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Chronic obstructive pulmonary disease (COPD) is a major incurable global health burden and is currently the 4th largest cause of death in the world. Importantly, much of the disease burden and health care utilisation in COPD is associated with the management of its comorbidities (e.g. skeletal muscle wasting, ischemic heart disease, cognitive dysfunction) and infective viral and bacterial acute exacerbations (AECOPD). Current pharmacological treatments for COPD are relatively ineffective and the development of effective therapies has been severely hampered by the lack of understanding of the mechanisms and mediators underlying COPD. Since comorbidities have a tremendous impact on the prognosis and severity of COPD, the 2015 American Thoracic Society/European Respiratory Society (ATS/ERS) Research Statement on COPD urgently called for studies to elucidate the pathobiological mechanisms linking COPD to its comorbidities. It is now emerging that up to 50% of COPD patients have metabolic syndrome (MetS) as a comorbidity. It is currently not clear whether metabolic syndrome is an independent co-existing condition or a direct consequence of the progressive lung pathology in COPD patients. As MetS has important clinical implications on COPD outcomes, identification of disease mechanisms linking COPD to MetS is the key to effective therapy. In this comprehensive review, we discuss the potential mechanisms linking MetS to COPD and hence plausible therapeutic strategies to treat this debilitating comorbidity of COPD.

Highlights • The present review summarizes the plausible molecular mechanism of specific LH capsules in the control of SARS-COV-2 infection and the inhibition of cytokine storms caused by IL-6. • Preclinical and clinical trials of LH capsules in COVID-19 conducted in and outside China are elaborated. • A promising antiviral mechanism of LH capsules is defined, and the mechanism involving the suppression of inflammatory cytokine storms is explained. • Active substances in LH capsules that dock in ACE2 to prevent S protein binding are highlighted., Background In December 2019, a novel coronavirus, SARS-CoV-2 caused a series of acute atypical respiratory diseases worldwide. However, there is still a lack of drugs with clear curative effects, and the clinical trial research of vaccines has not been completely finished. Purpose LH capsules are approved TCM patent medicine that are widely used for the treatment of respiratory tract infectious diseases caused by colds and flu. On April 12, 2020, LH capsules and granules were officially repurposed by the China Food and Drug Administration (CFDA) for patients with mild COVID-19 based on their safety and efficacy demonstrated through multicentre, randomized, controlled clinical trials. We hope to conduct a comprehensive review of it through modern pharmacy methods, and try to explain its possible mechanism. Methods Using the full names of LH capsules Lianhuaqingwen, Lianhua Qingwen andSARS-COV-2, COVID-19 as the keywords of the search terms, systemically search for existing related papers in various databases such as Web of Science and PubMed. And completed the collection of clinical data in ClinicalTrials.gov and Chinese Clinical Trial Registry. Last but not least, we have sorted out the anti-inflammatory and antiviral mechanisms of LH capsules through literature and Selleck. Results This review systematically sorted out the active ingredients in LH capsules. Furthermore, the related pharmacological and clinical trials of LH capsule on SARS-CoV-2, IAV and IBV were discussed in detail. Moreover, the present review provides the first summary of the potential molecular mechanism of specific substances in LH capsules involved in resistance to SARS-COV-2 infection and the inhibition of cytokine storm syndrome (CSS) caused by IL-6. Conclusion This review summarizes the available reports and evidence that support the use of LH capsules as potential drug candidates for the prevention and treatment of COVID-19. However, TCM exerts its effects through multiple targets and multiple pathways, and LH capsules are not an exception. Therefore, the relevant mechanisms need to be further improved and experimentally verified., Graphical abstract Image, graphical abstract

Graphical abstract, Highlights • COVID-19 has led to serious death and lacks treatment strategies. • Lianhua Qingwen is a commonly used Chinese patent medicine to treat viral infection. • Lianhua Qingwen has antiviral, anti-inflammatory and immunoregulatory activities. • Lianhua Qingwen combined with conventional treatment obviously improved COVID-19. • Lianhua Qingwen can be a complementary strategy for treating COVID-19., Background An outbreak of Coronavirus Disease 2019 (COVID-19) which was infected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is still spreading and has led to unprecedented health emergency over the world. Though no specific drug has been developed so far, emerging agents have been confirmed effective or potentially beneficial to restrain it. Lianhua Qingwen (LHQW) is a commonly used Chinese medical preparation to treat viral influenza, including in the fight against SARS in 2002–2003 in China. Recent data also showed that LHQW played a vigorous role in COVID-19 treatment. Purpose This review will elucidate the pre-clinical and clinical evidence of LHQW in lung protection and antiviral activities, and provide timely data delivery for the exploration of effective treatment strategies in the therapy of COVID-19. Study design and method The research data were obtained from the academic databases (up to August 8, 2020) including Pubmed, CNKI and Web of Science, on ethnobotany and ethno medicines. The search keywords for screening the literature information were “virus”, “COVID-19”, or “SARS-CoV-2”, and “Lianhua Qingwen”. The documents were filtered and summarized for final evaluation. Results The collected evidence demonstrated that LHQW exhibited benefits against COVID-19. Impressively, LHQW in conjunction with conventional treatment could significantly improve COVID-19 patients as a synergetic strategy. The mechanisms were mainly involved the antiviral activity, and regulation of inflammation response as well as immune function. Conclusion Although the data were far from adequate, the latest advances had shown the benefits of LHQW in COVID-19, especially in combination with other antiviral drugs. This review provides comprehensive evidence of LHQW as a complementary strategy for treating COVID-19. Nevertheless, imperious researches should be conducted to clarify the unconfirmed effects, regulatory mechanisms and adverse reactions of LHQW in treating COVID-19 by means of well designed randomized controlled trials.

Highlights • In AECOPD contribution of respiratory viruses is largely unclear. • Literature of the prevalence of respiratory viruses in AECOPD was systematically evaluated. • Rhino-/enterovirus, RSV and influenza virus are the most prevalent viruses in AECOPD. • Adenovirus, hMPV and bocavirus appear not to be associated with AECOPD. • Detection rates vary between respiratory tract for different viruses., Background Despite the increasing knowledge on the role of viruses in exacerbations of COPD (AECOPD), it is less clear which viruses are involved and to what extent they contribute to exacerbations. This review aims to systematically combine and evaluate the available literature of the prevalence of respiratory viruses in patients with AECOPD, detected by PCR. Methods An electronic search strategy was performed on PubMed and Embase and reference lists were screened for eligible studies. Cross-sectional, prospective studies and case-control studies were included. The primary outcome measure was the prevalence of respiratory viruses (adenovirus, bocavirus, coronavirus, EBV, hMPV, influenza, parainfluenza, rhino-/enterovirus, RSV) in respiratory secretions of patients during an AECOPD. Secondary outcomes were the odds of the presence of the viruses in different respiratory secretions and the odds of the presence of viruses in upper and lower respiratory tract (URT/LRT) samples. Results Nineteen studies with 1728 patients were included. Rhino-/enteroviruses (16.39%), RSV (9.90%) and influenza (7.83%) were the most prevalent viruses detected with lower detection rates of coronaviruses (4.08%) and parainfluenza (3.35%). Adenovirus (2.07%), hMPV (2.78%) and bocaviruses (0.56%) appear to be rare causative agents of AECOPD. Definitive conclusions regarding the role of EBV cannot be made. Seven of the eight analyzed viruses had a higher prevalence in LRT samples. Coronaviruses were detected more frequently in the URT. Conclusions Respiratory viruses are frequently detected in both URT and LRT samples in AECOPD with rhino-/enteroviruses, RSV and influenza viruses the most prevalent viruses. Detection rates vary between the two sites for different viruses.