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

This article reports the diagnosis and treatment of two children with coronavirus disease 2019 (COVID-19) and hypertension. Case 1 was a boy aged 13 years and 3 months, with the main manifestations of fever and dry cough; chest CT showed ground-glass opacities, and the nucleic acid test of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) yielded a positive result. Case 2 was a boy aged 13 years and 8 months and had no clinical symptoms; chest CT showed no abnormality, while the nucleic acid test of SARS-CoV-2 yielded a positive result. Both cases were shown with family aggregation of SARS-CoV-2 infection. They had obesity and a family history of hypertension. Continuous blood pressure monitoring in the resting state during hospitalization showed that blood pressure was above the 95% reference interval of normal value for children of the same age, and the two boys were given calcium channel blockers or β-receptor blockers and were then recovered. It is concluded that comprehensive management of children with COVID-19 and underlying cardiovascular diseases, including hypertension, should be taken seriously during the epidemic.
Adolescent ; Betacoronavirus ; Coronavirus Infections ; complications ; Humans ; Hypertension ; complications ; Male ; Pandemics ; Pneumonia, Viral ; complications

OBJECTIVE: To study the clinical features of coronavirus disease 2019 (COVID-19) in children aged <18 years. METHODS: A retrospective analysis was performed from the medical data of 23 children, aged from 3 months to 17 years and 8 months, who were diagnosed with COVID-19 in Jiangxi, China from January 21 to February 29, 2020. RESULTS: Of the 23 children with COVID-19, 17 had family aggregation. Three children (13%) had asymptomatic infection, 6 (26%) had mild type, and 14 (61%) had common type. Among these 23 children, 16 (70%) had fever, 11 (48%) had cough, 8 (35%) had fever and cough, and 8 (35%) had wet rales in the lungs. The period from disease onset or the first nucleic acid-positive detection of SARS-CoV-2 to the virus nucleic acid negative conversion was 6-24 days (median 12 days). Of the 23 children, 3 had a reduction in total leukocyte count, 2 had a reduction in lymphocytes, 2 had an increase in C-reactive protein, and 2 had an increase in D-dimer. Abnormal pulmonary CT findings were observed in 12 children, among whom 9 had patchy ground-glass opacities in both lungs. All 23 children received antiviral therapy and were recovered. CONCLUSIONS COVID-19 in children aged <18 years often occurs with family aggregation, with no specific clinical manifestation and laboratory examination results. Most of these children have mild symptoms and a good prognosis. Epidemiological history is of particular importance in the diagnosis of COVID-19 in children aged <18 years.
Adolescent ; Betacoronavirus ; Child ; Child, Preschool ; China ; Coronavirus Infections ; Humans ; Infant ; Pandemics ; Pneumonia, Viral ; Retrospective Studies

OBJECTIVE: To study the clinical and epidemiological features of children with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: The clinical data of 20 children who were diagnosed with asymptomatic SARS-CoV-2 infection from January 20 to March 4, 2020 were analyzed. RESULTS: Among the 20 children, there were 7 boys (35%) and 13 girls (65%), aged 8 months to 14 years (mean 8±5 years). All these children had no clinical manifestations and attended the hospital for an epidemiological history of SARS-CoV-2. Nineteen children were shown with family aggregation of SARS-CoV-2 infection. Nasopharyngeal swabs were PCR-positive for SARS-CoV-2 in all 20 children. There were 4 children (20%) of mild type, 16 children (80%) of common type, and no children of severe type or critical type. The mean peripheral blood leukocyte count was (6.8±3.5)×10/L, and 7 children had an abnormal peripheral blood leukocyte count, with an increase in 5 children and a reduction in 2 children. One child had a decreased absolute value of lymphocytes (0.87×10/L), 3 children had an increased erythrocyte sedimentation rate (20-42 mm/h), 7 children had an increased lactate dehydrogenase level (>400 U/L), and 4 children had an increased blood lactate level (>1.6 mmol/L). Chest CT showed single or multiple small nodule shadows, patchy shadows, and ground-glass shadows in the middle or lateral lobe of lungs or under the pleura in 13 children. CONCLUSIONS Pediatric cases of asymptomatic SARS-CoV-2 infection mostly occur with family aggregation. Most of the children with asymptomatic infection have no obvious abnormalities in blood routine and other laboratory tests. Changes in chest CT scan can be used as an aid for early diagnosis of asymptomatic infection in children.
Aged, 80 and over ; Betacoronavirus ; Child ; Child, Preschool ; Coronavirus Infections ; Female ; Humans ; Infant ; Male ; Pandemics ; Pneumonia, Viral

Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, the public-facility-turned temporary hospital (PFTH) has played an important role in preventing the spread of the epidemic. Wuchang PFTH is the first one to put into clinical practice and the last one suspended in Wuhan. The National Emergency Medical Rescue Team of the Second Xiangya Hospital of Central South University, together with other 13 medical teams (841 medical staff in total), have fulfilled the task for the treatment of non-severe COVID-19 patients, without any medical staff infected. The first author of the article was the only pediatrician working in the Wuchang PFTH. The author describes and summarizes the features/functions, management/operations, and advantages/challenges of the PFTH, in order to provide reference for medical institutions and relevant departments to deal with public health emergencies.
Betacoronavirus ; China ; Coronavirus Infections ; prevention & control ; Hospitals ; Humans ; Pandemics ; prevention & control ; Pneumonia, Viral ; prevention & control

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Adult ; Aged ; Aged, 80 and over ; Aging ; genetics ; immunology ; Betacoronavirus ; CD4-Positive T-Lymphocytes ; metabolism ; Cell Lineage ; Chromatin Assembly and Disassembly ; Coronavirus Infections ; immunology ; Cytokine Release Syndrome ; etiology ; immunology ; Cytokines ; biosynthesis ; genetics ; Disease Susceptibility ; Flow Cytometry ; methods ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Rearrangement ; Humans ; Immune System ; cytology ; growth & development ; immunology ; Immunocompetence ; genetics ; Inflammation ; genetics ; immunology ; Mass Spectrometry ; methods ; Middle Aged ; Pandemics ; Pneumonia, Viral ; immunology ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcriptome ; Young Adult

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Animals ; Antiviral Agents ; pharmacology ; therapeutic use ; Betacoronavirus ; drug effects ; physiology ; Binding Sites ; drug effects ; Cell Line ; Coronavirus Infections ; drug therapy ; virology ; Crotonates ; pharmacology ; Cytokine Release Syndrome ; drug therapy ; Drug Evaluation, Preclinical ; Gene Knockout Techniques ; Humans ; Influenza A virus ; drug effects ; Leflunomide ; pharmacology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; metabolism ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; Protein Binding ; drug effects ; Pyrimidines ; biosynthesis ; RNA Viruses ; drug effects ; physiology ; Structure-Activity Relationship ; Toluidines ; pharmacology ; Ubiquinone ; metabolism ; Virus Replication ; drug effects

The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.
Adoptive Transfer ; Alveolar Epithelial Cells ; pathology ; Animals ; Apoptosis ; Betacoronavirus ; Body Fluids ; metabolism ; CD4-Positive T-Lymphocytes ; immunology ; Clinical Trials as Topic ; Coinfection ; prevention & control ; therapy ; Coronavirus Infections ; complications ; immunology ; Disease Models, Animal ; Endothelial Cells ; pathology ; Extracorporeal Membrane Oxygenation ; Genetic Therapy ; methods ; Genetic Vectors ; administration & dosage ; therapeutic use ; Humans ; Immunity, Innate ; Inflammation Mediators ; metabolism ; Lung ; pathology ; physiopathology ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stem Cells ; physiology ; Multiple Organ Failure ; etiology ; prevention & control ; Pandemics ; Pneumonia, Viral ; complications ; immunology ; Respiratory Distress Syndrome, Adult ; immunology ; pathology ; therapy ; Translational Medical Research

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