Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents.

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

Long-term outcomes of COVID-19 convalescents: An 18.5-month longitudinal study in Wuhan.

OBJECTIVES: This study aimed to describe the full scope of long-term outcomes and the ongoing pathophysiological alterations among COVID-19 survivors. METHODS: We established a longitudinal cohort of 208 COVID-19 convalescents and followed them at 3.3 (interquartile range [IQR]: 1.3, 4.4, visit 1), 9.2 (IQR: 9.0, 9.6, visit 2), and 18.5 (IQR: 18.2, 19.1, visit 3) months after infection, respectively. Serial changes in multiple physical and psychological outcomes were comprehensively characterized. We, in addition, explored the potential risk factors of SARS-CoV-2 antibody response and sequelae symptoms. RESULTS: We observed continuous improvement of sequelae symptoms, lung function, chest computed tomography (CT), 6-minute walk test, and the Borg dyspnea scale, whereas sequelae symptoms (at least one) and abnormal chest CT patterns still existed in 45.2% and about 30% of participants at 18.5 months, respectively. Anxiety and depression disorders were alleviated for the convalescents, although depression status was sustained for a longer duration. CONCLUSIONS: Most COVID-19 convalescents had an overall improved physical and psychological health status, whereas sequelae symptoms, residual lesions on lung function, exercise impairment, and mental health disorders were still observed in a small proportion of participants at 18.5 months after infection. Implementing appropriate preventive and management strategies for the ever-growing COVID-19 population is warranted.

Humoral and cellular immunity of two-dose inactivated COVID-19 vaccination in Chinese children: A prospective cohort study.

Children are the high-risk group for COVID-19, and in need of vaccination. However, humoral and cellular immune responses of COVID-19 vaccine remain unclear in vaccinated children. To establish the rational immunization strategy of inactivated COVID-19 vaccine for children, the immunogenicity of either one dose or two doses of the vaccine in children was evaluated. A prospective cohort study of 322 children receiving inactivated COVID-19 vaccine was established in China. The baseline was conducted after 28 days of the first dose, and the follow-up was conducted after 28 days of the second dose. The median titers of receptor binding domain (RBD)-IgG, and neutralizing antibody (NAb) against prototype strain and Omicron variant after the second dose increased significantly compared to those after the first dose (first dose: 70.0, [interquartile range, 30.0-151.0] vs. second dose: 1261.0 [636.0-2060.0] for RBD-IgG; 2.5 [2.5-18.6] vs. 252.0 [138.6-462.1] for NAb against prototype strain; 2.5 [2.5-2.5] vs. 15.0 [7.8-26.5] for NAb against Omicron variant, all p < 0.05). The flow cytometry results showed that the first dose elicited SARS-CoV-2 specific cellular immunity, while the second dose strengthened SARS-CoV-2 specific IL-2+ or TNF-α+  monofunctional, IFN-γ+ TNF-α+  bifunctional, and IFN-γ- IL-2+ TNF-α+ multifunctional CD4+ T cell responses (p < 0.05). Moreover, SARS-CoV-2 specific memory T cells were generated after the first vaccination, including the central memory T cells and effector memory T cells. The present findings provide scientific evidence for the vaccination strategy of the inactive vaccines among children against COVID-19 pandemic.

Determinants of workplace safety towards SARS-Cov-2 and combating COVID-19 among non-healthcare workers in Hong Kong, Nanjing and Wuhan, China.

There has been no validated tool to assess workplace infection control towards SARS-Cov-2 in non-healthcare industries. In this first year survey during 07/2020-04/2021, 6684 workers were recruited from varied non-healthcare settings of Hong Kong, Nanjing and Wuhan of China and responded standard questionnaires containing information of prevention measures and policies implemented by companies and personal preventive behaviour towards infection control. All participants were randomly stratified into two sub-samples as training and validation sample. Workplace safety index towards SARS-Cov-2 (WSI-SC2) was developed and validated using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). We identified 14 manifest variables in WSI-SC2, with three sub-indices named "Workplace infection control measures and prevention", "Company occupational safety and health management and commitment" and "Worker's personal preventive behavior and awareness towards infectious control". WSI-SC2 obtained a good internal consistency reliability (Cronbach's alpha coefficients ranged: 0.76-0.91), good composite reliability (composite reliability ranged: 0.70-0.95) and satisfactory fit of the model (GFI = 0.95; SRMR = 0.05; RMSEA = 0.07). We further performed stratified analysis according to cities, and the index remained stable. Workers with higher scores of WSI-SC2 were more likely to uptake COVID-19 test. This multi-city large study developed a novel and validated tool that could horizontally measure the workplace safety towards SARS-Cov-2 in non-healthcare workers.

Association of current income and reduction in income during the COVID-19 pandemic with anxiety and depression among non-healthcare workers.

BACKGROUND: Many workers experienced income reduction during the coronavirus disease 2019 (COVID-19) pandemic, which may link to adverse mental health. AIMS: This study aimed to examine the association of current income and reduction in income during COVID-19 with anxiety and depression levels among non-healthcare workers. METHODS: This is a multi-city cross-sectional study. We used standardized questionnaires to collect information. We regrouped the current income and income reduction during COVID-19 according to the tertile and median value of each specific city. Depression, Anxiety and Stress Scales-21 item short version (DASS-21) was used to assess anxiety and depression levels. We performed multinomial logistic regression to examine the association of current and reduced income with anxiety and depression. Path models were developed to outline the potential modification/indirect effect of subsidies from government. RESULTS: Large income reduction and low current income were significantly associated with more anxiety/depression symptoms. Path analysis showed that government subsidies could not significantly alleviate the impact of reduced income on anxiety/depression. CONCLUSION: Our findings showed that large income reduction and low current income were independently associated with anxiety/depression, while these symptoms may not be ameliorated by one-off government funds. This study suggests the need for long-term policies (e.g. developing sustained economic growth policies) to mitigate negative impacts of the COVID-19.

Association of Public Health Interventions With the Epidemiology of the COVID-19 Outbreak in Wuhan, China.

IMPORTANCE: Coronavirus disease 2019 (COVID-19) has become a pandemic, and it is unknown whether a combination of public health interventions can improve control of the outbreak. OBJECTIVE: To evaluate the association of public health interventions with the epidemiological features of the COVID-19 outbreak in Wuhan by 5 periods according to key events and interventions. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, individual-level data on 32 583 laboratory-confirmed COVID-19 cases reported between December 8, 2019, and March 8, 2020, were extracted from the municipal Notifiable Disease Report System, including patients' age, sex, residential location, occupation, and severity classification. EXPOSURES: Nonpharmaceutical public health interventions including cordons sanitaire, traffic restriction, social distancing, home confinement, centralized quarantine, and universal symptom survey. MAIN OUTCOMES AND MEASURES: Rates of laboratory-confirmed COVID-19 infections (defined as the number of cases per day per million people), across age, sex, and geographic locations were calculated across 5 periods: December 8 to January 9 (no intervention), January 10 to 22 (massive human movement due to the Chinese New Year holiday), January 23 to February 1 (cordons sanitaire, traffic restriction and home quarantine), February 2 to 16 (centralized quarantine and treatment), and February 17 to March 8 (universal symptom survey). The effective reproduction number of SARS-CoV-2 (an indicator of secondary transmission) was also calculated over the periods. RESULTS: Among 32 583 laboratory-confirmed COVID-19 cases, the median patient age was 56.7 years (range, 0-103; interquartile range, 43.4-66.8) and 16 817 (51.6%) were women. The daily confirmed case rate peaked in the third period and declined afterward across geographic regions and sex and age groups, except for children and adolescents, whose rate of confirmed cases continued to increase. The daily confirmed case rate over the whole period in local health care workers (130.5 per million people [95% CI, 123.9-137.2]) was higher than that in the general population (41.5 per million people [95% CI, 41.0-41.9]). The proportion of severe and critical cases decreased from 53.1% to 10.3% over the 5 periods. The severity risk increased with age: compared with those aged 20 to 39 years (proportion of severe and critical cases, 12.1%), elderly people (≥80 years) had a higher risk of having severe or critical disease (proportion, 41.3%; risk ratio, 3.61 [95% CI, 3.31-3.95]) while younger people (<20 years) had a lower risk (proportion, 4.1%; risk ratio, 0.47 [95% CI, 0.31-0.70]). The effective reproduction number fluctuated above 3.0 before January 26, decreased to below 1.0 after February 6, and decreased further to less than 0.3 after March 1. CONCLUSIONS AND RELEVANCE: A series of multifaceted public health interventions was temporally associated with improved control of the COVID-19 outbreak in Wuhan, China. These findings may inform public health policy in other countries and regions.

The trans-omics landscape of COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill. Using integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, we report a trans-omics landscape for COVID-19. Our analyses find neutrophils heterogeneity between asymptomatic and critically ill patients. Meanwhile, neutrophils over-activation, arginine depletion and tryptophan metabolites accumulation correlate with T cell dysfunction in critical patients. Our multi-omics data and characterization of peripheral blood from COVID-19 patients may thus help provide clues regarding pathophysiology of and potential therapeutic strategies for COVID-19.

Road traffic and air pollution: Evidence from a nationwide traffic control during coronavirus disease 2019 outbreak.

Existing estimations of air pollution from automobile sources are based on either experiments or small-scale governmental interventions. China's nationwide traffic control during the coronavirus disease 2019 outbreak provided us a unique opportunity to assess the direct dose-effect relationship between vehicle density and air pollution. We found that, during the coronavirus disease 2019 outbreak, the nationwide reduced air pollution (except for O3) could be largely explained by traffic control measures. During the traffic control period, every doubling of vehicle density was associated with a decrease of 4.2 (2.0, 6.4) µg/m3 in PM2.5, 5.5 (2.9, 8.1) µg/m3 in PM10, 1.5 (0.9, 2.0) µg/m3 in NO2, and 0.04 (0.02, 0.07) mg/m3 in CO comparing cities with different vehicle densities. Similarly, for every 10% increase in the truck proportion, PM2.5 decreased by 12.3 (4.1, 20.6) µg/m3, PM10 decreased by 14.3 (4.6, 23.9) µg/m3, and CO decreased by 0.14 (0.05, 0.23) mg/m3. Moreover, the associations between vehicle density and reduction in PM2.5, PM10, and CO during the traffic control period were stronger and showed near-complete linearity in cities with low green coverage rate (All P < 0.05 for interaction). According to our estimation, PM2.5 emissions from every doubling of vehicle density can lead to over 8000 excess deaths per year, 66% of which were caused by cardiopulmonary diseases. This natural experiment study is the first to observe the dose-effect relationship between on-road traffic and traffic-generated air pollution, as well as the mitigating effect of urban greening. Findings provide key evidence to the assessment and control of traffic-generated air pollution and its public health impact.

Clinical Characteristics and Prognosis of 244 Cardiovascular Patients Suffering From Coronavirus Disease in Wuhan, China.

Background The coronavirus disease 2019 (COVID-19) has developed into a global outbreak. Patients with cardiovascular disease (CVD) with COVID-19 have different clinical characteristics and prognostic outcomes. This study aimed to summarize the clinical characteristics and laboratory indicators of patients with COVID-19 with CVD, especially the critically ill patients. Methods and Results This study included 244 patients diagnosed with COVID-19 and CVD (hypertension, coronary heart disease, or heart failure). The patients were categorized into critical (n=36) and noncritical (n=208) groups according to the interim guidance of China's National Health Commission. Clinical, laboratory, and outcome data were collected from the patients' medical records and compared between the 2 groups. The average body mass index of patients was significantly higher in the critical group than in the noncritical group. Neutrophil/lymphocyte ratio, and C-reactive protein, procalcitonin, and fibrinogen, and d-dimer levels at admission were significantly increased in the critical group. The all-cause mortality rate among cases of COVID-19 combined with CVD was 19.26%; the proportion of coronary heart disease and heart failure was significantly higher in deceased patients than in recovered patients. High body mass index, previous history of coronary heart disease, lactic acid accumulation, and a decrease in the partial pressure of oxygen were associated with death. Conclusions All-cause mortality in patients with COVID-19 with CVD in hospitals is high. The high neutrophil/lymphocyte ratio may be a predictor of critical patients. Overweight/obesity combined with coronary heart disease, severe hypoxia, and lactic acid accumulation resulting from respiratory failure are related to poor outcomes. Registration URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2000029865.

Reconstruction of the full transmission dynamics of COVID-19 in Wuhan.

As countries in the world review interventions for containing the pandemic of coronavirus disease 2019 (COVID-19), important lessons can be drawn from the study of the full transmission dynamics of its causative agent-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)- in Wuhan (China), where vigorous non-pharmaceutical interventions have suppressed the local outbreak of this disease1. Here we use a modelling approach to reconstruct the full-spectrum dynamics of COVID-19 in Wuhan between 1 January and 8 March 2020 across 5 periods defined by events and interventions, on the basis of 32,583 laboratory-confirmed cases1. Accounting for presymptomatic infectiousness2, time-varying ascertainment rates, transmission rates and population movements3, we identify two key features of the outbreak: high covertness and high transmissibility. We estimate 87% (lower bound, 53%) of the infections before 8 March 2020 were unascertained (potentially including asymptomatic and mildly symptomatic individuals); and a basic reproduction number (R0) of 3.54 (95% credible interval 3.40-3.67) in the early outbreak, much higher than that of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS)4,5. We observe that multipronged interventions had considerable positive effects on controlling the outbreak, decreasing the reproduction number to 0.28 (95% credible interval 0.23-0.33) and-by projection-reducing the total infections in Wuhan by 96.0% as of 8 March 2020. We also explore the probability of resurgence following the lifting of all interventions after 14 consecutive days of no ascertained infections; we estimate this probability at 0.32 and 0.06 on the basis of models with 87% and 53% unascertained cases, respectively-highlighting the risk posed by substantial covert infections when changing control measures. These results have important implications when considering strategies of continuing surveillance and interventions to eventually contain outbreaks of COVID-19.