Evaluation of antibody kinetics and durability in healthy individuals vaccinated with inactivated COVID-19 vaccine (CoronaVac): A cross-sectional and cohort study in Zhejiang, China.

Background: Although inactivated COVID-19 vaccines are proven to be safe and effective in the general population, the dynamic response and duration of antibodies after vaccination in the real world should be further assessed. Methods: We enrolled 1067 volunteers who had been vaccinated with one or two doses of CoronaVac in Zhejiang Province, China. Another 90 healthy adults without previous vaccinations were recruited and vaccinated with three doses of CoronaVac, 28 days and 6 months apart. Serum samples were collected from multiple timepoints and analyzed for specific IgM/IgG and neutralizing antibodies (NAbs) for immunogenicity evaluation. Antibody responses to the Delta and Omicron variants were measured by pseudovirus-based neutralization tests. Results: Our results revealed that binding antibody IgM peaked 14-28 days after one dose of CoronaVac, while IgG and NAbs peaked approximately 1 month after the second dose then declined slightly over time. Antibody responses had waned by month 6 after vaccination and became undetectable in the majority of individuals at 12 months. Levels of NAbs to live SARS-CoV-2 were correlated with anti-SARS-CoV-2 IgG and NAbs to pseudovirus, but not IgM. Homologous booster around 6 months after primary vaccination activated anamnestic immunity and raised NAbs 25.5-fold. The neutralized fraction subsequently rose to 36.0% for Delta (p=0.03) and 4.3% for Omicron (p=0.004), and the response rate for Omicron rose from 7.9% (7/89)-17.8% (16/90). Conclusions: Two doses of CoronaVac vaccine resulted in limited protection over a short duration. The inactivated vaccine booster can reverse the decrease of antibody levels to prime strain, but it does not elicit potent neutralization against Omicron; therefore, the optimization of booster procedures is vital. Funding: Key Research and Development Program of Zhejiang Province; Key Program of Health Commission of Zhejiang Province/ Science Foundation of National Health Commission; Major Program of Zhejiang Municipal Natural Science Foundation; Explorer Program of Zhejiang Municipal Natural Science Foundation.

Safety and immunogenicity of heterologous recombinant protein subunit vaccine (ZF2001) booster against COVID-19 at 3-9-month intervals following two-dose inactivated vaccine (CoronaVac).

Background: In response to SARS-CoV-2 mutations and waning antibody levels after two-dose inactivated vaccines, we assessed whether a third dose of recombinant protein subunit vaccine (ZF2001) boosts immune responses. Methods: An open-label single-center non-random trial was conducted on people aged 18 years and above at five sites in China. All participants received a two-dose inactivated vaccine (CoronaVac) as their prime doses within 3-9 months of the trial. Primary outcomes were safety and immunogenicity, primarily the geometric mean titers (GMTs) of neutralizing antibodies to live wildtype SARS-CoV-2. Results: A total of 480 participants (median age, 51; range 21-84 years) previously vaccinated with two-dose CoronaVac received a third booster dose of ZF2001 3-4, 5-6, or 7-9-months later. The overall incidence of adverse reactions within 30 days after vaccination was 5.83% (28/480). No serious adverse reactions were reported after the third dose of ZF2001. GMTs in the 3-4-, 5-6-, and 7-9-month groups before vaccination were 3.96, 4.60, and 3.78, respectively. On Day 14, GMTs increased to 33.06, 47.51, and 44.12, respectively. After the booster, GMTs showed no significant difference among the three prime-boost interval groups (all P>0.05). Additionally, GMTs in older adults were lower than those in younger adults on Day 14 for the three groups (P=0.0005, P<0.0001, and P<0.0001). Conclusion: Heterologous boosting with ZF2001 was safe and immunogenic, and prime-boost intervals did not affect the immune response. The immune response was weaker in older than younger adults.

Knowledge, attitudes, and practices toward COVID-19: A cross-sectional study during normal management of the epidemic in China.

Background: The COVID-19 pandemic is striking the world with serious public health and economic losses. Complying with precautionary measures is affected by knowledge, attitudes, and practices (KAP) toward COVID-19 among the general public, so it is urgent to know the public's awareness of COVID-19 as to promote the epidemic management of COVID-19 in China. Methods: An online sample of Chinese residents was recruited. We administered a self-developed online KAP survey comprising 39 questions regarding awareness of COVID-19, transmission mode, symptoms, preventive measures, and respondents' attitudes and practices with respect to COVID-19. The total score of each item (knowledge, attitudes, and practices) adopts the ten points system, score of KAP is 30 points. Descriptive statistics, analysis of variance, and binomial logistic regression were used in the statistical analysis. Results: Among respondents, average scores for COVID-19-related knowledge, attitudes, and practice were 8.94 ± 0.79, 5.97 ± 1.58, and 7.03 ± 3.14, respectively. 91.2% were aware that COVID-19 is an acute viral infection and 99.95% knew that wearing a mask is one way to prevent COVID-19 infection. Participants correctly identified the symptoms of COVID-19 with a high accuracy rate of over 85%. Conclusion: Many adults in the present study had adequate knowledge, a positive attitude and engaged in correct practices against COVID-19. People in China have a high awareness of epidemic prevention and control. However, conducting KAP surveys among people with different demographic characteristics at different stages of the epidemic is important to improve public health education and implement proper COVID-19 prevention and control measures.

Knowledge, attitudes, and practices toward COVID-19: A cross-sectional study during normal management of the epidemic in China

Background The COVID-19 pandemic is striking the world with serious public health and economic losses. Complying with precautionary measures is affected by knowledge, attitudes, and practices (KAP) toward COVID-19 among the general public, so it is urgent to know the public's awareness of COVID-19 as to promote the epidemic management of COVID-19 in China. Methods An online sample of Chinese residents was recruited. We administered a self-developed online KAP survey comprising 39 questions regarding awareness of COVID-19, transmission mode, symptoms, preventive measures, and respondents' attitudes and practices with respect to COVID-19. The total score of each item (knowledge, attitudes, and practices) adopts the ten points system, score of KAP is 30 points. Descriptive statistics, analysis of variance, and binomial logistic regression were used in the statistical analysis. Results Among respondents, average scores for COVID-19-related knowledge, attitudes, and practice were 8.94 ± 0.79, 5.97 ± 1.58, and 7.03 ± 3.14, respectively. 91.2% were aware that COVID-19 is an acute viral infection and 99.95% knew that wearing a mask is one way to prevent COVID-19 infection. Participants correctly identified the symptoms of COVID-19 with a high accuracy rate of over 85%. Conclusion Many adults in the present study had adequate knowledge, a positive attitude and engaged in correct practices against COVID-19. People in China have a high awareness of epidemic prevention and control. However, conducting KAP surveys among people with different demographic characteristics at different stages of the epidemic is important to improve public health education and implement proper COVID-19 prevention and control measures.

Factors associated with neutralizing antibody levels induced by two inactivated COVID-19 vaccines for 12 months after primary series vaccination.

Background: BBIBP-CorV and CoronaVac inactivated COVID-19 vaccines are widely-used, World Health Organization-emergency-listed vaccines. Understanding antibody level changes over time after vaccination is important for booster dose policies. We evaluated neutralizing antibody (nAb) titers and associated factors for the first 12 months after primary-series vaccination with BBIBP-CorV and CoronaVac. Methods: Our study consisted of a set of cross-sectional sero-surveys in Zhejiang and Shanxi provinces, China. In 2021, we enrolled 1,527 consenting 18-59-year-olds who received two doses of BBIBP-CorV or CoronaVac 1, 3, 6, 9, or 12 months earlier and obtained blood samples and demographic and medical data. We obtained 6-month convalescent sera from 62 individuals in Hebei province. Serum nAb titers were measured by standard micro-neutralization cytopathic effect assay in Vero cells with ancestral SARS-CoV-2 strain HB01. We used the first WHO International Standard (IS) for anti-SARS-CoV-2 immunoglobulin (NIBSC code 20/136) to standardized geometric mean concentrations (IU/mL) derived from the nAb geometric mean titers (GMT over 1:4 was considered seropositive). We analyzed nAb titer trends using Chi-square and factors related to nAb titers with logistic regression and linear models. Results: Numbers of subjects in each of the five month-groupings ranged from 100 to 200 for each vaccine and met group-specific target sample sizes. Seropositivity rates from BBIBP-CorV were 98.0% at 1 month and 53.5% at 12 months, and GMTs were 25.0 and 4.0. Respective seropositivity rates from CoronaVac were 90.0% and 62.5%, and GMTs were 20.2 and 4.1. One-, three-, six-, nine-, and twelve-month GMCs were 217.2, 84.1, 85.7, 44.6, and 10.9 IU/mL in BBIBP-CorV recipients and 195.7, 94.6, 51.7, 27.6, and 13.4 IU/mL in CoronaVac recipients. Six-month convalescent seropositivity was 95.2%; GMC was 108.9 IU/mL. Seropositivity and GMCs were associated with age, sex, and time since vaccination. Conclusions: Neutralizing Ab levels against ancestral SARS-CoV-2 from BBIBP-CorV or CoronaVac vaccination were similar and decreased with increasing time since vaccination; over half of 12-month post-vaccination subjects were seropositive. Seropositivity and GMCs from BBIBP-CorV and CoronaVac six and nine months after vaccination were similar to or slightly lower than in six-month convalescent sera. These real-world data suggest necessity of six-month booster doses.

Immunogenicity and immune-persistence of the CoronaVac or Covilo inactivated COVID-19 Vaccine: a 6-month population-based cohort study.

Background: Owing to the coronavirus disease 2019 (COVID-19) pandemic and the emergency use of different types of COVID-19 vaccines, there is an urgent need to consider the effectiveness and persistence of different COVID-19 vaccines. Methods: We investigated the immunogenicity of CoronaVac and Covilo, two inactivated vaccines against COVID-19 that each contain inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The levels of neutralizing antibodies to live SARS-CoV-2 and the inhibition rates of neutralizing antibodies to pseudovirus, as well as the immunoglobulin (Ig)G and IgM responses towards the spike (S) and nucleocapsid (N) protein of SARS-CoV-2 at 180 days after two-dose vaccination were detected. Results: The CoronaVac and Covilo vaccines induced similar antibody responses. Regarding neutralizing antibodies to live SARS-CoV-2, 77.9% of the CoronaVac vaccine recipients and 78.3% of the Covilo vaccine recipients (aged 18-59 years) seroconverted by 28 days after the second vaccine dose. Regarding SARS-CoV-2-specific antibodies, 97.1% of the CoronaVac vaccine recipients and 95.7% of the Covilo vaccine recipients seroconverted by 28 days after the second vaccine dose. The inhibition rates of neutralizing antibody against a pseudovirus of the SARS-CoV-2 Delta variant were significantly lower compared with those against a pseudovirus of wildtype SARS-CoV-2. Associated with participant characteristics and antibody levels, persons in the older age group and with basic disease, especially a chronic respiratory disease, tended to have lower anti-SARS-CoV-2 antibody seroconversion rates. Conclusion: Antibodies that were elicited by these two inactivated COVID-19 vaccines appeared to wane following their peak after the second vaccine dose, but they persisted at detectable levels through 6 months after the second vaccine dose, and the effectiveness of these antibodies against the Delta variant of SARS-CoV-2 was lower than their effectiveness against wildtype SARS-CoV-2, which suggests that attention must be paid to the protective effectiveness, and its persistence, of COVID-19 vaccines on SARS-CoV-2 variants.

Distinguishing COVID-19 From Influenza Pneumonia in the Early Stage Through CT Imaging and Clinical Features.

Background: Both coronavirus disease 2019 (COVID-19) and influenza pneumonia are highly contagious and present with similar symptoms. We aimed to identify differences in CT imaging and clinical features between COVID-19 and influenza pneumonia in the early stage and to identify the most valuable features in the differential diagnosis. Methods: Seventy-three patients with COVID-19 confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and 48 patients with influenza pneumonia confirmed by direct/indirect immunofluorescence antibody staining or RT-PCR were retrospectively reviewed. Clinical data including course of disease, age, sex, body temperature, clinical symptoms, total white blood cell (WBC) count, lymphocyte count, lymphocyte ratio, neutrophil count, neutrophil ratio, and C-reactive protein, as well as 22 qualitative and 25 numerical imaging features from non-contrast-enhanced chest CT images were obtained and compared between the COVID-19 and influenza pneumonia groups. Correlation tests between feature metrics and diagnosis outcomes were assessed. The diagnostic performance of each feature in differentiating COVID-19 from influenza pneumonia was also evaluated. Results: Seventy-three COVID-19 patients including 41 male and 32 female with mean age of 41.9 ± 14.1 and 48 influenza pneumonia patients including 30 male and 18 female with mean age of 40.4 ± 27.3 were reviewed. Temperature, WBC count, crazy paving pattern, pure GGO in peripheral area, pure GGO, lesion sizes (1-3 cm), emphysema, and pleural traction were significantly independent associated with COVID-19. The AUC of clinical-based model on the combination of temperature and WBC count is 0.880 (95% CI: 0.819-0.940). The AUC of radiological-based model on the combination of crazy paving pattern, pure GGO in peripheral area, pure GGO, lesion sizes (1-3 cm), emphysema, and pleural traction is 0.957 (95% CI: 0.924-0.989). The AUC of combined model based on the combination of clinical and radiological is 0.991 (95% CI: 0.980-0.999). Conclusion: COVID-19 can be distinguished from influenza pneumonia based on CT imaging and clinical features, with the highest AUC of 0.991, of which crazy-paving pattern and WBC count play most important role in the differential diagnosis.

A Survey of Awareness of COVID-19 Knowledge, Willingness and Influencing Factors of COVID-19 Vaccination.

New vaccines are being developed in response to the coronavirus disease 2019 (COVID-19) pandemic. Vaccination provides a crucial preventive approach for managing COVID-19. We investigated adults' willingness to take COVID-19 vaccines in the Zhejiang province, and their cognitions regarding COVID-19, when the COVID-19 vaccine is authorized under Emergency Use Administration. An online survey was conducted from September to October 2020, which included social-demographic characteristics, risk perception, acceptance and influencing factors in relation to COVID-19 vaccines. Multivariate logistic regression was performed to identify the influencing factors of vaccination acceptance. Of the participants, 70% intended to be vaccinated when the COVID-19 vaccine was approved under Emergency Use Administration, among 2171 valid questionnaires. Logistic regression revealed that being male, having a high cognitive score regarding COVID-19, the belief that the COVID-19 vaccine is safe and effective, and the belief that one will be infected with SARS-CoV-2 this fall and winter, were associated with a greater probability of accepting vaccination. Respondents with junior college/university education or above were less likely to accept vaccination. Concerns about the safety and effectiveness of the vaccine were the main factors hindering vaccination acceptance. Health education is important for promoting accurate public knowledge regarding COVID-19 vaccination.

Differences in Clinical and Imaging Presentation of Pediatric Patients with COVID-19 in Comparison with Adults.

PURPOSE: To characterize and compare the initial clinical and imaging features of coronavirus disease 2019 (COVID-19) in pediatric and adult patients undergoing chest CT. MATERIALS AND METHODS: A total of 61 patients, consisting of 47 adults (aged 18 years or older) and 14 pediatric patients (aged younger than 18 years) with laboratory-confirmed COVID-19 confirmed by real-time reverse-transcription polymerase chain reaction between January 25 and February 15, 2020, were enrolled in this study. All patients underwent chest CT within 3 days after the initial reverse transcription polymerase chain reaction test. The clinical presentation, serum markers, and CT findings were assessed and compared between the adult and pediatric patients. RESULTS: Fever was less common in pediatric patients than in adults (six of 14, 42.9% vs 39 of 47, 83%; P = .008). Leukopenia or normal, lymphopenia or normal, and increased or normal C-reactive protein level were common in both groups with no difference (P > .05). Compared with the adults, pediatric patients had a lower rate of positive CT findings and a milder clinical grade (P = .004 and P = .001, respectively). At chest CT, the number of pulmonary lobes involved was found to be reduced in pediatric patients when compared with adults (P = .012). Subpleural distribution of lung opacities was a dominant feature in both groups, whereas bronchial distribution was more common in the pediatric group (P = .048). Among the CT features in adults, ground-glass opacities (GGOs) were the most common finding (24 of 43, 53.5%), followed by GGO with consolidation (14 of 43, 27.9%). In pediatric patients, GGOs accounted for 42.9% (three of seven), bronchial wall thickening occurred in 28.6% (two of seven), and GGOs with consolidations and nodular opacities occurred in 14.3% (one of seven). However, these CT features did not differ in the two groups, except for bronchial wall thickening, which was more commonly found in pediatric patients (P = .048). In addition, the semiquantitative scores of lung involvement were higher in adults than in pediatric patients (8.89 ± 4.54 vs 1.86 ± 2.41; P < .001). CONCLUSION: Compared with adults, pediatric patients with COVID-19 showed distinctive clinical and CT features. Pediatric patients tend to have milder clinical symptoms, fewer positive results at CT, and less extensive involvement at imaging. Bronchial wall thickening was relatively more frequent on CT images from pediatric patients with COVID-19 in comparison with adults.Supplemental material is available for this article.© RSNA, 2020.

Atypical presentations of coronavirus disease 2019 (COVID-19) from onset to readmission.

BACKGROUND: To investigate the CT imaging and clinical features of three atypical presentations of coronavirus disease 2019 (COVID-19), namely (1) asymptomatic, (2) CT imaging-negative, and (3) re-detectable positive (RP), during all disease stages. METHODS: A consecutive cohort of 79 COVID-19 patients was retrospectively recruited from five independent institutions. For each presentation type, all patients were classified into atypical vs. typical groups (i.e., asymptomatic vs.symptomatic, CT imaging-negative vs. CT imaging-positive, and RP and non-RP,respectively). The chi-square test, Student's t test, and Kruskal-Wallis H test were performed to compare CT imaging and clinical features of atypical vs. typical patients for all three presentation categories. RESULTS: In our COVID-19 cohort, we found 12.7% asymptomatic patients, 13.9% CT imaging-negative patients, and 8.9% RP patients. The asymptomatic patients had fewer hospitalization days (P=0.043), lower total scores for bilateral lung involvement (P< 0.001), and fewer ground-glass opacities (GGOs) in the peripheral area (P< 0.001) than symptomatic patients. The CT imaging-negative patients were younger (P=0.002), had a higher lymphocyte count (P=0.038), had a higher lymphocyte rate (P=0.008), and had more asymptomatic infections (P=0.002) than the CT imaging-positive patients. The RP patients with moderate COVID-19 had lower total scores of for bilateral lung involvement (P=0.030) and a smaller portion of the left lung affected (P=0.024) than non-RP patients. Compared to their first hospitalization, RP patients had a shorter hospitalization period (P< 0.001) and fewer days from the onset of illness to last RNA negative conversion (P< 0.001) at readmission. CONCLUSIONS: Significant CT imaging and clinical feature differences were found between atypical and typical COVID-19 patients for all three atypical presentation categories investigated in this study, which may help provide complementary information for the effective management of COVID-19.

A diagnostic model for coronavirus disease 2019 (COVID-19) based on radiological semantic and clinical features: a multi-center study.

OBJECTIVES: Rapid and accurate diagnosis of coronavirus disease 2019 (COVID-19) is critical during the epidemic. We aim to identify differences in CT imaging and clinical manifestations between pneumonia patients with and without COVID-19, and to develop and validate a diagnostic model for COVID-19 based on radiological semantic and clinical features alone. METHODS: A consecutive cohort of 70 COVID-19 and 66 non-COVID-19 pneumonia patients were retrospectively recruited from five institutions. Patients were divided into primary (n = 98) and validation (n = 38) cohorts. The chi-square test, Student's t test, and Kruskal-Wallis H test were performed, comparing 1745 lesions and 67 features in the two groups. Three models were constructed using radiological semantic and clinical features through multivariate logistic regression. Diagnostic efficacies of developed models were quantified by receiver operating characteristic curve. Clinical usage was evaluated by decision curve analysis and nomogram. RESULTS: Eighteen radiological semantic features and seventeen clinical features were identified to be significantly different. Besides ground-glass opacities (p = 0.032) and consolidation (p = 0.001) in the lung periphery, the lesion size (1-3 cm) is also significant for the diagnosis of COVID-19 (p = 0.027). Lung score presents no significant difference (p = 0.417). Three diagnostic models achieved an area under the curve value as high as 0.986 (95% CI 0.966~1.000). The clinical and radiological semantic models provided a better diagnostic performance and more considerable net benefits. CONCLUSIONS: Based on CT imaging and clinical manifestations alone, the pneumonia patients with and without COVID-19 can be distinguished. A model composed of radiological semantic and clinical features has an excellent performance for the diagnosis of COVID-19. KEY POINTS: • Based on CT imaging and clinical manifestations alone, the pneumonia patients with and without COVID-19 can be distinguished. • A diagnostic model for COVID-19 was developed and validated using radiological semantic and clinical features, which had an area under the curve value of 0.986 (95% CI 0.966~1.000) and 0.936 (95% CI 0.866~1.000) in the primary and validation cohorts, respectively.

CT image visual quantitative evaluation and clinical classification of coronavirus disease (COVID-19).

OBJECTIVES: To explore the relationship between the imaging manifestations and clinical classification of COVID-19. METHODS: We conducted a retrospective single-center study on patients with COVID-19 from Jan. 18, 2020 to Feb. 7, 2020 in Zhuhai, China. Patients were divided into 3 types based on Chinese guideline: mild (patients with minimal symptoms and negative CT findings), common, and severe-critical (patients with positive CT findings and different extent of clinical manifestations). CT visual quantitative evaluation was based on summing up the acute lung inflammatory lesions involving each lobe, which was scored as 0 (0%), 1 (1-25%), 2 (26-50%), 3 (51-75%), or 4 (76-100%), respectively. The total severity score (TSS) was reached by summing the five lobe scores. The consistency of two observers was evaluated. The TSS was compared with the clinical classification. ROC was used to test the diagnosis ability of TSS for severe-critical type. RESULTS: This study included 78 patients, 38 males and 40 females. There were 24 mild (30.8%), 46 common (59.0%), and 8 severe-critical (10.2%) cases, respectively. The median TSS of severe-critical-type group was significantly higher than common type (p < 0.001). The ICC value of the two observers was 0.976 (95% CI 0.962-0.985). ROC analysis showed the area under the curve (AUC) of TSS for diagnosing severe-critical type was 0.918. The TSS cutoff of 7.5 had 82.6% sensitivity and 100% specificity. CONCLUSIONS: The proportion of clinical mild-type patients with COVID-19 was relatively high; CT was not suitable for independent screening tool. The CT visual quantitative analysis has high consistency and can reflect the clinical classification of COVID-19. KEY POINTS: • CT visual quantitative evaluation has high consistency (ICC value of 0.976) among the observers. The median TSS of severe-critical type group was significantly higher than common type (p < 0.001). • ROC analysis showed the area under the curve (AUC) of TSS for diagnosing severe-critical type was 0.918 (95% CI 0.843-0.994). The TSS cutoff of 7.5 had 82.6% sensitivity and 100% specificity. • The proportion of confirmed COVID-19 patients with normal chest CT was relatively high (30.8%); CT was not a suitable screening modality.