Between March 4 and June 15, 2020, 2041 patients were flagged in the electronic health record with a diagnosis of COVID-19 and pneumonia. A total of 539 patients were excluded based on eligibility criteria (less than 18 years of age, pregnant, other formulations of corticosteroids or hospitalized for less than 2 days). As defined by the prior study, the propensity score matched sample was constructed out of 759 patients (380 in no methylprednisolone and 379 in methylprednisolone). (Table 1, Tables S1, Figures S1-S2) (32) After an examination of the proportional hazard assumption, methylprednisolone, and Fractional inspired oxygen (FiO2) significantly violated it (both with P < 0.0001). (32) The supremum test also indicated that non-proportionality was observed in other variables such as nursing home, lack of taste or smell, WBC < 11,000 cells/ml, creatinine > 1.5 ng/mL, respiratory rate > 22 bpm, hydroxychloroquine (HCQ), methylprednisolone, high dose methylprednisolone (HDMP), low dose methylprednisolone (LDMP), calcium, and initial diastolic blood pressure.
Table 1
Characteristics of hospitalized COVID-19 patients treated with or without Methylprednisolone (n = 759)
| No Methylprednisolone (n = 380) | Methylprednisolone (n = 379) | |
Level | Count (%) | Count (%) | P-Value |
Age in years | 65 (54,80) | 64(55,74) | 0.0230 |
Age ≥ 60 years | 254(66.67) | 244(64.55) | 0.2436 |
Male | 237(62.20) | 242(64.02) | 0.5775 |
Weight (kg) | 81.67(70.30,96.00) | 83.90(71.70,99.80) | 0.8758 |
BMI ≥ 30 kg/m2 | 179(46.98) | 181(47.88) | 0.6767 |
Black | 58(15.30) | 44(11.80) | 0.2500 |
White | 178(46.97) | 160(42.90) | 0.2500 |
Asian/Indian | 25(6.60) | 133(35.66) | 0.2500 |
Hispanic | 118(31.13) | 181(47.88) | 0.2500 |
Non-smoker | 278(78.31) | 251(74.04) | 0.2334 |
Smoker (Former or Current) | 77(21.69) | 88(25.96) | 0.2334 |
Fever | 250(65.79) | 294(77.78) | 0.0003 |
Shortness of breath | 248(65.09) | 298(79.05) | < .0001 |
Cough | 242(63.68) | 270(71.43) | 0.0191 |
Altered Mental Status | 63(16.54) | 41(10.85) | 0.0032 |
GI | 76(20.00) | 81(21.49) | 0.5211 |
Anosmia or Ageusia | 6(1.59) | 9(2.45) | 0.5930 |
Duration of Symptoms PTA in days | 5.00(2.00,7.00) | 5.00(3.00,7.00) | 0.0699 |
Diabetes | 143(37.53) | 138(36.51) | 0.6521 |
COPD | 20(5.25) | 28(7.41) | 0.2482 |
Asthma | 24(6.30) | 37(9.81) | 0.0741 |
Hypertension | 225(59.06) | 219(57.94) | 0.5525 |
Cancer | 43(11.29) | 43(11.38) | 0.9013 |
Cerebrovascular Accident | 18(4.74) | 14(3.70) | 0.3692 |
Coronary Artery Disease | 29(7.61) | 28(7.41) | 0.8886 |
Arrhythmia | 41(10.79) | 30(7.94) | 0.1213 |
Renal Failure | 28(7.35) | 31(8.20) | 0.6682 |
Rheumatologic disorder | 10(2.62) | 19(5.04) | 0.0588 |
qSOFA 0 | 224(58.49) | 222(58.42) | 0.7647 |
qSOFA 1 | 130(33.94) | 130(34.21) | 0.7647 |
qSOFA 2 | 28(7.31) | 26(6.84) | 0.7647 |
qSOFA 3 | 1(0.26) | 2(0.53) | 0.7647 |
Temperature | 98.80(97.70,100.40) | 99.30(98.00,100.70) | 0.1284 |
Heart Rate | 95.00(84.00,108.00) | 97.00(86.00,108.00) | 0.1438 |
Arterial pressure | 92.33(83.33,100.50) | 90.67(81.83,99.33) | 0.0870 |
Respiratory Rate | 19.00(18.00,22.00) | 20.00(18.00,22.00) | 0.3231 |
O2 Sat < 94% | 215(56.43) | 217(57.41) | 0.6733 |
Nasal Cannula | 160(82.05) | 131(65.83) | 0.2500 |
High Flow | 6(3.08) | 15(7.54) | 0.2500 |
CPAP | 1(0.51) | 2(1.01) | 0.2500 |
BiPAP | 0(0.00) | 2(1.01) | 0.2500 |
Non-rebreather | 26(13.33) | 46(23.12) | 0.2500 |
Mechanical Ventilation | 35(11.15) | 129(39.33) | < .0001 |
WBC | 6.65(5.10,9.20) | 6.50(5.10, 9.50) | 1.0000 |
HGB | 13.40(12.30,14.50) | 13.50(12. 20,14.70) | 0.6746 |
PLT | 203.00(161.00,257.0 0) | 189.00(14 7.00,252. 00) | 0.2736 |
ALC | 0.90(0.60,1.30) | 0.80(0.60, 1.10) | 0.0031 |
IL6 | 12.00(5.00,39.00) | 15.00(5.0 0,36.00) | 0.2678 |
CRP | 9.88(4.99,17.31) | 12.67(6.8 4,19.08) | 0.0047 |
D-dimer | 1.09(0.65,2.20) | 1.44(0.72, 3.13) | 0.1155 |
Ferritin | 729.50(325.50,1404. 00) | 867.00(41 8.00,1548 .00) | 0.0675 |
Creatinine | 1.01(0.80,1.50) | 1.01(0.80, 1.35) | 0.2630 |
Troponin | 0.03(0.01,0.30) | 0.02(0.01, 0.09) | 0.0732 |
BNP | 131.85(40.30,1000.5 5) | 88.80(26. 20,362.00 ) | 0.2110 |
Hydroxychloroquine | 269(71.93) | 317(88.55 ) | < .0001 |
Azithromycin | 255(68.55) | 264(73.54 ) | 0.0728 |
Remdesivir | 3(0.82) | 10(2.82) | 0.0196 |
Tocilizumab | 13(3.53) | 63(17.65) | < .0001 |
Convalescent Plasma | 0(0.00) | 4(28.57) | < .0001 |
The main cause of mortality was ARDS, regardless of whether they received methylprednisolone or not and no confirmed concomitant bacterial pneumonia or pneumothoraxes. In those who received methylprednisolone, we performed a Kaplan Meier plot for patients who had persistent hypoxemia (S/F ratio < 315 on both day 1 and day 7) versus those who had no persistent hypoxemia (S/F ratio < 315 on day 1 but S/F ratio > 315 on day 7). Those who had persistent hypoxemia (n = 200), mortality was 86 patients (43%) with in-hospital-survival median 31 days [IQR: 22–48 days] compared to those with no persistent hypoxemia had a mortality of 8 patients (9.6%), in-hospital-survival median 60 days; IQR 25–60 days. (HR = 2.52 95% CI 1.23–5.15); P = 0.0385. (Fig. 1)
Among the racial/ethnic groups with improved hypoxemia and with persistent hypoxemia, there was statistically significant difference with in-hospital survival (P = 0.0474). (Fig. 2) However, there was no statistically significant difference with in-hospital survival those with improved hypoxemia on day 7 between Asians, Indians, Blacks and non-white Hispanics (S/F > 315) (n = 16) versus Whites (n = 19) (P = 0.1138) or in-hospital-survival with persistent hypoxemia on day 7 between Asians, Indians, Blacks, and non-White Hispanics (n = 91) versus Whites (n = 70) (P = 0.06).
We wanted to determine the discriminatory ability of the biomarkers (IL-6 CRP, d-dimer and ferritin) for hypoxemia (S/F < 315). (Table S3) At < 7 days from admission, the AUROC for IL-6 was 0.756 (CI 0.626,0.886), D-dimer 0.644 (CI 0.485,0.802), CRP 0.659(CI 0.510,0.809), and ferritin 0.527(CI 0.368,0.687). (Fig. 3) At ≥ 7 days from admission, the AUROC for IL-6 was 0.697(CI 0.571,0.822), D-dimer was 0.729(CI 0.617,0.842), CRP was 0.570(0.448,0.691) and ferritin was 0.556(CI 0.423,0.689). (Fig. 4)