Based on the predefined inclusion and exclusion criteria, the final sample resulted in 167 patients. From these, 56 patients died during hospitalization or follow-up. Due to the importance of a timely description of lung abnormalities, we evaluated only the first 44 consecutively included patients six months after hospital discharge. There were no missing cases. All patients will have a 1-year evaluation, as defined in the original protocol.
Table 1 described demographic information. 70% of the patients were male, and the mean age was 54 years. The mean body mass index was 30, and the mean Charlson comorbidity index was 1.63. The mean length of ICU stay was 12 days and the mean length of hospital stay was 16 days. The need for mechanical ventilation was 23% of the sample. The mean SAPS III score was 48, and the mean respiratory SOFA was 2.8 at admission (D1) and 2.0 72 hours after (D3). These variables were not statistically different compared to the remaining 67 patients not included in this preliminary analysis.
Table 1
– General patients’ characteristics
Variables | N(%) | Mean (SD) |
Age, Years | | 54(11) |
Gender, Male Female | 31(70) 13(30) | |
BMI | | 30(5.0) |
Extent of lung involvement at admission 25 to 50% > 50% | 15(40) 23(60) | |
Charlson Comorbidity Index | | 1.63(1.2) |
Corticosteroids, yes | 40 (91) | |
SAPS III | | 48(12.2) |
Respiratory SOFA D1 D3 | | 2.8(1.0) 2.0(1.4) |
SOFA D1 D3 | | 3.7(1.9) 2.9(2.6) |
C-reactive protein, mg/L D1 D3 | | 118(84) 108(96) |
ICU admission Yes No | 31(70) 13(30) | |
ICU length of stay, days | | 12(9.1) |
Invasive mechanical ventilation Yes No | 10(23) 34(77) | |
Days on Mechanical Ventilation | | 13(7.7) |
Length of hospital stay, Days. | | 16(10.3) |
SD - standard deviation; BMI - Body mass index; SAPS III - Simplified Acute Physiology Score 3; SOFA - sequential organ failure assessment score; ICU - intensive care unit; N - number of participants. |
Lung CT scan abnormalities were ground-glass (15 from 24) and fibrosis (9 from 24). Thus 24 (60%) of the patients had persistent lesions on CT-scan. Table 2 presented the relation of acute-phase variables and the persistence of lung abnormalities on the CT-scan 6-months after hospital discharge. In the univariate analysis, no single variable was associated with CT-scan lesions. However, c-reactive protein (CRP) at D1 and D3 and respiratory SOFA at D3 reached the threshold and were included in the regression analysis. Only CRP levels were marginally, but not significantly, related to the persistence of CT-scan lesions (Table 2).
Table 2
Variables associated with the persistence of lesions on lung computed tomography scan 6-months after hospital discharge.
Variables | Present (n = 24) | Absence (n = 20) | p-valuea | RR (CI 95%)b |
Age, years, mean (SD) | 54(11) | 54(11) | 0.99 | NA |
Gender Male. n (%) | 16(66) | 15(75) | 0.55 | NA |
BMI mean (SD) | 31(4.8) | 30(5.4) | 0.64 | NA |
Extent of lung involvement at admissionc n (%) 25 to 50% > 50% | 8(38) 13(62) | 7(41) 10(59) | 0.85 | NA |
Charlson Comorbidity Index mean (SD) | 1.8(1.2) | 1.4(1.2) | 0.34 | NA |
SAPS III mean (SD) | 47(14.4) | 48(10.6) | 0.91 | NA |
Respiratory SOFA D1. mean (SD) D3. mean (SD) | 2.9(1.1) 2.4(1.3) | 2.7(0.9) 1.8(1.5) | 0.56 0.16* | NA 1.04 (0.7–1.5) |
SOFA D1. Mean (SD) D3. Mean (SD) | 3.6(1.7) 3.0(2.5) | 3.9(2.2) 2.7(2.8) | 0.59 0.67 | NA NA |
C-reactive protein, mg/L D1. Mean (SD) D3. Mean (SD) | 99(72) 79(54) | 146(96) 164(133) | 0.13 0.08* | NA 0.98 (0.98-1.0) |
ICU yes, n(%) | 31(55) | 14(45) | 0.95 | NA |
ICU length of stay, days mean (SD) | 12(9.9) | 11(8.3) | 0.65 | NA |
Mechanical ventilation yes, n(%) | 4(40) | 6(60) | 0.29 | NA |
Days on Mechanical Ventilation mean (SD) | 14(8.2) | 12(7.9) | 0.63 | NA |
Length of hospital stay Days. Mean (SD) | 17(11.4) | 15(8.9) | 0.61 | NA |
SD – standard deviation; RR- Relative Risk; CI – confidence interval; NA – not applied; BMI – Body mass index; SAPS III – Simplified Acute Physiology Score 3; SOFA – sequential organ failure assessment score; ICU – intensive care unit; N – number of participants;* p < 0.20 variables included in the binary logistic regression. a p-value from the univariate analysis. bRR form the regression analysis. c for six patients, CT scan, was not performed at hospital admission. |
In the 6MWT (Table 3), 15 (35%) patients had a significant desaturation. In the univariate analysis, desaturation was associated with female gender, Charlson comorbidity index, and respiratory SOFA D3. Only the female gender was independently associated with desaturation in 6MWT. Of these 15 patients, 10 (66%) had persistence of CT scan alterations, being 6 (60%) ground-glass and 4 (40%) fibrotic lesions.
Table 3
Variables associated with desaturation in the 6-minute walk test 6-months after hospital discharge.
Variables | Present (n = 15) | Absence (n = 29) | p-valuea | RR (IC 95%)b |
Age, years, mean(SD) | 56(10) | 52.7(11) | 0.24 | NA |
Gender Male. n (%) | 6 (40) | 25(86) | 0.001* | 0.13 (0.03–0.6) |
BMI mean (SD) | 32(6.8) | 30(3.8) | 0.52 | NA |
Extent of lung involvement at admissionc n (%) 25 to 50% > 50% | 4(27) 11(73) | 12(50) 12(50) | 0.08 | NA |
Charlson Comorbidity Index mean (SD) | 2.1(1.2) | 1.4(1.1) | 0.044* | 1.5 (0.8–2.9) |
SAPS III mean (SD) | 53(15.0) | 46(10.1) | 0.15 | NA |
Respiratory SOFA D1. mean (SD) D3. mean (SD) | 2.9 (1.2) 2.6(1.1) | 2.7(0.9) 1.8(1.5) | 0.50 0.045* | NA 1.06 (0.8–1.4) |
SOFA D1. mean (SD) D3. mean (SD) | 3.6(1.7) 3.6(2.8) | 3.6(1.7) 2.4(2.4) | 0.73 0.15 | NA NA |
C-reactive protein, mg/L D1. mean (SD) D3. mean (SD) | 88(45) 91 (89) | 136(96) 122(102) | 0.07 0.40 | NA NA |
ICU yes, n(%) | 11 (73) | 20 (69) | 0.76 | NA |
ICU length of stay, days mean (SD) | 14(8.0) | 10(9.6) | 0.279 | NA |
Mechanical Ventilation yes, n(%) | 4 (27) | 6 (21) | 0.65 | NA |
Days on Mechanical Ventilation mean (SD) | 15(5.3) | 11(9.2) | 0.750 | NA |
Length of hospital stay Days. mean (SD) | 20(10.3) | 14(9.9) | 0.485 | NA |
SD - standard deviation; RR- Relative Risk; CI - confidence interval; NA - not applied; BMI - Body mass index; SAPS III - Simplified Acute Physiology Score 3; SOFA - sequential organ failure assessment score; ICU - intensive care unit; N - number of participants;* p < 0.20 and included in the binary logistic regression. a p-value from the univariate analysis. bRR form the regression analysis. c for five patients, CT scan was not performed at hospital admission. |
Only 8 (18%) of the patients had a significant (< 80% of predicted value) decrease in FEV1. When analyzing the FEV1 (Table 4), age was significantly associated with an abnormal FEV1. Interestingly, all patients that had reduced FEV1 had more than 50% of ground-glass at hospital admission. However, due to the low number of events, every attempt to perform a binary regression resulted in an overfitted model. Of these eight patients, 2 (25%) had persistence of CT scan alterations, being 1 (50%) ground-glass and 1 (50%) fibrotic lesions.
Table 4
Variables associated with a decreased forced expiratory volume in one second 6-months after hospital discharge.
Variables | Present (n = 8) | Absence (n = 36) | p-valuea |
Age years. mean(SD) | 60(5) | 53(11) | 0.015* |
Gender Male. n (%) | 6 (75) | 25(10) | 0.75 |
BMI mean (SD) | 32(5.4) | 30(5.0) | 0.35 |
Extent of lung involvement at admissionb n (%) 25 to 50% > 50% | 0(0.0) 7(100) | 15(48) 16(52) | 0.029* |
Charlson Comorbidity Index mean (SD) | 2.1(0.8) | 1.5(1.2) | 0.11 |
SAPS III mean (SD) | 50(15.2) | 48(12.0) | 0.71 |
Respiratory SOFA D1. mean (SD) D3. mean (SD) | 2.9(1.2) 2.0(1.4) | 2.8(0.9) 2.1(1.4) | 0.80 0.87 |
SOFA D1. mean (SD) D3. mean (SD) | 3.9(2.8) 2.6(2.1) | 3.7(1.7) 2.9(2.8) | 0.81 0.76 |
C-reactive protein, mg/L D1. mean (SD) D3. mean (SD) | 108(103) 129(172) | 122(80) 103(70) | 0.70 0.72 |
ICU yes, n(%) | 5(62) | 26(72) | 0.59 |
ICU length of stay, days mean (SD) | 14(11.6) | 11(8.7) | 0.51 |
Mechanical Ventilation yes, n(%) | 2(25) | 8(22) | 0.86 |
Days on Mechanical Ventilation mean (SD) | 18(7.8) | 11(7.4) | 0.25 |
Length of hospital stay Days. mean (SD) | 19(11.3) | 15(10.0) | 0.35 |
SD - standard deviation; BMI - Body mass index; FEV1 - forced expiratory volume in one second; SAPS III - Simplified Acute Physiology Score 3; SOFA - sequential organ failure assessment score; ICU - intensive care unit; N - number of participants. a p-value from the univariate analysis. b for six patients CT scan was not performed at hospital admission. * Due to the low number of events, it was not possible to perform binary regression analysis. |
When analyzing DLCO (Table 5), 19 (43%) of patients presented a significant decrease. In the univariate analysis age, gender and Charlson comorbidity index were significantly associated with a reduction in DLCO, but only gender was independently associated with a decrease in diffusion. Of these 19 patients, 11 (58%) had persistence of CT scan alterations, being 6 (54%) ground-glass and 5 (36%) fibrotic lesions.
Table 5
Variables associated with a decreased carbon monoxide diffusion 6-months after hospital discharge.
Variables | Present (n = 19) | Absence (n = 25) | p-valuea | RR (IC 95%)b |
Age years. mean(SD) | 59(9) | 50(11) | 0.008* | 1.03 (0.9–1.2) |
Gender Male. n (%) | 9(47) | 22(88) | 0.003* | 0.7 (0.006-0.7) |
BMI mean (SD) | 30(5.6) | 31(4.7) | 0.73 | NA |
Extent of lung involvement at admissionc n (%) 25 to 50% > 50% | 5(36) 9(64) | 10(42) 14(58) | 0.72 | NA |
Charlson Comorbidity Index, mean (SD) | 2.1(1.3) | 1.3(1.0) | 0.02* | 1.9 (0.65–5.6) |
SAPS III mean (SD) | 48(10.6) | 48(14) | 0.88 | NA |
Respiratory SOFA D1. mean (SD) D3. mean (SD) | 2.68(1.00) 2.32(1.25) | 2.88(0.97) 1.87(1.51) | 0.51 0.30 | NA NA |
SOFA D1. mean (SD) D3. mean (SD) | 3.3(2.2) 3.0(2.0) | 4.0(1.6) 2.8(3.1) | 0.21 0.88 | NA NA |
C-reactive protein, mg/L D1. mean (SD) D3. mean (SD) | 96(63) 83(51) | 137(96) 132(121) | 0.16 0.16* | NA 0.99 (0.97–1.005) |
ICU yes, n(%) | 14(74) | 17(68) | 0.68 | NA |
ICU length of stay, days mean (SD) | 12(6.8) | 11(10.8) | 0.68 | NA |
Mechanical Ventilation yes, n(%) | 3(16) | 7(28) | 0.34 | NA |
Days on Mechanical Ventilation mean (SD) | 13(5.5) | 12(8.8) | 0.87 | NA |
Length of hospital stay Days. mean (SD) | 17(8.6) | 15(11.4) | 0.48 | NA |
SD - standard deviation; RR- Relative Risk; CI - confidence interval; NA - not applied; BMI - Body mass index; SAPS III - Simplified Acute Physiology Score 3; SOFA - sequential organ failure assessment score; ICU - intensive care unit; N - number of participants; a p-value from the univariate analysis. bRR form the regression analysis. c for six patients, CT scan was not performed at hospital admission. |
MIP assessed respiratory muscle strength and was decreased in 19 (43%) patients (Table 6). Age, gender, and Charlson comorbidity index were associated with reduced MIP in the univariate analysis, but no one variable was independently associated with this outcome. It was observed a marginal, non-significant association with gender and Charlson comorbidity index. Of these 19 patients, 11 (58%) had persistence of CT scan alterations, being 7 (64%) ground-glass and 4 (36%) fibrotic lesions.
Table 6
Variables associated with a decreased Maximum Inspiratory Pressure 6-months after hospital discharge.
Variables | Present (n = 19) | Absence (n = 25) | p-valuea | RR (IC 95%)b |
Age years. mean(SD) | 57(9.0) | 51(11.6) | 0.05* | 0.96(0.86–1.08) |
Gender Male. n (%) | 10(53) | 20(80) | 0.03* | 0.25(0.05–1.16) |
BMI mean (SD) | 30(6.0) | 31(4.4) | 0.71 | NA |
Extent of lung involvement at admissionc n (%) 25 to 50% > 50% | 7(40) 9(60) | 9(41) 13(59) | 0.96 | NA |
Charlson Comorbidity Index mean (SD) | 2.2(1.3) | 1.2(1.0) | 0.008* | 2.6(0.8-8.0) |
SAPS III mean (SD) | 45(10.0) | 50(13.6) | 0.36 | NA |
Respiratory SOFA D1. mean (SD) D3. mean (SD) | 2.8(0.8) 2.3(1.2) | 2.7(1.1) 1.9(1.6) | 0.65 0.36 | NA NA |
SOFA D1. mean (SD) D3. mean (SD) | 3.9(1.6) 3.0(2.1) | 3.6(2.2) 2.9(3.1) | 0.71 0.78 | NA NA |
C-reactive protein, mg/L D1. mean (SD) D3. mean (SD) | 138(70) 97(53) | 100(97) 125(128) | 0.22 0.45 | NA NA |
ICU yes, n(%) | 14(74) | 16(64) | 0.62 | NA |
ICU length of stay, days mean (SD) | 10(7.4) | 13(10.7) | 0.42 | NA |
Mechanical Ventilation yes, n(%) | 5(26) | 5(20) | 0.67 | NA |
Days on Mechanical Ventilation mean (SD) | 9(8.1) | 16(6.1) | 0.21 | NA |
Length of hospital stay Days. mean (SD) | 16(8.3) | 16(11.6) | 0.92 | NA |
SD - standard deviation; RR- Relative Risk; CI - confidence interval; NA - not applied; BMI - Body mass index; SAPS III - Simplified Acute Physiology Score 3; SOFA - sequential organ failure assessment score; ICU - intensive care unit; N - number of participants; a p-value from the univariate analysis. b RR form the regression analysis. c for six patients CT scan was not performed at hospital admission. |
The impact of these dysfunctions on the BI was measured. Both the presence of desaturation on 6MWT (mean BI 91 ± 25 vs 74 ± 27) and reduced VEF1 (mean BI 89 ± 24 vs 68 ± 32) were significantly associated with lower BI scores (p < 0.05). DCLO was marginally but not significantly associated with lower BI scores (mean BI 92 ± 23 vs 76 ± 30, p = 0.06). There was no association between MIP and the extension of CT lesions and BI scores. When desaturation on 6MWT, FEV1 and DCLO entered in a linear regression only FEV1 (p = 0.019) and marginally DCLO (p = 0.06) were associated with lower Barthel scores (R square for the model 0.28).
Additionally, both the presence of desaturation on 6MWT (mean mMRC 0.8 ± 0.8 vs 1.7 ± 1.4) and reduced DCLO (mean mMRC 0.8 ± 1.2 vs 1.6 ± 1.0) were significantly associated with higher mMRC scores (p < 0.05). FEV1 and the extension of CT lesions were marginally, but not significantly associated with higher mMRC scores (mean mMRC 1.0 ± 1.0 vs 1.6 ± 1.7, p = 0.17 for FEV1; 0.9 ± 1.1 vs 1.3 ± 1.2, p = 0.17 for CT lesions). There was no association between MIP and mMRC scores. When desaturation on 6MWT, FEV1, DCLO, and CT lesions entered in a linear regression only FEV1 (p = 0.017) and marginally DCLO (p = 0.12) were associated with higher mMRC scores (R square for the model 0.32).