Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors
Abstract
1. Introduction
2. Experimental Section
2.1. Study Design and Patient Selection
2.2. Baseline Variables
2.3. Outcome Assessment
2.4. Statistical Analysis
3. Results
3.1. Patients Characteristics at Baseline
3.2. In-Hospital Outcomes
3.3. Survivors Versus Nonsurvivors
3.4. Mild Versus Severe Forms of COVID-19 Infection
3.5. ACEIs Versus ARBs and Poor Outcomes
4. Discussion
4.1. Main Results in Brief
4.2. Hypothetical Pathogenic Mechanisms of RASi Impact on COVID-19 Evolution
4.3. Poor Prognosis Risk Factors
4.4. ACEIs Versus ARBs
4.5. Evidence in the Available Literature
4.6. Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Overall Cohort | PS Cohort | |||||
---|---|---|---|---|---|---|
RASi N(%)/M(IQR) | RASi-Free N(%)/M(IQR) | p-Value | RASi N(%)/M(IQR) | RASi-Free N(%)/M(IQR) | p-Value | |
N | 282 | 490 | 113 | 113 | ||
Age (years) | 75 (66–83) | 64 (50–75) | <0.001 | 73 (64–84) | 73 (61–85) | 0.61 |
Age ≥ 65 years old | 221 (78.4) | 243 (49.6) | <0.001 | 84 (74.3) | 80 (70.8) | 0.65 |
Male | 170 (60.3) | 274 (55.9) | 0.27 | 68 (60.2) | 61 (54) | 0.42 |
BMI (kg/m2) (N = 662) | 28 (25–33) | 27 (24–31) | 0.004 | 27 (24–31) | 26 (24–31) | 0.69 |
eGFR (mL/min/1.73 m2) on admission (N = 756) | 68 (44–84) | 88 (68.5–102.5) | <0.001 | 70 (44–84) | 77 (43–93) | 0.26 |
eGFR ≥ 90 | 45 (16) | 231 (48.6) | 22 (19.6) | 35 (30.9) | 0.07 | |
60 ≤ eGFR < 90 | 122 (43.4) | 143 (30.1) | 44 (39.3) | 32 (28.3) | 0.11 | |
30 ≤ eGFR < 60 | 76 (27) | 66 (13.9) | 32 (28.6) | 27 (23.9) | 0.51 | |
eGFR < 30 | 38 (13.5) | 35 (7.4) | 14 (12.5) | 19 (16.8) | 0.47 | |
Cardiovascular risk factors | ||||||
Hypertension (N = 769) | 273 (96.8) | 158 (32.4) | <0.001 | 104 (92) | 104 (92) | 1 |
Diabetes (N = 769) | 134 (47.5) | 85 (17.5) | <0.001 | 40 (35.4) | 34 (30.1) | 0.48 |
Dyslipidemia (N = 769) | 166 (58.9) | 107 (21.9) | <0.001 | 60 (53.1) | 56 (49.6) | 0.69 |
Smoking (history or current) (N = 671) | 70 (27.9) | 85 (20.2) | 0.029 | 35 (31) | 34 (30.1) | 1 |
Obesity (N = 690) | 107 (42.1) | 134 (30.7) | 0.003 | 35 (31) | 35 (31) | 1 |
Medical history | ||||||
Heart disease (N = 768) | 83 (29.4) | 41 (8.4) | <0.001 | 22 (19.5) | 23 (20.3) | 1 |
Ischemic heart disease | 65 (23) | 26 (5.3) | <0.001 | 14 (12.4) | 12 (10.6) | 0.83 |
Chronic heart failure | 24 (8.5) | 19 (3.9) | 0.011 | 7 (6.2) | 10 (8.8) | 0.61 |
HFrEF | 16 (5.7) | 8 (1.6) | 0.004 | 4 (3.5) | 4 (3.5) | 1 |
Chronic kidney disease (N = 769) | 61 (21.6) | 51 (10.5) | <0.001 | 26 (23) | 31 (27.4) | 0.54 |
Chronic respiratory disease (N = 769) | 35 (12.4) | 56 (11.5) | 0.80 | 12 (10.6) | 16 (14.2) | 0.53 |
COPD | 22 (7.8) | 23 (4.7) | 0.11 | 8 (7.1) | 10 (8.9) | 0.79 |
Active cancer | 19 (6.7) | 34 (6.9) | 1 | 5 (4.4) | 11 (9.7) | 0.20 |
Cognitive impairment (N = 768) | 48 (17.1) | 47 (9.7) | 0.003 | 18 (15.9) | 20 (17.7) | 0.85 |
VTE (N = 769) | 27 (9.6) | 31 (6.4) | 0.138 | 13 (11.5) | 14 (12.4) | 1 |
Admission treatment | ||||||
Antithrombotic treatment on admission | 159 (56.8) | 108 (22.2) | <0.001 | 55 (48.7) | 53 (46.9) | 0.89 |
Antiplatelet (N = 766) | 107 (38.4) | 61 (12.5) | <0.001 | 40 (35.4) | 28 (24.8) | 0.11 |
Anticoagulation (N = 765) | 61 (21.9) | 57 (11.7) | <0.001 | 16 (14.2) | 28 (24.8) | 0.07 |
Antihypertensive drugs (N = 767) | ||||||
Diuretics | 116 (41.4) | 60 (12.3) | <0.001 | 42 (37.2) | 41 (36.3) | 1 |
Beta-blockers | 121 (43.4) | 94 (19.3) | <0.001 | 46 (40.7) | 52 (46) | 0.50 |
COVID-19 diagnosis | ||||||
Positive PCR | 282 (100) | 490 (100) | - | 113 (100) | 113 (100) | |
Low-dose chest CT | 230 (81.6) | 388 (79.2) | 0.42 * | 91 (97.8) | 81 (94.2) | 0.38 * |
normal | 3 (1.3) | 14 (3.6) | 2 (2.2) | 5 (5.8) | ||
uncertain abnormalities | 5 (2.2) | 7 (1.8) | 2 (2.2) | 3 (3.5) | ||
minimal abnormalities (<10%) | 33 (14.3) | 51 (13.1) | 14 (15) | 9 (10.5) | ||
moderate abnormalities (10–25%) | 78 (33.9) | 128 (33) | 27 (29) | 33 (38.4) | ||
important abnormalities (25–50%) | 54 (23.5) | 108 (27.8) | 29 (31.2) | 19 (22.1) | ||
severe abnormalities (50–75%) | 43 (18.7) | 65 (16.8) | 16 (17.2) | 14 (16.3) | ||
critical abnormalities (>75%) | 14 (6.1) | 15 (3.9) | 3 (3.2) | 3 (3.5) | ||
COVID-19 infection severity indicators | ||||||
Oxygen therapy flow rate of >5 L/min | 172 (61) | 247 (50.4) | 0.015 | 67 (59.8) | 55 (51.4) | 0.26 |
Intubation/HNFO therapy/NIV | 82 (29.1) | 151 (30.8) | 0.67 | 38 (33.6) | 30 (26.5) | 0.31 |
Intubation | 80 (28.4) | 140 (28.6) | 1 | 38 (33.6) | 26 (23) | 0.10 |
HFNO therapy/NIV | 11(3.9) | 2 (0.4) | 0.14 | 0 | 4 (3.5) | 0.12 |
CT scan extension > 25% (N = 618) | 111 (48.3) | 188 (48.5) | 1 | 0 | 4 (3.5) | 0.12 |
CRP ≥ 100 mg/L (N = 746) | 182 (65.7) | 293 (62.5) | 0.42 | 71 (64.5) | 68 (60.2) | 0.59 |
D-dimer count ≥ 1500 µg/L (N = 350) | 99 (76.1) | 151 (68.6) | 0.16 | 48 (82.8) | 35 (70) | 0.18 |
Lymphopenia < 1000/µL (N = 753) | 208 (174) | 347 (73.5) | 0.95 | 85 (75.9) | 86 (77.5) | 0.90 |
hs-cTnl ≥ 100 ng/L (N = 376) | 37 (24.8) | 40 (17.6) | 0.12 | 14 (20.9) | 12 (21.4) | 1 |
Total N(%)/M(IQR) | RASi N(%)/M(IQR) | RASi-Free N(%)/M(IQR) | p-Value | |
---|---|---|---|---|
N | 772 | 282 | 490 | |
Death | 173 (21.5) | 82 (29.1) | 91 (18.6) | <0.001 |
Death/intubation | 322 (41.7) | 133 (47.2) | 189 (38.6) | 0.019 |
Death/intubation/HFNO therapy/NIV | 332 (43) | 133 (47.2) | 199 (40.6) | 0.077 |
Death/intubation/HFNO therapy/NIV/oxygen flow rate of ≥5 L | 438 (56.7) | 179 (63.5) | 259 (52.9) | 0.004 |
Death/intubation/HFNO therapy/NIV/oxygen flow rate of ≥10 L | 358 (46.4) | 144 (51) | 214 (43.7) | 0.047 |
Acute renal impairment (N = 767) | 212 (27.6) | 105 (37.5) | 107 (22) | <0.001 |
Severe sepsis or septic shock (N = 698) | 132 (18.9) | 55 (22.2) | 77 (17.1) | 0.103 |
Pulmonary bacterial infection (N = 747) | 60 (8) | 25 (9.2) | 35 (7.4) | 0.36 |
Multiple organ deficiency (N = 767) | 36 (4.5) | 16 (5.7) | 20 (4.1) | 0.31 |
VTE | 61 (7.9) | 21 (7.4) | 40 (8.2) | 0.72 |
AF (N = 748) | 37 (4.9) | 14 (5.2) | 23 (4.8) | 0.83 |
Stroke | 20 (2.6) | 10 (3.5) | 10 (0.2) | 0.21 |
Major bleeding | 37 (4.8) | 14 (5) | 23 (4.7) | 0.87 |
Encephalitis | 15 (1.9) | 6 (2.1) | 9 (1.8) | 0.86 |
Liver injury (N = 748) | 18 (1.6) | 5 (1.8) | 13 (2.7) | 0.60 |
Hospital length of stay | 11 (6–21) | 12 (7–24) | 10 (6–20) | 0.45 |
Hospital length of stay of ≥30 days | 128 (16.6) | 51 (18.1) | 77 (15.7) | 0.21 |
Total N (%)/m ± sd/ M(Q1–Q3) | Nonsurvivors N (%)/m ± sd/ M(Q1–Q3) | Survivors N (%)/m ± sd/ M(Q1–Q3) | p-Value | |
---|---|---|---|---|
N | 772 | 173 | 599 | |
Age (years) | 68 (56–79) | 79 (71–85) | 65 (53–76) | <0.001 |
Age ≥ 65 years old | 464 (60.1) | 156 (90.2) | 308 (51.4) | <0.001 |
Male | 444 (57.5) | 108 (62.4) | 336 (56.1) | 0.16 |
BMI (kg/m2) N = 662 | 28 (24–31) | 27 (24–31) | 28 (24–31) | 0.10 |
Cardiovascular risk factors | ||||
Hypertension N = 769 | 431 (56) | 129 (74.6) | 302 (50.4) | <0.001 |
Diabetes N = 769 | 219 (28.5) | 62 (35.8) | 157 (26.2) | 0.012 |
Dyslipidemia N = 769 | 273 (35.5) | 80 (46.5) | 193 (32.3) | <0.001 |
Smoking (history or current) N = 671 | 155 (23.1) | 49 (31.4) | 106 (20.4) | 0.0042 |
Obesity N = 690 | 241 (34.9) | 50 (31.6) | 191 (35.9) | 0.32 |
Medical history | ||||
Heart disease N = 768 | 124 (16.1) | 37 (21.5) | 87 (14.6) | 0.029 |
Ischemic heart disease | 91 (11.8) | 58 (19.1) | 33 (9.7) | <0.001 |
Chronic heart failure N = 769 | 43 (5.6) | 21 (12.2) | 22 (3.7) | <0.001 |
HFrEF | 24 (3.1) | 12 (6.9) | 12 (2) | <0.001 |
Chronic kidney disease N = 769 | 112 (14.6) | 55 (31.9) | 57 (9.5) | <0.001 |
Chronic respiratory disease N = 769 | 91 (11.8) | 26 (15.1) | 65 (10.8) | 0.13 |
COPD | 45 (5.9) | 14 (8.1) | 31 (5.2) | 0.14 |
Active cancer | 53 (6.9) | 26 (15) | 27 (4.5) | <0.001 |
Cognitive impairment N = 768 | 95 (12.4) | 46 (36.4) | 49 (8.2) | <0.001 |
VTE N = 769 | 58 (7.5) | 19 (11) | 39 (6.5) | 0.048 |
Admission treatment | ||||
Antithrombotic treatment | 267 (34.8) | 99 (57.9) | 168 (28.2) | <0.001 |
Antiplatelet N = 767 | 168 (21.9) | 57 (33.3) | 111 (18.6) | <0.001 |
Anticoagulation N = 766 | 118 (15.4) | 52 (30.5) | 66 (11.1) | <0.001 |
Antihypertensive drugs | ||||
ACE or ARBs | 282 (36.5) | 82 (47.4) | 200 (33.4) | 0.001 |
Diuretics | 176 (22.9) | 69 (40.6) | 107 (17.9) | <0.001 |
Beta-blockers | 215 (28.1) | 70 (41.2) | 145 (24.3) | <0.001 |
COVID-19 diagnosis | ||||
Positive PCR | 772 (100) | 173 (100) | 599 (100) | |
Low-dose CT | 618 (80) | 118 (68.2) | 500 (83.5) | <0.001 * |
normal | 17 (2.8) | 2 (1.1) | 15 (2.5) | 0.67 § |
uncertain abnormalities | 12 (1.9) | 6 (3.5) | 6 (1) | |
minimal (<10%) | 84 (13.6) | 9 (5.2) | 75 (12.5) | |
moderate (10–25%) | 206 (33.3) | 22 (12.7) | 184 (30.7) | |
important (25–50%) | 162 (26.2) | 36 (20.8) | 126 (21) | |
severe (50–75%) | 108 (17.5) | 33 (19.1) | 75 (12.5) | |
critical (>75%) | 29 (4.7) | 10 (5.8) | 19 (3.2) | |
COVID-19 infection severity indicators | ||||
Oxygen flow rate of ≥5 L/min | 378 (48.9) | 135 (78) | 243 (40.6) | <0.001 |
HFNO therapy/NIV/OTI | 233 (30.2) | 74 (42.8) | 159 (26.5) | <0.001 |
OTI | 220 (28.5) | 71 (41) | 149 (24.9) | <0.001 |
HFNO therapy/NIV | 13 (1.7) | 3 (1.7) | 10 (1.7) | 1 |
CRP ≥ 100 mg/L (N = 746) | 476 (63.7) | 133 (80.6) | 343 (59) | <0.001 |
Ddimer count ≥ 1500 µg/L (N = 350) | 250 (71.4) | 72 (91.1) | 178 (65.7) | <0.001 |
Lymphopenia < 1000/µL (N = 753) | 555 (73.7) | 147 (86.5) | 408 (70) | <0.001 |
hs-cTnl ≥ 100 ng/L (N = 376) | 77 (20.5) | 37 (40.6) | 40 (14) | <0.001 |
In-hospital treatment | ||||
Anticoagulant N = 769 | 625 (81.3) | 141 (82.4) | 484 (80.9) | 0.73 |
preventive | 479 (62.2) | 84 (49.1) | 395 (66) | |
therapeutic | 145 (19) | 56 (32.7) | 89 (14.9) | |
ACEIs/ARBs | 125 (16.2) | 28 (16.2) | 97 (16.2) | 1 |
Antiviral | 286 (37) | 55 (31.8) | 231 (38.6) | 0.65 |
lopinavir/ritonavir | 153 (19.8) | 29 (16.7) | 124 (20.7) | |
remdesivir | 7 (0.9) | 0 | 7 (1.2) | |
oseltamivir | 2 (0.5) | 1 (0.6) | 1 (0.2) | |
hydoxychroloquine | 140(18.1) | 30 (17.3) | 110 (18.4) | |
IFN | 4 (0.5) | 0 | 4 (0.7) | |
Antibiotics | 634 (82.1) | 141 (81.5) | 493(82.3) | 0.32 |
amoxicillin/clavulanic acid | 239 (31) | 31 (17.9) | 208 (34.7) | |
3GC | 414 (53.6) | 109 (63) | 305 (50.9) | |
macrolide | 321 (41.6) | 74 (42.8) | 247 (41.2) | |
quinolone | 13 (1.7) | 5 (2.9) | 8 (1.3) | |
other | 3 (0.4) | 2 (1.2) | 1 (0.2) |
Outcome | ACEIs N (%) n = 129 | ARBs N (%) n = 152 | Unadjusted OR ACEIs vs. ARBs (95%CI) | p-Value |
---|---|---|---|---|
Death | 44 (34.1) | 37 (24.3) | 1.60 (0.95–2.71) | 0.072 |
Severe pneumonia | 86 (66.6) | 92 (60.5) | 1.30 (0.80–2.13) | 0.288 |
Acute renal insufficiency | 42 (32.6) | 64 (42.1) | 0.66 (0.40–1.08) | 0.100 |
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Cordeanu, E.-M.; Jambert, L.; Severac, F.; Lambach, H.; Tousch, J.; Heitz, M.; Mirea, C.; Hamadé, A.; Younes, W.; Frantz, A.-S.; et al. Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors. J. Clin. Med. 2020, 9, 3472. https://doi.org/10.3390/jcm9113472
Cordeanu E-M, Jambert L, Severac F, Lambach H, Tousch J, Heitz M, Mirea C, Hamadé A, Younes W, Frantz A-S, et al. Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors. Journal of Clinical Medicine. 2020; 9(11):3472. https://doi.org/10.3390/jcm9113472
Chicago/Turabian StyleCordeanu, Elena-Mihaela, Lucas Jambert, Francois Severac, Hélène Lambach, Jonathan Tousch, Marie Heitz, Corina Mirea, Amer Hamadé, Waël Younes, Anne-Sophie Frantz, and et al. 2020. "Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors" Journal of Clinical Medicine 9, no. 11: 3472. https://doi.org/10.3390/jcm9113472
APA StyleCordeanu, E.-M., Jambert, L., Severac, F., Lambach, H., Tousch, J., Heitz, M., Mirea, C., Hamadé, A., Younes, W., Frantz, A.-S., Merdji, H., Schini-Kerth, V., Bilbault, P., Meziani, F., Ohlmann, P., Andres, E., & Stephan, D. (2020). Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors. Journal of Clinical Medicine, 9(11), 3472. https://doi.org/10.3390/jcm9113472