Household transmission of SARS-CoV-2 during the Omicron wave in Shanghai, China：a case-ascertained study (preprint)

Since late 2021, the highly transmissible SARS-CoV-2 Omicron variant has driven a new surge of infections across the world. We used a case-ascertained study to determine the features of household transmission of SARS-CoV-2 Omicron variant in Shanghai, China. We collected detailed information on 323 pediatric cases and their 951 household members, all received consecutively intensive RT-PCR testing. We estimated the transmission parameters. Both secondary infection attack rates (SARI) and secondary clinical attack rates (SARC) among adult household contacts were computed, through which the transmission heterogeneities in infectivity and susceptibility were characterized and the vaccine effectiveness were estimated. The mean incubation period and serial interval of Omicron variant were estimated to be 4.6±2.1 days and 3.9±3.7 days. The overall SARI and SARC among adult household contacts were 77.11% (95% confidence interval [CI]: 73.58%-80.63%) and 67.03% (63.09%-70.98%). We found higher household susceptibility in females, while infectivity was not significantly different in primary cases by age, sex, vaccination status and clinical severity. Full vaccination and booster vaccination of inactivated vaccines were 14.8% (5.8%-22.9%) and 18.9% (9.0%-27.7%) effective against Omicron infection and 21.5% (10.4%-31.2%) and 24.3% (12.3%-34.7%) effective against symptomatic disease. Overall, we found high household transmission during the Omicron wave in Shanghai due to asymptomatic and pre-symptomatic transmission in the context of city-wide lockdown, indicating the importance of early detection and timely isolation of SARS-CoV-2 infections and quarantine of close contacts. Marginal effectiveness of inactivated vaccines against Omicron infection poses great challenge for prevention and control of the SARS-CoV-2 Omicron variant.

Household transmission of SARS-CoV-2 during the Omicron wave in Shanghai, China:a case-ascertained study (preprint)

Background Since late 2021, the highly transmissible SARS-CoV-2 Omicron variant has driven a new surge of infections across the world. We used a case-ascertained study to determine the features of household transmission of SARS-CoV-2 Omicron variant in Shanghai, China. Methods We collected detailed information on 323 pediatric cases and their 951 household members in April 2022 during the Omicron outbreak. All household members received consecutively intensive RT-PCR testing for SARS-CoV-2 and routine symptom monitoring within 14 days after exposure to a confirmed case. We described the characteristics of study participants and estimated the transmission parameters. Both secondary infection attack rates (SAR I ) and secondary clinical attack rates (SAR C ) among adult household contacts were computed, through which the transmission heterogeneities in infectivity and susceptibility were characterized and the vaccine effectiveness were estimated. Results We estimated the mean incubation period of SARS-CoV-2 Omicron variant to be 4.6 (median: 4.4, IQR: 3.1-6.0) days and the mean serial interval to be 3.9 (median:4.0, IQR: 1.4-6.5) days. The overall SAR I and SAR C among adult household contacts were 77.11% (95% confidence interval [CI]: 73.58%-80.63%) and 67.03% (63.09%-70.98%). We found higher household susceptibility in females, while infectivity was not significantly different in primary cases by age, sex, vaccination status and clinical severity. The estimated VEs of full vaccination was 14.8% (95% CI: 5.8%-22.9%) against Omicron infection and 21.5% (95% CI: 10.4%-31.2%) against symptomatic disease. The booster vaccination was 18.9% (95% CI: 9.0%-27.7%) and 24.3% (95% CI: 12.3%-34.7%) effective against infection and symptomatic disease, respectively. Conclusions We found high household transmission during the Omicron wave in Shanghai due to asymptomatic and pre-symptomatic transmission in the context of city-wide lockdown, indicating the importance of early detection and timely isolation of SARS-CoV-2 infections and quarantine of close contacts. Marginal effectiveness of inactivated vaccines against Omicron infection poses great challenge for prevention and control of the SARS-CoV-2 Omicron variant.

Projecting the impact of the introduction of SARS-CoV-2 Omicron variant in China in the context of waning immunity after vaccination (preprint)

After the adoption of a dynamic zero-COVID strategy in China for nearly two years, whether and for how long this policy can remain in place is unclear. The debate has thus shifted towards the identification of mitigation strategies capable to prevent the disruption of the healthcare system, should a nationwide epidemic caused by the SARS-CoV-2 Omicron variant start to unfold. To this aim, we developed a mathematical model of SARS-CoV-2 transmission tailored to the unique immunization and epidemiological situation of China. We find that the level of immunity induced by the current vaccination campaign would be insufficient to prevent overwhelming the healthcare system and major losses of human lives. Instead, a synergetic strategy would be needed and based on 1) a heterologous booster vaccination campaign, 2) treating 50% of symptomatic cases with an antiviral with an 80% efficacy in preventing severe outcomes, and 3) the adoption of non-pharmaceutical interventions (NPIs) capable of reducing Rt to ≤2. Protecting vulnerable individuals by ensuring accessibility to vaccines and antivirals, and maintaining a certain degree of NPIs should be emphasised in a future mitigation policy, possibly supported by strengthening critical care capacity and the development of highly efficacious vaccines with long-lasting immunity.

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

Summary Background Hundreds 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. Methods We 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 target populations of countries according to their national immunization program policies. Findings Use 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. Interpretation There is wide country-level disparity and inequity in COVID-19 vaccines rollout, suggesting large gaps in immunity, especially in low-income countries.

Projecting the transition of COVID-19 burden towards the young population while vaccines are rolled out: a modelling study (preprint)

Objectives SARS-CoV-2 infection causes most cases of severe illness and fatality in older age groups. In China, over 99% of individuals aged ⩾12 years have been fully vaccinated against COVID-19 (albeit with vaccines developed against historical lineages), while 65.0% children aged 3–11 years have been vaccinated their first doses (as of November 12, 2021). Here, we aimed to assess whether, in this vaccination landscape, the importation of Delta variant infections could shift the COVID-19 burden from adults to children. Methods We developed an age-structured susceptible-infectious-removed model of SARS-CoV-2 transmission dynamics to simulate epidemics triggered by the importation of Delta variant infections and project the age-specific incidence of SARS-CoV-2 infections, cases, hospitalisations, intensive care unit (ICU) admissions, and deaths. Results In the context of the vaccination programme targeting individuals aged ≥12 years (as it was the case until mid-October 2021), and in the absence of non-pharmaceutical interventions, the importation of Delta variant infections could have led to widespread transmission and substantial disease burden in mainland China, even with vaccination coverage as high as 97% across the eligible age groups. Extending the vaccination roll-out to include children aged 3–11 years (as it was the case since the end of October 2021) is estimated to dramatically decrease the burden of symptomatic infections and hospitalisations within this age group (54% and 81%, respectively, when considering a vaccination coverage of 99%), but would have a low impact on protecting infants (aged 0–2 years). Conclusions Our findings highlight the importance of including children among the target population and the need to strengthen vaccination efforts by increasing vaccine effectiveness.

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 (preprint)

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.

A booster dose is immunogenic and will be needed for older adults who have completed two doses vaccination with CoronaVac: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial (preprint)

ImportanceWhether herd immunity through mass vaccination is sufficient to curb SARS-CoV-2 transmission requires an understanding of the duration of vaccine-induced immunity, and the necessity and timing of booster doses. Objective: To evaluate immune persistence of two priming doses of CoronaVac, and immunogenicity and safety of a third dose in healthy adults [≥]60 years. Design, setting, and participants: We conducted a vaccine booster study built on a single-center, randomized, double-blind phase 1/2 trial of the two-dose schedule of CoronaVac among healthy adults[≥]60 years in Hebei, China. We examined neutralizing antibody titres six months or more after the second dose in all participants. We provided a third dose to 303 participants recruited in phase 2 trial to assess their immune responses. InterventionsTwo formulations (3 g, and 6 g) were used in phase 1 trial, and an additional formulation of 1.5 g was used in phase 2 trial. All participants were given two doses 28 days apart and followed up 6 months after the second dose. Participants in phase 2 received a third dose 8 months after the second dose. Main outcomes and measuresGeometric mean titres (GMT) of neutralizing antibodies to live SARS-CoV-2 and adverse events were assessed at multiple time points following vaccination. ResultsNeutralizing antibody titres dropped below the seropositive cutoff of 8 at 6 months after the primary vaccination in all vaccine groups in the phase 1/2 trial. A third dose given 8 months or more after the second dose significantly increased neutralizing antibody levels. In the 3 g group (the licensed formulation), GMT increased to 305 [95%CI 215.3-432.0] on day 7 following the third dose, an approximately 7-fold increase compared with the GMT 28 days after the second dose. All solicited adverse reactions reported within 28 days after a booster dose were of grade 1 or 2 severity. Conclusion and relevanceNeutralizing antibody titres declined substantially six months after two doses of CoronaVac among older adults. A booster dose rapidly induces robust immune responses. This evidence could help policymakers determine the necessity and the timing of a booster dose for older adults. Trial registrationClinicalTrials.gov (NCT04383574).

Immunogenicity and safety of a third dose, and immune persistence of CoronaVac vaccine in healthy adults aged 18-59 years: interim results from a double-blind, randomized, placebo-controlled phase 2 clinical trial (preprint)

Background Large-scale vaccination is being implemented globally with CoronaVac, an inactivated vaccine against coronavirus disease 2019 (COVID-19). Immunogenicity and safety profiles of homologous two-dose schedules have been published. We report interim results of immune persistence, and the immunogenicity and safety of a third dose of CoronaVac. Methods In this ongoing, placebo-controlled, double-blind phase 2 trial in 18-to-59-year-olds, we randomly assigned subjects, 1:1:1:1, to one of four schedules to receive a third dose, 28 days or 6 months after two two-dose regimens (14-day or 28-day apart): schedule 1 days 0, 14, 42; schedule 2 days 0, 14, 194; schedule 3 days 0, 28, 56; schedule 4 days 0, 28, 208. For each schedule, participants were randomly assigned to either a medium-dose group (3 μg per 0.5 mL of aluminum hydroxide diluent per dose), a high-dose group (6 μg), or a placebo group (2:2:1). The primary outcome was geometric mean titers (GMTs) of neutralizing antibody to live SARS-CoV-2. Results Overall, 540 participants received a third dose. In the 3 μg group, neutralizing antibody titers induced by the first two doses declined after 6-8 months to below the seropositive cutoff (GMT: 4.1 [95%CI 3.3-5.2] for Schedule 2 and 6.7 [95%CI 5.2-8.6] for Schedule 4 ). When a third dose was given 6-8 months after a second dose, GMTs assessed 14 days later increased to 137.9 [95%CI 99.9-190.4] for Schedule 2 , and 143.1 [95%CI 110.8-184.7] for Schedule 4 , approximately 3-fold above Schedule 1 and Schedule 3 GMTs after third doses. Similar patterns were observed for the 6 μg group. The severity of solicited local and systemic adverse reactions reported within 28 days after the third dose were grade 1 to grade 2 in all vaccination cohorts. None of the fourteen serious adverse events were considered to be related to vaccination. Conclusions A third dose of CoronaVac administered 6 or more months after a second dose effectively recalled specific immune response to SARS-CoV-2, resulting in a remarkable increase in antibody levels, and indicating that a two-dose schedule generates good immune memory. Optimizing the timing of a booster dose should take into account immunogenicity, vaccine efficacy/effectiveness, local epidemic situation, infection risk, and vaccine supply. (Funded by the National Key Research and Development Program, Beijing Science and Technology Program and National Science Fund for Distinguished Young Scholars; ClinicalTrials.gov number, NCT04352608 .)

Surveillance for Adverse Events Following Immunization With COVID-19 Vaccines in Dalian, China (preprint)

Background: Coronavirus disease 2019 (COVID-19) vaccines have been administered in priority populations in China since December 15, 2020. This study aims to assess the safety of the COVID-19 vaccination programme in Dalian, China.Methods: Passive surveillance for adverse events following immunization (AEFIs) with COVID-19 vaccines was performed by the Dalian Center for Disease Control and Prevention (CDC). Data were collected through June 8, 2021, from the Chinese National Adverse Events Following Immunization System (CNAEFIS) and were verified by local and upper-level CDCs.Findings: A total of 7.12 million doses of vaccine were administered from November 27, 2020, through June 8, 2021, and 623 vaccinees reported adverse events, resulting in a rate of 87.5 events per one million doses. The age-specific rates of AEFIs ranged from 74.0 per one million doses among persons aged 45 to 59 years to 102.0 per one million doses among persons aged 18 to 44 years; the manufacturer-specific rates ranged from 81.1 to 125.2 per one million doses. Among the 623 AEFIs, 544 (87.3%; rate, 76.4 per one million doses) were confirmed as common minor vaccine reactions. Very rare cases of anaphylaxis after vaccination were reported (5 cases; 0.7 per one million doses). Seven cases of AEFIs were classified as serious; however, available information indicated that there was no causal relationship with COVID-19 vaccination.Interpretation: No major safety concerns were identified during the COVID-19 vaccination campaign. There was no evidence of an increased risk of serious adverse events (SAEs).Funding Information: The study was supported by grants from the National Science Fund for Distinguished Young Scholars (No. 81525023), Key Emergency Project of Shanghai Science and Technology Committee (No. 20411950100).Declaration of Interests: H.Y. has received research funding from Sanofi Pasteur GlaxoSmithKline, Yichang HEC Changjiang Pharmaceutical Company, and Shanghai Roche Pharmaceutical Company. None of those research funding is related to development of COVID-19 vaccines. All other authors report no competing interests.

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

To 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; over 3.6 billion vaccine doses have been administered as of July 2021. However, it remains to be seen whether herd immunity will be within reach of these programs, especially as more transmissible SARS-CoV-2 variants continue to emerge. To address this question, we developed a data-driven model of SARS-CoV-2 transmission for Shanghai, China, a population with low prior immunity from natural infection. We found that extending the vaccination program to individuals aged 3-17 years plays a key role to reach herd immunity for the original SARS-CoV-2 lineages. With a vaccine efficacy 74% against infection, vaccine-induced herd immunity would require coverages of 93% or higher. Herd immunity for new variants, such as Alpha or Delta, can only be achieved with more efficacious vaccines and coverages above 80-90%. A continuation of the current pace of vaccination in China would reach 72% coverage by September 2021; although this program would fail to reach herd immunity it would reduce deaths by 95-100% in case of an outbreak. Efforts should be taken to increase population's confidence and willingness to be vaccinated and to guarantee highly efficacious vaccines against more transmissible variants of concern.

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

Background Immunity 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. Methods We 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. Findings We 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). Interpretation Our 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. Funding Chinese National Science Fund for Distinguished Young Scholars Research in context Evidence before this study Several 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 study In 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 evidence Our 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.

Dynamic optimization of COVID-19 vaccine prioritization in the context of limited supply (preprint)

Strategic prioritization of COVID-19 vaccines is urgently needed, especially in light of the limited supply that is expected to last for most, if not the entire, 2021. Dynamically adapting the allocation strategy to the evolving epidemiological situation could thus be critical during this initial phase of vaccine rollout. We developed a data-driven mechanistic model of SARS-CoV-2 transmission to explore optimal vaccine prioritization strategies in China that aim at reducing COVID-19 burden measured through different metrics. We found that reactively adapting the vaccination program to the epidemiological situation (i.e., allocate vaccine to a target group before reaching full coverage of other groups with initial higher priority) can be highly beneficial as such strategies are capable to simultaneously achieve different objectives (e.g., minimizing the number of deaths and of infections). The highest priority categories are broadly consistent under different hypotheses about vaccine efficacy, differential vaccine efficacy in preventing infection vs. disease, vaccine hesitancy, and SARS-CoV-2 transmissibility. Our findings also suggest that boosting the daily capacities up to 2.5 million courses (0.17% rollout speed) or higher could greatly reduce COVID-19 burden should a new wave start to unfold in China with reproduction number equal to 1.5 or lower. Finally, we estimate that a high vaccine supply in the early phase of the vaccination campaign is key to achieve large gains of strategic prioritizations.

Can a COVID-19 vaccination program guarantee the return to a pre-pandemic lifestyle? (preprint)

COVID-19 vaccination has been initiated in several countries to control SARS-CoV-2 transmission. Whether and when non-pharmaceutical interventions (NPIs) can be lifted as vaccination builds up remains key questions. To address them, we built a data-driven SARS-CoV-2 transmission model for China. We estimated that, to prevent local outbreaks to escalate to major widespread epidemics, stringent NPIs need to remain in place at least one year after the start of vaccination. Should NPIs be capable to keep the reproduction number (Rt) around 1.3, vaccination could reduce up to 99% of COVID-19 burden and bring Rt below the epidemic threshold in 9 months. Maintaining strict NPIs throughout 2021 is of paramount importance to reduce COVID-19 burden while vaccines are distributed, especially in large populations with little natural immunity.

Can a COVID-19 vaccination program guarantee the return to a pre-pandemic lifestyle? (preprint)

COVID-19 vaccination programs have been initiated in several countries to control SARS-CoV-2 transmission and return to a pre-pandemic lifestyle. However, understanding when non-pharmaceutical interventions (NPIs) can be lifted as vaccination builds up and how to update priority groups for vaccination in real-time remain key questions for policy makers. To address these questions, we built a data-driven model of SARS-CoV-2 transmission for China. We estimated that, to prevent local outbreaks to escalate to major widespread epidemics, stringent NPIs need to remain in place at least one year after the start of vaccination. Should NPIs be capable to keep the reproduction number (Rt) around 1.3, a vaccination program could reduce up to 99% of COVID-19 burden and bring Rt below the epidemic threshold in about 9 months. Maintaining strict NPIs throughout 2021 is of paramount importance to reduce COVID-19 burden while vaccines are distributed to the population, especially in large populations with little natural immunity.

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

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.

Disease burden and clinical severity of the first pandemic wave of COVID-19 in Wuhan, China (preprint)

The pandemic of novel coronavirus disease 2019 (COVID-19) began in Wuhan, China, where a first wave of intense community transmission was cut short by interventions. Using multiple data source, we estimated the disease burden and clinical severity of COVID-19 by age in Wuhan from December 1, 2019 to March 31, 2020. We adjusted estimates for sensitivity of laboratory assays and accounted for prospective community screenings and healthcare seeking behaviors. Rates of symptomatic cases, medical consultations, hospitalizations and deaths were estimated at 796 (95%CI: 703-977), 489 (472-509), 370 (358-384), and 36.2 (35.0-37.3) per 100,000 persons, respectively. The COVID-19 outbreak in Wuhan had higher burden than the 2009 influenza pandemic or seasonal influenza, and that clinical severity was similar to that of the 1918 influenza pandemic. Our comparison puts the COVID-19 pandemic into context and could be helpful to guide intervention strategies and preparedness for the potential resurgence of COVID-19.

Age profile of susceptibility, mixing, and social distancing shape the dynamics of the novel coronavirus disease 2019 outbreak in China (preprint)

Strict interventions were successful to control the novel coronavirus (COVID-19) outbreak in China. As transmission intensifies in other countries, the interplay between age, contact patterns, social distancing, susceptibility to infection and disease, and COVID-19 dynamics remains unclear. To answer these questions, we analyze contact surveys data for Wuhan and Shanghai before and during the outbreak and contact tracing information from Hunan Province. Daily contacts were reduced 7-9 fold during the COVID-19 social distancing period, with most interactions restricted to the household. Children 0-14 years were 59% (95% CI 7-82%) less susceptible than individuals 65 years and over. A transmission model calibrated against these data indicates that social distancing alone, as implemented in China during the outbreak, is sufficient to control COVID-19. While proactive school closures cannot interrupt transmission on their own, they reduce peak incidence by half and delay the epidemic. These findings can help guide global intervention policies.

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

Background The 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. Methods We 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. Results The 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. Conclusion Our 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.

Psychological responses, behavioral changes and public perceptions during the early phase of the COVID-19 outbreak in China: a population based cross-sectional survey (preprint)

Objective: To investigate psychological and behavioral responses to the threat of SARS-CoV-2 infections and their associations with public perceptions in China Design: Cross sectional population-based telephone survey via random digital dialing between 1 and 10 February, 2020 Setting: Wuhan (the epicentre and quarantined city), and Shanghai (a typical major city with close transportation link with Wuhan) Participants: Random sample of 510 residents in Wuhan and 501 residents in Shanghai aged above 18 Main outcome measures: Anxiety (measured by the 7-item generalized anxiety disorder [GAD-7] scale), recommended and avoidance behaviors (engaged in all six behaviors such as increasing surface cleaning and reducing going out). Results: The prevalence rates of moderate or severe anxiety (score [≥]10 on GAD-7) were 32.7% (n=167) among Wuhan participants and 20.4% (n=102) among Shanghai participants. 78.6% (n=401) of Wuhan participants and 63.9% (n=320) of Shanghai participants had carried out all six precautionary behaviors. For both measures, Wuhan participants were more responsive to the outbreak (p<0.001). Controlling for personal characteristics, logistic regression results suggested that risks of moderate or severe anxiety were positively associated with perceived susceptibility (odds ratio 1.6, 95% confidence interval 1.3-1.8) and severity of the disease (1.6, 1.4-1.9) and confusion about information reliability (1.6, 1.5-1.9). Having confidence in taking measures to protect oneself against the disease was associated with a lower risk (0.6, 0.5-0.7). The strongest predictor of behavioral change was perceived severity (1.2, 1.1-1.4), followed by confusion about information reliability (1.1, 1.0-1.3). Conclusions: Psychological and behavioral responses to COVID-19 have been dramatic during the rising phase of the outbreak. Our results support efforts for timely dissemination of accurate and reliable information to address the high anxiety level.