Coronavirus disease 2019 (COVID-19) is associated with immune dysregulation and cytokine storm. Exploring the immuneinflammatory characteristics of COVID-19 patients is essential to reveal pathogenesis and predict progression. In this study, COVID-19 patients showed decreased CD3 + , CD4 + , and CD8 + T cells but increased neutrophils in circulation, exhibiting upregulated neutrophil-to-lymphocyte and neutrophil-to-CD8 + T cell ratio. IL-6, TNF-a, IL-1b, IL-18, IL-12/IL-23p40, IL-10, Tim-3, IL-8, neutrophil extracellular trap-related proteinase 3, and S100A8/A9 were elevated, whereas IFN-g and C-type lectin domain family 9 member A (clec9A) were decreased in COVID-19 patients compared with healthy controls. When compared with influenza patients, the expressions of TNF-a, IL-18, IL-12/IL-23p40, IL-8, S100A8/A9 and Tim-3 were significantly increased in critical COVID-19 patients, and carcinoembryonic Ag, IL-8, and S100A8/A9 could serve as clinically available hematologic indexes for identifying COVID-19 from influenza. Moreover, IL-6, IL-8, IL-1b, TNF-a, proteinase 3, and S100A8/A9 were increased in bronchoalveolar lavage fluid of severe/critical patients compared with moderate patients, despite decreased CD4 + T cells, CD8 + T cells, B cells, and NK cells. Interestingly, bronchoalveolar IL-6, carcinoembryonic Ag, IL-8, S100A8/A9, and proteinase 3 were found to be predictive of COVID-19 severity and may serve as potential biomarkers for predicting COVID-19 progression and potential targets in therapeutic intervention of COVID-19.

This study aimed to evaluate the efficacy of Chinese herbal medicine (CHM) in patients with severe/ critical coronavirus disease 2019 (COVID-19). In this retrospective study, data were collected from 662 patients with severe/critical COVID-19 who were admitted to a designated hospital to treat patients with severe COVID-19 in Wuhan before March 20, 2020. All patients were divided into an exposed group (CHM users) and a control group (non-users). After propensity score matching in a 1:1 ratio, 156 CHM users were matched by propensity score to 156 non-users. No significant differences in seven baseline clinical variables were found between the two groups of patients. All-cause mortality was reported in 13 CHM users who died and 36 non-users who died. After multivariate adjustment, the mortality risk of CHM users was reduced by 82.2% (odds ratio 0.178, 95% CI 0.076-0.418; P < 0.001) compared with the non-users. Secondly, age (odds ratio 1.053, 95% CI 1.023-1.084; P < 0.001) and the proportion of severe/critical patients (odds ratio 0.063, 95% CI 0.028-0.143; P < 0.001) were the risk factors of mortality. These results show that the use of CHM may reduce the mortality of patients with severe/ critical COVID-19.

Increased heme levels, anemia, and desaturation occur during infection. We aimed to compare the levels of heme, heme oxygenase-1 (HO-1), ferritin, and bilirubin in coronavirus disease 2019 (COVID-19) patients at different saturation levels. Heme and HO-1 enzyme levels significantly increased in the low SpO 2 group, but further studies are required.

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BACKGROUND The global outbreak of human severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection represents an urgent need for readily available, accurate and rapid diagnostic tests. Nucleic acid testing of respiratory tract specimens for SARS-CoV-2 is the current gold standard for diagnosis of coronavirus disease 2019 (COVID-19). However, the diagnostic accuracy of reverse transcription polymerase chain reaction (RT-PCR) tests for detecting SARS-CoV-2 nucleic acid may be lower than optimal. The detection of SARS-CoV-2-specific antibodies should be used as a serological non-invasive tool for the diagnosis and management of SARS-CoV-2 infection. AIM To investigate the diagnostic value of SARS-CoV-2 IgM/IgG and nucleic acid detection in COVID-19. METHODS We retrospectively analyzed 652 suspected COVID-19 patients, and 206 non-COVID-19 patients in Wuhan Integrated TCM and Western Medicine Hospital. Data on SARS-CoV-2 nucleic acid tests and serum antibody tests were collected to investigate the diagnostic value of nucleic acid RT-PCR test kits and immunoglobulin (Ig)M/IgG antibody test kits. The χ 2 test was used to compare differences between categorical variables. A 95% confidence interval (CI) was provided by the Wilson score method. All analyses were performed with IBM SPSS Statistics version 22.0 (IBM Corp., Armonk, NY, United States). RESULTS Of the 652 suspected COVID-19 patients, 237 (36.3%) had positive nucleic acid tests, 311 (47.7%) were positive for IgM, and 592 (90.8%) were positive for IgG. There was a significant difference in the positive detection rate between the IgM and IgG test groups ( P < 0.001). Using the RT-PCR results as a reference, the specificity, sensitivity, and accuracy of IgM/IgG combined tests for SARS-CoV-2 infection were 98.5%, 95.8%, and 97.1%, respectively. Of the 415 suspected COVID-19 patients with negative nucleic acid test results, 366 had positive IgM/IgG tests with a positive detection rate of 88.2%. CONCLUSION Our data indicate that serological IgM/IgG antibody combined test had high sensitivity and specificity for the diagnosis of SARS-CoV-2 infection, and can be used in combination with RT-PCR for the diagnosis of SARS-CoV-2 infection.

Most patients with metastatic hormone sensitive prostate cancer will progress to metastatic castration-resistant prostate cancer (mCRPC); Finding a highly effective, safe treatment with low recurrence rate has important clinical implications. Herein, we present a case of a 65-year-old man with castration-resistant prostate cancer treated by multi-protocol exploration. Magnetic resonance imaging (MRI) revealed prostate cancer invading the bladder, seminal vesicle glands, and peritoneum with pelvic lymph node metastasis. Transrectal B ultrasound puncture of prostate tissue was performed, and the pathological diagnosis was prostatic adenocarcinoma. CTC (Circulating tumor cell) gene test was performed in peripheral blood, and the result showed BRCA1 gene mutation. The patient died of tumor complications after trying docetaxel combined with cisplatin chemotherapy, PARP inhibitor (nilaparib), PD-1 inhibitor (tislelizumab) and other treatments. This patient showed that the selection of an individualized combination chemotherapy regimen based on genetic testing results benefited the patient’s tumor control. When choosing a treatment regimen, problems such as failure to respond to re-chemotherapy and resistance to nilaparib may lead to deterioration of the condition.

Objective: To evaluate the safety and efficacy of transurethral plasmakinetic enucleation of the prostate (PKERP) vs. transurethral resection of the prostate (TURP) in elderly patients aged ≥80 years with benign prostate hyperplasia.Materials and Methods: We conducted a retrospective analysis of the PKERP (n = 123) and TURP (n = 143) in patients aged ≥80 years at urology department of The Third Xiangya Hospital of Central South University from January 2016 to October 2019. Then the preoperative, intraoperative, and postoperative data of different indicators were compared between the two groups. The follow-up was done at 3 months, 1 year after surgical treatment.Results: No significant differences were observed between the two groups for the baseline characteristics, including age, prostate volume, prostate-specific antigen (PSA) level, concurrent disease, maximum urinary flow rate (MFR), international prostate symptoms score (IPSS), and quality of life (QoL) score. The operative time, hemoglobin decrease, and postoperative flushing time were significantly lower in the PKERP group compared with the TURP group. However, no significant differences were observed between both groups for postoperative hospital stay, incidence of transurethral resection syndrome (TURS), prostatic capsular perforation, and genuine urinary incontinence. The follow-up results showed that the MFR of the PKERP group was significantly higher than the TURP group at 1 year after surgery.Conclusion: Compared with TURP, PKERP is a safe and efficacious method for treating patients aged ≥80 years with benign prostate hyperplasia, and it may improve long-term urination symptoms.

Background Using a computational approach, NL-CVX1 was developed by Neoleukin Therapeutics, Inc. to create a de novo protein that both blocks SARS-CoV-2 infection and is highly resilient to viral escape. In this study we evaluated the efficacy of NL-CVX1 against variants of the original SARS-CoV-2 strain, including important viral variants of concern (VOC) such as B.1.1.7, B.1.351, and P.1. Methods The relative binding affinity of NL-CVX1 to the SARS-CoV-2 viral spike protein of VOC was measured using biolayer interferometry (Octet). A competitive ELISA measured the ability of NL-CVX1 to compete with hACE2 for binding to the receptor binding domain (RBD) of the SARS-CoV-2 S protein from the original strain and VOC. The activity of NL-CVX1 in preventing viral infection was assessed by evaluating the cytopathic effects (CPE) of SARS-CoV-2 in a transmembrane protease, serine 2-expressing Vero E6 cell line (Vero E6/TMPRSS2) and determining the viral load using quantitative real-time reverse transcriptase polymerase chain reaction in infected cells. A K18hACE2 mouse model of SARS CoV-2 infection was used to study the dose-response of NL-CVX1 anti-viral activity in vivo. Results NL-CVX1 binds the RBD of different VOC of SARS-CoV-2 at low nanomolar concentrations (Fig 1; Kd &lt; 1-~5 nM). When competing with hACE2, NL-CVX1 achieved 100% inhibition against hACE2 binding to the RBD of different VOC with IC50s values ranging from 0.7-53 nM (Fig 2). NL-CVX1 neutralized the B.1.1.7 variant as efficiently as the original strain in Vero E6/TMPRSS2 cells, with EC50 values of 16 nM and 101.2 nM, respectively (Fig 3). In mice, we found that a single intranasal dose of 100 µg NL-CVX1 prevented clinically significant SARS-CoV-2 infection and protected mice from succumbing to infection. Results from additional in vitro and in vivo experiments to be conducted this summer will be presented. Figure 1. NL-CVX1 binds the RBD from multiple strains of SARS-CoV-2 at low nanomolar concentrations. Figure 2. NL-CVX1 achieves 100% inhibition against all strains tested, including SARS-CoV-2 VOC. Figure 3. NL-CVX1 neutralizes the B.1.1.7 variant as efficiently as the original SARS-CoV-2 strain. Conclusion In vitro and in vivo data (Fig 4) demonstrate that NL-CVX1 is a promising drug candidate for the prevention and treatment of COVID-19. As a hACE2 mimetic, it is resilient to antibody escape mutations found in SARS-CoV-2 VOC. NL-CVX1 further demonstrates the power and utility of de novo protein design for developing proteins as human therapeutics. Figure 4. NL-CVX1 is effective in preventing clinically significant SARS-CoV-2 viral infection in a K18hACE2 mouse model. Disclosures Matthew Walker, PhD, Neoleukin Therapeutics, Inc. (Employee, Other Financial or Material Support, Ownership options and stock.) Laurie Tatalick, DVM, PhD, DACVP, Neoleukin Therapeutics, Inc. (Consultant, Other Financial or Material Support, Ownership options and stock.) Marianne Riley, BS, Neoleukin Therapeutics, Inc. (Employee, Other Financial or Material Support, Ownership options and stock.) Kevin Yu, BS, MS, Neoleukin Therapeutics, Inc. (Employee, Other Financial or Material Support, Ownership options and stock.) Luis M. Blancas-Mejia, PhD, Neoleukin Therapeutics, Inc. (Employee, Other Financial or Material Support, Ownership options and stock.) Daniel-Adriano Silva, PhD, Neoleukin Therapeutics, Inc. (Advisor or Review Panel member, Other Financial or Material Support, Ownership of Neoleukin options and stock) David Shoultz, PhD, MBA, Neoleukin Therapeutics, Inc. (Employee, Other Financial or Material Support, Ownership options and stock.) Goncalo Bernardes, PhD, Neoleukin Therapeutics, Inc. (Consultant, Advisor or Review Panel member, Shareholder) Hui-Ling Yen, PhD, Neoleukin Therapeutics, Inc. (Grant/Research Support)Saiba AG (Other Financial or Material Support, Received donation from Saiba AG)