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.

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.

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.

Liver and Kidney Function Biomarkers, Blood Cell Traits and Risk of Severe COVID-19: A Mendelian Randomization Study.

The pandemic of Coronavirus disease 2019 (COVID-19) has posed an enormous threat to human health. According to observational studies, abnormal liver and kidney functions and blood cell traits were associated with severe COVID-19, yet the causal risk factors for COVID-19 severity and the underlying mechanism remained elusive. We performed Mendelian randomization analyses to assess the potential causal role of eight liver function biomarkers, one kidney function biomarker, and 14 hematological traits on COVID-19 severity using genetic association summary statistics from Europeans. Our findings showed that albumin, direct bilirubin, white blood cell count, neutrophil count, lymphocyte count, and mean corpuscular hemoglobin are casually associated with the risk of severe COVID-19. Notably, lymphocyte count and mean corpuscular hemoglobin had an independent effect on severe COVID-19 risk. These causal evidences provide insights into directions for the risk stratification of individuals with abnormal liver function or blood cell indices and motivate more studies to unveil the roles of these abnormalities in COVID-19 pathogenesis.

Dynamics and Correlation Among Viral Positivity, Seroconversion, and Disease Severity in COVID-19 : A Retrospective Study.

BACKGROUND: The understanding of viral positivity and seroconversion during the course of coronavirus disease 2019 (COVID-19) is limited. OBJECTIVE: To describe patterns of viral polymerase chain reaction (PCR) positivity and evaluate their correlations with seroconversion and disease severity. DESIGN: Retrospective cohort study. SETTING: 3 designated specialty care centers for COVID-19 in Wuhan, China. PARTICIPANTS: 3192 adult patients with COVID-19. MEASUREMENTS: Demographic, clinical, and laboratory data. RESULTS: Among 12 780 reverse transcriptase PCR tests for severe acute respiratory syndrome coronavirus 2 that were done, 24.0% had positive results. In 2142 patients with laboratory-confirmed COVID-19, the viral positivity rate peaked within the first 3 days. The median duration of viral positivity was 24.0 days (95% CI, 18.9 to 29.1 days) in critically ill patients and 18.0 days (CI, 16.8 to 19.1 days) in noncritically ill patients. Being critically ill was an independent risk factor for longer viral positivity (hazard ratio, 0.700 [CI, 0.595 to 0.824]; P < 0.001). In patients with laboratory-confirmed COVID-19, the IgM-positive rate was 19.3% in the first week, peaked in the fifth week (81.5%), and then decreased steadily to around 55% within 9 to 10 weeks. The IgG-positive rate was 44.6% in the first week, reached 93.3% in the fourth week, and then remained high. Similar antibody responses were seen in clinically diagnosed cases. Serum inflammatory markers remained higher in critically ill patients. Among noncritically ill patients, a higher proportion of those with persistent viral positivity had low IgM titers (<100 AU/mL) during the entire course compared with those with short viral positivity. LIMITATION: Retrospective study and irregular viral and serology testing. CONCLUSION: The rate of viral PCR positivity peaked within the initial few days. Seroconversion rates peaked within 4 to 5 weeks. Dynamic laboratory index changes corresponded well to clinical signs, the recovery process, and disease severity. Low IgM titers (<100 AU/mL) are an independent risk factor for persistent viral positivity. PRIMARY FUNDING SOURCE: None.

Risk factors for mortality of critically ill patients with COVID-19 receiving invasive ventilation.

Rationale: Early invasive ventilation may improve outcomes for critically ill patients with COVID-19. The objective of this study is to explore risk factors for 28-day mortality of COVID-19 patients receiving invasive ventilation. Methods: 74 consecutive adult invasively ventilated COVID-19 patients were included in this retrospective study. The demographic and clinical data were compared between survivors and non-survivors, and Cox regression analysis was used to explore risk factors for 28-day mortality. The primary outcome was 28-day mortality after initiation of invasive ventilation. Secondary outcome was the time from admission to intubation. Results: Of 74 patients with COVID-19, the median age was 68.0 years, 53 (71.6%) were male, 47 (63.5%) had comorbidities with hypertension, and diabetes commonly presented. The most frequent symptoms were fever and dyspnea. The median time from hospital admission to intubation was similar in survivors and non-survivors (6.5 days vs. 5.0 days). The 28-day mortality was 81.1%. High Sequential Organ Failure Assessment (SOFA) score (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.23-1.92; p < 0.001) and longer time from hospital admission to intubation (HR, 2.41; 95% CI, 1.15-5.07; p = 0.020) were associated with 28-day mortality in invasively ventilated COVID-19 patients. Conclusions: The mortality of invasively ventilated COVID-19 patients was particularly striking. Patients with high SOFA score and receiving delayed invasive ventilation were at high risk of mortality.

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.