DNA Methylation Levels of the ACE2 Promoter Are Not Associated with Post-COVID-19 Symptoms in Individuals Who Had Been Hospitalized Due to COVID-19
Abstract
:1. Introduction
2. Methods
2.1. Participants
2.2. Genome DNA Collection
2.3. Differentially Methylation Profiling
2.4. Collection Data
2.5. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Post-COVID-19 Fatigue (n = 174) | No Post-COVID-19 Fatigue (n = 105) | p Value | |
---|---|---|---|
Age, mean (SD), years | 57.0 (12.5) | 55.7 (13.1) | 0.423 |
Gender, male/female (%) * | 74 (42.5%)/100 (57.5%) | 69 (65.7%)/36 (34.3%) | 0.007 * |
Weight, mean (SD), kg | 81.5 (18.0) | 80.5 (15.0) | 0.675 |
Height, mean (SD), cm | 166.5 (11.5) | 169.0 (9.2) | 0.679 |
Number of medical conditions | 1.3 (1.0) | 1.1 (1.0) | 0.523 |
Pre-existing medical conditions, n (%) | |||
Hypertension | 58 (33.3%) | 37 (35.25%) | 0.791 |
Diabetes | 21 (12.1%) | 8 (7.6%) | 0.264 |
Cardiovascular Diseases | 12 (6.9%) | 8 (7.6%) | 0.829 |
Asthma | 20 (11.5%) | 11 (10.5%) | 0.805 |
Obesity | 60 (34.5%) | 25 (23.8%) | 0.118 |
Chronic Obstructive Pulmonary Disease | 3 (1.7%) | 2 (1.9%) | 0.913 |
Number of COVID-19-onset symptoms, mean (SD) | 3.25 (1.0) | 3.1 (1.0) | 0.218 |
Days at hospital, mean (SD) | 7.0 (5.8) | 8.6 (10.0) | 0.136 |
Intensive Care Unit (ICU) admission | |||
Yes/No, n (%) | 8 (4.5%)/166 (95.5%) | 2 (2%)/103 (98%) | 0.326 |
CpG1 methylation (%) | 93.3 (4.0) | 93.7 (3.2) | 0.335 |
CpG2 methylation (%) | 40.4 (7.4) | 39.4 (7.3) | 0.259 |
CpG3 methylation (%) | 43.6 (9.0) | 42.8 (8.1) | 0.437 |
CpG4 methylation (%) | 45.5 (8.0) | 45.6 (7.8) | 0.937 |
CpG5 methylation (%) | 0.6 (0.3) | 0.6 (0.4) | 0.804 |
Post-COVID-19 Dyspnea at Rest (n = 36) | No Post-COVID-19 Dyspnea at Rest (n = 243) | p Value | |
---|---|---|---|
Age, mean (SD), years | 55.0 (15.5) | 57.7 (12.4) | 0.421 |
Gender, male/female (%) | 11 (30.5%)/25 (69.5%) | 132 (64.3%)/111 (45.7%) | 0.07 |
Weight, mean (SD), kg | 81.0 (20.0) | 81.9 (16.5) | 0.933 |
Height, mean (SD), cm | 165.5 (8.7) | 168.0 (9.5) | 0.501 |
Number of medical conditions | 1.3 (1.0) | 1.3 (1.0) | 0.724 |
Pre-existing medical conditions, n (%) | |||
Hypertension | 13 (36.1%) | 82 (33.7%) | 0.820 |
Diabetes | 7 (19.4%) | 22 (9.0%) | 0.081 |
Cardiovascular Diseases | 1 (2.8%) | 19 (7.8%) | 0.291 |
Asthma | 4 (11.1%) | 27 (11.1%) | 0.636 |
Obesity | 14 (38.9%) | 71 (29.2%) | 0.327 |
Chronic Obstructive Pulmonary Disease | 1 (2.8%) | 4 (1.7%) | 0.636 |
Number of COVID-19-onset symptoms, mean (SD) | 3.4 (1.0) | 3.2 (1.0) | 0.125 |
Days at hospital, mean (SD) | 8.7 (5.8) | 7.9 (9.0) | 0.617 |
Intensive Care Unit (ICU) admission | |||
Yes/No, n (%) | 1 (2.8%)/35 (97.2%) | 9 (3.7%)/107 (96.3%) | 0.623 |
CpG1 methylation (%) | 93.0 (4.5) | 93.5 (3.6) | 0.350 |
CpG2 methylation (%) | 37.9 (8.3) | 40.3 (7.2) | 0.061 |
CpG3 methylation (%) | 40.7 (10.0) | 43.7 (8.4) | 0.054 |
CpG4 methylation (%) | 44.3 (9.7) | 45.7 (7.6) | 0.322 |
CpG5 methylation (%) | 0.6 (0.25) | 0.6 (0.4) | 0.623 |
Post-COVID-19 Dyspnea on Exertion (n = 188) | No Post-COVID-19 Dyspnea Exertion (n = 91) | p Value | |
---|---|---|---|
Age, mean (SD), years | 56.5 (13.2) | 56.5 (12.0) | 0.997 |
Gender, male/female (%) * | 82 (43.6%)/106 (56.4%) | 61 (67.0%)/30 (33.0%) | 0.008 * |
Weight, mean (SD), kg | 81.0 (17.5) | 81.1 (15.0) | 0.967 |
Height, mean (SD), cm | 166.5 (9.5) | 169.0 (9.6) | 0.282 |
Number of medical conditions | 1.3 (1.0) | 1.1 (1.0) | 0.205 |
Pre-existing medical conditions, n (%) | |||
Hypertension | 62 (33.0%) | 33 (36.25%) | 0.659 |
Diabetes | 20 (10.6%) | 9 (9.9%) | 0.855 |
Cardiovascular Diseases | 14 (7.5%) | 6 (6.6%) | 0.802 |
Asthma | 24 (12.8%) | 7 (7.7%) | 0.233 |
Obesity | 64 (34.0%) | 21 (23.1%) | 0.120 |
Chronic Obstructive Pulmonary Disease | 3 (1.6%) | 2 (2.2%) | 0.727 |
Number of COVID-19-onset symptoms, mean (SD) | 3.2 (1.0) | 3.25 (1.0) | 0.637 |
Days at hospital, mean (SD) | 8.2 (9.6) | 7.6 (6.2) | 0.608 |
Intensive Care Unit (ICU) admission | |||
Yes/No, n (%) | 7 (3.7%)/181 (96.3%) | 3 (3.3%)/88 (96.7%) | 0.538 |
CpG1 methylation (%) | 93.2 (4.2) | 94.1 (2.5) | 0.052 |
CpG2 methylation (%) | 40.2 (7.6) | 39.7 (6.9) | 0.578 |
CpG3 methylation (%) | 43.4 (8.9) | 43.0 (8.5) | 0.681 |
CpG4 methylation (%) | 45.7 (8.1) | 45.4 (7.5) | 0.742 |
CpG5 methylation (%) | 0.6 (0.35) | 0.6 (0.35) | 0.517 |
Post-COVID-19 Memory Loss (n = 87) | No Post-COVID-19 Memory Loss (n = 192) | p Value | |
---|---|---|---|
Age, mean (SD), years | 57.9 (12.3) | 55.8 (13.0) | 0.204 |
Gender, male/female (%) | 8 (44.7%)/49 (56.3%) | 107 (54.7%)/87 (45.3%) | 0.222 |
Weight, mean (SD), kg | 81.2 (16.9) | 81.0 (16.8) | 0.867 |
Height, mean (SD), cm | 166.7 (9.5) | 168.0 (9.5) | 0.469 |
Number of medical conditions | 1.45 (1.0) | 1.2 (1.0) | 0.07 |
Pre-existing medical conditions, n (%) | |||
Hypertension | 35 (40.2%) | 60 (31.25%) | 0.233 |
Diabetes * | 14 (16.1%) | 15 (7.8%) | 0.046 * |
Cardiovascular Diseases | 6 (6.9%) | 14 (7.3%) | 0.909 |
Asthma * | 16 (18.4%) | 15 (7.8%) | 0.014 * |
Obesity | 24 (27.6%) | 61 (31.8%) | 0.557 |
Chronic Obstructive Pulmonary Disease | 0 (0.0%) | 5 (2.6%) | 0.132 |
Number of COVID-19-onset symptoms, mean (SD) * | 3.4 (0.8) | 3.1 (1.1) | 0.04 * |
Days at hospital, mean (SD) | 9.1 (12.3) | 7.5 (6.4) | 0.159 |
Intensive Care Unit (ICU) admission | |||
Yes/No, n (%) | 4 (4.6%)/83 (95.4%) | 6 (3.1%)/186 (96.9%) | 0.09 |
CpG1 methylation (%) | 93.1 (4.9) | 93.6 (3.1) | 0.263 |
CpG2 methylation (%) | 41.1 (7.1) | 39.5 (7.4) | 0.096 |
CpG3 methylation (%) | 44.6 (8.3) | 42.7 (8.7) | 0.087 |
CpG4 methylation (%) | 46.5 (7.8) | 45.1 (7.9) | 0.177 |
CpG5 methylation (%) | 0.6 (0.25) | 0.6 (0.4) | 0.086 |
Post-COVID-19 Brain Fog (n = 41) | No Post-COVID-19 Brain Fog (n = 238) | p Value | |
---|---|---|---|
Age, mean (SD), years | 55.1 (12.8) | 56.7 (12.8) | 0.459 |
Gender, male/female (%) | 17 (41.5%)/24 (58.5%) | 126 (52.9%)/112 (47.1%) | 0.331 |
Weight, mean (SD), kg | 81.6 (19.0) | 81.0 (16.3) | 0.805 |
Height, mean (SD), cm | 166.5 (9.9) | 167.5 (9.5) | 0.580 |
Number of medical conditions | 1.35 (1.0) | 1.3 (1.0) | 0.331 |
Pre-existing medical conditions, n (%) | |||
Hypertension | 11 (26.83%) | 84 (35.3%) | 0.390 |
Diabetes | 6 (14.6%) | 23 (9.7%) | 0.361 |
Cardiovascular Diseases | 1 (2.5%) | 19 (8.0%) | 0.221 |
Asthma | 7 (17.1%) | 24 (10.1%) | 0.215 |
Obesity | 14 (34.1%) | 71 (29.8%) | 0.643 |
Chronic Obstructive Pulmonary Disease | 0 (0.0%) | 5 (2.1%) | 0.353 |
Number of COVID-19-onset symptoms, mean (SD) | 3.4 (0.9) | 3.15 (1.0) | 0.142 |
Days at hospital, mean (SD) | 7.5 (7.0) | 8.1 (9.0) | 0.673 |
Intensive Care Unit (ICU) admission | |||
Yes/No, n (%) | 2 (4.9%)/39 (95.1%) | 8 (3.3%)/230 (96.7%) | 0.657 |
CpG1 methylation (%) | 93.7 (4.4) | 93.4 (3.7) | 0.748 |
CpG2 methylation (%) | 41.4 (6.6) | 39.8 (7.5) | 0.197 |
CpG3 methylation (%) | 44.6 (8.1) | 43.1 (8.8) | 0.306 |
CpG4 methylation (%) | 46.7 (7.5) | 45.4 (8.0) | 0.319 |
CpG5 methylation (%) | 0.6 (0.4) | 0.65 (0.35) | 0.612 |
Post-COVID-19 Concentration Loss (n = 42) | No Post-COVID-19 Concentration Loss (n = 237) | p Value | |
---|---|---|---|
Age, mean (SD), years | 54.5 (12.4) | 57.0 (12.9) | 0.311 |
Gender, male/female (%) * | 16 (28.1%)/26 (61.9%) | 127 (54.6%)/110 (46.4%) | 0.007 * |
Weight, mean (SD), kg | 80.7 (16.4) | 81.0 (16.9) | 0.898 |
Height, mean (SD), cm | 165.5 (9.75) | 167.0 (9.5) | 0.202 |
Number of medical conditions | 1.3 (1.0) | 1.3 (1.0) | 0.989 |
Pre-existing medical conditions, n (%) | |||
Hypertension | 14 (33.3%) | 81 (34.2%) | 0.931 |
Diabetes | 2 (4.8%) | 27 (11.4%) | 0.219 |
Cardiovascular Diseases | 2 (4.8%) | 18 (7.6%) | 0.525 |
Asthma | 4 (9.5%) | 27 (11.4%) | 0.737 |
Obesity | 19 (45.2%) | 66 (27.8%) | 0.06 |
Chronic Obstructive Pulmonary Disease | 0 (0.0%) | 5 (2.1%) | 0.346 |
Number of COVID-19-onset symptoms, mean (SD) | 3.3 (1.1) | 3.2 (1.0) | 0.554 |
Days at hospital, mean (SD) | 8.5 (7.7) | 7.9 (8.8) | 0.708 |
Intensive Care Unit (ICU) admission | |||
Yes/No, n (%) | 2 (4.7%)/40 (95.3%) | 8 (3.4%)/229 (94.6%) | 0.657 |
CpG1 methylation (%) | 93.1 (4.5) | 93.5 (3.6) | 0.497 |
CpG2 methylation (%) | 38.9 (7.6) | 40.1 (7.3) | 0.292 |
CpG3 methylation (%) | 42.2 (8.6) | 43.5 (8.7) | 0.368 |
CpG4 methylation (%) | 43.5 (7.6) | 45.9 (8.0) | 0.066 |
CpG5 methylation (%) | 0.6 (0.3) | 0.6 (0.4) | 0.506 |
Post-COVID-19 Gastrointestinal Symptoms (n = 25) | No Post-COVID-19 Gastrointestinal Symptoms (n = 254) | p Value | |
---|---|---|---|
Age, mean (SD), years | 55.0 (14.1) | 56.6 (12.7) | 0.536 |
Gender, male/female (%) | 11 (44.0%)/14 (56.0%) | 132 (52.0%)/122 (48.0%) | 0.586 |
Weight, mean (SD), kg | 81.2 (21.2) | 81.0 (16.4) | 0.947 |
Height, mean (SD), cm | 168.5 (12.7) | 167.5 (9.2) | 0.475 |
Number of medical conditions | 1.2 (1.0) | 1.3 (1.0) | 0.523 |
Pre-existing medical conditions, n (%) | |||
Hypertension | 10 (40.0%) | 85 (33.5%) | 0.593 |
Diabetes | 1 (4.0%) | 28 (11.0%) | 0.299 |
Cardiovascular Diseases | 1 (4.0%) | 19 (7.5%) | 0.535 |
Asthma | 3 (12.0%) | 28 (11.0%) | 0.889 |
Obesity | 50 (20.0%) | 80 (31.5%) | 0.320 |
Chronic Obstructive Pulmonary Disease | 1 (4.0%) | 4 (1.6%) | 0.387 |
Number of COVID-19-onset symptoms, mean (SD) | 3.35 (0.8) | 3.2 (1.0) | 0.408 |
Days at hospital, mean (SD) | 5.7 (2.5) | 8.2 (9.0) | 0.168 |
Intensive Care Unit (ICU) admission | |||
Yes/No, n (%) | 0 (0.0%)/25 (100%) | 10 (3.9%)/244 (96.1%) | 0.412 |
CpG1 methylation (%) | 91.3 (6.0) | 93.7 (3.4) | 0.002 |
CpG2 methylation (%) | 40.5 (8.0) | 40.0 (7.3) | 0.711 |
CpG3 methylation (%) | 42.2 (9.2) | 43.4 (8.6) | 0.527 |
CpG4 methylation (%) | 44.3 (9.5) | 45.7 (7.7) | 0.411 |
CpG5 methylation (%) | 0.55 (0.45) | 0.6 (0.35) | 0.295 |
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Fernández-de-las-Peñas, C.; Díaz-Gil, G.; Gil-Crujera, A.; Gómez-Sánchez, S.M.; Ambite-Quesada, S.; Torres-Macho, J.; Ryan-Murua, P.; Franco-Moreno, A.; Pellicer-Valero, O.J.; Arendt-Nielsen, L.; et al. DNA Methylation Levels of the ACE2 Promoter Are Not Associated with Post-COVID-19 Symptoms in Individuals Who Had Been Hospitalized Due to COVID-19. Microorganisms 2024, 12, 1304. https://doi.org/10.3390/microorganisms12071304
Fernández-de-las-Peñas C, Díaz-Gil G, Gil-Crujera A, Gómez-Sánchez SM, Ambite-Quesada S, Torres-Macho J, Ryan-Murua P, Franco-Moreno A, Pellicer-Valero OJ, Arendt-Nielsen L, et al. DNA Methylation Levels of the ACE2 Promoter Are Not Associated with Post-COVID-19 Symptoms in Individuals Who Had Been Hospitalized Due to COVID-19. Microorganisms. 2024; 12(7):1304. https://doi.org/10.3390/microorganisms12071304
Chicago/Turabian StyleFernández-de-las-Peñas, César, Gema Díaz-Gil, Antonio Gil-Crujera, Stella M. Gómez-Sánchez, Silvia Ambite-Quesada, Juan Torres-Macho, Pablo Ryan-Murua, Anabel Franco-Moreno, Oscar J. Pellicer-Valero, Lars Arendt-Nielsen, and et al. 2024. "DNA Methylation Levels of the ACE2 Promoter Are Not Associated with Post-COVID-19 Symptoms in Individuals Who Had Been Hospitalized Due to COVID-19" Microorganisms 12, no. 7: 1304. https://doi.org/10.3390/microorganisms12071304