Statin and aspirin as adjuvant therapy in hospitalised patients with SARS-CoV-2 infection: a randomised clinical trial (RESIST trial)

DOI record: { "DOI": "10.1186/s12879-022-07570-5", "ISSN": [ "1471-2334" ], "URL": "http://dx.doi.org/10.1186/s12879-022-07570-5", "abstract": "<jats:title>Abstract</jats:title><jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>Statins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There is a need for a randomised controlled trial.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>In this single-center, open-label, randomised controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalisation, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement ≥ 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>The primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C, and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P = 0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit [Atorvastatin: HR 1.0 (95% CI 0.41–2.46) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27–1.81) P = 0.46]. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>Among patients admitted with mild to moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination of the two does not prevent clinical deterioration.</jats:p>\n <jats:p><jats:italic>Trial Registry Number</jats:italic> CTRI/2020/07/026791 (<jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"http://ctri.nic.in\">http://ctri.nic.in</jats:ext-link>; registered on 25/07/2020)</jats:p>\n </jats:sec>", "alternative-id": [ "7570" ], "article-number": "606", "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "8 March 2022" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "27 May 2022" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "9 July 2022" }, { "group": { "label": "Declarations", "name": "EthicsHeading" }, "name": "Ethics", "order": 1 }, { "group": { "label": "Ethics approval and consent to participate", "name": "EthicsHeading" }, "name": "Ethics", "order": 2, "value": "The trial was conducted in accordance with the 1964 Helsinki Declaration and its later amendments. The trial was approved by the institutional ethical committee (attached). Informed consent was obtained from all participants." }, { "group": { "label": "Consent for publication", "name": "EthicsHeading" }, "name": "Ethics", "order": 3, "value": "Not applicable." }, { "group": { "label": "Competing interests", "name": "EthicsHeading" }, "name": "Ethics", "order": 4, "value": "We declare no competing interests." } ], "author": [ { "affiliation": [], "family": "Ghati", "given": "Nirmal", "sequence": "first" }, { "affiliation": [], "family": "Bhatnagar", "given": "Sushma", "sequence": "additional" }, { "affiliation": [], "family": "Mahendran", "given": "Manjit", "sequence": "additional" }, { "affiliation": [], "family": "Thakur", "given": "Abhishek", "sequence": "additional" }, { "affiliation": [], "family": "Prasad", "given": "Kshitij", "sequence": "additional" }, { "affiliation": [], "family": "Kumar", "given": "Devesh", "sequence": "additional" }, { "affiliation": [], "family": "Dwivedi", "given": "Tanima", "sequence": "additional" }, { "affiliation": [], "family": "Mani", "given": "Kalaivani", "sequence": "additional" }, { "affiliation": [], "family": "Tiwari", "given": "Pawan", "sequence": "additional" }, { "affiliation": [], "family": "Gupta", "given": "Ritu", "sequence": "additional" }, { "affiliation": [], "family": "Mohan", "given": "Anant", "sequence": "additional" }, { "affiliation": [], "family": "Saxena", "given": "Anita", "sequence": "additional" }, { "affiliation": [], "family": "Guleria", "given": "Randeep", "sequence": "additional" }, { "affiliation": [], "family": "Deepti", "given": "Siddharthan", "sequence": "additional" } ], "container-title": "BMC Infectious Diseases", "container-title-short": "BMC Infect Dis", "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2022, 7, 9 ] ], "date-time": "2022-07-09T07:02:59Z", "timestamp": 1657350179000 }, "deposited": { "date-parts": [ [ 2022, 7, 9 ] ], "date-time": "2022-07-09T07:03:24Z", "timestamp": 1657350204000 }, "indexed": { "date-parts": [ [ 2022, 7, 10 ] ], "date-time": "2022-07-10T12:41:02Z", "timestamp": 1657456862818 }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2022, 7, 9 ] ] }, "journal-issue": { "issue": "1", "published-print": { "date-parts": [ [ 2022, 12 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2022, 7, 9 ] ], "date-time": "2022-07-09T00:00:00Z", "timestamp": 1657324800000 } }, { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2022, 7, 9 ] ], "date-time": "2022-07-09T00:00:00Z", "timestamp": 1657324800000 } } ], "link": [ { "URL": "https://link.springer.com/content/pdf/10.1186/s12879-022-07570-5.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/article/10.1186/s12879-022-07570-5/fulltext.html", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/content/pdf/10.1186/s12879-022-07570-5.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "prefix": "10.1186", "published": { "date-parts": [ [ 2022, 7, 9 ] ] }, "published-online": { "date-parts": [ [ 2022, 7, 9 ] ] }, "published-print": { "date-parts": [ [ 2022, 12 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.1093/ehjcvp/pvaa042", "author": "V Castiglione", "doi-asserted-by": "publisher", "first-page": "258", "issue": "4", "journal-title": "Eur Heart J Cardiovasc Pharmacother", "key": "7570_CR1", "unstructured": "Castiglione V, Chiriacò M, Emdin M, Taddei S, Vergaro G. Statin therapy in COVID-19 infection. Eur Heart J Cardiovasc Pharmacother. 2020;6(4):258–9.", "volume": "6", "year": "2020" }, { "DOI": "10.1097/CCM.0b013e318225742c", "author": "D Makris", "doi-asserted-by": "publisher", "first-page": "2440", "issue": "11", "journal-title": "Crit Care Med", "key": "7570_CR2", "unstructured": "Makris D, Manoulakas E, Komnos A, Papakrivou E, Tzovaras N, Hovas A, Zintzaras E, Zakynthinos E. Effect of pravastatin on the frequency of ventilator-associated pneumonia and on intensive care unit mortality: open-label, randomized study. Crit Care Med. 2011;39(11):2440–6.", "volume": "39", "year": "2011" }, { "DOI": "10.1001/jama.2013.280031", "author": "L Papazian", "doi-asserted-by": "publisher", "first-page": "1692", "issue": "16", "journal-title": "JAMA", "key": "7570_CR3", "unstructured": "Papazian L, Roch A, Charles PE, Penot-Ragon C, Perrin G, Roulier P, Goutorbe P, Lefrant JY, Wiramus S, Jung B, Perbet S, Hernu R, Nau A, Baldesi O, Allardet-Servent J, Baumstarck K, Jouve E, Moussa M, Hraiech S, Guervilly C, Forel JM. Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: a randomized clinical trial. JAMA. 2013;310(16):1692–700.", "volume": "310", "year": "2013" }, { "DOI": "10.1161/01.CIR.0000138932.17956.F1", "author": "Y Almog", "doi-asserted-by": "publisher", "first-page": "880", "issue": "7", "journal-title": "Circulation", "key": "7570_CR4", "unstructured": "Almog Y, Shefer A, Novack V, Maimon N, Barski L, Eizinger M, Friger M, Zeller L, Danon A. Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation. 2004;110(7):880–5.", "volume": "110", "year": "2004" }, { "DOI": "10.1592/phco.29.6.621", "author": "PP Dobesh", "doi-asserted-by": "publisher", "first-page": "621", "issue": "6", "journal-title": "Pharmacotherapy", "key": "7570_CR5", "unstructured": "Dobesh PP, Klepser DG, McGuire TR, Morgan CW, Olsen KM. Reduction in mortality associated with statin therapy in patients with severe sepsis. Pharmacotherapy. 2009;29(6):621–30.", "volume": "29", "year": "2009" }, { "DOI": "10.1016/j.amjcard.2020.08.004", "author": "CS Kow", "doi-asserted-by": "publisher", "first-page": "153", "journal-title": "Am J Cardiol", "key": "7570_CR6", "unstructured": "Kow CS, Hasan SS. Meta-analysis of effect of statins in patients with COVID-19. Am J Cardiol. 2020;134:153–5.", "volume": "134", "year": "2020" }, { "DOI": "10.1055/s-0040-1722307", "author": "D Onorato", "doi-asserted-by": "publisher", "first-page": "392", "issue": "4", "journal-title": "Semin Thromb Hemost", "key": "7570_CR7", "unstructured": "Onorato D, Pucci M, Carpene G, Henry BM, Sanchis-Gomar F, Lippi G. Protective effects of statins administration in European and north American patients infected with COVID-19: a meta-analysis. Semin Thromb Hemost. 2021;47(4):392–9.", "volume": "47", "year": "2021" }, { "DOI": "10.1136/postgradmedj-2020-139172", "author": "R Pal", "doi-asserted-by": "publisher", "first-page": "354", "journal-title": "Postgrad Med J", "key": "7570_CR8", "unstructured": "Pal R, Banerjee M, Yadav U, Bhattacharjee S. Statin use and clinical outcomes in patients with COVID-19: an updated systematic review and meta-analysis. Postgrad Med J. 2021;98:354.", "volume": "98", "year": "2021" }, { "DOI": "10.1016/j.dsx.2020.08.023", "author": "TI Hariyanto", "doi-asserted-by": "publisher", "first-page": "1613", "issue": "6", "journal-title": "Diabetes Metab Syndr", "key": "7570_CR9", "unstructured": "Hariyanto TI, Kurniawan A. Statin therapy did not improve the in-hospital outcome of coronavirus disease 2019 (COVID-19) infection. Diabetes Metab Syndr. 2020;14(6):1613–5.", "volume": "14", "year": "2020" }, { "DOI": "10.1016/j.diabet.2020.101220", "author": "AJ Scheen", "doi-asserted-by": "publisher", "issue": "6", "journal-title": "Diabetes Metab", "key": "7570_CR10", "unstructured": "Scheen AJ. Statins and clinical outcomes with COVID-19: meta-analyses of observational studies. Diabetes Metab. 2020;47(6): 101220.", "volume": "47", "year": "2020" }, { "DOI": "10.4049/jimmunol.0900477", "author": "T Morris", "doi-asserted-by": "publisher", "first-page": "2089", "issue": "3", "journal-title": "J Immunol", "key": "7570_CR11", "unstructured": "Morris T, Stables M, Hobbs A, de Souza P, Colville-Nash P, Warner T, Newson J, Bellingan G, Gilroy DW. Effects of low-dose aspirin on acute inflammatory responses in humans. J Immunol. 2009;183(3):2089–96.", "volume": "183", "year": "2009" }, { "DOI": "10.1001/jama.2016.6330", "author": "DJ Kor", "doi-asserted-by": "publisher", "first-page": "2406", "issue": "22", "journal-title": "JAMA", "key": "7570_CR12", "unstructured": "Kor DJ, Carter RE, Park PK, Festic E, Banner-Goodspeed VM, Hinds R, Talmor D, Gajic O, Ware LB, Gong MN. Effect of aspirin on development of ARDS in at-risk patients presenting to the emergency department: the LIPS-a randomized clinical trial. JAMA. 2016;315(22):2406–14.", "volume": "315", "year": "2016" }, { "DOI": "10.1111/irv.12421", "author": "B Glatthaar-Saalmüller", "doi-asserted-by": "publisher", "first-page": "85", "issue": "1", "journal-title": "Influenza Other Respir Viruses", "key": "7570_CR13", "unstructured": "Glatthaar-Saalmüller B, Mair KH, Saalmüller A. Antiviral activity of aspirin against RNA viruses of the respiratory tract-an in vitro study. Influenza Other Respir Viruses. 2017;11(1):85–92.", "volume": "11", "year": "2017" }, { "DOI": "10.1016/j.phrs.2020.104950", "author": "M Viecca", "doi-asserted-by": "publisher", "first-page": "104950", "journal-title": "Pharmacol Res", "key": "7570_CR14", "unstructured": "Viecca M, Radovanovic D, Forleo GB, Santus P. Enhanced platelet inhibition treatment improves hypoxemia in patients with severe Covid-19 and hypercoagulability. A case control, proof of concept study. Pharmacol Res. 2020;158:104950.", "volume": "158", "year": "2020" }, { "DOI": "10.1213/ANE.0000000000005292", "author": "JH Chow", "doi-asserted-by": "publisher", "first-page": "930", "issue": "4", "journal-title": "Anesth Analg", "key": "7570_CR15", "unstructured": "Chow JH, Khanna AK, Kethireddy S, Yamane D, Levine A, Jackson AM, McCurdy MT, Tabatabai A, Kumar G, Park P, Benjenk I, Menaker J, Ahmed N, Glidewell E, Presutto E, Cain S, Haridasa N, Field W, Fowler JG, Trinh D, Johnson KN, Kaur A, Lee A, Sebastian K, Ulrich A, Peña S, Carpenter R, Sudhakar S, Uppal P, Fedeles BT, Sachs A, Dahbour L, Teeter W, Tanaka K, Galvagno SM, Herr DL, Scalea TM, Mazzeffi MA. Aspirin use is associated with decreased mechanical ventilation, intensive care unit admission, and in-hospital mortality in hospitalized patients with coronavirus disease 2019. Anesth Analg. 2021;132(4):930–41.", "volume": "132", "year": "2021" }, { "DOI": "10.1371/journal.pone.0246825", "author": "TF Osborne", "doi-asserted-by": "publisher", "issue": "2", "journal-title": "PLoS ONE", "key": "7570_CR16", "unstructured": "Osborne TF, Veigulis ZP, Arreola DM, Mahajan SM, Röösli E, Curtin CM. Association of mortality and aspirin prescription for COVID-19 patients at the Veterans Health Administration. PLoS ONE. 2021;16(2): e0246825.", "volume": "16", "year": "2021" }, { "DOI": "10.1111/jcmm.16198", "author": "S Yuan", "doi-asserted-by": "publisher", "first-page": "1263", "issue": "2", "journal-title": "J Cell Mol Med", "key": "7570_CR17", "unstructured": "Yuan S, Chen P, Li H, Chen C, Wang F, Wang DW. Mortality and pre-hospitalization use of low-dose aspirin in COVID-19 patients with coronary artery disease. J Cell Mol Med. 2021;25(2):1263–73.", "volume": "25", "year": "2021" }, { "key": "7570_CR18", "unstructured": "RECOVERY Collaborative Group; Horby PW, Pessoa-Amorim G, Staplin N, Emberson JR, Campbell M, Spata E, Peto L, Brunskill NJ, Tiberi S, Chew V, Brown T, Tahir H, Ebert B, Chadwick D, Whitehouse T, Sarkar R, Graham C, Baillie JK, Basnyat B, Buch MH, Chappell LC, Day J, Faust SN, Hamers RL, Jaki T, Juszczak E, Jeffery K, Lim WS, Montgomery A, Mumford A, Rowan K, Thwaites G, Mafham M, Haynes R, Landray MJ. Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. medRxiv 2021:2021.06.08.21258132." }, { "DOI": "10.1186/s13063-020-04840-y", "author": "N Ghati", "doi-asserted-by": "publisher", "first-page": "902", "issue": "1", "journal-title": "Trials", "key": "7570_CR19", "unstructured": "Ghati N, Roy A, Bhatnagar S, Bhati S, Bhushan S, Mahendran M, Thakur A, Tiwari P, Dwivedi T, Mani K, Gupta R, Mohan A, Garg R, Saxena A, Guleria R, Deepti S. Atorvastatin and Aspirin as Adjuvant Therapy in Patients with SARS-CoV-2 Infection: a structured summary of a study protocol for a randomised controlled trial. Trials. 2020;21(1):902.", "volume": "21", "year": "2020" }, { "DOI": "10.1111/j.1365-2249.2012.04564.x", "author": "A Iwata", "doi-asserted-by": "publisher", "first-page": "234", "issue": "2", "journal-title": "Clin Exp Immunol", "key": "7570_CR20", "unstructured": "Iwata A, Shirai R, Ishii H, Kushima H, Otani S, Hashinaga K, Umeki K, Kishi K, Tokimatsu I, Hiramatsu K, Kadota J. Inhibitory effect of statins on inflammatory cytokine production from human bronchial epithelial cells. Clin Exp Immunol. 2012;168(2):234–40.", "volume": "168", "year": "2012" }, { "DOI": "10.1016/j.intimp.2013.05.016", "author": "AC Melo", "doi-asserted-by": "publisher", "first-page": "57", "issue": "1", "journal-title": "Int Immunopharmacol", "key": "7570_CR21", "unstructured": "Melo AC, Valença SS, Gitirana LB, Santos JC, Ribeiro ML, Machado MN, Magalhães CB, Zin WA, Porto LC. Redox markers and inflammation are differentially affected by atorvastatin, pravastatin or simvastatin administered before endotoxin-induced acute lung injury. Int Immunopharmacol. 2013;17(1):57–64.", "volume": "17", "year": "2013" }, { "DOI": "10.1128/mBio.00638-15", "author": "AL Totura", "doi-asserted-by": "publisher", "first-page": "e00638", "issue": "3", "journal-title": "MBio", "key": "7570_CR22", "unstructured": "Totura AL, Whitmore A, Agnihothram S, Schäfer A, Katze MG, Heise MT, Baric RS. Toll-like receptor 3 signaling via TRIF contributes to a protective innate immune response to severe acute respiratory syndrome coronavirus infection. MBio. 2015;6(3):e00638-e715.", "volume": "6", "year": "2015" }, { "DOI": "10.1016/j.bbrc.2014.02.091", "author": "X Yuan", "doi-asserted-by": "publisher", "first-page": "292", "issue": "1", "journal-title": "Biochem Biophys Res Commun", "key": "7570_CR23", "unstructured": "Yuan X, Deng Y, Guo X, Shang J, Zhu D, Liu H. Atorvastatin attenuates myocardial remodeling induced by chronic intermittent hypoxia in rats: partly involvement of TLR-4/MYD88 pathway. Biochem Biophys Res Commun. 2014;446(1):292–7.", "volume": "446", "year": "2014" }, { "DOI": "10.1001/jamacardio.2020.1286", "author": "M Madjid", "doi-asserted-by": "publisher", "first-page": "831", "issue": "7", "journal-title": "JAMA Cardiol", "key": "7570_CR24", "unstructured": "Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential effects of coronaviruses on the cardiovascular system: a review. JAMA Cardiol. 2020;5(7):831–40.", "volume": "5", "year": "2020" }, { "DOI": "10.1128/mBio.00398-20", "doi-asserted-by": "crossref", "key": "7570_CR25", "unstructured": "Fedson DS, Opal SM, Rordam OM. Hiding in plain sight: an approach to treating patients with severe COVID-19 infection. mBio 2020;11(2)." }, { "DOI": "10.7326/M20-2003", "author": "D Wichmann", "doi-asserted-by": "publisher", "first-page": "268", "issue": "4", "journal-title": "Ann Intern Med", "key": "7570_CR26", "unstructured": "Wichmann D, Sperhake JP, Lütgehetmann M, Steurer S, Edler C, Heinemann A, Heinrich F, Mushumba H, Kniep I, Schröder AS, Burdelski C, de Heer G, Nierhaus A, Frings D, Pfefferle S, Becker H, Bredereke-Wiedling H, de Weerth A, Paschen HR, Sheikhzadeh-Eggers S, Stang A, Schmiedel S, Bokemeyer C, Addo MM, Aepfelbacher M, Püschel K, Kluge S. Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study. Ann Intern Med. 2020;173(4):268–77.", "volume": "173", "year": "2020" }, { "DOI": "10.1016/j.avsg.2020.08.087", "author": "I Cheruiyot", "doi-asserted-by": "publisher", "first-page": "273", "journal-title": "Ann Vasc Surg", "key": "7570_CR27", "unstructured": "Cheruiyot I, Kipkorir V, Ngure B, Misiani M, Munguti J, Ogeng’o J. Arterial thrombosis in coronavirus disease 2019 patients: a rapid systematic review. Ann Vasc Surg. 2021;70:273–81.", "volume": "70", "year": "2021" }, { "DOI": "10.1046/j.1365-2036.2000.00723.x", "author": "S Somasundaram", "doi-asserted-by": "publisher", "first-page": "639", "issue": "5", "journal-title": "Aliment Pharmacol Ther", "key": "7570_CR28", "unstructured": "Somasundaram S, Sigthorsson G, Simpson RJ, Watts J, Jacob M, Tavares IA, Rafi S, Roseth A, Foster R, Price AB, Wrigglesworth JM, Bjarnason I. Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the rat. Aliment Pharmacol Ther. 2000;14(5):639–50.", "volume": "14", "year": "2000" }, { "DOI": "10.1084/jem.20040566", "author": "MJ Paul-Clark", "doi-asserted-by": "publisher", "first-page": "69", "issue": "1", "journal-title": "J Exp Med", "key": "7570_CR29", "unstructured": "Paul-Clark MJ, Van Cao T, Moradi-Bidhendi N, Cooper D, Gilroy DW. 15-epi-lipoxin A4-mediated induction of nitric oxide explains how aspirin inhibits acute inflammation. J Exp Med. 2004;200(1):69–78.", "volume": "200", "year": "2004" }, { "DOI": "10.1111/j.1462-5822.2007.00902.x", "author": "I Mazur", "doi-asserted-by": "publisher", "first-page": "1683", "issue": "7", "journal-title": "Cell Microbiol", "key": "7570_CR30", "unstructured": "Mazur I, Wurzer WJ, Ehrhardt C, Pleschka S, Puthavathana P, Silberzahn T, Wolff T, Planz O, Ludwig S. Acetylsalicylic acid (ASA) blocks influenza virus propagation via its NF-kappaB-inhibiting activity. Cell Microbiol. 2007;9(7):1683–94.", "volume": "9", "year": "2007" } ], "reference-count": 30, "references-count": 30, "relation": {}, "resource": { "primary": { "URL": "https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-022-07570-5" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [ "Infectious Diseases" ], "subtitle": [], "title": "Statin and aspirin as adjuvant therapy in hospitalised patients with SARS-CoV-2 infection: a randomised clinical trial (RESIST trial)", "type": "journal-article", "update-policy": "http://dx.doi.org/10.1007/springer_crossmark_policy", "volume": "22" }