Proteomic and Metabolomic Characterization of COVID-19 Patient Sera.

Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model was validated using 10 independent patients, 7 of which were correctly classified. Targeted proteomics and metabolomics assays were employed to further validate this molecular classifier in a second test cohort of 19 COVID-19 patients, leading to 16 correct assignments. We identified molecular changes in the sera of COVID-19 patients compared to other groups implicating dysregulation of macrophage, platelet degranulation, complement system pathways, and massive metabolic suppression. This study revealed characteristic protein and metabolite changes in the sera of severe COVID-19 patients, which might be used in selection of potential blood biomarkers for severity evaluation.

Prediction of severe illness due to COVID-19 based on an analysis of initial Fibrinogen to Albumin Ratio and Platelet count.

Concomitant coagulation disorder can occur in severe patients withCOVID-19, but in-depth studies are limited. This study aimed to describe the parameters of coagulation function of patients with COVID-19 and reveal the risk factors of developing severe disease. This study retrospectively analyzed 113patients with SARS-CoV-2 infection in Taizhou Public Health Center. Clinical characteristics and indexes of coagulation function were collected. A multivariate Cox analysis was performed to identify potential biomarkers for predicting disease progression. Based on the results of multivariate Cox analysis, a Nomogram was built and the predictive accuracy was evaluated through the calibration curve, decision curve, clinical impact curve, and Kaplan-Meier analysis. Sensitivity, specificity, predictive values were calculated to assess the clinical value. The data showed that Fibrinogen, FAR, and D-dimer were higher in the severe patients, while PLTcount, Alb were much lower. Multivariate Cox analysis revealed that FAR and PLT count were independent risk factors for disease progression. The optimal cutoff values for FAR and PLT count were 0.0883 and 135*109/L, respectively. The C-index [0.712 (95% CI = 0.610-0.814)], decision curve, clinical impact curve showed that Nomogram could be used to predict the disease progression. In addition, the Kaplan-Meier analysis revealed that potential risk decreased in patients with FAR<0.0883 and PLT count>135*109/L.The model showed a good negative predictive value [(0.9474 (95%CI = 0.845-0.986)].This study revealed that FAR and PLT count were independent risk factors for severe illness and the severity of COVID-19 might be excluded when FAR<0.0883 and PLT count>135*109/L.

Enhanced antitumor efficacy using epirubicin and schisandrin B co-delivery liposomes modified with PFV via inhibiting tumor metastasis.

As a malignant tumor, breast cancer is very prone to metastasis. Chemotherapy is one of the most common means for treating breast cancer. However, due to the serious metastasis and the poor targeting effect of traditional chemotherapeutic drugs, even after years of efforts, the therapeutic effect is still unsatisfied. Therefore, in this study, we constructed a kind of PFV modified epirubicin plus schisandrin B liposomes to solve the above disadvantages. In vitro experiments showed that the targeting liposomes with ideal physicochemical property could increase the cytotoxicity of MDA-MB-435S cells, destroy the formation of vasculogenic mimicry (VM), and inhibit tumor invasion and migration. Action mechanisms indicated that the inhibition of targeting liposomes on tumor metastasis was attributed to the regulation of the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), vimentin (VIM), and E-cadherin (E-cad). In vivo pharmacodynamic experiments showed that the targeting liposomes could significantly improve the antitumor effect in mice. H&E staining and TUNEL results showed that the targeting liposomes could promote the apoptosis of tumor cells. Hence, the PFV modified epirubicin plus schisandrin B liposomes constructed in this study provided a new therapeutic strategy for breast cancer.

Efficacy of the neutralizing antibodies after the booster dose on SARS-CoV-2 Omicron variant and a two-year longitudinal antibody study on Wild Type convalescents.

OBJECTIVES: Waning vaccine-induced immunity and emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants which may lead to immune escape, pose a major threat to the COVID-19 pandemic. Currently, enhanced efficacy of the neutralization antibodies (NAb) produced after the booster dose of vaccinations against the Omicron variant is the main focus of vaccine strategy research. In this study we have analyzed the potency of the NAbs and IgGs produced after the third vaccine dose in patients infected with Omicron variant and wild-type (WT) SARS-CoV-2. METHODS: We enrolled 75 patients with Omicron variant breakthrough infections, and 87 patients with WT infections. We recorded the clinical characteristics and vaccination information of all patients and measured the NAb and anti-S1 (spike protein) + N (nucleocapsid protein) IgG-binding antibodies against SARS-CoV-2 in serum samples of Omicron variant-infected patients at admission, and patients with WT COVID-19 infection from the time of admission and discharge, and one-year to two-years follow-ups. RESULTS: Our results demonstrated higher NAb levels, fewer clinical symptoms, and faster viral shedding in Omicron variant infected patients vaccinated with the booster dose. Hybrid immunity (natural infection plus vaccination) induces higher NAb levels than vaccine-only immunity. NAb and IgG levels decreased significantly at one-year follow-up in WT convalescents with natural infection. The NAb and IgG levels in booster-vaccinated COVID-19 patients were higher than those in two-dose-vaccinated patients. CONCLUSION: Our results suggest that booster vaccinations are required to improve the level of protective NAbs. Moreover, our data provide important evidence for vaccination strategies based on existing vaccines.

Differences Between Omicron Infections and Fever Outpatients: Comparison of Clinical Manifestations and Initial Routine Hematology Indicators.

Purpose: We evaluated the differences between patients with SARS-CoV-2 Omicron variant infections and Fever outpatients, so that prevention and control measures can be taken in time. Patients and Methods: This study retrospectively analyzed 65 patients with SARS-CoV-2 Omicron variant. Sixty-nine age- and sex-matched Fever outpatients were enrolled during the same period of time. We also reanalyzed data from 81 SARS-CoV-2 Wild-Type-infected patients. We compared the clinical characteristics and initial indexes of routine tests among the 3 groups. Results: A total of 93.8% of the patients with Omicron infections had clinical symptoms, and the major symptoms were cough, fever and pharyngalgia. Pharyngalgia was a specific manifestation in Omicron group compared to Wild-Type group. The white blood cell of the Omicron group was lower than that of the Fever group [5.0 (3.6-6.1) vs 10.1 (7.6-12.9) ×109/L, P < 0.001]. The neutrophil count in Omicron group was lower than that in Fever and Wild-Type group [2.6 (1.8-3.9) vs 8.1 (5.9-10.9), P < 0.001; 2.6 (1.8-3.9) vs 3.4 (2.5-4.7) ×109/L, P < 0.001]. The white blood cell and neutrophil counts were lower in Omicron group than in the Fever group. The top 5 major symptoms were fever, cough, pharyngalgia, headache and expectoration. Conclusion: There are differences between the patients with Omicron infections and Fever outpatients, both in clinical manifestations and initial routine hematology indicators. We hope to provide some clues for early identification combined with a history of living in the epidemic area.

Clinical practice of rapid antigen tests for SARS-CoV-2 Omicron variant: A single-center study in China.

Responding to the fast-spreading SARS-CoV-2 Omicron variant, to improve screening efficiency, rapid antigen tests (RATs) were first added as a supplementary detection method in China in mid-March, 2022. What and how big a role RATs should play need to be supported by clinical data. Here, RAT performance and relevant factors in comparison with nucleic acid amplification tests (NAATs) were assessed in Omicron-infected inpatients. From the NAAT results, nasopharyngeal swabs (NPs) performed better than oropharyngeal swabs (OPs). RATs tested on NAAT positive NPs performed better than those with OP-positive samples. The RAT positivity rate was strongly associated with high levels of N and OFR1ab genes, especially in NPs where patients also had significantly longer hospital stays and shorter days from symptom onset to RAT testing. Self-performed RATs had a detection accuracy that was comparable to professionally performed RATs when the subjects were well guided. The antigen negative rate of the studied patients was 100% at discharge. These findings suggest that, in addition to a supplementary detection role, RATs can be an important strategy for evaluating the disease progression of Omicron-infected inpatients. This study provides important clinical data to support better rules regarding RATs under China's COVID-19 prevention and control policy.

Longitudinal observation of viral load in patients infected with Omicron variant and its relationship with clinical symptoms.

Objective: In 2022, a new coronavirus variant (Omicron) infection epidemic broke out in Shanghai, China. However, it is unclear whether the duration of this omicron variant is different from that of the prototype strain. Methods: We retrospectively analyzed 157 cases of Omicron variant infection in Taizhou Public Health Center from March 29, 2022, to April 18, 2022, and observed the dynamics of nucleic acid Ct values during the admission and discharge of patients. Clinical and laboratory indicators of these patients were also obtained. Results: Compared to the prototype strain, the Omicron variant showed a broad population susceptibility in infected individuals (regardless of age and presence of underlying disease) and had slight damage to the immune system and renal function; the viral loads peaked was 2-3 days from disease onset; the median duration of omicron variant was 15-18 days; the nucleic acid Ct value of nasopharyngeal swabs of infected patients is lower than that of throat swabs, and the Ct value of oropharyngeal swabs is unstable during the recovery period. Conclusion: Therefore, we found that the time to peak viral load of this Omicron variant was 2-3 days after the onset of the disease, and the duration was 15-18 days; symptomatic patients had higher viral load and longer hospitalization time. This finding will provide a basis for understanding omicron variants and formulating the national prevention and control strategy.

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.

A novel compound heterozygous mutations in protein C gene causing neonatal purpura fulminans.

: Neonatal purpura fulminans is a rare, life-threatening disease caused by severe congenital deficiency of protein C (PC) because of homozygous or compound heterozygous mutations in the PROC gene. Mutation analysis plays a critical role in diagnosing the disorder and offering prenatal guidance. In this study, we identified a genetic defect in the PROC gene leading to neonatal purpura fulminans. The propositus had very low PC activity (4%) and PC antigen activity (5%). DNA screening of the whole PROC gene revealed two compound heterozygous mutations in exon8 (c.795_796insA) and exon9 (c.1206_1207insG). These two variations led to the compound heterozygous mutations of Gly266Argfs4 and Pro405Alafs20, which were inherited from the patient's father and mother, respectively. His older sister is heterozygous for the Gly266Argfs4 mutation. The inserted nucleotides alter the protein by introducing a stop codon at the subsequent AA position, resulting in a truncated protein compared with the wild type. We deduced that the compound heterozygous mutations are responsible for the PC deficiency, the Gly266Argfs4 mutation has been confirmed to be a novel mutation.