Structural and componential design: new strategies regulating the behavior of lipid-based nanoparticles in vivo.

Lipid-based nanoparticles have made a breakthrough in clinical disease as delivery systems due to their biocompatibility, thermal and long-term stability, high loading ability, simplicity of preparation, inexpensive production costs, and scalable manufacturing production. In particular, during the COVID-19 pandemic, this delivery system served as a vital vaccine component for virus confrontation. To obtain effective drug delivery, lipid-based nanoparticles should reach the desired sites with high efficiency, enter target cells, and release drugs. The structures and compositions of lipid-based nanoparticles can be modified to regulate these behaviors in vivo to enhance the therapeutic effects. Herein, we briefly review the development of lipid-based nanoparticles, from simple self-assembled nanovesicle-structured liposomes to multifunctional lipid nanoparticles. Subsequently, we summarize the strategies that regulate their tissue distribution, cell internalization, and drug release, highlighting the importance of the structural and componential design. We conclude with insights for further research to advance lipid-based nanotechnology.

Comparative research on the development of college students' physical fitness based on online physical education during the COVID-19 pandemic.

BACKGROUND: There are few studies that focus on the impact of online physical education teaching on college students during the coronavirus disease 2019 (COVID-19) pandemic. This research focuses on the impact of online physical education among medical school students in China by comparing physical fitness test results for three consecutive years from 2019 to 2021. METHOD: This study is a longitudinal survey. The subjects of the experiments were students enrolled in a medical school who completed a physical fitness test for three consecutive years from 2019 to 2021. The student subjects were divided into two groups, namely, male and female. The test indices included body mass index (BMI), vital capacity (VC), 50-metre run, sit-and-reach, standing long jump, pull-up (male), 1000-metre run (male), sit-ups (female) and 800-metre run (female). Repeated measures ANOVA method was used in physical fitness test indices at three consecutive time points ranging from 2019 to 2021. The Greenhouse-Geisser correction was applied when Mauchly's hypothesis test did not meet the assumption of sphericity, and the Bonferroni method was used for pairwise comparisons. RESULTS: A total of 3360 students (1490 males and 1870 females) completed physical fitness tests in three consecutive years from 2019 to 2021. The proportion of overweight and obesity in male students was significantly higher than that in female students (28.0% vs. 12.7%). For all subjects, in 2020, the BMI and VC indexes improved, while the 800-/1000-metre running indexes declined. In 2021, all indexes except sit-and-reach increased. CONCLUSION: The pairwise comparisons of physical fitness test results from 2019 to 2021 show that online physical education is effective in improving all items except long-distance running. Future research needs to involve a larger and geographically more dispersed sample to further analyse the effectiveness of online physical education.

Impact of Isolation measures on pregnancy outcome during the COVID-19 pandemic.

This study aims to explore the impact of isolation measures implemented during the COVID-19 pandemic on childbirth outcomes in pregnant women. The design was a retrospective cohort study. The pregnant women during the outbreak lockdown and isolation from February 1 to April 30, 2020, were defined as the exposed population, and the pregnant women in the same time frame in 2019 as the non-exposed population. All data for the study were obtained from the National Health Care Data Platform of Shandong University. Generalized linear regression models were used to analyze the differences in pregnancy outcomes between the two study groups. A total of 34,698 pregnant women from Shandong Province, China in the data platform met the criteria and were included in the study. The proportions were 11.53% and 8.93% for macrosomia in the exposed and the non-exposed groups and were 3.47% and 4.37% for low birth weight infants, respectively, which were significantly different. They were 22.55% and 25.94% attributed to average exposed effect for macrosomia and low birth weight infants. Meanwhile, the mean weight and standard deviation of full-term infants in the exposure group were 3414.80 ± 507.43 g, which were significantly higher than in the non-exposed group (3347.22 ± 502.57 g, P < 0.001). The effect of exposure was significant in the third trimester. In conclusion, the isolation during the COVID-19 pandemic increases the birth weight of infants and the probability of macrosomia, regardless of which trimester in isolation a pregnant woman was, while the third trimester is the sensitive window of exposure. Our findings provide a basis for health care and policy development during pregnancy in COVID-19, due to COVID-19 still showing a pandemic trend around the world in 2022.

A digitized catalog of COVID-19 epidemiology data

COVID-19 is now rapidly spreading worldwide. While the majority of COVID-19 patients show only mild or moderate symptoms, some could deteriorate quickly and may succumb to a sudden death. It is therefore important to identify who will be more likely to develop severe outcomes and be treated with particular or preventive care. Here in this literature survey, we collected epidemiologic and clinical data from 36 articles on 51,270 patients with different severity of COVID-19, aiming to characterize the population that are prone to severe condition and bad outcomes. These data reveal that old males and those with high BMI or underlying diseases, especially cardiovascular disease, hypertension and diabetes, are overrepresented among severe cases. High leukocyte and lymphopenia are common features in severe and critical patients. Upon deterioration of the disease, both CD4 and CD8 T cells are decreased, while almost all serum cytokines, especially pro-inflammatory cytokines, increased.

Analysis of clinical features of 76 cured patients of COVID-19

Objective: To analyze clinical features of cured patients with 2019 novel coronavirus pneumonia (COVID-19), and summarize experience, in order to guide epidemic prevention work.

Immunogenicity and Safety of Inactivated SARS-CoV-2 Vaccine in People Living with HIV: A Cross-Sectional Study (preprint)

Background: To analyze the efficacy and safety of SARS-CoV-2 inactivated vaccine in people living with HIV (PLWH).Methods: A total of 143 PLWH were included in the study. All patients were confirmed with HIV-1 infection. We also enrolled 50 healthy individuals vaccinated with two doses of SARS-CoV-2 vaccine as controls. A commercially available magnetic chemiluminescence enzyme immunoassay kit was used to detected serum IgG and IgM against SARS-CoV-2.Findings: Serum levels of SARS-CoV-2-specific IgG were significantly higher in the control group than in the PLWH group (P=0.001). Overall, 76% of individuals in the control group achieved IgG seroconversion after vaccination compared with 58% in the PLWH group (P=0.024). The time after vaccination in IgG seronegative PLWH was significantly longer compared with PLWH with IgG seropositive (43.38 ± 34.96 vs 30.27 ± 20.12 days, P=0.005). In PLWH with IgG seropositivity, CD4+ T cell counts before antiretroviral therapy (ART) (P=0.015) and at IgG detection (P<0.001) were higher. Multivariable analysis indicated CD4+ T cells at IgG detection (OR=1.004, P=0.006) and time after vaccination (OR=0.977, P=0.014) were independently associated with humoral response in PLWH after vaccination. Neutralizing antibody (NeuAb) titers in PLWH against wild type SARS-CoV-2 were similar compared with the Control group (P=0.160). The proportion of seropositive NeuAb against wild type SARS-CoV-2 were also similar (95% in Control group vs 97% in PLWH group, P=0.665). Similar results were obtained when NeuAb were detected against the delta variants with similar titers (P=0.355) and with similar proportion of humoral response (P=0.588). All side effects observed in our study were mild and self-limiting. There was no significant difference in occurrence of side effects in the control and PLWH groups. Interpretation: The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in PLWH.Funding: This study was supported by Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (No. LC2016PY003).Declaration of Interest: None of the authors have competing interests to disclose.Ethical Approval: The study was performed in accordance with the Declaration of Helsinki and was approved by the Institutional Ethics Committee of Nanfang Hospital (NFEC-2021-178).

Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms.

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) as common life-threatening lung diseases with high mortality rates are mostly associated with acute and severe inflammation in lungs. With increasing in-depth studies of ALI/ARDS, significant breakthroughs have been made, however, there are still no effective pharmacological therapies for treatment of ALI/ARDS. Especially, the novel coronavirus pneumonia (COVID-19) is ravaging the globe, and causes severe respiratory distress syndrome. Therefore, developing new drugs for therapy of ALI/ARDS is in great demand, which might also be helpful for treatment of COVID-19. Natural compounds have always inspired drug development, and numerous natural products have shown potential therapeutic effects on ALI/ARDS. Therefore, this review focuses on the potential therapeutic effects of natural compounds on ALI and the underlying mechanisms. Overall, the review discusses 159 compounds and summarizes more than 400 references to present the protective effects of natural compounds against ALI and the underlying mechanism.

Sensitive and rapid on-site detection of SARS-CoV-2 using a gold nanoparticle-based high-throughput platform coupled with CRISPR/Cas12-assisted RT-LAMP.

The outbreak of corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a global pandemic. The high infectivity of SARS-CoV-2 highlights the need for sensitive, rapid and on-site diagnostic assays of SARS-CoV-2 with high-throughput testing capability for large-scale population screening. The current detection methods in clinical application need to operate in centralized labs. Though some on-site detection methods have been developed, few tests could be performed for high-throughput analysis. We here developed a gold nanoparticle-based visual assay that combines with CRISPR/Cas12a-assisted RT-LAMP, which is called Cas12a-assisted RT-LAMP/AuNP (CLAP) assay for rapid and sensitive detection of SARS-CoV-2. In optimal condition, we could detect down to 4 copies/µL of SARS-CoV-2 RNA in 40 min. by naked eye. The sequence-specific recognition character of CRISPR/Cas12a enables CLAP a superior specificity. More importantly, the CLAP is easy for operation that can be extended to high-throughput test by using a common microplate reader. The CLAP assay holds a great potential to be applied in airports, railway stations, or low-resource settings for screening of suspected people. To the best of our knowledge, this is the first AuNP-based colorimetric assay coupled with Cas12 and RT-LAMP for on-site diagnosis of COVID-19. We expect CLAP assay will improve the current COVID-19 screening efforts, and make contribution for control and mitigation of the pandemic.

Early clinical manifestation and pulmonary imaging analysis of patients with novel coronavirus pneumonia

Objective: To investigate the early clinical characteristics and radiographic changes in confirmed novel coronavirus (COVID-19) and COVID-19 excluded patients.

High levels of soluble CD25 in COVID-19 severity suggest a divergence between anti-viral and pro-inflammatory T-cell responses.

OBJECTIVES: We aimed to gain an understanding of the paradox of the immunity in COVID-19 patients with T cells showing both functional defects and hyperactivation and enhanced proliferation. METHODS: A total of 280 hospitalised patients with COVID-19 were evaluated for cytokine profiles and clinical features including viral shedding. A mouse model of acute infection by lymphocytic choriomeningitis virus (LCMV) was applied to dissect the relationship between immunological, virological and pathological features. The results from the mouse model were validated by published data set of single-cell RNA sequencing (scRNA-seq) of immune cells in bronchoalveolar lavage fluid (BALF) of COVID-19 patients. RESULTS: The levels of soluble CD25 (sCD25), IL-6, IL-8, IL-10 and TNF-α were higher in severe COVID-19 patients than non-severe cases, but only sCD25 was identified as an independent risk factor for disease severity by multivariable binary logistic regression analysis and showed a positive association with the duration of viral shedding. In agreement with the clinical observation, LCMV-infected mice with high levels of sCD25 demonstrated insufficient anti-viral response and delayed viral clearance. The elevation of sCD25 in mice was mainly contributed by the expansion of CD25+CD8+ T cells that also expressed the highest level of PD-1 with pro-inflammatory potential. The counterpart human CD25+PD-1+ T cells were expanded in BALF of COVID-19 patients with severe disease compared to those with modest disease. CONCLUSION: These results suggest that high levels of sCD25 in COVID-19 patients probably result from insufficient anti-viral immunity and indicate an expansion of pro-inflammatory T cells that contribute to disease severity.

Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China.

BACKGROUND: In December 2019, coronavirus 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China. METHODS: Demographic and clinical data of all confirmed cases with COVID-19 on admission at Tongji Hospital from 10 January to 12 February 2020 were collected and analyzed. The data on laboratory examinations, including peripheral lymphocyte subsets, were analyzed and compared between patients with severe and nonsevere infection. RESULTS: Of the 452 patients with COVID-19 recruited, 286 were diagnosed as having severe infection. The median age was 58 years and 235 were male. The most common symptoms were fever, shortness of breath, expectoration, fatigue, dry cough, and myalgia. Severe cases tend to have lower lymphocyte counts, higher leukocyte counts and neutrophil-lymphocyte ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most severe cases demonstrated elevated levels of infection-related biomarkers and inflammatory cytokines. The number of T cells significantly decreased, and were more impaired in severe cases. Both helper T (Th) cells and suppressor T cells in patients with COVID-19 were below normal levels, with lower levels of Th cells in the severe group. The percentage of naive Th cells increased and memory Th cells decreased in severe cases. Patients with COVID-19 also have lower levels of regulatory T cells, which are more obviously decreased in severe cases. CONCLUSIONS: The novel coronavirus might mainly act on lymphocytes, especially T lymphocytes. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis, and treatment of COVID-19.

Comparison of clinical and microbiological diagnoses for older adults with COVID-19 in Wuhan: a retrospective study.

BACKGROUND: The potential differences between a clinical diagnosis of coronavirus disease 2019 (COVID-19) (i.e., symptoms without positive virus test) and a microbiological diagnosis (i.e., positive virus test results) of COVID-19 are not known. AIMS: This study explored the differences between the two types of COVID-19 diagnosis among older patients in terms of clinical characteristics and outcomes. METHODS: A total of 244 inpatients aged ≥ 60 years with COVID-19 were included in this study, of whom 52 were clinically diagnosed and 192 were microbiologically diagnosed. Clinical and laboratory data on hospital admission and outcomes (discharged or died in hospital) of all patients were retrieved from medical records retrospectively. Patients who met the criteria for clinical diagnosis with negative virus test results were assigned to the clinical diagnosis group, whereas those with positive virus test results were assigned to the microbiological diagnosis group. After univariate analyses, two propensity score analyses [i.e., covariate adjustment using propensity score (CAPS) and propensity score matching (PSM)] were conducted to control bias. RESULTS: The clinical and microbiological diagnosis groups demonstrated significant differences in outcomes and in the majority of laboratory findings. After propensity score analyses, many differences between the two groups disappeared and the rate of mortality had no statistically significant difference (P = 0.318 and 0.828 for CAPS and PSM, respectively). CONCLUSIONS: Patients with similar signs, symptoms, and laboratory and imaging findings as confirmed COVID-19 cases may have a similar mortality risk, regardless of the virus test results, and require timely intervention to reduce their mortality.

Clinical characteristics of 312 hospitalized older patients with COVID-19 in Wuhan, China.

OBJECTIVES: Much of the previous research on COVID-19 was based on all population. But substantial numbers of severe episodes occur in older patients. There is a lack of data about COVID-19 in older adults. The aims of this study were to analyze the clinical characteristics of older adult patients with COVID-19. METHODS: Retrospective study of older patients hospitalized with COVID-19 from February 1 st to March 31 st, 2020 was conducted in the Sino-French New City Branch of Tongjing Hospital in Wuhan, China. According to the degree of severity of COVID-19 during hospitalization, 312 older patients were divided into non-severe and severe cases. RESULTS: the mean age of the patients was 69.2 ± 7.3 years, and 47.4 % of patients had exposure history. 77.2 % of patients had a co-morbidity, with hypertension being the most common (57.1 %), followed by diabetes (38.8 %) and cardiovascular disease (29.8 %). Multivariable regression showed increasing odds of severe COVID-19 associated with age(OR 1.59, 95 %CI 1.13-2.08), SOFA score(OR 5.89, 95 %CI 3.48-7.96), APACHEⅡ score(OR 3.13, 95 %CI 1.85-5.62), platelet count＜125 × 109/L(OR 2.36, 95 %CI 1.03-4.14), d-dimer (OR 4.37, 95 %CI 2.58-7.16), creatinine＞133 µmol/L(OR 1.85, 95 %CI 1.12-3.04), interleukin-6(OR 4.32, 95 %CI 2.07-7.13), and lung consolidation(OR 1.94, 95 %CI 1.45-4.27) on admission. The most common complication was acute respiratory distress syndrome (35.6 %), followed by acute cardiac injury (33.0 %) and coagulation disorders (30.8 %). 91.7 % of patients were prescribed antiviral therapy, followed by immune globulin (52.9 %) and systemic glucocorticoids (43.6 %). 21.8 % of patients received invasive ventilation, 1.92 % for extracorporeal membrane oxygenation. The overall mortality was 6.73 %, and mortality of severe patients was 17.1 %, which was higher than non-severe patients (0.962 %). CONCLUSIONS: Older patients with COVID-19 had much more co-morbidity, complications and mortality. More attention should be paid to older patients with COVID-19.

Gendered effects on inflammation reaction and outcome of COVID-19 patients in Wuhan.

BACKGROUND: The rapid outbreak of coronavirus disease 2019 (COVID-19) has turned into a public health emergency of international concern. Epidemiological research has shown that sex is associated with the severity of COVID-19, but the underlying mechanism of sex predisposition remains poorly understood. We aim to study the gendered differences in inflammation reaction, and the association with severity and mortality of COVID-19. METHODS: In this retrospective study, we enrolled 548 COVID-19 inpatients from Tongji Hospital from 26 January to 5 February 2020, and followed up to 3 March 2020. Epidemiological, demographic and clinical features, and inflammatory indexes were collected and compared between males and females. The Cox proportional hazard regression model was applied to identify the gendered effect on mortality of COVID-19 after adjusting for age, comorbidity, and smoking history. The multiple linear regression method was used to explore the influence of sex on inflammation reaction. RESULTS: Males had higher mortality than females did (22.2% vs 10.4%), with an hazard ratio of 1.923 (95% confidence interval, 1.181-3.130); elder age and comorbidity were significantly associated with decease of COVID-19 patients. Excess inflammation reaction was related to severity of COVID-19. Male patients had greater inflammation reaction, with higher levels of interleukin 10, tumor necrosis factor-α, lactose dehydrogenase, ferritin, and hyper-sensitive C-reactive protein, but a lower lymphocyte count than females adjusted by age and comorbidity. CONCLUSIONS: Sex, age, and comorbidity are critical risk factors for mortality of COVID-19. Excess innate immunity and proinflammation activity, and deficiency in adaptive immunity response promote males, especially elder males, to develop a cytokine storm, causing potential acute respiratory distressed syndrome, multiple organ failure and decease.

Risk Factors for Mortality in 244 Older Adults With COVID-19 in Wuhan, China: A Retrospective Study.

BACKGROUND/OBJECTIVES: Previous studies have reported that older patients may experience worse outcome(s) after infection with severe acute respiratory syndrome coronavirus-2 than younger individuals. This study aimed to identify potential risk factors for mortality in older patients with coronavirus disease 2019 (COVID-19) on admission, which may help identify those with poor prognosis at an early stage. DESIGN: Retrospective case-control. SETTING: Fever ward of Sino-French New City Branch of Tongji Hospital, Wuhan, China. PARTICIPANTS: Patients aged 60 years or older with COVID-19 (n = 244) were included, of whom 123 were discharged and 121 died in hospital. MEASUREMENTS: Data retrieved from electronic medical records regarding symptoms, signs, and laboratory findings on admission, and final outcomes of all older patients with COVID-19, were retrospectively reviewed. Univariate and multivariate logistic regression analyses were used to explore risk factors for death. RESULTS: Univariate analysis revealed that several clinical characteristics and laboratory variables were significantly different (ie, P < .05) between discharged and deceased patients. Multivariable logistic regression analysis revealed that lymphocyte (LYM) count (odds ratio [OR] = 0.009; 95% confidence interval [CI] = 0.001-0.138; P = .001) and older age (OR = 1.122; 95% CI = 1.007-1.249; P = .037) were independently associated with hospital mortality. White blood cell count was also an important risk factor (P = .052). The area under the receiver operating characteristic curve in the logistic regression model was 0.913. Risk factors for in-hospital death were similar between older men and women. CONCLUSION: Older age and lower LYM count on admission were associated with death in hospitalized COVID-19 patients. Stringent monitoring and early intervention are needed to reduce mortality in these patients. J Am Geriatr Soc 68:E19-E23, 2020.

Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan.

BACKGROUND: In December 2019, the coronavirus disease 2019 (COVID-19) outbreak occurred in Wuhan. Data on the clinical characteristics and outcomes of patients with severe COVID-19 are limited. OBJECTIVE: We sought to evaluate the severity on admission, complications, treatment, and outcomes of patients with COVID-19. METHODS: Patients with COVID-19 admitted to Tongji Hospital from January 26, 2020, to February 5, 2020, were retrospectively enrolled and followed-up until March 3, 2020. Potential risk factors for severe COVID-19 were analyzed by a multivariable binary logistic model. Cox proportional hazard regression model was used for survival analysis in severe patients. RESULTS: We identified 269 (49.1%) of 548 patients as severe cases on admission. Older age, underlying hypertension, high cytokine levels (IL-2R, IL-6, IL-10, and TNF-α), and high lactate dehydrogenase level were significantly associated with severe COVID-19 on admission. The prevalence of asthma in patients with COVID-19 was 0.9%, markedly lower than that in the adult population of Wuhan. The estimated mortality was 1.1% in nonsevere patients and 32.5% in severe cases during the average 32 days of follow-up period. Survival analysis revealed that male sex, older age, leukocytosis, high lactate dehydrogenase level, cardiac injury, hyperglycemia, and high-dose corticosteroid use were associated with death in patients with severe COVID-19. CONCLUSIONS: Patients with older age, hypertension, and high lactate dehydrogenase level need careful observation and early intervention to prevent the potential development of severe COVID-19. Severe male patients with heart injury, hyperglycemia, and high-dose corticosteroid use may have a high risk of death.

Novel Coronavirus Infection in Hospitalized Infants Under 1 Year of Age in China

Previous studies suggest that COVID-19 is more likely to infect older adult men, particularly those with chronic comorbidities.2-4 Few infections in children have been reported. We identified all infected infants in China and described demographic, epidemiologic, and clinical features.