dr Sharon Alroy-Preis (SA-P) to respond to our letter but, because she did not provide any formal response, they decided not to publish our letter. We tweeted The Lancet's response and published a substack article highlighting that we were now aware of additional problems with the paper relating to SA-P’s relationship with Pfizer. These media posts got 1.5 million reads within 24 hours. On 11 January 2023 we received an email from The Lancet apologising for the ‘sub-standard experience’ and that they were now inviting us to publish the original letter or an update to it, suggesting the update ‘reflect more current experience with the vaccine’. On 12 January 2023 we submitted our updated letter (they stipulated a maximum of 350 words). On 13 January 2023 we got a response from The Lancet saying they had decided against publishing the letter, asserting that any claim questioning the efficacy and safety of the Pfizer vaccine was ‘misinformation’ and that they did not consider the position of SA-P an undeclared conflict of interest or a challenge to the integrity of the data.
... Knowing mRNA vaccination-related secondary effects is essential for radiologists and oncologists to prevent false interpretations during diagnostic imaging procedures [8]. ...
Article
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Background COVID-19 vaccination of the population has a great importance, especially in oncological patients. The high incidence of vaccine-associated hypermetabolic lymphadenopathy (VAHL) makes a difficulty in the diagnosis of PET-CT of oncological patients. They should be vaccinated in the side opposite to the expected malignant LNs to avoid unnecessary biopsy and change in therapy. The aim of this study was to assess the role of PET-CT in detection of VAHL after the 2nd dose of Pfizer-BioNTech vaccine in lymphoma patients and compare the incidence of VAHL among lymphoma patients treated with B cell depletion therapy during the 6 months prior to vaccination and those treated > 6 months before vaccination. Results This study comprised 120 lymphoma patients, referred for FDG PET/CT 1–3 weeks after the 2nd dose of Pfizer-BioNTech COVID-19 vaccine. Hypermetabolic LNs were identified in 55%. The incidence of VAHL in lymphoma patients treated with anti-CD20 antibody rituximab during the 6 months prior to vaccination (9%) was significantly lower compared with other lymphoma patients treated with anti-CD20 antibody rituximab > 6 months before vaccination (91%). The incidence and grades of VAHL are significantly high within the 1st week after the 2nd dose of Pfizer-BioNTech vaccine in patients younger than 60 years of age. Only 7 of 37 patients with negative serology had VAHL on PET-CT, whereas 10 of 26 patients with decreased anti-spike titers and 49 of 57 patients with increased anti-spike titers had VAHL on PET-CT. Conclusions VAHL makes challenges in the interpretation of FDG PET/CT in oncology patients. Accurate data collection, regarding the time and site of COVID vaccination, is important to help radiologists in identifying the cause of abnormal nodal FDG uptake. We suggest to schedule FDG PET-CT for lymphoma patients at least 3 weeks after the 2nd dose of Pfizer-BioNTech vaccine.
... The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/jpm13020278/s1, Figure S1: Descriptive overview of the tests within OCS-Bridge; Figure S2: Scatterplots for visual assessment of the association between covariates (by column) and cognitive deficit (by row) before surgery (A1); Figure S3: Scatterplots for visual assessment of the association between covariates (by column) and cognitive deficit (by row) early after surgery (A2); Figure S4: Scatterplots for visual assessment of the association between covariates (by column) and change in cognitive deficit status (by row) between A1 and A2; Figure S5: Prevalence of cognitive deficit in normal control population (N), and at A1, A2 and A3 for each cognitive domain observed in our cohort, shown both as histograms (A) and pictorial representations (B); Figure S6: Risk of cognitive deficit at A1 and A2 in our glioblastoma cohort shown alongside other common intuitively understood risks [66][67][68][69]; Table S1: Summary of cognitive deficit across all cognitive tests at A1 for each patient in the cohort; Table S2: Summary of cognitive deficit across all cognitive tests at A2 for each patient in the cohort; Table S3: Summary of cognitive deficit across all cognitive tests at A3 for each patient in the cohort; Table S4: Co-variate raw data; Table S5: Summary of univariate logistic regression model of the association between covariates and cognitive deficit. Effect size is expressed as odds ratio (OR) with 95% confidence intervals; Table S6: Summary of multivariate logistic regression model of the association between covariates and cognitive deficit at A1; Table S7: Summary of multivariate logistic regression model of the association between stepwise-selected covariates and cognitive deficit at A1; Table S8: Summary of univariate logistic regression model of the association between covariates and cognitive deficit at A2; Table S9: Summary of multivariate logistic regression model of the association between covariates and cognitive deficit at A2; Table S10: Summary of multivariate logistic regression model of the association between stepwise-selected covariates and cognitive deficit at A2; Table S11: Summary of univariate logistic regression model of the association between covariates and cognitive deficit at A1A2; Table S12: Summary of multivariate logistic regression model of the association between covariates and cognitive deficit at A1A2; Table S13: Summary of multivariate logistic regression model of the association between stepwise-selected covariates and cognitive deficit at A1A2; Table S14: Summary of comparison of cognitive deficit by cognitive domain between A1 and A2 using McNemar's test to account for matching within the cohort; Table S15: Summary of comparison of cognitive deficit by cognitive test between A1 and A2 using McNemar's test to account for matching within the cohort. ...
Article
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Glioblastoma and the surgery to remove it pose high risks to the cognitive function of patients. Little reliable data exist about these risks, especially postoperatively before radiotherapy. We hypothesized that cognitive deficit risks detected before surgery will be exacerbated by surgery in patients with glioblastoma undergoing maximal treatment regimens. We used longitudinal electronic cognitive testing perioperatively to perform a prospective, longitudinal, observational study of 49 participants with glioblastoma undergoing surgery. Before surgery (A1), the participant risk of deficit in 5/6 cognitive domains was increased compared to normative data. Of these, the risks to Attention (OR = 31.19), Memory (OR = 97.38), and Perception (OR = 213.75) were markedly increased. These risks significantly increased in the early period after surgery (A2) when patients were discharged home or seen in the clinic to discuss histology results. For participants tested at 4–6 weeks after surgery (A3) before starting radiotherapy, there was evidence of risk reduction towards A1. The observed risks of cognitive deficit were independent of patient-specific, tumour-specific, and surgery-specific co-variates. These results reveal a timeframe of natural recovery in the first 4–6 weeks after surgery based on personalized deficit profiles for each participant. Future research in this period could investigate personalized rehabilitation tools to aid the recovery process found.
... Following the first two doses, high vaccine effectiveness was reported by real-world observational studies. Initial induction in immunogenicity 1 followed by reduction in infections, disease, hospitalization and death were reported [2][3][4] , as well as reduction in infectivity among breakthrough cases 5 By April 3, 2021, over 90% of Israeli adult population aged ±60 was vaccinated with two doses (with a 21 day interval between doses) 6 . Yet, with time, waning of this protective effect was reported, both in immunogenicity as well as in vaccine effectiveness against infections and hospitalizations 7,8 resulting in a fourth pandemic surge in Israel dominated by the Delta VOC. ...
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BACKGROUND Following the emergence of the Omicron variant of concern, we investigated immunogenicity, efficacy and safety of BNT162b2 or mRNA1273 fourth dose in an open-label, clinical intervention trial. METHODS Primary end-points were safety and immunogenicity and secondary end-points were vaccine efficacy in preventing SARS-CoV-2 infections and COVID-19 symptomatic disease. The two intervention arms were compared to a matched control group. Eligible participants were healthcare-workers (HCW) vaccinated with three BNT162b2 doses, and whose IgG antibody levels were ≤700 BAU (40-percentile). IgG and neutralizing titers, direct neutralization of live VOCs, and T-cell activation were assessed. All participants were actively screened for SARS-CoV-2 infections on a weekly basis. RESULTS Of 1050 eligible HCW, 154 and 120 were enrolled to receive BNT162b2 and mRNA1273, respectively, and compared to 426 age-matched controls. Recipients of both vaccine types had a ∼9-10-fold increase in IgG and neutralizing titers within 2 weeks of vaccination and an 8-fold increase in live Omicron VOC neutralization, restoring titers to those measured after the third vaccine dose. Breakthrough infections were common, mostly very mild, yet, with high viral loads. Vaccine efficacy against infection was 30% (95%CI:-9% to 55%) and 11% (95%CI:-43% to +43%) for BNT162b2 and mRNA1273, respectively. Local and systemic adverse reactions were reported in 80% and 40%, respectively. CONCLUSIONS The fourth COVID-19 mRNA dose restores antibody titers to peak post-third dose titers. Low efficacy in preventing mild or asymptomatic Omicron infections and the infectious potential of breakthrough cases raise the urgency of next generation vaccine development. Trial registration number clicaltrials.gov : NCT05231005 , NCT05230953
... To prevent the further spread of the emerging virus, mRNA vaccinations (BNT162b2 manufactured by P zer-BioNTech and mRNA-1273 manufactured by Moderna) were rst administered to humans in 2021 [3][4][5][6][7]. The neutralizing antibody titers were shown to peak within two weeks following secondary vaccination [3,8], thereby effectively reducing SARS-CoV-2 infections, hospitalizations, and death [9,10]. However, neutralizing antibody titers and vaccine e cacy decrease over time and are negatively affected by new emerging variants [11][12][13][14][15][16][17]. ...
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Background Amid the Coronavirus Disease 2019 pandemic, we aimed to demonstrate the accuracy of the fingertip whole blood sampling test (FWT) in measuring the antibody titer and uncovering its dynamics shortly after booster vaccination. Methods Mokobio SARS-CoV-2 IgM & IgG Quantum Dot immunoassay (Mokobio Biotechnology R&D Center Inc., MD, USA) was used as a point-of-care FWT in 226 health care workers (HCWs) who had received two doses of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) at least 8 months prior. Each participant tested their antibody titers before and after the third-dose booster up to 14-days. Results The effect of the booster was observed as early as the fourth day after vaccination, which exceeded the detection limit (> 30,000 U/mL) by 2.3% on the fifth day, 12.2% on the sixth day, and 22.5% after the seventh day. Significant positive correlations were observed between the pre- and post-vaccination (the seventh and eighth days) antibody titers (correlation coefficient, 0.405; p < 0.001). Conclusion FWT is useful for examining antibody titers as a point-of-care test. Rapid response of antibody titer started as early as the fourth day post-vaccination, while the presence of weak responders to mRNA vaccination was indicated.
... After infection, immunity to the SARS-CoV-2 virus that causes COVID-19 has been shown to vary in duration and efficacy [1][2]. There was evidence from clinical trials that vaccines can provide significant immunity in both previously infected and naive subjects, with vaccination success rates ranging from 92% for documented infection to 87% hospitalisation to a staggering 92% severe disease [3][4][5]. ...
Article
Objective: To compare the outcomes in term of hospital stay and mortality between vaccinated and nonvaccinated covid-19 patients. Study Design: Prospective/Observational Place and Duration: The study was conducted at Medicine department of Fauji Foundation Hospital Rawalpindi and Pak International Medical College Hayatabad Peshawar for six months duration from December 2020 to May 2021. Methodology: One hundred ten patients of either gender with covid-19 disease were enrolled. All the patients were confirmed with RT PCR. Patients were randomly divided in to two groups. Group I (vaccinated) comprised of 45 patients and group II (non-vaccinated) comprised of 65 patients. Severity of disease, hospital stay and mortality were compared between both groups. Data was analyzed by SPSS 24.0. Results: There were 74 (67.27%) males while 36 (32.73%) patients were females. Mean age of patients was 50.54±12.76 years. Mean BMI was 26.23±2.44 kg/m2. 10 (22.22%) patients in vaccinated group and 40 (61.54%) in nonvaccinated group had severe covid-19 disease, a significant difference was observed regarding severity of disease between both groups with p-value <0.05. Mortality rate and hospital stay were also high in nonvaccinated patients as compared to vaccinated (p-value <0.05). Conclusion: It is concluded that non-vaccinated patients of covid-19 had prolonged hospital stay and high rate of severity of disease and mortality as compared to vaccinated patients. Keywords: Covid-19, Vaccination, Severity, Hospital Stay, Mortality
... Clinical trials revealed, "A two-dose regimen of BNT162b2 (30 μg per dose, given 21 days apart) was found to be safe and 95% effective against Covid-19 after a 2-month follow-up" [3]. A study of the effectiveness of the BNT162b2 vaccine in a non-controlled-real-world-setting also determined that the vaccine was safe and effective across a "range of outcomes across diverse populations" [4]. Two doses of the vaccine were effective in decreasing the risk of documented infection, symptomatic COVID-19, hospitalization, and severe . ...
Article
The COVID-19 pandemic changed the socio-economic fabric of communities around the world. To determine the emerging needs of human service agencies our research team conducted agency assessments within the greater Houston metropolis. A convenience sample of agencies (n=17) currently providing social work internship placements was surveyed between April 2021 and July 2021. Results revealed emerging needs that schools of social work should consider during the COVID-19 response. Some include the need for interdisciplinary intern teams, technology training for social workers, dual degrees, and macro-level skills. We recommend enhancing university-community partnerships to meet the emerging humanitarian and workforce needs of the community.
... On June 3, 2021 more than 5 million people were at least 7 days after the second dose of the vaccine, only 40/day new patients were reported, with zero daily mortality. Efficiency and safety of the vaccination process in Israel was clearly demonstrated [3]. The vaccine prevented infection, symptoms, hospitalization or severe disease in 92%, 94%, 87% and 92%, respectively. ...
Article
A cluster of young patients with myocarditis after SARS-CoV-2 RNA vaccination, started several days up to 2 weeks after the second shot, was reported in Israel, without a solid evidence for a cause and effect sequence of events, or any scientific, peer review publication. Most of the patients were young men who recovered with or without steroid therapy, but one 22 year-old woman died within 72 hours from start of the symptoms (chest pain and fatigue) with elevated troponin and CRP, ECG changes but normal echocardiogram. After injection of RNA the body manufactures the S protein and starts synthesize antibodies against it. My speculation is that the connection between S protein and the receptor ACE2, which is abundant on the myocardium, builds a stabile complex with high antigenicity. Antibodies attached to this complex which is now under attack by both – antibodies and T-cells. The result is severe inflammation and cytokine storm. Another possible explanation is the presence of a mediator between the receptor (ACE2) and S protein such as Defensin 5, and a complex of higher molecular weight and antigenicity causing a severe immunological attack.
... To our knowledge, this is the first report regarding the connection of COVID-19 vaccination status with the morbidity of COVID-19 in South Korea.This study demonstrates the reduced risk of severe cases of the COVID-19 vaccinated population. In line with this, several recent studies have reported the preventive effects of COVID-19 vaccine.[14][15][16] In a case-controlled study in Israel, it was documented that the ...
... We aimed to emulate a target trial assessing the effectiveness of booster vaccination with BNT162b2 against COVID-19 outcomes (6) (7), by comparing fully vaccinated adults who did and did not receive a booster vaccine dose. We used the OpenSAFELY-TPP linked primary care database covering around 40% of English residents. ...
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Background The UK COVID-19 vaccination programme delivered its first “booster” doses in September 2021, initially in groups at high risk of severe disease then across the adult population. The BNT162b2 Pfizer-BioNTech vaccine was used initially, with Moderna mRNA-1273 subsequently also used. Methods We used the OpenSAFELY-TPP database, covering 40% of English primary care practices and linked to national coronavirus surveillance, hospital episodes, and death registry data, to estimate the effectiveness of boosting with BNT162b2 compared with no boosting in eligible adults who had received two primary course vaccine doses between 16 September and 16 December 2021 when the Delta variant of SARS-CoV-2 was dominant. Follow up was for up to 10 weeks. Each booster recipient was matched with an unboosted control on factors relating to booster priority status and prior immunisation. Additional factors were adjusted for in Cox models estimating hazard ratios (HRs). Outcomes were positive SARS-CoV-2 test, COVID-19 hospitalisation, COVID-19 death and non-COVID-9 death. Booster vaccine effectiveness was defined as 1−HR. Results Among 4,352,417 BNT162b2 booster recipients matched with unboosted controls, estimated effectiveness of a booster dose compared with two doses only was 50.7% (95% CI 50.1-51.3) for positive SARS-CoV-2 test, 80.1% (78.3-81.8) for COVID-19 hospitalisation, 88.5% (85.0-91.1) for COVID-19 death, and 80.3% (79.0-81.5) for non-COVID-19 death. Estimated effectiveness was similar among those who had received a BNT162b2 or ChAdOx1-S two-dose primary vaccination course, but effectiveness against severe COVID-19 was slightly lower in those classified as clinically extremely vulnerable (76.3% (73.1-79.1) for COVID-19 hospitalisation, and 85.1% (79.6-89.1) for COVID-19 death). Estimated effectiveness against each outcome was lower in those aged 18-65 years than in those aged 65 and over. Conclusion Our findings are consistent with strong protection of BNT162b2 boosting against positive SARS-CoV-2 test, COVID-19 hospitalisation, and COVID-19 death.
... Instead of the actual antigen, more recent vaccinations contain the recipe for making them and this will boost their immune system to respond (WHO, 2021d). The epidemiological literature has previously demonstrated the efficacy of COVID-19 vaccinations in decreasing viral transmission, severe illnesses, hospitalizations, and mortality (Dagan et al., 2021;Voysey et al., 2021). Vaccines have been proven in clinical studies to reduce the risk of developing and spreading COVID-19, as well as the severity of virus (Abu-Raddad, Chemaitelly and Butt, 2021;Pritchard et al., 2021). ...
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This paper empirically investigates two sides of the COVID-19 vaccinations. The first part is a study of the vaccination efficacy and its impact on the number of new cases and new deaths, using the daily doses data of Eight different COVID-19 vaccination for a sample of 30 countries around the world. The second part is a study of the financial benefits for the same eight vaccines producers’ companies. The event study method is adopted in this research to explore the abnormal returns and its accumulations, the event date is January 30, 2020. The Vaccine’s efficacy results show that (Moderna, Oxford/Astrazeneca, and Novavax V) proved efficacy in reducing new cases and new deaths. Meanwhile, Cansino’s vaccine was effective in reducing the number of new cases only. On the other hand, vaccines like (Pfizer/ Biontech, Sinovac, Johnson & Johnson, and Sinopharm/ Beijing) didn’t prove efficacy in reducing the number of new cases and new deaths. The Financial benefits results show that the vaccine manufacturers who achieved the benefits of abnormal returns in the presence of vaccine efficacy are (Oxford/AstraZeneca and Novavax). While other manufacturers did not achieve the benefits of abnormal returns. The results also show that the pharmaceutical companies that achieved benefits on the cumulative abnormal returns in the presence of the vaccine efficacy are (Oxford/AstraZeneca, Novavax, Moderna, and CanSino). Meanwhile, the rest of manufacturers achieved cumulative abnormal returns but they are not effective in reducing the numbers of neither new cases nor new deaths.
... SARS-CoV-2 infection in pregnancy is associated with several severe consequences (1, 2), highlighting the need for prevention measures against SARS-CoV-2 infection. COVID-19 vaccines have been shown to be highly effective against SARS-CoV-2 infection, severe COVID-19, and death in clinical trials and in real-world settings (7,43). However, despite cohort studies and ongoing clinical trials in this population (44, 45), evidence of their safety and efficacy are limited to date, which contributes to immunization hesitancy (14,46). ...
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Objectives The low COVID-19 vaccine uptake rate among pregnant women is mainly due to safety concerns about COVID-19 vaccines due to limited safety evidence. Our goal was to evaluate the safety of COVID-19 vaccination during pregnancy with up-to-date evidence. Methods A comprehensive search of MEDLINE, EMBASE, the Cochrane Library, and clinicaltrials.gov was performed on April 5th, 2022, and updated on May 25th, 2022. Studies evaluating the association of COVID-19 vaccination during pregnancy with adverse maternal and neonatal outcomes were included. Two reviewers independently performed the risk of bias assessment and data extraction. Inverse variance random effect meta-analyses were performed to pool outcome data. Results Forty-three observational studies were included. COVID-19 vaccination [96,384 (73.9%) BNT162b2, 30,889 (23.7%) mRNA-1273, and 3,172 (2.4%) other types] during pregnancy [23,721 (18.3%) in the first trimester, 52,778 (40.5%) in the second trimester, and 53,886 (41.2%) in the third trimester].was associated with reduced risks of stillbirth or neonatal death (OR, 0.74; 95% CI, 0.60–0.92). Sensitivity analysis restricted to studies in participants without COVID-19 showed that the pooled effect was not robust. COVID-19 vaccination during pregnancy was not associated with congenital anomalies (OR, 0.83; 95% CI, 0.63–1.08), preterm birth (OR, 0.98; 95% CI, 0.90–1.06), NICU admission or hospitalization (OR, 0.94; 95% CI, 0.84–1.04), an Apgar score at 5 min <7 (OR, 0.93; 95% CI, 0.86–1.01), low birth weight (OR, 1.00; 95% CI, 0.88–1.14), miscarriage (OR, 0.99; 95% CI, 0.88–1.11), cesarean delivery (OR, 1.07; 95% CI, 0.96–1.19), or postpartum hemorrhage (OR, 0.91; 95% CI, 0.81–1.01). Conclusions COVID-19 vaccination during pregnancy was not associated with any of the adverse neonatal or maternal outcomes studied. Interpretation of study findings is limited by the types and timing of vaccination. The vaccinations in our study received during pregnancy were primarily mRNA vaccines administered in the second and third trimester. Future RCTs and meta-analysis are warranted to evaluate the efficacy and long-term effects of the COVID-19 vaccines. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022322525 , identifier: PROSPERO, CRD42022322525.
... Mitigation of the COVID-19 pandemic was observed after commencing the mass vaccination programs, especially in regions with high vaccination coverage. [1] The ChAdOx1 nCoV-19 was the first approved vaccine in Sri Lanka and the vaccination program commenced on January 29, 2021, with the immunization of healthcare workers in the country. ...
Article
Objectives: Actual world data on vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are imperative for future immunization decisions. We studied the reactogenicity and IgG response in a cohort dually vaccinated with the ChAdOx1 nCoV-19 vaccine. Methods: This prospective study recruited 494 ChAdOx1 nCoV-19 vaccine recipients at the University Hospital KDU between January 30 and February 5, 2021, and followed up for 9 months. The two doses of the vaccine were administered 3-month apart, followed by a booster dose with the BNT162b2 (Pfizer-BioNTech) vaccine 6 months later. One-week post-vaccination surveillance ascertained the reactogenicity of the vaccine. Seroprevalence of IgG antibodies before each vaccination dose was determined using a commercially available quantitative ELISA kit (WANTAI SARS-CoV-2 IgG Quantitative ELISA Beijing China). Reactogenicity profiles after vaccination doses were compared. Association of pre-vaccination seropositivity and demographic variables with antibody levels was assessed. Results: Reactogenicity was reported by 78.5% (329/419) and 25.4% (104/410) participants after the first and second doses, respectively, with a significantly high mean total score of vaccine-related symptoms following the first dose (P = 0.015). Post-first dose seroconversion rate was 97.1%, and the immune response was more robust among pre-vaccination seropositive participants and females. Following the second dose, 100% seroconversion was observed. Subgroup analysis of 196 participants revealed persistent antibodies at nine months with a rise in the previously measured levels among 78.1% compared to 21.9% with declining titers. Antibody waning was significantly associated with pre-vaccination seropositivity (P = 0.015) and female gender (P = 0.022). Conclusions: High seroconversion rates and longevity of antibody response in the absence of serious concerns regarding reactogenicity suggest that the vaccine is immunogenic and safe. Significant antibody waning among females and pre-vaccination seropositive participants warrant further research.
... In another study comparing CoronaVac with BNT162b2 (mRNA vaccine), there was a negative correlation between age and neutralizing antibody formation. Accordingly, the neutralizing antibody titer was significantly lower in the group vaccinated with CoronaVac than those receiving BNT162b2 (3,18,19). ...
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Aim: COVID-19 is an important public health problem in world and Turkey. The present study aimed to compare the clinical and laboratory findings and mortality rates among vaccinated and unvaccinated COVID-19 inpatients.Material and Method: We included patients receiving inpatient treatment in COVID-19 wards of our hospital between April 25 and October 22, 2021. The patients were divided into two groups: those with and without the COVID-19 vaccine. We extracted patient information from anamnesis files and the hospital information system. Then, we recorded the patients’ epidemiological and laboratory findings and vaccination status. Patients with at least two doses of the COVID-19 vaccine were considered “vaccinated.” We performed Fisher’s exact test and Chi-square test to analyze the data. All statistical analyses were performed in SPSS, and a p-value <0.05 was accepted as statistically significant.Results: The study included 63 vaccinated and 83 unvaccinated patients. With a mean age of 71.4±12.3 years, thirty (47.6%) of the vaccinated patients were females, and 33 (52.3%) were males. Of the unvaccinated ones, 40 (48.1%) were females, while 43 (51.8%) were males (mean age=52.2±14.4 years). The mean age was significantly higher in the vaccinated group than in the unvaccinated group (p<0.01). While 82.5% of the vaccinated patients received two doses, 17.5% received three doses of the COVID vaccine. Besides, 95.3% of the patients received their first dose of inactivated vaccine (Sinovac, China) and 4.7% of an mRNA vaccine (BioNTech, Germany). We found that comorbidities were significantly more prevalent in the vaccinated group than in the unvaccinated group (44 (69.8%) vaccinated and 34 (40.9%) unvaccinated patients had a comorbid disease, p<0.01). Among the accompanying diseases, hypertension was significantly more prevalent in the vaccinated group than in the unvaccinated group (p<0.01). Considering their laboratory findings, the vaccinated patients had significantly higher leukocyte, troponin, and ferritin values than the unvaccinated patients (p=0.008). Consequently, five (57.9) of the vaccinated patients and 4 (4.8%) of the unvaccinated patients died (p=0.05). Conclusion: Similar mortality rates between our vaccinated and unvaccinated patients may be attributed to the fact that the vaccinated group was relatively older, had more comorbid diseases, and received their second dose after an average of 100.6 days following their first dose of inactivated vaccine. In conclusion, further clinical research involving more cases that received different COVID-19 vaccines is needed to uncover the factors affecting mortality and morbidity among vaccinated patients.
... These data, together with the fact that the receptor binding domain (RBD) of the SARS-CoV-2 spike protein is the main target of neutralizing antibodies (53, 151 (139,152). All have demonstrated high rates of efficacy in preventing COVID-19, especially protecting against severe disease and death (153)(154)(155)(156)(157)(158). Since vaccination protocols started in December 2020 with BNT162b2 vaccine, it has been estimated that global anti-SARS-CoV-2 vaccination saved nearly 20 million lives in its first year of application (159). ...
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SARS-CoV-2-specific T cell response has been proven essential for viral clearance, COVID-19 outcome and long-term memory. Impaired early T cell-driven immunity leads to a severe form of the disease associated with lymphopenia, hyperinflammation and imbalanced humoral response. Analyses of acute SARS-CoV-2 infection have revealed that mild COVID-19 course is characterized by an early induction of specific T cells within the first 7 days of symptoms, coordinately followed by antibody production for an effective control of viral infection. In contrast, patients who do not develop an early specific cellular response and initiate a humoral immune response with subsequent production of high levels of antibodies, develop severe symptoms. Yet, delayed and persistent bystander CD8+ T cell activation has been also reported in hospitalized patients and could be a driver of lung pathology. Literature supports that long-term maintenance of T cell response appears more stable than antibody titters. Up to date, virus-specific T cell memory has been detected 22 months post-symptom onset, with a predominant IL-2 memory response compared to IFN-γ. Furthermore, T cell responses are conserved against the emerging variants of concern (VoCs) while these variants are mostly able to evade humoral responses. This could be partly explained by the high HLA polymorphism whereby the viral epitope repertoire recognized could differ among individuals, greatly decreasing the likelihood of immune escape. Current COVID-19-vaccination has been shown to elicit Th1-driven spike-specific T cell response, as does natural infection, which provides substantial protection against severe COVID-19 and death. In addition, mucosal vaccination has been reported to induce strong adaptive responses both locally and systemically and to protect against VoCs in animal models. The optimization of vaccine formulations by including a variety of viral regions, innovative adjuvants or diverse administration routes could result in a desirable enhanced cellular response and memory, and help to prevent breakthrough infections. In summary, the increasing evidence highlights the relevance of monitoring SARS-CoV-2-specific cellular immune response, and not only antibody levels, as a correlate for protection after infection and/or vaccination. Moreover, it may help to better identify target populations that could benefit most from booster doses and to personalize vaccination strategies.
... An accepted statistical method for estimating treatment efficacy across populations in an uncontrolled context is to use prospective data to simulate a target trial (15,16) . ...
... The effectiveness of the BNT162b2 vaccine is detected at 92% after the second dose in Israel after nationwide mass vaccination. 4,6 Vaccines registered and put into use by countries differ according to national policies. Public instilled with BioNTech/ Pfizer, Sinovac, and Turkovac vaccines against to COVID-19 in Turkey. ...
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It was aimed to make a retrospective analysis of the vaccines administered in the vaccine unit of our hospital since the beginning of the COVID-19 pandemic. The study was carried out retrospectively from the vaccination records our hospital, 14 January 2021 to 01 July 2022. In the 18-month period, a total of 75079 (100%) vaccines were administered, 59386 (79%) were Biontech and 15693 (21%) were Sinovac vaccines. Only Sinovac was available until June, therefore, 66% of the Sinovac vaccines were administered in the first five months period. After the Biontech vaccine started to be applied in our hospital, the rates of Sinovac vaccination have declined drastically. When the epidemic and vaccination graphs were examined separately, inverse correlation was found between the peak points of the epidemic and vaccine graphics. Biontech was found to be the most preferred vaccine by individuals against COVID-19 in this study.
... A considerable number of randomized clinical trials have confirmed the safety and efficacy of COVID-19 vaccines [3][4][5], and many observational cohort studies and test-negative case-control studies on vaccine effectiveness have reported a significant reduction in infection, hospitalization, and progression to severe disease including death [6][7][8][9][10]. However, these previous studies have been Western-centric, and the number of studies from Asia, especially Japan, is small. ...
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Background: Many previous studies have reported COVID-19 vaccine effectiveness, but there are few studies in Japan. This community-based, retrospective observational study investigated the association between vaccination status and COVID-19-related health outcomes in COVID-19 patients by SARS-CoV-2 variant type. Methods: The study participants were 24,314 COVID-19 patients aged 12 or older whose diagnoses were reported to the Nara Prefecture Chuwa Public Health Center from April 2021 to March 2022, during periods when the alpha, delta, and omicron variants of COVID-19 were predominant. The outcome variables were severe health consequences (SHC) (i.e., ICU admission and COVID-19-related death), hospitalization, and extension of recovery period. The explanatory variable was vaccination status at least 14 days prior to infection. Covariates included gender, age, population size, the number of risk factors for aggravation, and the number of symptoms at diagnosis. The generalized estimating equations of the multivariable Poisson regression models were used to estimate the adjusted incidence proportion (AIP) and 95% confidence interval (CI) for each health outcome. We performed stratified analyses by SARS-CoV-2 variant type, but the association between vaccination status and COVID-19-related health outcomes was stratified only for the delta and omicron variants due to the small number of vaccinated patients during the alpha variant. Results: Of the 24,314 participants, 255 (1.0%) had SHC; of the 24,059 participants without SHC, 2,102 (8.7%) were hospitalized; and of the 19,603 participants without SHC, hospitalization, and missing data on recovery period, 2,960 (15.1%) had extension of recovery period. Multivariable Poisson regression models showed that regardless of SARS-CoV-2 variant type or health outcome, those who received two or more vaccine doses had significantly lower risk of health outcomes than those who did not receive the vaccine, and there was a dose-response relationship in which the AIP for health outcomes decreased with an increased number of vaccinations. Conclusion: A higher number of vaccinations were associated with lower risk of COVID-19-related health outcomes, not only in the delta variant but also in the omicron variant. Our findings suggest that increasing the number of COVID-19 vaccine doses can prevent severe disease and lead to early recovery of patients not requiring hospitalization. Fullsize Image
... Профиль безопасности вакцины BNT162b2 характеризовался кратковременной болью от слабой до умеренной в месте инъекции, утомляемостью и головной болью. Частота серьезных НЯ была низкой и аналогичной в группах вакцинированных и плацебо [7,8]. ...
Article
During the spread of an increasing number of new variants of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), it is extremely important not only to assess the immunogenicity and efficacy, butalso the safety of various combinations of vaccines. Excessive immune response and associated signs and symptoms may occur with varying frequency as expected from the use of vaccines. Aim. To compare the reactogenicity of various (heterologous and homologous) vaccination regimens in a prospective observational study. Material and methods . In individuals aged ≥18 years, in the absence of contraindications to vaccination, two types of vaccines were used at primary vaccination and revaccination: Gam-COVID-Vac and CoviVac: group I (n=97) — Gam-COVID-Vac at each stage of primary and booster vaccination ; group II (n=7) — Gam-COVID-Vck at each stage of primary vaccination, CoviVac at each stage of revaccination; group III (n=42) — CoviVac at each stage of primary vaccination, Gam-COVID-Vac at each stage of revaccination; group IV (n=38) — CoviVac at each stage of primary and secondary vaccination. In all participants, the dynamics of IgG to SARS-CoV-2 spike glycoprotein receptor-binding domain and T-cell immunity to SARS-CoV-2 were determined over time. To control the plasma hemostasis, the method of dynamic thrombophotometry was used. Local and systemic adverse events were assessed. Results. The number of vaccinated individuals with a rise in body temperature above 37 ⁰ C after the 1 st stage of revaccination was significantly (p<0,05) more in group I (37,5%) and group II (57,1%) compared with vaccinated persons of IV group. At the same time, after the 2 nd stage of revaccination, in general, a smaller percentage of vaccinated persons with hyperthermia was noted. In group I, a higher percentage of persons (22,9%) complaining of the appearance of weakness after stage I of revaccination was noted compared to vaccinated persons of group IV — 5,2%. An increase in the fibrin clot growth rate was noted in group III at the stage of revaccination. Conclusion. The use of various revaccination schemes (homologous and heterologous) was not associated with the development of serious adverse events. The resulting local and systemic reactions were shortlived and did not require hospitalization. More pronounced systemic reactions were noted in the form of a short-term fever and weakness when using the Gam-COVID-Vac. No cases of arterial or venous thrombosis were registered during the follow-up period.
... vaccines are considered a safe means to reduce COVID-19 incidence [1,2] and to prevent severe morbidity or mortality [3]. However, reducing the burden of disease via comprehensive vaccination requires widespread willingness to be vaccinated [4], and such willingness has been wavering or suboptimal in several countries, including Germany [5,6]. ...
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Background Willingness to vaccinate against coronavirus disease 2019 (COVID-19), which is vital to successful vaccination campaigns, is wavering and suboptimal. In Germany, quantitative research highlighted concerns regarding the safety and efficacy of COVID-19 vaccines as barriers to uptake, but qualitative insights regarding individuals’ decisions about COVID-19 vaccines and how personal perceptions reflect or refute existing behavioral theories are lacking. Methods To identify how individuals make COVID-19 vaccination decisions within real-life contexts, we conducted 33 semi-structured, in-depth qualitative interviews with individuals in Germany between March and April 2021 using maximum variation sampling, focusing on perceptions of COVID-19 vaccines. Analysis, informed by a framework approach, began in the field via debriefings and was amplified upon the conclusion of data collection. Results Four interconnected themes (deliberation, context, emotion, trust) shaped respondents’ decisions about vaccination. Personal deliberation regarding benefits and risks of vaccines and perceptions of the broader social and political context sparked a spectrum of emotions that underpinned vaccination decisions. Trust in science and researchers emerged as a powerful protective factor facilitating the decision to get vaccinated even amidst a rapidly changing context and disconcerting information. Conclusions Our findings add to ongoing debates about the breadth of vaccination decisions by highlighting how respondents are influenced by their perceptions of the political context and the emotional heft of their decisions. The role of cognitive evaluation, context, and emotions mirrors other decision-making frameworks, particularly the Risk as Feelings Theory. We extend on the elements of this theory by highlighting trust as a protective factor when making decisions particularly in highly uncertain contexts. Success of vaccination campaigns, more important than ever as new variants of COVID-19 emerge, is interwoven with an ability to bolster trust in science. Communicating public-health decisions and information about vaccines transparently without instilling fear offers promising chances to strengthen public trust in COVID-19 vaccines. Trial registration German Clinical Trials Register ( DRKS00024505 ).
... The modeling framework may also be adapted to assess the influence of COVID-19 vaccination on patient behavior. New cases of COVID-19 are expected to decrease if nationwide vaccination is effective, and this may mitigate restrictions on patients' clinical activities [23]. Moreover, this modeling framework can be reconfigured to assess the impact of COVID-19 on the management of patients with other chronic conditions such as HIV, diabetes, etc., for whom regular clinic visits, prescription refills, and access to medical facilities are also integral to the management of their condition [24][25][26][27]. ...
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Managing inflammatory bowel disease (IBD) is a major challenge for physicians and patients during the COVID-19 pandemic. To understand the impact of the pandemic on patient behaviors and disruptions in medical care, we used a combination of population-based modeling, system dynamics simulation, and linear optimization. Synthetic IBD populations in Tokyo and Hokkaido were created by localizing an existing US-based synthetic IBD population using data from the Ministry of Health, Labor, and Welfare in Japan. A clinical pathway of IBD-specific disease progression was constructed and calibrated using longitudinal claims data from JMDC Inc for patients with IBD before and during the COVID-19 pandemic. Key points considered for disruptions in patient behavior (demand) and medical care (supply) were diagnosis of new patients, clinic visits for new patients seeking care and diagnosed patients receiving continuous care, number of procedures, and the interval between procedures or biologic prescriptions. COVID-19 had a large initial impact and subsequent smaller impacts on demand and supply despite higher infection rates. Our population model (Behavior Predictor) and patient treatment simulation model (Demand Simulator) represent the dynamics of clinical care demand among patients with IBD in Japan, both in recapitulating historical demand curves and simulating future demand during disruption scenarios, such as pandemic, earthquake, and economic crisis.
... Two doses of the BNT162b2 mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are safe and effective in immunocompetent subjects [1][2][3]. However, the waning of the vaccine's protection over time against symptomatic infection after two doses of the vaccine has been reported among the immunocompetent and, more so, immunocompromised individuals [4][5][6][7][8]. ...
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The immune responses of liver transplant (LT) recipients after the third boost of the BNT162b2mRNA vaccine improved. This study evaluates the durability of the immune response of LT recipients after the third boost, its predictors, and the impact of emerging variants. The receptor-binding domain IgG was determined at median times of 22 (first test) and 133 days (second test) after the administration of the third boost. IgG antibody titers > 21.4 BAU/mL were defined as a positive response. The neutralization efficacies of the vaccine against the wild-type, Omicron, and Delta variants were compared in the first test. The 59 LT recipients were of a median age of 61 years (range 25–82); 53.5% were male. Following administration of the third dose, the positive immune response decreased from 81.4% to 76.3% between the first and second tests, respectively, (p < 0.0001). The multivariate analysis identified CNI monotherapy (p = 0.02) and hemoglobin > 12 g/dL (p = 0.02) as independent predictors of a maintained positive immune response 133 days after the third dose. The geometric mean titers of Omicron neutralization were significantly lower than the wild-type and Delta virus (21, 137, 128, respectively; p < 0.0001). The immune response after the third BNT162b2mRNA vaccine dose decreased significantly in LT recipients. Further studies are required to evaluate the efficacy of the fourth vaccine dose and the durability of the immune response.
... This finding is in agreement with other studies reported in the literature. Dagan et al. suggested that the COVID-19 vaccination was highly effective at preventing severe outcomes after infection, causing decreases in hospitalization, severe illness and death [36]. Most of the symptomatic BIs reported by Raju Vaishya et al. did not require intensive care unit admission, and there were no deaths during the study period [37]. ...
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Background: The aim of this study was to determine the characteristics, clinical course and outcomes of COVID-19 breakthrough infections (BIs) among healthcare workers (HCWs) of an Italian University Hospital. Methods: A retrospective observational study was conducted on 6111 HCWs, from January 2021 to February 2022. The study population was offered the full vaccination with BNT162b2 mRNA COVID-19 vaccine. To allow return to work after BI, the protocol required one negative nasopharyngeal RT-PCR swab followed by a medical examination to assess the HCW's health status. Laboratory tests, instrumental tests and specialist evaluations were carried out if necessary. Results: The cases of BIs observed numbered 582 (9.7%). The frequency of BIs was significantly higher in females than in males (67% vs. 33%; p = 0.03), and in nurses than in all other professional categories (p = 0.001). A total of 88% of the HCWs affected by BI were still symptomatic after the negative swab. None of the instrumental tests carried out showed any new findings of pathological significance. All cases showed progressive disappearance of symptoms, such that no cases of long COVID and no hospitalization or deaths were recorded. Conclusions: Our results confirm that SARS-CoV-2 infections occur even after a full vaccination course; however, the clinical course is favorable and severe outcomes are reduced.
... In the Kingdom of Saudi Arabia (KSA), the overall number of cases and deaths has exceeded 747,436 and 9008, respectively [2]. Together with the applied safety measures to stop the virus transmission, a COVID-19 vaccine is believed to slow the outbreak, save lives, and minimize the burden on the healthcare system [3][4][5][6][7][8]. Furthermore, COVID-19 control measures were helpful in tackling other infectious conditions, such as tuberculosis [9]. ...
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Simultaneously with the development of the COVID-19 vaccination plan for minors, it is critical to understand the reasons related to parental COVID-19 vaccination hesitancy. This study aims to determine the reasons associated with vaccination hesitancy among parents, and the prevalence and the characteristics of the parents who are hesitant to allow their children aged between 5 to 11 years old to be administered the COVID-19 vaccines. A web-based questionnaire was used to perform this study between May 2022 to September 2022 in Saudi Arabia (SA). Several factors, personal and social, affected the participants’ willingness to vaccinate their children with the COVID-19 vaccines. The age of the parents was found to have a significant impact on their decision to vaccinate their children. Those between the age of 40–49 years of age were the most willing to vaccinate (almost 41%) compared to those 50 years or older who were most resistant to vaccination. Female participants were more resistant to vaccinating their children compared to their male counterparts. Saudis were more resistant to vaccinating their children compared to the non-Saudi participants. Those private sector-employed parents were the most willing to vaccinate (16.6%), followed by those working in the governmental sector (13.8%). About 40.7% of non-healthcare workers were resistant to vaccinating their minor compared to healthcare workers (8.7%). In conclusion, the study presents several factors that affect the parental willingness to vaccinate their children in SA. These factors should be properly addressed when developing public health strategies to promote the COVID-19 vaccination of children in SA.
... Furthermore, administration of a third booster dose has also been shown to be effective in reducing covid-19 cases and severe illness. [29][30][31][32][33] Despite the cumulative evidence of the covid-19 vaccines' ability to reduce disease burden and severity, whether immunisation protects against the long term sequelae of breakthrough covid-19 infection is still unknown. [34][35][36] The main objective of this study was to compare the long term incidence of a large set of health outcomes between uninfected people and patients with mild covid-19. ...
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Objectives To determine the clinical sequelae of long covid for a year after infection in patients with mild disease and to evaluate its association with age, sex, SARS-CoV-2 variants, and vaccination status. Design Retrospective nationwide cohort study. Setting Electronic medical records from an Israeli nationwide healthcare organisation. Population 1 913 234 Maccabi Healthcare Services members of all ages who did a polymerase chain reaction test for SARS-CoV-2 between 1 March 2020 and 1 October 2021. Main outcome measures Risk of an evidence based list of 70 reported long covid outcomes in unvaccinated patients infected with SARS-CoV-2 matched to uninfected people, adjusted for age and sex and stratified by SARS-CoV-2 variants, and risk in patients with a breakthrough SARS-CoV-2 infection compared with unvaccinated infected controls. Risks were compared using hazard ratios and risk differences per 10 000 patients measured during the early (30-180 days) and late (180-360 days) time periods after infection. Results Covid-19 infection was significantly associated with increased risks in early and late periods for anosmia and dysgeusia (hazard ratio 4.59 (95% confidence interval 3.63 to 5.80), risk difference 19.6 (95% confidence interval 16.9 to 22.4) in early period; 2.96 (2.29 to 3.82), 11.0 (8.5 to 13.6) in late period), cognitive impairment (1.85 (1.58 to 2.17), 12.8, (9.6 to 16.1); 1.69 (1.45 to 1.96), 13.3 (9.4 to 17.3)), dyspnoea (1.79 (1.68 to 1.90), 85.7 (76.9 to 94.5); 1.30 (1.22 to 1.38), 35.4 (26.3 to 44.6)), weakness (1.78 (1.69 to 1.88), 108.5, 98.4 to 118.6; 1.30 (1.22 to 1.37), 50.2 (39.4 to 61.1)), and palpitations (1.49 (1.35 to 1.64), 22.1 (16.8 to 27.4); 1.16 (1.05 to 1.27), 8.3 (2.4 to 14.1)) and with significant but lower excess risk for streptococcal tonsillitis and dizziness. Hair loss, chest pain, cough, myalgia, and respiratory disorders were significantly increased only during the early phase. Male and female patients showed minor differences, and children had fewer outcomes than adults during the early phase of covid-19, which mostly resolved in the late period. Findings remained consistent across SARS-CoV-2 variants. Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnoea and similar risk for other outcomes compared with unvaccinated infected patients. Conclusions This nationwide study suggests that patients with mild covid-19 are at risk for a small number of health outcomes, most of which are resolved within a year from diagnosis.
... There are two common alternative statistical approaches to estimating vaccine effectiveness. The first approach is the emulated trial design (e.g., [48]), which matches subjects with the same covariates in an observational study to emulate a randomized trial. This design offers more robustness against misspecification of the functional form by which booster status and infection risk depend on covariates, but requires a larger dataset to enable matching simultaneously on all covariates. ...
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Background: While booster vaccinations clearly reduce the risk of severe Coronavirus Disease 2019 (COVID-19) and death, the impact of boosters on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections has not been fully characterized: Doing so requires understanding their impact on asymptomatic and mildly symptomatic infections that often go unreported but nevertheless play an important role in spreading SARS-CoV-2. We sought to estimate the impact of COVID-19 booster doses on SARS-CoV-2 infections in a vaccinated population of young adults during an Omicron BA.1-predominant period. Methods and findings: We implemented a cohort study of young adults in a college environment (Cornell University's Ithaca campus) from a period when Omicron BA.1 was the predominant SARS-CoV-2 variant on campus (December 5 to December 31, 2021). Participants included 15,800 university students who completed initial vaccination series with vaccines approved by the World Health Organization for emergency use, were enrolled in mandatory at-least-weekly surveillance polymerase chain reaction (PCR) testing, and had no positive SARS-CoV-2 PCR test within 90 days before the start of the study period. Robust multivariable Poisson regression with the main outcome of a positive SARS-CoV-2 PCR test was performed to compare those who completed their initial vaccination series and a booster dose to those without a booster dose. A total of 1,926 unique SARS-CoV-2 infections were identified in the study population. Controlling for sex, student group membership, date of completion of initial vaccination series, initial vaccine type, and temporal effect during the study period, our analysis estimates that receiving a booster dose further reduces the rate of having a PCR-detected SARS-CoV-2 infection relative to an initial vaccination series by 56% (95% confidence interval [42%, 67%], P < 0.001). While most individuals had recent booster administration before or during the study period (a limitation of our study), this result is robust to the assumed delay over which a booster dose becomes effective (varied from 1 day to 14 days). The mandatory active surveillance approach used in this study, under which 86% of the person-days in the study occurred, reduces the likelihood of outcome misclassification. Key limitations of our methodology are that we did not have an a priori protocol or statistical analysis plan because the analysis was initially done for institutional research purposes, and some analysis choices were made after observing the data. Conclusions: We observed that boosters are effective, relative to completion of initial vaccination series, in further reducing the rate of SARS-CoV-2 infections in a college student population during a period when Omicron BA.1 was predominant; booster vaccinations for this age group may play an important role in reducing incidence of COVID-19.
... A durable mucosal immunity at this site is therefore a highly desired outcome in a COVID-vaccination. One of the most immunogenic COVID-19 vaccines -the BNT162b2 (Comirnaty ® ) mRNA vaccine induces high titres of systemic SARS-CoV-2 spike-specific antibodies (2,3). In the oral cavity and saliva, it conveys virus-binding antibodies highly correlative to neutralizing capacity. ...
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Coevolution of microbiome and immunity at mucosal sites is essential for our health. Whether the oral microbiome, the second largest community after the gut, contributes to the immunogenicity of COVID-19 vaccines is not known. We investigated the baseline oral microbiome in individuals in the COVAXID clinical trial receiving the BNT162b2 mRNA vaccine. Participants (n=115) included healthy controls (HC; n=57) and people living with HIV (PLHIV; n=58) who met the study selection criteria. Vaccine-induced Spike antibodies in saliva and serum from 0 to 6 months were assessed and comparative analyses were performed against the individual salivary 16S ASV microbiome diversity. High- versus low vaccine responders were assessed on general, immunological, and oral microbiome features. Our analyses identified oral microbiome features enriched in high- vs. low-responders among healthy and PLHIV participants. In low-responders, an enrichment of Gram-negative, anaerobic species with proteolytic activity were found including Campylobacter, Butyrivibrio, Selenomonas, Lachnoanaerobaculum, Leptotrichia, Megasphaera, Prevotella and Stomatobaculum. In high-responders, enriched species were mainly Gram-positive and saccharolytic facultative anaerobes: Abiotrophia, Corynebacterium, Gemella, Granulicatella, Rothia, and Haemophilus. Combining identified microbial features in a classifier using the area under the receiver operating characteristic curve (ROC AUC) yielded scores of 0.879 (healthy controls) to 0.82 (PLHIV), supporting the oral microbiome contribution in the long-term vaccination outcome. The present study is the first to suggest that the oral microbiome has an impact on the durability of mucosal immunity after Covid-19 vaccination. Microbiome-targeted interventions to enhance long-term duration of mucosal vaccine immunity may be exploited.
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Background: Vaccinations play a critical role in mitigating the impact of COVID-19 and other diseases. Past research has linked misinformation to increased hesitancy and lower vaccination rates. Gaps remain in our knowledge about the main drivers of vaccine misinformation on social media and effective ways to intervene. Objective: Our longitudinal study has two primary objectives: (i) to investigate the patterns of prevalence and contagion of COVID-19 vaccine misinformation on Twitter in 2021; and (ii) to identify the main spreaders of vaccine misinformation. Given our results, we also question what are the likely drivers of misinformation and its spread, providing insights for potential interventions. Methods: We collected almost 300M English-language tweets related to COVID-19 vaccines using a list of over 80 relevant keywords over a period of 12 months. We then extracted and labeled news articles at the source level, based on third-party lists of low-credibility and mainstream news sources, and measured the prevalence of different kinds of information. We also considered suspicious YouTube videos shared on Twitter. We focused our analysis of vaccine misinformation spreaders on verified and automated Twitter accounts.Our findings show a relatively low prevalence of low-credibility information compared to the entirety of mainstream news. However, the most popular low-credibility sources had reshare volumes comparable to many mainstream sources, and larger volumes than authoritative sources such as the U.S. Centers for Disease Control and Prevention and the World Health Organization. Throughout the year, we observed an increasing trend in the prevalence of low-credibility news about vaccines. We also observed a considerable amount of suspicious YouTube videos shared on Twitter. Tweets by a small group of about 800 "superspreaders" verified by Twitter accounted for approximately 35% of all reshares of misinformation on an average day, with the top superspreader (@RobertKennedyJr) responsible for over 13% of retweets. Finally, low-credibility news and suspicious YouTube videos were more likely to be shared by automated accounts. Results: Our findings show a relatively low prevalence of low-credibility information compared to the entirety of mainstream news. However, the most popular low-credibility sources had reshare volumes comparable to many mainstream sources, and larger volumes than authoritative sources such as the U.S. Centers for Disease Control and Prevention and the World Health Organization. Throughout the year, we observed an increasing trend in the prevalence of low-credibility news about vaccines. We also observed a considerable amount of suspicious YouTube videos shared on Twitter. Tweets by a small group of about 800 "superspreaders" verified by Twitter accounted for approximately 35% of all reshares of misinformation on an average day, with the top superspreader (@RobertKennedyJr) responsible for over 13% of retweets. Finally, low-credibility news and suspicious YouTube videos were more likely to be shared by automated accounts. Conclusions: The wide spread of misinformation around COVID-19 vaccines on Twitter during 2021 shows that there was an audience for this type of content. Our findings are also consistent with the hypothesis that superspreaders are driven by financial incentives that allow them to profit from health misinformation. Despite high-profile cases of deplatformed misinformation superspreaders, our results show that in 2021 a few individuals still played an outsize role in the spread of low-credibility vaccine content. As a result, social media moderation efforts would be better served by focusing on reducing the online visibility of repeat-spreaders of harmful content, especially during public health crises.
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The unanticipated continued deep-rooted trend of the Severe Acute Respiratory Syndrome Corona-virus-2 the originator pathogen of the COVID-19 persists posing concurrent anxiety globally. More effort is affixed in the scientific arena via continuous investigations in a prolific effort to understand the transmission dynamics and control measures in eradication of the epidemic. Both pharmaceutical and non-pharmaceutical containment measure protocols have been assimilated in this effort. In this study, we develop a modified SEIR deterministic model that factors in alternative-amalgamation of use of COVID Alert SA app and vaccination against the COVID-19 to the Republic of South Africa's general public in an endeavor to discontinue the chain of spread for the pandemic. We analyze the key properties of the model not limited to positivity, boundedness, and stability. We authenticate the model by fitting it to the Republic of South Africa's cumulative COVID-19 cases reported data utilizing the Maximum Likelihood Estimation algorithm implemented in fitR package. Sensitivity analysis and simulations for the model reveal that simultaneously-gradually increased implementation of the COVID Alert SA app use and vaccination against COVID-19 to the public substantially accelerate reduction in the plateau number of COVID-19 infections across all the observed vaccine efficacy scenarios. More fundamentally, it is discovered that implementing at least 12% app use (mainly for the susceptible population not vaccinated) with simultaneous vaccination of over 12% of the susceptible population majorly not using the app using a vaccine of at least 50% efficacy would be sufficient in eradicating the pandemic over relatively shorter time span.
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The objective of our study was to determine the joint protective effect of a previous SARS-CoV-2 infection and vaccination on the risk of a new infection and hospitalization. Two case–control studies nested in a cohort of COVID-19 patients cared for by the Local Health Unit (LHU) of Vercelli, Italy, were performed, one to estimate the risk of infection and the second to estimate the risk of hospitalization. Each new infection and hospitalization was matched with up to 4 disease-free subjects who were the same age, sex and index date (i.e., controls). Study subjects were followed up from cohort entry date to disease outcome, end of follow-up or emigration. Vaccination was associated with a 36% (OR 0.64; 95%CI 0.62–0.66) and 90% (OR 0.10; 95%CI 0.07–0.14) reduction in the risk of infection and hospitalization, respectively. Prior infection was associated with a 65% (OR 0.35; 95%CI 0.30–0.40) and 90% (OR 0.10; 95%CI 0.07–0.14) reduction in the risk of infection and hospitalization, respectively. Vaccinated and recovered subjects showed a 63% (OR 0.37; 95%CI 0.34–0.14) and 98% (OR 0.02; 95%CI 0–0.13) reduction in the risk of infection and hospitalization, respectively. Vaccination remains an essential public health tool for preventing severe forms of COVID-19. Our study shows that vaccination or previous infection has a strong protective effect against Sars-CoV-2 hospitalization. The protective role against infection appears to be present although with a lower efficacy rate than that presented in the RCTs.
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Introduction The BNT162b2 mRNA-based vaccine has shown high efficacy in preventing COVID-19 infection but there are limited data on the types and persistence of the humoral and T cell responses to such a vaccine. Methods Here, we dissect the vaccine-induced humoral and cellular responses in a cohort of six healthy recipients of two doses of this vaccine. Results and discussion Overall, there was heterogeneity in the spike-specific humoral and cellular responses among vaccinated individuals. Interestingly, we demonstrated that anti-spike antibody levels detected by a novel simple automated assay (Jess) were strongly correlated (r=0.863, P<0.0001) with neutralizing activity; thus, providing a potential surrogate for neutralizing cell-based assays. The spike-specific T cell response was measured with a newly modified T-spot assay in which the high-homology peptide-sequences cross-reactive with other coronaviruses were removed. This response was induced in 4/6 participants after the first dose, and all six participants after the second dose, and remained detectable in 4/6 participants five months post-vaccination. We have also shown for the first time, that BNT162b2 vaccine enhanced T cell responses also against known human common viruses. In addition, we demonstrated the efficacy of a rapid ex-vivo T cell expansion protocol for spike-specific T cell expansion to be potentially used for adoptive-cell therapy in severe COVID-19, immunocompromised individuals, and other high-risk groups. There was a 9 to 13.7-fold increase in the number of expanded T cells with a significant increase of anti-spike specific response showing higher frequencies of both activation and cytotoxic markers. Interestingly, effector memory T cells were dominant in all four participants’ CD8+ expanded memory T cells; CD4+ T cells were dominated by effector memory in 2/4 participants and by central memory in the remaining two participants. Moreover, we found that high frequencies of CD4+ terminally differentiated memory T cells were associated with a greater reduction of spike-specific activated CD4+ T cells. Finally, we showed that participants who had a CD4+ central memory T cell dominance expressed a high CD69 activation marker in the CD4+ activated T cells.
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Background and aims: We retrospectively assessed the clinical Pfizer's mRNA SARS-CoV-2 BNT162b2 vaccination outcomes and the serologic impact on liver transplant (LT) recipients. Patients and methods: One hundred and sixty-seven LT cases followed between March 1, 2020 and September 25, 2021, and were stratified into two groups: (1) 37 LT recipients after SARS-CoV-2 infection before vaccine era and (2) 130 LT recipients vaccinated with 2 doses without earlier SARS-CoV-2 exposure. Serum SARS-CoV-2 spike immunoglobulins (anti-S) were assessed 7 days following vaccination (Liaison assay). Results: In addition to the 37 nonvaccinated cases (22.2% of total group) who experienced SARS-CoV-2 infection (34 symptomatic and 3 asymptomatic), another 8 vaccinated symptomatic recipients (4.8%) were infected (5 from the third and three from the fourth waves). Three of the 45 infected cases died (6.7%) before the vaccine program. Vaccinated group: of the 130 LT vaccinated recipients, 8 (6.2%) got infected postvaccination (added to the infected group) and were defined as clinical vaccine failure; 38 (29.2%) were serological vaccine failure (total failure 35.4%), and 64.6% cases were serological vaccine responders (anti-S≥19 AU/mL). Longer post-LT interval and lower consumption of immunosuppressants (steroids, FK506, and mycophenolate mofetil) correlated with favorable SARS-CoV-2 vaccine response. Mammalian target of rapamycin inhibitors improved vaccine outcomes associated with lower FK506 dosages and serum levels. Patients with anti-S levels <100 AU/mL risked losing serologic response or being infected with SARS-CoV-2. A booster dose achieved an effective serologic response in a third of failures and most responders, securing better and possibly longer protection. Conclusion: Pfizer's BNT162b2 vaccine seems to lessen SARS-CoV-2 morbidity and mortality of LT recipients even with weak serological immunogenicity. Switching mycophenolate mofetil to mammalian target of rapamycin inhibitors might be effective before boosters in vaccine failure cases. A booster vaccine should be considered for nonresponders and low-responders after the second dose.
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Intramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable “sterilizing immunity” at the mucosal level. Our study uncovers a strong temporary neutralizing mucosal component of immunity, emanating from intramuscular administration of an mRNA vaccine. We show that saliva of BNT162b2 vaccinees contains temporary IgA targeting the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus-2 spike protein and demonstrate that these IgAs mediate neutralization. RBD-targeting IgAs were found to associate with the secretory component, indicating their bona fide transcytotic origin and their polymeric multivalent nature. The mechanistic understanding of the high neutralizing activity provided by mucosal IgA, acting at the first line of defense, will advance vaccination design and surveillance principles and may point to novel treatment approaches and new routes of vaccine administration and boosting.
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Background The role of vaccination on Covid-19 severity in neurological patients is still unknown. We aim at describing clinical characteristics and outcomes of breakthrough and unvaccinated Covid-19 patients hospitalized for neurological disorders. Methods Two hundred thirty-two Covid-19 patients were admitted to a neuro-Covid Unit form March 2021 to February 2022. Out of the total sample, 74 (32%) were full vaccinated. The prevalence, clinical characteristics and final outcomes of neurological syndromes were compared between vaccinated and unvaccinated cases. Results Breakthrough vaccinated cases were older (years 72.4+16.3 vs 67.0+18.9 years, p=0.029), showed higher pre-admission comorbidity score and Clinical Frailty scale score (4.46+1.6 vs 3.75+2.0, p=0.008) with no differences in terms of disease progression or mortality rate (16.2% vs 15.2%), compared to full-dose vaccinated patients. Cox-regression analysis showed age and NEWS2 score as the variables with a significant relation to mortality between the two groups, independently from pre-morbid conditions and inflammatory response. Conclusion This study on breakthrough COVID-19 infection could help identify vulnerable neurological patients with higher risk of poor outcomes.
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Background: The cardinal method for preventing future SARS-CoV-2 infections, hospitalizations, long-term sequelae, and death is COVID-19 vaccination, despite the possibility that the epidemiology of COVID-19 may change as new variants appear. There is little research on the vaccination status of adult COVID-19 patients and the role of vaccines in mitigating the severity and clinical presentation of COVID-19 patients among local population in Kerala. Objectives were to assess vaccination status and clinical profile of adult COVID-19 patients in Arpookara, Panchayath in Kerala and its association with disease severity and outcome among same. Methods: A cross sectional study was conducted in Arpookara Panchayath in central Kerala, among adult COVID-19 patients during the months of September and October 2021. The required 380 samples were selected by simple random sampling and data was collected by interviewing the subjects using semi structured questionnaire. Results: It was found that 46.1% of the study population were unvaccinated, whereas 30.8% of the population were partially vaccinated and 23.1% were fully vaccinated at the time of COVID-19 infection. A significantly higher proportion of unvaccinated population required hospital admissions, oxygen support and ICU stay when compared to those who took at least one dose of vaccine. Conclusions: Increasing the vaccination coverage of at least single dose of vaccine can reduce rate of hospital admission, ICU stay, oxygen requirement and can improve the outcome of disease. Steps to increase vaccine coverage should be implemented for better outcome of COVID-19 disease as well as to reduce the admission load on the hospitals.
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Conclusions: We concluded that vaccine doses were associated with consistently improved the rate and risk ratio of seroconversion in patients living with HIV, highlighting the significance of booster vaccination for patients living with HIV. Objective: To quantify the pooled rate and risk ratio of seroconversion following the uncomplete, complete, or booster dose of COVID-19 vaccines in patients living with HIV. Method: Pubmed, Embase and Cochrane library were searched for eligible studies published from inception to 13th, September 2022. The pooled rate and risk ratio of seroconversion were assessed using the Freeman-Tukey double arcsine method and Mantel-Haenszel approach, respectively. Random-effects model was preferentially used as the primary approach to pool results across studies. This systematic review and meta-analysis protocol was registered with PROSPERO (CRD42022359603). Results: In this meta-analysis, we comprehensively analyzed 50 studies with a total of 7160 patients living with HIV. We demonstrated that only 75.0% (56.4% to 89.9%) patients living with HIV achieved a seroconversion after uncomplete vaccination, which improved to 89.3% (84.2% to 93.5%) after complete vaccination, and 98.4% (94.8% to 100%) after booster vaccination. The seroconversion rates were significantly lower compared to controls at all the stages, while the risk ratios for uncomplete, complete, and booster vaccination were 0.87 (0.77 to 0.99), 0.95 (0.92 to 0.98), and 0.97 (0.94 to 0.99), respectively. Notably, meta-regression and subgroup analyses suggested that year of publication, study location and vaccine type could cause the difference of the pooled rate or risk ratio of seroconversion for patients living with HIV after complete vaccination. Sensitivity analysis did not much change the results. Conclusions: We concluded that vaccine doses were associated with consistently improved the rate and risk ratio of seroconversion in patients living with HIV, highlighting the significance of booster vaccination for patients living with HIV.
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Background The new types of mRNA-containing lipid nanoparticle vaccines BNT162b2 and mRNA-1273 and the adenovirus-based vaccine AZD1222 were developed against SARS-CoV-2 and code for its spike (S) protein. Several studies have investigated short-term antibody (Ab) responses after vaccination.Objective However, the impact of these new vaccine formats with unclear effects on the long-term Ab response – including isotype, subclass, and their type of Fc glycosylation – is less explored.Methods Here, we analyzed anti-S Ab responses in blood serum and the saliva of SARS-CoV-2 naïve and non-hospitalized pre-infected subjects upon two vaccinations with different mRNA- and adenovirus-based vaccine combinations up to day 270.ResultsWe show that the initially high mRNA vaccine-induced blood and salivary anti-S IgG levels, particularly IgG1, markedly decrease over time and approach the lower levels induced with the adenovirus-based vaccine. All three vaccines induced, contrary to the short-term anti-S IgG1 response with high sialylation and galactosylation levels, a long-term anti-S IgG1 response that was characterized by low sialylation and galactosylation with the latter being even below the corresponding total IgG1 galactosylation level. Instead, the mRNA, but not the adenovirus-based vaccines induced long-term IgG4 responses – the IgG subclass with inhibitory effector functions. Furthermore, salivary anti-S IgA levels were lower and decreased faster in naïve as compared to pre-infected vaccinees. Predictively, age correlated with lower long-term anti-S IgG titers for the mRNA vaccines. Furthermore, higher total IgG1 galactosylation, sialylation, and bisection levels correlated with higher long-term anti-S IgG1 sialylation, galactosylation, and bisection levels, respectively, for all vaccine combinations.Conclusion In summary, the study suggests a comparable “adjuvant” potential of the newly developed vaccines on the anti-S IgG Fc glycosylation, as reflected in relatively low long-term anti-S IgG1 galactosylation levels generated by the long-lived plasma cell pool, whose induction might be driven by a recently described TH1-driven B cell response for all three vaccines. Instead, repeated immunization of naïve individuals with the mRNA vaccines increased the proportion of the IgG4 subclass over time which might influence the long-term Ab effector functions. Taken together, these data shed light on these novel vaccine formats and might have potential implications for their long-term efficacy.
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Background Understanding the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination will enable accurate counseling and inform evolving vaccination strategies. Little is known about antibody response following booster vaccination in people living with HIV (PLWH). Methods We enrolled SARS-CoV-2 vaccinated PLWH and controls without HIV in similar proportions based on age and comorbidities. Participants completed surveys on prior SARS-CoV-2 infection, vaccination, and comorbidities, and provided self-collected dried blood spots (DBS). Quantitative anti-spike IgG and surrogate viral neutralization assays targeted wild-type (WT), Delta, and Omicron variants. We also measured quantitative anti-nucleocapsid IgG. The analysis population had received full SARS-CoV-2 vaccination plus one booster dose. Bivariate analyses for continuous outcomes utilized Wilcoxon tests and multivariate analysis used linear models. Results The analysis population comprised 140 PLWH and 75 controls with median age 58 and 55 years, males 95% and 43%, and DBS collection on 112 and 109 days after the last booster dose, respectively. Median CD4 count among PLWH was 760 cells/mm ³ and 91% had an undetectable HIV-1 viral load. Considering WT, Delta, and Omicron variants, there was no significant difference in mean quantitative anti-spike IgG between PLWH (3.3, 2.9, 1.8) and controls (3.3, 2.9, 1.8), respectively ( p -values=0. 771, 0.920, 0.708). Surrogate viral neutralization responses were similar in PLWH (1.0, 0.9, and 0.4) and controls (1.0, 0.9, 0.5), respectively ( p -values=0.594, 0.436, 0.706). Conclusions PLWH whose CD4 counts are well preserved and persons without HIV have similar anti-spike IgG antibody levels and viral neutralization responses after a single SARS-CoV-2 booster vaccination.
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COVID-19 has emerged as a pandemic leading to a global public health crisis of unprecedented morbidity. A comprehensive insight into the imaging of COVID-19 has enabled early diagnosis, stratification of disease severity, and identification of potential sequelae. The evolution of COVID-19 can be divided into early infectious, pulmonary, and hyperinflammatory phases. Clinical features, imaging features, and management are different among the three phases. In the early stage, peripheral ground-glass opacities are predominant CT findings, and therapy directly targeting SARS-CoV-2 is effective. In the later stage, organizing pneumonia or diffuse alveolar damage pattern are predominant CT findings and anti-inflammatory therapies are more beneficial. The risk of severe disease or hospitalization is lower in breakthrough or Omicron variant infection compared with nonimmunized or Delta variant infections. The protection rates of the fourth dose of mRNA vaccination were 34% and 67% against overall infection and hospitalizations for severe illness, respectively. After acute COVID-19 pneumonia, most residual CT abnormalities gradually decreased in extent, but they may remain as linear or multifocal reticular or cystic lesions. Advanced insights into the pathophysiologic and imaging features of COVID-19 along with vaccine benefits have improved patient care, but emerging knowledge of post-COVID-19 condition, or long COVID, also presents radiology with new challenges.
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Vaccine protects against B1.1.7 variant The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B1.1.7 (VOC 202012/01) variant that emerged in late 2020 in the United Kingdom has many changes in the spike protein gene. Three of these are associated with enhanced infectivity and transmissibility, and there are concerns that B.1.1.7 might compromise the effectiveness of the vaccine. Muik et al. compared the neutralization efficacy of sera from 40 subjects immunized with the BioNTech-Pfizer mRNA vaccine BNT162b2 against a pseudovirus bearing the Wuhan reference strain or the lineage B.1.1.7 spike protein (see the Perspective by Altmann et al. ). Serum was derived from 40 subjects in two age groups 21 days after the booster shot. The vaccine remained effective against B.1.1.7 with a slight but significant decrease in neutralization that was more apparent in participants under 55 years of age. Thus, the vaccine provides a significant “cushion” of protection against this variant. Science , this issue p. 1152 ; see also p. 1103
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Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results Download a PDF of the Research Summary. The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)
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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 Download a PDF of the Research Summary. 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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Studies suggest that pregnant women might be at increased risk for severe illness associated with coronavirus disease 2019 (COVID-19) (1,2). This report provides updated information about symptomatic women of reproductive age (15-44 years) with laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19. During January 22-October 3, CDC received reports through national COVID-19 case surveillance or through the National Notifiable Diseases Surveillance System (NNDSS) of 1,300,938 women aged 15-44 years with laboratory results indicative of acute infection with SARS-CoV-2. Data on pregnancy status were available for 461,825 (35.5%) women with laboratory-confirmed infection, 409,462 (88.7%) of whom were symptomatic. Among symptomatic women, 23,434 (5.7%) were reported to be pregnant. After adjusting for age, race/ethnicity, and underlying medical conditions, pregnant women were significantly more likely than were nonpregnant women to be admitted to an intensive care unit (ICU) (10.5 versus 3.9 per 1,000 cases; adjusted risk ratio [aRR] = 3.0; 95% confidence interval [CI] = 2.6-3.4), receive invasive ventilation (2.9 versus 1.1 per 1,000 cases; aRR = 2.9; 95% CI = 2.2-3.8), receive extracorporeal membrane oxygenation (ECMO) (0.7 versus 0.3 per 1,000 cases; aRR = 2.4; 95% CI = 1.5-4.0), and die (1.5 versus 1.2 per 1,000 cases; aRR = 1.7; 95% CI = 1.2-2.4). Stratifying these analyses by age and race/ethnicity highlighted disparities in risk by subgroup. Although the absolute risks for severe outcomes for women were low, pregnant women were at increased risk for severe COVID-19-associated illness. To reduce the risk for severe illness and death from COVID-19, pregnant women should be counseled about the importance of seeking prompt medical care if they have symptoms and measures to prevent SARS-CoV-2 infection should be strongly emphasized for pregnant women and their families during all medical encounters, including prenatal care visits. Understanding COVID-19-associated risks among pregnant women is important for prevention counseling and clinical care and treatment.
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Vaccine effectiveness studies are subject to biases due to depletion-of-persons at risk of infection, or at especially high risk of infection, at different rates from different groups (depletion-of-susceptibles bias), a problem that can also lead to biased estimates of waning effectiveness, including spurious inference of waning when none exists. An alternative study design to identify waning is to study only vaccinated persons, and compare for each day the incidence in persons with earlier or later dates of vaccination to assess waning in vaccine protection as a function of vaccination time (namely whether earlier vaccination would result in lower subsequent protection compared to later vaccination). Prior studies suggested under what conditions this alternative would yield correct estimates of waning. Here we define the depletion-of-susceptibles process formally and show mathematically that for influenza vaccine waning studies, a randomised trial or corresponding observational study that compares incidence at a specific calendar time among individuals vaccinated at different times before the influenza season begins will not be vulnerable to depletion-of-susceptibles bias in its inference of waning as a function of vaccination time under the null hypothesis that none exists, and will – if waning does actually occur – underestimate the extent of waning. Such a design is thus robust in the sense that a finding of waning in that inference framework reflects actual waning of vaccine-induced immunity. We recommend such a design for future studies of waning, whether observational or randomised.
Article
Many available vaccines have demonstrated post-exposure effectiveness, but no published systematic reviews have synthesized these findings. We searched the PubMed database for clinical trials and observational human studies concerning the post-exposure vaccination effects, targeting infections with Food and Drug Administration licensed vaccine plus dengue, hepatitis E, malaria, and tick borne encephalitis, which have licensed vaccines outside of the U.S. Studies concerning animal models, serologic testing, and pipeline vaccines were excluded. Eligible studies were evaluated by definition of exposure, and their attempt at distinguishing pre- and post-exposure effects was rated on a scale of 1-4. We screened 4518 articles and ultimately identified 14 clinical trials and 31 observational studies for this review, amounting to 45 eligible articles spanning 7 of the 28 vaccine-preventable diseases. For secondary attack rate, this body of evidence found the following medians for post-exposure vaccination effectiveness: hepatitis A: 85% (IQR: 28; 5 sources), hepatitis B: 85% (IQR: 22; 5 sources), measles: 83% (IQR: 21; 8 sources), varicella: 67% (IQR: 48; 9 sources), smallpox: 45% (IQR: 39; 4 sources), and mumps: 38% (IQR: 7; 2 sources). For case fatality proportions resulting from rabies and smallpox, the vaccine efficacies had medians of 100% (IQR: 0; 6 sources) and 63% (IQR: 50; 8 sources) postexposure. Although mainly used for preventive measures, many available vaccines can modify or preclude disease if administered after exposure. This post-exposure effectiveness could be important to consider during vaccine trials and while developing new vaccines.
Article
Ideally, questions about comparative effectiveness or safety would be answered using an appropriately designed and conducted randomized experiment. When we cannot conduct a randomized experiment, we analyze observational data. Causal inference from large observational databases (big data) can be viewed as an attempt to emulate a randomized experiment—the target experiment or target trial—that would answer the question of interest. When the goal is to guide decisions among several strategies, causal analyses of observational data need to be evaluated with respect to how well they emulate a particular target trial. We outline a framework for comparative effectiveness research using big data that makes the target trial explicit. This framework channels counterfactual theory for comparing the effects of sustained treatment strategies, organizes analytic approaches, provides a structured process for the criticism of observational studies, and helps avoid common methodologic pitfalls.
Article
In lifetesting, medical follow-up, and other fields the observation of the time of occurrence of the event of interest (called a death) may be prevented for some of the items of the sample by the previous occurrence of some other event (called a loss). Losses may be either accidental or controlled, the latter resulting from a decision to terminate certain observations. In either case it is usually assumed in this paper that the lifetime (age at death) is independent of the potential loss time; in practice this assumption deserves careful scrutiny. Despite the resulting incompleteness of the data, it is desired to estimate the proportion P(t) of items in the population whose lifetimes would exceed t (in the absence of such losses), without making any assumption about the form of the function P(t). The observation for each item of a suitable initial event, marking the beginning of its lifetime, is presupposed. For random samples of size N the product-limit (PL) estimate can be defined as follows: List and label the N observed lifetimes (whether to death or loss) in order of increasing magnitude, so that one has \(0 \leqslant t_1^\prime \leqslant t_2^\prime \leqslant \cdots \leqslant t_N^\prime .\) Then \(\hat P\left( t \right) = \Pi r\left[ {\left( {N - r} \right)/\left( {N - r + 1} \right)} \right]\), where r assumes those values for which \(t_r^\prime \leqslant t\) and for which \(t_r^\prime\) measures the time to death. This estimate is the distribution, unrestricted as to form, which maximizes the likelihood of the observations. Other estimates that are discussed are the actuarial estimates (which are also products, but with the number of factors usually reduced by grouping); and reduced-sample (RS) estimates, which require that losses not be accidental, so that the limits of observation (potential loss times) are known even for those items whose deaths are observed. When no losses occur at ages less than t the estimate of P(t) in all cases reduces to the usual binomial estimate, namely, the observed proportion of survivors.
Article
There is considerable interest in using propensity score (PS) statistical techniques to address questions of causal inference in psychological research. Many PS techniques exist, yet few guidelines are available to aid applied researchers in their understanding, use, and evaluation. In this study, the authors give an overview of available techniques for PS estimation and PS application. They also provide a way to help compare PS techniques, using the resulting measured covariate balance as the criterion for selecting between techniques. The empirical example for this study involves the potential causal relationship linking early-onset cannabis problems and subsequent negative mental health outcomes and uses data from a prospective cohort study. PS techniques are described and evaluated on the basis of their ability to balance the distributions of measured potentially confounding covariates for individuals with and without early-onset cannabis problems. This article identifies the PS techniques that yield good statistical balance of the chosen measured covariates within the context of this particular research question and cohort.
Article
Noncausal associations between exposures and outcomes are a threat to validity of causal inference in observational studies. Many techniques have been developed for study design and analysis to identify and eliminate such errors. Such problems are not expected to compromise experimental studies, where careful standardization of conditions (for laboratory work) and randomization (for population studies) should, if applied properly, eliminate most such noncausal associations. We argue, however, that a routine precaution taken in the design of biologic laboratory experiments--the use of "negative controls"--is designed to detect both suspected and unsuspected sources of spurious causal inference. In epidemiology, analogous negative controls help to identify and resolve confounding as well as other sources of error, including recall bias or analytic flaws. We distinguish 2 types of negative controls (exposure controls and outcome controls), describe examples of each type from the epidemiologic literature, and identify the conditions for the use of such negative controls to detect confounding. We conclude that negative controls should be more commonly employed in observational studies, and that additional work is needed to specify the conditions under which negative controls will be sensitive detectors of other sources of error in observational studies.
Article
The hazard ratio (HR) is the main, and often the only, effect measure reported in many epidemiologic studies. For dichotomous, non–time-varying exposures, the HR is defined as the hazard in the exposed groups divided by the hazard in the unexposed groups. For all practical purposes, hazards can be thought of as incidence rates and thus the HR can be roughly interpreted as the incidence rate ratio. The HR is commonly and conveniently estimated via a Cox proportional hazards model, which can include potential confounders as covariates.
Article
The basic objective of this paper is to evaluate an age-comorbidity index in a cohort of patients who were originally enrolled in a prospective study to identify risk factors for peri-operative complications. Two-hundred and twenty-six patients were enrolled in the study. The participants were patients with hypertension or diabetes who underwent elective surgery between 1982 and 1985 and who survived to discharge. Two-hundred and eighteen patients survived until discharge. These patients were followed for at least five years post-operatively. The estimated relative risk of death for each comorbidity rank was 1.4 and for each decade of age was 1.4. When age and comorbidity were modelled as a combined age-comorbidity score, the estimated relative risk for each combined age-comorbidity unit was 1.45. Thus, the estimated relative risk of death from an increase of one in the comorbidity score proved approximately equal to that from an additional decade of age. The combined age-comorbidity score may be useful in some longitudinal studies to estimate relative risk of death from prognostic clinical covariates.
Efficacy and safety of the mRNA-1273
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Study to describe the safety, tolerability, immunogenicity, and efficacy of RNA vaccine candidates against COVID-19 in healthy individuals
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Coronavirus: 80 cases of South African variant discovered in Israel. Jerusalem Post
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80 cases of South African variant discovered in Israel
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