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The investigating group aims at performing an observational, prospective study that involves the evaluation of circulating biomarkers predictive of clinical evolution in patients suffering from COVID-19 disease.
In particular, the aim will be to verify whether there are transcripts or cytokines / chemokines in peripheral blood, modulated differently in patients with COVID-19, distinguished on the basis of the evolution towards more severe clinical pictures that require patient intubation or that show signs of cardiovascular damage.
The study will be based on the transcriptional analysis of the entire genome and serum protein to evaluate the expression of a broad spectrum of cytokines and chemokines. Genome analysis will allow the genotype to be correlated to the identified gene expression profiles.
Study design This observational, prospective, monocentric study will make use of the recruitment of consecutive patients with COVID-19. Enrollment will last 6 months or, considering the desirable drop in infections in the next few weeks, until exhaustion of enrolled patients. Enrollment will be followed by 18 months dedicated to transcriptomics and seroproteomics investigations, for a total duration of the study of 24 months.
All patients will receive optimal medical therapy, and will undergo laboratory or instrumental examinations (chest x-ray, CT, echocardiography) as needed.
Blood samples will be taken at the entrance and then twice a week for the duration of the hospitalization (generally 2-3 weeks).
Anamnesis will be noted for all patients. In addition, at all times, patients will undergo clinical evaluation and the following laboratory tests, which include:
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| Measure | Description | Time Frame |
|---|---|---|
| Circulating markers for COVID-19 signature | Identify circulating transcripts (coding and non-coding for proteins) or cytokines and chemokines which, alone or in combination (COVID19_signature), are predictive of adverse events (death, endotracheal intubation) and the prognostic capacity of COVID19_signature in the prediction of adverse events in additional to the use of standard clinical parameters | From ICU/ward admission for 8 weeks follow/up |
| Measure | Description | Time Frame |
|---|---|---|
| COVID-19 signature and adverse cardiovascular events | Evaluate the association of COVID19_signature with adverse cardiovascular events. Adverse cardiovascular events are defined: death from cardiovascular causes, acute coronary syndrome, troponin T levels greater than the ninety-ninth percentile of the upper reference limit, stroke, cardiac arrhythmias, development of heart failure, venous thromboembolism |
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Inclusion Criteria:
Exclusion Criteria:
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240 patients with COVID-19 will be recruited, including up to 60 patients from the intensive care and 180 from the specialized COVID19 departments of the IRCCS Policlinico San Donato. The sample size is estimated based on the average length of hospitalization of the patients and the maximum capacity of the clinical and laboratory units involved in the study.
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| Name | Affiliation | Role |
|---|---|---|
| Marco Ranucci, MD | IRCCS Policlinico S. Donato | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| IRCCS Policlinico San Donato | San Donato Milanese | MI | 20097 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29052924 | Background | Yin Y, Wunderink RG. MERS, SARS and other coronaviruses as causes of pneumonia. Respirology. 2018 Feb;23(2):130-137. doi: 10.1111/resp.13196. Epub 2017 Oct 20. | |
| 32098422 | Background | Xu J, Zhao S, Teng T, Abdalla AE, Zhu W, Xie L, Wang Y, Guo X. Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV. Viruses. 2020 Feb 22;12(2):244. doi: 10.3390/v12020244. |
| Label | URL |
|---|---|
| World Health Organization. Novel coronavirus (2019-nCoV) SITUATION REPORT - 1 21 JANUARY 2020 | View source |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D017563 | Lung Diseases, Interstitial |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
Not provided
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Serum, plasma, whole blood, PBMC samples
| From ICU/ward admission for 8 weeks follow/up |
| COVID-19 related coagulation pattern | Evaluate, in a subset of 20 patients, the characteristics of the coagulation pattern with specific tests for thrombin generation and fibrinolysis. | From ICU/ward admission for 8 weeks follow/up |
| 31967327 | Background | Chen Y, Liu Q, Guo D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J Med Virol. 2020 Apr;92(4):418-423. doi: 10.1002/jmv.25681. Epub 2020 Feb 7. |
| 32004165 | Background | Ren LL, Wang YM, Wu ZQ, Xiang ZC, Guo L, Xu T, Jiang YZ, Xiong Y, Li YJ, Li XW, Li H, Fan GH, Gu XY, Xiao Y, Gao H, Xu JY, Yang F, Wang XM, Wu C, Chen L, Liu YW, Liu B, Yang J, Wang XR, Dong J, Li L, Huang CL, Zhao JP, Hu Y, Cheng ZS, Liu LL, Qian ZH, Qin C, Jin Q, Cao B, Wang JW. Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study. Chin Med J (Engl). 2020 May 5;133(9):1015-1024. doi: 10.1097/CM9.0000000000000722. |
| 32132184 | Background | Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science. 2020 Mar 27;367(6485):1444-1448. doi: 10.1126/science.abb2762. Epub 2020 Mar 4. |
| 32056249 | Background | Liu J, Zheng X, Tong Q, Li W, Wang B, Sutter K, Trilling M, Lu M, Dittmer U, Yang D. Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV. J Med Virol. 2020 May;92(5):491-494. doi: 10.1002/jmv.25709. Epub 2020 Feb 21. |
| 32302448 | Background | Ranucci M, Ballotta A, Di Dedda U, Baryshnikova E, Dei Poli M, Resta M, Falco M, Albano G, Menicanti L. The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. J Thromb Haemost. 2020 Jul;18(7):1747-1751. doi: 10.1111/jth.14854. Epub 2020 May 6. |
| 32172672 | Background | Fung SY, Yuen KS, Ye ZW, Chan CP, Jin DY. A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses. Emerg Microbes Infect. 2020 Mar 14;9(1):558-570. doi: 10.1080/22221751.2020.1736644. eCollection 2020. |
| 17049503 | Background | Keidar S, Kaplan M, Gamliel-Lazarovich A. ACE2 of the heart: From angiotensin I to angiotensin (1-7). Cardiovasc Res. 2007 Feb 1;73(3):463-9. doi: 10.1016/j.cardiores.2006.09.006. Epub 2006 Sep 19. |
| 32139904 | Background | Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020 May;17(5):259-260. doi: 10.1038/s41569-020-0360-5. |
| 29365305 | Background | Kwong JC, Schwartz KL, Campitelli MA, Chung H, Crowcroft NS, Karnauchow T, Katz K, Ko DT, McGeer AJ, McNally D, Richardson DC, Rosella LC, Simor A, Smieja M, Zahariadis G, Gubbay JB. Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection. N Engl J Med. 2018 Jan 25;378(4):345-353. doi: 10.1056/NEJMoa1702090. |
| 27438105 | Background | Nguyen JL, Yang W, Ito K, Matte TD, Shaman J, Kinney PL. Seasonal Influenza Infections and Cardiovascular Disease Mortality. JAMA Cardiol. 2016 Jun 1;1(3):274-81. doi: 10.1001/jamacardio.2016.0433. |
| 32007143 | Background | Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30. |
| 32031570 | Background | Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585. |
| 31986264 | Background | Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. |
| 12781535 | Background | Peiris JS, Chu CM, Cheng VC, Chan KS, Hung IF, Poon LL, Law KI, Tang BS, Hon TY, Chan CS, Chan KH, Ng JS, Zheng BJ, Ng WL, Lai RW, Guan Y, Yuen KY; HKU/UCH SARS Study Group. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003 May 24;361(9371):1767-72. doi: 10.1016/s0140-6736(03)13412-5. |
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| 29843589 | Background | Zhao S, Li CI, Guo Y, Sheng Q, Shyr Y. RnaSeqSampleSize: real data based sample size estimation for RNA sequencing. BMC Bioinformatics. 2018 May 30;19(1):191. doi: 10.1186/s12859-018-2191-5. |
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |