Table 2.
Multi-system phenotyping: serial electrocardiography, biomarkers of inflammation, metabolism, renal function, haemostasis, and heart, lung, and kidney imaging at 28–60 days post-discharge
| All | Control | COVID-19 | P-value | |
|---|---|---|---|---|
| Electrocardiogram | ||||
| Myopericarditis criteria | ||||
| Admission | N = 37 | N = 10 | N = 27 | |
| 7 (19%) | 0 (0%) | 7 (26%) | 0.155 | |
| Enrolment | N = 36 | N = 10 | N = 26 | |
| 7 (19%) | 0 (0%) | 7 (27%) | 0.155 | |
| 28–60 days post-discharge | N = 35 | N = 10 | N = 25 | |
| 2 (6%) | 0 (0%) | 2 (8%) | 1.000 | |
| CT chest 28–60 days post-discharge | ||||
| N = 35 | N = 9 | N = 26 | ||
| Ground glass opacity and/or consolidation | 15 (43%) | 0 (0%) | 15 (58%) | 0.004 |
| Reticulation and/or architectural distortion | 11 (31%) | 0 (0%) | 11 (42%) | 0.033 |
| Atelectasis | 3 (9%) | 0 (0%) | 3 (12%) | 0.553 |
| Pulmonary arterial thrombus | 1 (3%) | 0 (0%) | 1 (4%) | 1.000 |
| Visual estimate of % of total lung area abnormal | 16.4 ± 23.9 | 0.0 ± 0.0 | 22.0 ± 25.4 | 0.015 |
| CT coronary angiogram 28–60 days post-discharge | ||||
| N = 35 | N = 9 | N = 26 | ||
| Coronary calcium—Agatston score | 52 ± 102 | 16 ± 47 | 65 ± 114 | 0.224 |
| MESA percentile | 63.9 ± 25.1 | 41.0 ±- | 65.5 ± 25.2 | 0.365 |
| Obstructive coronary artery disease | 4 (12%) | 0 (0%) | 4 (16%) | 0.554 |
| FFRCT patient-level (all coronary arteries) 28–60 days post-discharge | ||||
| N = 33 | N = 9 | N = 24 | ||
| Median FFRCT | 0.92 ± 0.04 | 0.94 ± 0.01 | 0.92 ± 0.04 | 0.133 |
| Minimum FFRCT ≤ 0.8 | 11 (33%) | 1 (11%) | 10 (42%) | 0.212 |
| Cardiac MRI 28–60 days post-discharge | ||||
| N = 34 | N = 9 | N = 25 | ||
| LV end diastolic volume index, mL/m2 | 74.0 ± 14.1 | 79.1 ± 14.2 | 72.2 ± 13.9 | 0.209 |
| LV end systolic volume index, mL/m2 | 31.5 ± 9.8 | 31.1 ± 9.8 | 31.7 ± 10.0 | 0.891 |
| LV ejection fraction, % | 58.0 ± 7.7 | 61.2 ± 6.4 | 56.9 ± 7.9 | 0.153 |
| LV mass, g | 103.4 ± 29.9 | 124.8 ± 25.5 | 95.7 ± 27.9 | 0.010 |
| RV end diastolic volume index, mL/m2 | 73.3 ± 15.6 | 85.7 ± 10.4 | 68.6 ± 14.7 | 0.003 |
| RV end systolic volume index, mL/m2 | 31.7 ± 8.2 | 34.3 ± 5.6 | 30.8 ± 8.9 | 0.285 |
| RV ejection fraction, % | 55.8 ± 9.9 | 59.9 ± 5.6 | 54.3 ± 10.7 | 0.150 |
| Myocardial tissue characterization | ||||
| N = 34 | N = 9 | N = 25 | ||
| Increased global T1 (>1233 ms) | 9 (26%) | 2 (22%) | 7 (28%) | 1.000 |
| Increased global T2 (>44 ms) | 0 (0%) | 0 (0%) | 0 (0%) | 1.000 |
| T2 ratio (myocardium/serratus anterior muscle) | 1.68 ± 0.22 | 1.64 ± 0.12 | 1.70 ± 0.25 | 0.561 |
| Increased global extracellular volume (>27.4%) | 15 (44%) | 1 (11%) | 14 (56%) | 0.047 |
| Late gadolinium enhancement | ||||
| N = 35 | N = 10 | N = 25 | ||
| Myocardial late gadolinium enhancement | 3 (9%) | 0 (0%) | 3 (12%) | 0.549 |
| Ischaemic distribution | 1 (3%) | 0 (0%) | 1 (4%) | 1.000 |
| Non-ischaemic distribution | 2 (6%) | 0 (0%) | 2 (8%) | 1.000 |
| Myocardial inflammation (Lake Louise criteria) | ||||
| No evidence (0/2) | 13 (37%) | 10 (100%) | 3 (12%) | 0.001 |
| Probable (1/2) | 10 (29%) | 0 (0%) | 10 (40%) | |
| Definite (2/2) | 12 (34%) | 0 (0%) | 12 (48%) | |
| Renal MRI | ||||
| N = 35 | N = 10 | N = 25 | ||
| Average volume of right and left kidneys, mL | 159 ± 35 | 173 ± 32 | 154 ± 35 | 0.141 |
| Average cortex T1 of right and left kidneys, ms | 1541 ± 71 | 1507 ± 68 | 1555 ± 68 | 0.073 |
| Average medulla T1 of right and left kidneys, ms | 1967 ± 74 | 1974 ± 70 | 1964 ± 77 | 0.747 |
| Average T1 corticomedullary differentiation of kidneys | 0.78 ± 0.03 | 0.76 ± 0.02 | 0.79 ± 0.02 | 0.004 |
| Biomarkers at enrolment, central laboratory | ||||
| N = 36 | N = 10 | N = 26 | ||
| eGFR, mL/min/1.73 m2 | 95 (81, 102) | 95 (91, 101) | 93 (81, 103) | 0.891 |
| C-reactive protein, mg/L | 2.8 (1.1, 5.8) | 1.4 (0.9, 3.6) | 3.2 (1.3, 6.7) | 0.120 |
| NT pro BNP, ng/L | 80 (45, 163) | 65 (42, 81) | 140 (73, 219) | 0.068 |
| Total bilirubin, μmol/L | 5.4 (4.1, 8.6) | 10.4 (8.5, 12.6) | 4.9 (3.7, 6.4) | 0.003 |
| Total cholesterol, mmol/L | 5.30 ± 1.34 | 4.93 ± 0.97 | 5.44 ± 1.44 | 0.317 |
| Triglycerides, mmol/L | 2.68 ± 1.77 | 1.83 ± 1.29 | 3.01 ± 1.85 | 0.074 |
| HDL cholesterol, mmol/L | 1.11 ± 0.22 | 1.13 ± 0.21 | 1.10 ± 0.22 | 0.659 |
| ICAM-1, ng/mL | 503 (419, 633) | 410 (384, 444) | 582 (495, 685) | <0.001 |
| VCAM-1, ng/mL | 858 (692, 1164) | 654 (636, 728) | 981 (823, 1254) | 0.002 |
| Endothelin-1, pg/mL | 2.2 (1.9, 2.7) | 2.8 (2.1, 3.0) | 2.1 (1.8, 2.3) | 0.039 |
| IL-6, pg/mL | 3.9 (2.9, 5.8) | 3.2 (1.8, 4.6) | 4.6 (2.9, 6.4) | 0.080 |
| ST2, ng/mL | 21.1 (17.0, 28.3) | 20.0 (14.8, 24.0) | 23.2 (18.2, 30.6) | 0.165 |
| p-selectin, ng/mL | 69 (53, 86) | 46 (38, 62) | 70 (60, 86) | 0.164 |
| D-dimer, ng/mL | 207 ± 221 | 107 ± 67 | 247 ± 249 | 0.090 |
| Fibrinogen, g/L | 3.69 ± 1.49 | 2.88 ± 1.00 | 4.01 ± 1.55 | 0.041 |
| Factor VIII, IU/dL | 160 ± 91 | 93 ± 44 | 187 ± 92 | 0.004 |
| Antithrombin, IU/dL | 110 ± 16 | 105 ± 16 | 112 ± 15 | 0.198 |
| Protein S | 95.1 ± 23.7 | 95.1 ± 30.2 | 95.1 ± 21.4 | 0.998 |
| Protein C | 130.1 ± 29.6 | 112.9 ± 26.5 | 136.9 ± 28.4 | 0.028 |
| VWF: GP1bR | 209 ± 124 | 114 ± 41 | 248 ± 126 | 0.003 |
| VWF: Ag | 209 ± 116 | 151 ± 51 | 233 ± 127 | 0.059 |
| Biomarkers at 28–60 days post-discharge, central laboratory (control group samples from enrolment visit) | ||||
| N = 37 | N = 10 | N = 27 | ||
| eGFR, mL/min/1.73 m2 | 94 (80, 99) | 95 (91, 101) | 92 (78, 97) | 0.502 |
| C-reactive protein, mg/L | 1.9 (1.1, 3.3) | 1.4 (0.9, 3.6) | 2.0 (1.4, 3.2) | 0.698 |
| NT proBNP, ng/L | 80 (61, 115) | 65 (42, 81) | 84 (70, 183) | 0.068 |
| D-dimer, ng/mL | 137 ± 103 | 107 ± 67 | 151 ± 115 | 0.265 |
| ICAM-1, ng/mL | 419 (363, 503) | 410 (384, 444) | 450 (362, 555) | 0.400 |
| VCAM-1, ng/mL | 671 (643, 953) | 654 (636, 728) | 841 (652, 974) | 0.183 |
| Endothelin-1, pg/mL | 2.3 (2.1, 3.0) | 2. 86 (2.1, 3.0) | 2.3 (2.1, 2.7) | 0.327 |
| IL-6, pg/mL | 2.4 (1.8, 4.4) | 3.2 (1.8, 4.6) | 2.4 (1.8, 4.0) | 0.845 |
| ST2, ng/mL | 20.4 (14.9, 23.3) | 20.0 (14.8, 24.0) | 20.4 (15.2, 23.1) | 0.969 |
| p-selectin, ng/mL | 59 (50, 82) | 46 (38, 62) | 60 (52, 82) | 0.172 |
| Prothrombin time, s | 11.1 ± 0.9 | 11.3 ± 0.8 | 11.0 ± 0.9 | 0.321 |
| D-dimer, ng/mL | 137 ± 103 | 107 ± 67 | 151 ± 115 | 0.265 |
| Fibrinogen, g/L | 3.09 ± 0.90 | 2.88 ± 1.00 | 3.19 ± 0.86 | 0.375 |
| Factor VIII, IU/dL | 131 ± 54 | 93 ± 44 | 147 ± 50 | 0.005 |
| Antithrombin, IU/dL | 111 ± 17 | 105 ± 16 | 113 ± 17 | 0.187 |
| Protein S | 97.4 ± 22.4 | 95.1 ± 30.2 | 98.4 ± 18.8 | 0.701 |
| Protein C | 120.7 ± 24.3 | 112.9 ± 26.5 | 124.1 ± 23.0 | 0.227 |
| VWF: GP1bR | 123 ± 48 | 114 ± 41 | 127 ± 50 | 0.460 |
| VWF: Ag | 153 ± 60 | 151 ± 51 | 154 ± 64 | 0.900 |
Summaries are mean ± SD, median (IQR), or N (%). P-values from t-test, Wilcoxon–Mann–Whitney test, or Fisher's exact test. All P-values are two-sided. No adjustments were made for multiple comparisons.
CMR, cardiovascular magnetic resonance; CT, computed tomography; eGFR, glomerular filtration rate; ΝΤ-proBNP, N-terminal pro-brain natriuretic peptide; eGFR (CKD-EPI), estimated glomerular filtration rate using the chronic kidney disease epidemiology (CKD-EPI equation); LV, left ventricle; MESA, multi-ethnic study of atherosclerosis; NT-proBNP, N-terminal pro-B-type natriuretic peptide; RV, right ventricle; T1, longitudinal relaxation time; T2, transverse relaxation time; vWF: Ag, von Willebrand factor antigen.
aCategorical data are summarized as frequency and percentage and compared between groups using Fisher's exact tests. Continuous data are summarized as mean and standard deviation, or median, and interquartile range (IQR, defined as the upper and lower quartiles) and compared between groups using Kruskal–Wallis tests.