Insufficient epitope-specific T cell clones are responsible for impaired cellular immunity to inactivated SARS-CoV-2 vaccine in older adults.

Aging is a critical risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efficacy. The immune responses to inactivated vaccine for older adults, and the underlying mechanisms of potential differences to young adults, are still unclear. Here we show that neutralizing antibody production by older adults took a longer time to reach similar levels in young adults after inactivated SARS-CoV-2 vaccination. We screened SARS-CoV-2 variant strains for epitopes that stimulate specific CD8 T cell response, and older adults exhibited weaker CD8 T-cell-mediated responses to these epitopes. Comparison of lymphocyte transcriptomes from pre-vaccinated and post-vaccinated donors suggested that the older adults had impaired antigen processing and presentation capability. Single-cell sequencing revealed that older adults had less T cell clone expansion specific to SARS-CoV-2, likely due to inadequate immune receptor repertoire size and diversity. Our study provides mechanistic insights for weaker response to inactivated vaccine by older adults and suggests the need for further vaccination optimization for the old population.

Revealing the Impact of COVID-19 on Urban Residential Travel Structure Based on Floating Car Trajectory Data: A Case Study of Nantong, China

The volume of residential travel with different purposes follows relatively stable patterns in a specific period and state;therefore, it can reflect the operating status of urban traffic and even indicate urban vitality. Recent research has focused on changes in the spatiotemporal characteristics of urban mobility affected by the pandemic but has rarely examined the impact of COVID-19 on the travel conditions and psychological needs of residents. To quantitatively assess travel characteristics during COVID-19, this paper proposed a method by which to determine the purpose of residential travel by combining urban functional areas (UFAs) based on machine learning. Then, the residential travel structure, which includes origin-destination (OD) points, residential travel flow, and the proportion of flows for different purposes, was established. Based on taxi trajectory data obtained during the epidemic in Nantong, China, the case study explores changes in travel flow characteristics under the framework of the residential travel structure. Through comparison of the number and spatial distribution of OD points in the residential travel structure, it is found that residential travel hotspots decreased significantly. The ratios of commuting and medical travel increased from 43.8% to 45.7% and 7.1% to 8.1%, respectively. Conversely, the ratios of other travel types all decreased sharply. Moreover, under Maslow's hierarchy of needs model, further insights into the impacts of COVID-19 on changes in residential psychological needs are discussed in this paper. This work can provide a reference for decision makers to cope with the change in urban traffic during a public health emergency, which is beneficial to the sustainable healthy development of cities.

Structural Differences of PM2.5 Spatial Correlation Networks in Ten Metropolitan Areas of China

The cross-impact of environmental pollution among cities has been reported in more research works recently. To implement the coordinated control of environmental pollution, it is necessary to explore the structural characteristics and influencing factors of the PM2.5 spatial correlation network from the perspective of the metropolitan area. This paper utilized the gravity model to construct the PM2.5 spatial correlation network of ten metropolitan areas in China from 2019 to 2020. After analyzing the overall characteristics and node characteristics of each spatial correlation network based on the social network analysis (SNA) method, the quadratic assignment procedure (QAP) regression analysis method was used to explore the influence mechanism of each driving factor. Patent granted differences, as a new indicator, were also considered during the above. The results showed that: (1) In the overall network characteristics, the network density of Chengdu and the other three metropolitan areas displayed a downward trend in two years, and the network density of Wuhan and Chengdu was the lowest. The network density and network grade of Hangzhou and the other four metropolitan areas were high and stable, and the network structure of each metropolitan area was unstable. (2) From the perspective of the node characteristics, the PM2.5 spatial correlation network all performed trends of centralization and marginalization. Beijing-Tianjin-Hebei and South Central Liaoning were “multi-core” metropolitan areas, and the other eight were “single-core” metropolitan areas. (3) The analysis results of QAP regression illustrated that the top three influencing factors of the six metropolitan areas were geographical locational relationship, the secondary industrial proportion differences, respectively, and patent granted differences, and the other metropolitan areas had no dominant influencing factors.

Maternal Anxiety Symptoms and Chinese Adolescents' Mental Health During the COVID-19 Pandemic: The Protective Role of Adolescents' Self-Compassion.

The COVID-19 outbreak triggered dramatic changes to family life. Parents, especially mothers, were found to experience more psychological distress during the pandemic, which may have had an impact on their children's mental health. The primary goal of this study was to examine the potential protective role of adolescents' self-compassion in the relationship between maternal anxiety and adolescents' mental health during the COVID-19 pandemic. Participants included 5,720 adolescents (48.9% girls; M age = 11.60, SD age = 1.36) and their mothers from Zhengzhou city, Henan province, in Mainland China. Adolescents reported their level of self-compassion, PTSD symptoms, and negative affect during the COVID-19 pandemic. Mothers reported their own anxiety symptoms and their children's depression and anxiety symptoms. Results indicated that older female adolescents reported higher levels of PTSD symptoms and negative affect and lower levels of self-compassion than their counterparts. Maternal anxiety during the COVID-19 pandemic was consistently positively associated with adolescents' psychological maladjustment. These associations were buffered by adolescents' self-compassion. Specifically, adolescents with higher levels of self-compassion were found to be less psychologically affected by their mothers' anxiety during the COVID-19 pandemic. Findings highlighted the possibility of improving adolescents' mental health through fostering their self-compassion during the COVID-19 pandemic.

An engineered nano-liposome-human ACE2 decoy neutralizes SARS-CoV-2 Spike protein-induced inflammation in both murine and human macrophages.

Rationale: Macrophages are the frontline immune cells in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Angiotensin-converting enzyme 2 (ACE2) serves as the binding receptor to SARS-CoV-2 Spike glycoprotein for fusion and internalization into the human host cells. However, the mechanisms underlying SARS-CoV-2-elicited macrophage inflammatory responses remain elusive. Neutralizing SARS-CoV-2 by human ACE2 (hACE2) decoys has been proposed as a therapeutic approach to ameliorate SARS-CoV-2-stimulated inflammation. This study aims to investigate whether an engineered decoy receptor can abrogate SARS-CoV-2-induced macrophage inflammation. Methods: hACE2 was biotinylated to the surface of nano-liposomes (d = 100 nm) to generate Liposome-human ACE2 complex (Lipo-hACE2). Lentivirus expressing Spike protein (D614G) was also created as a pseudo-SARS-CoV-2 (Lenti-Spike). Liposome-hACE2 was used as a decoy receptor or competitive inhibitor to inhibit SARS-CoV-2 or Lenti-Spike-induced macrophage inflammation in vitro and in vivo. Results: Both SARS-CoV-2 and Lenti-Spike stimulated strong inflammatory responses by inducing the expression of key cytokine and chemokines, including IL-1ß, IL-6, TNFα, CCL-2, and CXCL-10, in murine and human macrophages in vitro, whereas Lipo-hACE2 decoy abolished these effects in macrophages. Furthermore, intravenous injection of Lenti-Spike led to increased macrophage and tissue inflammation in wild type mice, which was also abolished by Lipo-hACE2 treatment. Mechanistically, Spike protein stimulated macrophage inflammation by activating canonical NF-κB signaling. RNA sequencing analysis revealed that Lenti-Spike induced over 2,000 differentially expressed genes (DEGs) in murine macrophages, but deficiency of IκB kinase ß (IKKß), a key regulator for NF-κB activation, abrogated Lenti-Spike-elicited macrophage inflammatory responses. Conclusions: We demonstrated that the engineered Lipo-hACE2 acts as a molecular decoy to neutralize SARS-CoV-2 or Spike protein-induced inflammation in both murine and human macrophages, and activation of the canonical IKKß/NF-κB signaling is essential for SARS-CoV-2-elicited macrophage inflammatory responses.

Inflammation/coagulopathy/fibrinolysis: Dynamic indicators of COVID-19 progression in patients with moderate COVID-19 in Wenzhou, China.

BACKGROUND: The majority of the coronavirus disease 2019 (COVID-19) non-survivors meet the criteria for disseminated intravascular coagulation (DIC). Although timely monitoring of clotting hemorrhagic development during the natural course of COVID-19 is critical for understanding pathogenesis, diagnosis, and treatment of the disease, however, limited data are available on the dynamic processes of inflammation/coagulopathy/fibrinolysis (ICF). METHODS: We monitored the dynamic progression of ICF in patients with moderate COVID-19. Out of 694 COVID-19 inpatients from 10 hospitals in Wenzhou, China, we selected 293 adult patients without comorbidities. These patients were divided into different daily cohorts according to the COVID-19 onset-time. Furthermore, data of 223 COVID-19 patients with comorbidities and 22 critical cases were analyzed. Retrospective data were extracted from electronic medical records. RESULTS: The virus-induced damages to pre-hospitalization patients triggered two ICF fluctuations during the 14-day course of the disease. C-reactive protein (CRP), fibrinogen, and D-dimer levels increased and peaked at day 5 (D) 5 and D9 during the 1st and 2nd fluctuations, respectively. The ICF activities were higher during the 2nd fluctuation. Although 12-day medication returned high CRP concentrations to normal and blocked fibrinogen increase, the D-dimer levels remained high on days 17 ±â€¯2 and 23 ±â€¯2 days of the COVID-19 course. Notably, although the oxygenation index, prothrombin time and activated partial thromboplastin time were within the normal range in critical COVID-19 patients at administration, 86% of these patients had a D-dimer level > 500 µg/L. CONCLUSION: COVID-19 is linked with chronic DIC, which could be responsible for the progression of the disease. Understanding and monitoring ICF progression during COVID-19 can help clinicians in identifying the stage of the disease quickly and accurately and administering suitable treatment.

Daily routines, parent-child conflict, and psychological maladjustment among Chinese children and adolescents during the COVID-19 pandemic.

Family lives have been changed dramatically due to the stay-at-home orders implemented during the coronavirus disease 2019 (COVID-19) outbreak. A variety of factors serve to increase the risk for children and adolescents in developing mental health issues during the prolonged stay-at-home period. The primary aim of this study was to examine a complex conceptual model linking daily routines, parent-child conflict, and indices of psychological maladjustment during the COVID-19 pandemic in a large sample of Chinese children and adolescents. Participants were N = 1,594 children and adolescents (50.6% girls; Mage = 13.13, SDage = 1.54) and their mothers, from Zhengzhou in Mainland China. Multisource assessments include youth self-reports of loneliness, depressive symptoms, and perceived conflict with parents during the stay-at-home period, as well as maternal reports of their child's daily routines during this time. Among the results, parent-child conflict mediated the relations between daily routines and indices of psychological maladjustment, such that a lack of routine predicted greater parent-child conflict, which in turn was associated with higher levels of loneliness and symptoms of depression. Further, results from multiple group analyses revealed that associations between daily routines and maladjustment were stronger among boys than girls-as well as stronger among primary school children than middle school adolescents. Findings highlighted the importance of maintaining regular routines for children's and adolescents' mental health during the COVID-19 pandemic. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Sex- and age-specific clinical and immunological features of coronavirus disease 2019.

To simultaneously determine clinical and immunological responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old females and males, 681 coronavirus disease 2019 (COVID-19) patients and 369 normal controls (NCs) were analyzed based on age and sex classifications using multiple linear regression analysis. Compared to the age-matched NCs, both young and old male and female non-comorbid COVID-19 patients had lower lymphocyte counts and alanine aminotransferase (ALT) concentration, and only young male and female patients had lower neutrophil counts. Compared to young patients, both old males and females had significantly higher plasma ALT and AST concentrations. Compared to young and old females, age-matched males had higher plasma ALT and AST concentrations, but only young males had higher C-reactive protein (CRP) concentration. Compared to females, old males, but not young males, showed higher incidence of critical illness. Compared to young patients, old females had more leukocyte and neutrophil counts above the normal upper limit and B cell count below the normal lower limit (NLL), while old males had more lymphocyte and natural killer (NK) cell counts below the NLL. No sex or age associations with B cell and NK cell counts were observed. However, there were age-dependent decreases in CD8+ T-cell counts in both male and female COVID-19 patients. Age was negatively associated with CD8+ T cell counts but positively associated with neutrophil count, CRP, ALT, and AST concentrations, and sex (females) was negatively associated with neutrophil count, CRP, ALT, and AST concentrations. The present study suggests that SARS-CoV-2 infection mainly induced 1) beneficial sex (female)-related differences regarding reduced COVID-19 disease severity and negative associations with inflammatory responses and liver damage, and 2) harmful age-related differences relating to negative associations with CD8+ T cell count and positive associations with inflammatory responses and liver damage. Thus, sex and age are biological variables that should be considered in the prevention and treatment of COVID-19.

Age cohorts stratified according to age-distributions of COVID-19 morbidity statistics identify uniquely age-dependent CD3+CD8+ T-cell lymphocytopenia in COVID-19 patients without comorbidities on admission.

If age boundaries are arbitrarily or roughly defined, age-related analyses can result in questionable findings. Here, we aimed to delineate the uniquely age-dependent immune features of coronavirus disease 2019 (COVID-19) in a retrospective study of 447 patients, stratified according to age distributions of COVID-19 morbidity statistics into well-defined age-cohorts (2-25y, 26-38y, 39-57y, 58-68y, and 69-79y). Age-dependent susceptibilities and severities of the disease were observed in COVID-19 patients. A comparison of the lymphocyte counts among the five age-groups indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection led to age-dependent lymphopenia. Among the lymphocyte subsets, the CD8+ T cell count alone was significantly and age-dependently decreased (520, 385, 320, 172, and 139 n/µl in the five age-groups, respectively). In contrast, the CD4+ T cell, B cell, and natural killer cell counts did not differ among age-cohorts. Age and CD8+ T cell counts (r=‒0.435, p<0.0001) were negatively correlated in COVID-19 patients. Moreover, SARS-CoV-2 infection age-dependently increased the plasma C-reactive protein concentrations (2.0, 5.0, 9.0, 11.6, and 36.1 mg/L in the five age-groups, respectively). These findings can be used to elucidate the role of CD8+ T cells in age-related pathogenesis and to help develop therapeutic strategies for COVID-19.

A COVID-19 descriptive study of life after lockdown in Wuhan, China.

On 8 April 2020, the Chinese government lifted the lockdown and opened up public transportation in Wuhan, China, the epicentre of the COVID-19 pandemic. After 76 days in lockdown, Wuhan residents were allowed to travel outside of the city and go back to work. Yet, given that there is still no vaccine for the virus, this leaves many doubting whether life will indeed go back to normal. The aim of this research was to track longitudinal changes in motivation for self-isolating, life-structured, indicators of well-being and mental health after lockdown was lifted. We have recruited 462 participants in Wuhan, China, prior to lockdown lift between 3 and 7 April 2020 (Time 1), and have followed up with 292 returning participants between 18 and 22 April 2020 (Time 2), 284 between 6 and 10 May 2020 (Time 3), and 279 between 25 and 29 May 2020 (Time 4). This four-wave study used latent growth models to examine how Wuhan residents' psychological experiences change (if at all) within the first two months after lockdown was lifted. The Stage 1 manuscript associated with this submission received in-principle acceptance (IPA) on 2 June 2020. Following IPA, the accepted Stage 1 version of the manuscript was preregistered on the OSF at https://osf.io/g2t3b. This preregistration was performed prior to data analysis. Generally, our study found that: (i) a majority of people still continue to value self-isolation after lockdown was lifted; (ii) by the end of lockdown, people perceived gradual return to normality and restored structure of everyday life; (iii) the psychological well-being slightly improved after lockdown was lifted; (iv) people who used problem solving and help-seeking as coping strategies during lockdown had better well-being and mental health by the end of the lockdown; (v) those who experienced more disruptions in daily life during lockdown would display more indicators of psychological ill-being by the end of the lockdown.

A single-dose mRNA vaccine provides a long-term protection for hACE2 transgenic mice from SARS-CoV-2 (preprint)

The rapid expansion of COVID-19 pandemic has made the development of a SARS-CoV-2 vaccine a global health and economic priority. Taking advantages of versatility and rapid development, three SARS-CoV-2 mRNA vaccine candidates has entered clinical trials with a two-dose immunization regimen. However, the waning antibodies response in convalescent patients after SARS-CoV-2 infection and the emergence of human re-infection have raised widespread concern about a short duration of SARS-CoV-2 vaccine protection. Here, we developed a nucleoside-modified mRNA vaccine in lipid-encapsulated form which encoded SARS-CoV-2 RBD, termed as mRNA-RBD. A single immunization of mRNA-RBD elicited both robust neutralizing antibody and cellular response, and conferred a near-complete protection against wild SARS-CoV-2 infection in lungs of hACE2 transgenic mice. Noticeably, high levels of neutralizing antibodies response induced by mRNA-RBD vaccination could maintain for at least 6.5 months and conferred a long-term remarkable protection for hACE2 transgenic mice against SARS-CoV-2 infection in sera transfer study. These data demonstrated that a single dose of mRNA-RBD provided long-term protection against SARS-CoV-2 challenge.

The value of lymphocyte count in determining the severity of COVID-19 and estimating the time for nucleic acid test results to turn negative.

Peripheral blood lymphocyte count is shown to be decreased in patients with COVID-19 in the early stage of the disease. The degree of lymphocyte count reduction is related to COVID-19 severity and could be used as an indicator to reflect the disease severity. Our aim was to investigate the value of lymphocyte count in determining COVID-19 severity and estimating the time for SARS-CoV-2 nucleic acid test results to turn negative. We retrospectively analyzed clinical data of 201 patients with severe and critical COVID-19. The patients were admitted to the West Campus of Union Hospital of Tongji Medical College of Huazhong University of Science and Technology. The data included age, gender, chronic disease, lymphocyte count, and SARS-CoV-2 nucleic acid test results. The age of patients in critically ill group was higher than in severely ill group (p = 0.019). The lymphocyte count of critically ill patients was lower than of severely ill patients. The cutoff value of lymphocyte count to distinguish between the critically ill and the severely ill was 0.735 × 109/L (p = 0.001). The cutoff value of lymphocyte count for SARS-CoV-2 nucleic acid test results turning negative in severely and critically ill patients with chronic diseases (hypertension, diabetes, and coronary heart disease) was 0.835 × 109/L (p = 0.017). The cutoff value of lymphocyte count for SARS-CoV-2 nucleic acid test results turning negative in severely and critically ill male patients was 0.835 × 109/L (p < 0.0001). Lymphocyte count could be an effective indicator to predict COVID-19 severity. It may also be useful in determining the time for nucleic acid test results to turn negative in COVID-19 patients with underlying chronic diseases or male COVID-19 patients with severe and critical conditions.