The Role of Adaptive Immunity in COVID-19 Associated Myocardial Injury

COVID Clinical Trial

Official title:

The Role of Adaptive Immunity in COVID-19 Associated Myocardial Injury

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04340921
• Other study ID #: 282289
• Status: Withdrawn
• Start date: May 14, 2020
• Est. completion date: April 14, 2023

Study information

• Verified date: April 2023
• Source: Barts & The London NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

COVID-19 is associated with complications including ARDS and myocardial injury, which informs prognosis and patient outcome. The laboratory plans to perform immunophenotyping of peripheral T-cells in patients with COVID-19 and complications (ARDS, ITU admission, myocardial injury) and map this against clinical patient outcomes. The aim is to determine if there is a specific T-cell immunophenotype associated with COVID-19 and/or complications, which can be used to inform prognosis and potential therapies.

Description:

Infection with the novel coronavirus COVID-19 is designated a pandemic by the World Health Organisation (WHO).COVID-19 infection can result in severe lung inflammation which, when present, dominates the clinical course for most patients. However, other organs may also be involved and the cardiovascular (CV) system appears to have complex interactions with COVID-19. Published reports suggest evidence of heart muscle damage in 20-40% of hospitalised cases presenting as cardiac chest pain, heart failure, abnormal heart rhythms and cardiac death.

Many affected were previously well, but approximately half of those admitted to hospital COVID-19 have other medical problems, increasing in those requiring ITU admission or those that died. Patients with pre-existing CV conditions have some of the worst outcomes. Although pre-existing disorders reduce an individual's capacity to withstand severe illness, it is also likely that CV diseases may increase the risk of developing complicated COVID-19 disease. Our hypothesis is that immunological abnormalities acquired as a consequence of pre-existing disorders is responsible for this.

A question central to potential therapeutic options is the extent to which COVID-19 related myocardial injury results from viral replication (cytopathic), is immune mediated or is due to other mechanisms. Given that rapid onset cardiac injury can occur at 7-14 days after onset of COVID symptoms we propose to evaluate the contribution of adaptive T-cell mediated immunity in patients with and without myocardial injury. If successful, we may be able to identify treatments that suppress discrete components of the immune system to prevent myocardial damage without depressing protective immune function.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 14, 2023
• Est. primary completion date: April 14, 2023
• Gender: All
• Age group: 18 Years and older

Eligibility

Group 1: COVID-19 positive without evidence of myocardial injury (n=120). Inclusion criteria: All adult (age=18 but <100 years of age) inpatients with confirmed COVID-19 infection. Exclusion criteria: No biochemical evidence of acute myocardial injury (serum troponin>99th centile within previous 48-hour period)

Group 2: COVID-19 positive with myocarditis (n=20). Inclusion criteria: All adult (age=18 but <100 years of age) inpatients with confirmed COVID-19 infection and clinically suspected or confirmed myocarditis including evidence of acute myocardial injury (troponin >99th centile within the previous 48-hour period) at the time of recruitment.

Exclusion criteria: significant chronic kidney disease (eGFR =30 or dialysis-dependent) or septic shock at the time of initial assessment. We will also exclude patients with a diagnosis of chronic heart muscle disease and those with known significant chronic or acute obstructive coronary disease.

Group 3: Group 1 and 2 study participants with a complicated course (estimated 14-35 patients).

Inclusion criteria: Participants form Groups 1 and 2 in whom a prespecified complication ocurs will be included in a derived Group3.

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiovascular Disease Acute
• Cardiovascular Diseases
• COVID

Intervention

Biological:
• COVID-19 exposure
Observation only

Locations

Country	Name	City	State
United Kingdom	Barts Health Nhs Trust	London

Sponsors (2)

Lead Sponsor	Collaborator
Barts & The London NHS Trust	Queen Mary University of London

Country where clinical trial is conducted

United Kingdom, 

References & Publications (11)

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 — View Citation

Cooper LT Jr. Myocarditis. N Engl J Med. 2009 Apr 9;360(15):1526-38. doi: 10.1056/NEJMra0800028. — View Citation

Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020 Aug;81(5):537-540. doi: 10.1002/ddr.21656. Epub 2020 Mar 4. — View Citation

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 20 — View Citation

Komarowska I, Coe D, Wang G, Haas R, Mauro C, Kishore M, Cooper D, Nadkarni S, Fu H, Steinbruchel DA, Pitzalis C, Anderson G, Bucy P, Lombardi G, Breckenridge R, Marelli-Berg FM. Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and P — View Citation

Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. No abstract available. — View Citation

Ramchand J, Patel SK, Srivastava PM, Farouque O, Burrell LM. Elevated plasma angiotensin converting enzyme 2 activity is an independent predictor of major adverse cardiac events in patients with obstructive coronary artery disease. PLoS One. 2018 Jun 13;13(6):e0198144. doi: 10.1371/journal.pone.0198144. eCollection 2018. — View Citation

Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 May;46(5):846-848. doi: 10.1007/s00134-020-05991-x. Epub 2020 Mar 3. No abst — View Citation

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):106 — View Citation

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. — View Citation

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	T-cell immunophenotype	T-cell immunophenotype	12 months from enrollment
Secondary	Mortality	death, survival to discharge	12 months from enrolment
Secondary	ITU admission	Admission to the intensive care	12 months from enrolment
Secondary	Myocardial injury	Defined by troponin rise to >99th centile	12 months from enrolment