PMC:7110296 / 5605-18815 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/7110296","sourcedb":"PMC","sourceid":"7110296","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7110296","text":"Results\n\nBaseline characteristics\nA total of 701 patients were included in our study. Table 1 shows the clinical features of patients with COVID-19. Median age was 63 years, and 52.4% of patient were male. Median duration from illness onset to admission was 10 days. Of the total patients, 42.6% were reported as having ≥1 comorbidity: 2.0%, 1.9%, 33.4%, 14.3%, and 4.6% reported having, respectively, chronic kidney disease, chronic obstructive pulmonary disease, hypertension, diabetes, and tumor. Mean lymphocyte count was 0.9 ± 0.5 × 109/l below the lower limit of normal. Most patients had elevated levels of high-sensitivity C-reactive protein (83.0%) and erythrocyte sedimentation rate (81.6%), but elevated levels of procalcitonin were rare (9.8%). Coagulopathies were common in patients with COVID-19. In addition, mean serum lactose dehydrogenase (377 ± 195 U/l) was increased, especially in those with high baseline serum creatinine levels (Table 2 ).\nTable 1 Characteristics and outcomes of patients with COVID-2019\nVariables All patients Normal baseline serum creatinine Elevated baseline serum creatinine P value\nNumber 701 600 101\nAge, yr 63 (50–71) 61 (49–69) 73 (62–79) \u003c0.001\nMale patients 367 of 701 (52.4) 294 of 600 (49.0) 73 of 101 (72.3) \u003c0.001\nDays from illness onset to admission, d 10 (7–13) 10 (7–13) 9 (7–12) 0.381\nFever on admission 213 of 655 (32.5) 187 of 560 (33.4) 26 of 95 (27.4) 0.246\nSystolic blood pressure, mm Hg 128 (117–143) 128 (118–142) 128 (114–144) 0.942\nDiastolic blood pressure, mm Hg 79 (72–87) 79 (73–87) 77 (70–86) 0.282\nSevere disease 297 of 701 (42.4) 244 of 600 (40.7) 53 of 101 (52.5) 0.026\nAny comorbidity 297 of 698 (42.6) 237 of 598 (39.6) 60 of 100 (60.0) \u003c0.001\nChronic kidney disease 14 of 698 (2.0) 5 of 598 (0.8) 9 of 100 (9.0) \u003c0.001\nChronic obstructive pulmonary disease 13 of 698 (1.9) 9 of 598 (1.5) 4 of 100 (4.0) 0.191\nHypertension 233 of 698 (33.4) 185 of 598 (30.9) 48 of 100 (48.0) 0.001\nDiabetes 100 of 698 (14.3) 84 of 598 (14.0) 16 of 100 (16.0) 0.606\nTumor 32 of 698 (4.6) 28 of 598 (4.7) 4 of 100 (4.0) 0.965\nAdmission to intensive care unit 73 of 701 (10.4) 60 of 600 (10.0) 13 of 101 (12.8) 0.382\nAdministration of mechanical ventilation 97 of 701 (13.4) 75 of 600 (12.5) 22 of 101 (21.8) 0.012\nAcute kidney injury 36 of 701 (5.1) 24 of 600 (4.0) 12 of 101 (11.9) 0.001\n Stage 1 13 of 701 (1.9) 10 of 600 (1.7) 3 of 101 (3.0) 0.356\n Stage 2 9 of 701 (1.3) 4 of 600 (0.7) 5 of 101 (5.0)\n Stage 3 14 of 701 (2) 10 of 600 (1.7) 4 of 101 (4.0)\nIn-hospital death 113 of 701 (16.1) 79 of 600 (13.2) 34 of 101 (33.7) \u003c0.001\nCOVID-19, coronavirus disease 2019.\nData are presented as number/total (percentage) or median (interquartile range). The severity was staged based on the guidelines for diagnosis and treatment of COVID-19 (trial fifth edition) published by the Chinese National Health Commission on February 4, 2020.\nTable 2 Laboratory data of patients with COVID-19 on admission\nVariables All patients Normal baseline serum creatinine Elevated baseline serum creatinine P value\nLeukocyte count, × 10⁹/l 7.5 ± 7.5 7.2 ± 7.4 9.5 ± 8.0 0.005\nLymphocyte count, × 10⁹/l 0.9 ± 0.5 0.9 ± 0.5 0.8 ± 0.5 0.015\nHemoglobin, g/l 128 ± 17 127 ± 17 131 ± 20 0.110\nPlatelet count, × 10⁹/l 213 ± 94 216 ± 94 191 ± 94 0.014\nProthrombin time \u003e 14.5 s 260 of 670 (38.8) 215 of 573 (37.5) 45 of 97 (46.4) 0.097\nActivated partial thromboplastin time \u003e 42 s 210 of 495 (42.4) 171 of 423 (40.4) 39 of 72 (54.2) 0.029\nD-dimer \u003e 0.5 mg/l 512 of 661 (77.5) 424 of 563 (75.3) 88 of 98 (89.8) 0.002\nProcalcitonin ≥ 0.5 ng/ml 61 of 620 (9.8) 37 of 538 (6.9) 24 of 82 (29.3) \u003c0.001\nHigh-sensitivity C-reactive protein ≥ 10 mg/l 560 of 675 (83.0) 478 of 581 (82.3) 82 of 94 (87.2) 0.235\nErythrocyte sedimentation rate \u003e 15 mm/h 541 of 663 (81.6) 463 of 568 (81.5) 78 of 95 (82.1) 0.891\nAlanine aminotransferase, U/l 35 ± 38 36 ± 40 32 ± 29 0.206\nAspartate aminotransferase, U/l 42 ± 42 41 ± 43 47 ± 33 0.142\nTotal bilirubin, mmol/l 12 ± 23 11 ± 7 21 ± 57 0.061\nLactose dehydrogenase, U/l 377 ± 195 364 ± 180 458 ± 254 0.001\nCreatinine kinase, U/l 164 ± 233 149 ± 185 257 ± 410 0.108\nSodium, mmol/l 139 ± 5 138 ± 5 139 ± 7 0.373\nPotassium, mmol/l 4.2 ± 0.7 4.2 ± 0.7 4.5 ± 0 .7 \u003c0.001\nProteinuria\n Negative 248 of 442 (56.1) 232 of 389 (59.6) 16 of 53 (30.2) \u003c0.001\n 1+ 149 of 442 (33.7) 128 of 389 (32.9) 21 of 53 (39.6)\n 2+∼3+ 45 of 442 (10.2) 29 of 389 (7.5) 16 of 53 (30.2)\nHematuria\n Negative 324 of 442 (73.3) 299 of 389 (76.9) 25 of 53 (47.2) \u003c0.001\n 1+ 68 of 442 (15.4) 52 of 389 (13.4) 16 of 53 (133.3)\n 2+∼3+ 50 of 442 (11.3) 38 of 389 (9.8) 12 of 53 (22.6)\nBlood urea nitrogen, mmol/l 5.7 ± 3.9 4.8 ± 2.3 11 ± 7 \u003c0.001\nSerum creatinine, μmol/l 77 ± 31 68 ± 16 132 ± 39 \u003c0.001\neGFR, ml/min per 1.73 m2 87 ± 23 94 ± 17 48 ± 13 \u003c0.001\nPeak serum creatinine, μmol/l 91 ± 67 79 ± 48 163 ± 109 \u003c0.001\nCOVID-19, coronavirus disease 2019; eGFR, estimated glomerular filtration rate.\nData are presented as number/total (percentage) or mean ± SD.\n\nKidney abnormalities\nOn admission, serum creatinine and blood urea nitrogen (BUN) were elevated in 14.4% and 13.1% of the patients, respectively. Estimated glomerular filtration rate \u003c 60 ml/min per 1.73 m2 was reported in 13.1% of patients. During hospitalization, peak serum creatinine was 91 ± 67 μmol/l; 43.9% of patients had proteinuria, and relatively fewer patients (26.7%) had hematuria (Table 2). On admission, urethral catheterization was done in only 9.8% of patients, some of whom were due to the application of invasive mechanical ventilation. This indicated that the impact of catheterization on abnormal urinary analysis on admission was small.\nCompared with patients with normal serum creatinine, those who entered the hospital with an elevated serum creatinine were predominantly male and older and were more severely ill (Table 1). Moreover, patients with elevated baseline serum creatinine demonstrated a higher leukocyte count and lower lymphocyte and platelet counts. Coagulation pathway abnormalities, including prolonged activated partial thromboplastin time and higher D-dimer, were more common in patients with elevated baseline serum creatinine. The percentage of patients with increased procalcitonin, and the levels of aspartate aminotransferase and lactose dehydrogenase were also higher in patients with elevated baseline serum creatinine. Of note, the gap between peak and baseline serum creatinine was also much greater in patients with elevated baseline serum creatinine (Table 2).\n\nIncidence of AKI and in-hospital death\nDuring hospitalization, AKI occurred in 5.1% of patients. The incidence of AKI was significantly higher in patients with elevated baseline serum creatinine (11.9%) than in patients with normal baseline values (4.0%) (Table 1, Figure 1 ).\nFigure 1 Cumulative incidence of acute kidney injury of patients with coronavirus disease 2019 subgrouped by baseline serum creatinine.\nIn-hospital death occurred in 16.1% of patients. The median time to death was 6 days (interquartile range, 3–12 days). The incidence of in-hospital death in the patients with elevated baseline serum creatinine was 33.7%, which was significantly higher than in those with normal baseline serum creatinine (13.2%) (Table 1).\n\nAssociation of kidney disease indicators with in-hospital death\nKaplan-Meier analysis revealed a significantly higher in-hospital death rate for patients with kidney abnormalities, including elevated baseline serum creatinine, elevated baseline BUN, proteinuria, hematuria, and AKI (P \u003c 0.001) (Figure 2 ). Univariate Cox regression analysis showed that age above 65 years, male sex, and severe COVID-19 disease were associated with in-hospital death. In addition, the kidney disease indicators mentioned above were also associated with in-hospital death (Table 3 ). After adjusting for age, sex, disease severity, comorbidities, and lymphocyte count, the following were all associated with in-hospital death: proteinuria of any degree, hematuria of any degree, elevated baseline BUN, serum creatinine, peak serum creatinine \u003e 133 μmol/l, and AKI over stage 2 (Figure 3 ).\nFigure 2 Cumulative incidence for in-hospital death of patients with coronavirus disease 2019 subgrouped by kidney disease indicators. Shadows indicate the 95% confidence intervals of the corresponding estimates: (a) proteinuria, (b) hematuria, (c) baseline blood urea nitrogen (BUN), (d) baseline serum creatinine, (e) peak serum creatinine, and (f) acute kidney injury.\nTable 3 Univariate Cox regression analysis of association between kidney disease and in-hospital death in patients with coronavirus disease 2019\nVariables Hazard ratios 95% Confidence interval P value\nAge \u003e 65 yr 2.43 1.66–3.56 \u003c0.001\nSex, male 2.15 1.45–3.21 \u003c0.001\nSevere disease 6.10 3.86–9.64 \u003c0.001\nAny comorbidity 1.06 0.73–1.54 0.771\nLeukocyte count \u003e 10× 10⁹/l 1.06 0.73–1.54 0.771\nLymphocyte count \u003c 1.5 × 10⁹/l 1.02 0.70–1.48 0.931\nProteinuria\n Negative Reference Reference\n 1+ 4.12 1.97–8.62 \u003c0.001\n 2+∼3+ 10.92 5.00–23.86 \u003c0.001\nHematuria\n Negative Reference Reference\n 1+ 4.64 2.24–9.62 \u003c0.001\n 2+∼3+ 12.20 6.32–23.53 \u003c0.001\nElevated baseline blood urea nitrogen 7.15 4.92–10.39 \u003c0.001\nElevated baseline serum creatinine 2.99 2.00–4.47 \u003c0.001\nPeak serum creatinine \u003e133 μmol/l 5.88 3.90–8.87 \u003c0.001\nAcute kidney injury\n Stage 1 3.51 1.53–8.02 0.003\n Stage 2 6.24 2.73–14.27 \u003c0.001\n Stage 3 9.81 5.46–17.65 \u003c0.001\nThe severity was staged based on the guidelines for diagnosis and treatment of coronavirus disease 2019 (trial fifth edition) published by the Chinese National Health Commission on February 4, 2020. Comorbidities include chronic kidney disease, chronic obstructive pulmonary disease, hypertension, diabetes, and tumor.\nFigure 3 Association of kidney disease with in-hospital death in patients with coronavirus disease 2019 (COVID-19). Hazard ratios (HRs) of each variable were obtained using separate proportional hazard Cox models after adjustment for age, sex, disease severity, any comorbidity, and lymphocyte count. The severity was staged based on the guidelines for diagnosis and treatment of COVID-19 (trial fifth edition) published by the Chinese National Health Commission on February 4, 2020. Comorbidities include chronic kidney disease, chronic obstructive pulmonary disease, hypertension, diabetes, and tumor. 95% CI, 95% confidence interval.\n\nMedications\nThe medications before hospitalization were not available, thus we only summarized the medications during hospitalization in Table 4 . On the first day of admission, antivirus (73.0%), antibiotics (71.0%), and glucocorticoids (36.9%) were the 3 most common medications among patients with COVID-19, and the percentage of treatment with antivirus (P = 0.041) and glucocorticoid (P = 0.006) medications was significant higher in patients with AKI. However, when it comes to specific antivirus medications, including umifenovir, ganciclovir, interferon, lopinavir with ritonavir, oseltamivir, and ribavirin, there is no significant difference between patients with AKI and those without. Throughout the hospitalization, the percentage of medications increased, especially for antivirals, diuretics, and glucocorticoids. In addition, the percentages of diuretics during hospitalization were significantly higher in patients with AKI than in those without (72.2% vs. 6.2%, P \u003c 0.001).\nTable 4 Medications used on admission and during hospitalization\nDrugs Medications on admission Medications during hospitalization\nAll patients AKI Non-AKI P value All patients AKI Non-AKI P value\nRAAS inhibitors 33 of 701 (4.7) 0 of 36 (0.0) 33 of 665 (5.0) 0.334 41 of 701 (5.8) 0 of 36 (0.0) 41 of 665 (6.2) 0.242\nAntibiotics 498 of 701 (71.0) 27 of 36 (75.0) 471 of 665 (70.8) 0.591 600 of 701 (85.6) 35 of 36 (97.2) 565 of 665 (85.0) 0.041\nAntivirals 512 of 701 (73.0) 21 of 36 (58.3) 491 of 665 (73.8) 0.041 658 of 701 (93.9) 32 of 36 (88.9) 626 of 665 (94.1) 0.357\nUmifenovir 343 of 701 (48.9) 14 of 36 (38.9) 329 of 665 (49.5) 0.216 475 of 701 (67.8) 17 of 36 (47.2) 458 of 665 (68.9) 0.007\nGanciclovir 24 of 701 (3.4) 0 of 36 (0.0) 24 of 665 (3.6) 0.491 27 of 701 (3.9) 0 of 36 (0.0) 27 of 665 (4.1) 0.430\nInterferon 129 of 701 (18.4) 6 of 36 (16.7) 123 of 665 (18.5) 0.783 169 of 701 (24.1) 9 of 36 (25.0) 160 of 665 (24.1) 0.898\nLopinavir and ritonavir 74 of 701 (10.6) 2 of 36 (5.6) 72 of 665 (10.8) 0.469 196 of 701 (28.0) 4 of 36 (11.1) 192 of 665 (28.9) 0.021\nOseltamivir 39 of 701 (5.6) 1 of 36 (2.8) 38 of 665 (5.7) 0.707 79 of 701 (11.3) 1 of 36 (2.8) 78 of 665 (11.7) 0.166\nRibavirin 8 of 701 (1.1) 0 of 36 (0.0) 8 of 665 (1.2) 1.000 33 of 701 (4.7) 0 of 36 (0.0) 33 of 665 (5.0) 0.334\nAntidiabetic 68 of 701 (9.7) 3 of 36 (8.3) 65 of 665 (9.8) 1.000 119 of 701 (17.0) 4 of 36 (11.1) 115 of 665 (17.3) 0.336\nDiuretics 10 of 701 (1.4) 1 of 36 (2.8) 9 of 665 (1.4) 0.412 67 of 701 (9.6) 26 of 36 (72.2) 41 of 665 (6.2) \u003c0.001\nGlucocorticoids 259 of 701 (36.9) 21 of 36 (58.3) 238 of 665 (35.8) 0.006 387 of 701 (55.2) 22 of 36 (61.1) 365 of 665 (54.9) 0.465\nAKI, acute kidney injury; RAAS, renin-angiotensin-aldosterone system.\nRAAS inhibitors include 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