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 ; COVID-19 ; China ; Coronavirus Infections/therapy* ; Humans ; Pandemics/prevention & control* ; Pneumonia, Viral/therapy* ; SARS-CoV-2

Angiotensin II Type 1 Receptor Blockers/adverse effects* ; Angiotensin-Converting Enzyme 2 ; Angiotensin-Converting Enzyme Inhibitors/adverse effects* ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/etiology* ; Humans ; Pandemics ; Peptidyl-Dipeptidase A/physiology* ; Pneumonia, Viral/etiology* ; SARS-CoV-2

Betacoronavirus ; COVID-19 ; Coronavirus Infections/prevention & control* ; Humans ; Masks ; Pandemics/prevention & control* ; Pneumonia, Viral/prevention & control* ; SARS-CoV-2

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak occurred during the flu season around the world. This study aimed to analyze the impact of influenza A virus (IAV) exposure on COVID-19. METHODS: Seventy COVID-19 patients admitted to the hospital during January and February 2020 in Wuhan, China were included in this retrospective study. Serum tests including respiratory pathogen immunoglobulin M (IgM) and inflammation biomarkers were performed upon admission. Patients were divided into common, severe, and critical types according to disease severity. Symptoms, inflammation indices, disease severity, and fatality rate were compared between anti-IAV IgM-positive and anti-IAV IgM-negative groups. The effects of the empirical use of oseltamivir were also analyzed in both groups. For comparison between groups, t tests and the Mann-Whitney U test were used according to data distribution. The Chi-squared test was used to compare disease severity and fatality between groups. RESULTS: Thirty-two (45.71%) of the 70 patients had positive anti-IAV IgM. Compared with the IAV-negative group, the positive group showed significantly higher proportions of female patients (59.38% vs. 34.21%, χ = 4.43, P = 0.035) and patients with fatigue (59.38% vs. 34.21%, χ = 4.43, P = 0.035). The levels of soluble interleukin 2 receptor (median 791.00 vs. 1075.50 IU/mL, Z = -2.70, P = 0.007) and tumor necrosis factor α (median 10.75 vs. 11.50 pg/mL, Z = -2.18, P = 0.029) were significantly lower in the IAV-positive group. Furthermore, this group tended to have a higher proportion of critical patients (31.25% vs. 15.79%, P = 0.066) and a higher fatality rate (21.88% vs. 7.89%, P = 0.169). Notably, in the IAV-positive group, patients who received oseltamivir had a significantly lower fatality rate (0 vs. 36.84%, P = 0.025) compared with those not receiving oseltamivir. CONCLUSIONS The study suggests that during the flu season, close attention should be paid to the probability of IAV exposure in COVID-19 patients. Prospective studies with larger sample sizes are needed to clarify whether IAV increases the fatality rate of COVID-19 and to elucidate any benefits of empirical usage of oseltamivir.
Adult ; Aged ; Antibodies, Viral/blood* ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/mortality* ; Female ; Humans ; Immunoglobulin M/blood* ; Influenza A virus/immunology* ; Influenza, Human/complications* ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral/mortality* ; Retrospective Studies ; SARS-CoV-2 ; Severity of Illness Index

Adult ; Aged ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/diagnosis* ; Diagnosis, Differential ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia/diagnosis* ; Pneumonia, Viral/diagnosis* ; Retrospective Studies ; SARS-CoV-2

Aged ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/psychology* ; Family ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral/psychology* ; Retrospective Studies ; SARS-CoV-2 ; Severity of Illness Index

Betacoronavirus ; Biomedical Research ; COVID-19 ; Coronavirus Infections/mortality* ; Global Health ; Humans ; Pandemics ; Pneumonia, Viral/mortality* ; SARS-CoV-2

Corona virus disease 2019 (COVID-19) is a new type of coronavirus pneumonia, which is caused by infection of a novel coronavirus, SARS-CoV-2. The virus infects lung cells by binding angiotensin-converting enzyme 2 (ACE2) of cell surface, which leads to leukocyte infiltration, increased permeability of blood vessels and alveolar walls, and decreased surfactant in the lung, causing respiratory symptoms. The aggravation of local inflammation causes cytokine storm, resulting in systemic inflammatory response syndrome. In December 2019, a number of new pneumonia cases were reported by Wuhan Municipal Health Commission, after then a novel coronavirus was isolated and identified as SARS-CoV-2. To the date of Sep. 13th, 2020, COVID-19 is affecting 216 countries or regions, causing 28 637 952 cases, 917 417 deaths, and the mortality rate is 3.20%. This review will summarize the structure of SARS-CoV-2 and the pharmaceutical treatment of COVID-19, and their potential relationships.
Betacoronavirus ; COVID-19 ; Coronavirus Infections/drug therapy* ; Humans ; Pandemics ; Pneumonia, Viral ; SARS Virus ; SARS-CoV-2

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