Risk Factors Associated with the Spatiotemporal Spread of the SARS-CoV-2 Omicron BA.2 Variant - Shanghai Municipality, China, 2022.

What is already known about this topic?: Previous studies have explored the spatial transmission patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have assessed the associated risk factors. However, none of these studies have quantitatively described the spatiotemporal transmission patterns and risk factors for Omicron BA.2 at the micro (within-city) scale. What is added by this report?: This study highlights the heterogeneous spread of the 2022 Omicron BA.2 epidemic in Shanghai, and identifies associations between different metrics of spatial spread at the subdistrict level and demographic and socioeconomic characteristics of the population, human mobility patterns, and adopted interventions. What are the implications for public health practice?: Disentangling different risk factors might contribute to a deeper understanding of the transmission dynamics and ecology of coronavirus disease 2019 and an effective design of monitoring and management strategies.

Immunogenicity and Safety of Homologous Booster Doses of CoronaVac COVID-19 Vaccine in Elderly Individuals Aged 60 Years and Older: A Dosing Interval Study - Yunnan Province, China, 2021-2022.

What is already known about this topic?: Neutralization levels induced by inactivated vaccines rapidly wane after primary immunization, and a homologous booster can recall specific immune memory, resulting in a remarkable increase in antibody concentration. The optimal interval between primary and booster doses has yet to be determined. What is added by this report?: Booster doses given at three months or more after the two-dose regimen of the CoronaVac COVID-19 vaccine in elderly individuals aged 60 years and older triggered good immune responses. The geometric mean titers of neutralizing antibody on Day 14 after the booster doses increased by 13.3-26.2 fold of baseline levels, reaching 105.45-193.59 in groups with different intervals (e.g., 3, 4, 5, and 6 months). What are the implications for public health practice?: A 4- to 5-month interval between receiving the primary and booster series of CoronaVac could be an alternative to the 6-month interval in order to promote vaccine-induced immunity in elderly individuals. The findings support the optimization of booster immunization strategies.

A Retrospective Modeling Study of the Targeted Non-Pharmaceutical Interventions During the Xinfadi Outbreak in the Early Stage of the COVID-19 Pandemic - Beijing, China, 2020.

What is already known about this topic?: China has repeatedly contained multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks through a comprehensive set of targeted non-pharmaceutical interventions (NPIs). However, the effectiveness of such NPIs has not been systematically assessed. What is added by this report?: A multilayer deployment of case isolation, contact tracing, targeted community lockdowns, and mobility restrictions could potentially contain outbreaks caused by the SARS-CoV-2 ancestral strain, without the requirement of city-wide lockdowns. Mass testing could further aid in the efficacy and speed of containment. What are the implications for public health practice?: Pursuing containment in a timely fashion at the beginning of the pandemic, before the virus had the opportunity to spread and undergo extensive adaptive evolution, could help in averting an overall pandemic disease burden and be socioeconomically cost-effective.

Estimating Changes in Contact Patterns in China Over the First Year of the COVID-19 Pandemic: Implications for SARS-CoV-2 Spread - Four Cities, China, 2020.

Introduction: Previous studies have demonstrated significant changes in social contacts during the first-wave coronavirus disease 2019 (COVID-19) in Chinese mainland. The purpose of this study was to quantify the time-varying contact patterns by age in Chinese mainland in 2020 and evaluate their impact on the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: Diary-based contact surveys were performed for four periods: baseline (prior to 2020), outbreak (February 2020), post-lockdown (March-May 2020), and post-epidemic (September-November 2020). We built a Susceptible-Infected-Recovered (SIR) model to evaluate the effect of reducing contacts on transmission. Results: During the post-epidemic period, daily contacts resumed to 26.7%, 14.8%, 46.8%, and 44.2% of the pre-COVID levels in Wuhan, Shanghai, Shenzhen, and Changsha, respectively. This suggests a moderate risk of resurgence in Changsha, Shenzhen, and Wuhan, and a low risk in Shanghai. School closure alone was not enough to interrupt transmission of SARS-CoV-2 Omicron BA.5, but with the addition of a 75% reduction of contacts at the workplace, it could lead to a 16.8% reduction of the attack rate. To control an outbreak, concerted strategies that target schools, workplaces, and community contacts are needed. Discussion: Monitoring contact patterns by age is key to quantifying the risk of COVID-19 outbreaks and evaluating the impact of intervention strategies.

Modeling the Prediction on the Efficacy of a Homologous Third Dose of CoronaVac Against SARS-CoV-2 Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5 - China, 2020-2021.

What is already known about this topic?: Previous studies have reported vaccine efficacy or effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants for several vaccine platforms. However, there are currently few data on estimates of inactivated platform coronavirus disease 2019 (COVID-19) vaccines, especially against the globally dominant subvariant - Omicron BA.5. What is added by this report?: The study predicts vaccine efficacy against four Omicron subvariants - Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5 - after vaccination with a homologous third dose of CoronaVac across clinical endpoints and age groups. What are the implications for public health practice?: The results suggest that CoronaVac-elicited immunity may not provide adequate protection against Omicron subvariants after the homologous third dose, and a heterologous booster and Omicron-specific vaccination may be alternative strategies.

Epidemiological and clinical characteristics of respiratory syncytial virus and influenza infections in hospitalized children before and during the COVID-19 pandemic in Central China.

Background: Globally, the epidemiology of non-SARS-CoV-2 respiratory viruses like respiratory syncytial virus (RSV) and influenza virus was remarkably influenced by the implementation of non-pharmacological interventions (NPIs) during the COVID-19 pandemic. Our study explored the epidemiological and clinical characteristics of pediatric patients hospitalized with RSV or influenza infection before and during the pandemic after relaxation of NPIs in central China. Methods: This hospital-based prospective case-series study screened pediatric inpatients (age ≤ 14 years) enrolled with acute respiratory infections (ARI) for RSV or influenza infection from 2018 to 2021. The changes in positivity rates of viral detection, epidemiological, and clinical characteristics were analyzed and compared. Results: Median ages of all eligible ARI patients from 2018-2019 were younger than those from 2020-2021, so were ages of cases infected with RSV or influenza (RSV: 4.2 months vs. 7.2 months; influenza: 27.3 months vs. 37.0 months). Where the positivity rate for influenza was considerably decreased in 2020-2021 (1.4%, 27/1964) as compared with 2018-2019 (2.9%, 94/3275, P < 0.05), it was increased for RSV (11.4% [372/3275] vs. 13.3% [262/1964], P < 0.05) in the same period. The number of severe cases for both RSV and influenza infection were also decreased in 2020-2021 compared with 2018-2019. Conclusions: The implemented NPIs have had varied impacts on common respiratory viruses. A more effective prevention strategy for RSV infections in childhood is needed.

Transmission Dynamics and Epidemiological Characteristics of the SARS-CoV-2 Delta Variant - Hunan Province, China, 2021.

What is already known about this topic?: Little is known about the epidemiology, natural history, and transmission patterns of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant. Monitoring the evolution of viral fitness of SARS-CoV-2 in the host population is key for preparedness and response planning. What is added by this report?: We analyzed a successfully contained local outbreak of Delta that took place in Hunan, China, and provided estimates of time-to-key event periods, infectiousness over time, and risk factors for SARS-CoV-2 infection and transmission for a still poorly understood variant. What are the implications for public health practice?: Our findings simultaneously shed light on both the characteristics of the Delta variant, by identifying key age groups, risk factors, and transmission pathways, and planning a future response effort against SARS-CoV-2.

Epidemiological and clinical characteristics of respiratory syncytial virus and influenza infections in hospitalized children before and during the COVID‐19 pandemic in Central China

Background Globally, the epidemiology of non‐SARS‐CoV‐2 respiratory viruses like respiratory syncytial virus (RSV) and influenza virus was remarkably influenced by the implementation of non‐pharmacological interventions (NPIs) during the COVID‐19 pandemic. Our study explored the epidemiological and clinical characteristics of pediatric patients hospitalized with RSV or influenza infection before and during the pandemic after relaxation of NPIs in central China. Methods This hospital‐based prospective case‐series study screened pediatric inpatients (age ≤ 14 years) enrolled with acute respiratory infections (ARI) for RSV or influenza infection from 2018 to 2021. The changes in positivity rates of viral detection, epidemiological, and clinical characteristics were analyzed and compared. Results Median ages of all eligible ARI patients from 2018–2019 were younger than those from 2020–2021, so were ages of cases infected with RSV or influenza (RSV: 4.2 months vs. 7.2 months;influenza: 27.3 months vs. 37.0 months). Where the positivity rate for influenza was considerably decreased in 2020–2021 (1.4%, 27/1964) as compared with 2018–2019 (2.9%, 94/3275, P < 0.05), it was increased for RSV (11.4% [372/3275] vs. 13.3% [262/1964], P < 0.05) in the same period. The number of severe cases for both RSV and influenza infection were also decreased in 2020–2021 compared with 2018–2019. Conclusions The implemented NPIs have had varied impacts on common respiratory viruses. A more effective prevention strategy for RSV infections in childhood is needed.

Vaccination effects on post-infection outcomes in the Omicron BA.2 outbreak in Shanghai.

Omicron and its sublineages are currently predominant and have triggered epidemiological waves of SARS-CoV-2 around the world due to their high transmissibility and strong immune escape ability. Vaccines are key measures to control the COVID-19 burden. Omicron BA.2 caused a large-scale outbreak in Shanghai since March 2022 and resulted in over 0.6 million laboratory-confirmed infections. The vaccine coverage of primary immunization among residents aged 3 years and older in Shanghai exceeded 90%, and inactivated COVID-19 vaccines were mainly delivered. In the context of high vaccine coverage, we conducted a cohort study to assess vaccine effects on reducing the probability of developing symptoms or severity of disease in infections or nonsevere cases. A total of 48,243 eligible participants were included in this study, the majority of whom had asymptomatic infections (31.0%) and mild-to-moderate illness (67.9%). Domestically developed COVID-19 vaccines provide limited protection to prevent asymptomatic infection from developing into mild-to-moderate illness and durable protection to prevent nonsevere illness from progressing to severe illness caused by Omicron BA.2. Partial vaccination fails to provide effective protection in any situation. The level of vaccine effects on disease progression in the elderly over 80 years old was relatively lower compared with other age groups. Our study results added robust evidence for the vaccine performance against Omicron infection and could improve vaccine confidence.

Assessing the feasibility of sustaining SARS-CoV-2 local containment in China in the era of highly transmissible variants.

BACKGROUND: The SARS-CoV-2 containment strategy has been successful in mainland China prior to the emergence of Omicron. However, in the era of highly transmissible variants, whether it is possible for China to sustain a local containment policy and under what conditions China could transition away from it are of paramount importance at the current stage of the pandemic. METHODS: We developed a spatially structured, fully stochastic, individual-based SARS-CoV-2 transmission model to evaluate the feasibility of sustaining SARS-CoV-2 local containment in mainland China considering the Omicron variants, China's current immunization level, and nonpharmaceutical interventions (NPIs). We also built a statistical model to estimate the overall disease burden under various hypothetical mitigation scenarios. RESULTS: We found that due to high transmissibility, neither Omicron BA.1 nor BA.2 could be contained by China's pre-Omicron NPI strategies which were successful prior to the emergence of the Omicron variants. However, increased intervention intensity, such as enhanced population mobility restrictions and multi-round mass testing, could lead to containment success. We estimated that an acute Omicron epidemic wave in mainland China would result in significant number of deaths if China were to reopen under current vaccine coverage with no antiviral uptake, while increasing vaccination coverage and antiviral uptake could substantially reduce the disease burden. CONCLUSIONS: As China's current vaccination has yet to reach high coverage in older populations, NPIs remain essential tools to maintain low levels of infection while building up protective population immunity, ensuring a smooth transition out of the pandemic phase while minimizing the overall disease burden.

Estimation of disease burden and clinical severity of COVID-19 caused by Omicron BA.2 in Shanghai, February-June 2022.

An outbreak of COVID-19 caused by the SARS-CoV-2 Omicron BA.2 sublineage occurred in Shanghai, China from February 26 to June 30, 2022. We use official reported data retrieved from Shanghai municipal Health Commissions to estimate the incidence of infections, severe/critical infections, and deaths to assess the disease burden. By adjusting for right censoring and RT-PCR sensitivity, we provide estimates of clinical severity, including the infection fatality ratio, symptomatic case fatality ratio, and risk of developing severe/critical disease upon infection. The overall infection rate, severe/critical infection rate, and mortality rate were 2.74 (95% CI: 2.73-2.74) per 100 individuals, 6.34 (95% CI: 6.02-6.66) per 100,000 individuals and 2.42 (95% CI: 2.23-2.62) per 100,000 individuals, respectively. The severe/critical infection rate and mortality rate increased with age, noted in individuals aged 80 years or older. The overall fatality ratio and risk of developing severe/critical disease upon infection were 0.09% (95% CI: 0.09-0.10%) and 0.27% (95% CI: 0.24-0.29%), respectively. Having received at least one vaccine dose led to a 10-fold reduction in the risk of death for infected individuals aged 80 years or older. Under the repeated population-based screenings and strict intervention policies implemented in Shanghai, our results found a lower disease burden and mortality of the outbreak compared to other settings and countries, showing the impact of the successful outbreak containment in Shanghai. The estimated low clinical severity of this Omicron BA.2 epidemic in Shanghai highlight the key contribution of vaccination and availability of hospital beds to reduce the risk of death.

Epidemiological characteristics and transmission dynamics of the outbreak caused by the SARS-CoV-2 Omicron variant in Shanghai, China: A descriptive study.

Background: In early March 2022, a major outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spread rapidly throughout Shanghai, China. Here we aimed to provide a description of the epidemiological characteristics and spatiotemporal transmission dynamics of the Omicron outbreak under the population-based screening and lockdown policies implemented in Shanghai. Methods: We extracted individual information on SARS-CoV-2 infections reported between January 1 and May 31, 2022, and on the timeline of the adopted non-pharmaceutical interventions. The epidemic was divided into three phases: i) sporadic infections (January 1-February 28), ii) local transmission (March 1-March 31), and iii) city-wide lockdown (April 1 to May 31). We described the epidemic spread during these three phases and the subdistrict-level spatiotemporal distribution of the infections. To evaluate the impact on the transmission of SARS-CoV-2 of the adopted targeted interventions in Phase 2 and city-wide lockdown in Phase 3, we estimated the dynamics of the net reproduction number (Rt ). Findings: A surge in imported infections in Phase 1 triggered cryptic local transmission of the Omicron variant in early March, resulting in the largest outbreak in mainland China since the original wave. A total of 626,000 SARS-CoV-2 infections were reported in 99.5% (215/216) of the subdistricts of Shanghai until the end of May. The spatial distribution of the infections was highly heterogeneous, with 37% of the subdistricts accounting for 80% of all infections. A clear trend from the city center towards adjacent suburban and rural areas was observed, with a progressive slowdown of the epidemic spread (from 463 to 244 meters/day) prior to the citywide lockdown. During Phase 2, Rt remained well above 1 despite the implementation of multiple targeted interventions. The citywide lockdown imposed on April 1 led to a marked decrease in transmission, bringing Rt below the epidemic threshold in the entire city on April 14 and ultimately leading to containment of the outbreak. Interpretation: Our results highlight the risk of widespread outbreaks in mainland China, particularly under the heightened pressure of imported infections. The targeted interventions adopted in March 2022 were not capable of halting transmission, and the implementation of a strict, prolonged city-wide lockdown was needed to successfully contain the outbreak, highlighting the challenges for containing Omicron outbreaks. Funding: Key Program of the National Natural Science Foundation of China (82130093); Shanghai Rising-Star Program (22QA1402300).

Assessing spread risk of COVID-19 within and beyond China in early 2020

A novel coronavirus emerged in Wuhan in late 2019 and has caused the COVID-19 pandemic announced by the World Health Organization on March 12, 2020. This study was originally conducted in January 2020 to estimate the potential risk and geographic range of COVID-19 spread within and beyond China at the early stage of the pandemic. A series of connectivity and risk analyses based on domestic and international travel networks were conducted using historical aggregated mobile phone data and air passenger itinerary data. We found that the cordon sanitaire of Wuhan was likely to have occurred during the latter stages of peak population numbers leaving the city, with travellers departing into neighbouring cities and other megacities in China. We estimated that 59,912 air passengers, of which 834 (95% uncertainty interval: 478–1349) had COVID-19 infection, travelled from Wuhan to 382 cities outside of mainland China during the two weeks prior to the city’s lockdown. Most of these destinations were located in Asia, but major hubs in Europe, the US and Australia were also prominent, with a strong correlation seen between the predicted risks of importation and the number of imported cases found. Given the limited understanding of emerging infectious diseases in the very early stages of outbreaks, our approaches and findings in assessing travel patterns and risk of transmission can help guide public health preparedness and intervention design for new COVID-19 waves caused by variants of concern and future pandemics to effectively limit transmission beyond its initial extent.

Comparison of Neutralizing Antibody Response Kinetics in Patients with Hand, Foot, and Mouth Disease Caused by Coxsackievirus A16 or Enterovirus A71: A Longitudinal Cohort Study of Chinese Children, 2017-2019.

Hand, foot, and mouth disease (HFMD), which is mainly caused by coxsackievirus A16 (CVA16) or enterovirus A71 (EV-A71), poses a serious threat to children's health. However, the long-term dynamics of the neutralizing Ab (NAb) response and ideal paired-serum sampling time for serological diagnosis of CVA16-infected HFMD patients were unclear. In this study, 336 CVA16 and 253 EV-A71 PCR-positive HFMD inpatients were enrolled and provided 452 and 495 sera, respectively, for NAb detection. Random-intercept modeling with B-spline was conducted to characterize NAb response kinetics. The NAb titer of CVA16 infection patients was estimated to increase from negative (2.1, 95% confidence interval [CI]: 1.4-3.3) on the day of onset to a peak of 304.8 (95% CI: 233.4-398.3) on day 21 and then remained >64 until 26 mo after onset. However, the NAb response level of EV-A71-infected HFMD patients was much higher than that of CVA16-infected HFMD patients throughout. The geometric mean titer was significantly higher in severe EV-A71-infected patients than in mild patients, with a 2.0-fold (95% CI: 1.4-3.2) increase. When a 4-fold rise in titer was used as the criterion for serological diagnosis of CVA16 and EV-A71 infection, acute-phase serum needs to be collected at 0-5 d, and the corresponding convalescent serum should be respectively collected at 17.4 (95% CI: 9.6-27.4) and 24.4 d (95% CI: 15.3-38.3) after onset, respectively. In conclusion, both CVA16 and EV-A71 infection induce a persistent humoral immune response but have different NAb response levels and paired-serum sampling times for serological diagnosis. Clinical severity can affect the anti-EV-A71 NAb response.

Six-month follow-up of a booster dose of CoronaVac in two single-centre phase 2 clinical trials.

Determining the duration of immunity induced by booster doses of CoronaVac is crucial for informing recommendations for booster regimens and adjusting immunization strategies. In two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, immunogenicity and safety of four immunization regimens are assessed in adults aged 18 to 59 years and one immunization regimen in adults aged 60 years and older, respectively. Serious adverse events occurring within 6 months after booster doses are recorded as pre-specified secondary endpoints, geometric mean titres (GMTs) of neutralising antibodies one year after the 3-dose schedule immunization and 6 months after the booster doses are assessed as pre-specified exploratory endpoints, GMT fold-decreases in neutralization titres are assessed as post-hoc analyses. Neutralising antibody titres decline approximately 4-fold and 2.5-fold from day 28 to day 180 after third doses in adults aged 18-59 years of age and in adults aged 60 years and older, respectively. No safety concerns are identified during the follow-up period. There are increases in the magnitude and duration of humoral response with homologous booster doses of CoronaVac given 8 months after a primary two-dose immunization series, which could prolong protection and contribute to building our wall of population immunity. Trial number: NCT04352608 and NCT04383574.

Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials.

BACKGROUND: Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. METHODS: In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 µg dose or 6 µg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 µg, 3 µg, or 6 µg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 µg groups, since 3 µg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574. FINDINGS: 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 µg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. INTERPRETATION: A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. FUNDING: National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Modeling transmission of SARS-CoV-2 Omicron in China.

Having adopted a dynamic zero-COVID strategy to respond to SARS-CoV-2 variants with higher transmissibility since August 2021, China is now considering whether, and for how long, this policy can remain in place. The debate has thus shifted towards the identification of mitigation strategies for minimizing disruption to the healthcare system in the case of a nationwide epidemic. To this aim, we developed an age-structured stochastic compartmental susceptible-latent-infectious-removed-susceptible model of SARS-CoV-2 transmission calibrated on the initial growth phase for the 2022 Omicron outbreak in Shanghai, to project COVID-19 burden (that is, number of cases, patients requiring hospitalization and intensive care, and deaths) under hypothetical mitigation scenarios. The model also considers age-specific vaccine coverage data, vaccine efficacy against different clinical endpoints, waning of immunity, different antiviral therapies and nonpharmaceutical interventions. We find that the level of immunity induced by the March 2022 vaccination campaign would be insufficient to prevent an Omicron wave that would result in exceeding critical care capacity with a projected intensive care unit peak demand of 15.6 times the existing capacity and causing approximately 1.55 million deaths. However, we also estimate that protecting vulnerable individuals by ensuring accessibility to vaccines and antiviral therapies, and maintaining implementation of nonpharmaceutical interventions could be sufficient to prevent overwhelming the healthcare system, suggesting that these factors should be points of emphasis in future mitigation policies.

Assessing the transition of COVID-19 burden towards the young population while vaccines are rolled out in China.

SARS-CoV-2 infection causes most cases of severe illness and fatality in older age groups. Over 92% of the Chinese population aged ≥12 years has been fully vaccinated against COVID-19 (albeit with vaccines developed against historical lineages). At the end of October 2021, the vaccination programme has been extended to children aged 3-11 years. Here, we aim to assess whether, in this vaccination landscape, the importation of Delta variant infections could shift COVID-19 burden from adults to children. We developed an age-structured susceptible-infectious-removed model of SARS-CoV-2 transmission to simulate epidemics triggered by the importation of Delta variant infections and project the age-specific incidence of SARS-CoV-2 infections, cases, hospitalizations, intensive care unit admissions, and deaths. In the context of the vaccination programme targeting individuals aged ≥12 years, 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 89% 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 hospitalizations within this age group (39% and 68%, respectively, when considering a vaccination coverage of 87%), but would have a low impact on protecting infants. Our findings highlight the importance of including children among the target population and the need to strengthen vaccination efforts by increasing vaccine effectiveness.

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

BACKGROUND: Hundreds of millions of doses of coronavirus disease 2019 (COVID-19) vaccines have been administered globally, but progress on vaccination varies considerably between countries. We aimed 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 8 February 2022. 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. RESULTS: Messenger RNA and adenovirus vectored vaccines were the most commonly used COVID-19 vaccines in high-income countries, while adenovirus vectored vaccines were the most widely used vaccines worldwide (180 countries). One hundred ninety-two countries have authorized vaccines for the general public, with 40.1% (77/192) targeting individuals over 12 years and 32.3% (62/192) targeting those ≥ 5 years. Forty-eight and 151 countries have started additional-dose and booster-dose vaccination programs, respectively. Globally, there have been 162.1 doses administered per 100 individuals in target populations, with marked inter-region and inter-country heterogeneity. Completed vaccination series coverage ranged from 0.1% to more than 95.0% of country target populations, and numbers of doses administered per 100 individuals in target populations ranged from 0.2 to 308.6. Doses administered per 100 individuals in whole populations correlated with healthcare access and quality index (R2 = 0.59), socio-demographic index (R2 = 0.52), and gross domestic product per capita (R2 = 0.61). At least 6.4 billion doses will be required to complete interim vaccination programs-3.3 billion for primary immunization and 3.1 billion for additional/booster programs. Globally, 0.53 and 0.74 doses per individual in target populations are needed for primary immunization and additional/booster dose programs, respectively. CONCLUSIONS: There is wide country-level disparity and inequity in COVID-19 vaccines rollout, suggesting large gaps in immunity, especially in low-income countries.

Global landscape of SARS-CoV-2 genomic surveillance and data sharing.

Genomic surveillance has shaped our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. We performed a global landscape analysis on SARS-CoV-2 genomic surveillance and genomic data using a collection of country-specific data. Here, we characterize increasing circulation of the Alpha variant in early 2021, subsequently replaced by the Delta variant around May 2021. SARS-CoV-2 genomic surveillance and sequencing availability varied markedly across countries, with 45 countries performing a high level of routine genomic surveillance and 96 countries with a high availability of SARS-CoV-2 sequencing. We also observed a marked heterogeneity of sequencing percentage, sequencing technologies, turnaround time and completeness of released metadata across regions and income groups. A total of 37% of countries with explicit reporting on variants shared less than half of their sequences of variants of concern (VOCs) in public repositories. Our findings indicate an urgent need to increase timely and full sharing of sequences, the standardization of metadata files and support for countries with limited sequencing and bioinformatics capacity.