ABSTRACT
Since the outbreak of COVID-19 in the world, it has spread rapidly all over the world. Rapid and effective detection methods have been a focus of research. The SARS-CoV-2 N protein (NP) detection methods currently in use focus on specific recognition of antibodies, but the reagents are expensive and difficult to be produced. Here, aptamer-functionalized nanopipettes utilize the unique ion current rectification (ICR) of nanopipette to achieve rapid and highly sensitive detection of trace NP, and can significantly reduce the cost of NP detection. In the presence of NP, the surface charge at the tip of the nanopipette changes, which affects ion transport and changes the degree of rectification. Quantitative detection of NP is achieved through quantitative analysis. Relying on the high sensitivity of nanopipettes to charge fluctuations, this sensor platform achieves excellent sensing performance. The sensor platform exhibited a dynamic working range from 102-106 pg/mL with a detection limit of 73.204 pg/mL, which showed great potential as a tool for rapidly detecting SARS-CoV-2. As parallel and serial testing are widely used in the clinic to avoid missed diagnosis or misdiagnosis, we hope this platform can play a role in controlling the spread and prevention of COVID-19.
ABSTRACT
Background: Coronary artery calcification (CAC) is an independent risk factor of major adverse cardiovascular events; however, the impact of CAC on in-hospital death and adverse clinical outcomes in patients with coronavirus disease 2019 (COVID-19) remains unclear. Objective: To explore the association between CAC and in-hospital mortality and adverse events in patients with COVID-19. Methods: This multicenter retrospective cohort study enrolled 2067 laboratory-confirmed COVID-19 patients with definitive clinical outcomes (death or discharge) admitted from 22 tertiary hospitals in China between January 3, 2020 and April 2, 2020. Demographic, clinical, laboratory results, chest CT findings, and CAC on admission were collected. The primary outcome was in-hospital death and the secondary outcome was composed of in-hospital death, admission to intensive care unit (ICU), and requiring mechanical ventilation. Multivariable Cox regression analysis and Kaplan-Meier plots were used to explore the association between CAC and in-hospital death and adverse clinical outcomes. Results: The mean age was 50 years (SD,16) and 1097 (53.1%) were male. A total of 177 patients showed high CAC level, and compared with patients with low CAC, these patients were older (mean age: 49 vs. 69 years, P < 0.001) and more likely to be male (52.0% vs. 65.0%, P = 0.001). Comorbidities, including cardiovascular disease (CVD) ([33.3%, 59/177] vs. [4.7%, 89/1890], P < 0.001), presented more often among patients with high CAC, compared with patients with low CAC. As for laboratory results, patients with high CAC had higher rates of increased D-dimer, LDH, as well as CK-MB (all P < 0.05). The mean CT severity score in high CAC group was also higher than low CAC group (12.6 vs. 11.1, P = 0.005). In multivariable Cox regression model, patients with high CAC were at a higher risk of in-hospital death (hazard ratio [HR], 1.731; 95% CI 1.010-2.971, P = 0.046) and adverse clinical outcomes (HR, 1.611; 95% CL 1.087-2.387, P = 0.018). Conclusion: High CAC is a risk factor associated with in-hospital death and adverse clinical outcomes in patients with confirmed COVID-19, which highlights the importance of calcium load testing for hospitalized COVID-19 patients and calls for attention to patients with high CAC. Supplementary Information: The online version contains supplementary material available at 10.1007/s42058-021-00072-4.
ABSTRACT
BACKGROUND: Infections induced by influenza viruses, as well as coronavirus disease 19 (COVID-19) pandemic induced by severe acute respiratory coronavirus 2 (SARS-CoV-2) led to acute lung injury (ALI) and multi organ failure, during which traditional Chinese medicine (TCM) played an important role in treatment of the pandemic. The study aimed to investigate the effect of Indigo Naturalis on ALI induced by influenza A virus (IAV) in mice. METHOD: The anti-influenza and anti-inflammatory properties of aqueous extract of Indigo Naturalis (INAE) were evaluated in vitro. BALB/c mice inoculated intranasally with IAV (H1N1) were treated intragastrically with INAE (40, 80 and 160 mg/kg/day) 2 h later for 4 or 7 days. Animal lifespan and mortality were recorded. Expression of high mobility group box-1 protein (HMGB-1) and toll-like receptor 4 (TLR4) were evaluated through immunohistological staining. Inflammatory cytokines were also monitored by ELISA. RESULT: INAE inhibited virus replication on Madin-Darby canine kidney (MDCK) cells and decreased nitric oxide (NO) production from lipopolysaccharide (LPS)-stimulated peritoneal macrophages in vitro. The results showed that oral administration of 160 mg/kg of INAE significantly improved the lifespan (P < 0.01) and survival rate of IAV infected mice, improved lung injury and lowered viral replication in lung tissue (P < 0.01). Treatment with INAE (40, 80 and 160 mg/kg) significantly increased liver weight and liver index (P < 0.05), as well as weight and organ index of thymus and spleen at 160 mg/kg (P < 0.05). Serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels were reduced by INAE administration (P < 0.05). The expression of HMGB-1 and TLR4 in lung tissue were also suppressed. The increased production of myeloperoxidase (MPO) and methylene dioxyamphetamine (MDA) in lung tissue were inhibited by INAE treatment (P < 0.05). Treatment with INAE reduced the high levels of interferon α (IFN-α), interferon ß (IFN-ß), monocyte chemoattractant protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted factor (RANTES), interferon induced protein-10 (IP-10), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) (P < 0.05), with increased production of interferon γ (IFN-γ) and interleukin-10 (IL-10) (P < 0.05). CONCLUSION: The results showed that INAE alleviated IAV induced ALI in mice. The mechanisms of INAE were associated with its anti-influenza, anti-inflammatory and anti-oxidation properties. Indigo Naturalis might have clinical potential to treat ALI induced by IAV.
ABSTRACT
Background: The risk factors for adverse events of Coronavirus Disease-19 (COVID-19) have not been well described. We aimed to explore the predictive value of clinical, laboratory and CT imaging characteristics on admission for short-term outcomes of COVID-19 patients. Methods: This multicenter, retrospective, observation study enrolled 703 laboratory-confirmed COVID-19 patients admitted to 16 tertiary hospitals from 8 provinces in China between January 10, 2020 and March 13, 2020. Demographic, clinical, laboratory data, CT imaging findings on admission and clinical outcomes were collected and compared. The primary endpoint was in-hospital death, the secondary endpoints were composite clinical adverse outcomes including in-hospital death, admission to intensive care unit (ICU) and requiring invasive mechanical ventilation support (IMV). Multivariable Cox regression, Kaplan-Meier plots and log-rank test were used to explore risk factors related to in-hospital death and in-hospital adverse outcomes. Results: Of 703 patients, 55 (8%) developed adverse outcomes (including 33 deceased), 648 (92%) discharged without any adverse outcome. Multivariable regression analysis showed risk factors associated with in-hospital death included ≥ 2 comorbidities (hazard ratio [HR], 6.734; 95% CI; 3.239-14.003, p < 0.001), leukocytosis (HR, 9.639; 95% CI, 4.572-20.321, p < 0.001), lymphopenia (HR, 4.579; 95% CI, 1.334-15.715, p = 0.016) and CT severity score > 14 (HR, 2.915; 95% CI, 1.376-6.177, p = 0.005) on admission, while older age (HR, 2.231; 95% CI, 1.124-4.427, p = 0.022), ≥ 2 comorbidities (HR, 4.778; 95% CI; 2.451-9.315, p < 0.001), leukocytosis (HR, 6.349; 95% CI; 3.330-12.108, p < 0.001), lymphopenia (HR, 3.014; 95% CI; 1.356-6.697, p = 0.007) and CT severity score > 14 (HR, 1.946; 95% CI; 1.095-3.459, p = 0.023) were associated with increased odds of composite adverse outcomes. Conclusion: The risk factors of older age, multiple comorbidities, leukocytosis, lymphopenia and higher CT severity score could help clinicians identify patients with potential adverse events.