Cross-platform comparison of highly-sensitive immunoassays for inflammatory markers in a COVID-19 cohort (preprint)

A variety of commercial platforms are available for the simultaneous detection of multiple cytokines and associated proteins, often employing antibody pairs to capture and detect target proteins. In this study, we comprehensively evaluated the performance of three distinct platforms: the fluorescent bead-based Luminex assay, the proximity extension-based Olink assay, and a novel proximity ligation assay platform known as Alamar NULISAseq. These assessments were conducted on serum samples from the NIH IMPACC study, with a focus on three essential performance metrics: detectability, correlation, and differential expression. Our results reveal several key findings. Firstly, the Alamar platform demonstrated the highest overall detectability, followed by Olink and then Luminex. Secondly, the correlation of protein measurements between the Alamar and Olink platforms tended to be stronger than the correlation of either of these platforms with Luminex. Thirdly, we observed that detectability differences across the platforms often translated to differences in differential expression findings, although high detectability did not guarantee the ability to identify meaningful biological differences. Our study provides valuable insights into the comparative performance of these assays, enhancing our understanding of their strengths and limitations when assessing complex biological samples, as exemplified by the sera from this COVID-19 cohort.

The Impact of Post Embryo Transfer SARS-CoV-2 Infection on Pregnancy in In Vitro Fertilization: A Prospective Cohort Study (preprint)

ImportanceLimited knowledge exists on the effects of SARS-CoV-2 infection after embryo transfer, despite an increasing number of studies exploring the impact of previous SARS-CoV-2 infection on IVF outcomes. ObjectiveThis prospective cohort study aimed to assess the influence of SARS-CoV-2 infection at various time stages after embryo transfer on pregnancy outcomes in patients undergoing conventional in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI) treatment. DesignThe study was conducted at a single public IVF center in China. SettingThis was a population-based prospective cohort study. ParticipantsFemale patients aged 20 to 39 years, with a body mass index (BMI) between 18 and 30 kg/m2, undergoing IVF/ICSI treatment, were enrolled from September 2022 to December 2022, with follow-up until March 2023. ExposureThe pregnancy outcome of patients was compared between those SARS-CoV-2-infected after embryo transfer and those noninfected during the follow-up period. Main Outcomes and MeasuresThe pregnancy outcomes included biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate. ResultsA total of 857 female patients undergoing IVF/ICSI treatment were included in the analysis. We observed the incidence of SARS-CoV-2 infection within 10 weeks after embryo transfer. The biochemical pregnancy rate and implantation rate were lower in the infected group than the uninfected group (58.1% vs 65.9%; 36.6% vs 44.0%, respectively), but no statistically significant. Although, the clinical pregnancy rate was significant lower in the infection group when compared with the uninfected group (49.1%vs 58.2%, p < 0.05), after adjustment for confounders, this increased risk was no longer significant between the two groups (adjusted OR, 0.736, 95% CI, 0.518-1.046). With continued follow-up, a slightly higher risk of early miscarriage in the infected group compared to the uninfected group (9.3% vs 8.8%), but it was not significant (adjusted OR, 0.907, 95% CI, 0.414-1.986). Conclusions and RelevanceThe studys findings suggested that SARS-CoV-2 infection within 10 weeks after embryo transfer may have not significantly affect pregnancy outcomes. This evidence allays concerns and provides valuable insights for assisted reproduction practices. Key pointsO_ST_ABSQuestionC_ST_ABSDid the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after embryo transfer affect pregnancy outcomes? FindingsIn this prospective cohort study involving 857 patients, we made a pioneering discovery that SARS-CoV-2 infection following embryo transfer did not exhibit adverse impact on the biochemical pregnancy rate, embryo implantation rate, clinical pregnancy rate, and early miscarriage rate. MeaningThe evidence from this study alleviates existing concerns and offers new insights into the actual risk of SARS-CoV-2 infection after embryo transfer in assisted reproduction.

Social media use, psychological well-being and physical health during lockdown

In efforts to curb the spread of COVID-19, many countries have implemented a variety of lockdown and quarantine measures. With substantially reduced face-to-face interactions, many people may have relied heavily on social media for connection, information, and entertainment. However, little is known about the psychological and physical health implications of social media use during strict lockdown. The current study investigates the associations of social media use with psychological well-being and physical health among Wuhan residents (N = 1214). Our findings showed that non-COVID related self-disclosure was positively associated with psychological well-being, while COVID related information consumption and sharing were negatively associated with psychological well-being. Further, more generic use of social media was associated with lower psychological well-being, which in turn related to more somatic symptoms. Quarantined people used social media more frequently than non-quarantined people. Importantly, the negative association between social media use and psychological well-being was significantly stronger for quarantined people than unquarantined people. [ FROM AUTHOR] Copyright of Information, Communication & Society is the property of Routledge and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Identification and quantitative analysis of bioactive components from Potentilla kleiniana Wight et Arn with anti HIV-1 proteases activity.

Potentilla kleiniana Wight et Arn（PK, 'Wu Pi Feng' in Chinese） was recorded as Miao ethnic medicine for treatment of fever, cough, ulcer, and erysipelas for thousands years. This study aimed to evaluate the antiviral activity of four PK extracts and seven compounds by using HIV-1 protease (HIV-1 PR). In addition, Ultra-High Performance Liquid Chromatography and High Resolution Mass Spectrometry (UPLC-HRMS) was employed to identify the bioactive components. The toxicity assessment of the extracts was done before antiviral screening using a highly specific human aspartyl protease, renin protease by fluorimetric method. As a result, seven compounds and four extracts of PK inhibited HIV-1 PR with IC50 range from 0.009 to 0.36 mg/mL, and did not appreciably inhibit the general human protease renin. This study first demonstrated that four PK extracts, ellagic acid and ursolic acid potent inhibit HIV-1 protease, could be used as an efficacious drug candidate to treat SARS-CoV-2 infection.

Identification of Flavonoids from Scutellaria barbata D. Don as Inhibitors of HIV-1 and Cathepsin L Proteases and Their Structure-Activity Relationships.

Scutellaria barbata D. Don (SB, Chinese: Ban Zhi Lian), a well-known medicinal plant used in traditional Chinese medicine, is rich in flavonoids. It possesses antitumor, anti-inflammatory, and antiviral activities. In this study, we evaluated the inhibitory activities of SB extracts and its active components against HIV-1 protease (HIV-1 PR) and SARS-CoV2 viral cathepsin L protease (Cat L PR). UPLC/HRMS was used to identify and quantify the major active flavonoids in different SB extracts, and fluorescence resonance energy transfer (FRET) assays were used to determine HIV-1 PR and Cat L PR inhibitions and identify structure-activity relationships. Molecular docking was also performed, to explore the diversification in bonding patterns of the active flavonoids upon binding to the two PRs. Three SB extracts (SBW, SB30, and SB60) and nine flavonoids inhibited HIV-1 PR with an IC50 range from 0.006 to 0.83 mg/mL. Six of the flavonoids showed 10~37.6% inhibition of Cat L PR at a concentration of 0.1 mg/mL. The results showed that the introduction of the 4'-hydroxyl and 6-hydroxyl/methoxy groups was essential in the 5,6,7-trihydroxyl and 5,7,4'-trihydroxyl flavones, respectively, to enhance their dual anti-PR activities. Hence, the 5,6,7,4'-tetrahydroxyl flavone scutellarein (HIV-1 PR, IC50 = 0.068 mg/mL; Cat L PR, IC50 = 0.43 mg/mL) may serve as a lead compound to develop more effective dual protease inhibitors. The 5,7,3',4'-tetrahydroxyl flavone luteolin also showed a potent and selective inhibition of HIV-1 PR (IC50 = 0.039 mg/mL).

NULISA: a novel proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing (preprint)

The blood proteome holds great promise for precision medicine but poses daunting challenges due to the low abundance of the majority of plasma proteins and the vast dynamic range across the proteome. We report the development and validation of a novel proteomic analysis technology - NUcleic acid Linked Immuno-Sandwich Assay (NULISA) - that incorporates a dual capture and release mechanism to suppress the assay background to the minimum, thus drastically improving the signal-to-noise ratio. NULISA improves the sensitivity of the proximity ligation assay by over 10,000-fold to the attomolar level, which is enabled by antibody-conjugated DNA sequences that mediate the purification of immunocomplexes and contain target- and sample-specific barcodes for next-generation sequencing-based, highly multiplexed analysis. To demonstrate its performance and utility, we developed a 200-plex NULISA targeting 124 cytokines and chemokines and 80 other immune response-related proteins that demonstrated superior sensitivity for detecting low-abundance proteins and high concordance with other immunoassays. The ultra-high sensitivity enabled the detection of previously difficult-to-detect but biologically important, low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA uniquely addresses longstanding challenges in the proteomic analysis of liquid biopsy samples and makes broad and in-depth proteomic analysis accessible to the general research community and future diagnostic applications.

Hematopoietic stem cell transplantation activity in China 2020-2021 during the SARS-CoV-2 pandemic: a report from the Chinese Blood and Marrow Transplantation Registry Group.

Between 2020 and 2021, 31,525 hematopoietic stem cell transplantations (HSCTs) were reported to the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) throughout mainland China. In this report, we describe the activity and current trends for HSCT in China during the SARS-CoV-2 pandemic. In 2020, a total of 13,415 cases of HSCT were reported from 166 transplant teams, and 75% (10,042 cases) were allogeneic HSCTs. In 2021, a total of 18,110 cases of HSCT were reported from 174 transplant teams, and 70% (12,744 cases) were allogeneic HSCTs. Haploidentical donor (HID) transplantation accounted for 63% (7977 cases) of allogeneic HSCTs in 2021. The most common indications for allogeneic HSCT for malignant disease were acute myeloid leukemia (AML) (37%) and acute lymphoblastic leukemia (ALL) (23%), and the largest proportion of nonmalignant disease comprised aplastic anemia (AA) (13%). The PB stem cell source accounted for 41% of HIDs and 75% of MSDs. The BuCy-based regimen (57%) was the most popular conditioning regimen for allogeneic HSCT, followed by the BuFlu-based regimen (28%) and TBI-based regimen (11%). This survey provides comprehensive information about the current activities and might benefit clinical physicians' decision planning for HSCT.

Leveraging an established neighbourhood-level, open access wastewater monitoring network to address public health priorities: a population-based study.

BACKGROUND: Before the COVID-19 pandemic, the US opioid epidemic triggered a collaborative municipal and academic effort in Tempe, Arizona, which resulted in the world's first open access dashboard featuring neighbourhood-level trends informed by wastewater-based epidemiology (WBE). This study aimed to showcase how wastewater monitoring, once established and accepted by a community, could readily be adapted to respond to newly emerging public health priorities. METHODS: In this population-based study in Greater Tempe, Arizona, an existing opioid monitoring WBE network was modified to track SARS-CoV-2 transmission through the analysis of 11 contiguous wastewater catchments. Flow-weighted and time-weighted 24 h composite samples of untreated wastewater were collected at each sampling location within the wastewater collection system for 3 days each week (Tuesday, Thursday, and Saturday) from April 1, 2020, to March 31, 2021 (Area 7 and Tempe St Luke's Hospital were added in July, 2020). Reverse transcription quantitative PCR targeting the E gene of SARS-CoV-2 isolated from the wastewater samples was used to determine the number of genome copies in each catchment. Newly detected clinical cases of COVID-19 by zip code within the City of Tempe, Arizona were reported daily by the Arizona Department of Health Services from May 23, 2020. Maricopa County-level new positive cases, COVID-19-related hospitalisations, deaths, and long-term care facility deaths per day are publicly available and were collected from the Maricopa County Epidemic Curve Dashboard. Viral loads of SARS-CoV-2 (genome copies per day) measured in wastewater from each catchment were aggregated at the zip code level and city level and compared with the clinically reported data using root mean square error to investigate early warning capability of WBE. FINDINGS: Between April 1, 2020, and March 31, 2021, 1556 wastewater samples were analysed. Most locations showed two waves in viral levels peaking in June, 2020, and December, 2020-January, 2021. An additional wave of viral load was seen in catchments close to Arizona State University (Areas 6 and 7) at the beginning of the fall (autumn) semester in late August, 2020. Additionally, an early infection hotspot was detected in the Town of Guadalupe, Arizona, starting the week of May 4, 2020, that was successfully mitigated through targeted interventions. A shift in early warning potential of WBE was seen, from a leading (mean of 8·5 days [SD 2·1], June, 2020) to a lagging (-2·0 days [1·4], January, 2021) indicator compared with newly reported clinical cases. INTERPRETATION: Lessons learned from leveraging an existing neighbourhood-level WBE reporting dashboard include: (1) community buy-in is key, (2) public data sharing is effective, and (3) sub-ZIP-code (postal code) data can help to pinpoint populations at risk, track intervention success in real time, and reveal the effect of local clinical testing capacity on WBE's early warning capability. This successful demonstration of transitioning WBE efforts from opioids to COVID-19 encourages an expansion of WBE to tackle newly emerging and re-emerging threats (eg, mpox and polio). FUNDING: National Institutes of Health's RADx-rad initiative, National Science Foundation, Virginia G Piper Charitable Trust, J M Kaplan Fund, and The Flinn Foundation.

Inhibitors of HIV-1 and Cathepsin L Proteases Identified from the Insect Gall of Hypericum kouytchense.

Hypericum kouytchense Lévl is a semi-evergreen plant of the Hypericaceae family. Its roots and seeds have been used in a number of traditional remedies for antipyretic, detoxification, anti-inflammatory, antimicrobial and antiviral functions. However, to date, no bioactivity compounds have been characterized from the insect gall of H. kouytchens. In this study, we evaluated the antiviral activities of different extracts from the insect gall of H. kouytchen against cathepsin L, HIV-1 and renin proteases and identified the active ingredients using UPLC-HRMS. Four different polar extracts (HW, H30, H60 and H85) of the H. kouytchense insect gall exhibited antiviral activities with IC50 values of 10.0, 4.0, 3.2 and 17.0 µg/mL against HIV-1 protease; 210.0, 34.0, 24.0 and 30.0 µg/mL against cathepsin L protease; and 180.0, 65.0, 44.0 and 39.0 µg/mL against human renin, respectively. Ten compounds were identified and quantified in the H. kouytchense insect gall extracts. Epicatechin, eriodictyol and naringenin chalcone were major ingredients in the extracts with contents ranging from 3.9 to 479.2 µg/mg. For HIV-1 protease, seven compounds showed more than 65% inhibition at a concentration of 1000.0 µg/mL, especially for hypericin and naringenin chalcone with IC50 values of 1.8 and 33.0 µg/mL, respectively. However, only hypericin was active against cathepsin L protease with an IC50 value of 17100.0 µg/mL, and its contents were from 0.99 to 11.65 µg/mg. Furthermore, we attempted to pinpoint the interactions between the active compounds and the proteases using molecular docking analysis. Our current results imply that the extracts and active ingredients could be further formulated and/or developed for potential prevention and treatment of HIV or SARS-CoV-2 infections.

Effect of ambient air pollutants and meteorological variables on COVID-19 incidence.

OBJECTIVE: To determine whether ambient air pollutants and meteorological variables are associated with daily COVID-19 incidence. DESIGN: A retrospective cohort from January 25 to February 29, 2020. SETTING: Cities of Wuhan, Xiaogan, and Huanggang, China. PATIENTS: The COVID-19 cases detected each day. METHODS: We collected daily data of COVID-19 incidence, 8 ambient air pollutants (particulate matter of ≤2.5 µm [PM2.5], particulate matter ≤10 µm [PM10], sulfur dioxide [SO2], carbon monoxide [CO], nitrogen dioxide [NO2], and maximum 8-h moving average concentrations for ozone [O3-8h]) and 3 meteorological variables (temperature, relative humidity, and wind) in China's 3 worst COVID-19-stricken cities during the study period. The multivariate Poisson regression was performed to understand their correlation. RESULTS: Daily COVID-19 incidence was positively associated with PM2.5 and humidity in all cities. Specifically, the relative risk (RR) of PM2.5 for daily COVID-19 incidences were 1.036 (95% confidence interval [CI], 1.032-1.039) in Wuhan, 1.059 (95% CI, 1.046-1.072) in Xiaogan, and 1.144 (95% CI, 1.12-1.169) in Huanggang. The RR of humidity for daily COVID-19 incidence was consistently lower than that of PM2.5, and this difference ranged from 0.027 to 0.111. Moreover, PM10 and temperature also exhibited a notable correlation with daily COVID-19 incidence, but in a negative pattern The RR of PM10 for daily COVID-19 incidence ranged from 0.915 (95% CI, 0.896-0.934) to 0.961 (95% CI, 0.95-0.972, while that of temperature ranged from 0.738 (95% CI, 0.717-0.759) to 0.969 (95% CI, 0.966-0.973). CONCLUSIONS: Our data show that PM2.5 and humidity are substantially associated with an increased risk of COVID-19 and that PM10 and temperature are substantially associated with a decreased risk of COVID-19.

Cross-sectional survey following a longitudinal study on mental health and insomnia of people with sporadic COVID-19.

BACKGROUND: In the post-pandemic era, the emergence of sporadic cases of coronavirus disease 2019 (COVID-19) and the scale of the pandemic are unpredictable. Therefore, the impact of sporadic cases of COVID-19 and isolation measures on mental health and sleep in different groups of people need to be analyzed. AIM: To clarify the severity of psychological problems and insomnia of staff and community residents around a hospital with sporadic cases of COVID-19, and their relationship with quarantine location and long-term changes. METHODS: A cross-sectional survey was conducted on community residents and medical staff. Many of these medical staff had been subjected to different places of quarantine. Community residents did not experience quarantine. Hospital anxiety and depression scale (HADS), acute stress disorder scale (ASDS) and insomnia severity index (ISI) were used to evaluate anxiety and depression, acute stress disorder symptoms, and the severity of insomnia. Additionally, we conducted a 1-year follow-up study on medical staff, with related scales measurement immediately after and one year after the 2-wk quarantine period. RESULTS: We included 406 medical staff and 226 community residents. The total scores of ISI and subscale in HADS of community residents were significantly higher than that of medical staff. Further analysis of medical staff who experienced quarantine showed that 134 were quarantined in hotels, 70 in hospitals and 48 at home. Among all subjects, the proportions of HADS, ASDS and ISI scores above normal cutoff value were 51.94%, 19.17% and 31.11%, respectively. Multivariable logistic regression analysis found that subjects with higher total ASDS scores had a greater risk to develop anxiety and depression. The total ISI score for medical staff in hotel quarantine was significantly higher than those in home quarantine. Total 199 doctors and nurses who completed the 1-year follow-up study. Compared with baseline, HADS and ASDS scores decreased significantly one year after the end of quarantine, while ISI scores did not change significantly. CONCLUSION: Sporadic COVID-19 cases had a greater psychological impact on residents in surrounding communities, mainly manifested as insomnia and depressive symptoms. Hotel quarantine aggravated the severity of insomnia in medical staff, whose symptoms lasted ≥ 1 year.

Discovery of the Cryptic Sites of SARS-CoV-2 Papain-like Protease and Analysis of Its Druggability.

In late 2019, a new coronavirus (CoV) caused the outbreak of a deadly respiratory disease, resulting in the COVID-19 pandemic. In view of the ongoing pandemic, there is an immediate need to find drugs to treat patients. SARS-CoV-2 papain-like cysteine protease (PLpro) not only plays an important role in the pathogenesis of the virus but is also a target protein for the development of inhibitor drugs. Therefore, to develop targeted inhibitors, it is necessary to analyse and verify PLpro sites and explore whether there are other cryptic binding pockets with better activity. In this study, first, we detected the site of the whole PLpro protein by sitemap of Schrödinger (version 2018), the cavity of LigBuilder V3, and DeepSite, and roughly judged the possible activated binding site area. Then, we used the mixed solvent dynamics simulation (MixMD) of probe molecules to induce conformational changes in the protein to find the possible cryptic active sites. Finally, the TRAPP method was used to predict the druggability of cryptic pockets and analyse the changes in the physicochemical properties of residues around these sites. This work will help promote the research of SARS-CoV-2 PLpro inhibitors.

COVID-19 infection with keratitis as the first clinical manifestation

AIM To report a case which keratitis is the first clinical manifestation of COVID-19 that occurred 3d earlier than the common COVID-19 symptoms. METHODS Regular slit lamp examination, corneal scraping test, and chest computed tomography (CT) were performed for patients with COVID-19 infection. The ophthalmologic treatment included ganciclovir eye drop (50 mg/mL, 6 times/d). The treatment for diarrhea included Guifu Lizhong pills (TID). The antiviral therapy consisted of oseltamivir (75 mg capsule Q12H);therapy preventing bacterial infection consisted of azithromycin (250 mg tablet QD) and moxifloxacin (0.4 g tablet Q12H);and therapy for cough relief and fever prevention consisted of Chinese herbal decoction. RESULTS A 35-year-old male suddenly suffered pain, photophobia, and tears in his right eye for one day without systemic COVID-19 symptoms. Patient was diagnosed with keratitis, which was seemingly different from common keratitis. Ganciclovir eye drop was initiated. The corneal scraping test for COVID-19 was positive. The chest CT images were abnormal confirming the diagnosis of COVID-19 infection. The antiviral and antibacterial therapies were initiated. Chinese herbal therapy was used for cough relief and fever prevention. After roughly two weeks, patient recovered from COVID-19. CONCLUSION A new type of keratitis, atypical keratitis, is a clinical manifestation of COVID-19, and this clinical manifestation could appear 3d earlier than fever and cough. The earlier a COVID-19 clinical manifestation is identified, the earlier can a patient be directed to stay at home, and significantly fewer people would be infected.

A C-terminal glutamine recognition mechanism revealed by E3 ligase TRIM7 structures.

The E3 ligase TRIM7 has emerged as a critical player in viral infection and pathogenesis. However, the mechanism governing the TRIM7-substrate association remains to be defined. Here we report the crystal structures of TRIM7 in complex with 2C peptides of human enterovirus. Structure-guided studies reveal the C-terminal glutamine residue of 2C as the primary determinant for TRIM7 binding. Leveraged by this finding, we identify norovirus and SARS-CoV-2 proteins, and physiological proteins, as new TRIM7 substrates. Crystal structures of TRIM7 in complex with multiple peptides derived from SARS-CoV-2 proteins display the same glutamine-end recognition mode. Furthermore, TRIM7 could trigger the ubiquitination and degradation of these substrates, possibly representing a new Gln/C-degron pathway. Together, these findings unveil a common recognition mode by TRIM7, providing the foundation for further mechanistic characterization of antiviral and cellular functions of TRIM7.

Contribution of CD4+ T cell-mediated inflammation to diarrhea in patients with COVID-19.

OBJECTIVES: This study aimed to explore the role of CD4+ T cells in the mechanisms of COVID-19 related diarrhea. METHODS: We analyzed lymphocyte subsets in patients with COVID-19 and the expression of angiotensin-converting enzyme 2 (ACE2), the transmembrane protease serine 2, and CD4+ T cell-related indicators in the colon were compared between patients with and without diarrhea. Correlation analyses were performed for ACE2 and other indicators to identify the relationship between SARS-CoV-2 infection and CD4+ mediated inflammation. The expression and distribution of CD4+ T cell-associated chemokines and their receptors were detected to determine the possibility of migration of CD4+ T cells to inflammation sites. RESULTS: The CD4+ T cell counts and percentages and CD4/CD8 ratio showed the most significant differences between the 2 groups. The diarrhea group expressed higher levels of ACE2, T-box expressed in T cells (Tbet), and tumor necrosis factor-alpha (TNFα) at both the mRNA and protein levels, with no difference from the nondiarrhea group for the percentage of ACE2+TNFα+ cells, indicating an indirect association between ACE2 and TNFα. The mRNA expression of CXCL10, CXCL11, and CXCR3 and the number of CD4+CXCR3+T cells were increased in the diarrhea group. CONCLUSIONS: CD4+ T cell-mediated inflammation may contribute to COVID-19 related diarrhea. CXCR3+ mediated migration of CD4+ T cells into the gut may perpetuate inflammation.

Persistent Endothelial Dysfunction in Coronavirus Disease-2019 Survivors Late After Recovery.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can result in an endothelial dysfunction in acute phase. However, information on the late vascular consequences of COVID-19 is limited. METHODS: Brachial artery flow-mediated dilation (FMD) examination were performed, and inflammatory biomarkers were assessed in 86 survivors of COVID-19 for 327 days (IQR 318-337 days) after recovery. Comparisons were made with 28 age-matched and sex-matched healthy controls and 30 risk factor-matched patients. RESULTS: Brachial artery FMD was significantly lower in the survivors of COVID-19 than in the healthy controls and risk factor-matched controls [median (IQR) 7.7 (5.1-10.7)% for healthy controls, 6.9 (5.5-9.4)% for risk factor-matched controls, and 3.5(2.2-4.6)% for COVID-19, respectively, p < 0.001]. The FMD was lower in 25 patients with elevated tumor necrosis factor (TNF)-α [2.7(1.2-3.9)] than in 61 patients without elevated TNF-α [3.8(2.6-5.3), p = 0.012]. Furthermore, FMD was inversely correlated with serum concentration of TNF-α (r = -0.237, p = 0.007). CONCLUSION: Survivors of COVID-19 have a reduced brachial artery FMD, which is inversely correlated with increased serum concentration of TNF-α. Prospective studies on the association of endothelial dysfunction with long-term cardiovascular outcomes, especially the early onset of atherosclerosis, are warranted in survivors of COVID-19.

Why Controlling the Asymptomatic Infection Is Important: A Modelling Study with Stability and Sensitivity Analysis

The large proportion of asymptomatic patients is the major cause leading to the COVID-19 pandemic which is still a significant threat to the whole world. A six-dimensional ODE system (SEIAQR epidemical model) is established to study the dynamics of COVID-19 spreading considering infection by exposed, infected, and asymptomatic cases. The basic reproduction number derived from the model is more comprehensive including the contribution from the exposed, infected, and asymptomatic patients. For this more complex six-dimensional ODE system, we investigate the global and local stability of disease-free equilibrium, as well as the endemic equilibrium, whereas most studies overlooked asymptomatic infection or some other virus transmission features. In the sensitivity analysis, the parameters related to the asymptomatic play a significant role not only in the basic reproduction number R0. It is also found that the asymptomatic infection greatly affected the endemic equilibrium. Either in completely eradicating the disease or achieving a more realistic goal to reduce the COVID-19 cases in an endemic equilibrium, the importance of controlling the asymptomatic infection should be emphasized. The three-dimensional phase diagrams demonstrate the convergence point of the COVID-19 spreading under different initial conditions. In particular, massive infections will occur as shown in the phase diagram quantitatively in the case R0>1. Moreover, two four-dimensional contour maps of Rt are given varying with different parameters, which can offer better intuitive instructions on the control of the pandemic by adjusting policy-related parameters.

Subjective health status: an easily available, independent, robust and significant predictive factor at the prometaphase of vaccination programs for the vaccination behavior of Chinese adults.

BACKGROUND: The World Health Organization (WHO) proposed COVID-19 vaccination as an emergent and important method to end the COVID-19 pandemic. Since China started vaccination programs in December 2020, vaccination has spread to provinces and municipalities nationwide. Previous research has focused on people's vaccination willingness and its influencing factors but has not examined vaccination behavior. We examine the effectiveness of psychosocial factors in predicting vaccination behavior. METHODS: A cross-sectional online survey was performed among Chinese adults on 8 May and 4 June 2021. The statistical analysis of the data included univariate analysis, receiver operator characteristics (ROC) analysis and ordinal multiclassification logistic regression model analysis. RESULTS: Of the 1300 respondents, 761 (58.5%) were vaccinated. Univariate analysis showed that a high education level and good subjective health status were protective factors for vaccination behavior, while suffering from chronic diseases was a risk factor. ROC analysis showed that subjective health status (AUC = 0.625, 95% CI: 0.594-0.656, P < 0.001) was the best predictor of vaccination behavior. Logistic regression analysis with subjective health status as a dependent variable indicated that older age, female sex, depression, neurasthenia, obsession, hypochondriasis and chronic disease were significant risk factors, while positive coping tendencies were a significant protective factor. CONCLUSION: Our study found a simple and effective marker, subjective health status, that can predict vaccination behavior. This finding can guide future epidemic prevention work.

The willingness of Chinese adults to receive the COVID-19 vaccine and its associated factors at the early stage of the vaccination programme: a network analysis.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has been a continuous global threat since the first identification of the disease in December 2019. COVID-19 vaccination is a crucial preventive approach that can halt this pandemic. However, many factors affect the willingness of the public to be vaccinated against COVID-19 at the early stage of the vaccination programme. We used network analysis to investigate the interrelation of vaccination willingness and its associated factors. METHODS: A population-representative sample of 539 Chinese adults completed a battery of online self-assessments, including those on vaccination willingness, health status, attitude towards vaccines, COVID-19-related psychological elements and other variables. Network analysis was performed using the R qgraph package. RESULTS: In total, 445 (82.6%) participants scored high on their willingness to vaccinate. Attitude towards vaccines, the influence of people around an individual and health status were directly significantly related to vaccination willingness. The betweenness of age was the highest and, the emotional states had the strongest centrality. LIMITATIONS: Network analysis is not sufficient to determine the causal relationships of the links between nodes. In addition, there are other latent essential elements that were not evaluated. Finally, the sample size was relatively small. CONCLUSION: Network analysis showed that attitude toward vaccines and emotional states are the most critical factors affecting vaccination willingness, which indicates that we should pay attention to the impact of the dissemination of Internet information on vaccination willingness and public emotional states during a pandemic which is very important for promoting vaccination programs.

JD.com: Operations Research Algorithms Drive Intelligent Warehouse Robots to Work

JD.com pioneered same-day delivery as a standard service in China's business-to-consumer e-commerce sector in 2010. To balance the urgent need to meet growing demands while maintaining high-quality logistics services, the company built intelligent warehouses that use analytics to significantly improve warehouse efficiency. The brain of the intelligent warehouse system is the dispatching algorithm for storage rack-moving robots, which makes real-time dispatching decisions among robots, racks, and workstations after solving large-scale integer programs in seconds. The intelligent warehouse technology has helped the company decrease its fulfillment expense ratio to a world-leading level of 6.5%. The construction of intelligent warehouses has led to estimated annual savings of hundreds of millions of dollars. In 2020, JD.com delivered 90% of its first-party-owned retail orders on the same day or on the day after the order was placed. The agility of such intelligent warehouses has allowed JD.com to handle 10 times the normal volume of orders during peak sales seasons and has also helped the company respond quickly to COVID-19 and ensure the rapid recovery of production capabilities.