Table 1.
Demographics, Clinical Characteristics, and RAS Profiles of Patients with COVID-19 and Influenza
| Baseline Characteristics, Medication, and Outcome | |||||
|---|---|---|---|---|---|
| COVID-19 (n = 126) |
Comparator: Influenza (n = 27) |
P Value |
|||
| Nonsevere COVID-19 (n = 94) | Severe COVID-19 (n = 32) | Nonsevere vs. Severe COVID-19 | Severe COVID-19 vs. Influenza | ||
| Demographics | |||||
| Age, yr | 59 (47–77) | 68 (53–74) | 58 (49–64) | 0.207 | <0.05 |
| Sex, F | 34 (36.2) | 7 (21.9) | 11 (40.7) | 0.136 | 0.067 |
| BMI | 27.2 (24.5–30.6) | 25.7 (20.5–42.5) | n.a. | 0.740 | n.a. |
| Comorbidities | |||||
| Diabetes | 28 (30.1) | 11 (35.5) | 3 (13.6) | 0.577 | 0.075 |
| Hypertension | 47 (50.5) | 20 (64.5) | 2 (9.1) | 0.176 | <0.001 |
| COPD | 7 (7.5) | 6 (19.4) | 3 (13.6) | 0.063 | 0.585 |
| RAS inhibitor comedication | |||||
| ACEi | 16 (17.2) | 2 (6.5) | 2 (9.1) | 0.141 | 0.720 |
| ARB | 14 (15.1) | 8 (25.8) | 2 (9.1) | 0.175 | 0.125 |
| Antiviral medication | |||||
| Hydroxychloroquine | 8 (8.5) | 6 (18.8) | n.a. | 0.111 | n.a. |
| Lopinavir/ritonavir | 19 (20.2) | 11 (34.4) | n.a. | 0.104 | n.a. |
| Remdesivir | 4 (4.3) | 10 (31.2) | n.a. | <0.001 | n.a. |
| Convalescent plasma | 2 (2.1) | 4 (12.5) | n.a. | <0.05 | n.a. |
| Camostat | 25 (26.6) | 0 (0.0) | n.a. | <0.001 | n.a. |
| Immunomodulatory medication | |||||
| Tocilizumab | 1 (1.1) | 6 (18.8) | n.a. | <0.001 | n.a. |
| Steroids | 8 (8.6) | 11 (34.4) | n.a. | <0.001 | n.a. |
| Laboratory values | |||||
| Baseline CRP,* mg/L | 46.7 (19.5–82.7) | 120.90 (65.0–283.7) | 69.8 (32.1–226.1) | <0.001 | 0.188 |
| Maximum CRP,† mg/L | 58.9 (19.9–112.5) | 188.70 (102 –324.3) | 314.0 (211.9–338.2) | <0.001 | <0.05 |
| Baseline D-dimer,* mg/L | 0.96 (0.62–1.97) | 1.81 (0.82–4.27) | n.a. | <0.05 | n.a. |
| Maximum D-dimer,† mg/L | 1.63 (0.68–3.00) | 6.45 (2.67–15.55) | n.a. | <0.001 | n.a. |
| Baseline creatinine,* mg/dl | 0.86 (0.71–1.12) | 1.20 (0.78–1.50) | 1.29 (0.91–1.67) | <0.05 | 0.316 |
| Maximum creatinine,† mg/dl | 0.94 (0.76–1.17) | 1.42 (0.93–2.24) | 2.13 (1.47–3.46) | <0.001 | <0.05 |
| Baseline IL-6,* pg/ml | 25.1 (9.8–50.2) | 152.00 (68.8–369.3) | n.a. | <0.001 | n.a. |
| Maximum IL-6,† pg/ml | 25.8 (9.8–56.6) | 368.50 (138.5–1,448.5) | n.a. | <0.001 | n.a. |
| Severity of disease | |||||
| SOFA score | n.a. | 9 (8–11) | 9 (8–11) | n.a. | 0.551 |
| Outcome | |||||
| Length of hospital stay, d | 16 (10–26.5) | 31 (28–45) | 41 (25–66) | <0.001 | <0.05 |
| Death | 4 (4.3) | 11 (34.4) | 8 (29.6) | <0.001 | 0.581 |
| RAS Profiles | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| COVID-19 |
P Value |
|||||||||
| Nonsevere COVID-19 |
Severe COVID-19 |
Nonsevere: Early vs. Late COVID-19 | Severe: Early vs. Late COVID-19 | Early: Severe vs. Nonsevere COVID-19 | Late: Severe vs. Nonsevere COVID-19 | Severe COVID-19 vs. Influenza | ||||
| Days 0–3 (Early) | Days 9–11 (Late) | Days 0–3 (Early) | Days 9–11 (Late) | Comparator: Influenza | ||||||
| ACE2, ng/ml | 1.3 (1.0–2.4) | 3.2 (1.8–4.7) | 2.1 (1.3–3.0) | 15.1 (9.8–31.8) | 3.5 (2.3–6.6) | <0.001 | <0.001 | 0.078 | <0.001 | <0.001 |
| Angiotensin II, pmol/L | 47.7 (16.3–131.7) | 32.9 (9.3–78.2) | 165.7 (61.2–680.6) | 95.7 (37.5–250.0) | 114.4 (27.0–435.2) | 0.105 | 0.259 | <0.01 | <0.01 | 0.378 |
| Angiotensin 1–7, pmol/L | 1.5 (1.5–5.0) | 1.5 (1.5–3.7) | 10.8 (5.1–50.7) | 49.8 (14.6–132.0) | 21.0 (59–92.1) | 0.681 | 0.103 | <0.001 | <0.001 | 0.551 |
| Angiotensin-1–7–to–angiotensin-II ratio | 0.05 (0.03–0.15) | 0.10 (0.04–0.22) | 0.07 (0.04–0.13) | 0.31 (0.21–0.72) | 0.17 (0.10–0.47) | 0.129 | <0.001 | 0.545 | <0.001 | 0.671 |
Definition of abbreviations: ACE2 = angiotensin-converting enzyme 2; ACEi = ACE inhibitor; ARB = angiotensin receptor blocker; BMI = body mass index; COPD = chronic obstructive pulmonary disease; COVID-19 = coronavirus disease; CRP=C-reactive protein; n.a. = not applicable; RAS = renin–angiotensin system; SOFA = Sequential Organ Failure Assessment.
Continuous variables are presented as medians (quartile 1–quartile 3); binary variables are presented as n (%). Baseline characteristics and medication were compared using Student’s t, χ2, and Fisher’s exact tests, when appropriate, whereas laboratory data and ACE2 and RAS metabolite concentrations were compared by Mann-Whitney U tests. RAS metabolites and ACE2 in influenza samples were compared with the average value across all available time points in patients with severe COVID-19. The influenza cohort was assembled retrospectively using serum samples obtained for clinical routine and stored at the Department of Virology of the Medical University of Vienna. Longitudinal sampling in individuals with influenza was therefore not available for RAS profiling, as samples were obtained at different time points during the course of their disease (ranging from Day 0 to Day 21 after hospitalization). Significant P values are given in bold.
First value.
Highest value. Regarding the comparisons between patients with influenza and those with severe COVID-19, note that these comparisons were done between single measurements per patient (in patients with influenza) and averages across all time points per patient (in patients with severe COVID-19).