Effect of Traditional Chinese Medicine in patients with COVID-19: A multi-center retrospective cohort study (preprint)

Background Traditional Chinese medicine (TCM) has been applied in the treatment of COVID-19 in China, but its effectiveness and safety need evaluation.Methods A multi-center retrospective cohort study was carried out, with cumulative TCM treatment period of ≥ 3 days during hospitalization as exposure. Data came from consecutive inpatients in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting, and the Cox proportional hazards regression model was used for statistical analysis.Results A total of 2272 COVID-19 patients were included, including 1684 in the TCM group and 588 in the control group. Compared with the control group, the hazard ratio for the deterioration rate in the TCM group was 0.52 [95% CI: (0.41, 0.64), P < 0.001]. The results were consistent across patients of varying severity at admission, and two sensitivity analyses confirmed the robustness of the results. In addition, the hazard ratio for all-cause mortality in the TCM group was 0.29 (95% CI = 0.19–0.44, P < 0.001). For safety, the proportion of patients with abnormal liver function or renal function in the TCM group was smaller.Conclusion This real-world study indicates that the addition of a full course of TCM therapy to basic conventional treatment, may reduce the deterioration rate and all-cause mortality of COVID-19 patients with safety. This result can provide evidence to support the current treatment of COVID-19 and new respiratory infectious diseases in the future. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific TCM interventions.Trial registration: ChiCTR, ChiCTR2200062917. Registered 23 August 2022, http://www.chictr.org.cn/showproj.aspx?proj=171556.

Jinhua Qinggan Granules for Nonhospitalized COVID-19 Patients: a Double-Blind, Placebo-Controlled, Randomized Controlled Trial (preprint)

Background: Key findings from the World Health Organization Expert Meeting on Evaluation of Traditional Chinese Medicine in treating COVID-19 reported that TCMs are beneficial, particularly for mild-to-moderate cases. The efficacy of Jinhua Qinggan Granules (JHQG) in COVID-19 patients with mild symptoms has yet to be clearly defined. Methods: We conducted a phase 2/3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with JHQR in mild, nonhospitalized, laboratory-confirmed COVID-19 patients. Participants were randomly assigned to receive 5g/sacket of JHQG or placebo granules orally thrice daily for 10 days. The primary outcomes were the improvement in clinical symptoms and proportion tested negative on viral PCR after treatment. Secondary outcomes were the time to recovery from clinical symptoms and changes in white blood cells (WBC) and acute phase reactants (C-reactive protein (CRP) and ferritin) 10 days after treatment. Results: A total of 300 patients were randomly assigned to receive JHQG (150 patients) and placebo (150 patients). Baseline characteristics were similar in the two groups. In the modified intention-to-treat analysis, JHQG showed greater clinical efficacy (82.67%) after 10 days of treatment compared with the placebo group (10.74%) (rate difference: 71.93%; 95% CI 64.09 - 79.76). The proportion of patients with a negative PCR after treatment were comparable (rate difference: -4.67%; 95% CI -15.76 - 6.42). While all changes in WBC, ferritin, and CRP levels showed a statistically significant decline in JHQG (p<=0.044) after treatment, but not the latter in placebo (p=0.077). The median time to recovery of COVID-19 related symptoms including cough, sputum, sore throat, dyspnea, headache, nasal obstruction, fatigue, and myalgia were shorter in the JHQG group compared to the placebo group (P<0.001 for all). 3 patients experienced mild to moderate adverse events during the treatment period in the JHQG group. Findings were similar between the modified intention-to-treat and the per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen. Conclusions: JHQG is a safe and effective TCM for the treatment of mild COVID-19 patients.

Randomized controlled study of a diagnosis and treatment plan for moderate coronavirus disease 2019 that integrates Traditional Chinese and Western Medicine.

OBJECTIVE: To investigate the clinical efficacy and safety of a diagnosis and treatment plan for moderate coronavirus disease 2019 (COVID-19) that integrates traditional Chinese (TCM) and western medicine. METHODS: One hundred twenty patients with moderate COVID-19 were randomized 1∶2 to the control group ( = 40) and experimental group ( = 80). Both groups received conventional western medicine treatment, and the experimental group also received TCM decoction. Over a 2-week period from diagnosis, we observed the time to clinical recovery (TTCR), rate of improvement on lung computed tomography (CT) imaging, time to defervescence, cough remission time, hospital discharge rate, average hospitalization stay, modified Medical Research Council (mMRC) scale score, clinical cure rate, laboratory findings, incidence of progression to severe or critical disease, and adverse events. RESULTS: Among 120 enrolled patients, 108 completed the study. The baseline data did not differ between the experimental and control groups (all > 0.05). After treatment, the TTCR, rate of lung CT imaging improvement, time to defervescence, cough remission time, hospital discharge rate, average hospitalization stay (among discharged patients), mMRC scale score, clinical cure rate, and rates of normal values for laboratory findings were better in the experimental group than in the control group ( < 0.05 or < 0.01). The incidence of progression to severe or critical disease and the incidence of adverse events did not differ between the two groups ( > 0.05). CONCLUSION: The diagnosis and treatment plan integrating Chinese and western medicine showed improved clinical efficacy compared with western medicine alone for patients with moderate COVID-19 and is worthy of clinical promotion and application.

Diagnostic Performance of a Blood Urea Nitrogen to Creatinine Ratio-Based Nomogram for Predicting in-Hospital Mortality in COVID-19 Patients (preprint)

Background: The novel coronavirus disease (COVID-19) is leading to high morbidity and mortality. This study aimed to test whether blood urea nitrogen-to-creatinine ratios (BCR) is a predictor of poor prognosis in patients with COVID-19. Method: From 9,165 generally healthy subjects, we calculated ranges of “normal” BCR values. 416 COVID-19 patients were randomly assigned to training cohort and validation cohort contained 337, 79 patients, respectively. The prognostic ability of abnormal BCR range was assessed using a Logistic regression. Development a nomogram for predicting in-hospital mortality incorporated age, sex and BCR. The model discrimination was assessed using the calibration curves and concordance index in training and validation cohort. The predictive accuracy and clinical values of the nomogram was measured by decision curve analysis (DCA) and clinical impact curve analysis (CICA). Results: Among 337 COVID-19 patients, 13.4% and 11.3% were classified into higher and lower than normal range group, respectively. The BCR was identified as an independent risks factor for death in COVID-19 patients (P<0.0001), with area under the curve (AUC) 0.768; 95%CI: 0.717-0.819). Kaplan-Meier curves for all-cause mortality outcomes showed that patients with above normal range of BCR had worse prognosis (p<0.0001). Logistic regression analysis revealed that BCR above the normal range was independently associated with death in COVID-19 patients (Odds ratio 7.54; 95%CI: 1.55-36.66; P=0.012). ROC curves showed that the nomogram had good discrimination in the training cohort (AUC 0.838; 95%CI 0.795–0.880) and the validation cohort (AUC 0.929; 95%CI 0.869-0.989). Using maximum Youden index, the cutoff values of 59.8 points, the sensitivity and specificity were 75.4% and 81%. The calibration curves showed good agreement between nomogram prediction and actual observation. DCA and CICA indicated the clinical usefulness of the prediction nomogram. Conclusion: BCR was a useful prognostic factor for COVID-19 patients. Development of an individualized prediction nomogram BCR-based, which can effectively predict the risk of mortality, and then, help clinicians to improve individual treatment, make clinical decisions timely and early.

Effect of continuous renal replacement therapy on all-cause mortality in COVID-19 patients undergoing invasive mechanical ventilation: a retrospective cohort study (preprint)

BackgroundFor the coronavirus disease 2019 (COVID-19), critically ill patients had a high mortality rate. We aimed to assess the association between prolonged intermittent renal replacement therapy (PIRRT) and mortality in patients with COVID-19 undergoing invasive mechanical ventilation. MethodsIn this retrospective cohort study, we included all patients with COVID-19 undergoing invasive mechanical ventilation from February 12nd to March 2nd, 2020. All patients were followed until death or March 28th, and all survivors were followed for at least 30 days. ResultsFor 36 hospitalized COVID-19 patients with invasive mechanical ventilation, the mean age was 69.4 ({+/-} 10.8) years, and 30 patients (83.3%) were men. Twenty-two (61.1%) patients received PIRRT (PIRRT group) and 14 cases (38.9%) were managed with conventional strategy (non-PIRRT group). There were no differences in age, sex, comorbidities, complications, treatments and most of the laboratory findings. During median follow-up period of 9.5 (interquartile range 4.3-33.5) days, 13 of 22 (59.1%) patients in the PIRRT group and 11 of 14 (78.6%) patients in the non-PIRRT group died. Kaplan-Meier analysis demonstrated prolonged survival in patients in the PIRRT group compared with that in the non-PIRRT group (P = 0.042). The association between PIRRT and a reduced risk of mortality remained significant in three different models, with adjusted hazard ratios varying from 0.332 to 0.398. Higher levels of IL-2 receptor, TNF-, procalcitonin, prothrombin time, and NT-proBNP were significantly associated with an increased risk of mortality in patients with PIRRT. ConclusionPIRRT may be beneficial for the treatment of COVID-19 patients with invasive mechanical ventilation. Further prospective multicenter studies with larger sample sizes are required.