{"doi":"10.1016/j.ebiom.2020.103019","title":"The role for the metagenome in the pathogenesis of COVID-19","abstract":"The novel corona virus SARS-CoV-2 infection and the COVID-19 pandemic has become an unrelenting worldwide catastrophe of public health and an economic emergency. A key question concerning COVID-19 is why most infected persons do not develop severe disease, while others become critically ill [[1]Yang X. Yu Y. Xu J. Shu H. Xia J. Liu H. Wu Y. Zhang L. Yu Z. Fang M. Yu T. Wang Y. Pan S. Zou X. Yuan S. Shang Y Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.Lancet Respir Med. 2020; (PubMed PMID: 32105632; PMCID: PMC7102538)https://doi.org/10.1016/S2213-2600(20)30079-5Summary Full Text Full Text PDF Scopus (6641) Google Scholar]. We know that this dichotomy is related to age, gender, immunosuppression and comorbidities [[1]Yang X. Yu Y. Xu J. Shu H. Xia J. Liu H. Wu Y. Zhang L. Yu Z. Fang M. Yu T. Wang Y. Pan S. Zou X. Yuan S. Shang Y Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.Lancet Respir Med. 2020; (PubMed PMID: 32105632; PMCID: PMC7102538)https://doi.org/10.1016/S2213-2600(20)30079-5Summary Full Text Full Text PDF Scopus (6641) Google Scholar]. But many persons who are young succumb to the virus, and we need to know why. In a relatively short time, several major advances in the field led to the decoding of the viral genome, and modes of transmission, as well as mechanisms of immune response to the infection that mostly succeeds in clearance [[2]García L.F Immune response, inflammation, and the clinical spectrum of COVID-19.Front Immunol. 2020; 11https://doi.org/10.3389/fimmu.2020.01441Crossref Scopus (436) Google Scholar]. However, a significant percent of cases develop runaway inflammation that fails to clear the infection and result in sepsis like multi-organ failure and death [[2]García L.F Immune response, inflammation, and the clinical spectrum of COVID-19.Front Immunol. 2020; 11https://doi.org/10.3389/fimmu.2020.01441Crossref Scopus (436) Google Scholar]. Unlike SARS and MERS infections that result in higher morbidity, COVID-19 manifests in a highly variable response based on the pathophysiological status of the host. We propose that the metagenome directly contributes to this variable response (Fig. 1). Age and metabolic disorders such as obesity and type 2 diabetes are major risk factors for COVID-19 severity [[3]Petrilli C.M. Jones S.A. Yang J. Rajagopalan H. O'Donnell L. Chernyak Y. Tobin K.A. Cerfolio R.J. Francois F. Horwitz L.I Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study.BMJ. 2020; (369:m1966)https://doi.org/10.1136/bmj.m1966Crossref PubMed Scopus (1676) Google Scholar]. A common factor associated with aging and other COVID-19 risk factors is the dysbiosis of gut microbiota and resulting low grade inflammation with loss of epithelial barrier function [[4]Tilg H. Zmora N. Adolph T.E. Elinav E The intestinal microbiota fuelling metabolic inflammation.Nat Rev Immunol. 2020; 20 (Epub 2019/08/08PubMed PMID: 31388093): 40-54https://doi.org/10.1038/s41577-019-0198-4Crossref PubMed Scopus (493) Google Scholar]. An early study by Li et al. in Wuhan, reported a mean interval of 9.1–12.5 days between the onset of illness and hospitalization [[5]Li Q. Guan X. Wu P. Wang X. Zhou L. Tong Y. Ren R. Leung K.S.M. Lau E.H.Y. Wong J.Y. Xing X. Xiang N. Wu Y. Li C. Chen Q. Li D. Liu T. Zhao J. Liu M. Tu W. Chen C. Jin L. Yang R. Wang Q. Zhou S. Wang R. Liu H. Luo Y. Liu Y. Shao G. Li H. Tao Z. Yang Y. Deng Z. Liu B. Ma Z. Zhang Y. Shi G. Lam T.T.Y. Wu J.T. Gao G.F. Cowling B.J. Yang B. Leung G.M. Feng Z Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia.N Engl J Med. 2020; 382 (Epub 2020/01/30PubMed PMID: 31995857; PMCID: PMC7121484): 1199-1207https://doi.org/10.1056/NEJMoa2001316C","journal":"EBioMedicine","year":2020,"id":69352,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9576,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":367316,"name":"Bodduluri Haribabu","orcid":"0000-0002-8261-3294","position":1,"is_corresponding":false},{"id":367315,"name":"Robert P. Friedland","orcid":"0000-0001-5721-1843","position":0,"is_corresponding":true}],"reference_count":13,"raw_metadata":null,"created_at":"2026-07-18T21:42:22.705573Z","pmid":"33038769","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}