Reducedhumoral response against variants of concern in childhood solid cancer patients compared to adult patients and healthy children after SARS-CoV-2 vaccination.

Introduction: Although there is extended research on the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in adult cancer patients (ACP), the immunogenicity to the variants of concern (VOCs) in childhood cancer patients (CCP) and safety profiles are now little known. Methods: A prospective, multi-center cohort study was performed by recruiting children with a solid cancer diagnosis and childhood healthy control (CHC) to receive standard two-dose SARS-CoV-2 vaccines. An independent ACP group was included to match CCP in treatment history. Humoral response to six variants was performed and adverse events were followed up 3 months after vaccination. Responses to variants were compared with ACP and CHC by means of propensity score-matched (PSM) analysis. Results: The analysis included 111 CCP (27.2%, median age of 8, quartile 5.5-15 years), 134 CHC (32.8%), and 163 ACP (40.0%), for a total 408 patients. Pathology included carcinoma, neural tumors, sarcoma, and germ cell tumors. Median chemotherapy time was 7 (quartile, 5-11) months. In PSM sample pairs, the humoral response of CCP against variants was significantly decreased, and serology titers (281.8 ± 315.5 U/ml) were reduced, as compared to ACP (p< 0.01 for the rate of neutralization rate against each variant) and CHC (p< 0.01 for the rate of neutralization against each variant) groups. Chemotherapy time and age (Pearson r ≥ 0.8 for all variants) were associated with the humoral response against VOCs of the CHC group. In the CCP group, less than grade II adverse events were observed, including 32 patients with local reactions, and 29 patients had systemic adverse events, including fever (n = 9), rash (n = 20), headache (n = 3), fatigue (n = 11), and myalgia (n = 15). All reactions were well-managed medically. Conclusions: The humoral response against VOCs after the CoronaVac vaccination in CCP was moderately impaired although the vaccine was safe. Age and chemotherapy time seem to be the primary reason for poor response and low serology levels.

[Impacts of COVID-19 Lockdown on Air Quality in Shenzhen in Spring 2022].

The short-term reduction of air pollutant emissions is an important emergency control measure for avoiding air pollution exceedances in Chinese cities. However, the impacts of short-term emission reductions on the air qualities in southern Chinese cities in spring has not been fully explored. We analyzed the changes in air quality in Shenzhen, Guangdong before, during, and after a city-wide lockdown associated with COVID-19 control during March 14 to 20, 2022. Stable weather conditions prevailed before and during the lockdown, such that local air pollution was strongly affected by local emissions. In-situ measurements and WRF-GC simulations over the Pearl River Delta (PRD) both showed that, due to reductions in traffic emissions during the lockdown, the concentrations of nitrogen dioxide (NO2), respirable particulate matter (PM10), and fine particulate matters (PM2.5) in Shenzhen decreased by (-26±9.5)%, (-28±6.4)%, and (-20±8.2)%, respectively. However, surface ozone (O3) concentration did not change significantly[(-1.0±6.5)%]. TROPOMI satellite observations of formaldehyde and nitrogen dioxide column concentrations indicated that the ozone photochemistry in the PRD in spring 2022 was mainly controlled by the volatile organic compound (VOCs) concentrations and was not sensitive to the reduction in nitrogen oxide (NOx) concentrations. Reduction in NOx may even have increased O3, because the titration of O3 by NOx was weakened. Due to the small spatial-temporal extent of emission reductions, the air quality effects caused by this short-term urban-scale lockdown were weaker than the air quality effects across China during the widespread COVID-19 lockdown in 2020. Future air quality management in South China cities should consider the impacts of NOx emission reduction on ozone and focus on the co-reduction scenarios of NOx and VOCs.

Thyroid function and associated mood changes after COVID-19 vaccines in patients with Hashimoto thyroiditis.

Context: Severe acute respiratory syndrome-coronavirus 2 (COVID-19) vaccines may incur changes in thyroid functions followed by mood changes, and patients with Hashimoto thyroiditis (HT) were suggested to bear a higher risk. Objectives: We primarily aim to find whether COVID-19 vaccination could induce potential subsequent thyroid function and mood changes. The secondary aim was to find inflammatory biomarkers associated with risk. Methods: The retrospective, multi-center study recruited patients with HT receiving COVID-19-inactivated vaccines. C-reactive proteins (CRPs), thyroid-stimulating hormones (TSHs), and mood changes were studied before and after vaccination during a follow-up of a 6-month period. Independent association was investigated between incidence of mood state, thyroid functions, and inflammatory markers. Propensity score-matched comparisons between the vaccine and control groups were carried out to investigate the difference. Results: Final analysis included 2,765 patients with HT in the vaccine group and 1,288 patients in the control group. In the matched analysis, TSH increase and mood change incidence were both significantly higher in the vaccine group (11.9% versus 6.1% for TSH increase and 12.7% versus 8.4% for mood change incidence). An increase in CRP was associated with mood change (p< 0.01 by the Kaplan-Meier method) and severity (r = 0.75) after vaccination. Baseline CRP, TSH, and antibodies of thyroid peroxidase (anti-TPO) were found to predict incidence of mood changes. Conclusion: COVID-19 vaccination seemed to induce increased levels and incidence of TSH surge followed by mood changes in patients with HT. Higher levels of pre-vaccine serum TSH, CRP, and anti-TPO values were associated with higher incidence in the early post-vaccine phase.

Involvement of the STING signaling in COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has cast a notorious damage to the public health and global economy. The Stimulator of Interferon Genes (STING) is a crucial element of the host antiviral pathway and plays a pivotal but complex role in the infection and development of COVID-19. Herein, we discussed the antagonistic mechanism of viral proteins to the STING pathway as well as its activation induced by host cells. Specifically, we highlighted that the persistent activation of STING by SARS-CoV-2 led to abnormal inflammation, and STING inhibitors could reduce the excessive inflammation. In addition, we also emphasized that STING agonists possessed antiviral potency against diverse coronavirus and showed adjuvant efficacy in SARS-CoV-2 vaccines by inducing IFN responses.

TRIM18 is a critical regulator of viral myocarditis and organ inflammation.

BACKGROUND: Infections by viruses including severe acute respiratory syndrome coronavirus 2 could cause organ inflammations such as myocarditis, pneumonia and encephalitis. Innate immunity to viral nucleic acids mediates antiviral immunity as well as inflammatory organ injury. However, the innate immune mechanisms that control viral induced organ inflammations are unclear. METHODS: To understand the role of the E3 ligase TRIM18 in controlling viral myocarditis and organ inflammation, wild-type and Trim18 knockout mice were infected with coxsackievirus B3 for inducing viral myocarditis, influenza A virus PR8 strain and human adenovirus for inducing viral pneumonia, and herpes simplex virus type I for inducing herpes simplex encephalitis. Mice survivals were monitored, and heart, lung and brain were harvested for histology and immunohistochemistry analysis. Real-time PCR, co-immunoprecipitation, immunoblot, enzyme-linked immunosorbent assay, luciferase assay, flow cytometry, over-expression and knockdown techniques were used to understand the molecular mechanisms of TRIM18 in regulating type I interferon (IFN) production after virus infection in this study. RESULTS: We find that knockdown or deletion of TRIM18 in human or mouse macrophages enhances production of type I IFN in response to double strand (ds) RNA and dsDNA or RNA and DNA virus infection. Importantly, deletion of TRIM18 protects mice from viral myocarditis, viral pneumonia, and herpes simplex encephalitis due to enhanced type I IFN production in vivo. Mechanistically, we show that TRIM18 recruits protein phosphatase 1A (PPM1A) to dephosphorylate TANK binding kinase 1 (TBK1), which inactivates TBK1 to block TBK1 from interacting with its upstream adaptors, mitochondrial antiviral signaling (MAVS) and stimulator of interferon genes (STING), thereby dampening antiviral signaling during viral infections. Moreover, TRIM18 stabilizes PPM1A by inducing K63-linked ubiquitination of PPM1A. CONCLUSIONS: Our results indicate that TRIM18 serves as a negative regulator of viral myocarditis, lung inflammation and brain damage by downregulating innate immune activation induced by both RNA and DNA viruses. Our data reveal that TRIM18 is a critical regulator of innate immunity in viral induced diseases, thereby identifying a potential therapeutic target for treatment.

Parent Acceptance toward Inactivated COVID-19 Vaccination in Children with Acute Lymphoblastic Leukemia: The Power of Oncologist and Alliance.

Objectives: The current study aims to survey the willingness of parents to vaccinate their children, who are childhood acute lymphoblastic leukemia survivors (CALLS), and identify factors associated with vaccine acceptance. Methods: Parents of CALLS on/off treatment, with the general condition of being amendable to vaccination, were recruited for interviews with attending oncologists about COVID-19 vaccination acceptance from July to November 2021 in China. After controlling for socioeconomic factors, the Association of Oncologists' recommendations and parent−oncologist alliance with acceptance status were investigated. For validation, propensity score-matched (PSM) analysis was used. Results: A total of 424 families were included in the study, with CALLS mean remission age of 5.99 ± 3.40 years. Among them, 91 (21.4%) agreed, 168 (39.6%) hesitated, and 165 (38.9%) parents disagreed with the vaccination. The most common reason that kept parents from vaccinating their children was lack of recommendations from professional personnel (84/165, 50.9%), and massive amounts of internet information (78/175, 44.6%) was the main nonhealthcare resource against vaccination. Logistic regression analysis showed that only the recommendation from the oncologist was associated with parents' vaccine acceptance (OR = 3.17, 95% CI = 1.93−5.20), as demonstrated by PSM comparison (42 in recommendation group vs. 18 in nonrecommendation group among 114 pairs, p < 0.001). An exploratory analysis revealed that parents with a better patient−oncologist alliance had a significantly higher level of acceptance (65.6% in alliance group vs. 15.6% in nonalliance group among 32 pairs, p < 0.001). Conclusions: Due to a lack of professional recommendation resources and the potential for serious consequences, parents were generally reluctant to vaccinate their CALLS. The recommendation of oncologists, which was influenced by the parent−oncologist alliance, significantly increased acceptance. This study emphasizes the critical role of oncologists in vaccinating cancer survivors and can be used to promote COVID-19 vaccines among vulnerable populations.

Evolution Model and Simulation Study of the Public Risk Perception of COVID-19.

The evolution of the public perception of the risk in public health emergencies is closely related to risk response behavior. There are few systematic explanations and empirical studies on how the individual receiving the risk information affects the change in the individual risk perception through internal mechanisms in the context of COVID-19. Based on the understanding of the existing research, this paper constructs the evolution model of the public risk perception level based on the limited memory theory and a simulation analysis is performed. The results are as follows: memory rate, association rate, information reception and information stimulation in a single period of time have significant indigenous effects on the risk perception; when the amount of information received and the information stimulus remain unchanged, the public's risk perception follows a monotonic upward trend, but there is an upper limit function, and the upper limit is determined by the memory rate and association rate, and the influence of the association rate is higher than that of the memory rate; When the amount of information received and the information stimulus changes, the public's risk perception will also change, and there is a lag effect, which is determined by the memory rate. The impact of the acceptance of the information on the risk perception is greater than that of the information stimulus.

Serial negative response after standard and third (Booster) dose of COVID-19 inactivated vaccine is associated with low vitamin D levels in patients with solid cancers.

Introduction: The response is poorly understood to the third dose in patients with cancer who failed the standard dose of inactivated SARS-CoV-2 vaccines (CoronaVac). We aim to assess the immune response to the third dose and identify whether vitamin D deficiency is associated with serial serologic failure in patients with cancer. Methods: Solid cancer patients (SCP-N) and healthy controls (HCs) who were seronegative after the standard-dose vaccines in our previous study were prospectively recruited, from October 2021 to February 2022, to receive the third dose vaccines and anti-SARS-CoV-2S antibodies were measured. SCP-N who failed the third dose (serial seronegative group, SSG) were matched by propensity scores with the historical standard-dose positive cancer patient group (robust response group, RRG). An exploratory analysis was carried out to validate the role of vitamin D on the serology response. Results: The multi-center study recruited 97 SCP-N with 279 positive controls as RRG and 82 negative controls as HC group. The seroconversion rate after third-dose vaccination was higher in SCP-N than in HC (70.6% vs. 29.4%, p < 0.01). The matched comparison showed that patients in SSG had a significantly lower level of vitamin D and consumption rate than RRG or RRG-B (RRG with third-dose positive) (all p < 0.01). None had serious (over grade II) adverse events after the third dose. Conclusion: Solid cancer patients with second-dose vaccine failure may have a relatively poor humoral response to the third dose of COVID-19 vaccines as compared with the seronegative HC group. The consecutively poor humoral response could be associated with poor vitamin D levels and intake. Vitamin D status and cancer-related immune compromise may jointly affect the humoral response following booster vaccination.

An Investigation on Chinese Public Acceptance of COVID-19 Prevention Measures.

China has basically succeeded in bringing the COVID-19 epidemic under control, thanks to a timely series of effective prevention and control measures taken by the Chinese government. In this study, a public acceptance questionnaire of epidemic prevention measures was designed to investigate the influencing factors of public acceptance. A total of 2062 samples were collected from 8 March 2020 to 9 April 2020, and Independent-Samples T-Test and One-way ANOVA were used to analyze the data collected in the questionnaire in SPSS version 22.0. The results show that age and educational level have a significant influence on public acceptance. With the development of the epidemic, the acceptability grew generally higher. The public acceptance of traffic measures is the highest. This study summarises China's scientific experience in the fight against COVID-19 and the differences in public acceptance. It can provide a positive reference for the development of epidemic prevention in other countries.

Synthesis and pharmacological evaluation of choroquine derivatives bearing long aminated side chains as antivirus and anti-inflammatory agents.

Starting from the antimalarial drugs chloroquine and hydroxychloroquine, we conducted a structural optimization on the side chain of chloroquine by introducing amino substituted longer chains thus leading to a series of novel aminochloroquine derivatives. Anti-infectious effects against SARS-Cov2 spike glycoprotein as well as immunosuppressive and anti-inflammatory activities of the new compounds were evaluated. Distinguished immunosuppressive activities on the responses of T cell, B cell and macrophages upon mitogen and pathogenic signaling were manifested. Compounds 9-11 displayed the most promising inhibitory effects both on cellular proliferation and on the production of multiple pro-inflammatory cytokines, including IL-17, IFN-γ, IL-6, IL-1ß and TNF-α, which might be insightful in the pursuit of treatment for immune disorders and inflammatory diseases.

A graphene oxide coated tapered microfiber acting as a super-sensor for rapid detection of SARS-CoV-2.

COVID-19 is a new strain of highly contagious coronavirus, and at present, more than 221.4 million people have been infected with this virus, and the death toll exceeds 2793398. Early and fast detection of COVID-19 from infected individuals is critical to limit its spreading. Here, we report an innovative approach to detect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein by combining DNA/RNA oligomers as aptamers and a graphene oxide (GO) coated optical microfiber as a sensor system. The DNA/RNA aptamers can effectively capture the SARS-CoV-2 N protein in vitro, with the GO coated optical microfiber aptasensor for real-time monitoring of the SARS-CoV-2 N protein. Due to the extremely high surface-to-volume ratio and excellent optical and biochemical properties of the GO surface layer, the fixing effect of the microfiber surface is significantly improved and the lowest limit of detection (LOD) is 6.25 × 10-19 M. Furthermore, in order to prove the feasibility of this sensing method in clinical applications, we use this sensor to detect the N protein mixed in fetal bovine serum (FBS) samples. The experimental results show that the biosensor can quickly and effectively detect the N protein (1 × 10-9 M) in a complex sample matrix within 3 minutes. These findings suggest that this approach can be utilized for quantitative monitoring of coronavirus particles due to its high sensitivity, which can help to quickly exclude patients who do not have the infection. Collectively, the optical microfiber sensor system could be expected to become an important platform for the diagnosis of coronavirus due to its simple detection scheme and easy miniaturization.

Exploration of CT manifestations of different clinical types of novel coronavirus pneumonia.

BACKGROUND: To explore computed tomography (CT) characteristics of the 2019 novel coronavirus (COVID-19) pneumonia and explore variations among the different clinical types. METHODS: Clinical and CT imaging data of 43 patients diagnosed with COVID-19 in our hospital and the cooperative hospital between January 15-30, 2020 were collected (27 male and 16 female). Patients were classified as common type (26 cases, 60%), severe type (14 cases, 33%) or critical type (three cases, 7%) according to the new coronavirus pneumonia treatment scheme (sixth edition). Patient clinical data and CT images were analyzed and evaluated. RESULTS: Fever was the main symptom in common type COVID-19 cases (23/26, 88.46%). Both severe and critical type COVID-19 patients had fever and cough symptoms, and dyspnea was observed in all three critical COVID-19 patients. CT manifestations in the common type COVID-19 cohort were bilateral involvement (20/26, 71%), multiple lesions (14/26, 54%), ground-glass density shadow (17/26, 65%), and some cases were accompanied by local consolidation (9/26, 35%), which is consistent with early stage COVID-19 CT performance. CT manifestations in the severe and critical types involved both lungs. Severe COVID-19 cases predominantly consisted of multiple mixed-density lesions (10/14, 71%), and a few patients showed diffuse lung glass density shadows in both lungs (4/14, 29%), which is consistent with the progression stage COVID-19 CT performance. Critical COVID-19 cases exhibited mixed-density lesions, and two cases displayed "white lung", which is the CT manifestation at the severe COVID-19 stage. Only one critical COVID-19 patient had pleural effusion. CONCLUSIONS: The CT manifestations of COVID-19 are specific and there are variations between different clinical types. Thus, CT is an important clinical tool for early diagnosis and assessment of the severity of COVID-19.