The results of this multicenter retrospective cohort study of 2272 patients showed that full-course of TCM treatment can reduce the risk of deterioration events (HR = 0.52), and death events (HR = 0.29), in patients with COVID-19. Two sensitivity analyses confirmed the robustness of the findings. In addition, the results of subgroup analysis can preliminarily indicate that TCM treatment can reduce the deterioration rate of patients in most cases, and the more severe the patient's condition, the greater the effect of TCM may be.
In previous clinical trials, the relative risk (RR) of TCM intervention on deterioration rate was in the range of 0.00-0.50 [13–16]. Although TCM tends to reduce the deterioration rate, some research results are not statistically significant due to the small sample size. Meanwhile, due to the achievements of China's epidemic prevention and control, as well as medical ethics considerations, some RCTs cannot be implemented according to the established plan[24]. Therefore, the results of the previous study have certain limitations.
However, based on real-world data from a large sample, this study showed that patients in the TCM group had 0.52 times the chance of disease deterioration at the next time point compared with the control group. Considering that the control group of this study included patients who received TCM for 1 or 2 days, rather than patients who did not use TCM at all, the effectiveness of the control group could be overestimated, and the effectiveness of the TCM group could be underestimated. Therefore, the actual effectiveness of the TCM group may be better. The results of this study illustrate that TCM can be used in the clinical treatment of COVID-19 at various stages, it reduces the risk of deterioration, and is safe. The reduction in the deterioration rate also means that TCM treatment can reduce the risk of mild and moderate cases progressing to severe, and severe progressing to critical or even death.
In a previous national retrospective registry study, compared with patients who did not take Qingfei Paidu Decoction, the application of Qingfei Paidu Decoction significantly reduced mortality [1.2% vs. 4.8%, HR = 0.50, 95% CI: (0.37, 0.66)]. This effect size is smaller than the results of this study [11]. We believe that the control group of this study (patients who did not take Qingfei Paidu Decoction) may have used other TCM interventions, thus overestimating the effectiveness of the control group and reducing the effect size of the study. But in general, the effect of TCM intervention on reducing mortality is worthy of recognition.
As an acute infectious disease, COVID-19 is epidemic and contagious. It belongs to the category of "plague" in TCM. Most of the COVID-19 patients in Wuhan have symptoms of fever, cough, fatigue, poor appetite, and thick and greasy tongue coating. The syndrome differentiation of TCM should focus on “dampness toxin” [25]. In clinical treatment, Chinese herbal medicines for resolving dampness, clearing heat, dispelling wind and removing toxins can be applied. Oral Chinese patent medicines such as Lianhua Qingwen Capsules can be used for clearing heat and detoxifying. In severe cases, Xuebijing Injection and other Chinese patent medicine injections can also be used to assist Western medicine treatment [26]. Previous studies have found that TCM mainly plays the roles of antiviral, anti-inflammatory, immune regulation and organ protection in the treatment of COVID-19 [27–29]. In view of the definite effectiveness of TCM on a variety of acute infectious diseases [8], TCM interventions should still have a certain effect on patients infected with new variant strains of COVID-19, but this needs further research and verification.
This study provides new evidence for TCM treatment of COVID-19. Firstly, this study took deterioration rate and mortality as outcomes. Deterioration rate and mortality are the most important and objective outcomes in the evaluation of COVID-19. Since there is low incidence of death, preventing further deterioration is more important for most COVID-19 patients [30]. Secondly, the sample size of this study is three times the largest sample size of previous observational studies evaluating deterioration rates, which means this study also has good statistical power in subgroup analysis. Thirdly, the data for this study was derived from consecutive patients from four medical centers in Wuhan. Therefore, this study can be used as a supplement to RCTs in providing new and reliable medical evidence for TCM in the treatment of COVID-19 in a real-world setting.
The results of this study still have some limitations. Firstly, since this study is an observational study, the influence of confounding factors on the results cannot be completely ruled out. However, we performed IPTW for confounders typically considered in comparative effects studies, making baseline characteristics comparable between the two groups, and the IPTW-adjusted model had a similar hazard ratio in reducing the rate of deterioration as the unadjusted model. Thus, suggesting that the reduction in the deterioration rate is mainly related to the application of TCM. Secondly, the SARS-CoV-2 strain of the patients included in this study is partially different from the currently prevalent SARS-CoV-2 Omicron variant in clinical features (such as infectivity and immune escape) [31]. However, considering the wide applicability of TCM and the exact curative effect on various variant strains, the results of this study can still provide evidence to support the current treatment of COVID-19 and new respiratory infectious diseases in the future [32]. Lastly, there is a certain clinical heterogeneity in the specific TCM interventions in the TCM group in this study. Although we describe the specific use of TCM in patients with different states, there may be differences in the effectiveness of different interventions on patients. Therefore, we can only evaluate the overall effectiveness of TCM on COVID-19. The efficacy of each specific intervention still needs further research.