Clinical characteristics and host immunity responses of SARS-CoV-2 Omicron variant BA.2 with deletion of ORF7a, ORF7b and ORF8.

BACKGROUND: The pathogenicity and virulence of the Omicron strain have weakened significantly pathogenesis of Omicron variants. Accumulating data indicated accessory proteins play crucial roles in host immune evasion and virus pathogenesis of SARS-CoV-2. Therefore, the impact of simultaneous deletion of accessory protein ORF7a, ORF7b and ORF8 on the clinical characteristics and specific immunity in Omicron breakthrough infected patients (BIPs) need to be verified. METHODS: Herein, plasma cytokines were identified using a commercial Multi-cytokine detection kit. Enzyme-linked immunosorbent assay and pseudovirus neutralization assays were utilized to determine the titers of SARS-CoV-2 specific binding antibodies and neutralizing antibodies, respectively. In addition, an enzyme-linked immunospot assay was used to quantify SARS-CoV-2 specific T cells and memory B cells. RESULTS: A local COVID-19 outbreak was caused by the Omicron BA.2 variant, which featured a deletion of 871 base pairs (∆871 BA.2), resulting in the removal of ORF7a, ORF7b, and ORF8. We found that hospitalized patients with ∆871 BA.2 had significantly shorter hospital stays than those with wild-type (WT) BA.2. Plasma cytokine levels in both ∆871 BA.2 and WT BA.2 patients were within the normal range of reference, and there was no notable difference in the titers of SARS-CoV-2 ancestor or Omicron-specific binding IgG antibodies, neutralizing antibody titers, effector T cells, and memory B cells frequencies between ∆871 BA.2 and WT BA.2 infected adult patients. However, antibody titers in ∆871 BA.2 infected adolescents were higher than in adults. CONCLUSIONS: The simultaneous deletion of ORF7a, ORF7b, and ORF8 facilitates the rapid clearance of the BA.2 variant, without impacting cytokine levels or affecting SARS-CoV-2 specific humoral and cellular immunity in Omicron-infected individuals.

An N-glycopeptide MS/MS data analysis workflow leveraging two complementary glycoproteomic software tools for more confident identification and assignments.

Complete coverage of all N-glycosylation sites on the SARS-CoV2 spike protein would require the use of multiple proteases in addition to trypsin. Subsequent identification of the resulting glycopeptides by searching against database often introduces assignment errors due to similar mass differences between different permutations of amino acids and glycosyl residues. By manually interpreting the individual MS2 spectra, we report here the common sources of errors in assignment, especially those introduced by the use of chymotrypsin. We show that by applying a stringent threshold of acceptance, erroneous assignment by the commonly used Byonic software can be controlled within 15%, which can be reduced further if only those also confidently identified by a different search engine, pGlyco3, were considered. A representative site-specific N-glycosylation pattern could be constructed based on quantifying only the overlapping subset of N-glycopeptides identified at higher confidence. Applying the two complimentary glycoproteomic software in a concerted data analysis workflow, we found and confirmed that glycosylation at several sites of an unstable Omicron spike protein differed significantly from those of the stable trimeric product of the parental D614G variant.

Evaluation of Coronavirus Disease 2019 Burnout Syndrome Among Healthcare Workers in Taizhou, China.

Objectives: To evaluate COVID-19 burnout syndrome among healthcare workers in Taizhou, China. Methods: A total of 1,103 qualified healthcare workers in Taizhou were included in the study. The Maslach Burnout Inventory-General Survey (MBI-GS) was used to assess burnout syndrome. Results: Among the healthcare workers surveyed, 25.9% experienced COVID-19 burnout syndrome, including 22.3% and 3.6% with mild and moderate burnout, respectively. Multivariate linear regression models revealed associations with emotional exhaustion among healthcare workers, as follows: occupation, education level and professional qualifications. Professional efficacy was impacted by the pandemic, as follows: sex and occupation. The following factors were associated with cynicism among healthcare workers: occupation and underlying disease. Occupation (medical technician vs. physician, ß = -7.40, 95% confidence interval: -12.09 to -2.71, p = 0.002) was significantly related to MBI-GS scores after adjusting for confounding factors. Conclusion: COVID-19 burnout syndrome was common among healthcare workers in Taizhou, China, and its impact was more burdensome to physicians.

Digital Magnetic Detection of Biomolecular Interactions with Single Nanoparticles.

Biomolecular interactions compose a fundamental element of all life forms and are the biological basis of many biomedical assays. However, current methods for detecting biomolecular interactions have limitations in sensitivity and specificity. Here, using nitrogen-vacancy centers in diamond as quantum sensors, we demonstrate digital magnetic detection of biomolecular interactions with single magnetic nanoparticles (MNPs). We first developed a single-particle magnetic imaging (SiPMI) method on 100 nm-sized MNPs with negligible magnetic background, high signal stability, and accurate quantification. The single-particle method was performed on biotin-streptavidin interactions and DNA-DNA interactions in which a single-base mismatch was specifically differentiated. Subsequently, SARS-CoV-2-related antibodies and nucleic acids were examined by a digital immunomagnetic assay derived from SiPMI. In addition, a magnetic separation process improved the detection sensitivity and dynamic range by more than 3 orders of magnitude and also the specificity. This digital magnetic platform is applicable to extensive biomolecular interaction studies and ultrasensitive biomedical assays.

Immunity against Delta and Omicron variants elicited by homologous inactivated vaccine booster in kidney transplant recipients.

Background: A third mRNA vaccine booster is recommended to improve immunity against SARS-CoV-2 in kidney transplant recipients (KTRs). However, the immunity against SARS-CoV-2 Ancestral strain and Delta and Omicron variants elicited by the third dose of inactivated booster vaccine in KTRs remains unknown. Methods: The blood parameters related to blood cells count, hepatic function, kidney function, heart injury and immunity were explored clinically from laboratory examinations. SARS-CoV-2 specific antibody IgG titer was detected using an enzyme-linked immunosorbent assay. Cellular immunity was analyzed using interferon-γ enzyme-linked immunospot assay. Results: The results showed that there were no severe adverse effects and apparent changes of clinical laboratory biomarkers in KTRs and healthy volunteers (HVs) after homologous inactivated vaccine booster. A third dose of inactivated vaccine booster significantly increased anti-Ancestral-spike-trimer-IgG and anti-Ancestral-receptor binding domain (RBD)-IgG titers in KTRs and HVs compared with the second vaccination. However, the anti-Delta-RBD-IgG and anti-Omicron-RBD-IgG titers were significantly lower than anti-Ancestral-RBD-IgG titer in KTRs and HVs after the third dose. Notably, only 25.6% (10/39) and 10.3% (4/39) of KTRs had seropositivity for anti-Delta-RBD-IgG and anti-Omicron-RBD-IgG after booster, which were significantly lower than HVs (anti-Delta-RBD-IgG: 100%, anti-Omicron-RBD-IgG: 77.8%). Ancestral strain nucleocapsid protein and spike specific T cell frequency after booster was not significantly increased in KTRs compared with the second dose, significantly lower than that in HVs. Moreover, 33.3% (12/36), 14.3% (3/21) and 14.3% (3/21) of KTRs were positive for the Ancestral strain and Delta and Omicron spike-specific T cells, which were significantly lower than HVs (Ancestral: 80.8%, Delta: 53.8%, and Omicron: 57.7%). Conclusions: A third dose of inactivated booster vaccine may significantly increase humoral immunity against the Ancestral strain in KTRs, while humoral and cellular immunity against the Delta and Omicron variants were still poor in KTRs.

Ad5-nCoV booster and Omicron variant breakthrough infection following two doses of inactivated vaccine elicit comparable antibody levels against Omicron variants.

Little information is available for antibody levels against SARS-CoV-2 variants of concern induced by Omicron breakthrough infection and a third booster with an inactivated vaccine (InV) or Ad5-nCoV in people with completion of two InV doses. Plasma was collected from InV pre-vaccinated Omicron-infected patients (OIPs), unvaccinated OIPs between 0 and 22 days, and healthy donors (HDs) 14 days or 6 months after the second doses of an InV and 14 days after a homogenous booster or heterologous booster of Ad5-nCoV. Anti-Wuhan-, Anti-Delta-, and Anti-Omicron-receptor binding domain (RBD)-IgG titers were detected using enzyme-linked immunosorbent assay. InV pre-vaccinated OIPs had higher anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers compared to unvaccinated OIPs. Anti-Wuhan-RBD-IgG titers sharply increased in InV pre-vaccinated OIPs 0-5 days postinfection (DPI), while the geometric mean titers (GMTs) of anti-Delta- and anti-Omicron-RBD-IgG were 3.3-fold and 12.0-fold lower. Then, the GMT of anti-Delta- and anti-Omicron-RBD-IgG increased to 35 112 and 28 186 during 11-22 DPI, about 2.6-fold and 3.2-fold lower, respectively, than the anti-Wuhan-RBD-IgG titer. The anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers declined over time in HDs after two doses of an InV, with 25.2-fold, 5.6-fold, and 4.5-fold declination, respectively, at 6 months relative to the titers at 14 days after the second vaccination. Anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers elicited by a heterologous Ad5-nCoV booster were significantly higher than those elicited by an InV booster, comparable to those in InV pre-vaccinated OIPs. InV and Ad5-nCoV boosters could improve humoral immunity against Omicron variants. Of these, the Ad5-nCoV booster is a better alternative.

Respiratory viral testing and antibacterial treatment in patients hospitalized with community-acquired pneumonia.

OBJECTIVE: Viruses are more common than bacteria in patients hospitalized with community-acquired pneumonia. Little is known, however, about the frequency of respiratory viral testing and its associations with antimicrobial utilization. DESIGN: Retrospective cohort study. SETTING: The study included 179 US hospitals. PATIENTS: Adults admitted with pneumonia between July 2010 and June 2015. METHODS: We assessed the frequency of respiratory virus testing and compared antimicrobial utilization, mortality, length of stay, and costs between tested versus untested patients, and between virus-positive versus virus-negative patients. RESULTS: Among 166,273 patients with pneumonia on admission, 40,787 patients (24.5%) were tested for respiratory viruses, 94.8% were tested for influenza, and 20.7% were tested for other viruses. Viral assays were positive in 5,133 of 40,787 tested patients (12.6%), typically for influenza and rhinovirus. Tested patients were younger and had fewer comorbidities than untested patients, but patients with positive viral assays were older and had more comorbidities than those with negative assays. Blood cultures were positive for bacterial pathogens in 2.7% of patients with positive viral assays versus 5.3% of patients with negative viral tests (P < .001). Antibacterial courses were shorter for virus-positive versus -negative patients overall (mean 5.5 vs 6.4 days; P < .001) but varied by bacterial testing: 8.1 versus 8.0 days (P = .60) if bacterial tests were positive; 5.3 versus 6.1 days (P < .001) if bacterial tests were negative; and 3.3 versus 5.2 days (P < .001) if bacterial tests were not obtained (interaction P < .001). CONCLUSIONS: A minority of patients hospitalized with pneumonia were tested for respiratory viruses; only a fraction of potential viral pathogens were assayed; and patients with positive viral tests often received long antibacterial courses.

Effects of Tocilizumab on Adults With COVID-19 Pneumonia: A Meta-Analysis.

Background: Coronavirus disease-2019 (COVID-19), a worldwide disaster, has already affected lots of people. Effective care and therapy are currently being evaluated in full swing. Purpose: Our purpose was to investigate the effects of tocilizumab, an interleukin-6 receptor inhibitor, on treatment of adult patients with COVID-19 pneumonia. Data Sources Study Selection and Data Extraction: We conducted a meta-analysis and searched for relevant studies on Pubmed, Embase, and the Cochrane Library without restrictions on language from inception until February 1, 2021. Fifteen studies were included for this meta-analysis. Two authors independently selected and screened these studies, assessed the quality of included studies, and extracted related information. Results: Fifteen studies were included in this meta-analysis. The main studies showed that tocilizumab was associated with lower mortality (risk ratio = 0.62, 95% confidence interval = 0.46-0.83; and hazard ratio = 0.61, 95% confidence interval = 0.51-0.72). Using tocilizumab might also affect biochemistry indicators (lowered C-reactive protein and ferritin, increased lymphocyte count). Conclusion: These current bodies of evidence could indicate that early use of tocilizumab was associated with lower mortality in adult patients with COVID-19. Early use of tocilizumab could reduce the mortality rate of adult patients with COVID-19 without obvious fatal side effects, which may be a treatment option in patients with COVID-19 pneumonia. Systematic Review Registration: The study protocol was registered on PROSPERO (ID:242811).

Immunity against Delta and Omicron variants elicited by homologous inactivated vaccine booster in kidney transplant recipients

Background A third mRNA vaccine booster is recommended to improve immunity against SARS-CoV-2 in kidney transplant recipients (KTRs). However, the immunity against SARS-CoV-2 Ancestral strain and Delta and Omicron variants elicited by the third dose of inactivated booster vaccine in KTRs remains unknown. Methods The blood parameters related to blood cells count, hepatic function, kidney function, heart injury and immunity were explored clinically from laboratory examinations. SARS-CoV-2 specific antibody IgG titer was detected using an enzyme-linked immunosorbent assay. Cellular immunity was analyzed using interferon-γ enzyme-linked immunospot assay. Results The results showed that there were no severe adverse effects and apparent changes of clinical laboratory biomarkers in KTRs and healthy volunteers (HVs) after homologous inactivated vaccine booster. A third dose of inactivated vaccine booster significantly increased anti-Ancestral-spike-trimer-IgG and anti-Ancestral-receptor binding domain (RBD)-IgG titers in KTRs and HVs compared with the second vaccination. However, the anti-Delta-RBD-IgG and anti-Omicron-RBD-IgG titers were significantly lower than anti-Ancestral-RBD-IgG titer in KTRs and HVs after the third dose. Notably, only 25.6% (10/39) and 10.3% (4/39) of KTRs had seropositivity for anti-Delta-RBD-IgG and anti-Omicron-RBD-IgG after booster, which were significantly lower than HVs (anti-Delta-RBD-IgG: 100%, anti-Omicron-RBD-IgG: 77.8%). Ancestral strain nucleocapsid protein and spike specific T cell frequency after booster was not significantly increased in KTRs compared with the second dose, significantly lower than that in HVs. Moreover, 33.3% (12/36), 14.3% (3/21) and 14.3% (3/21) of KTRs were positive for the Ancestral strain and Delta and Omicron spike-specific T cells, which were significantly lower than HVs (Ancestral: 80.8%, Delta: 53.8%, and Omicron: 57.7%). Conclusions A third dose of inactivated booster vaccine may significantly increase humoral immunity against the Ancestral strain in KTRs, while humoral and cellular immunity against the Delta and Omicron variants were still poor in KTRs.

Long-term impacts of non-occupational wildfire exposure on human health: A systematic review.

The intensity and frequency of wildfires is increasing globally. The systematic review of the current evidence on long-term impacts of non-occupational wildfire exposure on human health has not been performed yet. To provide a systematic review and identify potential knowledge gaps in the current evidence of long-term impacts of non-occupational exposure to wildfire smoke and/or wildfire impacts on human health. We conducted a systematic search of the literature via MEDLINE, Embase and Scopus from the database inception to July 05, 2022. References from the included studies and relevant reviews were also considered. The Newcastle-Ottawa Scale (NOS) and a validated quality assessment framework were used to evaluate the quality of observational studies. Study results were synthesized descriptively. A total of 36 studies were included in our systematic review. Most studies were from developed countries (11 in Australia, 9 in Canada, 7 in the United States). Studies predominantly focused on mental health (21 studies, 58.33%), while evidence on long-term impacts of wildfire exposure on health outcomes other than mental health is limited. Current evidence indicated that long-term impacts of non-occupational wildfire exposure were associated with mortality (COVID-19 mortality, cardiovascular disease mortality and acute myocardial disease mortality), morbidity (mainly respiratory diseases), mental health disorders (mainly posttraumatic stress disorder), shorter height of children, reduced lung function and poorer general health status. However, no significant associations were observed for long-term impacts of wildfire exposure on child mortality and respiratory hospitalizations. The population-based high-quality evidence with quantitative analysis on this topic is still limited. Future well-designed studies considering extensive wildfire smoke air pollutants (e.g., particulate matter, ozone, nitrogen oxides) and estimating risk coefficient values for extensive health outcomes (e.g., mortality, morbidity) are warranted to fill current knowledge gaps.

Omicron variants breakthrough infection elicited higher specific memory immunity than third dose booster in healthy vaccinees.

Homologous booster, heterologous booster, and Omicron variants breakthrough infection (OBI) could improve the humoral immunity against Omicron variants. Questions concerning about memory B cells (MBCs) and T cells immunity against Omicron variants, features of long-term immunity, after booster and OBI, needs to be explored. Here, comparative analysis demonstrate antibody and T cell immunity against ancestral strain, Delta and Omicron variants in Omicron breakthrough infected patients (OBIPs) are comparable to that in Ad5-nCoV boosted healthy volunteers (HVs), higher than that in inactivated vaccine (InV) boosted HVs. However, memory B cells (MBCs) immunity against Omicron variants was highest in OBIPs, followed by Ad5-nCoV boosted and InV boosted HVs. OBIPs and Ad5-nCoV boosted HVs have higher classical MBCs and activated MBCs, and lower naïve MBCs and atypical MBCs relative to both vaccine boosted HVs. Collectively, these data indicate Omicron breakthrough infection elicit higher MBCs and T cells against SARS-CoV-2 especially Omicron variants relative to homologous InV booster and heterologous Ad5-nCoV booster.

Determinants of the willingness of medical staff to vaccinate their children with a booster dose of the COVID-19 vaccine in Taizhou, China.

The study aimed to determine the willingness of medical staff to have their children vaccinated with a COVID-19 booster in Taizhou, China. From March 21 to April 19, 2022, an online questionnaire survey was conducted to assess the willingness of medical staff to vaccinate their children with a booster dose of the COVID-19 vaccine. Of the 1,252 medical staff in a tertiary grade hospital in Taizhou who were invited to answer the structured questionnaire, 514 (41.1%) samples had valid information for further data analysis. Four hundred thirty-seven medical staff (85.0%) were willing to have their children receive vaccine boosters. After adjustments for confounding factors, the opinion ('Do you think your child needs a booster vaccination against COVID-19?') (yes vs. no, OR = 6.91, 95% CI: 3.29-14.54), the viewpoint ('What are your thoughts the effectiveness of COVID-19 vaccine boosters for children?' (≥12 vs. <12, OR = 13.81, 95% CI: 4.03-), and the attitude ('Your attitude to whether your child is boosting the Covid-19 vaccine?') (yes vs. no, OR = 4.66, 95% CI: 2.30-9.44) were significantly associated with their willingness to have their children receive a COVID-19 vaccine booster. A moderate percentage of the respondents expressed willingness to have their children receive booster vaccines. The findings implied that factors affecting medical staffs' willingness to vaccinate their children with a COVID-19 vaccine booster included viewpoint, opinion, and attitudes.

Relationship between nosocomial infections and coronavirus disease 2019 in the neurosurgery unit: clinical characteristics and outcomes from a Chinese Tertiary-Care Hospital.

BACKGROUND: The COVID-19 pandemic has raised awareness of infection prevention and control. We found that the incidence of nosocomial infection in neurosurgery has changed. This study aimed to evaluate the impact of "coronavirus disease 2019 (COVID-19) prevention and control measures" on nosocomial infections in neurosurgery. METHODS: To explore changes in nosocomial infections in neurosurgery during the COVID-19 pandemic, the clinical data of inpatients undergoing neurosurgery at Taizhou Hospital of Zhejiang Province between January 1 and April 30, 2020 (COVID-19 era) were first analyzed and then compared with those from same period in 2019 (first pre-COVID-19 era). We also analyzed data between May 1 and December 31, 2020 (post-COVID-19 era) at the same time in 2019 (second pre-COVID-19 era). RESULTS: The nosocomial infection rate was 7.85% (54/688) in the first pre-COVID-19 era and 4.30% (26/605) in the COVID-19 era (P = 0.01). The respiratory system infection rate between the first pre-COVID-19 and COVID-19 eras was 6.1% vs. 2.0% (P < 0.01), while the urinary system infection rate was 1.7% vs. 2.0% (P = 0.84). Between the first pre-COVID-19 and COVID-19 eras, respiratory system and urinary infections accounted for 77.78% (42/54) vs. 46.15% (12/26) and 22.22% (12/54) vs. 46.15% (12/26) of the total nosocomial infections, respectively (P < 0.01). Between the second pre-COVID-19 and post-COVID-19 eras, respiratory system and urinary accounted for 53.66% (44/82) vs. 40.63% (39/96) and 24.39% (20/82) vs. 40.63% (39/96) of the total nosocomial infections, respectively (P = 0.02). CONCLUSIONS: The incidence of nosocomial infections in neurosurgery reduced during the COVID-19 pandemic. The reduction was primarily observed in respiratory infections, while the proportion of urinary infections increased significantly.

Evaluation of burnout among stay-behind healthcare workers during the current Omicron wave of COVID-19 in Taizhou, China.

Background: Since February 2022, a new Omicron wave of COVID-19 emerged in Shanghai, China. Many healthcare workers came to Shanghai from hospitals of other parts of China as aid workers. Hospitals in areas with mild COVID-19 outbreaks will inevitably be understaffed, it is likely to cause job burnout of stay-behind healthcare workers. Stay-behind healthcare workers were those who had not been dispatched to support COVID-19 prevention and control in other regions. This study was designed to evaluate the burnout among stay-behind healthcare workers in the current COVID-19 Omicron wave in Taizhou, China. Methods: A population-based, anonymous, cross-sectional online survey was designed in the Wen-Juan Xing platform. The survey was sent to all stay-behind healthcare workers of the hospital (n = 1739) from April 29 to May 3, 2022. The Maslach Burnout Inventory-General Survey (MBI-GS) was used for the burnout survey. For univariate analysis, the χ2 test and one way ANOVA were used to assess differences in categorical variables and continuous variables, respectively. The effect of independent associated risk factors on each type of burnout was examined using the multinomial logistic regression model. Results: A total of 434 participants completed the survey invitation effectively. A total of 71.2% of stay-behind healthcare workers experienced burnout during COVID-19, including 54.8% experiencing mild to moderate burnout and 16.4% experiencing severe burnout. Night shift, depression, social support, positive coping and number of children appeared to be significantly related to mild to moderate burnout. Night shift, depression, social support, positive coping, number of children, professional title, and anxiety appeared to be significantly related to severe burnout. Conclusion: Job burnout among stay-behind healthcare workers was an important problem during the current Omicron wave of COVID-19. Night shift, depression, social support, positive coping, and number of children were associated with mild to moderate and severe burnout. Anxiety and professional title were associated with severe burnout.

Parental hesitancy towards vaccinating their children with a booster dose against COVID-19: Real-world evidence from Taizhou, China.

INTRODUCTION: Parental vaccine-hesitancy can lead to delays or refusal to vaccinate children despite the availability of vaccines. This is a population-based, cross-sectional study investigating whether parents in China are hesitant to vaccinate their children with a COVID-19 vaccine booster. METHODS: Parents in Taizhou, China, responded to a self-reported online questionnaire on their hesitancy to vaccinate their children with a COVID-19 vaccine booster. Of the 1252 parents who were invited to answer the structured questionnaire, 514 (41.1%) samples had valid data for data analysis. RESULTS: A total of 41.8% of participants were hesitant to give their children a COVID-19 vaccine booster. After adjusting for confounders, parental gender (female vs. male parent, OR=0.56 95% CI: 0.32-0.87), parental opinion (yes vs. no, OR=0.17, 95% CI: 0.09-0.30), parental attitudes (yes vs. no, OR=0.28, 95% CI: 0.16-0.50), the presence of people around them who are generally hesitant to receive COVID-19 booster vaccines for children (yes vs. no, OR=0.14, 95%CI: 0.08-0.23), the individual hesitancy of people around them to administer booster COVID-19 vaccines to children (yes vs. no, OR=0.02, 95%CI: 0.02-0.22), and parents' hesitancy to receive a booster vaccine for their children showed significant correlation. The disparity of factors related to booster vaccine-hesitancy for children between fathers and mothers was also found. CONCLUSIONS: We found that a moderate proportion of parents reported that they were hesitant to give their children a COVID-19 vaccine booster. The results suggest that an in-depth, dynamic assessment and further health education planning are necessary to reduce Chinese parents' hesitancy to vaccinate their children.

Long-term improvement of air quality associated with lung function benefits in Chinese young adults: A quasi-experiment cohort study.

INTRODUCTION: Long-term exposure to air pollution is associated with lung function impairment. However, whether long-term improvements in air quality could improve lung function is unclear. OBJECTIVES: To examine whether the reduction of long-term air pollution was associated with lung function improvement among Chinese young adults. METHODS: We conducted a prospective quasi-experiment cohort study with 1731 college students in Shandong, China from September 2019 to September 2020, covering COVID-19 lockdown period. Data on air pollution concentrations were obtained from China Environmental Monitoring Station. Lung function indicators included forced vital capacity (FVC), forced expiratory volume in 1st second (FEV1) and forced expiratory flow at 50 % of FVC (FEF50%). We used linear mixed-effects model to examine the associations between the change of air pollutants concentrations and the change of lung function, and additional adjustments for indoor air pollution (IAP) source. We also conducted stratified analysis by sex. RESULTS: Compared with 2019, the mean FVC, FEV1 and FEF50% were elevated by 414.4 ml, 321.5 ml, and 28.4 ml/s respectively in 2020. Every 5 µg/m3 decrease in annual average PM2.5 concentrations was associated with 36.0 ml [95 % confidence interval (CI):6.0, 66.0 ml], 46.1 ml (95 % CI:16.7, 75.5 ml), and 124.2 ml/s (95 % CI:69.5, 178.9 ml/s) increment in the FVC, FEV1, and FEF50%, respectively. Similar associations were found for PM10. The estimated impact was almost unchanged after adjusting for IAP source. There was no significant effect difference between males and females. CONCLUSION: Long-term improvement of air quality can improve lung function among young adults. Stricter policies on improving air quality are needed to protect human health.

Biophysical and structural characterizations of the effects of mutations on the structure-activity relationships of SARS-CoV-2 spike protein.

Mutations on the spike (S) protein of SARS-CoV-2 could induce structural changes that help increase viral transmissibility and enhance resistance to antibody neutralization. Here, we report a robust workflow to prepare recombinant S protein variants and its host receptor angiotensin-convert enzyme 2 (ACE2) by using a mammalian cell expression system. The functional states of the S protein variants are investigated by cryo-electron microscopy (cryo-EM) and negative staining electron microscopy (NSEM) to visualize their molecular structures in response to mutations, receptor binding, antibody binding, and environmental changes. The folding stabilities of the S protein variants can be deduced from morphological changes based on NSEM imaging analysis. Differential scanning calorimetry provides thermodynamic information to complement NSEM. Impacts of the mutations on host receptor binding and antibody neutralization are in vitro by kinetic binding analyses in addition to atomic insights gleaned from cryo-electron microscopy (cryo-EM). This experimental strategy is generally applicable to studying the molecular basis of host-pathogen interactions.

A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants.

BACKGROUND: With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy. METHODS: We report an mRNA-based vaccine using an engineered "hybrid" receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. RESULTS: A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. CONCLUSIONS: These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.

The Issues of the Authorization for Emergency Use of Vaccines and Relief for Victims of Vaccination

COVID-19 ravaged the world, and due to the special circumstances of emergency preventive needs, the vaccine was approved to be marketed under the emergency use authorization without completing clinical trials. Since the unknown and potential risks borne by the vaccinees are higher, the injuries caused by the vaccination are compensated by the relief system. As to the manufacture or importation of the vaccination under special approval, the central authority could have made its own review and decision to approve it or reject. However, the actual decision is given to the expert review meeting giving advisories. And the situation in respect of the review of injury compensation of the preventive vaccination is similar with it. The competent authority is suspected of controlling the results of the evaluation by the selection of expert members and relieving itself of responsibility. If a civil servant of the competent authority or an outside expert selected by it during the examination process of the vaccine approved for the national use commits any illegal misconduct of breaches of professionalism and causes injury to the vaccine recipient, a national compensation to the both sides could be filed at the same time. Nevertheless, all of the accused should be restricted that he couldn't claim a right for compensation to a third party in respect of the same issue of injury. Additionally, all vaccines, no matter they are manufactured domestically or imported under special approval, should be included in the scope of the vaccine victimization remedies, and the EUA program should be considered leniently, and the unknown and potential risks of the insufficient medical evidence shouldn't be borne by the vaccine recipients.