Longitudinal proteomic investigation of COVID-19 vaccination (preprint)

Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac) at a 28-day interval. Using TMT-based proteomics, we identified 1715 serum and 7342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC's potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning.

A Large-Scale Clinical Validation Study Using nCapp Cloud Plus Terminal by Frontline Doctors for the Rapid Diagnosis of COVID-19 and COVID-19 pneumonia in China

Background The outbreak of coronavirus disease 2019 (COVID-19) has become a global pandemic acute infectious disease, especially with the features of possible asymptomatic carriers and high contagiousness. Currently, it is difficult to quickly identify asymptomatic cases or COVID-19 patients with pneumonia due to limited access to reverse transcription-polymerase chain reaction (RT-PCR) nucleic acid tests and CT scans. Goal This study aimed to develop a scientific and rigorous clinical diagnostic tool for the rapid prediction of COVID-19 cases based on a COVID-19 clinical case database in China, and to assist doctors to efficiently and precisely diagnose asymptomatic COVID-19 patients and cases who had a false-negative RT-PCR test result. Methods With online consent, and the approval of the ethics committee of Zhongshan Hospital Fudan University (NCT04275947, B2020-032R) to ensure that patient privacy is protected, clinical information has been uploaded in real-time through the New Coronavirus Intelligent Auto-diagnostic Assistant Application of cloud plus terminal (nCapp) by doctors from different cities (Wuhan, Shanghai, Harbin, Dalian, Wuxi, Qingdao, Rizhao, and Bengbu) during the COVID-19 outbreak in China. By quality control and data anonymization on the platform, a total of 3,249 cases from COVID-19 high-risk groups were collected. The effects of different diagnostic factors were ranked based on the results from a single factor analysis, with 0.05 as the significance level for factor inclusion and 0.1 as the significance level for factor exclusion. Independent variables were selected by the step-forward multivariate logistic regression analysis to obtain the probability model. Findings We applied the statistical method of a multivariate regression model to the training dataset (1,624 cases) and developed a prediction model for COVID-19 with 9 clinical indicators that are accessible. The area under the receiver operating characteristic (ROC) curve (AUC) for the model was 0.88 (95% CI: 0.86, 0.89) in the training dataset and 0.84 (95% CI: 0.82, 0.86) in the validation dataset (1,625 cases). Discussion With the assistance of nCapp, a mobile-based diagnostic tool developed from a large database that we collected from COVID-19 high-risk groups in China, frontline doctors can rapidly identify asymptomatic patients and avoid misdiagnoses of cases with false-negative RT-PCR results.

Evaluation of Immune Response and Disease Flares in Metabolic-Associated Fatty Liver Disease (MAFLD) Patients Following SARS-CoV-2 Vaccination: A Prospective Study (preprint)

Background: The ongoing COVID-19 pandemic has led to the focused application of resources toward developing vaccines to prevent COVID-19. However, the efficacy and safety profiles of vaccines against SARS-CoV-2 in patients with metabolic associated fatty liver disease (MAFLD) are still unknown. We aimed to evaluate the safety, tolerability, seroreactivity, and disease flares after SARS-CoV-2 vaccination in MAFLD patients.Methods: For this prospective observational study, we recruited patients receiving two doses SARS-CoV-2 vaccine (CoronaVac). Neutralizing antibody to the SARS-CoV-2 spike receptor-binding domain and IgG to SARS-COV-2 spike-specific were evaluated on Day 0, Day 28, Day 57, and Day 180. All participants with available data were included in the safety and immunogenicity, and disease flares analyses.Findings: 50 MAFLD patients and 50 healthy controls receiving a 0-28 interval vaccination procedure were enrolled. The seroconversion rates of neutralizing antibodies were 16% in MAFLD group (Log10 Geometric Mean Titers (GMT): median 0·783, IQR: 0·719-0·971) and 32% in non-MAFLD group (0·884, IQR: 0·716-1·027) on day 28, and 82% in MAFLD group (1·206, IQR: 1·053-1·467), 90% of non-MAFLD group (1·360, IQR: 1·130-1·464) on day 57, respectively. However, the neutralizing antibody titer in two groups fell below the seropositivity cut-off value on day 180 (MAFLD group 0.928, IQR: 0·773-1·057 vs. non-MAFLD group 0·907, IQR: 0·810-1·009). There was no significant difference in the overall incidence of adverse reactions after two-dose vaccinations between two groups. Furthermore. disease flares were not found in MAFLD group after two-dose vaccinations. On multivariable analysis, NAFLD fibrosis score was negatively associated with seropositive of neutralizing antibody on 180 days (OR 0·03, 95% CI 0·001-0·58, P = 0·022).Interpretation: Two-dose regimen of CoronaVac vaccination in MAFLD patients was safe and well tolerated. MAFLD patients showed a robust immune response after SARS-COV-2 vaccination, which conferred 82% protection against COVID-19 and vaccination does not affect MAFLD disease status.Clinical Trial Registration Details: This trial had been registered in Chinese ClinicalTrials.gov (ChiCTR2100042717).Funding Information: Project of Key Medical Disciplines of Hangzhou, the Health and Science and Technology Planning Project of Hangzhou municipal Health Commission (No. A20210205).Declaration of Interests: JP Shi reports grants from Project of Key Medical Disciplines of Hangzhou for the Department of infectious & Hepatology. QR Zhu reports grants from the Health and Science and Technology Planning Project of Hangzhou municipal Health Commission, during the conduct of the study. All authors declare no competing interests. Ethics Approval Statement: The study was approved by local Hospital Ethics Committee (2021(E2)-KS-049) and written informed consent was obtained from patients involved before enrolment when data were collected.

Release of inhalable particles and viable microbes to the air during packaging peeling: Emission profiles and mechanisms.

Packaging is necessary for preserving and delivering products and has significant impacts on human health and the environment. Particle matter (PM) may be released from packages and transferred to the air during a typical peeling process, but little is known about this package-to-air migration route of particles. Here, we investigated the emission profiles of total and biological particles, and the horizontal and vertical dispersion abilities and community structure of viable microbes released from packaging to the air by peeling. The results revealed that a lot of inhalable particles and viable microbes were released from package to the air in different migration directions, and this migration can be regulated by several factors including package material, effective peeling area, peeling speed and angles, as well as the characteristics of the migrant itself. Dispersal of package-borne viable microbes provides direct evidence that viable microbes, including pathogens, can survive the aerosolization caused by peeling and be transferred to air over different distances while remaining alive. Based on the experimental data and visual proof in movies, we speculate that nonbiological particles are package fibers fractured and released to air by the external peeling force exerted on the package and that microbe dispersal is attributed to surface-borne microbe suspension by vibration caused by the peeling force. This investigation provides new information that aerosolized particles can deliver package-borne substances and viable microbes from packaging to the ambient environment, motivating further studies to characterize the health effects of such aerosolized particles and the geographic migration of microbes via packaging.

Rethinking the geography of gentrification: From a scale perspective

This article proposes that the lens of scale may potentially yield fresh insights into the comparative research on gentrification. First, the flows of capital, people, and knowledge in re-scaling furnish a point of departure for a holistic theory of planetary gentrification and a vital reference point for comparison. Second, to harness upscaling and downscaling in tandem, comparative studies should adequately connect gentrification with similar regional/local ontologies to obtain greater ontological power. The disadvantaged should take advantage of a loose and shifting alliance among the pro-gentrification forces to find a “real choice” (instead of a “perfect choice”) for those affected. Moreover, a pragmatic solution is opprobrium against predatory flows, particularly the flows of capital, whose nature is defined by local peculiarities.

Emergency Biosafety Management Practice in Laboratory of Shelter Hospital.

At the end of 2019, the novel coronavirus infection outbroke in Wuhan, Hubei Province. On Feb. 2, 2020, Wuhan, as the worst-hit region, began to build "shelter hospital" rapidly to treat patients with mild illness. The shelter hospital has multiple functions such as emergency treatment, surgical treatment and clinical test, which can adapt to emergency medical rescue tasks. Based on the characteristics that shelter hospital only treats patients with mild illness, tests of shelter laboratory, including coronavirus nucleic acid detection, IgM/IgG antibody serology detection, monitoring and auxiliary diagnosis and/or a required blood routine, urine routine, C-reactive protein, calcitonin original, biochemical indicators (liver enzymes, myocardial enzymes, renal function, etc.) and blood coagulation function test etc, were used to provide important basis for the diagnosis and treatment of the disease. In order to ensure laboratory biosafety, it is necessary to first evaluate the harm level of various specimens. In the laboratory biosafety management, the harm level assessment of microorganisms is the core work of biosafety, which is of great significance to guarantee biosafety. As an emergency deployment affected by the environment, shelter laboratory must possess strong mobility. This paper will explore how to combine the biosafety model of traditional laboratory with the particularity of shelter laboratory to carry out effective work in response to the current epidemic.

Clinical Characteristics and Short-Term Outcomes of Severe Patients with COVID-19 in Wuhan, China (preprint)

ObjectiveA novel pneumonia (COVID-19) which is sweeping the globe was started in December, 2019, in Wuhan, China. Most deaths occurred in severe and critically cases, but information on prognostic risk factors for severe ill patients is incomplete. Further research is urgently needed to guide clinicians, so we prospectively evaluate the clinical outcomes of 114 severe ill patients with COVID-19 for short-term in the Union Hospital in Wuhan, China. MethodsIn this single-centered, prospective and observational study, we enrolled 114 severe ill patients with confirmed COVID-19 from Jan 23, 2020 to February 22, 2020. Epidemiological, demographic and laboratory information were collected at baseline, data on treatment and outcome were collected until the day of death or discharge or for the first 28 days after severe ill diagnosis, whichever was shorter. Univariate and multivariate Cox proportional hazard models were used to determine hazard ratios (HRs) and 95% confidence intervals (CIs) of poor outcome. ResultsAmong enrolled 114 patients, 94 (82.5%) had good outcome while 20 (17.5%) had poor outcome. No significant differences were showed in age, gender and the prevalence of coexisting disorders between outcome groups. Results of multivariate Cox analyses indicated that higher levels of oxygen saturation (HR, 0.123; 95% CI, 0.041-0.369), albumin (HR, 0.060; 95% CI, 0.008-0.460) and arterial partial pressure of oxygen (HR, 0.321; 95% CI, 0.106-0.973) were associated with decreased risk of developing poor outcome within 28 days. In the other hand, higher levels of leucocytes (HR, 5.575; 95% CI, 2.080-14.943), neutrophils (HR, 2.566; 95% CI, 1.022-6.443), total bilirubin (HR, 6.171; 95% CI, 2.458- 15.496), globulin (HR, 2.526; 95% CI, 1.027-6.211), blood urea nitrogen (HR, 5.640; 95% CI, 2.193-14.509), creatine kinase-MB (HR, 3.032; 95% CI, 1.203-7.644), lactate dehydrogenase (HR, 4.607; 95% CI, 1.057-20.090), hypersensitive cardiac troponin I (HR, 5.023; 95% CI, 1.921-13.136), lactate concentration (HR,15.721; 95% CI, 2.099-117.777), Interleukin-10 (HR, 3.551; 95% CI, 1.280-9.857) and C-reactive protein (HR, 5.275; 95% CI, 1.517-18.344) were associated with increased risk of poor outcome development. We also found that traditional Chinese medicine can significantly improve the patients condition, which is conducive to the transformation from severe to mild. ConclusionIn summary, we firstly reported this single-centered, prospective and observational study for short-term outcome in severe patients with COVID-19. We found that cytokine storm and uncontrolled inflammation responses, liver, kidney, cardiac dysfunction may play important roles in final outcome of severe ill patients with COVID-19. Our study will provide clinicians to be benefit to rapidly estimate the likelihood risk of short-term poor outcome for severe patients.