Thrombosis and bleeding in COVID-19 patients requiring extracorporeal membrane oxygenation: A systematic review and meta-analysis

Background Extracorporeal membrane oxygenation (ECMO) and COVID-19 significantly impact on coagulation system. A systematic review and meta-analysis were performed to explore the prevalence of thrombotic and bleeding events in COVID-19 patients supported with ECMO, summarize anticoagulation regimens, and guide future research. Methods Cochrane, EMBASE, Scopus, and PubMed were searched for studies examining thrombosis and bleeding in COVID-19 patients requiring ECMO. The primary outcomes were prevalence of different types of hemorrhage and thrombosis. The pooled estimated rates and relative risk (RR) were calculated to summarize the outcomes. Results Twenty-three peer-reviewed studies involving 6,878 subjects were included. For thrombotic events, the prevalence of circuit thrombosis was 21.5% (95% CI: 15.5%–27.6%;1,532 patients);ischemic stroke was 2.6% (95% CI: 1.5%–3.7%;5,926 patients);and pulmonary embolism (PE) was 11.8% (95% CI: 6.8%–16.8%;5,853 patients). For bleeding events, 37.4% of patients experienced major hemorrhage (95% CI: 28.1%–46.8%;1,558 patients) and 9.9% experienced intracranial hemorrhage (ICH) (95% CI: 7.8%–12.1%;6,348 patients). COVID-19 cases on ECMO complicated with more ICH than non-COVID-19 patients on respiratory ECMO [RR=2.23 (95% CI: 1.32–3.75)]. Anticoagulation strategies varied among centers. Conclusions Circuit thrombosis and major bleeding were the most common thrombotic and bleeding events. The incidence of ICH was significantly higher when ECMO was indicated for COVID-19 than for other respiratory diseases. There is no evidence for stronger anticoagulation practice and remains no consistent anticoagulation strategy to reduce the occurrence of thrombosis and bleeding under the double "hit” of COVID-19 and ECMO.

SARS-CoV-2 E protein-induced THP-1 pyroptosis is reversed by Ruscogenin.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an emerging pathogenic coronavirus, has been reported to cause excessive inflammation and dysfunction in multiple cells and organs, but the underlying mechanisms remain largely unknown. Here we showed exogenous addition of SARS-CoV-2 envelop protein (E protein) potently induced cell death in cultured cell lines, including THP-1 monocytic leukemia cells, endothelial cells, and bronchial epithelial cells, in a time- and concentration-dependent manner. SARS-CoV-2 E protein caused pyroptosis-like cell death in THP-1 and led to GSDMD cleavage. In addition, SARS-CoV-2 E protein upregulated the expression of multiple pro-inflammatory cytokines that may be attributed to activation of NF-κB, JNK and p38 signal pathways. Notably, we identified a natural compound, Ruscogenin, effectively reversed E protein-induced THP-1 death via inhibition of NLRP3 activation and GSDMD cleavage. In conclusion, these findings suggested that Ruscogenin may have beneficial effects on preventing SARS-CoV-2 E protein-induced cell death and might be a promising treatment for the complications of COVID-19.

Thrombosis and bleeding in patients with COVID-19 requiring extracorporeal membrane oxygenation: a systematic review and meta-analysis.

Background: Extracorporeal membrane oxygenation (ECMO) and COVID-19 significantly impact the coagulation system. A systematic review and meta-analysis were performed to explore the prevalence of thrombotic and bleeding events in patients with COVID-19 supported with ECMO, summarize anticoagulation regimens, and guide future research. Methods: Cochrane, EMBASE, Scopus, and PubMed were searched for studies examining thrombosis and bleeding in patients with COVID-19 requiring ECMO. The primary outcomes were the prevalences of different types of hemorrhage and thrombosis. The pooled estimated rates and relative risk (RR) were calculated to summarize the outcomes. Results: Twenty-three peer-reviewed studies involving 6878 subjects were included. For thrombotic events, the prevalence of circuit thrombosis was 21.5% (95% CI: 15.5%-27.6%; 1532 patients), that of ischemic stroke was 2.6% (95% CI: 1.5%-3.7%; 5926 patients), and that of pulmonary embolism (PE) was 11.8% (95% CI: 6.8%-16.8%; 5853 patients). For bleeding events, 37.4% of the patients experienced major hemorrhage (95% CI: 28.1%-46.8%; 1558 patients) and 9.9% experienced intracranial hemorrhage (ICH; 95% CI: 7.8%-12.1%; 6348 patients). COVID-19 cases on ECMO were complicated with more ICH than patients without COVID-19 on respiratory ECMO [RR = 2.23 (95% CI: 1.32-3.75)]. Anticoagulation strategies varied among centers. Conclusions: Circuit thrombosis and major bleeding were the most common thrombotic and bleeding events. The incidence of ICH was significantly higher when ECMO was indicated for COVID-19 than for other respiratory diseases. There is no evidence for stronger anticoagulation practice, and remains no consistent anticoagulation strategy to reduce the occurrence of thrombosis and bleeding under the double "hit" of COVID-19 and ECMO.

Neutrophil extracellular traps are increased after extracorporeal membrane oxygenation support initiation and present in thrombus: A preclinical study using sheep as an animal model.

BACKGROUND: The balance between thrombosis and hemostasis is a difficult issue during extracorporeal membrane oxygenation (ECMO) support. The pathogenesis leading to thrombotic complications during ECMO support is not well understood. Neutrophil extracellular traps (NETs) were reported to participate in thrombosis and have a key role in inflammation. This study aimed to explore the role of NETs in thrombosis during ECMO support and investigate NETs as a predictive biomarker for thrombotic complications during ECMO assistance. METHODS: Ten ovine models of ECMO support were established. Animals were then randomly divided into 2 groups (5 sheep/group): venoarterial (VA) ECMO group and venovenous (VV) ECMO group. The venous blood samples were collected at different time points. Markers of NETs were detected in plasma, neutrophils, and thrombi from the vessels and membrane. Moreover, circulating NETs levels in 8 adults treated in the intensive care unit (ICU) who received VA-ECMO and 8 healthy controls were detected; patient survival was also recorded. RESULTS: In vivo study showed that neutrophils and NETs markers (dsDNA and citH3) levels were significantly elevated 6 h after ECMO compared to baseline. Isolated neutrophils from fresh blood at 6 h could release more NETs. dsDNA and citH3 levels were significantly higher in the VA mode than in the VV mode. NETs were found in thrombi from the vessel and membrane. Clinical data further revealed that dsDNA, citH3, and nucleosomes were higher in patients who received ECMO than in healthy controls. CONCLUSIONS: These data suggest NETs might be associated with thrombus during ECMO support, especially in the VA mode. These findings provide new insight into preventing thrombotic complications by targeting NETs. Also, NETs may potentially become an early warning biomarker for thrombosis under ECMO assistance.

How Has the COVID-19 Pandemic Changed Urban Consumers' Ways of Buying Agricultural Products? Evidence from Shanghai, China.

The COVID-19 pandemic has had a huge impact on people's consumption behavior and habits. This paper takes Shanghai, China as a case study and uses a questionnaire survey of urban residents in all districts in Shanghai from April to May in 2022. Herein, we empirically analyze the factors affecting shopping modes for agricultural products, describe how things have changed compared to before the outbreak of the pandemic, and explore the underlying mechanism. This paper can provide a policy reference for how to ensure the safety of people's food supply in the context of the COVID-19 pandemic. The results show that urban residents pay more attention to the basic attributes of agricultural products such as the quantity guarantee and health safety, and will adjust their consumption modes for agricultural products according to the needs of families and management. Compared with shopping malls and supermarkets, the quantity and quality assurance of community groups and e-commerce platforms can better meet the consumption situation of agricultural products during the pandemic period. The moderating effect of consumer commodity preference in the positive influence of safety evaluation on the transformation of shopping mode is significant. In general, online e-commerce platforms and community group buying have played a significant role in ensuring the acquisition of supplies needed by people during the COVID-19 pandemic. However, it remains to be determined whether the changes in the shopping modes for agricultural products of urban consumers brought by the current COVID-19 pandemic are long term or solidified.

Isoquinolinium-based photosensitizers with aggregation-induced emission characteristics for highly efficient photodynamic combat of viruses

Because of the prevalence of COVID-19, people are becoming increasingly aware of the importance of disinfection, which necessitates the development of convenient and efficient methods for inactivating pathogens. In this work, we report the application of three isoquinolinium-based aggregation-induced-emission-active photosensitizers (PSs) for photodynamic inactivation (PDI) of viruses at a low light intensity of 9 mW cm(-2). These three PSs could highly efficiently sensitize the production of reactive oxygen species and are applied to PDI of viruses. Their inactivation effects on viruses are evaluated by checking the cytopathic effect through examining the morphology of their host cells, investigating their protein expression in host cells by Western blot, immunofluorescence imaging of the viral proteins in host cells, quantifying the viral RNA levels after infection, and viral titering-median tissue culture infectious dose (TCID50) assay. The experimental results obtained clearly demonstrate the excellent PDI effect of these three PSs on viruses. Besides, we also explore the feasibility of employing these PSs for PDI of viruses on simulated high-touch surfaces, such as stainless steel and glass slides, on which these PSs demonstrate an even better PDI effect on all the three tested viruses. The PDI method described in this work is expected to innovate the disinfection practice in public areas.

Role of COVID-19 Vaccines in SARS-CoV-2 Variants.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a threat to the health of the global population. As the result of a global effort in the determination of origin, structure, and pathogenesis of SARS-CoV-2 and its variants, particularly such the variant of concern as Delta Variant and Omicron Variant, the understanding of SARS-CoV-2 are deepening and the development of vaccines against SARS-CoV-2 are ongoing. Currently, AstraZeneca-Vaxzevria/SII-Covishield vaccine, Janssen-Ad26.COV2.S vaccine, Moderna-mRNA-1273 vaccine, Pfizer BioNTech-Comirnaty vaccine and Sinovac-CoronaVac vaccine have been listed as WHO Emergency Use Listing (EUL) Qualified Vaccines by WHO. Because of the antigen escape caused by the mutation in variants, the effectiveness of vaccines, which are currently the main means of prevention and treatment, has been affected by varying degrees. Herein, we review the current status of mutations of SARS-CoV-2 variants, the different approaches used in the development of COVID-19 vaccines, and COVID-19 vaccine effectiveness against SARS-CoV-2 variants.

Molecular Engineering of Laser-Induced Graphene for Potential-Driven Broad-Spectrum Antimicrobial and Antiviral Applications.

Worldwide, countless deaths have been caused by the coronavirus disease 2019. In addition to the virus variants, an increasing number of fatal fungal infections have been reported, which further exacerbates the scenario. Therefore, the development of porous surfaces with both antiviral and antimicrobial capacities is of urgent need. Here, a cost-effective, nontoxic, and metal-free strategy is reported for the surface engineering of laser-induced graphene (LIG). The authors covalently engineer the surface potential of the LIG from -14 to ≈+35 mV (LIG+ ), enabling both high-efficiency antimicrobial and antiviral performance under mild conditions. Specifically, several candidate microorganisms of different types, including Escherichia coli, Streptomyces tenebrarius, and Candida albicans, are almost completely inactivated after 10-min solar irradiation. LIG+ also exhibits a strong antiviral effect against human coronaviruses: 99% HCoV-OC43 and 100% HCoV-229E inactivation are achieved after 20-min treatment. Such enhancement may also be observed against other types of pathogens that are heat-sensitive and oppositely charged. Besides, the covalent modification strategy alleviates the leaching problem, and the low cytotoxicity of LIG+ makes it advantageous. This study highlights the synergy of surface potential and photothermal effect in the inactivation of pathogens and it provides a direction for designing porous materials for airborne disease removal and water disinfection.

Chinese expert consensus on diagnosis and treatment of coagulation dysfunction in COVID-19.

Since December 2019, a novel type of coronavirus disease (COVID-19) in Wuhan led to an outbreak throughout China and the rest of the world. To date, there have been more than 1,260,000 COVID-19 patients, with a mortality rate of approximately 5.44%. Studies have shown that coagulation dysfunction is a major cause of death in patients with severe COVID-19. Therefore, the People's Liberation Army Professional Committee of Critical Care Medicine and Chinese Society on Thrombosis and Hemostasis grouped experts from the frontline of the Wuhan epidemic to come together and develop an expert consensus on diagnosis and treatment of coagulation dysfunction associated with a severe COVID-19 infection. This consensus includes an overview of COVID-19-related coagulation dysfunction, tests for coagulation, anticoagulation therapy, replacement therapy, supportive therapy and prevention. The consensus produced 18 recommendations which are being used to guide clinical work.

Comparative Analysis of 95 Patients with Different Severity in the Early Outbreak of COVID-19 in Wuhan, China.

OBJECTIVE: To explore the clinical characteristics of patients with different severity in the early outbreak of COVID-19, hoping to provide reference for clinical diagnosis and treatment. METHODS: We retrospectively analyzed the clinical data of 95 COVID-19 patients in Wuhan Red Cross Hospital of China from January 17 to February 13, 2020. All patients were investigated with epidemiological questionnaires. Outcomes were followed up until April 1, 2020. RESULTS: There were 53 males and 42 females, aged 22-84 years (mean 57.3 years). Clinical classification included 54 cases of common type, 27 cases of severe type, and 14 cases of critical type. Six patients had been exposed to the local Huanan seafood market. There were 38 clusters of COVID-19, including 27 family clusters and 11 work unit clusters. Common symptoms included fever (86 (90.5%) of 95), cough (73 (76.8%)), and fatigue (50 (52.6%)). Laboratory findings showed that the most common abnormalities were lymphopenia (75 (78.9%)), elevated D-dimer (60 (63.2%)), and elevated C-reactive protein (56 (58.9%)) on admission. All patients had abnormal chest computed tomography, showing patchy shadows or ground-glass opacities. Severe and critical cases were older, more likely to have shortness of breath, more likely to have underlying comorbidities, and more likely to have abnormal laboratory findings than common cases. The prognosis of patients with different degrees of severity was significantly different. All common and severe patients (100%) were cured and discharged from the hospital, while 10 (71.4%) of 14 critical patients died. CONCLUSIONS: COVID-19 has fast transmission speed and high pathogenicity. We must assess the severity of the disease and take corresponding treatment measures as early as possible.