Safety, Immunogenicity, and Effectiveness of Chinese-Made COVID-19 Vaccines in the Real World: An Interim Report of a Living Systematic Review.

Background: Several COVID-19 vaccines were developed and approved in China. Of these, the BIBB-CorV and CoronaVac inactivated whole-virion vaccines were widely distributed in China and developing countries. However, the performance of the two vaccines in the real world has not been summarized. Methods: A living systematic review based on findings from ongoing post-licensure studies was conducted, applying standardized algorithms. Articles published between 1 May 2020 and 31 May 2022 in English and Chinese were searched for in Medline, Embase, WanFang Data, medRxiv, bioRxiv, arXiv, SSRN, and Research Square, using SARS-CoV-2, COVID-19, and vaccine as the MeSH terms. Studies with estimates of safety, immunogenicity, and effectiveness from receiving the BIBB-CorV or CoronaVac vaccine that met the predefined screening criteria underwent a full-text review. The Joanna Briggs Institute's Critical Appraisal Checklist and the Cochrane risk of bias were used for assessment of the quality. A random-effects meta-regression model was applied to identify the potential impact factors on the vaccines' effectiveness. Results: In total, 32578 articles were identified, of these, 770 studies underwent a full-text review. Eventually, 213 studies were included. The pooled occurrence of solicited and unsolicited adverse events after any dose of either vaccine varied between 10% and 40%. The top five commonly reported rare adverse events were immunization stress-related responses (211 cases, 50.0%), cutaneous responses (43 cases, 10.2%), acute neurological syndrome (39 cases, 9.2%), anaphylaxis (17 cases, 4.0%), and acute stroke (16 cases, 3.8%). The majority (83.3%) recovered or were relieved within several days. The peak neutralization titers against the ancestral strain was found within 1 month after the completion of the primary series of either vaccine, with a GMT (geometric mean titer) of 43.7 (95% CI: 23.2-82.4), followed by a dramatic decrease within 3 months. At Month 12, the GMT was 4.1 (95% CI: 3.8-4.4). Homologous boosting could restore humoral immunity, while heterologous boosting elicited around sixfold higher neutralization titers in comparison with homologous boosting. The effectiveness of receiving either vaccine against death and severe disease was around 85% for both shortly after the primary series. At Month 12, the protection against death did not decline, while the protection against severe disease decreased to ~75%. Conclusions: Both the BIBP-CorV and CoronaVac inactivated vaccines are safe. Sustained vaccine effectiveness against death was determined 12 months after the primary series, although protection against severe disease decreased slightly over time. A booster dose could strengthen the waning effectiveness; however, the duration of the incremental effectiveness and the additional benefit provided by a heterologous booster need to be studied.

The COVID-19 Vaccines Evaluation Program: Implementation, Management, and Experiences, 2021-2023.

In 2021, China's domestically produced coronavirus disease 2019 (COVID-19) vaccines received approval from regulatory bodies and were administered worldwide. Due to a low number of infections within China during that period, it became imperative to evaluate the vaccines' real-world effectiveness through international studies. To facilitate this, China CDC launched the COVID-19 Vaccines Evaluation Program (COVEP). This program formed research collaboration agreements with health institutes across five World Health Organization regions, addressing key questions about vaccine performance through ten cooperative agreements. The findings from COVEP projects reinforced confidence, both domestically and globally, in the effectiveness of the vaccines produced in China. Moreover, the outcomes observed internationally were frequently mirrored by later studies conducted within China. COVEP thus pioneered a novel approach for fostering cross-national research collaborations, addressing significant public health issues and exemplifying a framework for international cooperation. This approach is in line with the strategic objectives and other development efforts of China CDC's national disease control and prevention initiatives.

The Epidemiological Characteristics and Spatiotemporal Clustering of Measles - China, 2005-2022.

Introduction: In recent years, the incidence of measles in China has consistently remained below 1 per 100,000 population, yet the disease has not been eliminated. This study aims to comprehensively analyze the epidemiological characteristics of measles from 2005 to 2022, identify high-risk populations and areas, and propose targeted interventions. Methods: We utilized data from the China Disease Prevention and Control Information System for our comprehensive analysis. Spatial autocorrelation was employed to examine the spatial clustering of measles, while spatiotemporal scanning analysis was used to detect spatiotemporal clustering to describe measles epidemiology during the study period. Results: Between 2005 and 2022, 732,218 measles cases were reported in China. Overall, the incidence of measles exhibited a downward trend, particularly during the periods of 2008-2011 and 2015-2022. In 2022, the incidence rate reached its historical low at 0.039 per 100,000 population. Measles predominantly affects young children. Since 2017, global spatial clustering has diminished, although hotspot areas persist in the western provinces. Spatial-temporal scanning identified a high-incidence cluster from 2005 to 2008, comprising 15 provinces in the western, central, and northern regions of China. Conversely, from 2016 to 2022, a low-incidence cluster was detected in the southern and central provinces. Conclusions: China has made significant progress in measles prevention and control. The recent low incidence and absence of substantial spatiotemporal clustering indicate that China is nearing measles elimination. However, there is a continuing need to enhance prevention and control efforts among very young children and in historic incidence hotspots in western provinces. Additionally, improving the diagnosis of vaccine-associated rash illnesses is essential.

Impact of National Immunization Strategies on Vaccine-Preventable Diseases - China, 1950-2021.

What is already known about this topic?: The incidences of vaccine-preventable diseases (VPDs) included in the Expanded Program on Immunization in China have decreased significantly in recent decades. What is added by this report?: This study summarizes the national incidences of nine VPDs and the seroprevalence of hepatitis B surface antigen (HBsAg) under different immunization strategies from 1950 through 2021 in China. The sharpest decreases in VPD incidence and under-5-year HBsAg seroprevalence occurred during the latest stage of the National Immunization Program. The decreases in VPD incidence were most prominent among children under five years of age. What are the implications for public health practice?: These findings provide valuable insights for vaccine value assessment and emphasize the importance of implementing immunization strategies in targeted populations.

Comparison of Statistical Signal Detection Methods in Adverse Events Following Immunization - China, 2011-2015.

Introduction: The current study aims to assess the performance of data mining techniques in detecting safety signals for adverse events following immunization (AEFI) using routinely obtained data in China. Four different methods for detecting vaccine safety signals were evaluated. Methods: The AEFI data from 2011 to 2015 was collected for our study. We analyzed the data using four different methods to detect signals: the proportional reporting ratio (PRR), reporting odds ratio (ROR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). Each method was evaluated at 1-3 thresholds for positivity. To assess the performance of these methods, we used the published signal rates as gold standards to determine the sensitivity and specificity. Results: The number of identified signals varied from 602 for PRR1 (with a threshold of 1) to 127 for MGPS1. When considering the common reactions as the reference standard, the sensitivity ranged from 0.9% for MGPS1/2 to 38.2% for PRR1/2, and the specificity ranged from 85.2% for PRR1 and ROR1 to 96.7% for MGPS1. When considering the rare reactions as the reference standard, PRR1, PRR2, ROR1, ROR2, and BCPNN exhibited the highest sensitivity (73.3%), while MGPS1 exhibited the highest specificity (96.9%). Discussion: For common reactions, the sensitivities were modest and the specificities were high. For rare reactions, both the sensitivities and specificities were high. Our study provides valuable insights into the selection of signal detection methods and thresholds for AEFI data in China.

Thirty Years of Experience of Acute Flaccid Paralysis Surveillance for Polio - China, 1993-2022.

Introduction: Detecting poliovirus infections proves to be highly challenging due to their asymptomatic nature and infectious potential, highlighting the crucial importance of effective detection methods in the context of polio eradication efforts. In many countries, including China, the primary approach for identifying polio outbreaks has been through acute flaccid paralysis (AFP) surveillance. In this study, we conducted an evaluation spanning three decades (1993-2022) to assess the effectiveness of AFP surveillance in China. Methods: Data on all AFP cases identified since 1993 and national-level AFP surveillance system quality indicators aligned with the World Health Organization (WHO) standards were collected for analysis. The quality indicators assess surveillance sensitivity, completeness, timeliness of detection notification, case investigation, and laboratory workup. Surveillance sensitivity is determined by the non-polio AFP (NPAFP) detection rate among children under 15 years of age. Results: Between 1993 and 2022, a total of 150,779 AFP cases were identified and reported. Within this pool, surveillance identified 95 cases of wild poliovirus (WPV) and 24 cases due to vaccine-derived poliovirus. From 1995 onwards, the detection rate of NPAFP cases consistently adhered to the WHO and national standards of ≥1 case per 100,000, falling between 1.38 and 2.76. Starting in 1997, all timeliness indicators consistently achieved the criteria of 80%, apart from the consistency in meeting standards set for the rate of positive specimens sent to the national laboratory. Conclusions: AFP surveillance has been instrumental in China's accomplishment of maintaining a polio-free status. The ongoing adherence to key performance indicators, ensuring sensitivity and prompt specimen collection, demonstrates that AFP surveillance is proficient in detecting poliovirus in China. As we move into the post-eradication phase, AFP surveillance remains crucial for the sustained absence of polioviruses in the long term.

Relative effectiveness of a heterologous booster dose with adenovirus type 5 vectored COVID-19 vaccine versus three doses of inactivated COVID-19 vaccine in adults during a nationwide outbreak of omicron predominance, in China: a retrospective, individually matched cohort-control study.

Effectiveness of heterologous booster regimes with ad5 vectored COVID-19 vaccine in a large, diverse population during the national-scale outbreak of SARS-CoV-2 omicron predominance in China has not been reported, yet. We conducted a large-scale cohort-control study in six provinces in China, and did a retrospective survey on the COVID-19 attack risk during this outbreak. Participant aged ≥18 years in five previous trials who were primed with 1 to 3 doses of ICV received heterologous booster with either intramuscular or orally inhaled ad5 vectored COVID-19 vaccine were included in the heterologous-trial cohort. We performed propensity score-matching at a ratio of 1:4 to match participants in the heterologous-trial cohort individually with the community individuals who received three-dose of ICV as a control (ICV-community cohort). From February 4 to April 10, 2023, 41504 (74.5%) of 55710 individuals completed the survey. The median time since the most recent vaccination to the onset of the symptoms of COVID-19 was 303.0 days (IQR 293.0-322.0). The attack rate of COVID-19 in the heterologous-trial cohort was 55.8%, while that in the ICV-community cohort was 64.6%, resulting in a relative effectiveness of 13.7% (95% CI 11.9 to 15.3). In addition, a higher relative effectiveness against COVID-19 associated outpatient visits, and admission to hospital was demonstrated, which was 25.1% (95% CI 18.9 to 30.9), and 48.9% (95% CI 27.0 to 64.2), respectively. The heterologous booster with ad5 vectored COVID-19 vaccine still offered some additional protection in preventing COVID-19 breakthrough infection versus homologous three-dose regimen with ICV, 10 months after vaccination.

Acceptance and willingness to pay for DTaP-HBV-IPV-Hib hexavalent vaccine among parents: A cross-sectional survey in China.

DTaP-HBV-IPV-Hib hexavalent vaccine has been used in high-income countries for many years to prevent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and invasive Haemophilus influenzae type b disease. Currently, no hexavalent vaccines have been approved for use in China. Evidence of parental acceptance and interest in hexavalent vaccines can help policy makers and manufacturers make decisions about entering the vaccine market and the immunization program in China. We measured parental acceptance and willingness-to-pay (WTP) for a hexavalent vaccine to provide such evidence. We conducted a cross-sectional survey of children's caregivers in 16 vaccination clinics in seven cities in China and obtained information on socio-demographics, knowledge of disease, confidence in vaccines, previous vaccination experience, and acceptance of and WTP for hexavalent vaccine. Multivariate logistic regression was used to determine factors influencing acceptance, and multivariate tobit regression was used to identify factors impacting WTP. Between April 28 and June 30, 2023, a total of 581 parents of children aged 0-6 years participated in the survey; 435 (74.87%, 95% CI:71.3%-78.4%) parents indicated acceptance of hexavalent vaccine. Residence location, parents' education level, experience paying for vaccination, and disease knowledge scores were key factors affecting parents' choices for vaccination. Mean (SD) and median (IQR) willingness to pay for full 4-dose course vaccination were 2266.66 (1177.1) CNY and 2400 (1600-2800) CNY. Children's age (p < .001), parents' education level (p = .024), and perceived price barriers (p < .001) were significantly associated with WTP. Parents have high acceptance and willingness to pay for hexavalent vaccine. The less money parents have to pay out of pocket, the more willing they can be to accept the vaccine. Therefore, acceptance may increase even further if the vaccine is covered by medical insurance, provided free of charge by the government, or if its price is reduced. Our results provide reference for optimizing and adjusting immunization strategies in China.

An Observational Prospective Cohort Study of Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection of an Aerosolized, Inhaled Adenovirus Type 5-Vectored Coronavirus Disease 2019 Vaccine Given as a Second Booster Dose in Guangzhou City, China.

Using a prospective, observational cohort study during the post-"dynamic COVID-zero" wave in China, we estimated short-term relative effectiveness against Omicron BA.5 infection of inhaled aerosolized adenovirus type 5-vectored ancestral strain coronavirus disease 2019 (COVID-19) vaccine as a second booster dose approximately 1 year after homologous boosted primary series of inactivated COVID-19 vaccine compared with no second booster. Participants reported nucleic acid or antigen test results weekly until they tested positive or completed predesignated follow-up. After excluding participants infected <14 days after study entry, relative effectiveness among the 6576 participants was 61% in 18- to 59-year-olds and 38% in ≥60-year-olds and was sustained for 12 weeks.

Neutralizing antibody levels associated with injectable and aerosolized Ad5-nCoV boosters and BA.2 infection.

BACKGROUND: Several COVID-19 vaccines are in widespread use in China. Few data exist on comparative immunogenicity of different COVID-19 vaccines given as booster doses. We aimed to assess neutralizing antibody levels raised by injectable and inhaled aerosolized recombinant adenovirus type 5 (Ad5)-vectored COVID-19 vaccine as a heterologous booster after an inactivated COVID-19 vaccine two-dose primary series. METHODS: Using an open-label prospective cohort design, we recruited 136 individuals who had received inactivated vaccine primary series followed by either injectable or inhaled Ad5-vectored vaccine and measured neutralizing antibody titers against ancestral SARS-CoV-2 virus and Omicron BA.1 and BA.5 variants. We also measured neutralizing antibody levels in convalescent sera from 39 patients who recovered from Omicron BA.2 infection. RESULTS: Six months after primary series vaccination, neutralizing immunity against ancestral SARS-CoV-2 was low and neutralizing immunity against Omicron (B.1.1.529) was lower. Boosting with Ad5-vectored vaccines induced a high immune response against ancestral SARS-CoV-2. Neutralizing responses against Omicron BA.5 were ≥ 80% lower than against ancestral SARS-CoV-2 in sera from prime-boost subjects and in convalescent sera from survivors of Omicron BA.2 infection. Inhaled aerosolized Ad5-vectored vaccine was associated with greater neutralizing titers than injectable Ad5-vectored vaccine against ancestral and Omicron SARS-CoV-2 variants. CONCLUSIONS: These findings support the current strategy of heterologous boosting with injectable or inhaled Ad5-vectored SARS-CoV-2 vaccination of individuals primed with inactivated COVID-19 vaccine.

Impact of Influenza and Pneumococcal Polysaccharide Vaccination on Economic Burden from Acute Exacerbations of Chronic Obstructive Pulmonary Disease - Hebei Province, China, November 2018 to November 2020.

What is already known on this topic?: Chronic obstructive pulmonary disease (COPD) exacerbations increase household economic burden, but there is limited evidence from prospective cohort studies in China about the impact of vaccination on economic burden. What is added by this report?: This study demonstrated the economic burden of COPD exacerbations, pneumonia, and hospitalization in COPD patients in China is substantial. Influenza vaccine and 23-valent pneumococcal polysaccharide vaccine (PPSV23), separately or together, were significantly associated with decreased economic burden. What are the implications for public health practice?: Our study supports evidence on recommendations that COPD patients in China are offered both influenza vaccine and PPSV23.

Survey on Immunization Services for Children with Medical Conditions - China, 2022.

What is already known about this topic?: Children with medical conditions frequently experience under-immunization. Ensuring high-quality immunization services is crucial for enhancing vaccination coverage levels; nevertheless, the state of immunization service provision for children with medical conditions in China remains unclear. What is added by this report?: Immunization support for children with medical conditions in China demonstrates considerable variability and may be inadequate. Primary obstacles to the provision of immunization services include an absence of comprehensive vaccination recommendations and assessment guidelines for specific medical conditions, as well as inconsistencies among vaccine recommendations, package inserts, and expert consensus statements pertaining to the vaccination of children with medical conditions. What are the implications for public health practice?: The examination of provincial practices in providing immunization services for children with medical conditions, as well as understanding the barriers faced by National Immunization Program providers in administering vaccinations, can contribute to the improvement of immunization services for this population in China.

Safety, immunogenicity and protection of heterologous boost with an aerosolised Ad5-nCoV after two-dose inactivated COVID-19 vaccines in adults: a multicentre, open-label phase 3 trial.

BACKGROUND: Aerosolised Ad5-nCoV is one of the first licensed mucosal respiratory vaccine against SARS-CoV-2 in the world; however, the safety profile of this vaccine has not been reported in a large population yet. METHODS: This multicentre, open-label phase 3 trial, done in 15 centres in six provinces (Jiangsu, Hunan, Anhui, Chongqing, Yunnan, Shandong) in China, aimed to evaluate the safety and immunogenicity of aerosolised Ad5-nCoV in healthy adults (members of the general population with no acute febrile disorders, infectious disease, serious cardiovascular diseases, serious chronic diseases or progressive diseases that cannot be controlled) at least 18 years old, who had received two doses of inactivated COVID-19 vaccine as their primary regimen. This study contained a non-randomly assigned safety cohort and a centrally randomly assigned (1:1) immunogenicity subcohort. The patients in the immunogenicity subcohort received aerosolised Ad5-nCov (aerosolised Ad5-nCoV group) or inactivated vaccine (inactivated COVID-19 group) The primary endpoints were the incidence of adverse reactions within 28 days following the booster vaccination with aerosolised Ad5-nCoV in the safety population (collected through a daily record of any solicited or unsolicited adverse events filled by each participant) and the geometric mean titre of neutralising antibodies at day 28 after the booster dose in the immunogenicity subcohort (measured with a pseudovirus neutralisation test). This study was registered with ClinicalTrials.gov, NCT05204589. FINDINGS: Between Jan 22, 2022, and March 12, 2022, we recruited 11 410 participants who were screened for eligibility, of whom 10 267 (99·8%) participants (5738 [55·9%] men, 4529 [44·1%] women; median age 53 years [18-92]) received the study drugs: 9847 (95·9%) participants in the open-label cohort to receive aerosolised Ad5-nCoV, and 420 (4·1%) in the immunogenicity subcohort (212 in the aerosolised Ad5-nCoV group and 208 in the inactivated vaccine group). Adverse reactions were reported by 1299 (13%) of 10 059 participants within 28 days after receiving the booster vaccination with aerosolised Ad5-nCoV, but most of the adverse reactions reported were mild to moderate in severity. Participants in the aerosolised Ad5-nCoV group had a significantly higher level of the neutralising antibodies against omicron BA.4/5 (GMT 107·7 [95% CI 88·8-130·7]) than did those in the inactivated vaccine group (17·2 [16·3-18·2]) at day 28. INTERPRETATION: The heterologous booster regimen with aerosolised Ad5-nCoV is safe and highly immunogenic, boosting both systemic and mucosal immunity against omicron subvariants. FUNDING: National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Assessing vaccine hesitancy using the WHO scale for caregivers of children under 3 years old in China.

Introduction: Vaccine hesitancy may increase infectious disease burden and impede disease control efforts, while few studies have measured such a phenomenon with a standardized tool in China. This study aimed to test the validation of the Vaccine Hesitancy Scale (VHS) developed by the WHO SAGE Working Group among caregivers and examine demographic characteristics associated with caregiver hesitancy in six provinces of China. Methods: Using a multistage sampling design, this study was conducted in 36 immunization clinics in six provinces from December 2019 to August 2020. Caregivers of children aged 0-3 years were included. The VHS was used to assess vaccine hesitancy. The construct validity and internal consistency of the scale were assessed. Associations between caregivers' characteristics and vaccine hesitancy were examined by simple and multiple linear regression models. Results: Of the 3,359 participants included, a two-factor structure within the scale was identified, consisting of "lack of confidence" (1.89 ± 0.53) and "risks" (3.20 ± 0.75). Caregivers engaged in medical work expressed more confidence and were less concerned about risks compared to those of non-medical staff (p < 0.05). Participants with higher income levels were more confident (p < 0.05), while those surveyed after the COVID-19 pandemic, who were mothers, who had an older child, or who were raising a second or above birth child, had less concern about risks (p < 0.05). Discussion: We found that the VHS had acceptable reliability and construct validity and caregivers' hesitancy was driven more by concerns about risks than by the lack of confidence. Countering these concerns will be particularly important among non-medical staff, lower income, child's fathers, having a younger child, or raising first-birth child groups.

Effectiveness of DTaP Against Pertussis in ≤2-Year-Old Children - Linyi Prefecture, Shandong Province, China, 2017-2019.

What is already known about this topic?: Vaccine effectiveness (VE) is positively correlated with the number of administered co-purified diphtheria, tetanus, and acellular pertussis vaccine (DTaP) doses. A matched case-control study conducted in Zhongshan City revealed that the co-purified DTaP VE against pertussis-related illnesses in children aged 4-11 months was 42% for one dose, 88% for two doses, and 95% for three doses, respectively. What is added by this report?: The results of this study contribute to the current body of research. We found that the VE of co-purified DTaP against pertussis-related illness and hospitalization increased substantially, ranging from 24%-26% after one dose to 86%-87% after four doses. What are the implications for public health practice?: The results of this study underscore the significance of prompt and comprehensive immunization using co-purified DTaP to decrease the incidence of pertussis. Additionally, these findings offer evidence supporting the modification of China's pertussis vaccination approach.

Multiple rib and vertebral fractures associated with Bordetella pertussis infection: a case report.

BACKGROUND: Pertussis is a highly contagious respiratory disease caused by the bacterium Bordetella pertussis, characterized by paroxysms of severe coughing, and predominantly affects children. We report the first case of multiple fractures in the ribs, lumbar spine, and sacrum associated with severe coughing caused by Bordetella pertussis infection in an adult. CASE PRESENTATION: A 49-year-old female presented with acute-onset chest wall pain for 3 weeks. Imaging results revealed multiple fractures in the ribs and vertebrae, as well as bilateral pleural effusion, pericardial effusion, right pneumothorax, and enlargement of the left parapharyngeal and subclavian lymph nodes. The patient's bone density scan, autoimmune antibodies, bone marrow biopsy, and sacral bone biopsy all came back normal. Imaging test results found no evidence of solid tumors or active TB infection. The patient later recalled having violent coughing prior to the onset of chest pain and several family members having similar symptoms. Her blood sample was sent to the CDC, revealing Bordetella pertussis toxin (PT) IgG titer of 110.68 IU/mL. The patient was diagnosed with pertussis and multiple stress fractures from violent coughing. Symptomatic treatments were administered, and the patient's symptoms improved. The patient was followed up 8 weeks later, she reported no more coughing or chest pain. CONCLUSIONS: Pertussis is not just a pediatric disease, but diagnosis in adults is challenging as patients may present with a myriad of confusing symptoms, such as multiple stress fractures due to violent coughing. Medical and epidemiological histories are key to reaching the correct diagnosis, which is essential for appropriate treatments to avoid further complications. Adult immunization should be suggested both for the protection of the adult population and to prevent transmission to children.

Real-World Effectiveness of Primary Series and Booster Doses of Inactivated Coronavirus Disease 2019 Vaccine Against Omicron BA.2 Variant Infection in China: A Retrospective Cohort Study.

BACKGROUND: China has been using inactivated coronavirus disease 2019 (COVID-19) vaccines as primary series and booster doses to protect the population from severe to fatal COVID-19. We evaluated primary and booster vaccine effectiveness (VE) against Omicron BA.2 infection outcomes. METHODS: This was a 13-province retrospective cohort study of quarantined close contacts of BA.2-infected individuals. Outcomes were BA.2 infection, COVID-19 pneumonia or worse, and severe/critical COVID-19. Absolute VE was estimated by comparison with an unvaccinated group. RESULTS: There were 289 427 close contacts ≥3 years old exposed to Omicron BA.2 cases; 31 831 turned nucleic acid amplification test-positive during quarantine, 97.2% with mild or asymptomatic infection, 2.6% with COVID-19 pneumonia, and 0.15% with severe/critical COVID-19. None died. Adjusted VE (aVE) against any infection was 17% for primary series and 22% when boosted. Primary series aVE in adults >18 years was 66% against COVID-19 pneumonia or worse and 91% against severe/critical COVID-19. Booster dose aVE was 74% against pneumonia or worse, and 93% against severe/critical COVID-19. CONCLUSIONS: Inactivated COVID-19 vaccines provided modest protection from infection, very good protection against pneumonia, and excellent protection against severe/critical COVID-19. Booster doses are necessary to provide strongest protection.

Real-world effectiveness and factors associated with effectiveness of inactivated SARS-CoV-2 vaccines: a systematic review and meta-regression analysis.

BACKGROUND: The two inactivated SARS-CoV-2 vaccines, CoronaVac and BBIBP-CorV, have been widely used to control the COVID-19 pandemic. The influence of multiple factors on inactivated vaccine effectiveness (VE) during long-term use and against variants is not well understood. METHODS: We selected published or preprinted articles from PubMed, Embase, Scopus, Web of Science, medRxiv, BioRxiv, and the WHO COVID-19 database by 31 August 2022. We included observational studies that assessed the VE of completed primary series or homologous booster against SARS-CoV-2 infection or severe COVID-19. We used DerSimonian and Laird random-effects models to calculate pooled estimates and conducted multiple meta-regression with an information theoretic approach based on Akaike's Information Criterion to select the model and identify the factors associated with VE. RESULTS: Fifty-one eligible studies with 151 estimates were included. For prevention of infection, VE associated with study region, variants, and time since vaccination; VE was significantly decreased against Omicron compared to Alpha (P = 0.021), primary series VE was 52.8% (95% CI, 43.3 to 60.7%) against Delta and 16.4% (95% CI, 9.5 to 22.8%) against Omicron, and booster dose VE was 65.2% (95% CI, 48.3 to 76.6%) against Delta and 20.3% (95% CI, 10.5 to 28.0%) against Omicron; primary VE decreased significantly after 180 days (P = 0.022). For the prevention of severe COVID-19, VE associated with vaccine doses, age, study region, variants, study design, and study population type; booster VE increased significantly (P = 0.001) compared to primary; though VE decreased significantly against Gamma (P = 0.034), Delta (P = 0.001), and Omicron (P = 0.001) compared to Alpha, primary and booster VEs were all above 60% against each variant. CONCLUSIONS: Inactivated vaccine protection against SARS-CoV-2 infection was moderate, decreased significantly after 6 months following primary vaccination, and was restored by booster vaccination. VE against severe COVID-19 was greatest after boosting and did not decrease over time, sustained for over 6 months after the primary series, and more evidence is needed to assess the duration of booster VE. VE varied by variants, most notably against Omicron. It is necessary to ensure booster vaccination of everyone eligible for SARS-CoV-2 vaccines and continue monitoring virus evolution and VE. TRIAL REGISTRATION: PROSPERO, CRD42022353272.

Effectiveness of Inactivated COVID-19 Vaccines against Delta-Variant COVID-19: Evidence from an Outbreak in Inner Mongolia Autonomous Region, China.

Phase 3 clinical trials and real-world effectiveness studies showed that China's two main inactivated COVID-19 vaccines are very effective against serious illness. In November 2021, an outbreak occurred in the Inner Mongolia Autonomous Region that provided an opportunity to assess the vaccine effectiveness (VE) of these inactivated vaccines against COVID-19 caused by the delta variant. We evaluated VE with a retrospective cohort study of close contacts of infected individuals, using a generalized linear model with binomial distribution and log-link function to estimate risk ratios (RR) and VE. A total of 8842 close contacts were studied. Compared with no vaccination and adjusted for age, presence of comorbidity, and time since last vaccination, full vaccination reduced symptomatic infection by 62%, pneumonia by 64% and severe COVID-19 by 90%; reductions associated with homologous booster doses were 83% for symptomatic infection, 92% for pneumonia and 100% for severe COVID-19. There was no significant decline in two-dose VE for any outcome for up to 325 days following the last dose. There were no differences by vaccine brand. Inactivated vaccines were effective against delta-variant illness, and were highly effective against pneumonia and severe COVID-19; VE was increased by booster doses.