{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:19:37Z","timestamp":1792027177544,"version":"4.4.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T00:00:00Z","timestamp":1657584000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T00:00:00Z","timestamp":1657584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K23HL138461-01A1"],"award-info":[{"award-number":["K23HL138461-01A1"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genome Med"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Antimicrobial resistance (AMR) is rising at an alarming rate and complicating the management of infectious diseases including lower respiratory tract infections (LRTI). Metagenomic next-generation sequencing (mNGS) is a recently established method for culture-independent LRTI diagnosis, but its utility for predicting AMR has remained unclear. We aimed to assess the performance of mNGS for AMR prediction in bacterial LRTI and demonstrate proof of concept for epidemiological AMR surveillance and rapid AMR gene detection using Cas9 enrichment and nanopore sequencing.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We studied 88 patients with acute respiratory failure between 07\/2013 and 9\/2018, enrolled through a previous observational study of LRTI. Inclusion criteria were age\u2009\u2265\u200918, need for mechanical ventilation, and respiratory specimen collection within 72\u00a0h of intubation. Exclusion criteria were decline of study participation, unclear LRTI status, or no matched RNA and DNA mNGS data from a respiratory specimen. Patients with LRTI were identified by clinical adjudication. mNGS was performed on lower respiratory tract specimens. The primary outcome was mNGS performance for predicting phenotypic antimicrobial susceptibility and was assessed in patients with LRTI from culture-confirmed bacterial pathogens with clinical antimicrobial susceptibility testing (<jats:italic>n<\/jats:italic>\u2009=\u200927 patients, <jats:italic>n<\/jats:italic>\u2009=\u200932 pathogens). Secondary outcomes included the association between hospital exposure and AMR gene burden in the respiratory microbiome (<jats:italic>n<\/jats:italic>\u2009=\u200988 patients), and AMR gene detection using Cas9 targeted enrichment and nanopore sequencing (<jats:italic>n<\/jats:italic>\u2009=\u200910 patients).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Compared to clinical antimicrobial susceptibility testing, the performance of respiratory mNGS for predicting AMR varied by pathogen, antimicrobial, and nucleic acid type sequenced. For gram-positive bacteria, a combination of RNA\u2009+\u2009DNA mNGS achieved a sensitivity of 70% (95% confidence interval (CI) 47\u201387%) and specificity of 95% (CI 85\u201399%). For gram-negative bacteria, sensitivity was 100% (CI 87\u2013100%) and specificity 64% (CI 48\u201378%). Patients with hospital-onset LRTI had a greater AMR gene burden in their respiratory microbiome versus those with community-onset LRTI (<jats:italic>p<\/jats:italic>\u2009=\u20090.00030), or those without LRTI (<jats:italic>p<\/jats:italic>\u2009=\u20090.0024). We found that Cas9 targeted sequencing could enrich for low abundance AMR genes by\u2009&gt;\u20092500-fold and enabled their rapid detection using a nanopore platform.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>mNGS has utility for the detection and surveillance of resistant bacterial LRTI pathogens.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13073-022-01072-4","type":"journal-article","created":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T23:02:22Z","timestamp":1657580542000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":102,"title":["Metagenomic prediction of antimicrobial resistance in critically ill patients with lower respiratory tract infections"],"prefix":"10.1186","volume":"14","author":[{"given":"Paula Hayakawa","family":"Serpa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianding","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazin","family":"Abdelghany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Crawford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Malcolm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saharai","family":"Caldera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Fung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"McGeever","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina L.","family":"Kalantar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Lyden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajani","family":"Ghale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Deiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma","family":"Neff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah B.","family":"Doernberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles Y.","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L.","family":"DeRisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn S.","family":"Calfee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R.","family":"Langelier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,12]]},"reference":[{"key":"1072_CR1","unstructured":"O\u2019Neill J. Tackling drug-resistant infections globally: final report and recommendations. London, UK May 16, 2016 2016. 2016; published online May 16. http:\/\/amr-review.org\/Publications."},{"key":"1072_CR2","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/j.molmed.2014.08.001","volume":"20","author":"AK Zaas","year":"2014","unstructured":"Zaas AK, Garner BH, Tsalik EL, Burke T, Woods CW, Ginsburg GS. The current epidemiology and clinical decisions surrounding acute respiratory infections. Trends Mol Med. 2014;20:579\u201388.","journal-title":"Trends Mol Med"},{"key":"1072_CR3","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1136\/thx.2004.030411","volume":"60","author":"MM van der Eerden","year":"2005","unstructured":"van der Eerden MM, Vlaspolder F, de Graaff CS, et al. Comparison between pathogen directed antibiotic treatment and empirical broad spectrum antibiotic treatment in patients with community acquired pneumonia: a prospective randomised study. Thorax. 2005;60:672\u20138.","journal-title":"Thorax"},{"key":"1072_CR4","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1056\/NEJMoa1500245","volume":"373","author":"S Jain","year":"2015","unstructured":"Jain S, Self WH, Wunderink RG, et al. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med. 2015;373:415\u201327.","journal-title":"N Engl J Med"},{"key":"1072_CR5","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1056\/NEJMra1403772","volume":"372","author":"DA Leffler","year":"2015","unstructured":"Leffler DA, Lamont JT. Clostridium difficile infection. N Engl J Med. 2015;372:1539\u201348.","journal-title":"N Engl J Med"},{"issue":"52","key":"1072_CR6","doi-asserted-by":"publisher","first-page":"E12353","DOI":"10.1073\/pnas.1809700115","volume":"115","author":"C Langelier","year":"2018","unstructured":"Langelier C, Kalantar KL, Moazed F, et al. Integrating host response and unbiased microbe detection for lower respiratory tract infection diagnosis in critically ill adults. Proc Natl Acad Sci USA. 2018;115(52):E12353\u201362 (201809700).","journal-title":"Proc Natl Acad Sci USA"},{"key":"1072_CR7","doi-asserted-by":"publisher","first-page":"3099","DOI":"10.1093\/jac\/dkaa257","volume":"75","author":"N Mahfouz","year":"2020","unstructured":"Mahfouz N, Ferreira I, Beisken S, von Haeseler A, Posch AE. Large-scale assessment of antimicrobial resistance marker databases for genetic phenotype prediction: a systematic review. J Antimicrob Chemother. 2020;75:3099\u2013108.","journal-title":"J Antimicrob Chemother"},{"key":"1072_CR8","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/s41587-019-0156-5","volume":"37","author":"T Charalampous","year":"2019","unstructured":"Charalampous T, Kay GL, Richardson H, et al. Nanopore metagenomics enables rapid clinical diagnosis of bacterial lower respiratory infection. Nat Biotechnol. 2019;37:783\u201392.","journal-title":"Nat Biotechnol"},{"key":"1072_CR9","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1186\/s12931-019-1218-4","volume":"20","author":"L Yang","year":"2019","unstructured":"Yang L, Haidar G, Zia H, et al. Metagenomic identification of severe pneumonia pathogens in mechanically-ventilated patients: a feasibility and clinical validity study. Respir Res. 2019;20:265.","journal-title":"Respir Res"},{"key":"1072_CR10","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1186\/s13073-021-00991-y","volume":"13","author":"T Charalampous","year":"2021","unstructured":"Charalampous T, Alcolea-Medina A, Snell LB, et al. Evaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded COVID-19 intensive care units. Genome Med. 2021;13:182.","journal-title":"Genome Med"},{"key":"1072_CR11","doi-asserted-by":"publisher","first-page":"1644","DOI":"10.21037\/atm-20-7081","volume":"8","author":"L Chao","year":"2020","unstructured":"Chao L, Li J, Zhang Y, Pu H, Yan X. Application of next generation sequencing-based rapid detection platform for microbiological diagnosis and drug resistance prediction in acute lower respiratory infection. Ann Transl Med. 2020;8:1644.","journal-title":"Ann Transl Med"},{"key":"1072_CR12","doi-asserted-by":"publisher","unstructured":"Quan J, Langelier C, Kuchta A, et al. FLASH: a next-generation CRISPR diagnostic for multiplexed detection of antimicrobial resistance sequences. Nucleic Acids Res 2019; published online May 22. https:\/\/doi.org\/10.1093\/nar\/gkz418.","DOI":"10.1093\/nar\/gkz418"},{"key":"1072_CR13","unstructured":"United States Centers for Disease Control and Prevention. CDC\/NHSN surveillance definitions for specific types of infections. 2021; published online Jan. https:\/\/www.cdc.gov\/nhsn\/pdfs\/pscmanual\/pcsmanual_current.pdf."},{"key":"1072_CR14","doi-asserted-by":"publisher","unstructured":"Kalantar KL, Carvalho T, de Bourcy CFA, et al. IDseq\u2014An open source cloud-based pipeline and analysis service for metagenomic pathogen detection and monitoring. Gigascience 2020; 9. https:\/\/doi.org\/10.1093\/gigascience\/giaa111.","DOI":"10.1093\/gigascience\/giaa111"},{"key":"1072_CR15","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15\u201321.","journal-title":"Bioinformatics"},{"key":"1072_CR16","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1534\/g3.113.005967","volume":"3","author":"JG Ruby","year":"2013","unstructured":"Ruby JG, Bellare P, Derisi JL. PRICE: software for the targeted assembly of components of (Meta) genomic sequence data. G3 (Bethesda). 2013;3:865\u201380.","journal-title":"G3 (Bethesda)"},{"key":"1072_CR17","doi-asserted-by":"publisher","first-page":"e284","DOI":"10.1016\/S2666-5247(21)00304-9","volume":"3","author":"A Tsitsiklis","year":"2022","unstructured":"Tsitsiklis A, Osborne CM, Kamm J, et al. Lower respiratory tract infections in children requiring mechanical ventilation: a multicentre prospective surveillance study incorporating airway metagenomics. Lancet Microbe. 2022;3:e284\u201393.","journal-title":"Lancet Microbe"},{"key":"1072_CR18","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1056\/NEJMoa1500245","volume":"373","author":"S Jain","year":"2015","unstructured":"Jain S, Self WH, Wunderink RG, et al. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med. 2015;373:415\u201327.","journal-title":"N Engl J Med"},{"key":"1072_CR19","doi-asserted-by":"publisher","unstructured":"Infection in Organ Transplantation - Fishman - 2017 - American Journal of Transplantation - Wiley Online Library. https:\/\/doi.org\/10.1111\/ajt.14208 (Accessed 21 Jul 2021).","DOI":"10.1111\/ajt.14208"},{"key":"1072_CR20","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1056\/NEJMoa1306801","volume":"370","author":"SS Magill","year":"2014","unstructured":"Magill SS, Edwards JR, Bamberg W, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014;370:1198\u2013208.","journal-title":"N Engl J Med"},{"key":"1072_CR21","doi-asserted-by":"publisher","first-page":"e61","DOI":"10.1093\/cid\/ciw353","volume":"63","author":"AC Kalil","year":"2016","unstructured":"Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63:e61-111.","journal-title":"Clin Infect Dis"},{"issue":"Suppl 2","key":"1072_CR22","doi-asserted-by":"publisher","first-page":"S27","DOI":"10.1086\/511159","volume":"44","author":"LA Mandell","year":"2007","unstructured":"Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America\/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44(Suppl 2):S27-72.","journal-title":"Clin Infect Dis"},{"key":"1072_CR23","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s13073-014-0090-6","volume":"6","author":"M Inouye","year":"2014","unstructured":"Inouye M, Dashnow H, Raven L-A, et al. SRST2: Rapid genomic surveillance for public health and hospital microbiology labs. Genome Med. 2014;6:90.","journal-title":"Genome Med"},{"key":"1072_CR24","doi-asserted-by":"publisher","first-page":"D566","DOI":"10.1093\/nar\/gkw1004","volume":"45","author":"B Jia","year":"2017","unstructured":"Jia B, Raphenya AR, Alcock B, et al. CARD 2017: expansion and model-centric curation of the comprehensive antibiotic resistance database. Nucleic Acids Res. 2017;45:D566\u201373.","journal-title":"Nucleic Acids Res"},{"key":"1072_CR25","unstructured":"CLSI. CLSI M100-ED31:2021 Performance Standards for Antimicrobial Susceptibility Testing, 31st Edition. 2021; published online March. http:\/\/em100.edaptivedocs.net\/dashboard.aspx."},{"key":"1072_CR26","unstructured":"Quan J, Langelier CR, Batson J, Crawford ED. FLASHit. Github. https:\/\/github.com\/czbiohub\/flash 2020."},{"key":"1072_CR27","doi-asserted-by":"publisher","unstructured":"Deng X, Achari A, Federman S, et al. Metagenomic sequencing with spiked primer enrichment for viral diagnostics and genomic surveillance. Nature Microbiology 2020; published online Jan 13. https:\/\/doi.org\/10.1038\/s41564-019-0637-9.","DOI":"10.1038\/s41564-019-0637-9"},{"key":"1072_CR28","unstructured":"Chiu CY, Stryke D. SURPI+, a rapid computational pipeline for comprehensive identification of pathogens from clinical metagenomic sequence data. Github. https:\/\/github.com\/chiulab\/SURPI-plus-dist 2019.\u00a0"},{"key":"1072_CR29","doi-asserted-by":"crossref","unstructured":"New England Biolabs. Improved library preparation with the NEBNext\u00ae UltraTM II DNA Library Prep Kit for Illumina. https:\/\/www.neb-online.de\/wp-content\/uploads\/2020\/03\/Improved-library-preparation-with-the-NEBNext-Ultra-II-DNA-Library-Prep-Kit-for-Illumina-E7645.pdf (Accessed 9 Dec 2021).","DOI":"10.17504\/protocols.io.j8epv5edv1bz\/v3"},{"key":"1072_CR30","doi-asserted-by":"publisher","first-page":"e61","DOI":"10.1093\/cid\/ciw353","volume":"63","author":"AC Kalil","year":"2016","unstructured":"Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63:e61-111.","journal-title":"Clin Infect Dis"},{"key":"1072_CR31","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s13073-015-0220-9","volume":"7","author":"AL Greninger","year":"2015","unstructured":"Greninger AL, Naccache SN, Federman S, et al. Rapid metagenomic identification of viral pathogens in clinical samples by real-time nanopore sequencing analysis. Genome Med. 2015;7:99. https:\/\/doi.org\/10.1186\/s13073-015-0220-9.","journal-title":"Genome Med"},{"key":"1072_CR32","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s13059-018-1462-9","volume":"19","author":"FJ Rang","year":"2018","unstructured":"Rang FJ, Kloosterman WP, de Ridder J. From squiggle to basepair: computational approaches for improving nanopore sequencing read accuracy. Genome Biol. 2018;19:90. https:\/\/doi.org\/10.1186\/s13059-018-1462-9.","journal-title":"Genome Biol"},{"key":"1072_CR33","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1186\/s13054-019-2632-1","volume":"23","author":"C-C Lee","year":"2019","unstructured":"Lee C-C, Lee C-H, Yang C-Y, Hsieh C-C, Tang H-J, Ko W-C. Beneficial effects of early empirical administration of appropriate antimicrobials on survival and defervescence in adults with community-onset bacteremia. Crit Care. 2019;23:363.","journal-title":"Crit Care"},{"key":"1072_CR34","unstructured":"Illumina, Inc. Run time estimates for each sequencing step on the Illumina sequencing platforms. 2020; published online May 15. https:\/\/emea.support.illumina.com\/bulletins\/2017\/02\/run-time-estimates-for-each-sequencing-step-on-illumina-sequenci.html (Accessed 9 Dec 2021)."},{"key":"1072_CR35","first-page":"e00138","volume":"59","author":"R Yee","year":"2021","unstructured":"Yee R, Dien Bard J, Simner PJ. The genotype-to-phenotype dilemma: how should laboratories approach discordant susceptibility results? J Clin Microbiol. 2021;59:e00138-e220.","journal-title":"J Clin Microbiol"},{"key":"1072_CR36","unstructured":"Langelier CR, Kalantar KL. Combined host and microbe NGS for lower respiratory tract infection diagnosis in critically ill adults microbial sequence reads. BioProject PRJNA450137, Sequence Read Archive. 2018. https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/?term=%20PRJNA450137."},{"key":"1072_CR37","unstructured":"Langelier CR, Hayakawa Serpa P. CAS9-mNGS detects antimicrobial resistant pathogens. BioProject PRJNA635133, Sequence Read Archive. 2020. https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/?term=PRJNA635133."},{"key":"1072_CR38","doi-asserted-by":"publisher","first-page":"5152","DOI":"10.1038\/s41467-021-25040-5","volume":"12","author":"A Sarma","year":"2021","unstructured":"Sarma A, Christenson SA, Byrne A, et al. Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS. Nat Commun. 2021;12:5152.","journal-title":"Nat Commun"}],"container-title":["Genome Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13073-022-01072-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13073-022-01072-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13073-022-01072-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T23:02:28Z","timestamp":1657580548000},"score":1,"resource":{"primary":{"URL":"https:\/\/genomemedicine.biomedcentral.com\/articles\/10.1186\/s13073-022-01072-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,12]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["1072"],"URL":"https:\/\/doi.org\/10.1186\/s13073-022-01072-4","relation":{},"ISSN":["1756-994X"],"issn-type":[{"value":"1756-994X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,12]]},"assertion":[{"value":"6 February 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 June 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 July 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Patients were enrolled via a previously described observational cohort study [, ] which was approved by the UCSF Institutional Review Board (IRB), which granted a waiver of initial consent for respiratory sampling. Informed consent was subsequently obtained from patients or their surrogates for continued study participation, following the previously detailed IRB protocol #17\u201324056 []. This research conformed to the principles of the Helsinki Declaration.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Consent to publish patient-related information was obtained as part of informed consent for study participation as described above.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"74"}}