Risk-benefit analysis of the AstraZeneca COVID-19 vaccine in Australia using a Bayesian network modelling framework

Thrombosis and Thromobocytopenia Syndrome (TTS) has been associated with the AstraZencea (AZ) COVID-19 vaccine. Australia has reported low TTS incidence of <3/100,000 after the first dose, with case fatality rate (CFR) of 5-6%. Risk-benefit analysis of vaccination has been challenging because of rapidly evolving data, changing levels of transmission, and age-specific variation in rates of TTS, COVID-19, and CFR. We aim to optimise risk-benefit analysis by developing a model that enables inputs to be updated rapidly as evidence evolves. A Bayesian network was used to integrate local and international data, government reports, published literature and expert opinion. The model estimates probabilities of outcomes under different scenarios of age, sex, low/medium/high transmission (0.05%/0.45%/5.76% of population infected over 6 months), SARS-CoV-2 variant, vaccine doses, and vaccine effectiveness. We used the model to compare estimated deaths from vaccine-associated TTS with i) COVID-19 deaths prevented under different scenarios, and ii) deaths from COVID-19 related atypical severe blood clots (cerebral venous sinus thrombosis & portal vein thrombosis). For a million people aged >70 years where 70% received first dose and 35% received two doses, our model estimated <1 death from TTS, 25 deaths prevented under low transmission, and >3000 deaths prevented under high transmission. Risks versus benefits varied significantly between age groups and transmission levels. Under high transmission, deaths prevented by AZ vaccine far exceed deaths from TTS (by 8 to >4500 times depending on age). Probability of dying from COVID-related atypical severe blood clots was 58-126 times higher (depending on age and sex) than dying from TTS. To our knowledge, this is the first example of the use of Bayesian networks for risk-benefit analysis for a COVID-19 vaccine. The model can be rapidly updated to incorporate new data, adapted for other countries, extended to other outcomes (e.g., severe disease), or used for other vaccines.

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A quantitative risk-benefit analysis of ChAdOx1 nCoV-19 vaccine among people under 60 in Italy

10.1101/2021.05.07.21256826 ◽

2021 ◽

Author(s):

Raffaele Palladino ◽

Daniele Ceriotti ◽

Damiano De Ambrosi ◽

Marta De Vito ◽

Marco Farsoni ◽

...

Keyword(s):

Sinus Thrombosis ◽

Age Groups ◽

Cerebral Venous Sinus Thrombosis ◽

European Medicines Agency ◽

Benefit Analysis ◽

Uncertainty Interval ◽

R Ratio ◽

Pharmacovigilance Risk Assessment Committee ◽

Excess Number ◽

Risk Benefit Analysis

ChAdOx1 nCoV-19 is a vaccine against the COVID-19 infection that was granted a conditional marketing authorization by the European Commission in January 2021. However, following a report from the Pharmacovigilance Risk Assessment Committee (PRAC) of European Medicines Agency, which reported an association with thrombo-embolic events (TEE), in particular Disseminated intravascular coagulation (DIC) and Cerebral venous sinus thrombosis (CVST), many European countries either limited to individuals older than 55-60 years or suspended its use. We used publicly available data to carry out a quantitative risk-benefit analysis of the vaccine among people under 60 in Italy. Specifically, we used data from PRAC, Eudravigilance and ECDC to estimate the excess number of deaths for TEE, DIC and CVST expected in vaccine users, stratified by age groups. We then used data from the National Institute of Health to calculate age-specific COVID-19 mortality rates in Italy. Preventable deaths were calculated assuming a 72% vaccine efficacy over an 8-month period. Finally, benefit-risk ratio of ChAdOx1 nCoV-19 vaccination was calculated as the ratio between preventable COVID-19 deaths and vaccine-related deaths, using Monte-Carlo simulations. We found that among subjects aged 20-29 years the benefit-risk [B-R] ratio was not clearly favorable (0.70; 95% Uncertainty Interval [UI]: 0.27-2.11). However, in the other age groups the benefits of vaccination largely exceeded the risks (for age 30-49, B-R ratio: 22.9: 95%UI: 10.1-186.4). For age 50-59, B-R ratio: 1577.1: 95%UI: 1176.9-2121.5). Although many countries have limited the use of the ChAdOx1 nCoV-19 vaccine, the benefits of using this vaccine clearly outweigh the risks in people older than 30 years. The use of this vaccine should be a strategic and fundamental part of the immunization campaign considering its safety and efficacy in preventing COVID-19 and its complications.

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Risk of Hospitalization, severe disease, and mortality due to COVID-19 and PIMS-TS in children with SARS-CoV-2 infection in Germany

10.1101/2021.11.30.21267048 ◽

2021 ◽

Author(s):

Anna-Lisa Sorg ◽

Markus Hufnagel ◽

Maren Doenhardt ◽

Natalie Diffloth ◽

Horst Schroten ◽

...

Keyword(s):

Children And Adolescents ◽

Absolute Risk ◽

Severe Disease ◽

Age Groups ◽

Case Fatality ◽

Admission Rate ◽

High Rate ◽

Disease Course ◽

Notification System ◽

Icu Admission

Background: Although children and adolescents have a lower burden of SARS-CoV-2-associated disease as compared to adults, assessing absolute risk among children remains difficult due to a high rate of undetected cases. However, without more accurate case numbers, reliable risk analyses are impossible. Methods: We combine data from three sources - a national seroprevalence study (the SARS-CoV-2 KIDS study), the German statutory notification system and a nationwide registry on children and adolescents hospitalized with either SARS-CoV-2 or Pediatric Inflammatory Multisystem Syndrome (PIMS-TS) - in order to provide reliable estimates on childrens hospitalization, intensive care admission and death due to COVID-19 and PIMS-TS. Results: While the overall hospitalization rate associated with SARS-CoV-2 infection was 35.9 per 10,000 children, ICU admission rate was 1.7 per 10,000 and case fatality was 0.09 per 10,000. Children without comorbidities were found to be significantly less likely to suffer from a severe or fatal disease course. The lowest risk was observed in children aged 5-11 without comorbidities. In this group, the ICU admission rate was 0.2 per 10,000 and case fatality could not be calculated, due to an absence of cases. The overall PIMS-TS rate was 1 per 4,000 SARS-CoV-2 infections, the majority being children without comorbidities. Conclusion: Overall, the SARS-CoV-2-associated burden of a severe disease course or death in children and adolescents is low. This seems particularly the case for 5-11-year-old children without comorbidities. By contrast, PIMS-TS plays a major role in overall disease burden among all pediatric age groups.

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Lessons From COVID-19 in Children: Key Hypotheses to Guide Preventative and Therapeutic Strategies

Clinical Infectious Diseases ◽

10.1093/cid/ciaa547 ◽

2020 ◽

Vol 71 (8) ◽

pp. 2006-2013 ◽

Cited By ~ 7

Author(s):

Tulika Singh ◽

Sarah M Heston ◽

Stephanie N Langel ◽

Maria Blasi ◽

Jillian H Hurst ◽

...

Keyword(s):

Disease Transmission ◽

Current Knowledge ◽

Severe Disease ◽

Age Groups ◽

Case Fatality ◽

Opportunity To Learn ◽

Therapeutic Strategies ◽

Future Research ◽

Epidemiologic Evidence ◽

Lower Case

Abstract The current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), reveals a peculiar trend of milder disease and lower case fatality in children compared with adults. Consistent epidemiologic evidence of reduced severity of infection in children across different populations and countries suggests there are underlying biological differences between children and adults that mediate differential disease pathogenesis. This presents a unique opportunity to learn about disease-modifying host factors from pediatric populations. Our review summarizes the current knowledge of pediatric clinical disease, role in transmission, risks for severe disease, protective immunity, as well as novel therapies and vaccine trials for children. We then define key hypotheses and areas for future research that can use the pediatric model of disease, transmission, and immunity to develop preventive and therapeutic strategies for people of all age groups.

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Epidemiology and Trends of Pertussis among Infants: United States, 2000–2015

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx162.010 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S5-S5 ◽

Cited By ~ 3

Author(s):

Catherine Bozio ◽

Tami Skoff ◽

Tracy Pondo ◽

Jennifer Liang

Keyword(s):

Negative Binomial ◽

Severe Disease ◽

Age Distribution ◽

Age Groups ◽

Case Fatality ◽

Annual Average ◽

Young Infants ◽

Hospitalization Rates ◽

The Impact ◽

Over Time

Abstract Background Pertussis, a cyclic respiratory disease, causes the greatest morbidity and mortality among infants, particularly those too young to be vaccinated. Following a resurgence of pertussis in the 1990s, a recommendation was made in 2012 to vaccinate during every pregnancy in order to prevent infant disease. We describe pertussis trends from 2000–2015 among U.S. infants aged <1 year. Methods We analyzed infant pertussis cases reported through the National Notifiable Diseases Surveillance System from 2000 to 2015. Incidence rates (cases per 100,000 population) among various age groups (<2, 2– <4, 4– <6, and 6–<12 months) were calculated using National Center for Health Statistics population estimates as denominators. Negative binomial regression was used to estimate the annual average percent change with a linear trend; P < 0.05 was significant. Results From 2000 to 2015, 48,909 infant pertussis cases and 255 deaths were reported; infants aged <2 months accounted for 38.7% of cases. The age distribution of infant cases was stable from 2000 to 2009 but changed from 2010 to 2015 (Fig. 1), as the proportion of cases aged 4–<12 months increased annually on average by 4.7% (P < 0.001). Annual incidence was highest among <2 month olds; however, rates increased among older infants (Fig. 2): 7% average annual increase among infants aged 4–<6 months and 11% among infants aged 6–<12 months (P < 0.001 for each). The proportion of infants hospitalized decreased over time in each age group (P < 0.001 for all) with the largest annual average declines among 4–<6 (−5.1%) and 6–<12 month (−5.9%) olds. For all age groups, hospitalization rates were relatively stable, but non-hospitalization rates increased (P < 0.05 for all). The case–fatality ratio (CFR) was highest among <2 month olds (1.6%); CFRs decreased over time among <2 and 2–< 4 month olds (P < 0.05 for each). Conclusion Pertussis incidence remains highest among infants aged <4 months, although the age distribution appears to be changing. Decreasing proportions of infants hospitalized may suggest a true decline in disease severity or an increase in reporting of less severe disease. Ongoing monitoring of infant pertussis is needed to better understand the impact of vaccinating pregnant women to prevent pertussis in young infants. Disclosures All authors: No reported disclosures.

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Serotype Replacement After the Introduction of the 13-valent Pneumococcal Conjugate Vaccine in Ontario, Canada, 2007-2018

University of Toronto Journal of Public Health ◽

10.33137/utjph.v1i1.33816 ◽

2020 ◽

Vol 1 (1) ◽

Author(s):

Allison H Yeung ◽

Shinthuja Wijayasri ◽

Sarah E Wilson ◽

Tara M Harris ◽

Sarah A Buchan ◽

...

Keyword(s):

Public Health ◽

Severe Disease ◽

Age Groups ◽

Pneumococcal Vaccination ◽

Case Fatality ◽

Vaccination Programs ◽

Hospitalization Rates ◽

Age Related ◽

Serotype Replacement ◽

Vaccine Type

Introduction: Invasive pneumococcal disease (IPD) is a disease of public health significance in Ontario, Canada, where publicly funded pneumococcal vaccination programs target children, older adults, and people at high risk of disease. Since the implementation of pneumococcal conjugate vaccines (PCV), serotype replacement has been documented, where non-PCV serotypes replace the niche created by the reduction in vaccine-preventable serotypes. Our objective was to determine whether there has been serotype replacement or a change in IPD severity in Ontario since implementation of the childhood 13-valent (PCV13) program by assessing IPD burden over a 12-year period (2007-2018). Methods: We included all confirmed IPD cases reported in Ontario’s integrated Public Health Information System (iPHIS) and defined the pre-PCV13 era (January 2007-December 2010) and post-PCV13 era (January 2011-December 2018). We grouped IPD serotypes according to associated vaccine type: PCV13; 23-valent polysaccharide vaccine (unique PPV23); and non-vaccine-preventable (NVP). We used population data to calculate incidence and hospitalization rates (per 100,000 population) by age group, vaccine type, and era. Results: In the post-PCV13 era, PCV13-specific incidence and hospitalization rates decreased, while the incidence and hospitalizations due to unique PPV23 and NVP serotypes increased; this was consistent across all age groups. The greatest decrease in incidence (RR=0.4) and hospitalizations (RR=0.4) was observed in children <5 years with PCV13 serotypes. There were no distinct age-related trends observed for case fatality ratios; the highest CFR was observed in adults ≥65 years. Conclusion: A shift in serotype distribution was seen across all age groups; IPD incidence and hospitalization rates due to PCV13 serotypes decreased after PCV13 implementation, but this reduction was offset by the increasing burden and severity of unique PPV23 and NVP serotypes. As IPD continues to be a severe disease, continued surveillance is required to better understand the growing burden of these serotypes and emergence of non-vaccine-preventable serotypes.

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COVID-19 Mortality Risk Assessment among Various Age Groups using Phylogenetic Analysis

10.20944/preprints202009.0487.v1 ◽

2020 ◽

Author(s):

Pawan Verma ◽

Rasha Elkaffas ◽

Oluwasefunmi C. Shodunke ◽

Pavlo Hrab ◽

Oluwatobiloba H. Adebayo ◽

...

Keyword(s):

Phylogenetic Analysis ◽

High Risk ◽

Mortality Risk ◽

Severe Disease ◽

Clinical Status ◽

Age Groups ◽

Case Fatality ◽

Low Risk ◽

Age Related ◽

Geographical Regions

The age-related mortality and morbidity risk of COVID-19 has been considered speculative without enough scientific evidence. This study aimed to collect more evidence on the association between patient age and risk of severe disease state and/or mortality from SARS-CoV-2 infection. Genomic dataset along with metadata (3608 samples) retrieved from GISAID from different geographical regions were grouped into 10 age groups (0-10, 11-20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90, 91-100 years) as well as high-risk or low-risk according to patient clinical status. Genomic sequences were aligned and analyzed using MAFFT and FASTTREE to build a phylogenetic tree in order to identify age-risk associations based on phylogenetic clustering. Case fatality rates (CFR), as well as the Odds ratio (OR) for high-risk outcomes, were calculated for different age groups. Results revealed that individuals aged between 25-50 years have the best immune response to the infection. On the other hand, disease fatality was higher in patients aging above 50 years. We created an application to calculate the OR of being at high risk given a certain age threshold from GISAID datasets. OR values increased between ages 1-10 years (1.271) and 11-20 years (1.313) but reduced at age range 21-30 years (1.290) and increased again for 61-70 years (2.465). CFR calculated for each of the age groups had peak values at 90-100 years (26.8%) and the lowest at 0-10 years (0%). The CFR for ages above 50 years was about twice greater (11.6%-26.8%) than that for ages below (0-6.6%). The phylogenetic analysis revealed that the majority of samples obtained from India showed low-risk among different age groups and were defined as clade GH. Another cluster from Singapore visualization showed unfavorable patient outcome across several age groups and were classified under clade O. To conclude, this study analyses showed a variety of age-risk associations. As scientists from different countries upload more genomes to globally shared databases, more evidence will reinforce mortality risk associations in COVID-19 patients.

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CLINICAL AND LABORATORY PECULIARITIES OF WHOOPING COUGH IN CHILDREN OF DIFFERENT AGE GROUPS

PEDIATRIA Journal named after G N SPERANSKY ◽

10.24110/0031-403x-2020-99-6-98-104 ◽

2020 ◽

Vol 99 (6) ◽

pp. 98-104

Author(s):

I.V. Babachenko ◽

◽

Y.V. Nesterova ◽

N.V. Skripchenko ◽

◽

...

Keyword(s):

Whooping Cough ◽

Severe Disease ◽

Respiratory Rhythm ◽

Age Groups ◽

Low Frequency ◽

Pertussis Infection ◽

Group 2 ◽

Sick Children ◽

Hematological Changes ◽

Group 1

Objective of the research: to present the clinical and laboratory peculiarities of modern whooping cough in hospitalized children of different ages. Materials and methods: сlinical and laboratory characteristics of whooping cough were analyzed in 88 hospitalized sick children aged 1 month to 18 years in groups of children: group 1 – children under 1 year old; group 2 – children 1–6 years old; group 3 – children 7–17 years old. DNA of causative agents of pertussis infection was isolated by PCR in nasopharyngeal swabs using a commercial kit AmpliSens®Bordetella multi-FL (Moscow). Results: children of group 1 in 90% (n=43) of cases were not vaccinated against whooping cough, severe forms were recorded in 17% (n=8) of children of the 1st year of life, and in 15% (n=7) – due to respiratory rhythm disturbances. The diagnosis was confirmed by PCR in 94% (n=45) of children, leukocytosis with lymphocytosis was detected in 81,5% (n=101). Along with hematological changes typical for whooping cough, 79% (n=38) of patients in the first year of life had thrombocytosis (>400×109/l), which was most pronounced in severe disease course 511,5 [425; 568,5]×109/l vs 421 [347; 505,5]×109/l; p<0,05, which has no tendency to decrease throughout the entire observation period and correlates with the level of leukocytes (rs=0,69; p<0,001). Patients over 7 years old in 88% (n=21) of cases were vaccinated against whooping cough, but 79% (n=27) hemograms had no characteristic changes, which, along with a low frequency of confirmation of the diagnosis by PCR 22% (n=4), made it difficult to diagnose whooping cough. Conclusion: children over 7 years of age may not have characteristic hematological changes and PCR diagnostics are insufficiently effective, which contributes to the spread of whooping cough in family foci.

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Role of efficient testing and contact tracing in mitigating the COVID-19 pandemic: a network modelling study

BMJ Open ◽

10.1136/bmjopen-2020-045886 ◽

2021 ◽

Vol 11 (7) ◽

pp. e045886

Author(s):

Yiying Hu ◽

Jianying Guo ◽

Guanqiao Li ◽

Xi Lu ◽

Xiang Li ◽

...

Keyword(s):

Real World ◽

Case Fatality ◽

Contact Tracing ◽

Secondary Outcome ◽

Time Interval ◽

Fatality Rate ◽

Real World Data ◽

Network Modelling ◽

World Data ◽

Quantitative Evidence

ObjectivesThis study quantified how the efficiency of testing and contact tracing impacts the spread of COVID-19. The average time interval between infection and quarantine, whether asymptomatic cases are tested or not, and initial delays to beginning a testing and tracing programme were investigated.SettingWe developed a novel individual-level network model, called CoTECT (Testing Efficiency and Contact Tracing model for COVID-19), using key parameters from recent studies to quantify the impacts of testing and tracing efficiency. The model distinguishes infection from confirmation by integrating a ‘T’ compartment, which represents infections confirmed by testing and quarantine. The compartments of presymptomatic (E), asymptomatic (I), symptomatic (Is), and death with (F) or without (f) test confirmation were also included in the model. Three scenarios were evaluated in a closed population of 3000 individuals to mimic community-level dynamics. Real-world data from four Nordic countries were also analysed.Primary and secondary outcome measuresSimulation result: total/peak daily infections and confirmed cases, total deaths (confirmed/unconfirmed by testing), fatalities and the case fatality rate. Real-world analysis: confirmed cases and deaths per million people.Results(1) Shortening the duration between Is and T from 12 to 4 days reduces infections by 85.2% and deaths by 88.8%. (2) Testing and tracing regardless of symptoms reduce infections by 35.7% and deaths by 46.2% compared with testing only symptomatic cases. (3) Reducing the delay to implementing a testing and tracing programme from 50 to 10 days reduces infections by 35.2% and deaths by 44.6%. These results were robust to sensitivity analysis. An analysis of real-world data showed that tests per case early in the pandemic are critical for reducing confirmed cases and the fatality rate.ConclusionsReducing testing delays will help to contain outbreaks. These results provide policymakers with quantitative evidence of efficiency as a critical value in developing testing and contact tracing strategies.

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Cost risk benefit analysis to support chemoprophylaxis policy for travellers to malaria endemic countries

Malaria Journal ◽

10.1186/1475-2875-10-130 ◽

2011 ◽

Vol 10 (1) ◽

Cited By ~ 17

Author(s):

Eduardo Massad ◽

Ben C Behrens ◽

Francisco AB Coutinho ◽

Ronald H Behrens

Keyword(s):

Benefit Analysis ◽

Risk Benefit Analysis ◽

Cost Risk

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Managing older adults’ fear of coronavirus disease: A new role for social work practice

Qualitative Social Work ◽

10.1177/1473325020973295 ◽

2020 ◽

pp. 147332502097329

Author(s):

Hamed Mortazavi

Keyword(s):

Older Adults ◽

Case Fatality Rate ◽

Severe Disease ◽

Case Fatality ◽

Social Work Practice ◽

World Health ◽

National Committee ◽

Fatality Rate ◽

Number Of Patients ◽

Incidence And Mortality

As the number of patients infected with the 2019 novel coronavirus disease (nCOVID-19) increases, the number of deaths has also been increasing. According to World Health Organization (WHO), as of 4 October 2020, 34,804,348 cases had tested positive for nCOVID-19 globally, which among them, 1,030,738 confirmed deaths had occurred, equivalent to a case-fatality rate of 2.96%. However, in comparison with global statistics, the incidence and mortality of the nCOVID-19 infection are higher in Iran. As reported by the National Committee on COVID-19 Epidemiology of Ministry of Health of Iran, the total number of patients with confirmed COVID-19 infection has reached 468,119, of which 26,746 have died, equivalent to a case-fatality rate of 5.71%. Currently, there is solid evidence that older adults are at a higher risk of severe disease following infection from COVID-19.

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