[Thymosin alpha 1 for the adjuvant treatment of coronavirus disease 2019: a retrospective cohort study].

OBJECTIVE: To evaluate the effect of thymosin alpha 1 on the prognosis of patients with coronavirus disease 2019 (COVID-19). METHODS: A retrospective cohort study was performed to collect clinical data of 95 patients treated by Shanghai Aid Medical Team in Wuhan Third Hospital during January 31, 2020 and March 4, 2020, who were confirmed COVID-19. They were divided into two groups according to whether they were treated with thymosin alpha 1 after admission. The 28-day mortality (primary outcome), and 28-ventilator-free-day, lymphocyte count (LYM) level, C-reactive protein (CRP) level (secondary outcomes) were compared between two groups. Survival analysis was performed using the Kaplan-Meier curve. The effect of thymosin alpha 1 on 28-day survival was evaluated with Cox regression model. RESULTS: Among the 95 patients, there were 31 cases in thymosin group and 64 cases in non-thymosin group; 29 patients died 28 days after admission, including 11 cases (35.5%) in thymosin group and 18 cases (28.1%) in non-thymosin group. Kaplan-Meier survival curve showed that thymosin alpha 1 could improve the 28-day survival of patients with COVID-19, but the univariate Cox model analysis showed that the difference was not statistically significant [hazard ratio (HR) = 0.48, 95% confidence interval (95%CI) was 0.20-1.14, P = 0.098]; multivariate Cox model analysis showed that thymosin alpha 1 was the factor to improve the 28-day mortality (HR = 0.15, 95%CI was 0.04-0.55, P = 0.004), old age (HR = 1.10, 95%CI was 1.05-1.15, P < 0.001), accompanied by chronic renal dysfunction (HR = 42.35, 95%CI was 2.77-648.64, P = 0.007), decrease of LYM at admission (HR = 0.15, 95%CI was 0.04-0.60, P = 0.007) and the use of methylprednisolone (HR = 4.59, 95%CI was 1.26-16.67, P = 0.021) were also risk factors for the increase of 28-day mortality. The use of immunoglobulin and antiviral drugs abidol and ganciclovir did not affect the 28-day mortality. After adjustment for age, gender, LYM and other factors, weighted multivariate Cox analysis model showed thymosin alpha 1 could significantly improve the 28-day survival of COVID-19 patients (HR = 0.45, 95%CI was 0.25-0.84, P = 0.012). In terms of secondary outcomes, no statistical difference (all P > 0.05) was found between two groups in days without ventilator at 28 days after admission (days: 17.97±13.56 vs. 20.09±12.67) and the increase of LYM at 7 days after admission [×109/L: -0.07 (-0.23, 0.43) vs. 0.12 (-0.54, 0.41)]. But the decrease of CRP at 7 days after admission in thymosin alpha group was significantly greater than that in non-thymosin group [mg/L: 39.99 (8.44, 82.22) vs. 0.53 (-7.78, 22.93), P < 0.05]. CONCLUSION: Thymosin alpha 1 may improve 28-day mortality and inflammation state in COVID-19 patients.

Myoglobin and troponin as prognostic factors in patients with COVID-19 pneumonia.

BACKGROUND: The outbreak of novel coronavirus pneumonia 2019 (COVID-19) has caused millions of deaths worldwide. It is well documented that troponin predicts the prognosis of patients. Myoglobin is not only an important marker of myocardial injury, but it indicates systemic muscle damage. However, its relationship with COVID-19 was rarely reported. The present study compared the predictive value of troponin and myoglobin on the final prognosis of COVID-19 patients by analyzing the clinical characteristics and serum levels of myoglobin and troponin in severe/critical COVID-19 patients. METHODS: We enrolled 499 consecutive eligible hospitalized patients with severe/critical COVID-19 from February 14 to March 24, 2020 at Leishenshan Hospital, Wuhan, China. Clinical characteristics and laboratory data were collected and compared between the patients who died and survived. We analyzed the receiver operating characteristic curves of myoglobin and troponin. Then, the patients were divided into myo+ group, myo- group, tro+ group, and tro- group, and survival curves were analyzed. The prognostic predictable values of myoglobin and troponin were further analyzed using Cox multifactorial analysis. RESULTS: Myoglobin and troponin were significantly elevated in the death group (134.4 [interquartile range (IQR) 24.80, 605] vs 38.02 [IQR 3.87, 11.73] ng/ml, p < 0.001), and troponin was also significantly elevated in the death group (0.01 [IQR 0.01, 0.01] vs 0.04 [IQR 0.02, 0.15] ng/ml, p < 0.001). The ROC curves demonstrated that the area under the curve when using myoglobin to predict patient death was 0.911, with a threshold of 1.17, which was equivalent to troponin. Kaplan-Meier survival analysis revealed a significantly lower survival curve in the myo+ group than the myo- group. Multifactor Cox survival analysis showed that troponin was no longer significant (HR = 0.98, 95% CI 0.92-1.03, p = 0.507), but elevated myoglobin was an independent predictor of death in COVID-19 patients (HR = 1.001, 95% CI 1.001-1.002, p < 0.001). The analysis of the Cox model for predicting patient death and plotting decision curves suggested that the single factor myoglobin model was superior to troponin, and the predictive value of the multifactor model was superior to the single-factor analyses. CONCLUSIONS: In severe/critical COVID-19 patients, myoglobin and troponin were predictors of mortality and the probability of conversion to critical illness, and myoglobin may be superior to troponin for predictive value.

ANTECEDENTES: El brote de la nueva neumonía por coronavirus 2019 (COVID-19) ha causado millones de muertes en todo el mundo. Está bien documentado que la troponina predice el pronóstico de los pacientes. La mioglobina no solo es un importante marcador de lesión miocárdica, sino que indica daño muscular sistémico. Sin embargo, su relación con la COVID-19 ha sido raramente comunicada. En el presente estudio se ha comparado el valor predictivo de la troponina y la mioglobina en el pronóstico final de los pacientes con COVID-19, analizando las características clínicas y los niveles séricos de mioglobina y troponina en pacientes con COVID-19 en estado grave o crítico. MÉTODOS: Se inscribió a 499 pacientes consecutivos elegibles hospitalizados con COVID-19 en estado grave o crítico del 14 de febrero al 24 de marzo de 2020 en el Hospital Leishenshan (Wuhan, China). Se recogieron las características clínicas y los datos de laboratorio y se compararon entre los pacientes que murieron y los que sobrevivieron. Se analizaron las curvas de características operativas del receptor de mioglobina y troponina. A continuación, se dividió a los pacientes en grupo myo+, grupo myo−, grupo tro+ y grupo tro−, y se analizaron las curvas de supervivencia. Los valores pronósticos de la mioglobina y la troponina se analizaron además mediante un análisis multifactorial de Cox. RESULTADOS: La mioglobina y la troponina estaban significativamente elevadas en el grupo de muerte (134,4; rango intercuartílico [RIQ: 24,80; 605] vs. 38,02; [RIQ: 3,87; 11,73] ng/ml; p < 0,001), y la troponina también estaba significativamente elevada en el grupo de muerte (0,01 [RIQ: 0,01; 0,01] vs. 0,04 [RIQ: 0,02; 0,15] ng/ml; p < 0,001). Las curvas ROC demostraron que el área bajo la curva al utilizar la mioglobina para predecir la muerte de los pacientes era de 0,911, con un umbral de 1,17, equivalente al de la troponina. El análisis de supervivencia de Kaplan-Meier reveló una curva de supervivencia significativamente menor en el grupo myo+ que en el grupo myo−. El análisis de supervivencia multifactorial de Cox mostró que la troponina ya no era significativa (HR = 0,98; IC 95%: 0,92-1,03; p = 0,507), pero la mioglobina elevada era un predictor independiente de muerte en los pacientes COVID-19 (HR = 1,001; IC 95%: 1,001-1,002; p < 0,001). El análisis del modelo de Cox para predecir la muerte de los pacientes y el trazado de las curvas de decisión indicaron que el modelo de mioglobina de un solo factor era superior al de la troponina y que el valor predictivo del modelo multifactorial era superior a los análisis de un solo factor. CONCLUSIONES: En los pacientes graves o críticos de COVID-19, la mioglobina y la troponina fueron predictores de la mortalidad y de la probabilidad de conversión a enfermedad crítica, y la mioglobina puede ser superior a la troponina en cuanto al valor predictivo.

m6A modification regulates lung fibroblast-to-myofibroblast transition through modulating KCNH6 mRNA translation.

Idiopathic pulmonary fibrosis (IPF) is a chronic, fatal lung disease characterized by progressive and non-reversible abnormal matrix deposition in lung parenchyma. Myofibroblasts originating mainly from resident fibroblasts via fibroblast-to-myofibroblast transition (FMT) are the dominant collagen-producing cells in pulmonary fibrosis. N6-methyladenosine (m6A) modification has been implicated in various biological processes. However, the role of m6A modification in pulmonary fibrosis remains elusive. In this study, we reveal that m6A modification is upregulated in a bleomycin (BLM)-induced pulmonary fibrosis mouse model, FMT-derived myofibroblasts, and IPF patient lung samples. Lowering m6A levels through silencing methyltransferase-like 3 (METTL3) inhibits the FMT process in vitro and in vivo. Mechanistically, KCNH6 is involved in the m6A-regulated FMT process. m6A modification regulates the expression of KCNH6 by modulating its translation in a YTH-domain family 1 (YTHDF1)-dependent manner. Together, our study highlights the critical role of m6A modification in pulmonary fibrosis. Manipulation of m6A modification through targeting METTL3 may become a promising strategy for the treatment of pulmonary fibrosis.

Myoglobin and troponin as prognostic factors in patients with COVID-19 pneumonia.

BACKGROUND: The outbreak of novel coronavirus pneumonia 2019 (COVID-19) has caused millions of deaths worldwide. It is well documented that troponin predicts the prognosis of patients. Myoglobin is not only an important marker of myocardial injury, but it indicates systemic muscle damage. However, its relationship with COVID-19 was rarely reported. The present study compared the predictive value of troponin and myoglobin on the final prognosis of COVID-19 patients by analyzing the clinical characteristics and serum levels of myoglobin and troponin in severe/critical COVID-19 patients. METHODS: We enrolled 499 consecutive eligible hospitalized patients with severe/critical COVID-19 from February 14 to March 24, 2020 at Leishenshan Hospital, Wuhan, China. Clinical characteristics and laboratory data were collected and compared between the patients who died and survived. We analyzed the receiver operating characteristic curves of myoglobin and troponin. Then, the patients were divided into myo+ group, myo- group, tro+ group, and tro- group, and survival curves were analyzed. The prognostic predictable values of myoglobin and troponin were further analyzed using Cox multifactorial analysis. RESULTS: Myoglobin and troponin were significantly elevated in the death group (134.4 [interquartile range (IQR) 24.80, 605] vs 38.02 [IQR 3.87, 11.73]ng/ml, p<0.001), and troponin was also significantly elevated in the death group (0.01 [IQR 0.01, 0.01] vs 0.04 [IQR 0.02, 0.15]ng/ml, p<0.001). The ROC curves demonstrated that the area under the curve when using myoglobin to predict patient death was 0.911, with a threshold of 1.17, which was equivalent to troponin. Kaplan-Meier survival analysis revealed a significantly lower survival curve in the myo+ group than the myo- group. Multifactor Cox survival analysis showed that troponin was no longer significant (HR=0.98, 95% CI 0.92-1.03, p=0.507), but elevated myoglobin was an independent predictor of death in COVID-19 patients (HR=1.001, 95% CI 1.001-1.002, p<0.001). The analysis of the Cox model for predicting patient death and plotting decision curves suggested that the single factor myoglobin model was superior to troponin, and the predictive value of the multifactor model was superior to the single-factor analyses. CONCLUSIONS: In severe/critical COVID-19 patients, myoglobin and troponin were predictors of mortality and the probability of conversion to critical illness, and myoglobin may be superior to troponin for predictive value.