Epidemiological Impact of SARS-CoV-2 Vaccination: Mathematical Modeling Analyses

This study aims to inform SARS-CoV-2 vaccine development/licensure/decision-making/implementation, using mathematical modeling, by determining key preferred vaccine product characteristics and associated population-level impacts of a vaccine eliciting long-term protection. A prophylactic vaccine with efficacy against acquisition (VES) ≥70% can eliminate the infection. A vaccine with VES <70% may still control the infection if it reduces infectiousness or infection duration among those vaccinated who acquire the infection, if it is supplemented with <20% reduction in contact rate, or if it is complemented with herd-immunity. At VES of 50%, the number of vaccinated persons needed to avert one infection is 2.4, and the number is 25.5 to avert one severe disease case, 33.2 to avert one critical disease case, and 65.1 to avert one death. The probability of a major outbreak is zero at VES ≥70% regardless of the number of virus introductions. However, an increase in social contact rate among those vaccinated (behavior compensation) can undermine vaccine impact. In addition to the reduction in infection acquisition, developers should assess the natural history and disease progression outcomes when evaluating vaccine impact.

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Epidemiological impact of SARS-CoV-2 vaccination: mathematical modeling analyses

10.1101/2020.04.19.20070805 ◽

2020 ◽

Cited By ~ 5

Author(s):

Monia Makhoul ◽

Houssein H. Ayoub ◽

Hiam Chemaitelly ◽

Shaheen Seedat ◽

Ghina R Mumtaz ◽

...

Keyword(s):

Decision Making ◽

Disease Progression ◽

Vaccine Development ◽

Severe Disease ◽

Herd Immunity ◽

Social Contact ◽

Population Level ◽

Contact Rate ◽

Disease Case ◽

Vaccine Impact

AbstractBackgroundSeveral SARS-CoV-2 vaccine candidates are currently in the pipeline. This study aims to inform SARS-CoV-2 vaccine development, licensure, decision-making, and implementation by determining key preferred vaccine product characteristics and associated population-level impact.MethodsVaccination impact was assessed at various efficacies using an age-structured mathematical model describing SARS-CoV-2 transmission and disease progression, with application for China.ResultsA prophylactic vaccine with efficacy against acquisition (VES) of ≥70% is needed to eliminate this infection. A vaccine with VES <70% will still have a major impact, and may control the infection if it reduces infectiousness or infection duration among those vaccinated who acquire the infection, or alternatively if supplemented with a moderate social-distancing intervention (<20% reduction in contact rate), or complemented with herd immunity. Vaccination is cost-effective. For a vaccine with VES of 50%, number of vaccinations needed to avert one infection is only 2.4, one severe disease case is 25.5, one critical disease case is 33.2, and one death is 65.1. Gains in effectiveness are achieved by initially prioritizing those ≥60 years. Probability of a major outbreak is virtually zero with a vaccine with VES ≥70%, regardless of number of virus introductions. Yet, an increase in social contact rate among those vaccinated (behavior compensation) can undermine vaccine impact.ConclusionsEven a partially-efficacious vaccine can offer a fundamental solution to control SARS-CoV-2 infection and at high cost-effectiveness. In addition to the primary endpoint on infection acquisition, developers should assess natural history and disease progression outcomes and/or proxy biomarkers, since such secondary endpoints may prove critical in licensure, decision-making, and vaccine impact.

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Mathematical modeling of endemic cholera transmission

The Journal of Infectious Diseases ◽

10.1093/infdis/jiab472 ◽

2021 ◽

Author(s):

Dennis L Chao

Keyword(s):

Mathematical Modeling ◽

Herd Immunity ◽

Population Level ◽

Additional Benefit ◽

Mass Vaccination ◽

The Cost ◽

Vaccination Campaigns ◽

The Impact ◽

Indirect Protection ◽

Endemic Cholera

Abstract Mathematical modeling can be used to project the impact of mass vaccination on cholera transmission. Here, we discuss two examples for which indirect protection from mass vaccination needs to be considered. In the first, we show that non-vaccinees can be protected by mass vaccination campaigns. This additional benefit of indirect protection improves the cost-effectiveness of mass vaccination. In the second, we model the use of mass vaccination to eliminate cholera. In this case, a high population level of immunity, including contributions from infection and vaccination, is required to reach the “herd immunity” threshold needed to stop transmission and achieve elimination.

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Age-targeted dose allocation can halve COVID-19 vaccine requirements

10.1101/2020.10.08.20208108 ◽

2020 ◽

Author(s):

Michael T. Meehan ◽

Daniel G. Cocks ◽

Jamie M. Caldwell ◽

James M. Trauer ◽

Adeshina I. Adekunle ◽

...

Keyword(s):

Mathematical Model ◽

Severe Disease ◽

Herd Immunity ◽

Population Level ◽

Morbidity And Mortality ◽

Effective Strategy ◽

Risk Of Infection ◽

Middle Aged ◽

Contact Rates ◽

Age Structured

ABSTRACTIn anticipation of COVID-19 vaccine deployment, we use an age-structured mathematical model to investigate the benefits of optimizing age-specific dose allocation to suppress the transmission, morbidity and mortality of SARS-CoV-2 and the associated disease, COVID-19. To minimize transmission, we find that the highest priority individuals across 179 countries are typically those between 30 and 59 years of age because of their high contact rates and higher risk of infection and disease. Conversely, morbidity and mortality are initially most effectively reduced by targeting 60+ year olds who are more likely to experience severe disease. However, when population-level coverage is sufficient — such that herd immunity can be achieved through targeted dose allocation — prioritizing middle-aged individuals becomes the most effective strategy to minimize hospitalizations and deaths. For each metric considered, we show that optimizing the allocation of vaccine doses can more than double their effectiveness.

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Improved diagnosis of SARS-CoV-2 by using Nucleoprotein and Spike protein fragment 2 in quantitative dual ELISA tests

10.1101/2021.04.07.21255024 ◽

2021 ◽

Author(s):

Carolina De Marco Verissimo ◽

Carol O'Brien ◽

Jesus Lopez Corrales ◽

Amber Dorey ◽

Krystyna Cwiklinski ◽

...

Keyword(s):

Severe Disease ◽

Herd Immunity ◽

Population Level ◽

The Novel ◽

Antibody Testing ◽

Protein Fragment ◽

Epidemiological Tool ◽

Novel Coronavirus ◽

Antibody Levels ◽

Antibody Tests

The novel Coronavirus, SARS-CoV-2, is the causative agent of the 2020 worldwide coronavirus pandemic. Antibody testing is useful for diagnosing historic infections of a disease in a population. These tests are also a helpful epidemiological tool for predicting how the virus spreads in a community, relating antibody levels to immunity and for assessing herd immunity. In the present study, SARS-CoV-2 viral proteins were recombinantly produced and used to analyse serum from individuals previously exposed, or not, to SARS-CoV-2. The nucleocapsid (Npro) and Spike subunit 2 (S2Frag) proteins were identified as highly immunogenic, although responses to the former were generally greater. These two proteins were used to develop two quantitative ELISA assays that when used in combination resulted in a highly reliable diagnostic test. Npro and S2Frag-ELISAs could detect at least 10% more true positive COVID-19 cases than the commercially available ARCHITECT test (Abbott). Moreover, our quantitative ELISAs also show that specific antibodies to SARS-CoV-2 proteins tend to wane rapidly even in patients that had developed severe disease. As antibody tests complement COVID-19 diagnosis and determine population-level surveillance during this pandemic, the alternative diagnostic we present in this study could play a role in controlling the spread of the virus.

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Personalized stratification of back to work risk amidst COVID-19: A machine learning approach (Preprint)

10.2196/preprints.22030 ◽

2020 ◽

Author(s):

Carson Lam ◽

Jacob Calvert ◽

Gina Barnes ◽

Emily Pellegrini ◽

Anna Lynn-Palevsky ◽

...

Keyword(s):

Machine Learning ◽

High Risk ◽

Learning Algorithm ◽

Severe Disease ◽

High Specificity ◽

Population Level ◽

The United States ◽

Health Condition ◽

Available P ◽

Severe Illness

BACKGROUND In the wake of COVID-19, the United States has developed a three stage plan to outline the parameters to determine when states may reopen businesses and ease travel restrictions. The guidelines also identify subpopulations of Americans that should continue to stay at home due to being at high risk for severe disease should they contract COVID-19. These guidelines were based on population level demographics, rather than individual-level risk factors. As such, they may misidentify individuals at high risk for severe illness and who should therefore not return to work until vaccination or widespread serological testing is available. OBJECTIVE This study evaluated a machine learning algorithm for the prediction of serious illness due to COVID-19 using inpatient data collected from electronic health records. METHODS The algorithm was trained to identify patients for whom a diagnosis of COVID-19 was likely to result in hospitalization, and compared against four U.S policy-based criteria: age over 65, having a serious underlying health condition, age over 65 or having a serious underlying health condition, and age over 65 and having a serious underlying health condition. RESULTS This algorithm identified 80% of patients at risk for hospitalization due to COVID-19, versus at most 62% that are identified by government guidelines. The algorithm also achieved a high specificity of 95%, outperforming government guidelines. CONCLUSIONS This algorithm may help to enable a broad reopening of the American economy while ensuring that patients at high risk for serious disease remain home until vaccination and testing become available.

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SARS-CoV-2 Biology Insights, Part IV.Antibody-Dependent Enhancement (ADE) and the tricky “Herd Immunity”: narrative review (Preprint)

10.2196/preprints.21599 ◽

2020 ◽

Author(s):

Laura Lafon-Hughes

Keyword(s):

Viral Infection ◽

Viral Entry ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Whooping Cough ◽

Common Knowledge ◽

Herd Immunity ◽

Life Quality ◽

Host Cells ◽

System P

BACKGROUND It is common knowledge that vaccination has improved our life quality and expectancy since it succeeded in achieving almost eradication of several diseases including chickenpox (varicella), diphtheria, hepatitis A and B, measles, meningococcal, mumps, pneumococcal, polio, rotavirus, rubella, tetanus and whooping cough (pertussis) Vaccination success is based on vaccine induction of neutralizing antibodies that help fight the infection (e.g. by a virus), preventing the disease. Conversely, Antibody-dependent enhancement (ADE) of a viral infection occurs when anti-viral antibodies facilitate viral entry into host cells and enhance viral infection in these cells. ADE has been previously studied in Dengue and HIV viruses and explains why a second infection with Dengue can be lethal. As already reviewed in Part I and Part II, SARS-Cov-2 shares with HIV not only 4 sequences in the Spike protein but also the capacity to attack the immune system. OBJECTIVE As HIV presents ADE, we wondered whether this was also the case regarding SARS-CoV-2. METHODS A literature review was done through Google. RESULTS SARS-CoV-2 presents ADE. As SARS, which does not have the 4 HIV-like inserts, has the same property, ADE would not be driven by the HIV-like spike sequences. CONCLUSIONS ADE can explain the failure of herd immunity-based strategies and will also probably hamper anti-SARS-CoV-2 vaccine development. As reviewed in Part I, there fortunately are promising therapeutic strategies for COVID-19, which should be further developed. In the meantime, complementary countermeasures to protect mainly the youth from this infection are presented to be discussed in Part V Viewpoint.

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Are We Paving the Way to Dig Out of the “Pandemic Hole”? A Narrative Review on SARS-CoV-2 Vaccination: From Animal Models to Human Immunization

Medical Sciences ◽

10.3390/medsci9030053 ◽

2021 ◽

Vol 9 (3) ◽

pp. 53

Author(s):

Giuseppe Tardiolo ◽

Pina Brianti ◽

Daniela Sapienza ◽

Pia dell’Utri ◽

Viviane Di Dio ◽

...

Keyword(s):

Animal Models ◽

Viral Vector ◽

Herd Immunity ◽

Population Level ◽

Narrative Review ◽

Therapeutic Interventions ◽

Preclinical Research ◽

Inactivated Vaccines ◽

Preclinical And Clinical Studies ◽

Social Upheaval

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new pathogen agent causing the coronavirus infectious disease (COVID-19). This novel virus originated the most challenging pandemic in this century, causing economic and social upheaval internationally. The extreme infectiousness and high mortality rates incentivized the development of vaccines to control this pandemic to prevent further morbidity and mortality. This international scenario led academic scientists, industries, and governments to work and collaborate strongly to make a portfolio of vaccines available at an unprecedented pace. Indeed, the robust collaboration between public systems and private companies led to resolutive actions for accelerating therapeutic interventions and vaccines mechanism. These strategies contributed to rapidly identifying safe and effective vaccines as quickly and efficiently as possible. Preclinical research employed animal models to develop vaccines that induce protective and long-lived immune responses. A spectrum of vaccines is worldwide under investigation in various preclinical and clinical studies to develop both individual protection and safe development of population-level herd immunity. Companies employed and developed different technological approaches for vaccines production, including inactivated vaccines, live-attenuated, non-replicating viral vector vaccines, as well as acid nucleic-based vaccines. In this view, the present narrative review provides an overview of current vaccination strategies, taking into account both preclinical studies and clinical trials in humans. Furthermore, to better understand immunization, animal models on SARS-CoV-2 pathogenesis are also briefly discussed.

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Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19

Nature Communications ◽

10.1038/s41467-021-21444-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Adam K. Wheatley ◽

Jennifer A. Juno ◽

Jing J. Wang ◽

Kevin J. Selva ◽

Arnold Reynaldi ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Vaccine Development ◽

Natural Infection ◽

Population Level ◽

Cell Dynamics ◽

Follicular Helper ◽

Cell Immunity ◽

Specific Igg ◽

Over Time

AbstractThe durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.

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Social contacts and other risk factors for respiratory infections among internally displaced people in Somaliland

10.1101/2021.08.20.21262338 ◽

2021 ◽

Author(s):

Kevin van Zandvoort ◽

Mohamed Omer Bobe ◽

Abdirahman Ibrahim Hassan ◽

Mohamed Ismail Abdi ◽

Mohamed Saed Ahmed ◽

...

Keyword(s):

Risk Factors ◽

Respiratory Infections ◽

Severe Disease ◽

Social Contact ◽

Physical Contact ◽

Cross Sectional ◽

Internally Displaced ◽

Internally Displaced People ◽

Social Mixing ◽

Displaced People

Background Populations affected by humanitarian crises experience high burdens of acute respiratory infections (ARI), potentially driven by risk factors for severe disease such as poor nutrition and underlying conditions, and risk factors that may increase transmission such as overcrowding and the possibility of high social mixing. However, little is known about social mixing patterns in these populations. Methods We conducted a cross-sectional social contact survey among internally displaced people (IDP) living in Digaale, a permanent IDP camp in Somaliland. We included questions on household demographics, shelter quality, crowding, travel frequency, health status, and recent diagnosis of pneumonia, and assessed anthropometric status in children. We calculated age-standardised social contact matrices to assess population mixing, and conducted regression analysis on risk factors for recent self-reported pneumonia. Results We found crowded households with high proportions of recent self-reported pneumonia (46% in children). 20% of children younger than five are stunted, and crude death rates are high in all age groups. ARI risk factors are common, but we did not find any significant associations with self-reported pneumonia. Participants reported around 10 direct contacts per day. Social contact patterns are assortative by age, and physical contact rates are very high (78%). Conclusions ARI risk factors are very common in this population, while the large degree of contacts that involve physical touch could further increase transmission. Such IDP settings potentially present a perfect storm of risk factors for ARIs and their transmission, and innovative approaches to address such risks are urgently needed.

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A narrative review on HPV vaccination among boys and men

Global Journal of Medical Research ◽

10.34257/gjmrfvol20is4pg9 ◽

2020 ◽

pp. 9-12

Author(s):

Vinod K Ramani ◽

Radheshyam Naik

Keyword(s):

Hpv Vaccine ◽

Hpv Vaccination ◽

Herd Immunity ◽

Population Level ◽

Hpv Infection ◽

Level Control ◽

Anogenital Warts ◽

Indian Context ◽

Present Generation ◽

The Cost

Apart from cervical cancer, Human papillomavirus (HPV) infection is associated with head and neck as well as other anogenital cancers such as vulva, vagina, anus, and penis. HPV vaccine provides specific protection against the disease and its subsequent manifestations.Vaccination programs for men tend to improve population-level control of HPV infection and directly prevent HPV related disease such as anogenital warts and oropharyngeal cancers in males. HPV vaccine does not treat existing infection or lesions/cancer and is intended for individuals before initiation fo sexual activity or any other form of exposure to HPV.Many programs across the globe do not include vaccination for boys because of the cost and little recognition of the emerging epidemic of HPV associated cancers in men. In the Indian context, as screening is not feasible for non-cervical HPV associated cancers, its incidence mostly among men will continue to rise until the present generation of vaccinated adolescents reaches their middle-age.Vaccination will reduce transmission rates and increase herd immunity. This in-turn, will prevent not just cervical cancers but also other HPV-associated malignancies among men and women.

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