Global diversity of policy, coverage, and demand of COVID-19 vaccines: a descriptive study

BackgroundHundreds of millions of doses of COVID-19 vaccines have been administered globally, but progress in vaccination varies considerably between countries. We aim to provide an overall picture of COVID-19 vaccination campaigns, including policy, coverage, and demand of COVID-19 vaccines. MethodsWe conducted a descriptive study of vaccination policy and doses administered data obtained from multiple public sources as of 23 October 2021. We used these data to develop coverage indicators and explore associations of vaccine coverage with socioeconomic and healthcare-related factors. We estimated vaccine demand as numbers of doses required to complete vaccination of countries target populations according to their national immunization program policies. FindingsUse of both mRNA and adenovirus vectored vaccines was the most commonly used COVID-19 vaccines formulary in high-income countries, while adenovirus vectored vaccines were the most widely used vaccines worldwide (176 countries). Almost all countries (98.3%, 173/176) have authorized vaccines for the general public, with 53.4% (94/176) targeting individuals over 12 years and 33.0% (58/176) targeting those [≥]18 years. Forty-one and sixty-seven countries have started additional-dose and booster-dose vaccination programs, respectively. Globally, there have been 116.5 doses administered per 100 target population, although with marked inter-region and inter-country heterogeneity. Completed vaccination series coverage ranged from 0% to more than 95.0% of country target populations, and numbers of doses administered ranged from 0 to 239.6 per 100 target population. Doses administered per 100 total population correlated with healthcare access and quality index (R2 = 0.58), socio-demographic index (R2 = 0.56), and GDP per capita (R2 = 0.65). At least 5.54 billion doses will be required to complete interim vaccination programs - 4.65 billion for primary immunization and 0.89 billion for additional/booster programs. Globally, 0.84 and 0.96 dose per individual in the target population are needed for primary immunization and additional/booster programs, respectively. InterpretationThere is wide country-level disparity and inequity in COVID-19 vaccines rollout, suggesting large gaps in immunity, especially in low-income countries. FundingKey Program of the National Natural Science Foundation of China, the US National Institutes of Health. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for articles in any language published up to October 21, 2021, using the following search terms: ("COVID-19" OR "SARS-CoV-2") AND ("vaccination" OR "vaccine") AND ("inequalit*" OR "inequity" OR "disparit*" OR "heterogeneity"). We also searched for dashboards associated with vaccine rollout from public websites. We identified several studies on tracking global inequalities of vaccine access, one of which constructed a COVID-19 vaccine dashboard (Our World in Data), and another that explored disparities in COVID-19 vaccination among different-income countries. However, we found no studies that depict global COVID-19 vaccination policies country-by-country and estimate demand for vaccine necessary to completely vaccinate countries designated target populations. Added value of this studyTo our knowledge, our study provides the most recent picture of COVID-19 vaccination campaigns, focusing on global vaccination policy and target-population demand. We found a diverse portfolio of vaccines in five technical platforms being administered globally, with 173 countries having authorized administration of vaccines to the general public in various age groups. We observed inter-region and inter-country heterogeneity in one-or-more-dose and full-dose coverage; countries with higher socio-demographic or health resource-related levels had higher coverage. We estimated dose-level demand for completing primary immunization programs and additional/booster dose programs separately. Implications of all the available evidenceWorldwide disparity and inequity of vaccine rollout implies that susceptibility among unvaccinated populations in some countries may impede or reverse pandemic control, especially in face of the emergence of variants and the dilemma of waning antibodies. Our findings suggest that global-level responses to the pandemic - financially, politically, and technically - are needed to overcome complex challenges that lie ahead.

Prediction of long-term kinetics of vaccine-elicited neutralizing antibody and time-varying vaccine-specific efficacy against the SARS-CoV-2 Delta variant by clinical endpoint

Evidence on vaccine-specific protection over time and boosting impact against the Delta variant across different clinical endpoints and age groups is urgently needed. To address this, we used a previously published model, combined with neutralization data for four vaccines - mRNA-1273, BNT162b2, NVX-CoV2373, and CoronaVac - to evaluate long-term dynamics of neutralizing antibody and to predict time-varying efficacy against the Delta variant by specific vaccine, age group, and clinical severity. We found that booster vaccination produces higher neutralization titers compared with titers observed following primary-series vaccination for all vaccines studied. We estimate the efficacies of mRNA-1273 and BNT162b2 against Delta variant infection to be 63.5% (95%CI: 51.4-67.3%) and 78.4% (95%CI: 72.2-83.5%), respectively, 14-30 days after the second dose, and that efficacies decreased to 36.0% (95%CI: 24.1-58.0%) and 38.5% (95%CI: 28.7-49.1%) 6-8 months later. After administration of booster doses, efficacies against the Delta variant would be 97.0% (95%CI: 96.4-98.5%) and 97.2% (95.7-98.1%). All four vaccines are predicted to provide good protection against severe illness from the Delta variant after both primary and booster vaccination. Long-term monitoring and surveillance of antibody dynamics and vaccine protection, as well as further validation of neutralizing antibody or other markers that can serve as correlates of protection against SARS-CoV-2 and its variants are needed to inform COVID-19 pandemic preparedness.

Herd immunity induced by COVID-19 vaccination programs to suppress epidemics caused by SARS-CoV-2 wild type and variants in China

BackgroundTo allow a return to a pre-COVID-19 lifestyle, virtually every country has initiated a vaccination program to mitigate severe disease burden and control transmission. However, it remains to be seen whether herd immunity will be within reach of these programs. MethodsWe developed a data-driven model of SARS-CoV-2 transmission for China, a population with low prior immunity from natural infection. The model is calibrated considering COVID-19 natural history and the estimated transmissibility of the Delta variant. Three vaccination programs are tested, including the one currently enacted in China and model-based estimates of the herd immunity level are provided. ResultsWe found that it is unlike to reach herd immunity for the Delta variant given the relatively low efficacy of the vaccines used in China throughout 2021, the exclusion of underage individuals from the targeted population, and the lack of prior natural immunity. We estimate that, assuming a vaccine efficacy of 90% against the infection, vaccine-induced herd immunity would require a coverage of 93% or higher of the Chinese population. However, even when vaccine-induced herd immunity is not reached, we estimated that vaccination programs can reduce SARS-CoV-2 infections by 53-58% in case of an epidemic starts to unfold in the fall of 2021. ConclusionsEfforts should be taken to increase populations confidence and willingness to be vaccinated and to guarantee highly efficacious vaccines for a wider age range.

Comprehensive mapping of neutralizing antibodies against SARS-CoV-2 variants induced by natural infection or vaccination

BackgroundImmunity after SARS-CoV-2 infection or vaccination has been threatened by recently emerged SARS-CoV-2 variants. A systematic summary of the landscape of neutralizing antibodies against emerging variants is needed. MethodsWe systematically searched PubMed, Embase, Web of Science, and 3 pre-print servers for studies that evaluated neutralizing antibodies titers induced by previous infection or vaccination against SARS-CoV-2 variants and comprehensively collected individual data. We calculated lineage-specific GMTs across different study participants and types of neutralization assays. FindingsWe identified 56 studies, including 2,483 individuals and 8,590 neutralization tests, meeting the eligibility criteria. Compared with lineage B, we estimate a 1.5-fold (95% CI: 1.0-2.2) reduction in neutralization against the B.1.1.7, 8.7-fold (95% CI: 6.5-11.7) reduction against B.1.351 and 5.0-fold (95% CI: 4.0-6.2) reduction against P.1. The estimated neutralization reductions for B.1.351 compared to lineage B were 240.2-fold (95% CI: 124.0-465.6) reduction for non-replicating vector platform, 4.6-fold (95% CI: 4.0-5.2) reduction for RNA platform, and 1.6-fold (95% CI: 1.2-2.1) reduction for protein subunit platform. The neutralizing antibodies induced by administration of inactivated vaccines and mRNA vaccines against lineage P.1 were also remarkably reduced by an average of 5.9-fold (95% CI: 3.7-9.3) and 1.5-fold (95% CI: 1.2-1.9). InterpretationOur findings indicate that the antibody response established by natural infection or vaccination might be able to effectively neutralize B.1.1.7, but neutralizing titers against B.1.351 and P.1 suffered large reductions. Standardized protocols for neutralization assays, as well as updating immune-based prevention and treatment, are needed. FundingChinese National Science Fund for Distinguished Young Scholars Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSeveral newly emerged SARS-CoV-2 variants have raised significant concerns globally, and there is concern that SARS-CoV-2 variants can evade immune responses that are based on the prototype strain. It is not known to what extent do emerging SARS-CoV-2 variants escape the immune response induced by previous infection or vaccination. However, existing studies of neutralizing potency against SARS-CoV-2 variants are based on limited numbers of samples and lack comparability between different laboratory methods. Furthermore, there are no studies providing whole picture of neutralizing antibodies induced by prior infections or vaccination against emerging variants. Therefore, we systematically reviewed and quantitively synthesized evidence on the degree to which antibodies from previous SARS-CoV-2 infection or vaccination effectively neutralize variants. Added value of this studyIn this study, 56 studies, including 2,483 individuals and 8,590 neutralization tests, were identified. Antibodies from natural infection or vaccination are likely to effectively neutralize B.1.1.7, but neutralizing titers against B.1.351 and P.1 suffered large reductions. Lineage B.1.351 escaped natural-infection-mediated neutralization the most, with GMT of 79.2 (95% CI: 68.5-91.6), while neutralizing antibody titers against the B.1.1.7 variant were largely preserved (254.6, 95% CI: 214.1-302.8). Compared with lineage B, we estimate a 1.5-fold (95% CI: 1.0-2.2) reduction in neutralization against the B.1.1.7, 8.7-fold (95% CI: 6.5-11.7) reduction against B.1.351 and 5.0-fold (95% CI: 4.0-6.2) reduction against P.1. The neutralizing antibody response after vaccinating with non-replicating vector vaccines against lineage B.1.351 was worse than responses elicited by vaccines on other platforms, with levels lower than that of individuals who were previously infected. The neutralizing antibodies induced by administration of inactivated vaccines and mRNA vaccines against lineage P.1 were also remarkably reduced by an average of 5.9-fold (95% CI: 3.7-9.3) and 1.5-fold (95% CI: 1.2-1.9). Implications of all the available evidenceOur findings indicate that antibodies from natural infection of the parent lineage of SARS-CoV-2 or vaccination may be less able to neutralize some emerging variants, and antibody-based therapies may need to be updated. Furthermore, standardized protocols for neutralizing antibody testing against SARS-CoV-2 are needed to reduce lab-to-lab variations, thus facilitating comparability and interpretability across studies.

Global, regional, and national estimates of target population sizes for COVID-19 vaccination

BackgroundCOVID-19 vaccine prioritization and allocation strategies that maximize health benefit through efficient use of limited resources are urgently needed. We aimed to provide global, regional, and national estimates of target population sizes for COVID-19 vaccination to inform country-specific immunization strategies on a global scale. MethodsBased on a previous study of international allocation for pandemic COVID-19 vaccines, we classified the entire world population into eleven priority groups. Information on priority groups was derived from a multi-pronged search of official websites, media sources and academic journal articles. The sizes of different priority groups were projected for 194 countries globally. ResultsOverall, the size of COVID-19 vaccine recipient population varied markedly by goals of the vaccination program and geography. The general population aged <60 years without any underlying condition accounts for the majority of the total population (5.2 billion people, 68%), followed by 2.3 billion individuals at risk of severe disease, and 246.9 million essential workers which are critical to maintaining a functional society. Differences in the demographic structure, presence of underlying conditions, and number of essential workers led to highly variable estimates of target populations both at the WHO region and country level. In particular, Europe has the highest share of essential workers (6.8%) and the highest share of individuals with underlying conditions (37.8%), two priority categories to maintain societal functions and reduce severe burden. In contrast, Africa has the highest share of healthy adults, school-age individuals, and infants (77.6%), which are the key groups to target to reduce community transmission. InterpretationThe sizeable distribution of target groups on a country and regional bases underlines the importance of equitable and efficient vaccine prioritization and allocation globally. The direct and indirect benefits of COVID-19 vaccination should be balanced by considering local differences in demography and health.

Serological evidence of human infection with SARS-CoV-2: a systematic review and meta-analysis

BackgroundA rapidly increasing number of serological surveys for anti-SARS-CoV-2 antibodies have been reported worldwide. A synthesis of this large corpus of data is needed. PurposeTo evaluate the quality of serological studies and provide a global picture of seroprevalence across demographic and occupational groups, and to provide guidance for conducting better serosurveys. Data sourcesWe searched PubMed, Embase, Web of Science, and 4 pre-print servers for English-language papers published from December 1, 2019 to September 25, 2020. Study selectionSerological studies evaluating SARS-CoV-2 seroprevalence in humans. Data extractionTwo investigators independently extracted data from studies. Data SynthesisMost of 230 serological studies, representing tests in >1,400,000 individuals, identified were of low quality based on a standardized study quality scale. In the 51 studies of higher quality, high-risk healthcare workers had higher seroprevalence of 17.1% (95% CI: 9.9-24.4%), compared to low-risk healthcare workers and general population of 5.4% (0.7-10.1%) and 5.3% (4.2-6.4%). Seroprevalence varied hugely across WHO regions, with lowest seroprevalence of general population in Western Pacific region (1.7%, 0.0-5.0%). Generally, the young (<20 years) and the old ([≥]65 years) were less likely to be seropositive compared to middle-aged (20-64 years) populations. Seroprevalence correlated with clinical COVID-19 reports, with pooled average of 7.7 (range: 2.0 to 23.1) serologically-detected-infections per confirmed COVID-19 case. LimitationsSome heterogeneity cannot be well explained quantitatively. ConclusionsThe overall quality of seroprevalence studies examined was low. The relatively low seroprevalence among general populations suggest that in most settings, antibody-mediated herd immunity is far from being reached. Given the relatively narrow range of estimates of the ratio of serologically-detected infections to confirmed cases across different locales, reported case counts may help provide insights into the true proportion of the population infected. Primary Funding sourceNational Science Fund for Distinguished Young Scholars (PROSPERO: CRD42020198253).

Transmission heterogeneities, kinetics, and controllability of SARS-CoV-2

A long-standing question in infectious disease dynamics is the role of transmission heterogeneities, particularly those driven by demography, behavior and interventions. Here we characterize transmission risk between 1,178 SARS-CoV-2 infected individuals and their 15,648 close contacts based on detailed contact tracing data from Hunan, China. We find that 80% of secondary transmissions can be traced back to 14% of SARS-CoV-2 infections, indicating substantial transmission heterogeneities. Regression analysis suggests a marked gradient of transmission risk scales positively with the duration of exposure and the closeness of social interactions, after adjusted for demographic and clinical factors. Population-level physical distancing measures confine transmission to families and households; while case isolation and contact quarantine reduce transmission in all settings. Adjusted for interventions, the reconstructed infectiousness profile of a typical SARS-CoV-2 infection peaks just before symptom presentation, with ~50% of transmission occurring in the pre-symptomatic phase. Modelling results indicate that achieving SARS-CoV-2 control would require the synergistic efforts of case isolation, contact quarantine, and population-level physical distancing measures, owing to the particular transmission kinetics of this virus.

Infectivity, susceptibility, and risk factors associated with SARS-CoV-2 transmission under intensive contact tracing in Hunan, China

BackgroundSeveral parameters driving the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unclear, including age-specific differences in infectivity and susceptibility, and the contribution of inapparent infections to transmission. Robust estimates of key time-to-event distributions remain scarce as well. MethodsWe collected individual records for 1,178 SARS-CoV-2 infected individuals and their 15,648 contacts identified by contact tracing and monitoring over the period from January 13 to April 02, 2020 in Hunan Province, China. We provide descriptive statistics of the characteristics of cases and their close contacts; we fitted distributions to time-to-key-events distributions and infectiousness profile over time; and we used generalized linear mixed model to estimate risk factors for susceptibility and transmissibility of SARS-CoV-2. ResultsWe estimated the mean serial interval at 5.5 days (95%CI -5.0, 19.9) and the mean generation time at 5.5 days (95%CI 1.7, 11.6). The infectiousness was estimated to peak 1.8 days before symptom onset, with 95% of transmission events occurring between 7.6 days before and 7.3 days after the date of symptom onset. The proportion of pre-symptomatic transmission was estimated to be 62.5%. We estimated that at least 3.5% of cases were generated asymptomatic individuals. SARS-CoV-2 transmissibility was not significantly different between working-age adults (15-59 years old) and other age groups (0-14 years old: p-value=0.16; 60 years and over: p-value=0.33), whilst susceptibility to SARS-CoV-2 infection was estimated to increase with age (p-value=0.03). In addition, transmission risk was higher for household contacts (p-value<0.001), decreased for higher generations within a cluster (second generation: odds ratio=0.13, p-value<0.001; generations 3-4: odds ratio=0.05, p-value<0.001, relative to generation 1), and decreased for infectors with a larger number of contacts (p-value=0.04). InterpretationOur findings warn of the possible relevant contribution of children to SARS-CoV-2 transmission. When lockdown interventions are in place, we found that odds of transmission are highest in the household setting but, with the relaxation of interventions, other settings (including schools) could bear a higher risk of transmission. Moreover, the estimated relevant fraction of pre-symptomatic and asymptomatic transmission highlight the importance of large-scale testing, contact tracing activities, and the use of personnel protective equipment during the COVID-19 pandemic.

Evolving epidemiology of novel coronavirus diseases 2019 and possible interruption of local transmission outside Hubei Province in China: a descriptive and modeling study

BackgroundThe COVID-19 epidemic originated in Wuhan City of Hubei Province in December 2019 and has spread throughout China. Understanding the fast evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy. MethodsWe collected individual information on 8,579 laboratory-confirmed cases from official publically sources reported outside Hubei in mainland China, as of February 17, 2020. We estimated the temporal variation of the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (Rt) at the provincial level. ResultsThe median age of the cases was 44 years, with an increasing of cases in younger age groups and the elderly as the epidemic progressed. The delay from symptom onset to hospital admission decreased from 4.4 days (95%CI: 0.0-14.0) until January 27 to 2.6 days (0.0-9.0) from January 28 to February 17. The mean incubation period was estimated at 5.2 days (1.8-12.4) and the mean serial interval at 5.1 days (1.3-11.6). The epidemic dynamics in provinces outside Hubei was highly variable, but consistently included a mix of case importations and local transmission. We estimate that the epidemic was self-sustained for less than three weeks with Rt reaching peaks between 1.40 (1.04-1.85) in Shenzhen City of Guangdong Province and 2.17 (1.69-2.76) in Shandong Province. In all the analyzed locations (n=10) Rt was estimated to be below the epidemic threshold since the end of January. ConclusionOur findings suggest that the strict containment measures and movement restrictions in place may contribute to the interruption of local COVID-19 transmission outside Hubei Province. The shorter serial interval estimated here implies that transmissibility is not as high as initial estimates suggested.