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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330227

ABSTRACT

Cytokine storm is a primary cause for multiple organ damage and death after severe infections, such as SARS-CoV-2. However, current single cytokine-targeted strategies display limited therapeutic efficacy. Here, we report that peritoneal M2 macrophages-derived extracellular vesicles (M2-EVs) are multi-target nanotherapeutics to resolve cytokine storm. In detail, primary peritoneal M2 macrophages exhibited superior anti-inflammatory potential than immobilized cell lines. Systemically administrated M2-EVs entered major organs and were taken up by phagocytes (e.g., macrophages). M2-EVs treatment effectively reduced excessive cytokine (e.g., TNF-α and IL-6) release in vitro and in vivo, thereby attenuated oxidative stress and multiple organ (lung, liver, spleen and kidney) damage in endotoxin-induced cytokine storm. Moreover, M2-EVs simultaneously inhibited multiple key proinflammatory pathways (e.g., NF-κB, JAK-STAT and p38 MAPK) by regulating complex miRNA-gene and gene-gene networks, and this effect was collectively mediated by many functional cargos (miRNAs and proteins) in EVs. In addition to the direct anti-inflammatory role, human peritoneal M2-EVs expressed angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2 spike protein, and thus could serve as nanodecoys to prevent SARS-CoV-2 pseudovirus infection in vitro. As cell-derived nanomaterials, the therapeutic index of M2-EVs can be further improved by genetic/chemical modification or loading with specific drugs. This study highlights that peritoneal M2-EVs are promising multifunctional nanotherapeutics to attenuate infectious diseases-related cytokine storm.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310373

ABSTRACT

Background: hepatic hemangioma is the most common benign tumor of the liver. However, patients with large hemangiomas that cause compression symptoms or that are at risk of rupture may need further intervention. It is necessary to explore additional minimally invasive and personalized treatment options. Case presentation : A 47-year-old female was diagnosed with right hepatic hemangioma for more than 10 years. Abdominal contrast-enhanced CT and CEUS revealed that there was a large hemangioma in the right liver, with a size of approximately 95x97x117 mm. Due to the patient's refusal of surgical treatment, hepatic artery embolization was performed in the first stage, then after 25 days of liver protection treatment, the liver function indexes decreased to normal levels. Then, B-ultrasound-guided microwave ablation of the giant hepatic hemangioma was performed. Ten days after the surgery, hepatobiliary ultrasonography showed that the hemangioma of the right liver was smaller than the previous size (the volume was reduced by approximately 30%). Then the patient was discharged from the hospital, and CT suggested that the hepatic hemangioma is significantly smaller two months after discharge. Because of COVID-19, the patient's CT examination was delayed. Conclusions: TAE combined with microwave ablation is a safe and effective minimally invasive treatment for hepatic hemangioma.

3.
Preprint in English | bioRxiv | ID: ppbiorxiv-438849

ABSTRACT

The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has sparked concern over the continued effectiveness of existing therapeutic antibodies and vaccines. Hence, together with increased genomic surveillance, methods to rapidly develop and assess effective interventions are critically needed. Here we report the discovery of SARS-CoV-2 neutralizing antibodies isolated from COVID-19 patients using a high-throughput platform. Antibodies were identified from unpaired donor B-cell and serum repertoires using yeast surface display, proteomics, and public light chain screening. Cryo-EM and functional characterization of the antibodies identified N3-1, an antibody that binds avidly (Kd,app = 68 pM) to the receptor binding domain (RBD) of the spike protein and robustly neutralizes the virus in vitro. This antibody likely binds all three RBDs of the trimeric spike protein with a single IgG. Importantly, N3-1 equivalently binds spike proteins from emerging SARS-CoV-2 variants of concern, neutralizes UK variant B.1.1.7, and binds SARS-CoV spike with nanomolar affinity. Taken together, the strategies described herein will prove broadly applicable in interrogating adaptive immunity and developing rapid response biological countermeasures to emerging pathogens.

4.
Curr Med Res Opin ; 37(3): 385-391, 2021 03.
Article in English | MEDLINE | ID: covidwho-1066084

ABSTRACT

OBJECTIVE: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains pandemic with considerable morbidity and mortality around the world. The aim of this study was to identify the predictors for clinical deterioration in patients with COVID-19 who did not show clinical deterioration upon hospital admission. METHODS: Two hundred fifty-seven patients with confirmed COVID-19 pneumonia admitted to Guangzhou Eighth People's Hospital between 23 January and 21 March 2020 were retrospectively enrolled. Demographic data, symptoms, laboratory values, comorbidities and treatments were all collected. The study endpoint was clinical deterioration within 20 days from hospital admission. Univariate and multivariable logistic regression methods were used to explore the risk factors associated with clinical deterioration. RESULTS: A total of 49 (19%) patients showed clinical deterioration after admission. Compared with patients that did not experience clinical deterioration, clinically deteriorated patients had more dyspnea, cough and myalgia (65.3% versus 29.3%) symptoms and more had comorbidities (89.8% versus 36.1%). Clinical and laboratory characteristics at admission that were associated with clinical deterioration included senior age, diabetes, hypertension, myalgia, higher temperature, systolic blood pressure, C-reactive protein (CRP), procalcitonin, activated partial thromboplastin time, aspartate aminotransferase, alanine transaminase, direct bilirubin, plasma creatinine, lymphocytopenia, thrombocytopenia, decreased albumin and bicarbonate concentration. Medical history of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, calcium channel blockers and metformin were also risk factors. CONCLUSION: The four best predictors for clinical deterioration were CRP, procalcitonin, age and albumin. A "best" multivariable prediction model, resulting from using a variable selection procedure, included senior age, presentation with myalgia, and higher level of CRP and serum creatinine (bias-corrected c-statistic = 0.909). Sensitivity and specificity corresponding to a cut point of CRP ≥18.45 mg/L for predicting clinical deterioration were 85% and 74%, respectively.


Subject(s)
C-Reactive Protein/analysis , COVID-19 , Clinical Deterioration , Noncommunicable Diseases , Procalcitonin/analysis , Serum Albumin/analysis , Age Factors , COVID-19/blood , COVID-19/epidemiology , COVID-19/physiopathology , COVID-19/therapy , China/epidemiology , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Noncommunicable Diseases/epidemiology , Noncommunicable Diseases/therapy , Retrospective Studies , Risk Assessment/methods , Risk Factors , SARS-CoV-2/isolation & purification , Sensitivity and Specificity
5.
Preprint in English | medRxiv | ID: ppmedrxiv-20237917

ABSTRACT

Decontaminating N95 respirators for reuse could mitigate shortages during the COVID-19 pandemic. We tested a portable UV-C light-emitting diode disinfection chamber and found that decontamination efficacy depends on mask model, material and location on the mask. This emphasizes the need for caution when interpreting efficacy data of UV-C decontamination methods.

6.
Preprint in English | medRxiv | ID: ppmedrxiv-20038935

ABSTRACT

With the capability of inducing elevated expression of ACE2, the cellular receptor for SARS-CoV-2, angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (ARBs/ACEIs) treatment may have a controversial role in both facilitating virus infection and reducing pathogenic inflammation. We aimed to evaluate the correlation of ARBs/ACEIs usage with the pathogenesis of COVID-19 in a retrospective, single-center study. 126 COVID-19 patients with preexisting hypertension at Hubei Provincial Hospital of Traditional Chinese Medicine (HPHTCM) in Wuhan from January 5 to February 22, 2020 were retrospectively allocated to ARBs/ACEIs group (n=43) and non-ARBs/ACEIs group (n=83) according to their antihypertensive medication. 125 age- and sex-matched COVID-19 patients without hypertension were randomly selected as non-hypertension controls. In addition, the medication history of 1942 hypertension patients that were admitted to HPHTCM from November 1 to December 31, 2019 before COVID-19 outbreak were also reviewed for external comparison. Epidemiological, demographic, clinical and laboratory data were collected, analyzed and compared between these groups. The frequency of ARBs/ACEIs usage in hypertension patients with or without COVID-19 were comparable. Among COVID-19 patients with hypertension, those received either ARBs/ACEIs or non-ARBs/ACEIs had comparable blood pressure. However, ARBs/ACEIs group had significantly lower concentrations of CRP (p=0.049) and procalcitonin (PCT, p=0.008). Furthermore, much lower proportion of critical patients (9.3% vs 22.9%; p=0.061), and a lower death rate (4.7% vs 13.3%; p=0.216) were observed in ARBs/ACEIs group than non-ARBs/ACEIs group, although these differences failed to reach statistical significance. Our findings thus support the use of ARBs/ACEIs in COVID-19 patients with preexisting hypertension.

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