The effect of Chinese herbal medicine on digestive system and liver functions should not be neglected in COVID-19: an updated systematic review and meta-analysis

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has spread rapidly around the world, with substantial mortality, since December 2019. To date, the relevant treatments to contain the disease include not only antiviral medications, antibacterial medications, steroids and human immunoglobulin, but Chinese herbal medicines (CHM) showing promise. CHM, recommended in national treatment guidelines in China, has been used to treat patients with COVID-19 effectively in clinic. Although, respiratory tract manifestations such as fever and cough are the most commonly reported symptoms in patients with COVID-19, digestive symptoms and liver injury are not uncommon in patients with COVID-19. Emerging data showed that the gastrointestinal tract and liver also represent target organs of SARS-CoV-2 on the basis of the findings that angiotensin-converting enzyme 2 (ACE2), the major receptor of SARS-CoV-2, is expressed in the gastrointestinal tract as well as liver cells.However, to the best of our knowledge, CHM as an adjuvant medicine for improving gastrointestinal symptoms and liver functions in COVID-19 has not been well studied with definitive results by the evidence assessment. Although the use of CHM shows promise, the evidence supporting its use in the treatment of COVID-19 remains limited, and thus our systematic review and meta‐analysis are necessary. We will conduct a systematic review and meta-analysis of emerging studies reporting gastrointestinal symptoms and liver function in COVID-19 patients treated with CHM plus conventional pharmacotherapy. A systematic literature search of the PubMed, ScienceDirect, Web of science, Scopus, Google Scholar, WorldCat Dissertations database and Index to Theses, PsycINFO, ProQuest, the Chinese National Knowledge Infrastructure, the VIP Information Database, and the Wanfang Database was conducted on November 8, 2020 (updated February 9, 2021) for relevant articles including accepted pre-proof publications in the last 1 year, to identify the latest information on COVID-19. The following grouped terms were used as search strategy and modified to suit each database to screen publications that might be valuable for the present review: (“coronavirus disease 2019” OR “COVID-19” OR “severe acute respiratory syndrome coronavirus 2” OR “SARS-CoV-2” OR “coronavirus” OR “novel coronavirus” OR “nCoV” OR “2019-nCoV”) AND (“Medicine, Chinese Traditional’ OR “Traditional Medicine, Chinese” OR “Chinese herbal medicine” OR “traditional Chinese medicine” OR “Chinese Traditional Medicine” OR “Chinese Medicine, Traditional” OR “Chinese medicine formulae“ OR “Chinese medicine formulations” OR “Chinese herb” OR “Chinese herb therapy” OR “herbal medicine” OR “herb remedy” OR “herb therapy” OR “Zhong Yi Xue” OR “Chung I Hsueh” OR “Hsueh, Chung I”). Given the urgency of treating COVID-19, a grey literature search was also performed. Furthermore, COVID-19 articles in the WHO database and some key journals in this field including New England Journal of Medicine, BMJ, the Lancet COVID-19 Resource Centre and JAMA were searched manually for potentially relevant publications. Additional articles were retrieved by hand based on the reference lists of relevant papers.