Reduced antibody response to COVID-19 vaccine composed of inactivated SARS-CoV-2 in diabetic individuals.

Background: Patients with type 2 diabetes mellitus (T2DM) are at increased risk for COVID-19 related morbidity and mortality. Antibody response to COVID-19 vaccine in T2DM patients is not very clear. The present work aims to evaluate the antibody response to the inactivated SARS-CoV-2 vaccine in this population. Methods: Two groups of subjects with no history of SARS-CoV-2 infection were included: 63 T2DM patients and 56 non-T2DM controls. Each participant received two doses of inactivated COVID-19 vaccine. IgG antibodies against the nucleocapsid (N) and spike (S) proteins of SARS-CoV-2 (anti-N/S IgG) and receptor binding domain (RBD) proteins (anti-RBD IgG) were quantitatively evaluated by the electrochemiluminescence immunoassays, respectively. Results: It was observed that the positive rates and titers of anti-N/S IgG and anti-RBD IgG in T2DM patients were significantly lower than those in controls, respectively (anti-N/S: 85.7 vs. 98.2%, P = 0.034; 25.48 vs. 33.58 AU/ml P = 0.011; anti-RBD: 85.7 vs. 96.4%, P = 0.044; 15.45 vs. 22.25 AU/ml, P = 0.019). Compared to non-T2DM subjects, T2DM patients with uncontrolled glycemia showed lower positive antibody rates and titers (anti-N/S IgG: 75% and 13.30 AU/ml; anti-RBD IgG: 75% and 11.91 AU/ml, respectively, all P < 0.05), while T2DM patients with controlled glycemia had similar positive antibody rates and titers (anti-N/S IgG: 94.3% and 33.65 AU/ml; and anti-RBD IgG: 94.3% and 19.82 AU/ml, respectively, all P > 0.05). Conclusion: In the analysis performed, the data indicate that T2DM patients with uncontrolled glycemia showed a lower level of IgG antibodies compared to non-diabetic controls and individuals with controlled glycemia when immunized with the inactivated COVID-19 vaccine.

A longitudinal study of humoral immune responses induced by a 3-dose inactivated COVID-19 vaccine in an observational, prospective cohort.

BACKGROUND: To determine the dynamic SARS-CoV-2 specific antibody levels induced by 3 doses of an inactivated COVID-19 vaccine, CoronaVac. An observational, prospective cohort study was performed with 93 healthy healthcare workers from a tertiary hospital in Nanjing, China. Serum SARS-CoV-2 specific IgM, IgG, and neutralizing antibodies (NAb) were measured at different time points among participants who received 3 doses of inactivated COVID-19 vaccine. RESULTS: 91.3% (85/93) and 100% (72/72) participants showed positive both for SARS-CoV-2 specific IgG and NAb after 2-dose CoronaVac and after 3-dose CoronaVac, respectively. Anti-SARS-CoV-2 IgG responses reached 91.21 (55.66-152.06) AU/mL, and surrogate NAb was 47.60 (25.96-100.81) IU/mL on day 14 after the second dose. Anti-SARS-CoV-2 IgG responses reached 218.29 (167.53-292.16) AU/mL and surrogate NAb was 445.54 (171.54-810.90) IU/mL on day 14 after the third dose. Additionally, SARS-CoV-2 specific surrogate neutralizing antibody titers were highly correlated with serum neutralization activities against Ancestral, Omicron, and Delta strains. Moreover, significantly higher SARS-CoV-2 IgG responses, but not NAb responses, were found in individuals with breakthrough infection when compared to that of 3-dose CoronaVac recipients. CONCLUSIONS: CoronaVac elicited robust SARS-CoV-2 specific humoral responses. Surrogate NAb assay might substitute for pseudovirus neutralization assay. Monitoring SARS-CoV-2 antibody responses induced by vaccination would provide important guidance for the optimization of COVID-19 vaccines.

The Third dose of CoronVac vaccination induces broad and potent adaptive immune responses that recognize SARS-CoV-2 Delta and Omicron variants.

The waning humoral immunity and emerging contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants resulted in the necessity of the booster vaccination of coronavirus disease 2019 (COVID-19). The inactivated vaccine, CoronaVac, is the most widely supplied COVID-19 vaccine globally. Whether the CoronaVac booster elicited adaptive responses that cross-recognize SARS-CoV-2 variants of concern (VoCs) among 77 healthy subjects receiving the third dose of CoronaVac were explored. After the boost, remarkable elevated spike-specific IgG and IgA responses, as well as boosted neutralization activities, were observed, despite 3.0-fold and 5.9-fold reduced neutralization activities against Delta and Omicron strains compared to that of the ancestral strain. Furthermore, the booster dose induced potent B cells and memory B cells that cross-bound receptor-binding domain (RBD) proteins derived from VoCs, while Delta and Omicron RBD-specific memory B cell recognitions were reduced by 2.7-fold and 4.2-fold compared to that of ancestral strain, respectively. Consistently, spike-specific circulating follicular helper T cells (cTfh) significantly increased and remained stable after the boost, with a predominant expansion towards cTfh17 subpopulations. Moreover, SARS-CoV-2-specific CD4+ and CD8+ T cells peaked and sustained after the booster. Notably, CD4+ and CD8+ T cell recognition of VoC spike was largely preserved compared to the ancestral strain. Individuals without generating Delta or Omicron neutralization activities had comparable levels of CD4+ and CD8+ T cells responses as those with detectable neutralizing activities. Our study demonstrated that the CoronaVac booster induced broad and potent adaptive immune responses that could be effective in controlling SARS-CoV-2 Delta and Omicron variants.

Evaluation of Molecular Point-of-Care Testing for Respiratory Pathogens in Children With Respiratory Infections: A Retrospective Case-Control Study.

Objectives: Overuse of antibiotics and antibiotic resistance are global healthcare problems. In pediatric patients with respiratory infections, viral and bacterial etiologies are challenging to distinguish, leading to irrational antibiotic use. Rapid and accurate molecular diagnostic testing methods for respiratory pathogens has been shown to facilitate effective clinical decision-making and guide antibiotic stewardship interventions in the developed regions, but its impacts on pediatric patient care in the developing countries remain unclear. Methods: In this single-center, retrospective case-control study, we compared demographics, clinical characteristics, especially microbiological findings, and antibiotic usage between pediatric patients with respiratory infection receiving FilmArray Respiratory Panel (FilmArray RP) testing and a matched routine testing control group. Our primary outcome was the duration of intravenous antibiotics treatment (DOT) during hospitalization. Results: Each group consisted of 346 children with a respiratory infection. In the FilmArray RP testing group, the DOT was shorter than that in the routine testing group (6.41 ± 3.67 days versus 7.23 ± 4.27 days; p = 0.006). More patients in the FilmArray RP testing group de-escalated antibiotic treatments within 72 hours of hospitalization (7.80%, 27/346 versus 2.60%, 9/346; p = 0.002). By contrast, fewer patients in the FilmArray RP testing group had escalated antibiotic treatments between 72 hours and seven days (7.80% versus 14.16%; p = 0.007). The cost of hospitalization was significantly lower in the FilmArray RP testing group ($ 1413.51 ± 1438.01 versus $ 1759.37 ± 1929.22; p = 0.008). Notably, the subgroup analyses revealed that the FilmArray RP test could shorten the DOT, improve early de-escalation of intravenous antibiotics within 72 hours of hospitalization, decline the escalation of intravenous antibiotics between 72 hours and seven days, and reduce the cost of hospitalization for both patient populations with or without underlying diseases. Conclusions: Molecular point-of-care testing for respiratory pathogens could help to reduce intravenous antibiotic use and health care costs of pediatric patients with respiratory infections in developing countries.

Dynamic SARS-CoV-2-specific B-cell and T-cell responses following immunization with an inactivated COVID-19 vaccine.

OBJECTIVE: The dynamic adaptive immune responses elicited by the inactivated virus vaccine CoronaVac remain elusive. METHODS: In a prospective cohort of 100 healthcare professionals naïve for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who received two doses of CoronaVac, we analysed SARS-CoV-2-specific humoral and cellular responses at four different timepoints, including before vaccination (T1), 2 weeks after the first dose (T2), 2 weeks after the booster dose (T3), and 8-10 weeks after the booster dose (T4). SARS-CoV-2-specific antibodies, serum neutralizing activities, peripheral B cells, CD4+ and CD8+ T cells and their memory subsets were simultaneously measured in this cohort. RESULTS: SARS-CoV-2 spike-specific IgG responses reached a peak (geometric mean titre (GMT) 54827, 30969-97065) after two doses and rapidly declined (GMT 502, 212-1190) at T4, whereas suboptimal IgA responses were detected (GMT 5, 2-9). Spike-specific circulating B cells (0.60%, 0.46-0.73% of total B cells) and memory B cells (1.18%, 0.92-1.44% of total memory B cells) were effectively induced at T3 and sustained over time (0.33%, 0.23-0.43%; 0.87%, 0.05-1.67%, respectively). SARS-CoV-2-specific circulating CD4+ T cells (0.57%, 0.47-0.66%) and CD8+ T cells (1.29%, 1.04-1.54%) were detected at T3. At T4, 0.78% (0.43-1.20%) of memory CD4+ T cells and 0.68% (0.29-1.30%) of memory CD8+ T cells were identified as SARS-CoV-2-specific, while 0.62% (0.51-0.75%) of CD4+ T cells and 0.47% (0.38-0.58%) of CD8+ T cells were SARS-CoV-2-specific terminally differentiated effector memory cells. Furthermore, age and interval between doses affected the magnitude of CoronaVac-induced immune responses. SARS-CoV-2 memory CD4+ T cells were strongly associated with both receptor binding domain (RBD)-specific memory B cells (r 0.87, p <0.0001) and SARS-CoV-2-specific memory CD8+ T cells (r 0.48, p <0.0001). CONCLUSIONS: CoronaVac induced robust circulating and memory B cell and T cell responses. Our study offers new insight into the underlying immunobiology of inactivated virus vaccines in humans and may have implications for vaccine strategies in the future.

Potent RBD-specific neutralizing rabbit monoclonal antibodies recognize emerging SARS-CoV-2 variants elicited by DNA prime-protein boost vaccination.

Global concerns arose as the emerged and rapidly spreading SARS-CoV-2 variants might escape host immunity induced by vaccination. In this study, a heterologous prime-boost immunization strategy for COVID-19 was designed to prime with a DNA vaccine encoding wild type (WT) spike protein receptor-binding domain (RBD) followed by S1 protein-based vaccine in rabbits. Four vaccine-elicited rabbit monoclonal antibodies (RmAbs), including 1H1, 9H1, 7G5, and 5E1, were isolated for biophysical property, neutralization potency and sequence analysis. All RmAbs recognized RBD or S1 protein with KD in the low nM or sub nM range. 1H1 and 9H1, but neither 7G5 nor 5E1, can bind to all RBD protein variants derived from B.1.351. All four RmAbs were able to neutralize wild type (WT) SARS-CoV-2 strain in pseudovirus assay, and 1H1 and 9H1 could neutralize the SARS-CoV-2 WT authentic virus with IC50 values of 0.136 and 0.026 µg/mL, respectively. Notably, 1H1 was able to neutralize all 6 emerging SARS-CoV-2 variants tested including D614G, B.1.1.7, B.1.429, P.1, B.1.526, and B.1.351 variants, and 5E1 could neutralize against the above 5 variants except P.1. Epitope binning analysis revealed that 9H1, 5E1 and 1H1 recognized distinct epitopes, while 9H1 and 7G5 may have overlapping but not identical epitope. In conclusion, DNA priming protein boost vaccination was an effective strategy to induce RmAbs with potent neutralization capability against not only SARS-CoV-2 WT strain but also emergent variants, which may provide a new avenue for effective therapeutics and point-of-care diagnostic measures.

SARS-CoV-2 serological antibody testing: problems of false detections and the solutions

The new type of coronavirus pneumonia poses a huge threat to the world. At present, serum antibody testing has become a key indicator for the diagnosis and epidemic control of the disease. In my country's "New Coronavirus Pneumonia Diagnosis and Treatment Plan (Trial Version 7)", the new coronavirus antibody test has been clearly established as the clinical diagnosis standard. In the actual clinical work process, the author found that there are false positive or false negative problems in the new coronavirus antibody test, which caused confusion in clinical interpretation. This article focuses on the design and principle of the new coronavirus antibody detection method, analyses the reasons that can cause false positive and false negative results, and points out the solutions, so as to promote a better understanding of the new coronavirus antibody detection, and provide a more comprehensive clinical experience Interpretation of results.

Examining Public Concerns and Attitudes toward Unfair Events Involving Elderly Travelers during the COVID-19 Pandemic Using Weibo Data.

The Chinese government has launched a digital health code system to detect people potentially exposed to the coronavirus 2019 (COVID-19) disease and to curb its spread. Citizens are required to show the health code on their smartphones when using public transport. However, many seniors are not allowed to use public transport due to their difficulties in obtaining health codes, leading to widespread debates about these unfair events. Traditionally, public perceptions and attitudes toward such unfair events are investigated using analytical methods based on interviews or questionnaires. This study crawled seven-month messages from Sina Weibo, the Chinese version of Twitter, and developed a hybrid approach integrating term-frequency-inverse-document-frequency, latent Dirichlet allocation, and sentiment classification. Results indicate that a rumor about the unfair treatment of elderly travelers triggered public concerns. Primary subjects of concern were the status quo of elderly travelers, the provision of transport services, and unfair event descriptions. Following the government's responses, people still had negative attitudes toward transport services, while they became more positive about the status quo of elderly travelers. These findings will guide government authorities to explore new forms of automated social control and to improve transport policies in terms of equity and fairness in future pandemics.

Racial Segregation, Testing Site Access, and COVID-19 Incidence Rate in Massachusetts, USA

The U.S. has merely 4% of the world population, but contains 25% of the world’s COVID-19 cases. Since the COVID-19 outbreak in the U.S., Massachusetts has been leading other states in the total number of COVID-19 cases. Racial residential segregation is a fundamental cause of racial disparities in health. Moreover, disparities of access to health care have a large impact on COVID-19 cases. Thus, this study estimates racial segregation and disparities in testing site access and employs economic, demographic, and transportation variables at the city/town level in Massachusetts. Spatial regression models are applied to evaluate the relationships between COVID-19 incidence rate and related variables. This is the first study to apply spatial analysis methods across neighborhoods in the U.S. to examine the COVID-19 incidence rate. The findings are: (1) Residential segregations of Hispanic and Non-Hispanic Black/African Americans have a significantly positive association with COVID-19 incidence rate, indicating the higher susceptibility of COVID-19 infections among minority groups. (2) Non-Hispanic Black/African Americans have the shortest drive time to testing sites, followed by Hispanic, Non-Hispanic Asians, and Non-Hispanic Whites. The drive time to testing sites is significantly negatively associated with the COVID-19 incidence rate, implying the importance of the accessibility of testing sites by all populations. (3) Poverty rate and road density are significant explanatory variables. Importantly, overcrowding represented by more than one person per room is a significant variable found to be positively associated with COVID-19 incidence rate, suggesting the effectiveness of social distancing for reducing infection. (4) Different from the findings of previous studies, the elderly population rate is not statistically significantly correlated with the incidence rate because the elderly population in Massachusetts is less distributed in the hotspot regions of COVID-19 infections. The findings in this study provide useful insights for policymakers to propose new strategies to contain the COVID-19 transmissions in Massachusetts.

KOH-activated porous biochar with high specific surface area for adsorptive removal of chromium (VI) and naphthalene from water: Affecting factors, mechanisms and reusability exploration

Herein, a high-performance porous biochar described as PBCKOH was successfully synthesized by two-step pyrolysis of corn straw with chemical activation of KOH, and was employed for the elimination of Cr(VI) and naphthalene (NAP) from water. Benefiting from KOH activation, the PBCKOH was found to possess huge specific surface area of 2183.80 m2/g and many well-developed micropores with average particle size of 2.75 nm and main pore diameters distribution from 1 to 2 nm. The PBCKOH presented an excellent adsorption performance with a theoretical monolayer uptake of 116.97 mg/g for Cr(VI) and a heterogeneous adsorption capacity of 450.43 mg/g for NAP. The uptake equilibrium was attained within about 120 min for Cr(VI), while about 180 min for NAP following avrami fractional-order model, revealing the existence of multiple kinetics during the adsorption. The thermodynamic results showed that the uptake of both Cr(VI) and NAP occurred spontaneously (-ΔG°), while in an endothermic nature for Cr(VI) (+ΔH°) and an exothermic characteristic for NAP (-ΔH°) with different randomness. Furthermore, the PBCKOH was believed to enhance the Cr(VI) adsorption mainly through the combination of electrostatic attraction, complexation, ion exchange and reduction action, while achieving the high NAP uptake by pore filling and π-πstacking interactions.