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 common adverse reactions caused by poly (ADP-ribose) polymerase (PARP) inhibitors include hematological toxicity, gastrointestinal toxicity and fatigue. The main prevention and treatment of hematological toxicity include: regular blood tests, referral to hematology department when routine treatment is ineffective, and being alert of myelodysplastic syndrome/acute myeloid leukemia. The key points to deal with gastrointestinal toxicity include: taking medicine at the right time, light diet, appropriate amount of drinking water, timely symptomatic treatment, prevention of expected nausea and vomiting, and so on. For fatigue, full assessment should be completed before treatment because the causes of fatigue are various; the management includes massage therapy, psychosocial interventions and drugs such as methylphenidate and Panax quinquefolius according to the severity. In addition, niraparib and fluzoparib can cause hypertension, hypertensive crisis and palpitation. Blood pressure and heart rate monitoring, timely symptomatic treatment, and multidisciplinary consultation should be taken if necessary. When cough and dyspnea occur, high resolution CT and bronchoscopy should be performed to exclude pneumonia. If necessary, PARP inhibitors should be stopped, and glucocorticoid and antimicrobial therapy should be given. Finally, more attention should be paid to drug interaction management, patient self-management and regular monitoring to minimize the risk and harm of adverse reactions of PARP inhibitors.
Humans ; Poly(ADP-ribose) Polymerase Inhibitors/adverse effects* ; Phthalazines/pharmacology* ; Poly(ADP-ribose) Polymerases ; Fatigue/drug therapy*

BACKGROUND: Corona virus disease 2019 (COVID-19) has spread around the world since its outbreak, and there is no ascertained effective drug up to now. Lianhua Qingwen (LHQW) has been widely used in China and overseas Chinese, which had some advantages in the treatment of COVID-19. OBJECTIVE: To evaluate the efficacy and safety of LHQW for COVID-19 by conducting a systematic review with meta-analysis. METHODS: A comprehensive literature search was conducted in 12 electronic databases from their establishment to October 30, 2021. Note Express 3.2.0 was used for screening of trials, and the data was independently extracted in duplicate by 2 researchers. The risk of bias of randomized controlled trials (RCTs) and retrospective studies were assessed by using the Cochrane collaboration tool and Newcastle Ottawa Scale, respectively, followed by data analysis using RevMan 5.3. The RCTs or retrospective studies to treat COVID-19 using LHQW were included. The intervention measures in the experimental group were LHQW alone or combined with chemical drugs (LCWC), and that in the control group were chemical drugs (CDs). Outcome measures included computed tomography (CT) recovery rate, disappearance rates of primary (fever, cough, fatigue), respiratory, gastrointestinal and other symptoms, exacerbation rate and adverse reaction. Subgroup analysis was conducted according to whether LHQW was combined with CDs and the different treatment methods in the control group. RESULTS: Nine trials with 1,152 participants with COVID-19 were included. The CT recovery rates of LHQW and LCWC were 1.36 and 1.32 times of CDs, respectively (P<0.05). Compared with CDs, LCWC remarkably increased the disappearance rates of fever, cough, fatigue, expectoration, shortness of breath, and muscle soreness (P<0.05). LHQW also obviously decreased the exacerbation rate, which was 0.45 times of CDs alone (P<0.05). There was no obvious difference between LCWC and CDs in adverse reaction (P>0.05). CONCLUSIONS LHQW was more suitable for treating COVID-19 patients with obvious expectoration, shortness of breath and muscle soreness. LHQW had advantages in treating COVID-19 with no obvious exacerbation. (PROSPERO No. CRD42021235937).
COVID-19/drug therapy* ; Cough/drug therapy* ; Drugs, Chinese Herbal/adverse effects* ; Dyspnea/drug therapy* ; Fatigue/drug therapy* ; Humans ; Myalgia/drug therapy*

This study aims to obtain higher-level evidence by overviewing the Meta-analysis of Lianhua Qingwen preparations in the treatment of viral diseases including influenza, coronavirus disease 2019(COVID-19), and hand, foot and mouth disease(HFMD). CNKI, Wanfang, VIP, China Clinical Trial Registry(ChiCTR), PubMed, EMbase, Web of Science, and Cochrane Library were searched for the Meta-analysis about the treatment of viral diseases with Lianhua Qingwen preparations from the database establishment to April 1, 2022. After literature screening and data extraction, AMSTAR2 and the grading of recommendations assessment, development and evaluations(GRADE) system were used to assess the methodological quality and evidence quality, respectively, and then the efficacy and safety outcomes of Lianhua Qingwen preparations in the treatment of viral diseases were summarized. Thirteen Meta-analysis were finally included, three of which were rated as low grade by AMSTAR2 and ten as very low grade. A total of 75 outcome indicators were obtained, involving influenza, COVID-19, and HFMD. According to the GRADE scoring results, the 75 outcome indicators included 5(6.7%) high-level indicators, 18(24.0%) mediate-level indicators, 25(33.3%) low-level evidence indicators, and 27(36.0%) very low-level indicators.(1)In the treatment of influenza, Lianhua Qingwen preparations exhibited better clinical efficacy than other Chinese patent medicines and Ribavirin and had similar clinical efficacy compared with Oseltamivir. Lianhua Qingwen preparations were superior to other Chinese patent medicines, Oseltamivir, and Ribavirin in alleviating clinical symptoms. They showed no significant differences from Oseltamivir or conventional anti-influenza treatment in terms of the time to and rate of negative result of viral nucleic acid test.(2)In the treatment of COVID-19, Lianhua Qingwen preparation alone or combined with conventional treatment was superior to conventional treatment in terms of total effective rate, main symptom subsidence rate and time, fever clearance rate, duration of fever, time to fever clearance, cough subsidence rate, time to cough subsidence, fatigue subsidence rate, time to fatigue subsidence, myalgia subsidence rate, expectoration subsidence rate, chest tightness subsidence rate, etc. Lianhua Qingwen preparations no difference from conventional treatment in terms of subsiding sore throat, nausea, diarrhea, loss of appetite, headache, and dyspnea. In terms of chest CT improvement rate, rate of progression to severe case, cure time, and hospitalization time, Lianhua Qingwen alone or in combination with conventional treatment was superior to conventional treatment.(3)In the treatment of HFMD, Lianhua Qingwen Granules was superior to conventional treatment in terms of total effective rate, average fever clearance time, time to herpes subsidence, and time to negative result of viral nucleic acid test.(4)In terms of safety, Lianhua Qingwen preparations led to low incidence of adverse reactions, all of which were mild and disappeared after drug withdrawal. The available evidence suggests that in the treatment of influenza, COVID-19, and HFMD, Lianhua Qingwen preparations can relieve the clinical symptoms, shorten the hospitalization time, and improve the chest CT. They have therapeutic effect and good safety in the treatment of viral diseases. However, due to the low quality of available studies, more high-quality clinical trials are needed to support the above conclusions.
Cough ; Drugs, Chinese Herbal/therapeutic use* ; Fatigue ; Fever/drug therapy* ; Humans ; Influenza, Human/drug therapy* ; Meta-Analysis as Topic ; Nonprescription Drugs/therapeutic use* ; Nucleic Acids/therapeutic use* ; Oseltamivir/therapeutic use* ; Ribavirin/therapeutic use* ; COVID-19 Drug Treatment

OBJECTIVE: To investigate the effect of M3P (containing Deer antler, Cordyceps sinensis, Rhodiola rosea, and Panax ginseng); an herbal remedy with the function of tonifying Kidney (Shen) and invigorating Spleen (Pi), replenishing qi and nourishing blood; on fatigue alleviation, endurance capacity and toxicity. METHODS: Swimming with weight-loading of 24 male ICR mice was used to evaluate the endurance capacity, and fatigue-related plasma biomarkers were determined. Mice were randomly assigned to control or M3P treatment groups with 6 mice for each group and were orally administered with M3P everyday for 8 weeks at doses 0, 10, 33 or 100 mg/kg. Swimming time to exhaustion was measured in a specialized water tank. Lliver and kidney functions, body weight, and hematological profile were determined to evaluate the safety and toxicity after long-term M3P administration. RESULTS: M3P supplementation 100 mg/kg significantly increased swimming endurance time up to approximate 2.4 folds of controls (P<0.05). The plasma concentrations of cortisol and hepatic glycogen content were significantly increased in mice received M3P (P<0.05, P<0.01 respectively). The lactic acid level and blood glucose were not changed after M3P treatment (P>0.05). The liver and kidney functions muscle damage biomarker creatine, body weight, and hemograms were not altered in M3P supplementation (P>0.05). CONCLUSION M3P supplementation may improve swimming endurance accompanied by increasing hepatic glycogen content and serum cortisol level without major toxicity.
Animals ; Body Weight ; Deer ; Dietary Supplements ; Fatigue/drug therapy* ; Hydrocortisone ; Liver Glycogen ; Male ; Mice ; Mice, Inbred ICR ; Muscle, Skeletal ; Swimming/physiology*

OBJECTIVE: To evaluate the effectiveness and safety of Baidu Jieduan Granules (BDJDG) to treat common type coronavirus disease 2019 (COVID-19). METHODS: This multicenter, retrospective, and observational clinical trial included 230 common COVID-19 patients in Leishenshan, Huangshi, and Laohekou Hospitals in Wuhan from January 21 to March 26, 2020. The included patients were further divided into two subgroups according to the use of supplemental oxygen, mild and moderate groups. During the first 14 d of hospitalization, all patients were administered BDJDG combined with conventional Western medicine, and observed for continuous 28 d. Primary outcomes were disease progression rate and discharge rate. Secondary outcomes included negative conversion time of nucleic acid, hospitalization duration, clinical symptom subsidence time, and symptom regression rate. RESULTS: A total of 230 common COVID-19 patients were analyzed (138 in moderate group and 92 in mild group). By day 28, the disease progression rate was 4.3% and the discharge rate was 95.7%. All mild cases recovered and were discharged from hospital. The median negative conversion time of nucleic acid of all 230 COVID-19 patients was 12 d [inter-quartile range (IQR) 3.5-17], the median hospitalization duration was 15 d (IQR 12-20). The median time to fever, cough, and fatigue recovery was 4 d (IQR 2-6), 8 d (IQR 5-12), and 8 d (IQR 5-11). The recovery rate of fever, cough, and fatigue was 94.6%, 90.5%, and 93.5%. The median time to clinical improvement was 12 d (IQR 10-17). Compared with the baseline, total leukocyte counts, neutrophil counts, lymphocyte counts, and platelet counts were increased significantly on days 7 and 14 (P<0.01). C-reactive protein markedly increased on day 3 and significantly decreased on days 7 and 14 (P<0.01). No serious adverse events occurred during treatment. CONCLUSION BDJDG may be effective and safe for treatment of common type COVID-19. (Registration No. ChiCTR2000030836).
C-Reactive Protein ; China ; Cough/drug therapy* ; Disease Progression ; Fatigue ; Fever ; Humans ; Nucleic Acids ; Oxygen ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome ; COVID-19 Drug Treatment

fatigue (37.5%), and hand-foot syndrome (27.08%). Most of them were grade 1–2, and no drug-related death occurred.CONCLUSIONS: Apatinib can improve the disease control rate of recurrent and metastatic cervical cancer when chemotherapy has failed, and the treatment is well tolerated. This represents that apatinib may be a new treatment option for metastatic cervical cancer patients.]]>
Adenocarcinoma ; Carcinoma, Adenosquamous ; Carcinoma, Squamous Cell ; Disease-Free Survival ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; Fatigue ; Follow-Up Studies ; Hand-Foot Syndrome ; Hemorrhage ; Humans ; Hypertension ; Leukopenia ; Molecular Targeted Therapy ; Neutropenia ; Proteinuria ; Radiotherapy ; Retrospective Studies ; Uterine Cervical Neoplasms

BACKGROUND/AIMS: This study was conducted to identify risk factors that predict vulnerability to cancer therapy on the basis of the clinical, geriatric, and quality of life assessment before starting treatment in elderly patients. METHODS: Seventy-five patients aged 65 years and over with newly diagnosed stage IV solid cancer receiving chemotherapy were analyzed. Clinical and laboratory data were collected. The geriatric assessment was performed using the Korean versions of the Modified Barthel Index, Instrumental Activities of Daily Living, Mini-Mental State Examination, and Geriatric Depression Scale. The European Organisation for Research and Treatment of Cancer Quality-of-Life Core Questionnaire (EORTC-QLQ-C30) was also performed. RESULTS: Forty-one patients stopped cancer treatment during or after the end of first-line therapy and were classified as the treatment interruption group. By univariate analysis, treatment interruption was associated with metastases to ≥ 2 distant sites, lower albumin level, lower EORTC-QLQ-C30 physical and role functioning scores, and higher EORTC-QLQ-C30 fatigue and appetite loss symptom scores. By multivariate analysis, treatment interruption was significantly associated with low score for the EORTC-QLQ-C30 physical functioning scale (odds ratio [OR], 1.020; 95% confidence interval [CI], 1.002 to 1.039; p = 0.030), and ≥ 2 sites of distant metastases (OR, 2.965; 95% CI, 1.012 to 8.681; p = 0.047). CONCLUSIONS: The EORTC-QLQ-C30 physical functioning score and metastases to ≥ 2 organs, which indicate a poor physical functional status and metastatic high tumor burden, were significantly associated with interruption of first-line treatment in elderly patients with cancer.
Activities of Daily Living ; Aged* ; Appetite ; Depression ; Drug Therapy ; Fatigue ; Geriatric Assessment ; Humans ; Multivariate Analysis ; Neoplasm Metastasis ; Quality of Life ; Risk Factors ; Tumor Burden

PURPOSE: This study was to identify changes in cognitive function and fatigue following chemotherapy in patients with stomach or colorectal cancer. METHODS: Of the participants, 67 underwent adjuvant chemotherapy, while 66 healthy participants made up the comparison group. Three assessment tools were used: 1) the Korean Mini-Mental State Examination; 2) Everyday Cognition; 3) Functional Assessment of Chronic Illness Therapy-Fatigue. The questionnaires were administered in three stages, before chemotherapy, towards the end of chemotherapy, and 6 months after the final chemotherapy session. Data were analyzed using descriptive statistics and repeated measures analysis of variance (RM ANOVA). RESULTS: At the post-chemotherapy stage, 38.8% of the patients who underwent adjuvant chemotherapy complained of subjective cognitive impairment and reported greater difficulty in the cognitive domains of attention and concentration, memory, and executive function. RM ANOVA revealed a significant decline in cognitive function after chemotherapy. However, improvement was observed six months after the completion of chemotherapy (F=42.68, p< .001). Cancer-related fatigue also showed similar patterns as observed in the case of cognitive function (F=44.76, p< .001). CONCLUSION: Chemotherapy was associated with increased cognitive decline and fatigue in cancer patients with cancer. Nursing intervention programs need to be developed to counteract cognitive decline and fatigue in patients undergoing chemotherapy.
Chemotherapy, Adjuvant ; Chronic Disease ; Cognition Disorders ; Cognition ; Colorectal Neoplasms ; Drug Therapy ; Executive Function ; Fatigue ; Gastrointestinal Neoplasms ; Healthy Volunteers ; Humans ; Longitudinal Studies ; Memory ; Nursing ; Prospective Studies ; Stomach

PURPOSE: Treatment targeting immune checkpoint with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has demonstrated efficacy and tolerability in the treatment of metastatic urothelial carcinoma (mUC). We investigated the efficacy and safety of atezolizumab in mUC patients who failed platinum-based chemotherapy. MATERIALS AND METHODS: A retrospective study using the Samsung Medical Center cancer chemotherapy registry was performed on 50 consecutive patients with mUC treated with atezolizumab, regardless of their PD-L1(SP142) status, as salvage therapy after chemotherapy failure between May 2017 and June 2018. Endpoints included overall response rate (RR), progression-free survival (PFS), and safety. RESULTS: Among 50 patients, men constituted 76% and the median age was 68 years (range, 46 to 82 years). Twenty-three patients (46%) received atezolizumab as second-line therapy. PD-L1 (SP142) status IC0/1 and IC2/3 were found in 21 (42%) and 21 (42%) of patients, respectively; in eight patients (16%), PD-L1 (SP142) expression was not available. Atezolizumab was generally well tolerated, with pruritus and fatigue being the most commonly observed toxicities. As a result, partial response was noted in 20 patients (40%), with 12 (24%) stable diseases. RRwas higherin IC2/3 (62%) than in IC0/1 patients (24%, p=0.013). The median PFS was 7.4 months (95% confidence interval, 3.4 to 11.4 months). As expected, PFS also was significantly longer in IC2/3 patients than in IC0/1 (median, 12.7 vs. 2.1 months; p=0.005). PFS was not significantly influenced by age, sex, performance status, number of previous chemotherapy, site of metastases, or any of the baseline laboratory parameters. CONCLUSION: In this retrospective study, atezolizumab demonstrated clinically efficacy and tolerability in unselected mUC patients who failed platinum-based chemotherapy.
Disease-Free Survival ; Drug Therapy ; Fatigue ; Humans ; Male ; Neoplasm Metastasis ; Pruritus ; Retrospective Studies ; Salvage Therapy