Evolving Clinical Manifestations and Outcomes in COVID-19 Patients: A Comparative Analysis of SARS-CoV-2 Variant Waves in a Romanian Hospital Setting
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Setting
2.2. Participants
2.3. Variables and Measurements
2.4. Statistical Analysis
3. Results
4. Discussion
4.1. Therapy
4.2. Duration of Hospitalization
4.3. Intensive Care Need
4.4. Outcome
4.5. Complications of COVID-19
4.5.1. Pulmonary Complications
Pulmonary Embolism
Pneumothorax/Pneumomediastinum
4.5.2. Extrapulmonary Manifestations
Liver Injury
Acute Kidney Injury
Ischemic/Hemorrhagic Stroke
Myocardial Infarction (MI)
Gastrointestinal (GI) Bleeding
4.6. Limitations and Strengths
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristic | Total (n = 9049) | Wuhan (n = 4197) 46.38% | Alpha (n = 1260) 13.92% | Delta (n = 1382) 15.27% | Omicron (n = 2210) 15.27% | p-Value |
---|---|---|---|---|---|---|
Demographic data | ||||||
Age (years), median (IQR) | 61 (44, 73) | 54.0 (40.0–67.0) | 63.0 (51.0–72.0) | 64.5 (51.0–75) | 70.0 (49.0–80.0) | <0.001 |
Age ≥ 65 years, n (%) | 3906 (43.16) | 1264 (30.12) | 577 (45.79) | 691 (50) | 1374 (62.17) | <0.001 |
Age ≥ 70 years, n (%) | 2951 (32.61) | 867 (20.66) | 421 (33.41) | 519 (37.55) | 1144 (51.76) | <0.001 |
Sex (female), n (%) | 4935 (54.54) | 2227 (53.06) | 626 (49.68) | 761 (55.07) | 1321 (59.77) | <0.001 |
Comorbidities | ||||||
Cardiovascular, n (%) | 4730 (52.27) | 1805 (43.01) | 749 (59.44) | 886 (64.11) | 1290 (58.37) | <0.001 |
Obesity, n (%) | 2335 (25.8) | 878 (20.92) | 561 (44.52) | 477 (34.52) | 419 (18.96) | <0.001 |
Diabetes, n (%) | 1720 (19.01) | 665 (15.84) | 277 (21.98) | 330 (23.88) | 448 (20.27) | <0.001 |
Neurological, n (%) | 915 (10.11) | 254 (6.05) | 119 (9.44) | 172 (12.45) | 370 (16.74) | <0.001 |
Pulmonary, (n (%) | 892 (9.86) | 264 (6.29) | 129 (10.24) | 191 (13.82) | 308 (13.94) | <0.001 |
Cancer, n (%) | 654 (7.23) | 229 (5.46) | 69 (5.48) | 102 (7.38) | 254 (11.49) | <0.001 |
Renal, n (%) | 484 (5.35) | 159 (3.79) | 55 (4.37) | 97 (7.02) | 173 (7.83) | <0.001 |
Hepatic, (n (%) | 429 (4.74) | 154 (3.67) | 50 (3.97) | 89 (6.44) | 136 (6.15) | <0.001 |
Vaccination status, n (%) | <0.001 | |||||
0/1 | 3813 (42.14) | 446 (10.63) | 1247 (98.97) | 1089 (78.8) | 1031 (46.65) | |
2 | 935 (10.33) | 1 (0.02) | 13 (1.03) | 272 (19.68) | 649 (29.37) | |
3 | 548 (6.06) | 0 (0) | 0 (0) | 21 (1.52) | 527 (23.85) | |
4 | 3 (0.03) | 0 (0) | 0 (0) | 0 (0) | 3 (0.14) | |
Prevaccination | 3750 (41.44) | 3750 (89.35) | 0 (0) | 0 (0) | 0 (0) | |
Severity form, n (%) | <0.001 | |||||
Asymptomatic | 549 (6.07) | 524 (12.49) | 7 (0.56) | 1 (0.07) | 17 (0.77) | |
Mild | 1811 (20.01) | 989 (23.56) | 103 (8.17) | 122 (8.83) | 597 (27.01) | |
Medium | 3829 (42.31) | 1996 (47.56) | 628 (49.84) | 368 (26.63) | 837 (37.87) | |
Severe | 1881 (20.79) | 548 (13.06) | 437 (34.68) | 416 (30.1) | 480 (21.72) | |
Critical | 979 (10.82) | 140 (3.34) | 85 (6.75) | 475 (34.37) | 279 (12.62) | |
Therapy | ||||||
Hydroxychloroquine, n (%) | 1736 (19.18) | 1680 (40.03) | 43 (3.41) | 13 (0.94) | 0 (0) | <0.001 |
Lopinavir/ritonavir, n (%) | 653 (7.22) | 653 (15.56) | 0 (0) | 0 (0) | 0 (0) | <0.001 |
Remdesivir, n (%) | 1468 (16.22) | 360 (8.58) | 345 (27.38) | 417 (30.17) | 346 (15.66) | <0.001 |
Favipiravir, n (%) | 3615 (39.95) | 433 (10.32) | 957 (75.95) | 1105 (79.96) | 1120 (50.68) | <0.001 |
Molnupiravir, n (%) | 177 (1.95) | 0 (0) | 0 (0) | 0 (0) | 177 (8.01) | <0.001 |
Casirivimab/imdevimab, n (%) | 152 (1.67) | 0 (0) | 0 (0) | 0 (0) | 152 (6.88) | <0.001 |
Corticotherapy, n (%) | 5012(55.39) | 1734 (41.32) | 1079 (85.63) | 1130 (81.77) | 1069 (48.37) | <0.001 |
Anakinra, n (%) | 952(10.52) | 152 (3.62) | 279 (22.14) | 392 (28.36) | 129 (5.84) | <0.001 |
Tocilizumab, n (%) | 411(4.54) | 153 (3.65) | 138 (10.95) | 94 (6.8) | 26 (1.18) | <0.001 |
Anticoagulant, n (%) | 7022 (77.6) | 2850 (67.91) | 1167 (92.62) | 1300 (94.07) | 1705 (77.15) | <0.001 |
Outcome | ||||||
Hospitalization time (days), median (IQR) | 7 (4, 12) | 7 (4–12) | 8 (5–12) | 10 (6–15) | 7 (4–12) | <0.001 |
ICU stay, n (%) | 1018 (11.25) | 392 (9.34) | 195 (15.48) | 208 (15.05) | 223 (10.09) | <0.001 |
In-hospital mortality, n (%) | 610 (6.74) | 162 (3.86) | 109 (8.65) | 188 (13.6) | 151 (6.83) | <0.001 |
Mortality in patients staying in ICU, n (%) | 432 (42.44) | 134 (34.18) | 77 (39.49) | 115 (55.29) | 106 (47.53) | <0.001 |
Complications | All | Wuhan (n = 4197) | Alpha (n = 1260) | Delta (n = 1382) | Omicron (n = 2210) | p-Value | Died | OR (95% CI) | p-Value |
---|---|---|---|---|---|---|---|---|---|
Pulmonary | |||||||||
PNX/PNMD, n (%) | 127 (1.4) | 34 (0.81) | 28 (2.22) | 41 (2.97) | 24 (1.09) | <0.001 | 78 (61.42) | 25.1 (17.38–36.27) | <0.001 |
PE, n (%) | 153 (1.69) | 34 (0.81) | 36 (2.86) | 47 (3.4) | 36 (1.63) | <0.001 | 43 (28.1) | 5.74 (4–8.25) | <0.001 |
Extrapulmonary | |||||||||
Other thrombotic events, n (%) | 82 (0.91) | 7 (0.17) | 10 (0.79) | 20 (1.45) | 45 (2.04) | <0.001 | 43 (28.1) | 10.32 (6.6–16.14) | <0.001 |
Liver injury, n (%) | 1564 (17.28) | 337 (8.03) | 360 (28.57) | 480 (34.73) | 387 (17.51) | <0.001 | 114 (7.29) | 1.11 (0.9–1.37) | 0.342 |
AKI, n (%) | 538 (5.95) | 66 (1.57) | 92 (7.3) | 136 (9.84) | 244 (11.04) | <0.001 | 222 (41.26) | 14.71 (12.05–17.96) | <0.001 |
Ischemic/hemorrhagic stroke, n (%) | 85 (0.94) | 18 (0.43) | 14 (1.11) | 7 (0.51) | 46 (2.08) | <0.001 | 37 (45.68) | 12.32 (7.89–19.23) | <0.001 |
MI, n (%) | 24 (0.27) | 5 (0.12) | 6 (0.48) | 3 (0.22) | 10 (0.45) | 0.023 | 7 (29.17) | 5.75 (2.38–13.92) | <0.001 |
Gastrointestinal bleeding, n (%) | 60 (0.66) | 18 (0.43) | 2 (0.16) | 10 (0.72) | 30 (1.36) | <0.001 | 28 (46.67) | 12.64 (7.56–21.13) | <0.001 |
Other hemorrhagic events, n (%) | 104 (1.15) | 11 (0.26) | 12 (0.95) | 8 (0.58) | 73 (3.3) | <0.001 | 27 (25.96) | 5.03 (3.22–7.86) | <0.001 |
Complications | ICU (n = 1018) | Infectious Diseases Ward (n = 8031) | OR (95% CI) | p-Value |
---|---|---|---|---|
PNX/PNMD, n (%) | 111 (10.9) | 16 (0.2) | 61.31 (36.14–104.01) | <0.001 |
PE, n (%) | 81 (7.96) | 72 (0.9) | 9.56 (6.91–13.22) | <0.001 |
Other thromboembolic events, n (%) | 39 (3.83) | 43 (0.54) | 7.4 (4.77–11.47) | <0.001 |
Liver injury, n (%) | 236 (23.18) | 1328 (16.54) | 1.52 (1.3–1.78) | <0.001 |
AKI, n (%) | 240 (23.58) | 298 (3.71) | 8.01 (6.65–9.63) | <0.001 |
Stroke ischemic/hemorrhagic n (%) | 47 (4.62) | 34 (0.42) | 11.38 (7.29–17.79) | <0.001 |
MI, n (%) | 13 (1.28) | 11 (0.14) | 9.43 (4.21–21.11) | <0.001 |
Gastrointestinal bleeding, n (%) | 32 (3.14) | 28 (0.35) | 9.28 (5.56–15.47) | <0.001 |
Other hemorrhagic events, n (%) | 53 (5.21) | 51 (0.64) | 8.59 (5.82–12.7) | <0.001 |
Characteristics | OR-Adjusted | (95% CI) | (95% BCa CI) | p |
---|---|---|---|---|
Age ≥ 65 years | 3.93 | (3.09–5.04) | (3.1–5.16) | <0.001 |
Neurological | 2.42 | (1.95–3) | (1.93–3.03) | <0.001 |
Cardiovascular | 2.13 | (1.69–2.71) | (1.68–2.77) | <0.001 |
Cancer | 1.98 | (1.5–2.58) | (1.48–2.64) | <0.001 |
Pulmonary | 1.73 | (1.37–2.18) | (1.35–2.23) | <0.001 |
Renal | 1.7 | (1.27–2.25) | (1.27–2.32) | <0.001 |
Hepatic | 1.58 | (1.1–2.21) | (1.05–2.25) | 0.011 |
Diabetes | 1.33 | (1.09–1.61) | (1.08–1.62) | 0.004 |
Sex (M vs. F) | 1.27 | (1.07–1.51) | (1.06–1.51) | 0.008 |
Obesity | 1.12 | (0.91–1.37) | (0.9–1.39) | 0.278 |
Wave | ||||
Delta vs. Wuhan | 2.87 | (2.26–3.65) | (2.23–3.63) | <0.001 |
Alpha vs. Wuhan | 1.71 | (1.31–2.23) | (1.32–2.2) | <0.001 |
Omicron vs. Wuhan | 1.28 | (0.99–1.66) | (0.98–1.67) | 0.063 |
Vaccinated | 0.36 | (0.27–0.48) | (0.26–0.48) | <0.001 |
Predicted Complications | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Liver Injury | AKI | PE | PNX/PNMD | Stroke | |||||||||||
Independent Predictors | OR | 95% CI | p | OR | 95% CI | p | OR | 95% CI | p | OR | (95% CI) | p | OR | 95% CI | p |
Age ≥ 65 years | 0.81 | 0.71–0.91 | <0.001 | 3.47 | 2.67–4.54 | <0.001 | 2.2 | 1.49–3.28 | <0.001 | 1.77 | (1.16–2.74) | 0.009 | 2.24 | 1.2–4.43 | 0.015 |
Sex (M vs. F) | 1.12 | 1–1.26 | 0.057 | 1.18 | 0.97–1.43 | 0.091 | 1.56 | 1.13–2.17 | 0.007 | 1.13 | (0.79–1.61) | 0.497 | 1.53 | 0.97–2.42 | 0.068 |
Cardiovascular | 1.75 | 1.36–2.26 | <0.001 | 1.04 | 0.71–1.53 | 0.859 | 1.2 | (0.79–1.85) | 0.401 | 1.4 | 0.79–2.61 | 0.264 | |||
Obesity | 1.28 | 1.13–1.46 | <0.001 | 1.27 | 1.02–1.57 | 0.028 | 0.86 | 0.58–1.24 | 0.425 | 0.92 | (0.6–1.38) | 0.698 | 0.73 | 0.4–1.27 | 0.288 |
Diabetes | 0.85 | 0.73–0.99 | 0.032 | 1.24 | 1–1.52 | 0.044 | 1.09 | (0.7–1.65) | 0.688 | 0.77 | 0.43–1.29 | 0.339 | |||
Pulmonary | 2.54 | (1.65–3.82) | <0.001 | ||||||||||||
Cancer | 0.83 | 0.66–1.04 | 0.113 | 1.32 | 0.98–1.76 | 0.063 | 0.82 | 0.41–1.47 | 0.535 | 1.53 | (0.82–2.63) | 0.15 | |||
Renal | 1.83 | 1.38–2.42 | <0.001 | ||||||||||||
Hepatic | 1.15 | 0.89–1.47 | 0.291 | ||||||||||||
Corticotherapy | 1.84 | 1.59–2.13 | <0.001 | 2.38 | 1.82–3.12 | <0.001 | |||||||||
Tocilizumab | 0.87 | 0.67–1.12 | 0.289 | 1.01 | 0.67–1.46 | 0.979 | |||||||||
Anakinra | 1.53 | 1.3–1.8 | <0.001 | 1.94 | 1.53–2.46 | <0.001 | |||||||||
Favipiravir | 1.35 | 1.17–1.55 | <0.001 | 0.41 | 0.34–0.51 | <0.001 | |||||||||
Remdesivir | 1.21 | 1.04–1.4 | 0.014 | 1.3 | 1.04–1.6 | 0.018 | |||||||||
Wave | |||||||||||||||
Alpha vs. Wuhan | 2.63 | 2.16–3.21 | <0.001 | 4.07 | 2.84–5.86 | <0.001 | 3.27 | 2.01–5.32 | <0.001 | 2.42 | (1.44–4.05) | <0.001 | 1.89 | 0.88–4.01 | 0.097 |
Delta vs. Wuhan | 3.76 | 3.09–4.58 | <0.001 | 5.68 | 4–8.11 | <0.001 | 4.46 | 2.83–7.1 | <0.001 | 3.43 | (2.13–5.56) | <0.001 | 0.65 | 0.24–1.59 | 0.358 |
Omicron vs. Wuhan | 2.55 | 2.1–3.09 | <0.001 | 7.24 | 5.32–9.97 | <0.001 | 2.51 | 1.49–4.2 | <0.001 | 1.42 | (0.78–2.51) | 0.238 | 3.81 | 2.02–7.5 | <0.001 |
Vaccinated | 0.79 | 0.66–0.94 | 0.008 | 0.72 | 0.55–0.92 | 0.01 | 0.33 | 0.18–0.59 | <0.001 | 0.36 | (0.18–0.69) | 0.003 | 0.54 | 0.28–1 | 0.058 |
Severe or critical | 5.1 | 2.93–9.32 | <0.001 |
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Briciu, V.; Leucuta, D.-C.; Muntean, M.; Radulescu, A.; Cismaru, C.; Topan, A.; Herbel, L.; Horvat, M.; Calin, M.; Dobrota, R.; et al. Evolving Clinical Manifestations and Outcomes in COVID-19 Patients: A Comparative Analysis of SARS-CoV-2 Variant Waves in a Romanian Hospital Setting. Pathogens 2023, 12, 1453. https://doi.org/10.3390/pathogens12121453
Briciu V, Leucuta D-C, Muntean M, Radulescu A, Cismaru C, Topan A, Herbel L, Horvat M, Calin M, Dobrota R, et al. Evolving Clinical Manifestations and Outcomes in COVID-19 Patients: A Comparative Analysis of SARS-CoV-2 Variant Waves in a Romanian Hospital Setting. Pathogens. 2023; 12(12):1453. https://doi.org/10.3390/pathogens12121453
Chicago/Turabian StyleBriciu, Violeta, Daniel-Corneliu Leucuta, Monica Muntean, Amanda Radulescu, Cristina Cismaru, Adriana Topan, Lucia Herbel, Melinda Horvat, Mihai Calin, Roxana Dobrota, and et al. 2023. "Evolving Clinical Manifestations and Outcomes in COVID-19 Patients: A Comparative Analysis of SARS-CoV-2 Variant Waves in a Romanian Hospital Setting" Pathogens 12, no. 12: 1453. https://doi.org/10.3390/pathogens12121453
APA StyleBriciu, V., Leucuta, D.-C., Muntean, M., Radulescu, A., Cismaru, C., Topan, A., Herbel, L., Horvat, M., Calin, M., Dobrota, R., & Lupse, M. (2023). Evolving Clinical Manifestations and Outcomes in COVID-19 Patients: A Comparative Analysis of SARS-CoV-2 Variant Waves in a Romanian Hospital Setting. Pathogens, 12(12), 1453. https://doi.org/10.3390/pathogens12121453