Coagulopathy in COVID-19 and anticoagulation clinical trials.

Severe acute respiratory disease coronavirus 2 (SARS-COV-2) first emerged in Wuhan, China, in December 2019 and has caused a global pandemic of a scale unprecedented in the modern era. People infected with SARS-CoV-2 can be asymptomatic, moderate symptomatic or develop severe COVID-19. Other than the typical acute respiratory distress syndrome (ARDS), patients with moderate or severe COVID-19 also develop a distinctive systemic coagulopathy, known as COVID-19-associated coagulopathy (CAC), which is different from sepsis-related forms of disseminated intravascular coagulation (DIC). Endotheliopathy or endotheliitis are other unique features of CAC. The endothelial cell perturbation can further increase the risk of thrombotic events in COVID-19 patients. In this review, we will summarize the current knowledge on COVID-19 coagulopathy and the possible mechanisms for the condition. We also discuss the results of clinical trials testing methods for mitigating thrombosis events in COVID-19 patients.

Macrophage ferroportin serves as a therapeutic target against bacteria-induced acute lung injury by promoting barrier restoration.

Acute respiratory distress syndrome (ARDS) is a common lung disorder that involves severe inflammatory damage in the pulmonary barrier, but the underlying mechanisms remain elusive. Here, we demonstrated that pulmonary macrophages originating from ARDS patients and mice caused by bacteria were characterized by increased expression of ferroportin (FPN). Specifically deleting FPN in myeloid cells conferred significant resistance to bacterial infection with improved survival by decreasing extracellular bacterial growth and preserving pulmonary barrier integrity in mice. Mechanistically, macrophage FPN deficiency not only limited the availability of iron to bacteria, but also promoted tissue restoration via growth factor amphiregulin, which is regulated by cellular iron-activated Yes-associated protein signaling. Furthermore, pharmacological treatment with C-Hep, the self-assembled N-terminally cholesterylated minihepcidin that functions in the degradation of macrophage FPN, protected against bacteria-induced lung injury. Therefore, therapeutic strategies targeting the hepcidin-FPN axis in macrophages may be promising for the clinical treatment of acute lung injury.

Traditional Chinese Medicine JingYinGuBiao Formula Therapy Improves the Negative Conversion Rate of SARS-CoV2 in Patients with Mild COVID-19.

Background: Traditional Chinese Medicine (TCM) JingYinGuBiao formula (JYGB) was recommended by the Expert consensus on Traditional Chinese Medicine diagnosis and treatment of COVID-19 infection in Shanghai. We evaluated the safety and efficacy of JYGB in treating mild COVID-19 patients. Methods: A prospective, double-blind, randomized, controlled trial was conducted (ClinicalTrial.gov registration number: ChiCTR2200058695). A total of 885 patients were randomized into the treatment group (administration of JYGB,n=508) or the control group (administration of TCM placebo, n=377) with 7-day treatment. The primary outcomes were the negative conversion rate and negative conversion time of SARS-CoV2 RNA. Secondary outcomes included the hospitalized days and symptom improvement. Results: A total of 490 and 368 patients in the treatment and control groups completed the study. The cumulative negative conversion rates at 2 days, 3 days, 4 days, and 6 days post randomization in the treatment group were all markedly higher than those in the control group (13.88% vs. 9.24%, P=0.04; 32.24% vs. 16.58%, P<0.001; 51.43% vs. 36.14%, P <0.001; 77.76% vs. 69.84%, P=0.008). Compared with the control group, after JYGB treatment, the median negative conversion time (4.0 [3.0-6.0] vs. 5.0 [4.0-7.0] days, P<0.001) and hospitalized days (6.0 [4.0-8.0] vs. 7.0 [5.0-9.0] days, P<0.001) were reduced. While the symptoms were improved, there were no significant differences in symptom disappearance rates between both groups. In addition, further sub-group analysis showed that for patients with interval time ≤4 days or patients≤ 60 years, the clinical effects of JYGB were more remarkable with an increase in cumulative negative conversion rates, a decrease in negative conversion time and hospitalized days. JYGB was well tolerated without any severe side effects. Conclusion: JYGB, a TCM prescription, improves the negative conversion rate of SARS-CoV2 in mild COVID-19 patients.

China–US Strategic Competition and the Descent of a Porous Curtain

Since the onset of the Coronavirus Disease 2019(COVID-19) global pandemic, Sino–US strategic rivalry has dramatically heightened to a pitch where there is a mounting discussion over whether or not China and the United States have embarked on a "new Cold War." There are three main views in this regard. The first is that China and the United States have indeed entered a new Cold War;the second is that China and the United States are heading for a new Cold War;and the third is that China and the United States will not descend into a new Cold War. Different views reflect different scholarly understandings of the essential properties of the Cold War concept. Fundamentally, the two core features of the Cold War were ideological confrontation and proxy war. Considering that current US–China strategic competition is in the technological rather than ideological domain, and that neither side has instigated any proxy war;however, the phrase "new Cold War" is inappropriate;that of "Porous Curtain" is more apt. The ever-narrowing power gap between China and the United States has undoubtedly prompted the US government's adoption of a policy of blockade and containment to curb China's rising power. However, the deep integration of the international system and historical inertia of US–China interaction preclude the US's complete isolation from China. This has resulted in bilateral relations of a more porous nature. Although the future may not be promising, competition does not necessarily lead to conflict. For this reason, managing the bilateral competitive relationship and striving towards coexistence under competition should be the key task of both countries. [ABSTRACT FROM AUTHOR] Copyright of Chinese Journal of International Politics is the property of Oxford University Press / USA 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.)

Hypertriglyceridemia during hospitalization independently associates with mortality in patients with COVID-19.

BACKGROUND: Alteration in blood triglyceride levels have been found in patients with coronavirus disease 2019 (COVID-19). However, the association between hypertriglyceridemia and mortality in COVID-19 patients is unknown. OBJECTIVE: To investigate the association between alteration in triglyceride level and mortality in hospitalized COVID-19 patients. METHODS: We conducted a retrospective study of 600 hospitalized patients with COVID-19 diagnosis (ICD10CM:U07.1) and/or SARS-CoV-2 positive testing results between March 1, 2020 and December 21, 2020 at a tertiary academic medical center in Milwaukee, Wisconsin. De-identified data, including demographics, medical history, and blood triglyceride levels were collected and analyzed. Of the 600 patients, 109 patients died. The triglyceride value on admission was considered the baseline and the peak was defined as the highest level reported during the entire period of hospitalization. Hypertriglyceridemia was defined as greater than 150 mg/dl. Logistic regression analyses were performed to evaluate the association between hypertriglyceridemia and mortality. RESULTS: There was no significant difference in baseline triglyceride levels between non-survivors (n = 109) and survivors (n = 491) [Median 127 vs. 113 mg/dl, p = 0.213]. However, the non-survivors had significantly higher peak triglyceride levels during hospitalization [Median 179 vs. 134 mg/dl, p < 0.001]. Importantly, hypertriglyceridemia independently associated with mortality [odds ratio=2.3 (95% CI: 1.4-3.7, p = 0.001)], after adjusting for age, gender, obesity, history of hypertension and diabetes, high CRP, high leukocyte count and glucocorticoid treatment in a multivariable logistic regression model. CONCLUSIONS: Hypertriglyceridemia during hospitalization is independently associated with 2.3 times higher mortality in COVID-19 patients. Prospective studies are needed to independently validate this retrospective analysis.

Rapid and ultrasensitive method for determination of aflatoxin M1 in milk

Aflatoxin M1 (AFM1) in milk is a problem of great concern. Current methods of detection require large instruments and need specific test sites. Therefore, it is necessary to establish a fast, convenient, and accurate detection method for AFM1. We established a system based on fluorescent microspheres containing a Eu³⁺ chelate named AFM1-POCT. These components comprised the AFM1-POCT kits. After refrigeration at 4 degrees C for 12 months, the intra and inter assay coefficients of variability (CVs) for the kits were 4% and 5%, respectively. AFM1-POCT compared well with ultra-high-performance liquid chromatography (UHPLC) determination in the range 0.0121-2 g/kg (paired samples test, P > 0.05). Aflatoxin B1 and G1 do not react with aflatoxin M1. By using the AFM1-POCT method, the detection time is shortened to 5 min, the accuracy is comparable to that of UHPLC, and convenience and range of application are improved.

[Clinical and laboratory characteristics of 215 cases of coronavirus disease 2019 with different prognosis].

OBJECTIVE: To analyze the clinical and laboratory characteristics of coronavirus disease 2019 (COVID-19) patients with different prognosis, and to provide evidence for the diagnosis and treatment of COVID-19. METHODS: The clinical and laboratory characteristics of 215 cases of confirmed COVID-19 patients admitted in the First People's Hospital of Tianmen City from January 18 to March 10, 2020 were retrospectively analyzed, including blood cell indexes, inflammatory indexes [C-reactive protein (CRP) and procalcitonin (PCT)], liver function, cardiac function, renal function, blood coagulation function, electrolyte, chest CT scan, and 2019 novel coronavirus (2019-nCoV) nucleic acid tests. The differences of above indexes in the two groups were compared and analyzed. In addition, 55 patients with other viral pneumonia were selected as the control group who admitted to the hospital from August 1 to November 30, 2019. The changes of laboratory indexes of COVID-19 group and control group were observed. RESULTS: In the 215 patients, 206 patients survived and 9 patients died. The average age of survival group was significantly lower than that in the death group, and the average length of hospital stay was significantly longer than the death group. (1) Clinical features: the proportion of underlying diseases in the death group was significantly higher than that in the survival group, such as dyspnea, sore throat, shiver, hypertension, diabetes, coronary heart disease, renal disease, and surgical history. There were no significant differences in other symptoms, signs and underlying diseases between the two group. (2) Laboratory test indexes of the two groups: in death group, white blood cell count [WBC (×109/L): 10.6 (4.0, 13.4) vs. 4.90 (3.92, 6.26)], neutrophils count [NEU (×109/L): 9.7 (3.4, 12.2) vs. 2.9 (2.1, 4.2)]; ratio of neutrophils to lymphocytes [NLR: 14.66 (5.19, 18.48) vs. 2.34 (1.47, 3.34)], CRP [mg/L: 130.21 (35.74, 210.86) vs. 17.90 (3.11, 50.23)], PCT [mg/L: 1.46 (0.45, 13.12) vs. 0.04 (0.02, 0.07)], lactate dehydrogenase [LDH (µmol×s-1×L-1): 4.80 (3.34, 7.37) vs. 3.77 (2.99, 5.12)], creatinine [Cr (µmol/L): 72.9 (69.6, 627.5) vs. 68.4 (55.5, 81.9)], D-dimer [mg/L: 0.86 (0.56, 3.32) vs. 0.39 (0.33, 0.58)], the area of ground glass opacity of chest CT scan [77.8% (7/9) vs. 35.0% (72/206)], the area of local patchy shadows [55.6% (5/9) vs. 17.5% (36/206)], the area of bilateral patchy shadows [100.0% (9/9) vs. 49.5% (102/206)] were significantly higher than those in survival group (all P < 0.01), lymphocyte count [LYM (×109/L): 0.6 (0.5, 0.8) vs. 1.3 (1.0, 1.6)], Na+ [mmol/L: 136.1 (131.0, 136.8) vs. 138.8 (136.5, 140.4)], Cl- [mmol/L: 97.7 (92.7, 100.9) vs. 102.7 (100.2, 104.3)], and carbon dioxide [CO2 (mmol/L): 23.0 (20.6, 28.5) vs. 29.2 (27.7, 30.9)] were significantly lower than those in survival group (all P < 0.05). (3) Laboratory test indicators in COVID-19 and control groups: in COVID-19 group, WBC, NEU, LYM, platelet count (PLT), coefficient of variation of red blood cell distribution width (RDW-CV), standard deviation of red blood cell distribution width (RDW-SD) and Cl- were significantly lower than those in control group, NLR, CRP, K+ and CO2 were significantly higher than those in control group. CONCLUSIONS: The major early symptoms of COVID-19 are fever, cough, chest tightness and fatigue. Age and underlying disease may be the risk factors which affect the prognosis of patients with COVID-19. The laboratory indexes such as WBC, NEU, LYM, CRP, PCT, LDH and Cr between death group and survival group were significantly abnormal in the early stages of COVID-19, which would have important implications for the prognosis of patients with COVID-19. Meanwhile, laboratory test indexes, including WBC, NEU, LYM, PLT, RDW-CV, RDW-SD, CRP, Cl-, K+ and CO2, also have important value in the differential diagnosis between COVID-19 and other viral pneumonia.

Novel coronavirus disease 2019 (COVID-19): relationship between chest CT scores and laboratory parameters.

PURPOSE: To quantify the severity of 2019 novel coronavirus disease (COVID-19) on chest CT and to determine its relationship with laboratory parameters. METHODS: Patients with real-time fluorescence polymerase chain reaction (RT-PCR)-confirmed COVID-19 between January 01 and February 18, 2020, were included in this study. Laboratory parameters were retrospectively collected from medical records. Severity of lung changes on chest CT of early, progressive, peak, and absorption stages was scored according to the percentage of lung involvement (5 lobes, scores 1-5 for each lobe, range 0-20). Relationship between CT scores and laboratory parameters was evaluated by the Spearman rank correlation. The Bonferroni correction adjusted significance level was at 0.05/4 = 0.0125. RESULTS: A total of 84 patients (mean age, 47.8 ± 12.0 years [standard deviation]; age range, 24-80 years) were evaluated. The patients underwent a total of 339 chest CT scans with a median interval of 4 days (interquartile range, 3-5 days). Median chest CT scores peaked at 4 days after the beginning of treatment and then declined. CT score of the early stage was correlated with neutrophil count (r = 0.531, P = 0.011). CT score of the progressive stage was correlated with neutrophil count (r = 0.502, P < 0.001), white blood cell count (r = 0.414, P = 0.001), C-reactive protein (r = 0.511, P < 0.001), procalcitonin (r = 0.423, P = 0.004), and lactose dehydrogenase (r = 0.369, P = 0.010). However, CT scores of the peak and absorption stages were not correlated with any parameter (P > 0.0125). No sex difference occurred regarding CT score (P > 0.05). CONCLUSION: Severity of lung abnormalities quantified on chest CT might correlate with laboratory parameters in the early and progressive stages. However, larger cohort studies are necessary.