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

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new zoonotic agent that emerged in December 2019, causes coronavirus disease 2019 (COVID-19). This infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. SARS-CoV-2 spreads primarily via respiratory droplets during close person-to-person contact in a closed space, especially a building. This article summarizes the environmental factors involved in SARS-CoV-2 transmission, including a strategy to prevent SARS-CoV-2 transmission in a building environment. SARS-CoV-2 can persist on surfaces of fomites for at least 3 days depending on the conditions. If SARS-CoV-2 is aerosolized intentionally, it is stable for at least several hours. SARS-CoV-2 is inactivated rapidly on surfaces with sunlight. Close-contact aerosol transmission through smaller aerosolized particles is likely to be combined with respiratory droplets and contact transmission in a confined, crowded, and poorly ventilated indoor environment, as suggested by some cluster cases. Although evidence of the effect of aerosol transmission is limited and uncertainty remains, adequate preventive measures to control indoor environmental quality are required, based on a precautionary approach, because COVID-19 has caused serious global damages to public health, community, and the social economy. The expert panel for COVID-19 in Japan has focused on the "3 Cs," namely, "closed spaces with poor ventilation," "crowded spaces with many people," and "close contact." In addition, the Ministry of Health, Labour and Welfare of Japan has been recommending adequate ventilation in all closed spaces in accordance with the existing standards of the Law for Maintenance of Sanitation in Buildings as one of the initial political actions to prevent the spread of COVID-19. However, specific standards for indoor environmental quality control have not been recommended and many scientific uncertainties remain regarding the infection dynamics and mode of SARS-CoV-2 transmission in closed indoor spaces. Further research and evaluation are required regarding the effect and role of indoor environmental quality control, especially ventilation.
Aerosols ; Air Pollution, Indoor/prevention & control* ; Betacoronavirus/physiology* ; COVID-19 ; Coronavirus Infections/transmission* ; Crowding ; Environment, Controlled ; Humans ; Pandemics/prevention & control* ; Pneumonia, Viral/transmission* ; SARS-CoV-2 ; Ventilation

OBJECTIVES: To explore the influential factors and titer trend of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific IgG antibody in convalescent patients with coronavirus disease 2019 (COVID-19), and to provide theoretical basis for the feasibility of clinical treatment of convalescent plasma. METHODS: Colloidal gold immunochromatography assay was used to detect the SARS-CoV-2 specific IgG antibody and its titer in 113 convalescent patients with COVID-19 who were followed up from February 19, 2020 to April 6, 2020. The basic characteristics and treatment factors of patients in the high titer group (antibody titer≥1꞉160, RESULTS: The difference in the clinical type of COVID-19, onset time, first admission C-reactive protein, absolute value of lymphocyte, absolute value of CD19 CONCLUSIONS Male COVID-19 patients might be more likely to produce high titer SARS-CoV-2 specific IgG antibodies than female. The peak level of SARS-CoV-2 specific IgG antibody in convalescent patients is maintained for a short period. Using plasma from convalescent COVID-19 patients for treatment should be within 28 d after discharge.
Antibodies, Viral ; Betacoronavirus ; COVID-19/therapy* ; Female ; Humans ; Immunization, Passive ; Immunoglobulin G ; Male ; Pandemics ; Pneumonia, Viral/epidemiology* ; SARS-CoV-2

Coronavirus disease 2019 (COVID-19) is now a major public health problem worldwide. Infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is extremely strong. The one major target of the virus is the lung, which leads to the deaths of respiratory distress syndrome and multiple organ failure. The kidney is also one of the main organs attacked by viruses, which directly damage the renal tubules through angiotensin converting enzyme-2 and cause cytokine storm, resulting in kidney damage and increasing the risk of death in the patients. Early investigation of risk factors for kidney injury, detection of kidney injury indicators, timely supporting treatment and renal replacement therapy for the existence of kidney injury patients are useful for reducing the mortality rate of COVID-19 patients.
Betacoronavirus ; COVID-19 ; Coronavirus Infections/epidemiology* ; Humans ; Kidney ; Pandemics ; Pneumonia, Viral/epidemiology* ; SARS-CoV-2

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major outbreak in the world. SARS-CoV-2 infection can not only involve in the respiratory system, but also cause severe nervous system damage. Studies have shown that SRAS-CoV-2 can invade the nervous system through hematogenous and transneuronal pathways, and may cause nervous system damage in patients with COVID-19 by inhibiting cellular immunity, hypoxemia, inflammation, inducing neuronal degeneration and apoptosis, and angiotensin converting enzyme 2 (ACE2) mechanism. It can lead to intracranial infection, toxic encephalopathy, acute cerebrovascular disease, muscle damage, peripheral nervous system injury, acute myelitis, demyelination disease or other nervous system diseases.
Betacoronavirus ; COVID-19 ; Coronavirus Infections/epidemiology* ; Humans ; Pandemics ; Peptidyl-Dipeptidase A ; Pneumonia, Viral/epidemiology* ; Research ; SARS-CoV-2

OBJECTIVE: To investigate the mental health status and its influencing factors among general population and healthcare professionals in Guangdong Province during COVID-19 pandemic. METHODS: A online questionnaire-based survey was conducted from March 11st to March 15th, 2020.The questionnaire consisted of 4 parts to survey the participants'basic information, understanding of COVID-19 outbreak-associated information, cognition of COVID-19 pandemic and status of anxiety and depression.A total of 1433 valid responses were collected, including 706 from the general population and 727 from healthcare professionals.Cronbach's α coefficient and exploratory factor analysis were used for reliability and validity assessment.Chi-square, Wilcoxon and Kruskal-Wallis test were used for univariate analysis and ordinal or nominal logistic regression was used for multivariate analysis of the data. RESULTS: There was no significant difference between the general population and the healthcare professionals in terms of anxiety, depression and cognition of COVID-19 outbreak after adjustment for demographic variables, but the levels of anxiety and depression of these participants were both higher than those before the pandemic.In the participants from the general population, multivariate logistic regressions showed an OR for anxiety of 1.93(1.18, 3.17) among those who spent 1-2 h a day in reading COVID-19-related news, while those who spent over 3 h had an OR value for anxiety of 1.88(1.14, 3.11);the unmarried individuals had a depression OR of 2.19(1.51, 3.18). Inaccurate cognition of COVID-19 outbreak was positive correlated with the occurrence of anxiety and depression.Unmarried individuals and those with higher educational levels had better cognition of COVID-19 outbreak.Among the healthcare professionals, multivariate logistic regressions suggested that insufficient rest time and worries about contracting the virus contributed to the occurrence of anxiety and depression.Among the nursing staff, the OR of obvious depression was 2.99(1.45, 6.18).Compared to healthcare professionals not working in designated hospital for COVID-19, those who work in the designated hospitals had ORs for obvious and severe depression of 0.48(0.25, 0.93) and 0.39(0.17, 0.89), respectively.Concerns over contracting the virus increased the possibility of incorrect cognition of COVID-19. CONCLUSIONS Psychological interventions are essential for both the general population and healthcare professionals, especially for unmarried individuals in the general population and the nursing staff.An excessive exposure to COVID-19-related information may have detrimental effects on the mental health.For healthcare professionals, sufficient rest needs to be ensured, and education programs on COVID-19 should be implemented among both residents and healthcare professionals to improve their mental health.
Anxiety/epidemiology* ; Betacoronavirus ; COVID-19 ; China/epidemiology* ; Coronavirus Infections ; Health Status ; Humans ; Pandemics ; Pneumonia, Viral ; Reproducibility of Results ; SARS-CoV-2

OBJECTIVE: To analyze the clinical manifestations of heart, liver and kidney damages in the early stage of COVID-19 to identify the indicators for these damages. METHODS: We analyzed the clinical features, underlying diseases, and indicators of infection in 12 patients with COVID-19 on the second day after their admission to our hospital between January 20 and February 20, 2020.The data including CK-MB, aTnI, BNP, heart rate, changes in ECG, LVEF (%), left ventricular general longitudinal strain (GLS, measured by color Doppler ultrasound) were collected.The changes of liver function biochemical indicators were dynamically reviewed.BUN, UCR, eGFR, Ccr, and UACR and the levels of MA, A1M, IGU, and TRU were recorded. RESULTS: The 12 patients included 2 severe cases, 8 common type cases, and 2 mild cases.Four of the patients presented with sinus tachycardia, ECG changes and abnormal GLS in spite of normal aTNI and LVEF; 1 patient had abnormal CKMB and BNP.On the first and third days following admission, the patients had normal ALT, AST and GGT levels.On day 7, hepatic function damage occurred in the severe cases, manifested by elevated ALT and AST levels.Abnormalities of eGFR, Ccr and UACR occurred in 8, 5 and 5 of the patients, respectively.Abnormal elevations of MA, A1M, IGU and TRU in urine protein were observed in 4, 4, 5, and 2 of the patients, respectively. CONCLUSIONS In patients with COVID-19, heart damage can be identified early by observing the GLS and new abnormalities on ECG in spite of normal aTNI and LVEF.Early liver injury is not obvious in these patients, but dynamic monitoring of the indicators of should be emplemented, especially in severe cases. In cases with normal CR and BUN, kidney damage can be detected early by calculating eGFR, Ccr and UACR and urine protein tests.
Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2

On May 15, 2020, the Lancet published an article titled Use of Herbal Drugs to Treat COVID-19 Should be with Caution. While this is true of all drugs, herbal and otherwise, the data may be biased and deserve a scientific response. We believe these types of reports will unfairly and negatively impact the field of integrative medicine as a whole, and must be answered with facts and statistics that more accurately represent the current situation.
Betacoronavirus ; Bias ; COVID-19 ; Coronavirus ; Coronavirus Infections/drug therapy* ; Drugs, Chinese Herbal ; Humans ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2

The coronavirus disease 2019(COVID-19) is raging in China and more than 20 other countries and regions since the middle of December 2019. Currently, there is no specific drug or vaccine besides symptomatic supportive therapy. Taking full advantage of the clinical experience of traditional Chinese medicine(TCM) in preventing and controlling major epidemics such as SARS, it is an important mission for TCM to propose effective formula with immediate response and solid evidence by using modern biomedical knowledge and techniques(molecular docking assisted TCM formulation for short). In view of the high homology between the gene sequences of the novel coronavirus and SARS virus, and the similarities between the two in terms of pathogenic mechanism and clinical manifestations, our team established a rapid screening and optimization model for the prevention and treatment of the novel coronavirus based on clinical experience and molecular docking technology. Firstly, the clinical team and the research team pre-developed and screened TCM formula by using "back-to-back" manner. Then, the formula was optimized and determined by comparing and analyzing the results of the two groups. The results showed that the research team screened out 46 active ingredients from candidate TCMs that could act on the novel coronavirus S-protein-binding site of human ACE2 protein, which were mainly attributed to 7 herbs such as Lonicerae Japonicae Flos and Mori Folium. The result was largely consistent with the formula raised by the clinical group, verifying and supporting its rationality. This provides evidence for the scientific and potential efficacy of the TCM prescription from the perspective of treatment target analysis, and also suggests that the TCM prescription has the potential to directly inhibit viral infection in addition to improving clinical symptoms or syndromes. Based on this, our team optimized and formed a new anti-coronavirus TCM prescription "Keguan Yihao", immediately providing the TCM prescription with certain clinical experience and objective evidence support for the prevention and treatment of new emergent infectious diseases in our hospital. The TCM prescription was combined with modern medicine symptomatic supportive treatment for clinical treatment, preliminary results showed better effect than symptomatic supportive therapy alone. This research has innovated the method mode in clinical practice and basic research integration of traditional Chinese medicine for the prevention and control of new emerging infectious diseases. It is of great significance to further improve the rapid response mechanism of TCM in face of major epidemics, and further improve the capability level of TCM to prevent and treat new emerging infectious diseases.
Angiotensin-Converting Enzyme 2 ; Angiotensin-Converting Enzyme Inhibitors/pharmacology* ; Betacoronavirus ; COVID-19 ; China ; Coronavirus Infections/drug therapy* ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Pandemics ; Peptidyl-Dipeptidase A/chemistry* ; Pneumonia, Viral/drug therapy* ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/chemistry* ; COVID-19 Drug Treatment

With the rapid outbreak of COVID-19, traditional Chinese medicine(TCM) has been playing an active role against the epidemic. However, the screening of TCM is limited by the development cycle and laboratory conditions, which greatly limits the screening speed. This study established optimization docking models and virtual screening to discovery potential active herbs for the prevention and treatment of the novel coronavirus based on molecular docking technology. The crystal structures of 3 CL protease(Mpro) and papain-like protease(PLP) were obtained from PDB database and homologous modeling respectively, and were used to conduct virtual screening of TCMD 2009 database by CDOCKER program. The ingredients scored in the top 100 were selected respectively, and the candidate herbs were ranked by the numbers of hit molecules. Based on Mpro inhibitors screening, 12 322 potential active components were obtained, and the representative active components included aster pentapeptide A, ligustrazine, salvianolic acid B, etc., and Zingiberis Rhizoma Recens, Asteris Radix et Rhizoma, Notoginseng Radix et Rhizoma, Chuanxiong Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Zingiberis Rhizoma, Dianthi Herba, Rhei Radix et Rhizoma, Cistanches Herba were obtained. While 11 294 potential active ingredients were obtained by PLP inhibitor screening, representative active ingredients included gingerketophenol, ginkgol alcohol, ferulic acid, etc., and Codonopsis Radix, Notopterygii Rhizoma et Radix, Zingiberis Rhizoma Recens, Ginkgo Semen, Chuanxiong Rhizoma, Trichosanthis Fructus, Paeoniae Radix Alba, Psoraleae Fructus, Sophorae Flavescentis Radix, Notoginseng Radix et Rhizoma, Angelicae Sinensis Radix were chosen. By combining the diagnosis and treatment scheme of Hunan province's and angiotensin converting enzyme 2(ACE2) inhibitors screening from literature, present study also discussed the rational application of candidate herbs to this epidemic situation. Trichosanthis Fructus obtained by PLP inhibitors screening and Fritillaria verticillata obtained by ACE2 inhibitors screening were parts of the Sangbei Zhisou Powder and Xiaoxianxiong Decoction, which might be applicable to the syndromes of cough and dyspnea. Rhei Radix et Rhizoma screened by Mpro and Trichosanthis Fructus screened by PLP were contained in Maxing Shigan Decoction and Xuanbai Chengqi Decoction, and could be applied to the syndromes of epidemic virus blocking lung. Mori Folium, Lonicerae Japonicae Flos and Forsythiae Fructus obtained by ACE2 inhibitors screening were included in the Sangju Decoction and Yinqiaosan, which might be applicable to the syndromes of warm pathogen attacking lung and cough and dyspnea. The results of this study are intended to provide a reference for the further development of traditional Chinese medicine to deal with the new epidemic.
Angiotensin-Converting Enzyme 2 ; Angiotensin-Converting Enzyme Inhibitors/pharmacology* ; Betacoronavirus/drug effects* ; COVID-19 ; Coronavirus Infections/drug therapy* ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Pandemics ; Peptidyl-Dipeptidase A ; Pneumonia, Viral/drug therapy* ; SARS-CoV-2 ; COVID-19 Drug Treatment