BACKGROUND: Over 65 million people have long COVID. Evidence for using Chinese herbal medicine (CHM) to treat long COVID is growing. A systematic review of evidence for guiding clinical decision is warranted. OBJECTIVE: To examine the effects and safety of CHM in alleviating the severity of dyspnea, fatigue, exercise intolerance, depression, anxiety and insomnia in long COVID adults based on registered randomized clinical trials (RCT). SEARCH STRATEGY: World Health Organization International Clinical Trials Registry Platform and Chinese Clinical Trial Registry were searched for registered trial protocols from database inception to February 10, 2023. English (PubMed, Embase, AMED and CINAHL) and Chinese databases (CNKI, Wanfang Data and CQVIP) were then searched to identify relevant publications from December 2019 through April 6, 2023. INCLUSION CRITERIA: Registered RCTs that compared the effects of Chinese herbal medicines or Chinese herbal formulas against a control treatment (i.e., the placebo or usual care) in adults with persistent symptoms of long COVID. The primary outcome of dyspnea, and secondary outcomes of fatigue, exercise intolerance, depression, anxiety and insomnia were measured using validated tools at the end of the treatment. DATA EXTRACTION AND ANALYSIS: Data were extracted, and eligible RCTs were evaluated using version 2 of the Cochrane risk-of-bias tool for randomized trials and Grading of Recommendations, Assessment, Development and Evaluations independently by two researchers. Effect sizes were estimated by random-effects modelling and mean difference (MD). Heterogeneity between trials was quantified by I². RESULTS: Among the 38 registered clinical trials we identified, seven RCTs (1,519 patients) were included in the systematic review. One RCT had a low overall risk of bias. Compared to the control, CHM reduces dyspnea on the Borg Dyspnea Scale score (MD = -0.2, 95% confidence interval [CI] = -0.65 to 0.25) with moderate certainty, and reduces fatigue on the Borg Scale (MD = -0.48, 95% CI = -0.74 to -0.22) with low certainty. CHM clinically reduces depression on Hamilton Depression Rating Scale score (MD = -6.00, 95% CI = -7.56 to -4.44) and anxiety on Hamilton Anxiety Rating Scale score (MD = -6.10, 95% CI = -7.67 to -4.53), and reduces insomnia on the Insomnia Severity Index (MD = -4.86, 95% CI = -12.50 to 2.79) with moderate certainty. Meta-analysis of two RCTs (517 patients) showed that CHM clinically improves exercise intolerance by increasing 6-minute walking distance (MD = -15.92, 95% CI = -10.20 to 42.05) with substantial heterogeneity (I² = 68%) and low certainty. CONCLUSION CHM is associated with a post-treatment clinical reduction in depression and anxiety in long COVID adults, compared to the control, but it does not have a strong treatment effect on dyspnea and insomnia. Effects of CHM on exercise intolerance and fatigue are uncertain, and the safety of using CHM remains questionable. Please cite this article as: Tsang MS, Zhou IW, Zhang AL, Xue CC. Chinese herbal medicine for dyspnea and persistent symptoms of long COVID: A systematic review and meta-analysis of randomized controlled trials. J Integr Med. 2025; 23(2): 126-137.
Humans ; Dyspnea/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Randomized Controlled Trials as Topic ; COVID-19/complications* ; Fatigue/drug therapy* ; SARS-CoV-2 ; Anxiety/drug therapy* ; Depression/drug therapy* ; Sleep Initiation and Maintenance Disorders/drug therapy* ; Betacoronavirus

Objective: To explore the clinical characteristics and prognosis of the new coronavirus 2019-nCoV patients combined with cardiovascular disease （CVD). Methods: A retrospective analysis was performed on 112 COVID-19 patients with CVD admitted to the western district of Union Hospital in Wuhan, from January 20, 2020 to February 15, 2020. They were divided into critical group (ICU, n=16) and general group (n=96) according to the severity of the disease and patients were followed up to the clinical endpoint. The observation indicators included total blood count, C-reactive protein (CRP), arterial blood gas analysis, myocardial injury markers, coagulation function, liver and kidney function, electrolyte, procalcitonin (PCT), B-type natriuretic peptide (BNP), blood lipid, pulmonary CT and pathogen detection. Results: Compared with the general group, the lymphocyte count (0.74 (0.34, 0.94)×10⁹/L vs. 0.99 (0.71, 1.29)×10⁹/L, P=0.03) was extremely lower in the critical group, CRP (106.98 (81.57, 135.76) mg/L vs. 34.34 (9.55,76.54) mg/L, P<0.001) and PCT (0.20 (0.15,0.48) μg/L vs. 0.11 (0.06,0.20) μg/L, P<0.001) were significantly higher in the critical group. The BMI of the critical group was significantly higher than that of the general group (25.5 (23.0, 27.5) kg/m² vs. 22.0 (20.0, 24.0) kg/m²，P=0.003). Patients were further divided into non-survivor group (17, 15.18%) group and survivor group (95, 84.82%). Among the non-survivors, there were 88.24% (15/17) patients with BMI> 25.0 kg/m², which was significantly higher than that of survivors (18.95% (18/95), P<0.001). Compared with the survived patients, oxygenation index (130 (102, 415) vs. 434 (410, 444), P<0.001) was significantly lower and lactic acid (1.70 (1.30, 3.00) mmol/L vs. 1.20 (1.10, 1.60) mmol/L, P<0.001) was significantly higher in the non-survivors. There was no significant difference in the proportion of ACEI/ARB medication between the critical group and the general group or between non-survivors and survivors （all P>0.05). Conclusion: COVID-19 patients combined with CVD are associated with a higher risk of mortality. Critical patients are characterized with lower lymphocyte counts. Higher BMI are more often seen in critical patients and non-survivor. ACEI/ARB use does not affect the morbidity and mortality of COVID-19 combined with CVD. Aggravating causes of death include fulminant inflammation, lactic acid accumulation and thrombotic events.
Betacoronavirus ; COVID-19 ; Cardiovascular Diseases/therapy* ; Coronavirus Infections/complications* ; Humans ; Pandemics ; Pneumonia, Viral/complications* ; Prognosis ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome

Objective: To identify the characteristics including clinical features and pulmonary computed tomography (CT) features of heart failure and COVID-19. Methods: This study was a retrospective study. A total of 7 patients with heart failure and 12 patients with COVID-19 in the Second Xiangya Hospital of Central South University between December 1, 2019 and February 15, 2020 were enrolled. The baseline clinical and imaging features of the two groups were statistically analyzed. Results: There was no significant difference in age and sex between the two groups(both P>0.05), but the incidence of epidemiological contact history, fever or respiratory symptoms in the COVID-19 group was significantly higher than that in the heart failure group (12/12 vs. 0, P<0.001; 12/12 vs. 4/7, P=0.013). While the proportion of cardiovascular diseases and impaired cardiac function was significantly less than that of the heart failure group(2/12 vs.7/7, P<0.001；0 vs.7/7, P<0.001). For imaging features, both groups had ground-glass opacity and thickening of interlobular septum, but the ratio of central and gradient distribution was higher in patients with heart failure than that in patients with COVID-19 (4/7 vs. 1/12, P=0.04). In heart failure group, the ratio of the expansion of pulmonary veins was also higher (3/7 vs. 0，P=0.013), and the lung lesions can be significantly improved after effective anti-heart failure treatment. Besides, there were more cases with rounded morphology in COVID-19 group（9/12 vs. 2/7, P=0.048）. Conclusions: More patients with COVID-19 have epidemiological history and fever or respiratory symptoms. There are significant differences in chest CT features, such as enlargement of pulmonary veins, lesions distribution and morphology between heart failure and COVID-19.
Betacoronavirus ; COVID-19 ; Coronavirus Infections/diagnostic imaging* ; Heart Failure/etiology* ; Humans ; Pandemics ; Pneumonia, Viral/diagnostic imaging* ; Retrospective Studies ; SARS-CoV-2 ; Tomography, X-Ray Computed

Objective: To evaluate the cardiovascular damage of patients with COVID-19, and determine the correlation of serum N-terminal pro B-type natriuretic peptide (NT-proBNP） and cardiac troponin-I (cTnI） with the severity of COVID-19, and the impact of concomitant cardiovascular disease on severity of COVID-19 was also evaluated. Methods: A cross-sectional study was designed on 150 consecutive patients with COVID-19 in the fever clinic of Tongji Hospital in Wuhan from January 19 to February 13 in 2020, including 126 mild cases and 24 cases in critical care. Both univariate and multivariate logistic regression were used to analyze the correlation of past medical history including hypertension, diabetes and coronary heart disease (CHD）, as well as the levels of serum NT-proBNP and cTnI to the disease severity of COVID-19 patients. Results: Age, hypersensitive C-reactive protein(hs-CRP) and serum creatinine levels of the patients were higher in critical care cases than in mild cases(all P<0.05). Prevalence of male, elevated NT-proBNP and cTnI, hypertension and coronary heart disease were significantly higher in critical cases care patients than in the mild cases(all P<0.05). Univariate logistic regression analysis showed that age, male, elevated NT-proBNP, elevated cTnI, elevated hs-CRP, elevated serum creatinine, hypertension, and CHD were significantly correlated with critical disease status(all P<0.05). Multivariate logistic regression analysis showed that elevated cTnI(OR=26.909，95%CI 4.086-177.226，P=0.001) and CHD (OR=16.609，95%CI 2.288-120.577，P=0.005) were the independent risk factors of critical disease status. Conclusions: COVID-19 can significantly affect the heart function and lead to myocardial injury. The past medical history of CHD and increased level of cTnI are 2 independent determinants of clinical disease status in patients with COVID-19.
Betacoronavirus ; Biomarkers/blood* ; COVID-19 ; Cardiovascular Diseases/virology* ; China ; Coronavirus Infections/pathology* ; Cross-Sectional Studies ; Female ; Humans ; Male ; Myocardium/pathology* ; Natriuretic Peptide, Brain/blood* ; Pandemics ; Peptide Fragments ; Pneumonia, Viral/pathology* ; Prognosis ; SARS-CoV-2 ; Troponin I/blood*

Angiotensin-Converting Enzyme 2 ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/pathology* ; Humans ; Pandemics ; Peptidyl-Dipeptidase A/physiology* ; Pneumonia, Viral/pathology* ; SARS-CoV-2

Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme 2 ; Betacoronavirus ; COVID-19 ; Cardiovascular Agents/pharmacology* ; Cardiovascular Diseases ; Coronavirus Infections/physiopathology* ; Humans ; Pandemics ; Peptidyl-Dipeptidase A/physiology* ; Pneumonia, Viral/physiopathology* ; SARS-CoV-2

Objective: To analyze the clinical characteristics of the severe or critically ill patients with novel coronavirus pneumonia (COVID-19), and evaluate the impact of complicated myocardial injury on the prognosis of these patients. Methods: A retrospective study was conducted in 54 patients who admitted to Tongji hospital from February 3, 2020 to February 24, 2020 and met the criteria of severe or critical conditions of COVID-19. The clinical characteristics and hospital mortality rate were analyzed and compared between the patients with or without myocardial injury, which was defined with 3 times higher serum cardiac troponin value. Results: The age of the 54 patients was 68.0(59.8, 74.3) years. Among all the patients, 24 (44.4%) patients were complicated with hypertension, 13 (24.1%) with diabetes, 8 (14.8%) with coronary heart disease, and 3 (5.6%) with previous cerebral infarction. During hospitalization, 24 (44.4%) of the patients were complicated with myocardial injury and 26 (48.1%) patients died in hospital. In-hospital mortality was significantly higher in patients with myocardial injury than in patients without myocardial injury (14 (60.9%) vs. 8 (25.8%), P=0.013). Moreover, the levels of C-reactive protein (153.6 (80.3, 240.7) ng/L vs. 49.8 (15.9, 101.9) ng/L) and N-terminal pro-B-type natriuretic peptide (852.0 (400.0, 2 315.3) ng/L vs. 197.0 (115.3, 631.0) ng/L) were significantly higher than patients without myocardial injury (all P<0.01). Conclusions: Prevalence of myocardial injury is high among severe or critically ill COVID-19 patients. Severe or critically ill COVID-19 patients with myocardial injury face a significantly higher risk of in-hospital mortality. The study suggests that it is important to monitor and manage the myocardial injury during hospitalization for severe or critically ill COVID-19 patients.
Aged ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/complications* ; Critical Illness ; Heart Injuries ; Humans ; Middle Aged ; Pandemics ; Pneumonia, Viral/complications* ; Retrospective Studies ; SARS-CoV-2

Angiotensin-Converting Enzyme 2 ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/physiopathology* ; Humans ; Pandemics ; Peptidyl-Dipeptidase A/physiology* ; Pneumonia, Viral/physiopathology* ; SARS-CoV-2

Objective: Present study investigated the mechanism of heart failure associated with coronavirus infection and predicted potential effective therapeutic drugs against heart failure associated with coronavirus infection. Methods: Coronavirus and heart failure were searched in the Gene Expression Omnibus (GEO) and omics data were selected to meet experimental requirements. Differentially expressed genes were analyzed using the Limma package in R language to screen for differentially expressed genes. The two sets of differential genes were introduced into the R language cluster Profiler package for gene ontology (GO) and Kyoto gene and genome encyclopedia (KEGG) pathway enrichment analysis. Two sets of intersections were taken. A protein interaction network was constructed for all differentially expressed genes using STRING database and core genes were screened. Finally, the apparently accurate treatment prediction platform (EpiMed) independently developed by the team was used to predict the therapeutic drug. Results: The GSE59185 coronavirus data set was searched and screened in the GEO database, and divided into wt group, ΔE group, Δ3 group, Δ5 group according to different subtypes, and compared with control group. After the difference analysis, 191 up-regulated genes and 18 down-regulated genes were defined. The GEO126062 heart failure data set was retrieved and screened from the GEO database. A total of 495 differentially expressed genes were screened, of which 165 were up-regulated and 330 were down-regulated. Correlation analysis of differentially expressed genes between coronavirus and heart failure was performed. After cross processing, there were 20 GO entries, which were mainly enriched in virus response, virus defense response, type Ⅰ interferon response, γ interferon regulation, innate immune response regulation, negative regulation of virus life cycle, replication regulation of viral genome, etc. There were 5 KEGG pathways, mainly interacting with tumor necrosis factor (TNF) signaling pathway, interleukin (IL)-17 signaling pathway, cytokine and receptor interaction, Toll-like receptor signaling pathway, human giant cells viral infection related. All differentially expressed genes were introduced into the STRING online analysis website for protein interaction network analysis, and core genes such as signal transducer and activator of transcription 3, IL-10, IL17, TNF, interferon regulatory factor 9, 2'-5'-oligoadenylate synthetase 1, mitogen-activated protein kinase 3, radical s-adenosyl methionine domain containing 2, c-x-c motif chemokine ligand 10, caspase 3 and other genes were screened. The drugs predicted by EpiMed's apparent precision treatment prediction platform for disease-drug association analysis were mainly TNF-α inhibitors, resveratrol, ritonavir, paeony, retinoic acid, forsythia, and houttuynia cordata. Conclusions: The abnormal activation of multiple inflammatory pathways may be the cause of heart failure in patients after coronavirus infection. Resveratrol, ritonavir, retinoic acid, amaranth, forsythia, houttuynia may have therapeutic effects. Future basic and clinical research is warranted to validate present results and hypothesis.
Betacoronavirus ; COVID-19 ; Computational Biology ; Coronavirus Infections/complications* ; Gene Expression Profiling ; Gene Ontology ; Heart Failure/virology* ; Humans ; Pandemics ; Pneumonia, Viral/complications* ; SARS-CoV-2

Betacoronavirus ; COVID-19 ; Cardiovascular Diseases/complications* ; Consensus ; Coronavirus Infections/epidemiology* ; Epidemics ; Humans ; Pandemics ; Pneumonia, Viral/epidemiology* ; SARS-CoV-2