Reactive mass vaccination campaign against cholera in the COVID-19 context in Cameroon: challenges, best practices and lessons learned.

INTRODUCTION: since 1971, Cameroon is facing a growing series of cholera epidemics despite all the efforts made by the government to address this huge public health threat. In 2020, in addition to the COVID-19 pandemic, Cameroon recorded a high cholera case fatality rate of 4.3% following epidemics noted in the South, Littoral and South-West regions. The Cameroon Ministry of Public Health, has thus organized a reactive vaccination campaign against cholera to address the high mortality rate in the affected health districts of those regions. The objective of this study was to describe the challenges, best practices and lessons learned drawing from daily experiences from this reactive vaccination campaign against cholera. METHODS: we conducted a cross-sectional study drawn from the results of the campaign. We had a target population of 631,109 participants aged 1 year and above resident of the targeted health areas. RESULTS: the overall vaccination coverage was 64.4% with a refusal rate ranging from 0-10% according to health districts. Vaccination coverage was the lowest among people aged 20 years and above. The main challenge was difficulty maintaining physical distanciation, the main best practice was the screening of all actors taking part at the vaccination against COVID-19 and we found that emphasizing on thorough population sensitization through quarter heads and social mobilizers and adequately programming the campaign during a good climate season is crucial to achieving good vaccination coverage. CONCLUSION: lessons learned from this study could serve to inform various agencies in the event of planning rapid mass vaccination programs during pandemics.

The role of childrens' vaccination for COVID-19-Pareto-optimal allocations of vaccines.

COVID-19 vaccines have been approved for children of age five and older in many countries. However, there is an ongoing debate as to whether children should be vaccinated and at what priority. In this work, we use mathematical modeling and optimization to study how vaccine allocations to different age groups effect epidemic outcomes. In particular, we consider the effect of extending vaccination campaigns to include the vaccination of children. When vaccine availability is limited, we consider Pareto-optimal allocations with respect to competing measures of the number of infections and mortality and systematically study the trade-offs among them. In the scenarios considered, when some weight is given to the number of infections, we find that it is optimal to allocate vaccines to adolescents in the age group 10-19, even when they are assumed to be less susceptible than adults. We further find that age group 0-9 is included in the optimal allocation for sufficiently high values of the basic reproduction number.

Evolution of resistance to COVID-19 vaccination with dynamic social distancing.

The greatest hope for a return to normalcy following the COVID-19 pandemic is worldwide vaccination. Yet, a relaxation of social distancing that allows increased transmissibility, coupled with selection pressure due to vaccination, will probably lead to the emergence of vaccine resistance. We analyse the evolutionary dynamics of COVID-19 in the presence of dynamic contact reduction and in response to vaccination. We use infection and vaccination data from six different countries. We show that under slow vaccination, resistance is very likely to appear even if social distancing is maintained. Under fast vaccination, the emergence of mutants can be prevented if social distancing is maintained during vaccination. We analyse multiple human factors that affect the evolutionary potential of the virus, including the extent of dynamic social distancing, vaccination campaigns, vaccine design, boosters and vaccine hesitancy. We provide guidelines for policies that aim to minimize the probability of emergence of vaccine-resistant variants.

Analysis of COVID-19 Risk Following a Ring Vaccination Intervention to Address SARS-CoV-2 Alpha Variant Transmission in Montreal, Canada.

Importance: Given limited COVID-19 vaccine availability early in the pandemic, optimizing immunization strategies was of paramount importance. Ring vaccination has been used successfully to control transmission of other airborne respiratory viruses. Objective: To assess the association of a ring vaccination intervention on COVID-19 spread in the initial epicenter of SARS-CoV-2 Alpha variant transmission in Montreal, Canada. Design, Setting, and Participants: This cohort study compared COVID-19 daily disease risk in 3 population-based groups of neighborhoods in Montreal, Canada, defined by their intervention-specific vaccine coverage at the neighborhood level: the primary intervention group (500 or more vaccinated persons per 10 000 persons), secondary intervention group (95 to 499), and control group (0 to 50). The groups were compared within each of 3 time periods: before intervention (December 1, 2020, to March 16, 2021), during and immediately after intervention (March 17 to April 17, 2021), and 3 weeks after the intervention midpoint (April 18 to July 18, 2021). Data were analyzed between June 2021 and November 2021. Exposures: Vaccination targeted parents and teachers of children attending the 32 schools and 48 childcare centers in 2 adjacent neighborhoods with highest local transmission (case counts) of Alpha variant shortly after its introduction. Participants were invited to receive 1 dose of mRNA vaccine between March 22 and April 9, 2021 (before vaccine was available to these age groups). Main Outcomes and Measures: COVID-19 risk in 3 groups of neighborhoods based on intervention-specific vaccine coverage. Results: A total of 11 794 residents were immunized, with a mean (SD) age of 43 (8) years (range, 16-93 years); 5766 participants (48.9%) lived in a targeted neighborhood, and 9784 (83.0%) were parents. COVID-19 risk in the primary intervention group was significantly higher than in the control group before (unadjusted risk ratio [RR], 1.58; 95% CI 1.52-1.65) and during (RR, 1.63; 95% CI, 1.52-1.76) intervention, and reached a level similar to the other groups in the weeks following the intervention (RR, 1.03; 95% CI, 0.94-1.12). A similar trend was observed when restricting to SARS-CoV-2 variants and persons aged 30 to 59 years (before: RR, 1.72; 95% CI, 1.63-1.83 vs after: RR, 1.01; 95% CI, 0.88-1.17). Conclusions and Relevance: Our findings show that ring vaccination was associated with a reduction in COVID-19 risk in areas with high local transmission of Alpha variant shortly after its introduction. Ring vaccination may be considered as an adjunct to mass immunization to control transmission in specific areas, based on local epidemiology.

SARS-CoV-2 Variant Tracking and Mitigation During In-Person Learning at a Midwestern University in the 2020-2021 School Year.

Importance: The COVID-19 pandemic led many higher education institutions to close campuses during the 2020-2021 academic year. As campuses prepared for a return to in-person education, many institutions were mandating vaccines for students and considering the same for faculty and staff. Objective: To determine the association between vaccination coverage and the levels and spread of SARS-CoV-2, even in the presence of highly-transmissible variants and congregate living, at a midsized university in the US. Design, Setting, and Participants: This case series was conducted at a midsized Midwestern university during the spring 2021 semester. The university developed a saliva-based surveillance program capable of high-throughput SARS-CoV-2 polymerase chain reaction testing and genomic sequencing with the capacity to deliver results in less than 24 hours. On April 7, 2021, the university announced a vaccine requirement for all students for the fall 2021 semester and announced the same requirement for faculty and staff on May 20, 2021. The university hosted an onsite mass vaccination clinic using the 2-dose Pfizer-BioNTech vaccine during April 8 to 15 and April 29 to May 6, 2021. Data were analyzed for 14 894 individuals from the university population who were tested for COVID-19 on campus from January 6 to May 20, 2021. Main Outcomes and Measures: Positive SARS-CoV-2 diagnosis was confirmed by quantitative reverse transcription-polymerase chain reaction of saliva specimens, and variant identity was assessed by quantitative reverse transcription-polymerase chain reaction and next-generation sequencing of viral genomes. Results: Between January 6 and May 20, 2021, the university conducted 196 185 COVID-19 tests for 14 894 individuals and identified 1603 positive cases. Within those positive cases, 950 individuals (59.3%) were male, 644 (40.2%) were female, 1426 (89.0%) were students, and 1265 (78.9%) were aged 17 to 22 years. Among the 1603 positive cases, 687 were identified via polymerase chain reaction of saliva specimens. The Alpha (B.1.1.7) variant constituted 218 of the 446 total positives sequenced (48.9%). By May 20, 2021, 10 068 of 11 091 students (90.8%), 814 of 883 faculty (92.2%), and 2081 of 2890 staff (72.0%) were vaccinated. The 7-day rolling average of positive cases peaked at 37 cases on February 17 but declined to zero by May 14, 2021. The 7-day moving average of positive cases was inversely associated with cumulative vaccination coverage, with a statistically significant Pearson correlation coefficient of -0.57 (95% CI, -0.68 to -0.44). Conclusions and Relevance: This case series study elucidated the association of a robust vaccination program with a statistically significant decrease in positive COVID-19 cases among the study population even in the presence of highly transmissible variants and congregate living.

Vaccine effectiveness of the first dose of ChAdOx1 nCoV-19 and BNT162b2 against SARS-CoV-2 infection in residents of long-term care facilities in England (VIVALDI): a prospective cohort study.

BACKGROUND: The effectiveness of SARS-CoV-2 vaccines in older adults living in long-term care facilities is uncertain. We investigated the protective effect of the first dose of the Oxford-AstraZeneca non-replicating viral-vectored vaccine (ChAdOx1 nCoV-19; AZD1222) and the Pfizer-BioNTech mRNA-based vaccine (BNT162b2) in residents of long-term care facilities in terms of PCR-confirmed SARS-CoV-2 infection over time since vaccination. METHODS: The VIVALDI study is a prospective cohort study that commenced recruitment on June 11, 2020, to investigate SARS-CoV-2 transmission, infection outcomes, and immunity in residents and staff in long-term care facilities in England that provide residential or nursing care for adults aged 65 years and older. In this cohort study, we included long-term care facility residents undergoing routine asymptomatic SARS-CoV-2 testing between Dec 8, 2020 (the date the vaccine was first deployed in a long-term care facility), and March 15, 2021, using national testing data linked within the COVID-19 Datastore. Using Cox proportional hazards regression, we estimated the relative hazard of PCR-positive infection at 0-6 days, 7-13 days, 14-20 days, 21-27 days, 28-34 days, 35-48 days, and 49 days and beyond after vaccination, comparing unvaccinated and vaccinated person-time from the same cohort of residents, adjusting for age, sex, previous infection, local SARS-CoV-2 incidence, long-term care facility bed capacity, and clustering by long-term care facility. We also compared mean PCR cycle threshold (Ct) values for positive swabs obtained before and after vaccination. The study is registered with ISRCTN, number 14447421. FINDINGS: 10 412 care home residents aged 65 years and older from 310 LTCFs were included in this analysis. The median participant age was 86 years (IQR 80-91), 7247 (69·6%) of 10 412 residents were female, and 1155 residents (11·1%) had evidence of previous SARS-CoV-2 infection. 9160 (88·0%) residents received at least one vaccine dose, of whom 6138 (67·0%) received ChAdOx1 and 3022 (33·0%) received BNT162b2. Between Dec 8, 2020, and March 15, 2021, there were 36 352 PCR results in 670 628 person-days, and 1335 PCR-positive infections (713 in unvaccinated residents and 612 in vaccinated residents) were included. Adjusted hazard ratios (HRs) for PCR-positive infection relative to unvaccinated residents declined from 28 days after the first vaccine dose to 0·44 (95% CI 0·24-0·81) at 28-34 days and 0·38 (0·19-0·77) at 35-48 days. Similar effect sizes were seen for ChAdOx1 (adjusted HR 0·32, 95% CI 0·15-0·66) and BNT162b2 (0·35, 0·17-0·71) vaccines at 35-48 days. Mean PCR Ct values were higher for infections that occurred at least 28 days after vaccination than for those occurring before vaccination (31·3 [SD 8·7] in 107 PCR-positive tests vs 26·6 [6·6] in 552 PCR-positive tests; p<0·0001). INTERPRETATION: Single-dose vaccination with BNT162b2 and ChAdOx1 vaccines provides substantial protection against infection in older adults from 4-7 weeks after vaccination and might reduce SARS-CoV-2 transmission. However, the risk of infection is not eliminated, highlighting the ongoing need for non-pharmaceutical interventions to prevent transmission in long-term care facilities. FUNDING: UK Government Department of Health and Social Care.

Effectiveness of BNT162b2 and ChAdOx1 nCoV-19 COVID-19 vaccination at preventing hospitalisations in people aged at least 80 years: a test-negative, case-control study.

BACKGROUND: On Dec 8, 2020, deployment of the first SARS-CoV-2 vaccination authorised for UK use (BNT162b2 mRNA vaccine) began, followed by an adenoviral vector vaccine ChAdOx1 nCoV-19 on Jan 4, 2021. Care home residents and staff, frontline health-care workers, and adults aged 80 years and older were vaccinated first. However, few data exist regarding the effectiveness of these vaccines in older people with many comorbidities. In this post-implementation evaluation of two COVID-19 vaccines, we aimed to determine the effectiveness of one dose in reducing COVID-19-related admissions to hospital in people of advanced age. METHODS: This prospective test-negative case-control study included adults aged at least 80 years who were admitted to hospital in two NHS trusts in Bristol, UK with signs and symptoms of respiratory disease. Patients who developed symptoms before receiving their vaccine or those who received their vaccine after admission to hospital were excluded, as were those with symptoms that started more than 10 days before hospital admission. We did logistic regression analysis, controlling for time (week), sex, index of multiple deprivations, and care residency status, and sensitivity analyses matched for time and sex using a conditional logistic model adjusting for index of multiple deprivations and care residency status. This study is registered with ISRCTN, number 39557. FINDINGS: Between Dec 18, 2020, and Feb 26, 2021, 466 adults were eligible (144 test-positive and 322 test-negative). 18 (13%) of 135 people with SARS-CoV-2 infection and 90 (34%) of 269 controls received one dose of BNT162b2. The adjusted vaccine effectiveness was 71·4% (95% CI 46·5-90·6). Nine (25%) of 36 people with COVID-19 infection and 53 (59%) of 90 controls received one dose of ChAdOx1 nCoV-19. The adjusted vaccine effectiveness was 80·4% (95% CI 36·4-94·5). When BNT162b2 effectiveness analysis was restricted to the period covered by ChAdOx1 nCoV-19, the estimate was 79·3% (95% CI 47·0-92·5). INTERPRETATION: One dose of either BNT162b2 or ChAdOx1 nCoV-19 resulted in substantial risk reductions of COVID-19-related hospitalisation in people aged at least 80 years. FUNDING: Pfizer.

Optimal vaccine allocation for COVID-19 in the Netherlands: A data-driven prioritization.

For the control of COVID-19, vaccination programmes provide a long-term solution. The amount of available vaccines is often limited, and thus it is crucial to determine the allocation strategy. While mathematical modelling approaches have been used to find an optimal distribution of vaccines, there is an excessively large number of possible allocation schemes to be simulated. Here, we propose an algorithm to find a near-optimal allocation scheme given an intervention objective such as minimization of new infections, hospitalizations, or deaths, where multiple vaccines are available. The proposed principle for allocating vaccines is to target subgroups with the largest reduction in the outcome of interest. We use an approximation method to reconstruct the age-specific transmission intensity (the next generation matrix), and express the expected impact of vaccinating each subgroup in terms of the observed incidence of infection and force of infection. The proposed approach is firstly evaluated with a simulated epidemic and then applied to the epidemiological data on COVID-19 in the Netherlands. Our results reveal how the optimal allocation depends on the objective of infection control. In the case of COVID-19, if we wish to minimize deaths, the optimal allocation strategy is not efficient for minimizing other outcomes, such as infections. In simulated epidemics, an allocation strategy optimized for an outcome outperforms other strategies such as the allocation from young to old, from old to young, and at random. Our simulations clarify that the current policy in the Netherlands (i.e., allocation from old to young) was concordant with the allocation scheme that minimizes deaths. The proposed method provides an optimal allocation scheme, given routine surveillance data that reflect ongoing transmissions. This approach to allocation is useful for providing plausible simulation scenarios for complex models, which give a more robust basis to determine intervention strategies.

SARS-CoV-2 and HIV-1: Should HIV-1-Infected Individuals in Sub-Saharan Africa Be Considered a Priority Group for the COVID-19 Vaccines?

Since its emergence in 2019 SARS-CoV-2 has proven to have a higher level of morbidity and mortality compared to the other prevailing coronaviruses. Although initially most African countries were spared from the devastating effect of SARS-CoV-2, at present almost every country has been affected. Although no association has been established between being HIV-1-infected and being more vulnerable to contracting COVID-19, HIV-1-infected individuals have a greater risk of developing severe COVID-19 and of COVID-19 related mortality. The rapid development of the various types of COVID-19 vaccines has gone a long way in mitigating the devastating effects of the virus and has controlled its spread. However, global vaccine deployment has been uneven particularly in Africa. The emergence of SARS-CoV-2 variants, such as Beta and Delta, which seem to show some subtle resistance to the existing vaccines, suggests COVID-19 will still be a high-risk infection for years. In this review we report on the current impact of COVID-19 on HIV-1-infected individuals from an immunological perspective and attempt to make a case for prioritising COVID-19 vaccination for those living with HIV-1 in Sub-Saharan Africa (SSA) countries like Malawi as one way of minimising the impact of COVID-19 in these countries.

The impact of prioritisation and dosing intervals on the effects of COVID-19 vaccination in Europe: an agent-based cohort model.

Different strategies have been used to maximise the effect of COVID-19 vaccination campaigns in Europe. We modelled the impact of different prioritisation choices and dose intervals on infections, hospitalisations, mortality, and public health restrictions. An agent-based model was built to quantify the impact of different vaccination strategies over 6 months. Input parameters were derived from published phase 3 trials and official European figures. We explored the effect of prioritising vulnerable people, care-home staff and residents, versus contagious groups; and the impact of dose intervals ranging from 3 to 12 weeks. Prioritising vulnerable people, rather than the most contagious, led to higher numbers of COVID-19 infections, whilst reducing mortality, hospital admissions, and public health restrictions. At a realistic vaccination speed of ≤ 0·1% population/day, separating doses by 12 weeks (vs a baseline scenario of 3 weeks) reduced hospitalisations, mortality, and restrictions for vaccines with similar first- and second-dose efficacy (e.g., the Oxford-AstraZeneca and Moderna vaccines), but not for those with lower first vs second-dose efficacy (e.g., the Pfizer/BioNTech vaccine). Mass vaccination will dramatically reduce the effect of COVID-19 on Europe's health and economy. Early vaccination of vulnerable populations will reduce mortality, hospitalisations, and public health restrictions compared to prioritisation of the most contagious people. The choice of interval between doses should be based on expected vaccine availability and first-dose efficacy, with 12-week intervals preferred over shorter intervals in most realistic scenarios.

Equitable and Feasible Distribution of SARS-CoV-2 Vaccines for All in Africa.

As the fight against the coronavirus disease 2019 (COVID-19) pandemic continues, the necessity for wide-scale, global vaccine rollout to reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and slow its mutation rate remains unassailable. The COVID-19 Vaccines Global Access (COVAX) initiative's campaign involves a proportional framework to finance and distribute SARS-CoV-2 vaccines in low- and middle-income countries. However, the COVAX framework has critical limitations, including limited funding and the failure to account for the special epidemic risks and needs of its participating nations, as recommended by the World Health Organization's Strategic Advisory Group of Experts on Immunization framework. These drawbacks disproportionately impact Africa, where many nations rely on COVAX as their main source of vaccines. The current plan to vaccinate only up to 20% of participating nations' populations is short-sighted from both epidemiologic and moral perspectives. COVAX must commit to vaccinating all of Africa and its initiative must be modified to account for the health and economic infrastructures in these countries. Lessons learned from successful vaccination campaigns, including the West African Ebola outbreak, have shown that vaccinating all of Africa is possible and feasible, and that infrastructure and human resources can support mass vaccination. To halt this global pandemic, global responsibility must be accepted to finance and equitably distribute SARS-CoV-2 vaccines to African nations. We urge COVAX to act swiftly to prevent Africa from becoming the new face of a persisting pandemic.

Sars-Cov-2 virus and vaccination; biological and statistical framework.

INTRODUCTION: The Development of the SARS-CoV-2 virus vaccine and its update on an ongoing pandemic is the first subject of the world health agenda. AREAS COVERED: First, we will scrutinize the biological features of the measles virus (MV), variola virus (smallpox virus), influenza virus, and their vaccines to compare them with the SARS-CoV-2 virus and vaccine. Next, we will discuss the statistical details of measuring the effectiveness of an improved vaccine. EXPERT OPINION: Amidst the pandemic, we ought to acknowledge our prior experiences with respiratory viruses and vaccines. In the planning stage of observational Phase-III vaccine effectiveness studies, the sample size, sampling method, statistical model, and selection of variables are crucial in obtaining high-quality and valid results.

Time-varying optimization of COVID-19 vaccine prioritization in the context of limited vaccination capacity.

Dynamically adapting the allocation of COVID-19 vaccines to the evolving epidemiological situation could be key to reduce COVID-19 burden. Here we developed a data-driven mechanistic model of SARS-CoV-2 transmission to explore optimal vaccine prioritization strategies in China. We found that a time-varying vaccination program (i.e., allocating vaccines to different target groups as the epidemic evolves) can be highly beneficial as it is capable of simultaneously achieving different objectives (e.g., minimizing the number of deaths and of infections). Our findings suggest that boosting the vaccination capacity up to 2.5 million first doses per day (0.17% rollout speed) or higher could greatly reduce COVID-19 burden, should a new wave start to unfold in China with reproduction number ≤1.5. The highest priority categories are consistent under a broad range of assumptions. Finally, a high vaccination capacity in the early phase of the vaccination campaign is key to achieve large gains of strategic prioritizations.

Application of the "immunization islands" model to improve quality, efficiency and safety of a COVID-19 mass vaccination site.

Abstract: After SARS-CoV-2 vaccines development came at an unprecedented speed, ensuring safe and efficient mass immunization, vaccine delivery be-came the major public health mandate. Although mass-vaccination sites have been identified as essential to curb COVID-19, their organization and functioning is challenging. In this paper we present the planning, implementation and evalua-tion of a massive vaccination center in Lombardy - the largest Region in Italy and the most heavily hit by the pandemic. The massive hub of Novegro (Milan), managed by the Gruppo Ospedaliero San Donato, opened in April 2021. The Novegro mass-immunization model was developed building a la-yout based on the available scientific evidence, on comparative analysis with other existing models and on the experience of COVID-19 immunization delivery of Gruppo Ospedaliero San Donato. We propose a "vaccine islands" mass-immunization model, where 4 physicians and 2 nurses operate in each island, with up to 10 islands functioning at the same time, with the capacity of providing up to 6,000 vaccinations per day. During the first week of activity a total of 37,900 doses were administered (2,700/day), most of them with Pfizer vaccine (85.8%) and first doses (70.9%). The productivity was 10.5 vaccines/hour/vaccine station. Quality, efficiency and safety were boosted by ad-hoc personnel training, quality technical infrastructure and the presence of a shock room. Constant process monitoring allowed to identify and promptly tackle process pitfalls, including vaccine refusals (0.36%, below expectations) and post-vaccinations adverse reactions (0.4%). Our innovative "vaccine islands" mass-immunization model might be scaled-up or adapted to other settings. The Authors consider that sharing best practices in immunization delivery is fundamen-tal to achieve population health during health emergencies.