Cost of vaccine delivery strategies in low- and middle-income countries during the COVID-19 pandemic

BackgroundThe COVID-19 pandemic has disrupted immunization services critical to the prevention of vaccine-preventable diseases in many low- and middle- income countries around the world. These services will need to be modified in order to minimize COVID-19 transmission and ensure the safety of health workers and the community. Additional budget will be required to implement these modifications that ensure safe delivery.MethodsUsing a simple modeling analysis, we estimated the additional resource requirements associated with modifications to supplementary immunization activities (campaigns) and routine immunization services via fixed sites and outreach in 2020 US dollars. We considered the following four categories of costs: (1) personal protective equipment (PPE) & infection prevention and control (IPC) measures for immunization sessions; (2) physical distancing and screening during immunization sessions; (3) delivery strategy changes, such as changes in session sizes and frequency; and (4) other operational cost increases, including additional social mobilization, training, and hazard pay to compensate health workers.ResultsWe found that implementing a range of measures to protect health workers and communities from COVID-19 transmission could result in a per-facility start-up cost of $466–799 for routine fixed-site delivery and $12–220 for routine outreach delivery, and $12–108 per immunization campaign site. A recurrent monthly cost of $137–1,024 for fixed-site delivery and $152–848 for outreach delivery per facility could be incurred, and a $0.32–0.85 increase in the cost per dose during campaigns.ConclusionsBy illustrating potential cost implications of providing immunization services through a range of strategies in a safe manner, these estimates can provide a benchmark for program managers and policy makers on the additional budget required. These findings can help country practitioners and global development partners planning the continuation of immunization services in the context of COVID-19.     

Modelling optimal vaccination strategies against COVID-19 in a context of Gamma variant predominance in Brazil

IntroductionBrazil experienced moments of collapse in its health system throughout 2021, driven by the emergence of variants of concern (VOC) combined with an inefficient initial vaccination strategy against Covid-19.ObjectivesTo support decision-makers in formulating COVID-19 immunization policy in the context of limited vaccine availability and evolving variants over time, we evaluate optimal strategies for Covid-19 vaccination in Brazil in 2021, when vaccination was rolled out during Gamma variant predominance.MethodsUsing a discrete-time epidemic model we estimate Covid-19 deaths averted, considering the currently Covid-19 vaccine products and doses available in Brazil; vaccine coverage by target population; and vaccine effectiveness estimates. We evaluated a 5-month time horizon, from early August to the end of December 2021. Optimal vaccination strategies compared the outcomes in terms of averted deaths when varying dose intervals from 8 to 12 weeks, and choosing the minimum coverage levels per age group required prior to expanding vaccination to younger target populations. We also estimated dose availability required over time to allow the implementation of optimal strategies.ResultsTo maximize the number of averted deaths, vaccine coverage of at least 80 % should be reached in older age groups before starting vaccination into subsequent younger age groups. When evaluating varying dose intervals for AZD1222, reducing the dose interval from 12 to 8 weeks for the primary schedule would result in fewer COVID-19 deaths, but this can only be implemented if accompanied by an increase in vaccine supply of at least 50 % over the coming six-months in Brazil.ConclusionCovid-19 immunization strategies should be tailored to local vaccine product availability and supply over time, circulating variants of concern, and vaccine coverage in target population groups. Modelling can provide valuable and timely evidence to support the implementation of vaccination strategies considering the local context, yet following international and regional technical evidence-based guidance.     

COVID-19 related immunization disruptions in Rajasthan,India: A retrospective observational study

IntroductionGovernments around the world suspended immunization outreach to control COVID-19 spread. Many have since resumed services with an emphasis on catch-up vaccinations. This paper evaluated immunization disruptions during India’s March-May 2020 lockdown and the extent to which subsequent catch-up efforts reversed them in Rajasthan, India.MethodsIn this retrospective observational study, we conducted phone surveys to collect immunization details for 2,144 children that turned one year old between January and October 2020. We used logistic regressions to compare differences in immunization timeliness and completed first-year immunization status among children that were due immunizations just before (unexposed), during (heavily exposed), and after (post-exposure) the lockdown.ResultsRelative to unexposed children, heavily exposed children were significantly less likely to be immunized at or before 9 months (OR 0.550; 95% CI 0.367–0.824; p = 0.004), but more likely to be immunized at 10–12 months (OR 1.761; 95% CI 1.196–2.591; p = 0.004). They were also less likely to have completed their key first-year immunizations (OR 0.624; 95% CI 0.478–0.816; p = 0.001) by the time of survey. In contrast, post-exposure children showed no difference in timeliness or completed first-year immunizations relative to unexposed children, despite their younger age. First-year immunization coverage among heavily exposed children decreased by 6.9 pp to 10.4 pp (9.7% to 14.0%). Declines in immunization coverage were larger among children in households that were poorer, less educated, lower caste, and residing in COVID red zones, although subgroup comparisons were not statistically significant.ConclusionDisruptions to immunization services resulted in children missing immunization during the lockdown, but catch-up efforts after it was eased ensured many children were reached at later ages. Nevertheless, catch-up was incomplete and children due their immunizations during the lockdown remained less likely to be fully immunized 4–5 months after it lifted, even as younger cohorts due immunizations in June or later returned to pre-lockdown schedules.     

Understanding COVID-19 vaccination willingness among youth: A survey study in the Netherlands

Vaccination of youth could be key to preventing future outbreaks of SARS-CoV-2. Given the limited direct health benefit for young people, it is important to understand how youth themselves perceive obtaining a vaccination. This survey study in a representative sample of Dutch youth aged 12–18 showed that 73% were willing to get vaccinated against COVID-19. In regression analyses, vaccination willingness was strongly related to age, perceived personal (protect own health) and societal benefits (to get rid of restrictive policies), and their peers’ and parents’ vaccination uptake. Negative associations with vaccination willingness were perceived side-effects and potential unknown long term consequences. On-going and transparent communication with up-to-date information about safety and risks, delivered by independent and trusted experts (as perceived by the recipients) seems important for addressing questions and concerns. Local information sessions for youth and parents where a vaccination can be obtained without appointment could have merit in addition to mass media communication.     

Prenatal maternal COVID-19 vaccination and pregnancy outcomes

BackgroundPrenatal maternal physiological changes may cause severe COVID-19 among pregnant women. The Pfizer-BioNTech COVID-19 vaccine (BNT162b2 mRNA) has been shown to be highly effective and it is recommended for individuals aged ≥16 years, including pregnant women, although the vaccine has not been tested on the latter.ObjectiveTo study the association between prenatal Pfizer-BioNTech COVID-19 vaccination, pregnancy course and outcomes.Study designA retrospective cohort study was performed, including all women who delivered between January and June 2021 at Soroka University Medical Center, the largest birth center in Israel. Excluded were women diagnosed with COVID-19 in the past, multiple gestations or unknown vaccination status. Pregnancy, delivery and newborn complications were compared between women who received 1 or 2-dose vaccines during pregnancy and unvaccinated women. Multivariable models were used to adjust for background characteristics.ResultsA total of 4,399 women participated in this study, 913 (20.8%) of which were vaccinated during pregnancy. All vaccinations occurred during second or third trimesters. As compared to the unvaccinated women, vaccinated women were older, more likely to conceive following fertility treatments, to have sufficient prenatal care, and of higher socioeconomic position. In both crude and multivariable analyses, no differences were found between the groups in pregnancy, delivery and newborn complications, including gestational age at delivery, incidence of small for gestational age and newborn respiratory complications.ConclusionsPrenatal maternal COVID-19 vaccine has no adverse effects on pregnancy course and outcomes. These findings may help pregnant women and health care providers to make informed decision regarding vaccination.     

Delay in childhood vaccinations during the COVID-19 pandemic

ObjectivesIn many jurisdictions, routine medical care was reduced in response to the COVID-19 pandemic. The objective of this study was to determine whether the frequency of on-time routine childhood vaccinations among children age 0–2 years was lower following the COVID-19 declaration of emergency in Ontario, Canada, on March 17, 2020, compared to prior to the pandemic.MethodsWe conducted a longitudinal cohort study of healthy children aged 0–2 years participating in the TARGet Kids! primary care research network in Toronto, Canada. A logistic mixed effects regression model was used to determine odds ratios (ORs) for delayed vaccination (> 30 days vs. ≤ 30 days from the recommended date) before and after the COVID-19 declaration of emergency, adjusted for confounding variables. A Cox proportional hazards model was used to explore the relationship between the declaration of emergency and time to vaccination.ResultsAmong 1277 children, the proportion of on-time vaccinations was 81.8% prior to the COVID-19 declaration of emergency and 62.1% after (p < 0.001). The odds of delayed vaccination increased (odds ratio = 3.77, 95% CI: 2.86–4.96), and the hazard of administration of recommended vaccinations decreased after the declaration of emergency (hazard ratio = 0.75, 95% CI: 0.60–0.92). The median vaccination delay time was 5 days (95% CI: 4–5 days) prior to the declaration of emergency and 17 days (95% CI: 12–22 days) after.ConclusionThe frequency of on-time routine childhood vaccinations was lower during the first wave of the COVID-19 pandemic. Sustained delays in routine vaccinations may lead to an increase in rates of vaccine-preventable diseases.Supplementary InformationThe online version contains supplementary material available at 10.17269/s41997-021-00601-9.     

Virtual primary care in high-income countries during the COVID-19 pandemic: Policy responses and lessons for the future

BackgroundTelemedicine, once defined merely as the treatment of certain conditions remotely, has now often been supplanted in use by broader terms such as ‘virtual care’, in recognition of its increasing capability to deliver a diverse range of healthcare services from afar. With the unexpected onset of COVID-19, virtual care (e.g. telephone, video, online) has become essential to facilitating the continuation of primary care globally. Over several short weeks, existing healthcare policies have adapted quickly and empowered clinicians to use digital means to fulfil a wide range of clinical responsibilities, which until then have required face-to-face consultations.ObjectivesThis paper aims to explore the virtual care policies and guidance material published during the initial months of the pandemic and examine their potential limitations and impact on transforming the delivery of primary care in high-income countries.MethodsA rapid review of publicly available national policies guiding the use of virtual care in General Practice was conducted. Documents were included if issued in the first six months of the pandemic (March to August of 2020) and focussed primarily on high-income countries. Documents must have been issued by a national health authority, accreditation body, or professional organisation, and directly refer to the delivery of primary care.ResultsWe extracted six areas of relevance: primary care transformation during COVID-19, the continued delivery of preventative care, the delivery of acute care, remote triaging, funding & reimbursement, and security standards.ConclusionVirtual care use in primary care saw a transformative change during the pandemic. However, despite the advances in the various governmental guidance offered, much work remains in addressing the shortcomings exposed during COVID-19 and strengthening viable policies to better incorporate novel technologies into the modern primary care clinical environment.     

U.S. public support for COVID-19 vaccine donation to low- and middle-income countries during the COVID-19 pandemic

As COVID-19 vaccines become available to the public, there will be a massive worldwide distribution effort. Vaccine distribution has historically been unequal primarily due to the inability of nations with developing economies to purchase enough vaccine to fully vaccinate their populations. Inequitable access to COVID-19 vaccines will not just cause humanitarian suffering, it will likely also be associated with increased economic suffering worldwide. This study focuses on the U.S. population and its beliefs about future COVID-19 vaccine donation by the U.S. to low- and middle-income countries.This study carried out a survey among 788 U.S. adults. Variables include demographics, COVID-19 vaccine priority status, COVID-19 vaccine donation beliefs, and Social Dominance Orientation.Analyses showed that older respondents were both less likely to endorse higher levels of COVID-19 vaccine donations and were more likely to want to wait until all in the U.S. who want the vaccine have received it; those who identified as Democrats were more likely to endorse higher levels of future COVID-19 vaccine donation than Republicans; and those scoring higher on SDO were both less likely to endorse higher levels of COVID-19 vaccine donations as well as more likely to want to wait until all in the U.S. who want the vaccine have received it. Policymakers, as well as healthcare providers and public health communication professionals, should give consideration to those messages most likely to engender support for global prevention efforts with each audience segment.     

Impact of COVID-19 vaccination in post-COVID cardiac complications

BackgroundAfter the acute infection, COVID-19 can produce cardiac complications as well as long-COVID persistent symptoms. Although vaccination against COVID-19 represented a clear reduction in both mortality and ICU admissions, there is very little information on whether this was accompanied by a decrease in the prevalence of post-COVID cardiac complications. The aim of this study was to analyze the relationship between COVID-19 vaccination and the prevalence of post-COVID cardiac injury assessed by echocardiogram, and long-COVID persistent cardiac symptoms. Methods: All patients who consulted for post-COVID evaluation 14 days after discharge from acute illness were included. Patients with heart disease were excluded. The relationship between complete vaccination scheme (at least two doses applied with 14 days or more since the last dose) and pathological echocardiographic findings, as well as the relationship of vaccination with persistent long-COVID symptoms, were evaluated by multivariate analysis, adjusting for age, sex and clinical variables that would have shown significant differences in univariate analysis. Results: From 1883 patients, 1070 patients (56.8%) suffered acute COVID-19 without a complete vaccination scheme. Vaccination was associated with lower prevalence of cardiac injury (1.35% versus 4.11%, adjusted OR 0.33; 95% CI 0.17–0.65, p=0.01). In addition, vaccinated group had a lower prevalence of persistent long-COVID symptoms compared to unvaccinated patients (10.7% versus 18.3%, adjusted OR 0.52; 95% CI 0.40–0.69, p<0.001). Conclusion: Vaccination against COVID-19 was associated with lower post-COVID cardiac complications and symptoms, reinforcing the importance of fully vaccinating the population.     

Clinical characteristics and outcome of hospitalized elderly patients with COVID- 19 after vaccine failure

We described clinical characteristics and outcome of 160 patients over 65 years (01 September to 31 August 2021) who had a first positive SARS-CoV-2 PCR- test more than 14 days after full vaccination and were hospitalized with COVID-19. Median age of included patients was 84 years, 61.2% were over 80 years; 50.6% were male and most (82.5%) has at least one comorbidity. Up to 84% received specific treatment against COVID-19, including 76.9% low-flow oxygen therapy. We found that overall mortality was 25.6% and 30.6% in those older than 80 years. A higher mortality was significantly associated with older age and treatment with tocilizumab. Our data showed that although COVID-19 vaccines continue protecting elderly patients against hospitalization and death and might improve the prognosis after hospitalization in patients with breakthrough infections, mortality in this population -especially in those older than 80 years- remains very high.     

Older adults: panoramic view on the COVID-19 vaccination

In December 2020, COVID-19 vaccination started in many countries, with which the world community hopes to stop the further spread of the current pandemic. More than 90% of sick and deceased patients belong to the category of older adults (65 years and older). This category of the population is most vulnerable to infectious diseases, so vaccination is the most effective preventive strategy, the need for which for older adults is indisputable. Here we briefly summarize information about age-related changes in the immune system and present current data on their impact on the formation of the immune response to vaccination. Older age is accompanied by the process of biological aging accompanied by involution of the immune system with increased susceptibility to infections and a decrease in the effect of immunization. Therefore, in the ongoing mass COVID-19 vaccination, the older adults are a growing public health concern. The authors provide an overview of the various types of COVID-19 vaccines approved for mass immunization of the population by the end of 2020, including older adults, as well as an overview of strategies and platforms to improve the effectiveness of vaccination of this population. In the final part, the authors propose for discussion a system for assessing the safety and monitoring the effectiveness of COVID-19 vaccines for the older adults.     

Guidance for design and analysis of observational studies of fetal and newborn outcomes following COVID-19 vaccination during pregnancy

COVID-19 vaccines are now being deployed as essential tools in the public health response to the global SARS-CoV-2 pandemic. Pregnant individuals are a unique subgroup of the population with distinctive considerations regarding risk and benefit that extend beyond themselves to their fetus/newborn. As a complement to traditional pharmacovigilance and clinical studies, evidence to comprehensively assess COVID-19 vaccine safety in pregnancy will need to be generated through observational epidemiologic studies in large populations. However, there are several unique methodological challenges that face observational assessments of vaccination during pregnancy, some of which may be more pronounced for COVID-19 studies. In this contribution, we discuss the most critical study design, data collection, and analytical issues likely to arise. We offer brief guidance to optimize the quality of such studies to ensure their maximum value for informing public health decision-making.     

UAE efforts in promoting COVID-19 vaccination and building vaccine confidence

The United Arab Emirates (UAE) is leading globally in many indicators for tackling the COVID-19 pandemic. This ranges from taking adequate preventive measures to the free vaccination drive and viable public health strategy. As of 18 August 2021, the UAE has significantly reduced the number of cases and successfully administered 17,454,250 doses. Furthermore, efforts and plans are underway to provide the third dose to high-risk people three months after completing the second dose and six months later to others. The UAE is considered one of the leaders globally for vaccinating “medically eligible” residents against COVID-19, with over 70% of the population currently fully vaccinated in the drive towards achieving herd immunity. The UAE's vaccination program is on track, covering a significant part of the population. The massive efforts of the National Vaccination Program's roll-out made by the UAE government and the various health authorities and stakeholders were vital for the general public's active participation in its success.     

Safety,immunogenicity, and immune persistence of two inactivated COVID-19 vaccines replacement vaccination in China: An observational cohort study

BackgroundTo mitigate a national shortage of WIBP-CorV COVID-19 vaccine, China’s regulator approved administering BBIBP-CorV after WIBP-CorV for completion of a primary series. In a pragmatic observational study, we compared immunogenicity and safety of a primary series of WIBP-CorV followed by BBIBP-CorV with a primary series of two doses of BBIBP-CorV.MethodsWe invited healthy 18–59-years-old adults who had already received either WIBP-CorV or BBIBP-CorV as their first dose in a primary series to participate in this observational cohort study. Subjects who had received WIBP-CorV as their first dose became the observation group; subjects who had received BBIBP-CorV as their first dose became the control group. All participants received BBIBP-CorV as their second dose. We obtained sera 1, 2, and 6 months after second doses for nAb titer measurement by micro-neutralization cytopathic effect assay with SARS-CoV-2 strain HB01, standardized with WHO International Standard for anti-SARS-CoV-2 immunoglobulin. Safety was assessed for the 7 days after administration of second doses.ResultsBetween March and December 2021, 275 subjects were included in the observation group and 133 in the control group. Neutralizing seropositivity (≥1:4) rates were 98.91 % and 99.25 % at 1 month and 53.16 % and 70.69 % at 6 months. One-month geometric mean titers (GMTs) were 21.33 and 22.45; one-month geometric mean concentrations (GMCs) were 227.71 IU/mL and 273.27 IU/mL. One to two months after vaccination, observation group seropositivity rates and titers were not significantly different to the control group’s. Adverse reaction rates were 11.27 % and 18.80 %, all mild or moderate in severity.ConclusionsBoth primary series were immunogenic; immunogenicity of WIBP-CorV followed by BBIBP-CorV was not different than immunogenicity following two doses of BBIBP-CorV for two months after vaccination; safety profiles were acceptable for both regimens. BBIBP-CorV can be used to complete a primary series that started with WIBP-CorV.     

mRNA-based COVID-19 booster vaccination is highly effective and cost-effective in Australia

BackgroundAustralia implemented an mRNA-based booster vaccination strategy against the COVID-19 Omicron variant in November 2021. We aimed to evaluate the effectiveness and cost-effectiveness of the booster strategy over 180 days.MethodsWe developed a decision-analytic Markov model of COVID-19 to evaluate the cost-effectiveness of a booster strategy (administered 3 months after 2nd dose) in those aged ≥ 16 years, from a healthcare system perspective. The willingness-to-pay threshold was chosen as A$ 50,000.ResultsCompared with 2-doses of COVID-19 vaccines without a booster, Australia's booster strategy would incur an additional cost of A$0.88 billion but save A$1.28 billion in direct medical cost and gain 670 quality-adjusted life years (QALYs) in 180 days of its implementation. This suggested the booster strategy is cost-saving, corresponding to a benefit-cost ratio of 1.45 and a net monetary benefit of A$0.43 billion. The strategy would prevent 1.32 million new infections, 65,170 hospitalisations, 6,927 ICU admissions and 1,348 deaths from COVID-19 in 180 days. Further, a universal booster strategy of having all individuals vaccinated with the booster shot immediately once their eligibility is met would have resulted in a gain of 1,599 QALYs, a net monetary benefit of A$1.46 billion and a benefit-cost ratio of 1.95 in 180 days.ConclusionThe COVID-19 booster strategy implemented in Australia is likely to be effective and cost-effective for the Omicron epidemic. Universal booster vaccination would have further improved its effectiveness and cost-effectiveness.     

Individual preferences for COVID-19 vaccination in China

BackgroundVaccinations are an effective choice to stop disease outbreaks, including COVID-19. There is little research on individuals' COVID-19 vaccination decision-making.ObjectiveWe aimed to determine individual preferences for COVID-19 vaccinations in China, and to assess the factors influencing vaccination decision-making to facilitate vaccination coverage.MethodsA D-efficient discrete choice experiment was conducted across six Chinese provinces selected by the stratified random sampling method. Vaccine choice sets were constructed using seven attributes: vaccine effectiveness, side-effects, accessibility, number of doses, vaccination sites, duration of vaccine protection, and proportion of acquaintances vaccinated. Conditional logit and latent class models were used to identify preferences.ResultsAlthough all seven attributes were proved to significantly influence respondents’ vaccination decision, vaccine effectiveness, side-effects and proportion of acquaintances vaccinated were the most important. We also found a higher probability of vaccinating when the vaccine was more effective; risks of serious side effects were small; vaccinations were free and voluntary; the fewer the number of doses; the longer the protection duration; and the higher the proportion of acquaintances vaccinated. Higher local vaccine coverage created altruistic herd incentives to vaccinate rather than free-rider problems. The predicted vaccination uptake of the optimal vaccination scenario in our study was 84.77%. Preference heterogeneity was substantial. Individuals who were older, had a lower education level, lower income, higher trust in the vaccine and higher perceived risk of infection, displayed a higher probability to vaccinate.ConclusionsPreference heterogeneity among individuals should lead health authorities to address the diversity of expectations about COVID-19 vaccinations. To maximize COVID-19 vaccine uptake, health authorities should promote vaccine effectiveness; pro-actively communicate the absence or presence of vaccine side effects; and ensure rapid and wide media communication about local vaccine coverage.     

Preferences for COVID-19 vaccination information and location: Associations with vaccine hesitancy,race and ethnicity

This study examined the association between preferences for being informed about the COVID-19 vaccine and where to receive it with vaccination intent and race/ethnicity. We conducted an online survey, oversampling Black and Latino panel members. The 1668 participants were 53.2% female, 34.8% White, 33.3% Black, and 31.8% Latino. Participants who were vaccine hesitant (answered “not sure” or “no” to vaccination intent) were more likely to prefer a conversation with their doctor compared to those who answered “yes” (25.0% and 23.4% vs 7.8%, P < .001, respectively). Among participants who responded “not sure”, 61.8% prefer to be vaccinated at a doctor’s office, compared with 35.2% of those who responded “yes” (P < .001). Preferred location differed by race/ethnicity (P < .001) with 67.6% of Black “not sure” participants preferring a doctor’s office compared to 60.2% of Latino and 54.9% of White “not sure” participants. These findings underscore the need to integrate healthcare providers into COVID-19 vaccination programs.