Dimethyloxalylglycine Attenuates Steroid-Associated Endothelial Progenitor Cell Impairment and Osteonecrosis of the Femoral Head by Regulating the HIF-1α Signaling Pathway.

Endothelial impairment and dysfunction are closely related to the pathogenesis of steroid-associated osteonecrosis of the femoral head (SONFH). Recent studies have showed that hypoxia inducible factor-1α (HIF-1α) plays a crucial role in endothelial homeostasis maintenance. Dimethyloxalylglycine (DMOG) could suppress HIF-1 degradation and result in nucleus stabilization by repressing prolyl hydroxylase domain (PHD) enzymatic activity. Our results showed that methylprednisolone (MPS) remarkably undermined biological function of endothelial progenitor cells (EPC) by inhibiting colony formation, migration, angiogenesis, and stimulating senescence of EPCs, while DMOG treatment alleviated these effects by promoting HIF-1α signaling pathway, as evidenced by senescence-associated ß-galactosidase (SA-ß-Gal) staining, colony-forming unit, matrigel tube formation, and transwell assays. The levels of proteins related to angiogenesis were determined by ELISA and Western blotting. In addition, active HIF-1α bolstered the targeting and homing of endogenous EPCs to the injured endothelium in the femoral head. Histopathologically, our in vivo study showed that DMOG not only alleviated glucocorticoid-induced osteonecrosis but also promoted angiogenesis and osteogenesis in the femoral head as detected by microcomputed tomography (Micro-CT) analysis and histological staining of OCN, TRAP, and Factor Ⅷ. However, all of these effects were impaired by an HIF-1α inhibitor. These findings demonstrate that targeting HIF-1α in EPCs may constitute a novel therapeutic approach for the treatment of SONFH.

Sleep quality was associated with adverse reactions after coronavirus disease 2019 vaccination among healthcare workers: A longitudinal paired study.

Background: Many countries have currently relied on various types of vaccines for the public to control the coronavirus disease 2019 (COVID-19) pandemic. The adverse reactions (ARs) after vaccination may affect vaccination coverage and confidence. However, whether sleep quality was associated with ARs after vaccination remains unclear. Methods: We designed a longitudinal paired study within a hospital setting. We collected data about the side effects within 7 days after two doses of scheduled vaccination among healthcare workers (HCWs). All HCWs were asked to complete a sleep survey indexed by the Pittsburgh Sleep Quality Index (PSQI) before vaccination and after a 1-month follow-up. Then, we explored the relationship between sleep quality before or after vaccination and the occurrence of ARs. Results: A total of 345 HCWs were recruited to receive COVID-19 vaccination. The sleep quality became worse after vaccination. All local and systemic reactions were mild or moderate in severity (32.46%), and no serious adverse event was reported. Binary logistic regression showed participants with poor sleep quality (PSQI > 5) than good sleep quality (PSQI ≤ 5) before the two doses of vaccination, respectively, exhibited 1.515 and 1.107 times risk of ARs after each vaccination (both p < 0.001). Conclusion: There is an apparently complex bidirectional relationship between sleep quality and COVID-19 vaccination adverse effects. Poor sleep quality significantly increases the risk of mild ARs after vaccination, while vaccination may cause a temporary decline in sleep quality.

Pulmonary Rehabilitation in Patients with COVID-19-A Protocol for Systematic Review and Meta-Analysis.

INTRODUCTION: Pulmonary rehabilitation (PR) is a well-established treatment for patients with chronic lung disease; however, its role in patients with COVID-19 has not been systematically studied. We provide a protocol outlining the methods and analyses that will be used in the systematic review. METHODS: The methodology of this systematic review protocol has been filed in PROSPERO under the registration number CRD42022301418. Five electronic databases (PubMed, Web of Science, Cochrane Library, EBSCO, and CNKI databases) will be searched from 2019 to 28 July 2022, using pre-determined search terms. Eligibility criteria will be defined using a PICOS framework. Pulmonary function, exercise capacity, and health-related quality of life will be the primary outcomes. Quantitative findings will be narratively synthesized, whilst argument synthesis combined with refutational analysis will be employed to synthesize qualitative data. RESULTS: The results will be presented by both meta-analysis and qualitative analysis. CONCLUSION: This protocol describes what will be the first systematic review to conduct a worldwide assessment of the effect of PR in patients with COVID-19. Because this is a systematic review and meta-analysis, no ethical approval is needed. The systematic review and meta-analysis will be published in a peer-reviewed journal and disseminated both electronically and in print.

A feasibility study of Covid-19 detection using breath analysis by high-pressure photon ionization time-of-flight mass spectrometry.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a tremendous threat to global health. polymerase chain reaction (PCR) and antigen testing have played a prominent role in the detection of SARS-CoV-2-infected individuals and disease control. An efficient, reliable detection tool is still urgently needed to halt the global COVID-19 pandemic. Recently, the food and drug administration (FDA) emergency approved volatile organic component (VOC) as an alternative test for COVID-19 detection. In this case-control study, we prospectively and consecutively recruited 95 confirmed COVID-19 patients and 106 healthy controls in the designated hospital for treatment of COVID-19 patients in Shenzhen, China. Exhaled breath samples were collected and stored in customized bags and then detected by high-pressure photon ionization time-of-flight mass spectrometry for VOCs. Machine learning algorithms were employed for COVID-19 detection model construction. Participants were randomly assigned in a 5:2:3 ratio to the training, validation, and blinded test sets. The sensitivity (SEN), specificity (SPE), and other general metrics were employed for the VOCs based COVID-19 detection model performance evaluation. The VOCs based COVID-19 detection model achieved good performance, with a SEN of 92.2% (95% CI: 83.8%, 95.6%), a SPE of 86.1% (95% CI: 74.8%, 97.4%) on blinded test set. Five potential VOC ions related to COVID-19 infection were discovered, which are significantly different between COVID-19 infected patients and controls. This study evaluated a simple, fast, non-invasive VOCs-based COVID-19 detection method and demonstrated that it has good sensitivity and specificity in distinguishing COVID-19 infected patients from controls. It has great potential for fast and accurate COVID-19 detection.

Driving force of COVID-19 among people living with HIV in Wuhan, China.

BACKGROUND: Although people living with HIV (PLWH) were considered to be at increased risk of SARS-CoV-2 infection, the driving force among this group of individuals is still not clear. METHODS: We investigated 1,709 PLWH through a telephone interview and identified 11 COVID-19 patients in four districts of Wuhan, China. The demographic features and major clinical characteristics of these patients were retrieved from the information management systems for COVID-19 patients of the four districts' CDC. Statistical analysis was performed to find out the driving force of COVID-19 among PLWH. RESULTS: The prevalence of COVID-19 in PLWH is 0.6% (95% CI: 0.2% - 1.0%), which is comparable to the overall population prevalence in Wuhan city (0.6%). Nine out of the 11 COVID-19 patients had relatively high CD4+ T lymphocyte count (>200/µl) and undetectable HIV viral load (<20 copies/ml), and ten of them were on antiretroviral therapy. Older PLWH with low CD4 + count, got HIV infected through homosexual activity, and had been diagnosed with HIV for a long time, were more likely to develop COVID-19. CONCLUSIONS: COVID-19 related morbidity rates were comparable between PLWH and the general population. Older age with low CD4 count, an extended period of HIV diagnosis, and treatment-naivety were potential driving forces of COVID-19 prevalence among PLWH. Strategies for preventing SARS-CoV-2 infection among PLWH with weak immune responses are required.

Development of septic shock and prognostic assessment in critically ill patients with coronavirus disease outside Wuhan, China.

BACKGROUND: The study aims to illustrate the clinical characteristics and development of septic shock in intensive care unit (ICU) patients confirmed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and to perform a comprehensive analysis of the association between septic shock and clinical outcomes in critically ill patients with coronavirus disease (COVID-19). METHODS: Patients confirmed with SARS-CoV-2 infection, who were admitted to the ICU of the Third People's Hospital of Shenzhen from January 1 to February 7, 2020, were enrolled. Clinical characteristics and outcomes were compared between patients with and without septic shock. RESULTS: In this study, 35 critically ill patients with COVID-19 were included. Among them, the median age was 64 years (interquartile range [IQR] 59-67 years), and 10 (28.4%) patients were female. The median ICU length of stay was 16 days (IQR 8-23 days). Three (8.6%) patients died during hospitalization. Nine (25.7%) patients developed septic shock in the ICU, and these patients had a significantly higher incidence of organ dysfunction and a worse prognosis than patients without septic shock. CONCLUSIONS: Septic shock is associated with a poor outcome in critically ill COVID-19 patients and is one of the hallmarks of the severity of patients receiving ICU care. A dysregulated immune response, uncontrolled inflammation, and coagulation disorders are strongly associated with the development and progression of COVID-19-related septic shock.

Severe COVID-19-associated sepsis is different from classical sepsis induced by pulmonary infection with carbapenem-resistant klebsiella pneumonia (CrKP).

PURPOSE: COVID-19 is also referred to as a typical viral septic pulmonary infection by 2019-nCoV. However, little is known regarding its characteristics in terms of systemic inflammation and organ injury, especially compared with classical bacterial sepsis. This article aims to investigate the clinical characteristics and prognosis between COVID-19-associated sepsis and classic bacterial-induced sepsis. METHODS: In this retrospective cohort study, septic patients with COVID-19 in the intensive care unit (ICU) of a government-designed therapy center in Shenzhen, China between January 14, 2020 and March 10, 2020, and septic patients induced by carbapenem-resistant klebsiella pneumonia (CrKP) admitted to the ICU of the Second People's Hospital of Shenzhen, China between January 1, 2014 and October 30, 2019 were enrolled. Demographic and clinical parameters including comorbidities, critical illness scores, treatment, and laboratory data, as well as prognosis were compared between the two groups. Risk factors for mortality and survival rate were analyzed using multivariable logistic regression and survival curve, respectively. RESULTS: A total of 107 patients with COVID-19 and 63 patients with CrKP were enrolled. A direct comparison between the two groups demonstrated more serious degrees of primary lung injury following 2019-nCoV infection (indicated by lower PaO2/FiO2), but milder systemic inflammatory response, lower sequential organ failure assessment score and better functions of the organs like heart, liver, kidney, coagulation, and circulation. However, the acquired immunosuppression presented in COVID-19 patients was more severe, which presented as lower lymphocyte counts (0.8×109/L vs. 0.9×109/L). Moreover, the proportion of COVID-19 patients treated with corticosteroid therapy and extracorporeal membrane oxygenation was larger compared with CrKP patients (78.5% vs. 38.1% and 6.5% vs. 0, respectively) who required less invasive mechanical ventilation (31.6% vs. 54.0%). The incidence of hospitalized mortality and length of ICU stay and total hospital stay were also lower or shorter in viral sepsis (12.1% vs. 39.7%, 6.5 days vs. 23.0 days and 21.0 days vs. 33.0 days, respectively) (all p < 0.001). Similar results were obtained after being adjusted by age, gender, comorbidity and PaO2/FiO2. Lymphocytopenia and high acute physiology and chronic health evaluation II scores were common risk factors for in-hospital death. While the death cases of COVID-19 sepsis mostly occurred at the later stages of patients' hospital stay. CONCLUSION: Critical COVID-19 shares clinical characteristics with classical bacterial sepsis, but the degree of systemic inflammatory response, secondary organ damage and mortality rate are less severe. However, following 2019-nCoV infection, the level of immunosuppression may be increased and thus induce in more death at the later stage of patients' hospitalstay.

Mechanism of Microbial Metabolite Leupeptin in the Treatment of COVID-19 by Traditional Chinese Medicine Herbs.

Coronavirus disease 2019 (COVID-19) has caused huge deaths and economic losses worldwide in the current pandemic. The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is thought to be an ideal drug target for treating COVID-19. Leupeptin, a broad-spectrum covalent inhibitor of serine, cysteine, and threonine proteases, showed inhibitory activity against Mpro, with a 50% inhibitory concentration (IC50) value of 127.2 µM in vitro in our study here. In addition, leupeptin can also inhibit SARS-CoV-2 in Vero cells, with 50% effective concentration (EC50) values of 42.34 µM. More importantly, various strains of streptomyces that have a broad symbiotic relationship with medicinal plants can produce leupeptin and leupeptin analogs to regulate autogenous proteases. Fingerprinting and structure elucidation using high-performance liquid chromatography (HPLC) and high-resolution mass spectrometry (HRMS), respectively, further proved that the Qing-Fei-Pai-Du (QFPD) decoction, a traditional Chinese medicine (TCM) formula for the effective treatment of COVID-19 during the period of the Wuhan outbreak, contains leupeptin. All these results indicate that leupeptin at least contributes to the antiviral activity of the QFPD decoction against SARS-CoV-2. This also reminds us to pay attention to the microbiomes in TCM herbs as streptomyces in the soil might produce leupeptin that will later infiltrate the medicinal plant. We propose that plants, microbiome, and microbial metabolites form an ecosystem for the effective components of TCM herbs. IMPORTANCE A TCM formula has played an important role in the treatment of COVID-19 in China. However, the mechanism of TCM action is still unclear. In this study, we identified leupeptin, a metabolite produced by plant-symbiotic actinomyces (PSA), which showed antiviral activity in both cell culture and enzyme assays. Moreover, leupeptin found in the QFPD decoction was confirmed by both HPLC fingerprinting and HRMS. These results suggest that leupeptin likely contributes to the antiviral activity of the QFPD decoction against SARS-CoV-2. This result gives us important insight into further studies of the PSA metabolite and medicinal plant ecosystem for future TCM modernization research.

COVID-19 associated anxiety enhances tinnitus

To investigate if the anxiety associated with coronavirus disease 2019 (COVID-19) is a promoting factor to tinnitus. A retrospective research design collected from 188 tinnitus patients, was used to compare the clinical characteristics of tinnitus between the patients in 2020 under pandemic pressure and those from the matching period in 2019. While anxiety was quantified using the Zung's Self-rating Anxiety Scale (SAS), tinnitus severity was evaluated using the Tinnitus Handicap Inventory (THI) questionnaire and the test of tinnitus loudness (TL). The assessments were repeated after the sound therapy plus educational counselling (STEC) for 38 patients in 2020 and 58 patients in 2019 and compared with EC alone therapy for 42 patients in 2020 and 17 patients in 2019. A large increase in anxiety was evident in 2020 in both case rate and SAS. The treatment of both methods was less effective in 2020. SAS, THI and TL were all deteriorated after the EC alone treatment in 2020, while an improvement was seen in 2019. This suggests that EC alone could not counteract the stress by COVID-19 at all, and the stress, if not managed well, can significantly increase the severity of tinnitus and associated anxiety. By using the EC subgroup in virtual control, we conclude that anxiety can serve as a promoting factor to tinnitus. We believe that this is the first study report that confirm the causative/promotive role of anxiety on tinnitus during COVID-19 pandemic.

Persistent lymphopenia after diagnosis of COVID-19 predicts acute respiratory distress syndrome: A retrospective cohort study

Background: Lymphopenia is a marker of immunosuppression after severe coronavirus disease-2019 (COVID-19) which is characterized by acute respiratory distress syndrome (ARDS). This study aimed to evaluate the relationships between persistent lymphopenia and ARDS. Methods: A retrospective cohort study of 125 patients with COVID-19 admitted to government-designated treatment center between 14 January 2020, and 20 March 2020 was conducted. We recorded all complete blood cell counts during the day 0th, 3rd, and 7th following the diagnosis of COVID-19. Patients were grouped based on the depression of the lymphocyte cell count, their return, or their failure to normal. The primary outcome was the occurrence of ARDS, and secondary outcomes included developing vital organ dysfunction and hospital lengths of stay. Results: 17.6% (22/125) patients developed ARDS. The lymphocyte counts with ARDS and non-ARDS were 0.94 × 109/L, 1.20 × 109/L at admission, respectively (p = 0.02). On the 3rd and 7th day, the median of lymphocyte count in ARDS was significantly lower than that of non-ARDS. Multivariable logistic regression, which was adjusting for potentially confounding factors (including age, comorbidities, and APACHE II score), showed that persistent lymphopenia within the 7th day was independently associated with ARDS (OR, 3.94 [95% CI, 1.26–12.33, p = 0.018). Further, patients with persistent lymphopenia had longer hospital lengths of stay (p < 0.001). Conclusion: The results showed persistent lymphopenia predicted ARDS after COVID-19. Further studies are needed to investigate whether immunostimulation of lymphocytes within 1 week can reduce ARDS occurrence in patients with COVID-19. [ABSTRACT FROM AUTHOR] Copyright of European Journal of Inflammation (Sage Publications, Ltd.) is the property of Sage Publications, Ltd. 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 abstract 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 abstract. (Copyright applies to all Abstracts.)

Clinical diagnosis of severe COVID-19: A derivation and validation of a prediction rule.

BACKGROUND: The widespread coronavirus disease 2019 (COVID-19) has led to high morbidity and mortality. Therefore, early risk identification of critically ill patients remains crucial. AIM: To develop predictive rules at the time of admission to identify COVID-19 patients who might require intensive care unit (ICU) care. METHODS: This retrospective study included a total of 361 patients with confirmed COVID-19 by reverse transcription-polymerase chain reaction between January 19, 2020, and March 14, 2020 in Shenzhen Third People's Hospital. Multivariate logistic regression was applied to develop the predictive model. The performance of the predictive model was externally validated and evaluated based on a dataset involving 126 patients from the Wuhan Asia General Hospital between December 2019 and March 2020, by area under the receiver operating curve (AUROC), goodness-of-fit and the performance matrix including the sensitivity, specificity, and precision. A nomogram was also used to visualize the model. RESULTS: Among the patients in the derivation and validation datasets, 38 and 9 participants (10.5% and 2.54%, respectively) developed severe COVID-19, respectively. In univariate analysis, 21 parameters such as age, sex (male), smoker, body mass index (BMI), time from onset to admission (> 5 d), asthenia, dry cough, expectoration, shortness of breath, asthenia, and Rox index < 18 (pulse oxygen saturation, SpO2)/(FiO2 × respiratory rate, RR) showed positive correlations with severe COVID-19. In multivariate logistic regression analysis, only six parameters including BMI [odds ratio (OR) 3.939; 95% confidence interval (CI): 1.409-11.015; P = 0.009], time from onset to admission (≥ 5 d) (OR 7.107; 95%CI: 1.449-34.849; P = 0.016), fever (OR 6.794; 95%CI: 1.401-32.951; P = 0.017), Charlson index (OR 2.917; 95%CI: 1.279-6.654; P = 0.011), PaO2/FiO2 ratio (OR 17.570; 95%CI: 1.117-276.383; P = 0.041), and neutrophil/lymphocyte ratio (OR 3.574; 95%CI: 1.048-12.191; P = 0.042) were found to be independent predictors of COVID-19. These factors were found to be significant risk factors for severe patients confirmed with COVID-19. The AUROC was 0.941 (95%CI: 0.901-0.981) and 0.936 (95%CI: 0.886-0.987) in both datasets. The calibration properties were good. CONCLUSION: The proposed predictive model had great potential in severity prediction of COVID-19 in the ICU. It assisted the ICU clinicians in making timely decisions for the target population.

Thymosin α1 therapy in critically ill patients with COVID-19: A multicenter retrospective cohort study.

BACKGROUND: COVID-19 characterized by refractory hypoxemia increases patient mortality because of immunosuppression effects. This study aimed to evaluate the efficacy of immunomodulatory with thymosin α1 for critical COVID-19 patients. METHODS: This multicenter retrospective cohort study was performed in 8 government-designated treatment centers for COVID-19 patients in China from Dec. 2019 to Mar. 2020. Thymosin α1 was administrated with 1.6 mg qd or q12 h for >5 days. The primary outcomes were the 28-day and 60-day mortality, the secondary outcomes were hospital length of stay and the total duration of the disease. Subgroup analysis was carried out according to clinical classification. RESULTS: Of the 334 enrolled COVID-19 patients, 42 (12.6%) died within 28 days, and 55 (16.5%) died within 60 days of hospitalization. There was a significant difference in the 28-day mortality between the thymosin α1 and non-thymosin α1-treated groups in adjusted model (P = 0.016), without obvious differences in the 60-day mortality and survival time in the overall cohort (P > 0.05). In the subgroup analysis, it was found that thymosin α1 therapy significantly reduced 28-day mortality (Hazards Ratios HR, 0.11, 95% confidence interval CI 0.02-0.63, P=0.013) via improvement of Pa02/FiO2 (P = 0.036) and prolonged the hospital length of stay (P = 0.024) as well as the total duration of the disease (P=0.001) in the critical type patients, especially those aged over 64 years, with white blood cell >6.8×109/L, neutrophil >5.3×109/L, lymphocyte < 0.73 × 109/L, PaO2/FiO2 < 196, SOFA > 3, and acute physiology and chronic health evaluation (APACHE) II > 7. CONCLUSION: These results suggest that treatment with thymosin α1 can markedly decrease 28-day mortality and attenuate acute lung injury in critical type COVID-19 patients.

The prognostic value of general laboratory testing in patients with COVID-19.

BACKGROUND: Lymphocyte count (LYM) of peripheral blood and some indices of general biochemical analysis had diagnostic and prognostic value for coronavirus disease 2019 (COVID-19), and the value of other remaining indices is rare. METHODS: A total of 94 patients with COVID-19 were enrolled at Renmin Hospital of Wuhan University. According to the severity of COVID-19, the patients were divided into three groups (moderate 49, severe 35, and critical 10), and 40 healthy cases were enrolled in the same period as healthy controls. The diagnostic and prognostic value of indices in peripheral blood cell count and general biochemical analysis was analyzed. RESULTS: Compared with healthy cases, the value differences in peripheral blood analysis in patients with COVID-19 were statistically significant (p < 0.01), the differences in LYM, neutrophil count (Neu), platelet count (PLT), and white blood cell count (WBC) were statistically significant among different severity of COVID-19 (p < 0.05). Compared with healthy cases, the differences in general biochemical results in patients with COVID-19 were statistically significant (p < 0.01), the value differences in direct bilirubin (DBIL), low-density lipoprotein cholesterol (LDL-Ch), and nitrogen (urea) were statistically significant among different severity of COVID-19 (p < 0.05). Neutrophil/lymphocyte ratio (NLR) had higher sensitivity and specificity for COVID-19 diagnosis. CONCLUSIONS: Some indices of peripheral blood cell count and general biochemical analysis were valuable in discriminating COVID-19 and predicting severity and adverse outcome of patients with COVID-19. For clinician, it is better to use more economical and easy-to-get indices to diagnose and predict the prognosis of COVID-19.

Detectable Serum Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load (RNAemia) Is Closely Correlated With Drastically Elevated Interleukin 6 Level in Critically Ill Patients With Coronavirus Disease 2019.

BACKGROUND: Although the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in respiratory specimens has been widely used to diagnose coronavirus disease 2019 (COVID-19), it is undeniable that serum SARS-CoV-2 nucleic acid (RNAemia) could be detected in a fraction of COVID-19 patients. However, it is not clear whether testing for RNAemia is correlated with the occurrence of cytokine storms or with the specific class of patients. METHODS: This study enrolled 48 patients with COVID-19 admitted to the General Hospital of Central Theater Command, People's Liberation Army, a designated hospital in Wuhan, China. The patients were divided into 3 groups according to the Diagnosis and Treatment of New Coronavirus Pneumonia (sixth edition) guidelines issued by the National Health Commission of China. Clinical and laboratory data were collected, and the serum viral load and interleukin 6 (IL-6) level were determined. RESULTS: Analysis of clinical characteristics of 48 cases of COVID-19 showed that RNAemia was diagnosed only in the critically ill group and seemed to reflect the severity of the disease. Furthermore, the level of the inflammatory cytokine IL-6 in critically ill patients increased significantly, almost 10 times that in other patients. More importantly, the extremely high IL-6 level was closely correlated with the detection of RNAemia (R = 0.902). CONCLUSIONS: Detectable serum SARS-CoV-2 RNA (RNAemia) in patients with COVID-19 was associated with elevated IL-6 concentration and poor prognosis. Because elevated IL-6 may be part of a larger cytokine storm that could worsen outcome, IL-6 could be a potential therapeutic target for critically ill patients with an excessive inflammatory response.

The Clinical Features and Prognostic Assessment of SARS-CoV-2 Infection-Induced Sepsis Among COVID-19 Patients in Shenzhen, China.

Background: The outbreak of the novel coronavirus disease (COVID-19) that began in December 2019 has posed a great threat to human health and caused a significant loss of life. In Shenzhen, 465 patients were confirmed to have COVID-19 as of August 31, 2020. In the present study, we aimed to describe the clinical characteristics of COVID-19 patients in Shenzhen and identify risk factors for the development of viral sepsis. Methods: In this retrospective study, patients who were confirmed to have a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and were admitted to the Third People's Hospital of Shenzhen from January 11 to April 27, 2020 were included in the cohort. Clinical data were extracted and followed up to May 10, 2020, by using predesigned data collection forms. Results: A total of 422 hospitalized COVID-19 patients were enrolled in this study, including 97 (23%) patients with viral sepsis at hospital admission and 325 (77%) non-septic patients. Patients with sepsis were much older than those without sepsis (57 vs. 43 years, P < 0.001) and presented with more comorbidities. Septic patients showed multiple organ dysfunction and significant abnormalities in immune- and inflammation-related biomarkers, and had poorer outcomes when compared to those without sepsis. Increased levels of interleukin-6, blood urea nitrogen, and creatine kinase were associated with the development of SARS-CoV-2-induced sepsis, and an elevated production of interleukin-6 was found to be an independent risk factor for the progression to critical illness among septic COVID-19 patients. Conclusions: SARS-CoV-2 infection-induced sepsis is critically involved in the severity and prognosis of COVID-19 patients by characterizing both aberrant immune response and uncontrolled inflammation. The development of sepsis might contribute to multiple organ dysfunction and poor outcomes in COVID-19 patients during hospitalization.

Clinical characteristics and prognostic factors of COVID-19 patients progression to severe: a retrospective, observational study.

The outbreak of coronavirus disease 2019 (COVID-19) has become a world-wide emergency. The severity of COVID-19 is highly correlated with its mortality rate. We aimed to disclose the clinical characteristics and prognostic factors of COVID-19 patients who developed severe COVID-19. The study enrolled cases (no=1848) with mild or moderate type of COVID-19 in Fangcang shelter hospital of Jianghan. A total of 56 patients progressed from mild or moderate to severe. We used least absolute shrinkage and selection operator regression model to select prognostic factors for this model. The case-severity rate was 3.6% in the shelter hospital. They were all symptomatic at admission. Fever, cough, and fatigue were the most common symptoms. Hypertension, diabetes and coronary heart diseases were common co-morbidities. Predictors contained in the prediction nomogram included fever, distribution of peak temperature (>38°C), myalgia or arthralgia and distribution of C-reactive protein (≥10 mg per L). The distribution of peak temperature (>38°C) on set, myalgia or arthralgia and C-reactive protein (≥10 mg per L) were the prognostic factors to identify the progression of COVID-19 patients with mild or moderate type. Early attention to these risk factors will help alleviate the progress of the COVID-19.

Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease.

COVID-19 was declared a pandemic on March 11 by WHO, due to its great threat to global public health. The coronavirus main protease (Mpro, also called 3CLpro) is essential for processing and maturation of the viral polyprotein, therefore recognized as an attractive drug target. Here we show that a clinically approved anti-HCV drug, Boceprevir, and a pre-clinical inhibitor against feline infectious peritonitis (corona) virus (FIPV), GC376, both efficaciously inhibit SARS-CoV-2 in Vero cells by targeting Mpro. Moreover, combined application of GC376 with Remdesivir, a nucleotide analogue that inhibits viral RNA dependent RNA polymerase (RdRp), results in sterilizing additive effect. Further structural analysis reveals binding of both inhibitors to the catalytically active side of SARS-CoV-2 protease Mpro as main mechanism of inhibition. Our findings may provide critical information for the optimization and design of more potent inhibitors against the emerging SARS-CoV-2 virus.

Driving Force of Covid-19 Among People Living With HIV/AIDS in Wuhan, China.

Background: Even people living with HIV/AIDS (PLWHA) were considered to be at increased risk of SARS-CoV-2 infection, the driving force among this group of individuals is still not clear. Methods : We investigated 1,701 PLWHA through a telephone interview and found 11 COVID-19 patients in four districts of Wuhan, China. The demographic features and major clinical characteristics of these patients were retrieved from the information management systems for COVID-19 patients of four districts' CDC. Statistical analysis was performed to find out the driving force of COVID-19 among PLWHA. Results : The incidence proportion of COVID-19 in PLWHA is 0.6% (95% CI: 0.2% - 1.0%), which is comparable to the overall population incidence rate in Wuhan city (0.6%). Nine out of the 11 COVID-19/AIDS patients had relatively high CD4+ T lymphocyte count (>200/µl) and undetectable HIV viral load (＜20 copies/ml), and ten of them were on antiretroviral therapy. PLWHA who were old, had low CD4+ T lymphocyte count, infected HIV through homosexual activity, and had been diagnosed for HIV for a long time, were more likely to develop COVID-19. Conclusions: PLWHA has comparable COVID-19 morbidity rates as the general population, and older age, low CD4 count, long length since HIV diagnosis, and treatment-naive were potential driving forces of COVID-19 occurrence among PLWHA. Strategies in preventing SARS-CoV-2 infection among PLWHA with worse immune responses are needed. Article Summary Line: As COVID-19 continues to spread around the world, people living with HIV/AIDS (PLWHA) are also at risk of infection with SARS-CoV-2. We investigated the factors associated with SARS-CoV-2 infection among PLWHA in Wuhan, China.