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

Betacoronavirus ; Clinical Protocols ; Coronavirus Infections ; diagnosis ; pathology ; therapy ; transmission ; Humans ; Pandemics ; Patient Discharge ; Pneumonia, Viral ; diagnosis ; pathology ; therapy ; transmission ; Triage

BACKGROUND: Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. METHODS: From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. RESULTS: Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. CONCLUSIONS LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.
Aged ; Betacoronavirus ; Coronavirus Infections ; complications ; mortality ; Extracorporeal Membrane Oxygenation ; Humans ; Lung Transplantation ; methods ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; complications ; mortality ; Pulmonary Fibrosis ; mortality ; surgery ; Respiratory Distress Syndrome, Adult ; mortality ; surgery

Betacoronavirus ; Coronavirus Infections ; rehabilitation ; Critical Illness ; Hospitalization ; Humans ; Medicine, Chinese Traditional ; Pandemics ; Patient Education as Topic ; Pneumonia, Viral ; rehabilitation ; Respiratory Therapy ; methods

Antibodies, Viral ; blood ; Betacoronavirus ; Coronavirus ; immunology ; Coronavirus Infections ; immunology ; Humans ; Immunoglobulin G ; blood ; Pandemics ; Pneumonia, Viral ; immunology

Betacoronavirus ; genetics ; Coronavirus Infections ; diagnosis ; Genetic Variation ; Humans ; Pandemics ; Pneumonia, Viral ; diagnosis ; Real-Time Polymerase Chain Reaction ; methods

BACKGROUND: The 2019 novel coronavirus has caused the outbreak of the acute respiratory disease in Wuhan, Hubei Province of China since December 2019. This study was performed to analyze the clinical characteristics of patients who succumbed to and who recovered from 2019 novel coronavirus disease (COVID-19). METHODS: Clinical data were collected from two tertiary hospitals in Wuhan. A retrospective investigation was conducted to analyze the clinical characteristics of fatal cases of COVID-19 (death group) and we compare them with recovered patients (recovered group). Continuous variables were analyzed using the Mann-Whitney U test. Categorical variables were analyzed by χ test or Fisher exact test as appropriate. RESULTS: Our study enrolled 109 COVID-19 patients who died during hospitalization and 116 recovered patients. The median age of the death group was older than the recovered group (69 [62, 74] vs. 40 [33, 57] years, Z = 9.738, P < 0.001). More patients in the death group had underlying diseases (72.5% vs. 41.4%, χ = 22.105, P < 0.001). Patients in the death group had a significantly longer time of illness onset to hospitalization (10.0 [6.5, 12.0] vs. 7.0 [5.0, 10.0] days, Z = 3.216, P = 0.001). On admission, the proportions of patients with symptoms of dyspnea (70.6% vs. 19.0%, χ = 60.905, P < 0.001) and expectoration (32.1% vs. 12.1%, χ = 13.250, P < 0.001) were significantly higher in the death group. The blood oxygen saturation was significantly lower in the death group (85 [77, 91]% vs. 97 [95, 98]%, Z = 10.625, P < 0.001). The white blood cell (WBC) in death group was significantly higher on admission (7.23 [4.87, 11.17] vs. 4.52 [3.62, 5.88] ×10/L, Z = 7.618, P < 0.001). Patients in the death group exhibited significantly lower lymphocyte count (0.63 [0.40, 0.79] vs. 1.00 [0.72, 1.27] ×10/L, Z = 8.037, P < 0.001) and lymphocyte percentage (7.10 [4.45, 12.73]% vs. 23.50 [15.27, 31.25]%, Z = 10.315, P < 0.001) on admission, and the lymphocyte percentage continued to decrease during hospitalization (7.10 [4.45, 12.73]% vs. 2.91 [1.79, 6.13]%, Z = 5.242, P < 0.001). Alanine transaminase (22.00 [15.00, 34.00] vs. 18.70 [13.00, 30.38] U/L, Z = 2.592, P = 0.010), aspartate transaminase (34.00 [27.00, 47.00] vs. 22.00 [17.65, 31.75] U/L, Z = 7.308, P < 0.001), and creatinine levels (89.00 [72.00, 133.50] vs. 65.00 [54.60, 78.75] μmol/L, Z = 6.478, P < 0.001) were significantly higher in the death group than those in the recovered group. C-reactive protein (CRP) levels were also significantly higher in the death group on admission (109.25 [35.00, 170.28] vs. 3.22 [1.04, 21.80] mg/L, Z = 10.206, P < 0.001) and showed no significant improvement after treatment (109.25 [35.00, 170.28] vs. 81.60 [27.23, 179.08] mg/L, Z = 1.219, P = 0.233). The patients in the death group had more complications such as acute respiratory distress syndrome (ARDS) (89.9% vs. 8.6%, χ = 148.105, P < 0.001), acute cardiac injury (59.6% vs. 0.9%, χ = 93.222, P < 0.001), acute kidney injury (18.3% vs. 0%, χ = 23.257, P < 0.001), shock (11.9% vs. 0%, χ = 14.618, P < 0.001), and disseminated intravascular coagulation (DIC) (6.4% vs. 0%, χ = 7.655, P = 0.006). CONCLUSIONS Compared to the recovered group, more patients in the death group exhibited characteristics of advanced age, pre-existing comorbidities, dyspnea, oxygen saturation decrease, increased WBC count, decreased lymphocytes, and elevated CRP levels. More patients in the death group had complications such as ARDS, acute cardiac injury, acute kidney injury, shock, and DIC.
Adult ; Aged ; Aged, 80 and over ; Betacoronavirus ; C-Reactive Protein ; analysis ; Coronavirus Infections ; complications ; mortality ; Female ; Humans ; Male ; Middle Aged ; Oxygen ; blood ; Pandemics ; Pneumonia, Viral ; complications ; mortality ; Retrospective Studies

Antiviral Agents ; therapeutic use ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; Humans ; Pandemics ; Pneumonia, Viral ; drug therapy

BACKGROUND: At the end of 2019, a novel coronavirus outbreak causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation. METHODS: The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks. DISCUSSION: The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019. TRIAL REGISTRATION ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.
Betacoronavirus ; drug effects ; Coronavirus Infections ; drug therapy ; Glucocorticoids ; adverse effects ; therapeutic use ; Humans ; Pandemics ; Pneumonia, Viral ; drug therapy ; Randomized Controlled Trials as Topic ; Severity of Illness Index

Adult ; Aged ; Antiviral Agents ; administration & dosage ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; Drug Therapy, Combination ; Humans ; Interferon-alpha ; administration & dosage ; Lopinavir ; administration & dosage ; Middle Aged ; Pandemics ; Pneumonia, Viral ; drug therapy ; Randomized Controlled Trials as Topic ; Ribavirin ; administration & dosage ; Ritonavir ; administration & dosage