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 survey the residents for their understanding of Coronavirus Disease 2019 (COVID-19)-related knowledge, attitude and practices (KAP) in two hard hit provinces of China to facilitate the governmental decisions on strategies against the disease. METHODS: We invited the participants from Hubei and Henan Provinces of China for an internetbased survey starting from 12:00 on February 21, 2020 to 12:00 on February 23. The survey included the general conditions, KAP of COVID-19, psychological status and living conditions of the residents. RESULTS: The effective response rate of the questionnaire was 98.9%. The mean (P25, P75) age of the participants was 19 (16, 40) years, and 54.3% of them were students. Social media were the most important source of information concerning the pandemic of the respondents. The respondents had a high awareness of person-to-person transmission of the virus through the respiratory tract or droplets but showed a relatively low level of awareness of the population susceptible to COVID-19 and its specific symptoms. The results of multivariate analysis showed that women, undergraduate students (including college students) and higher degree holders had better knowledge of COVID-19 ( < 0.05); the proportion of respondents who expressed to have different levels of psychological stressed such as worry, anxiety and panic reached 77.2%; 16.7% of the responders considered psychological interventions necessary for their psychological conditions; 63.6% of the respondents confessed a bias against the people returning from Hubei and Henan provinces, while 22.4% worried that they might be biased because of their residence in Hubei and Henan. The rate of personal protective equipment shortage was as high as 69.4%; the rates of the responders who would "covering the mouth and nose when coughing or sneezing", "properly use masks in accordance with regulations", "maintain proper hand hygiene ", "avoid gatherings with relatives and friends" and "refrain from going to public places" were 92.4%, 95.9%, 93.5%, 88.8% and 93.1%, respectively. Women and groups with good knowledge of the disease reported better protective behaviors against the diseases ( < 0.05). CONCLUSIONS The residents in Hubei and Henan Provinces have generally good KAP related to COVID-19, and the online platforms plays a positive role to in circulating epidemic-related information. It is essential to further increase the supply of the protective materials and pay more attention to the mental health of the residents during the pandemic, and psychological counseling and psychological protection should be provided if necessary.
Attitude ; Betacoronavirus ; Coronavirus Infections ; Female ; Humans ; Pandemics ; Pneumonia, Viral

OBJECTIVE: To explore the target, signaling pathways and their biological functions of Decoction in the treatment of COVID-19 based on network pharmacology and molecular docking technology. METHODS: The active components and target proteins in 21 drugs such as and in decoction were analyzed, and the signaling pathways and biological functions of the target proteins common with COVID-19 were screened by using TCMSP, Swiss Target Prediction, CooLGeN, GeneCards, DAVID and other databases. The network diagram of decoction was constructed using Gephi software. RESULTS: We identified 163 active ingredients, including MOL004798, MOL000519, MOL004824, MOL000554, MOL010428, and MOL013443, from 18 drugs in decoction (such as , , , , and ). These ingredients activate renin-angiotensin system signaling pathway and apoptosis signaling pathway by regulating 10 protein targets (ACE, ACE2, AGTR1, FURIN, TNF, CASP3, CASP6, DPP4, MCL1 and POLD1) to execute 42 biological functions such as renin-angiotensin regulation of blood volume and systemic arterial blood pressure to treat COVID-19. The results of preliminary molecular docking showed that MOL000519 (from ), MOL000554 (from ), MOL004798 (from ), MOL004824 (from ), MOL010428 (from ), and MOL013443 (from ) had good affinity with SARS-CoV-2 3CL hydrolase to form complexes with stable conformations and high binding activity (binding energy ≤- 5 kJ/mol). CONCLUSIONS decoction can treat COVID-19 through its multiple medicinal ingredients that have multiple targets and involve multiple signaling pathways for different biological functions. Our finding provides reference for further investigation into the pharmacological mechanism of decoction in treating COVID-19.
Betacoronavirus ; Coronavirus Infections ; drug therapy ; Drugs, Chinese Herbal ; Humans ; Molecular Docking Simulation ; Pandemics ; Pneumonia, Viral ; drug therapy

OBJECTIVE: To understand the distribution patterns and the factors influencing the interval between entry of mainland China and diagnosis in imported COVID-19 cases in Guangdong Province to provide evidence for formulating and implementing effective control measures. METHODS: We collected the data of imported COVID-19 cases from March 1st to April 10th, 2020 published on the official websites of Health Commission of Guangdong Province and local government of the cities in Guangdong Province for epidemiological analysis. Descriptive statistical methods were used to analyze the distribution patterns of the interval between entry of mainland China and diagnosis of the imported cases, and multivariate logistic regression was used to analyze the factors influencing the interval. RESULTS: A total of 179 imported cases were reported in Guangdong by April 10th, 2020. The average interval between entry of mainland China and diagnosis was 4.21 days with a median of 2 days. The interval was between 1 and 3 days in 69.8% of the cases. Multivariate logistic regression analysis showed that a negative result of the initial nucleic acid test (OR=5.205, 95% : 1.100-24.640, =0.038) and interval between entry of mainland China and a positive diagnosis >2 days (OR=85.654, 95%: 24.569-298.615, < 0.001) were risk factors for the finding delay. CONCLUSIONS The results of initial nucleic acid detection and the interval between entry of mainland China and a positive diagnosis of COVID-19 are the major contributing factors of delayed case detection. This finding suggests that strict quarantine and detection measures should be carried out for the personnel entering China to accurately and quickly identify the cases.
Betacoronavirus ; China ; Clinical Laboratory Techniques ; Coronavirus Infections ; diagnosis ; Delayed Diagnosis ; Humans ; Pandemics ; Pneumonia, Viral ; diagnosis

OBJECTIVE: To explore the clinical characteristics and outcomes of adult critically ill patients with COVID-19 and identify the risk factors correlated with in-hospital deaths. METHODS: This study was conducted among 20 confirmed adult cases of COVID-19 in the Intensive Care Unit (ICU) of Honghu People's Hospital in Jingzhou City, Hubei Province. According to the final outcome, the patients were divided into survivor group and death group with 10 patients each. The demographic data, clinical manifestations and signs, laboratory findings, treatment measures and clinical outcomes were obtained from electronic medical records to compare the clinical characteristics and outcomes between the two groups. Univariate logistic analysis was used to analyze the risk factors associated with in-hospital death. RESULTS: The mean age of patients with confirmed COVID-19 was 70 ± 12 years, and 40% of them were male. The patients were admitted to ICU 11 ± 9 days after symptom onset. The most common symptoms on admission were cough (19 cases), fatigue or myalgia (18 cases), fever (17 cases) and dyspnea (16 cases). Eleven (55%) of the patients had underlying diseases, among which hypertension was the most common (11 cases), followed by cardiovascular disease (4 cases) and diabetes (3 cases). Six (30%) of the patients received invasive mechanical ventilation and continued renal replacement therapy but eventually died. Acute cardiac injury was the most common complication (19 cases). Half of the patients died between the 2nd and 19th day after ICU admission. Compared with dead patients, the surviving patients had a lower average body weight (61.70±2.36 68.60±7.15 kg, =0.01) and a higher Glasgow Coma Index (14.69 ± 0.70 12.70 ± 2.45, =0.03), and were less likely to develop shock (2 10, =0.001) or acute respiratory distress syndrome (2 10, =0.001). CONCLUSIONS Critically ill patients with COVID-19 are generally older. A higher body weight and a lower lymphocyte count are potentially associated with a greater likeliness of fatality in ICU patients with COVID-19.
Aged ; Aged, 80 and over ; Betacoronavirus ; Coronavirus Infections ; Critical Illness ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; Retrospective Studies

OBJECTIVE: To explore the pharmacologically active ingredients in granules (TJQW) for treatment of coronavirus disease 2019 (COVID-19) in light of systemic pharmacology. METHODS: We performed database search, literature mining and drug-like index screening to identify the bioactive components in TJQW, the positive drugs for disease treatment and their therapeutic targets. The core disease target was investigated based on the cross-linking interaction of the bioactive components, positive drug and potential disease target, and the target proteins at the key nodes were analyzed by GO and KEGG analyses. Based on the therapeutic targets for COVID-19, virtual screening was conducted to screen the compounds in TJQW and construct the network cross-linking the key bioactive molecules in TJQW, key node targets of the disease, and the related biological pathways. RESULTS: We identified 159 compounds in TJQW and obtained 18 core proteins based on the cross-linking of the bioactive components, positive drugs and disease targets. The key node targets consisted of 22 targets including the latest 4 COVID-19 proteins. Virtual screening results showed that at least 14 compounds could bind with the core disease target proteins. The material basis of TJQW for COVID-19 treatment was explained in multi-pathway, multi-component and multi-target perspectives. In terms of the structural characteristics of the compounds, we screened the top 30 molecules with strong binding with the target proteins, among which flavonoids were the predominant components. CONCLUSIONS This investigation reveals the therapeutic mechanism of TJQW for COVID-19 involving multiple components, targets and pathways from the perspective of key bioactive molecules, disease key node targets and related biological pathways. We screened 30 active precursors from TJQW, which provides reference for the clinical application and further development of TJQW.
Betacoronavirus ; Coronavirus Infections ; drug therapy ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Pandemics ; Pneumonia, Viral ; drug therapy

OBJECTIVE: To analyze the clinical features of severe or critical ill adult patients with coronavirus disease (COVID-19). METHODS: The clinical data of 75 patients with severe or critical COVID-19 in Honghu People's Hospital from January to March in 2020 were collected. RESULTS: Of the 75 patients with COVID-19 pneumonia, 41 were male (54.67%) and 34 were female (45.33%) with a mean age of 67.53 ±12.37 years; 43 patients had severe and 32 had critical COVID-19, and 49.3% of the patients had underlying diseases. The main clinical manifestations included fever (78.67%) and coughing (70.67%). Compared with the severe patients, the critically ill patients had higher proportions of patients over 60 years old with elevated white blood cell count, increased prothrombin time, and higher levels of hsCRP, PCT, D-dimer, ALT, LDH, cTnI and NT-proBNP. Univariate logistic regression analysis showed that an age over 60 years, leukocytosis, hs-CRP elevation, prolonged prothrombin time, and increased levels of D-dimer, NT-proBNP and cTnI were associated with severe COVID-19. Multivariate logistic regression showed that an age over 60 years (OR=8.165, 95% : 1.483-45.576, =0.017), prolonged prothrombin time (OR=7.516, 95% : 2.568-21.998, =0.006) and elevated NT-proBNP (OR=6.194, 95% : 1.305-29.404, =0.022) were independent risk factors for critical type of COVID-19. CONCLUSIONS An age over 60 years, a prolonged prothrombin time and elevated NT-proBNP level are important clinical features of critically ill patients with COVID-19, and can be deemed as early warning signals for critical conditions of the disease.
Aged ; Betacoronavirus ; Coronavirus Infections ; Critical Illness ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; Retrospective Studies

OBJECTIVE: To identify the key biochemical indicators that affect the clinical type and outcomes of COVID-19 patients and explore the application of neutrophil/lymphocyte ratio (NLR) in COVID-19. METHODS: Ninety-three patients with confirmed diagnosis of COVID-19 admitted in Ezhou Central Hospital from February to April in 2020 were analyzed. Among them, 43 patients were selected from Intensive Care Unit (ICU) with the diagnosis of critical type of COVID-19, and 50 cases of common type were selected from the Department of Respiratory Medicine. The baseline data, blood routine test and biochemical indexes of the patients were collected on the first day of admission. NLRs of the patients were calculated, and COX survival analysis according to the NLR 4-category method was performed. The patients' outcomes were analyzed with receiver operating curves (ROCs). The patients were divided into two groups according to NLR cutoff value for comparison of the biochemical indexes. Based on the patients' outcomes, NLR cutoff value classification and clinical classification, multiple binary logistics regression was performed to screen the key variables and explore their significance in COVID-19. RESULTS: The NLR four-category method was not applicable for prognostic evaluation of the patients. The cut-off value of NLR for predict the prognosis of COVID-19 was 11.26, with a sensitivity of 0.903 and a specificity of 0.839; the laboratory indicators of the patients with NLR < 11.26 were similar to those in patients of the common type; the indicators were also similar between patients with NLR≥11.26 and those with critical type COVID-19. NLR, WBC, NEUT, PCT, DD, BUN, TNI, BNP, and LDH had significant effects on the clinical classification and outcome of the patients ( < 0.05); Cr, Ca, PH, and Lac had greater impact on the outcome of the patients ( < 0.05), while Na, PCO had greater impact on the clinical classification of the patients ( < 0.05). CONCLUSIONS NLR can be used as an important reference for clinical classification, prognostic assessment, and biochemical abnormalities of COVID-19. Patients of critical type more frequently have bacterial infection with more serious inflammatory reactions, severer heart, lung and kidney damages, and much higher levels of DD and LDH than those of the common type. NLR, NEUT, DD, TNI, BNP, LDH, Ca, PCT, PH, and Lac have obvious influence on the prognosis of COVID-19 and should be observed dynamically.
Betacoronavirus ; Coronavirus Infections ; Humans ; Lymphocytes ; Neutrophils ; Pandemics ; Pneumonia, Viral ; Prognosis ; ROC Curve ; Retrospective Studies

2019-nCoV epidemic was firstly reported at late December of 2019 and has caused a global outbreak of COVID-19 now. Saliva, a biofluid largely generated from salivary glands in oral cavity, has been reported 2019-nCoV nucleic acid positive. Besides lungs, salivary glands and tongue are possibly another hosts of 2019-nCoV due to expression of ACE2. Close contact or short-range transmission of infectious saliva droplets is a primary mode for 2019-nCoV to disseminate as claimed by WHO, while long-distance saliva aerosol transmission is highly environment dependent within indoor space with aerosol-generating procedures such as dental practice. So far, no direct evidence has been found that 2019-nCoV is vital in air flow for long time. Therefore, to prevent formation of infectious saliva droplets, to thoroughly disinfect indoor air and to block acquisition of saliva droplets could slow down 2019-nCoV dissemination. This review summarizes diagnostic value of saliva for 2019-nCoV, possibly direct invasion into oral tissues, and close contact transmission of 2019-nCoV by saliva droplets, expecting to contribute to 2019-nCoV epidemic control.
Betacoronavirus ; isolation & purification ; pathogenicity ; Clinical Laboratory Techniques ; Coronavirus Infections ; diagnosis ; transmission ; Humans ; Mouth ; virology ; Pandemics ; Peptidyl-Dipeptidase A ; metabolism ; Pharynx ; virology ; Pneumonia, Viral ; diagnosis ; transmission ; SARS Virus ; isolation & purification ; pathogenicity ; Saliva ; virology

This study aimed to understand the differences in clinical, epidemiological, and laboratory features between the new coronavirus disease 2019 (COVID-2019) and influenza A in children. Data of 23 hospitalized children with COVID-19 (9 boys, 5.7 ± 3.8 years old) were compared with age- and sex-matched 69 hospitalized and 69 outpatient children with influenza A from a hospital in China. The participants' epidemiological history, family cluster, clinical manifestations, and blood test results were assessed. Compared with either inpatients or outpatients with influenza A, children with COVID-19 showed significantly more frequent family infections and higher ratio of low fever (< 37.3 °C), but shorter cough and fever duration, lower body temperature, and lower rates of cough, fever, high fever (> 39 °C), nasal congestion, rhinorrhea, sore throat, vomiting, myalgia or arthralgia, and febrile seizures. They also showed higher counts of lymphocytes, T lymphocyte CD8, and platelets and levels of cholinesterase, aspartate aminotransferase, lactate dehydrogenase, and lactic acid, but lower serum amyloid, C-reactive protein, and fibrinogen levels and erythrocyte sedimentation rate, and shorter prothrombin time. The level of alanine aminotransferase in children with COVID-19 is lower than that in inpatients but higher than that in outpatients with influenza A. Pediatric COVID-19 is associated with more frequent family infection, milder symptoms, and milder immune responses relative to pediatric influenza A.
Betacoronavirus ; physiology ; Case-Control Studies ; Child ; Coronavirus Infections ; blood ; epidemiology ; immunology ; virology ; Female ; Humans ; Influenza, Human ; blood ; epidemiology ; immunology ; Male ; Pandemics ; Pneumonia, Viral ; blood ; epidemiology ; immunology ; virology