Figures
- FIGURE 1
Flow chart of the study. COVID-19: coronavirus disease 2019; ICU: intensive care unit; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TC: telephone consultation.
- FIGURE 2
High-resolution computed tomography (HRCT) image of the chest in a patient with mild fibrotic lung lesions 4 months after hospitalisation for coronavirus disease 2019 (COVID-19) compared with that during acute COVID-19. Coronal a) multiplanar reconstruction of an HRCT image of the chest during acute COVID-19 with extensive bilateral ground-glass opacities. Coronal b) multiplanar reconstructions and axial sections c) of an HRCT image of the chest from the same patient showing mild fibrotic lung lesions at 4 months, demonstrating small traction bronchiectasis close to the marginal fibrotic sequelae with a sub-pleural predominance.
- FIGURE 3
High-resolution computed tomography (HRCT) image of the chest in a patient with severe fibrotic lung lesions 4 months after hospitalisation for coronavirus disease 2019 (COVID-19) compared with that during acute COVID-19. Coronal a) multiplanar reconstruction of an HRCT image of the chest during acute COVID-19 with extensive bilateral ground-glass opacities and consolidations. Coronal b) multiplanar reconstructions and axial sections c) of an HRCT image of the chest from the same patient showing severe fibrotic lung lesions at 4 months, demonstrating diffuse traction bronchiectasis and association with ground-glass opacities.
- FIGURE 4
Distribution of patients evaluated at ambulatory care visits according to new-onset dyspnoea, fibrotic lung lesions on high-resolution computed tomography and decreased DLCO <70%. DLCO: diffusing capacity of the lung for carbon monoxide.
Tables
- TABLE 1
Baseline and hospitalisation characteristics of patients who were evaluated by telephone 4 months after hospital discharge according to the presence of new-onset dyspnoea
Available data All patients (478) Patients with new-onset dyspnoea (78) Patients without new-onset dyspnoea (400) p-value Demographic data Age, years 478 61.0±16.1 56.1±12.3 61.9±16.6 0.001 Women 478 201 (42.1%) 30 (38.5%) 171 (42.8%) 0.56 Body mass index, kg·m–2 351 28.8±5.6 29.0±5.1 28.8±5.8 0.69 Smoking No (<5 pack-years) 452 343 (75.9%) 60 (81.1%) 283 (74.9%) Former (≥5 pack-years) 452 83 (18.4%) 11 (14.9%) 72 (19.0%) 0.63 Active 452 26 (5.8%) 3 (4.1%) 23 (6.1%) Pre-COVID-19 comorbidities Respiratory disease COPD
478 17 (3.6%) 2 (2.6%) 15 (3.8%) 1 Other than COPD
478 75 (15.7%) 12 (15.4%) 63 (15.8%) 1 Hypertension 478 225 (47.1%) 30 (38.5%) 195 (48.8%) 0.12 Chronic heart disease 478 77 (16.1%) 4 (5.1%) 73 (18.2%) 0.007 Diabetes 478 128 (26.8%) 24 (30.8%) 104 (26.0%) 0.47 Chronic kidney disease 478 51 (10.7%) 2 (2.6%) 49 (12.2%) 0.02 Declared psychiatric disorder 478 42 (8.8%) 5 (6.4%) 37 (9.3%) 0.55 Neurodegenerative disorder 478 34 (7.1%) 0 (0%) 34 (8.5%) 0.02 Alcohol misuse 450 21 (4.7%) 3 (4.1%) 18 (4.8%) 1 Active cancer 478 18 (3.8%) 2 (2.6%) 16 (4.0%) 0.75 Other immunosuppression 478 18 (3.8%) 2 (2.6%) 16 (4.0%) 0.75 Long-term dialysis 478 17 (3.6%) 0 (0%) 17 (4.3%) 0.09 HIV infection 478 12 (2.5%) 1 (1.3%) 11 (2.8%) 0.7 Solid organ transplantation 478 9 (1.9%) 1 (1.3%) 8 (2.0%) 1 Liver disease 478 7 (1.5%) 2 (2.6%) 5 (1.3%) 0.32 Pregnancy 478 5 (1.1%) 0 (0%) 5 (1.3%) 1 Hospitalisation characteristics Total duration of hospitalisation, days 478 9 (4–15) 13 (7–23) 8 (4–14) <0.001 Hospitalisation in the ICU 478 142 (29.7%) 44 (56.4%) 98 (24.5%) <0.001 Duration of ICU stay, days 141 9 (4–19) 9 (4–21) 9 (4–19) 0.73 High flow oxygen 142 62 (43.7%) 20 (45.5%) 42 (42.9%) 0.92 Intubation during hospitalisation 142 73 (51.4%) 25 (56.8%) 48 (49.0%) 0.50 Duration of intubation, days 73 18 (11–32) 24 (12–38) 16 (11–27) 0.21 Pulmonary embolism 430 39 (9.1%) 14 (18.0%) 25 (6.8%) <0.001 Active anticoagulation (at the full therapeutic dose) 478 75 (15.7%) 30 (38.5%) 45 (11.2%) <0.001 Specific treatments during hospitalisation Azithromycin 478 120 (25.1%) 28 (35.9%) 92 (23.0%) 0.02 Anti-IL-6 478 37 (7.7%) 12 (15.4%) 25 (6.2%) 0.01 Hydroxychloroquine 478 32 (6.7%) 9 (11.5%) 23 (5.8%) 0.10 Corticosteroids 478 24 (5.0%) 1 (1.3%) 2 (5.8%) 0.15 Lopinavir/ritonavir 478 16 (3.4%) 6 (7.7%) 10 (2.5%) 0.03 Anti-IL-1 478 11 (2.3%) 3 (3.9%) 8 (2.0%) 0.40 Remdesivir 478 5 (1.1%) 1 (1.3%) 4 (1.0%) 0.59 Values are expressed as the median (interquartile range), mean±sd, or number and frequency. The p-values refer to a comparison between patients with and without new-onset dyspnoea. COPD: chronic obstructive pulmonary disease; COVID-19: coronavirus disease 2019; ICU: intensive care unit; IL: interleukin.
- TABLE 2
Characteristics of patients evaluated at the ambulatory care visit according to the presence of new-onset dyspnoea
Available data All (177) Patients with new-onset dyspnoea (78) Patients without new-onset dyspnoea (99) p-value Time from hospital discharge to the outpatient clinic, days 177 125 (107–144) 118 (105–140) 126 (108–146) 0.28 Assessment at the ambulatory care visit mMRC scale score for dyspnoea 177 <0.0001 0
87 (49.2%) 22 (28.2%) 65 (65.7%) 1–2
76 (42.9%) 48 (61.5%) 28 (28.3%) 3–4
14 (7.9%) 8 (10.3%) 6 (6.0%) New-onset cough 177 23 (13.0%) 15 (19.2%) 8 (8.1%) 0.04 6-min walk distance, m 161 462 (380–507) 450 (377–495) 474 (384–516) 0.35 Abnormal HRCT of the chest 171 108 (63.2%) 47 (61.0%) 61 (64.9%) 0.72 Reticulations 171 91 (53.2%) 41 (53.2%) 50 (53.2%) 1 Persistent ground-glass opacities 171 72 (42.1%) 36 (46.8%) 36 (38.3%) 0.30 Fibrotic lesions 171 33 (19.3%) 18 (23.1%) 15 (16.0%) 0.28 Pulmonary function tests FEV1, % pred 157 90.8±17.8 87.8±16.5 93.3±18.5 0.06 FEV1/VC, % pred 157 82.1±7.4 82.3±6.9 82.0±7.9 0.77 VC, % pred 152 89.1±16.4 85.6±16.3 92.1±16.0 0.02 TLC, % pred 149 82.8±15.3 80.0±15.2 85.1±15.0 0.04 DLCO, % pred 152 86.7±22.7 85.6±23.7 87.7±22.1 0.57 DLCO<70% 152 33 (21.7%) 17 (24.6%) 16 (19.3%) 0.55 Nijmegen score>22 168 36 (21.4%) 23 (29.5%) 13 (14.1%) 0.02 LVEF≤50% on echocardiography 83 10 (12.0%) 6 (15.0%) 4 (9.3%) 0.50 Values are expressed as the median (interquartile range), mean±sd, or number and frequency. The p-values refer to a comparison between patients with and without new-onset dyspnoea.
DLCO: diffusing capacity of the lungs for carbon monoxide; FEV1: forced expiratory volume in the first second of expiration; HRCT: high-resolution computed tomography; LVEF: left ventricular ejection fraction; mMRC: modified Medical Research Council; VC: vital capacity.
- TABLE 3
Lung abnormalities on HRCT at the ambulatory care visit (n=171)
Ground-glass opacities Ground-glass opacities, n (%) 72 (42.1%) Extent of ground-glass opacities 0% 98 (57.3%) 1–10% 50 (29.2%) 11–25% 19 (11.1%) 26–50% 3 (1.8%) Consolidations Consolidations n (%) 10 (5.9%) Extent of consolidations 0% 160 (93.6%) 1–10% 8 (4.7%) 11–25% 2 (1.2%) Reticulations and crazy paving Reticulations, n (%) 91 (53.2%) Crazy paving, n (%) 2 (1.2%) Fibrotic lesions Fibrotic lesions, n (%) 33 (19.3%) Extent of fibrotic lesions 0% 138 (80.7) 1–10% 17 (9.9%) 11–25% 13 (7.6%) 26–50% 2 (1.2%) Other abnormalities Emphysema, n (%) 11 (6.4%) Pleural effusion, n (%) 3 (1.8%) - TABLE 4
Baseline and hospitalisation characteristics of patients who were evaluated at ambulatory care visits according to the presence of fibrotic lesions in lungs
Available data All (171) Patients with fibrotic lesions (33) Patients without fibrotic lesions (138) p-value Demographic data Age, years 171 57.3±13.2 61.2±10.9 56.3±13.6 0.03 Women 171 65 (38.2%) 3 (9.1%) 56 (40.9%) 0.21 Body mass index, kg·m–2 159 29.1±5.4 28.2±4.9 29.4±5.5 0.24 Smoking No (<5 pack-years) 162 125 (77.2%) 22 (71.0%) 103 (78.6%) Former (≥5 pack-years) 162 24 (14.8%) 5 (16.1%) 19 (14.5%) 0.46 Active 162 13 (8.0%) 4 (12.9%) 9 (6.9%) Pre-COVID-19 comorbidities Respiratory disease COPD
170 5 (2.9%) 1 (3.0%) 4 (2.9%) 1 Other than COPD
170 30 (17.6%) 5 (15.2%) 25 (18.2%) 0.87 Hypertension 170 74 (43.5%) 12 (36.4%) 62 (45.3%) 0.47 Chronic heart disease 170 14 (8.2%) 3 (9.1%) 11 (8.0%) 0.74 Diabetes 170 51 (30.0%) 7 (21.2%) 44 (32.1%) 0.31 Chronic kidney disease 170 16 (9.4%) 1 (3.0%) 15 (10.9%) 0.32 Declared psychiatric disorder 170 10 (5.9%) 5 (15.2%) 5 (3.7%) 0.03 Neurodegenerative disorder 170 2 (1.2%) 0 (0%) 2 (1.5%) 1 Alcohol misuse 161 8 (5.0%) 1 (3.2%) 7 (5.4%) 1 Active cancer 170 3 (1.8%) 1 (3.0%) 2 (1.5%) 0.48 Other immunosuppression 170 7 (4.1%) 1 (3.0%) 6 (4.4%) 1.0 Long-term dialysis 170 6 (3.5%) 0 (0%) 6 (4.4%) 0.60 HIV infection 170 2 (1.2%) 0 (0%) 2 (1.5%) 1 Solid organ transplantation 170 4 (2.3%) 0 (0%) 4 (2.9%) 1 Liver disease 170 5 (2.9%) 0 (0%) 5 (3.7%) 0.58 Pregnancy 170 1 (0.6%) 0 (0%) 1 (0.7%) 1 Hospitalisation characteristics Total duration of hospitalisation, days 170 13 (6–25) 27 (15–44) 11 (5–17) <0.001 Hospitalisation in the ICU 170 94 (55.3%) 39 (87.9%) 65 (47.4%) <0.001 Duration of ICU stay, days 170 9 (4–22) 22 (5–33) 8 (3–14) 0.006 High flow oxygen 170 44 (46.8%) 18 (62.1%) 26 (40%) 0.08 Intubation during hospitalisation 170 49 (52.1%) 18 (62.1%) 31 (47.7%) 0.29 Duration of intubation, days 170 20 (12–34) 28 (16–43) 18 (10–25) 0.03 Pulmonary embolism 171 29 (17.0%) 13 (39.4%) 16 (11.6%) <0.001 Active anticoagulation (at the full therapeutic dose) 170 49 (28.8%) 15 (45.5%) 34 (24.8%) 0.03 Specific treatments during hospitalisation Azithromycin 170 53 (31.2%) 12 (36.4%) 41 (29.9%) 0.61 Anti-IL-6 170 26 (15.3%) 12 (36.4%) 14 (10.2%) 0.001 Hydroxychloroquine 170 18 (10.6%) 5 (15.2%) 13 (9.5%) 0.35 Corticosteroids 170 7 (4.1%) 3 (9.1%) 4 (2.9%) 0.13 Lopinavir/ritonavir 170 7 (4.1%) 2 (6.1%) 5 (3.7%) 0.62 Anti-IL-1 170 8 (4.7%) 3 (9.1%) 5 (3.7%) 0.19 Remdesivir 170 3 (1.8%) 0 (0%) 3 (2.2%) 1 Values are expressed as the median (interquartile range), mean±sd, or number and frequency. The p-values refer to a comparison between patients with and without fibrotic lesions.
COPD: chronic obstructive pulmonary disease; COVID-19: coronavirus disease 2019; ICU: intensive care unit; IL: interleukin.
- TABLE 5
Characteristics of patients evaluated at the ambulatory care visit according to the presence of fibrotic lesions in lungs
Available data All (171) Patients with fibrotic lesions (33) Patients without fibrotic lesions (138) p-value Time from hospital discharge to the outpatient clinic, days 171 122 (106–143) 109 (94–125) 127 (109–146) 0.004 Assessment at the ambulatory care visit New-onset dyspnoea 171 76 (44.4%) 18 (54.5%) 58 (42.0%) 0.28 mMRC scale score for dyspnoea 171 0.65 0
83 (48.5%) 15 (45.5%) 68 (49.3%) 1–2
74 (43.3%) 14 (42.4%) 60 (43.5%) 3–4
14 (8.2%) 4 (12.1%) 10 (7.2%) New-onset cough 171 22 (13.3%) 5 (15.1%) 17 (12.3%) 0.77 6-min walk distance, m 155 459 (378–504) 486 (401–510) 454 (375–498) 0.24 Abnormal HRCT of the chest 171 108 (63.5%) 33 (100%) 75 (54.5%) <0.001 Reticulations 171 91 (53.5%) 31 (93.9%) 60 (43.5%) <0.001 Persistent ground-glass opacities 171 72 (42.1%) 22 (66.6%) 50 (36.2%) 0.03 Pulmonary function tests FEV1, % pred 151 90.9±18.0 86.2±20.0 92.1±17.3 0.14 FEV1/VC, % 151 82.0±7.5 82.3±6.3 82.0±7.8 0.82 VC, % pred 146 89.2±16.3 80.6±20.0 91.5±14.4 0.007 TLC, % pred 143 82.6±15.2 74.1±13.7 84.9±14.8 <0.001 DLCO, % pred 146 86.5±22.8 73.3±17.9 89.7±22.8 <0.001 DLCO<70% 146 32 (21.9%) 12 (41.4%) 20 (17.1%) 0.01 Nijmegen score>22 162 35 (21.6%) 2 (6.3%) 33 (25.4%) 0.03 LVEF≤50% on echocardiography 80 10 (12.5%) 5 (19.2%) 5 (9.3%) 0.28 Values are expressed as the median (interquartile range), mean±sd, or number and frequency. The p-values refer to a comparison between patients with and without fibrotic lesions.
DLCO: diffusing capacity of the lungs for carbon monoxide; FEV1: forced expiratory volume in the first second of expiration; HRCT: high-resolution computed tomography; LVEF: left ventricular ejection fraction; mMRC: modified Medical Research Council; VC: vital capacity.
Supplementary Material
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Supplementary material 00479-2021.supplement
