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.

Landscape of SARS-CoV-2 genomic surveillance, public availability extent of genomic data, and epidemic shaped by variants: a global descriptive study

BackgroundGenomic surveillance has shaped our understanding of SARS-CoV-2 variants, which have proliferated globally in 2021. Characterizing global genomic surveillance, sequencing coverage, the extent of publicly available genomic data coupled with traditional epidemiologic data can provide evidence to inform SARS-CoV-2 surveillance and control strategies. MethodsWe collected country-specific data on SARS-CoV-2 genomic surveillance, sequencing capabilities, public genomic data, and aggregated publicly available variant data. We divided countries into three levels of genomic surveillance and sequencing availability based on predefined criteria. We downloaded the merged and deduplicated SARS-CoV-2 sequences from multiple public repositories, and used different proxies to estimate the sequencing coverage and public availability extent of genomic data, in addition to describing the global dissemination of variants. FindingsSince the start of 2021, the COVID-19 global epidemic clearly featured increasing circulation of Alpha, which was rapidly replaced by the Delta variant starting around May 2021 and reaching a global prevalence of 96.6% at the end of July 2021. SARS-CoV-2 genomic surveillance and sequencing availability varied markedly across countries, with 63 countries performing routine genomic surveillance and 79 countries with high availability of SARS-CoV-2 sequencing. Less than 3.5% of confirmed SARS-CoV-2 infections were sequenced globally since September 2020, with the lowest sequencing coverage in the WHO regions of Eastern Mediterranean, South East Asia, and Africa. Across different variants, 28-52% of countries with explicit reporting on variants shared less than half of their variant sequences in public repositories. More than 60% of demographic and 95% of clinical data were absent in GISAID metadata accompanying sequences. InterpretationOur findings indicated an urgent need to expand sequencing capacity of virus isolates, enhance the sharing of sequences, the standardization of metadata files, and supportive networks for countries with no sequencing capability. Research in context Evidence before this studyOn September 3, 2021, we searched PubMed for articles in any language published after January 1, 2020, using the following search terms: ("COVID-19" OR "SARS-CoV-2") AND ("Global" OR "Region") AND ("genomic surveillance" OR "sequencing" OR "spread"). Among 43 papers identified, few papers discussed the global diversity in genomic surveillance, sequencing, public availability of genomic data, as well as the global spread of SARS-CoV-2 variants. A paper from Furuse employed the publicly GISAID data to evaluate the SARS-CoV-2 sequencing effort by country from the perspectives of "fraction", "timeliness", and "openness". Another viewpoint paper by Case Western Reserve Universitys team discussed the impediments of genomic surveillance in several countries during the COVID-19 pandemic. The paper as reported by Campbell and colleagues used the GISAID data to present the global spread and estimated transmissibility of recently emerged SARS-CoV-2 variants. We also found several studies that reported the country-level genomic surveillance and spread of variants. To our knowledge, no research has quantitatively depicted the global SARS-CoV-2 genomic surveillance, sequencing ability, and public availability extent of genomic data. Added value of this studyThis study collected country-specific data on SARS-CoV-2 genomic surveillance, sequencing capabilities, public genomic data, and aggregated publicly available variant data as of 20 August 2021. We found that genomic surveillance strategies and sequencing availability is globally diverse. Less than 3.5% of confirmed SARS-CoV-2 infections were sequenced globally since September 2020. Our analysis of publicly deposited SARS-CoV-2 sequences and officially reported number of variants implied that the public availability extent of genomic data is low in some countries, and more than 60% of demographic and 95% of clinical data were absent in GISAID metadata accompanying sequences. We also described the pandemic dynamics shaped by VOCs. Implications of all the available evidenceOur study provides a landscape for global sequencing coverage and public availability extent of sequences, as well as the evidence for rapid spread of SRAS-CoV-2 variants. The pervasive spread of Alpha and Delta variants further highlights the threat of SARS-CoV-2 mutations despite the availability of vaccines in many countries. It raised an urgent need to do more work on defining the ideal sampling schemes for different purposes (e.g., identifying new variants) with an additional call to share these data in public repositories to allow for further rapid scientific discovery.

Combining antibody markers for serosurveillance of SARS-CoV-2 to estimate seroprevalence and time-since-infection

Serosurveillance is an important epidemiologic tool for SARS-CoV-2, used to estimate burden of disease and degree of population immunity. Which antibody biomarker, and the optimal number of biomarkers, has not been well-established, especially with the emerging rollout of vaccines globally. Here, we used random forest models to demonstrate that a single spike or receptor-binding domain (RBD) antibody was adequate for classifying prior infection, while a combination of two antibody biomarkers performed better than any single marker for estimating time-since-infection. Nucleocapsid antibodies performed worse than spike or RBD antibodies for classification, but is of utility for estimating time-since-infection, and in distinguishing infection-induced from vaccine-induced responses. Our analysis has the potential to inform the design of serosurveys for SARS-CoV-2, including decisions regarding number of antibody biomarkers measured.

The Specchio-COVID19 cohort study: a longitudinal follow-up of SARS-CoV-2 serosurvey participants in the canton of Geneva, Switzerland (Study protocol)

BackgroundThe COVID-19 pandemic has affected billions of people around the world both directly through the infection itself and indirectly through its economic, social and sanitary impact. Collecting data over time is essential for the understanding of the disease spread, the incidence of COVID19-like symptoms, the level and dynamics of immunity, as well as the long-term impact of the pandemic. ObjectiveThe objective of the study was to set up a longitudinal follow-up of adult participants of serosurveys carried out in the Canton of Geneva, Switzerland, during the COVID-19 pandemic. MethodsSerosurvey participants were invited to create an account on the dedicated digital platform Specchio-COVID19 (https://www.specchio-covid19.ch/). Upon registration, an initial questionnaire assessed socio-demographic and lifestyle characteristics (including housing conditions, physical activity, diet, alcohol and tobacco consumption), anthropometry, general health, and experience related to COVID-19 (symptoms, COVID-19 test results, quarantines, hospitalizations). Weekly, participants were invited to fill in a short questionnaire with updates on self-reported COVID-19-compatible symptoms, SARS-CoV-2 infection testing and vaccination. A more detailed questionnaire about mental health, well-being, risk perception, and changes in working conditions was proposed monthly. Supplementary questionnaires were proposed at regular intervals to assess more in depth the impact of the pandemic on physical and mental health, vaccination adherence, health care consumption and changes in health behaviors. At baseline, serology testing allowed to assess the spread of SARS-CoV-2 infection among the general population and subgroups of workers. Additionally, seropositive participants and a sample of randomly selected participants were invited for serologic testing at regular intervals in order to monitor both the seropersistance of anti-SARS-CoV-2 antibodies and the seroprevalence of anti-SARS-CoV-2 antibodies in the population of the Canton of Geneva. Ethics and disseminationThe study was approved by the Cantonal Research Ethics Commission of Geneva, Switzerland (CCER Project ID 2020-00881). Results will be disseminated in a variety of ways, via the Specchio-COVID19 platform, social media posts, press releases, and through regular scientific dissemination methods (open-access articles, conferences). Article summaryO_ST_ABSStrengths and limitationsC_ST_ABSO_LIThis is a large study with a diversified recruitment among the general population and mobilized workers. It will contribute to obtain a clearer picture of the impact of the COVID-19 pandemic, for both the general population and targeted subpopulations. C_LIO_LIA major strength of the study is the combined use of serological testing and questionnaires. While regular serological testing will help us to model evolution of the pandemic, self-reported data on socioeconomic characteristics, COVID-19-compatible symptoms, and general and mental health will allow us to monitor the progression of the COVID-19 pandemic as well as to thoroughly analyze its effects on several dimensions of health. C_LIO_LIThe longitudinal component of the study will provide insight into the extent and duration of immunity, as well as the long-term impact of the pandemic and the sanitary, social and economic measures associated with it. C_LIO_LIThe main limitation is that Specchio-COVID19 is based on self-reports with a risk of information bias. However, considering the pandemic context, participants are generally engaged to participate and to contribute to COVID-19 research. Further, at least half of the sample is based on random selection in the general population. C_LIO_LIThe study is primarily being conducted online, which may limit the generalizability of the findings, especially for the elderly and vulnerable populations, although internet access is extensive in Switzerland. Nonetheless, participants can use paper questionnaires to contribute to the major assessments. C_LI

Risk of reinfection after seroconversion to SARS-CoV-2: A population-based propensity-score matched cohort study

ImportanceSerological assays detecting specific IgG antibodies generated against the Spike protein following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection are being widely deployed in research studies and clinical practice. However, the duration and the effectiveness of the protection conferred by the immune response against future infection remains to be assessed in a large population. ObjectiveTo estimate the incidence of newly acquired SARS-CoV-2 infections in seropositive individuals from a population-based sample as compared to seronegative controls. DesignRetrospective longitudinal propensity-score matched cohort study. SettingA seroprevalence survey including a population-based representative sample of the population from the canton of Geneva (Switzerland) was conducted between April and June 2020, immediately after the first pandemic wave. Each individual included in the seroprevalence survey was linked to a state centralized registry compiling virologically confirmed SARS-CoV-2 infections since the beginning of the pandemic. ParticipantsParticipants aged twelve years old and over, who developed anti-spike IgG antibodies were matched one-to-two to seronegative controls, using a propensity-score including age, gender, immunodeficiency, body mass index, smoking status and education level. ExposureSARS-CoV-2 seropositivity. Main outcomes and measuresOur primary outcome was virologically confirmed SARS-CoV-2 infections which occurred from serological status assessment in April-June 2020 to the end of the second pandemic wave (January 2021). Additionally, incidence of infections, rate of testing and proportion of positive tests were analysed. ResultsAmong 8344 serosurvey participants, 498 seropositive individuals were selected and matched with 996 seronegative controls. After a mean follow-up of 35.6 (Standard Deviation, SD: 3.2) weeks, 7 out of 498 (1.4%) seropositive subjects had a positive SARS-CoV-2 test, of which 5 (1.0%) were considered as reinfections. By contrast, infection rate was significantly higher in seronegative individuals (15.5%, 154/996) during a similar mean follow-up of 34.7 (SD 3.2) weeks, corresponding to a 94% (95%CI 86% to 98%, P<0.001) reduction in the hazard of having a positive SARS-CoV-2 test for seropositive subjects. Conclusions and relevanceSeroconversion after SARS-CoV-2 infection confers protection to successive viral contamination lasting at least 8 months. These findings could help global health authorities establishing priority for vaccine allocation. Key points QuestionDo SARS-CoV-2 antibodies confer protection against future infection? FindingsIn this retrospective matched cohort study nested in a representative sample of the general population of Geneva, Switzerland, we observed a 94% reduction in the hazard of being infected among participants with antibodies against SARS-CoV-2, when compared to seronegative controls, >8 months after initial serology assessment. MeaningSeroconversion to SARS-CoV-2 is associated with a large and sustained protection against reinfection.

Insights into the practical effectiveness of RT-PCR testing for SARS-CoV-2 from serologic data, a cohort study

BackgroundVirologic detection of SARS-CoV-2 through Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) has limitations for surveillance. Serologic tests can be an important complementary approach. ObjectiveAssess the practical performance of RT-PCR based surveillance protocols, and the extent of undetected SARS-CoV-2 transmission in Shenzhen, China. DesignCohort study nested in a public health response. SettingShenzhen, China; January-May 2020. Participants880 PCR-negative close-contacts of confirmed COVID-19 cases and 400 residents without known exposure (main analysis). Fifty-seven PCR-positive case contacts (timing analysis). MeasurementsVirological testing by RT-PCR. Measurement of anti-SARS-CoV-2 antibodies in PCR-negative contacts 2-15 weeks after initial testing using total Ab ELISA. Rates of undetected infection, performance of RT-PCR over the course of infection, and characteristics of seropositive but PCR-negative individuals were assessed. ResultsThe adjusted seropositivity rate for total Ab among 880 PCR-negative close-contacts was 4.1% (95%CI, 2.9% to 5.7%), significantly higher than among residents without known exposure to cases (0.0%, 95%CI, 0.0% to 1.0%). PCR-positive cases were 8.0 times (RR; 95% CI, 5.3 to 12.7) more likely to report symptoms than the PCR-negative individuals who were seropositive, but otherwise similar. RT-PCR missed 36% (95%CI, 28% to 44%) of infected close-contacts, and false negative rates appear to be highly dependent on stage of infection. LimitationsNo serological data were available on PCR-positive cases. Sample size was limited, and only 20% of PCR-negative contacts met inclusion criteria. ConclusionEven rigorous RT-PCR testing protocols may miss a significant proportion of infections, perhaps in part due to difficulties timing testing of asymptomatics for optimal sensitivity. Surveillance and control protocols relying on RT-PCR were, nevertheless, able to contain community spread in Shenzhen. Funding sourceBill & Melinda Gates Foundation, Special Foundation of Science and Technology Innovation Strategy of Guangdong Province of China, and Key Project of Shenzhen Science and Technology Innovation Commission, Shenzhen, China

Assessing the impact of non-pharmaceutical interventions on SARS-CoV-2 transmission in Switzerland

Following the rapid dissemination of COVID-19 cases in Switzerland, large-scale non-pharmaceutical interventions (NPIs) were implemented by the cantons and the federal government between February 28 and March 20. Estimates of the impact of these interventions on SARS-CoV-2 transmission are critical for decision making in this and future outbreaks. We here aim to assess the impact of these NPIs on disease transmission by estimating changes in the basic reproduction number (R0) at national and cantonal levels in relation to the timing of these NPIs. We estimate the time-varying R0 nationally and in twelve cantons by fitting a stochastic transmission model explicitly simulating within hospital dynamics. We use individual-level data of >1,000 hospitalized patients in Switzerland and public daily reports of hospitalizations and deaths. We estimate the national R0 was 3.15 (95% CI: 2.13-3.76) at the start of the epidemic. Starting from around March 6, we find a strong reduction in R0 with a 85% median decrease (95% quantile range, QR: 83%-90%) to a value of 0.44 (95% QR: 0.27-0.65) in the period of March 29-April 5. At the cantonal-level R0 decreased over the course of the epidemic between 71% and 94%. We found that reductions in R0 were synchronous with changes in mobility patterns as estimated through smartphone activity, which started before the official implementation of NPIs. We found that most of the reduction of transmission is due to behavioural changes as opposed to natural immunity, the latter accounting for only about 3% of the total reduction in effective transmission. As Switzerland considers relaxing some of the restrictions of social mixing, current estimates of R0 well below one are promising. However most of inferred transmission reduction was due to behaviour change (<3% due to natural immunity buildup), with an estimated 97% (95% QR: 96.6%-97.2%) of the Swiss population still susceptible to SARS-CoV-2 as of April 24. These results warrant a cautious relaxation of social distance practices and close monitoring of changes in both the basic and effective reproduction numbers.

COVID-19: Projecting the impact in Rohingya refugee camps and beyond

BackgroundCOVID-19 could have even more dire consequences in refugees camps than in general populations. Bangladesh has confirmed COVID-19 cases and hosts almost 1 million Rohingya refugees from Myanmar with 600,000 concentrated in Kutupalong-Balukhali Expansion Site (age mean: 21 years, sd: 18 years, 52% female). Projections of the potential COVID-19 burden, epidemic speed, and healthcare needs in such settings are critical for preparedness planning. Methods and FindingsTo explore the potential impact of the introduction of SARS-CoV-2 in Kutupalong-Balukhali Expansion Site, we used a stochastic SEIR transmission model with parameters derived from emerging literature and age as the primary determinant of infection severity. We considered three scenarios with different assumptions about the transmission potential of SARS-CoV-2. From the simulated infections, we estimated hospitalizations, deaths, and healthcare needs expected, age-adjusted for the Kutupalong-Balukhali Expansion Site age distribution. Our findings suggest that a large-scale outbreak is likely after a single introduction of the virus into the camp with 61-92% of simulations leading to at least 1,000 people infected across scenarios. On average, in the first 30 days of the outbreak, we expect 18 (95% prediction interval (PI), 2-65), 54 (95% PI, 3-223), and 370 (95% PI, 4-1,850) people infected in the low, moderate, and high transmission scenarios, respectively. These reach 421,500 (95% PI, 376,300-463,500), 546,800 (95% PI, 499,300-567,000) and 589,800 (95% PI, 578,800-595,600) people infected in 12 months, respectively. Hospitalization needs exceeded the existing hospitalization capacity of 340 beds after 55-136 days between the low and high transmission scenarios. We estimate 2,040 (95% PI, 1,660-2,500), 2,650 (95% PI, 2,030-3,380), and 2,880 (95% PI, 2,090-3,830) deaths in the low, moderate and high transmission scenarios, respectively. Due to limited data at the time of analyses, we assumed that age was the primary determinant of infection severity and hospitalization. We expect that comorbidities and limited hospitalization and intensive care capacity may increase this risk, thus we may be underestimating the potential burden. ConclusionsOur findings suggest that a COVID-19 epidemic in a refugee settlement may have profound consequences, requiring large increases in healthcare capacity and infrastructure that may exceed what is currently feasible in these settings. Detailed and realistic planning for the worst-case in Kutupalong-Balukhali and all refugee camps worldwide must begin now. Plans should consider novel and radical strategies to reduce infectious contacts and fill health worker gaps while recognizing that refugees may not have access to national health systems. AUTHORS SUMMARYO_LSTWhy was this study done?C_LSTO_LIForcibly displaced populations, especially those who reside in settlements with high density, poor access to water and sanitation, and limited health services, are especially vulnerable to COVID-19. C_LIO_LIBangladesh, which has confirmed COVID-19 cases, hosts almost 900,000 Rohingya refugees from Myanmar in the Coxs Bazar district, approximately 600,000 of whom are concentrated in the Kutupalong-Balukhali Expansion Site. C_LIO_LIThe capacity to meet the existing health needs of this population is limited; an outbreak of COVID-19 within this population threatens to severely disrupt an already fragile situation. C_LIO_LIWe conducted this study to estimate the number of people infected, hospitalizations, and deaths that might occur in the Kutupalong-Balukhali Expansion Site to inform ongoing preparedness and response activities by the Bangladesh government, the United Nations agencies, and other national and international actors. C_LI O_LSTWhat did the researchers do and find?C_LSTO_LIUsing a dynamic model of SARS-CoV-2 transmission, we simulated how a COVID-19 outbreak could spread within the Expansion Site according to three possible transmission scenarios (high, moderate, and low). C_LIO_LIOur results suggest that a large-scale outbreak is very likely in this setting after a single infectious person enters the camp, with 0.5-91% of the population expected to be infected within the first three months and over 70-98% during the first year depending on the transmission scenario, should no effective interventions be put into place. C_LIO_LIHospitalization needs may exceed the existing hospitalization capacity of 340 beds after 55-136 days of introduction. C_LI O_LSTWhat do these findings mean?C_LSTO_LIA COVID-19 epidemic in a high population density refugee settlement may have profound consequences, requiring increases in healthcare capacity and infrastructure that exceed what is feasible in this setting. C_LIO_LIAs many of the approaches used to prevent and respond to COVID-19 in the most affected areas so far will not be practical in humanitarian settings, novel and untested strategies to protect the most vulnerable population groups should be considered, as well as innovative solutions to fill health workforce gaps. C_LI