Proteomic and metabolomic profiling of urine uncovers immune responses in patients with COVID-19.

The utility of the urinary proteome in infectious diseases remains unclear. Here, we analyzed the proteome and metabolome of urine and serum samples from patients with COVID-19 and healthy controls. Our data show that urinary proteins effectively classify COVID-19 by severity. We detect 197 cytokines and their receptors in urine, but only 124 in serum using TMT-based proteomics. The decrease in urinary ESCRT complex proteins correlates with active SARS-CoV-2 replication. The downregulation of urinary CXCL14 in severe COVID-19 cases positively correlates with blood lymphocyte counts. Integrative multiomics analysis suggests that innate immune activation and inflammation triggered renal injuries in patients with COVID-19. COVID-19-associated modulation of the urinary proteome offers unique insights into the pathogenesis of this disease. This study demonstrates the added value of including the urinary proteome in a suite of multiomics analytes in evaluating the immune pathobiology and clinical course of COVID-19 and, potentially, other infectious diseases.

Rapid immunoassay and clinical evaluation of the SARS-CoV-2 antibody assay on the real express-6 analyzer.

We developed a rapid and simple magnetic chemiluminescence enzyme immunoassay on the Real Express-6 analyzer, which could simultaneously detect immunoglobulin G and immunoglobulin M antibodies against SARS-CoV-2 virus in human blood within 18 min, and which could be used to detect clinical studies to verify its clinical efficacy. We selected blood samples from 185 COVID-19 patients confirmed by polymerase chain reaction and 271 negative patients to determine the clinical detection sensitivity, specificity, stability, and precision of this method. Meanwhile, we also surveyed the dynamic variance of viral antibodies during SARS-CoV-2 infection. This rapid immunoassay test has huge potential benefits for rapid screening of SARS-CoV-2 infection and may help clinical drug and vaccine development.

Risk factors for prolonged virus shedding of respiratory tract and fecal in adults with severe acute respiratory syndrome coronavirus-2 infection.

BACKGROUND: The dynamic alteration and comparative study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding pattern during treatment are limited. This study explores the potential risk factors influencing prolonged viral shedding in COVID-19. METHODS: A total of 126 COVID-19 patients were enrolled in this retrospective longitudinal study. A multivariate logistic regression analysis was carried out to estimate the potential risk factors. RESULTS: 38.1% (48/126) cases presented prolonged respiratory tract viral shedding, and 30 (23.8%) cases presented prolonged rectal swab viral shedding. Obesity (OR, 3.31; 95% CI, 1.08-10.09), positive rectal swab (OR, 3.43; 95% CI, 1.53-7.7), treatment by lopinavir/ritonavir with chloroquine phosphate (OR, 2.5; 95% CI, 1.04-6.03), the interval from onset to antiviral treatment more than 7 days (OR, 2.26; 95% CI, 1.04-4.93), lower CD4+ T cell (OR, 0.92; 95% CI, 0.86-0.99) and higher NK cells (OR, 1.11; 95% CI, 1.02-1.20) were significantly associated with prolonged respiratory tract viral shedding. CD3-CD56+ NK cells (OR, 0.87; 95% CI, 0.76-0.99) were related with prolonged fecal shedding. CONCLUSIONS: Obesity, delayed antiviral treatment, and positive SARS-CoV-2 for stool were independent risk factors for prolonged SARS-CoV-2 RNA shedding of the respiratory tract. A combination of LPV/r and abidol as the initial antiviral regimen was effective in shortening the duration of viral shedding compared with LPV/r combined with chloroquine phosphate. CD4+ T cell and NK cells were significantly associated with prolonged viral shedding, and further studies are to be warranted to determine the mechanism of immunomodulatory response in virus clearance.

Problematic Internet Usage and Self-Esteem in Chinese Undergraduate Students: The Mediation Effects of Individual Affect and Relationship Satisfaction.

The aim of this cross-sectional study was to examine the mediating effects of individual affect and relationship satisfaction on the relationship between self-esteem and Problematic Internet Use (PIU). Affect was measured using the Positive and Negative Affect Schedule (PANAS), relationship satisfaction was assessed using a positive and negative semantic dimension scale, self-esteem was measured using the Rosenberg Self-Esteem Scale, and PIU was measured using the Problematic Internet Use scale with a sample of 507 Chinese university students (Mage = 20.41 years, SD = 2.49). The relationships between the variables were tested using structural equation modelling with a multiple mediation model. The results revealed that negative affect and the negative semantic dimensions of relationship satisfaction mediated the relationship between self-esteem and PIU. The implications of the results and the study's theoretical contributions are discussed.

Population-based meta-analysis of chloroquine: informing chloroquine pharmacokinetics in COVID-19 patients.

AIMS: Chloroquine (CQ) has been repurposed to treat coronavirus disease 2019 (COVID-19). Understanding the pharmacokinetics (PK) in COVID-19 patients is essential to study its exposure-efficacy/safety relationship and provide a basis for a possible dosing regimen optimization. SUBJECT AND METHODS: In this study, we used a population-based meta-analysis approach to develop a population PK model to characterize the CQ PK in COVID-19 patients. An open-label, single-center study (ethical review approval number: PJ-NBEY-KY-2020-063-01) was conducted to assess the safety, efficacy, and pharmacokinetics of CQ in patients with COVID-19. The sparse PK data from 50 COVID-19 patients, receiving 500 mg CQ phosphate twice daily for 7 days, were combined with additional CQ PK data from 18 publications. RESULTS: A two-compartment model with first-order oral absorption and first-order elimination and an absorption lag best described the data. Absorption rate (ka) was estimated to be 0.559 h-1, and a lag time of absorption (ALAG) was estimated to be 0.149 h. Apparent clearance (CL/F) and apparent central volume of distribution (V2/F) was 33.3 l/h and 3630 l. Apparent distribution clearance (Q/F) and volume of distribution of peripheral compartment (Q3/F) were 58.7 l/h and 5120 l. The simulated CQ concentration under five dosing regimens of CQ phosphate were within the safety margin (400 ng/ml). CONCLUSION: Model-based simulation using PK parameters from the COVID-19 patients shows that the concentrations under the currently recommended dosing regimen are below the safety margin for side-effects, which suggests that these dosing regimens are generally safe. The derived population PK model should allow for the assessment of pharmacokinetics-pharmacodynamics (PK-PD) relationships for CQ when given alone or in combination with other agents to treat COVID-19.

Clinical features of COVID-19 convalescent patients with re-positive nucleic acid detection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a pandemic that has rapidly spread worldwide. Increasingly, confirmed patients being discharged according to the current diagnosis and treatment protocols, follow-up of convalescent patients is important to knowing about the outcome. METHODS: A retrospective study was performed among 98 convalescent patients with COVID-19 in a single medical center. The clinical features of patients during their hospitalization and 2-week postdischarge quarantine were collected. RESULTS: Among the 98 COVID-19 convalescent patients, 17 (17.3%) were detected positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid during 2-week postdischarge quarantine. The median time from discharge to SARS-CoV-2 nucleic acid re-positive was 4 days (IQR, 3-8.5).The median time from symptoms onset to final respiratory SARS-CoV-2 detection of negative result was significantly longer in re-positive group (34 days [IQR, 29.5-42.5]) than in non-re-positive group (19 days [IQR, 16-26]). On the other hand, the levels of CD3-CD56 + NK cells during hospitalization and 2-week postdischarge were higher in re-positive group than in non-re-positive group (repeated measures ANOVA, P = .018). However, only one case in re-positive group showed exudative lesion recurrence in pulmonary computed tomography (CT) with recurred symptoms. CONCLUSION: It is still possible for convalescent patients to show positive for SARS-CoV-2 nucleic acid detection, but most of the re-positive patients showed no deterioration in pulmonary CT findings. Continuous quarantine and close follow-up for convalescent patients are necessary to prevent possible relapse and spread of the disease to some extent.