Figures
- FIGURE 1
PRISMA flow diagram of the study.
- FIGURE 2
Variables associated with past COVID-19 disease severity. Association of demographic and functional parameters with mild/moderate and severe/critical COVID-19 disease. OR and corresponding 95%CI from unadjusted analysis (orange) and individual multivariable models for each parameter adjusting for confounding by age and sex (green).
- FIGURE 3
Characteristic radiological changes of a patient with severe sequelae 3 months after COVID-19 pneumonia. Extensive involvement of both lungs is present in a patient 3 months after a severe COVID-19 pneumonia. Diffuse mosaic attenuation pattern in all lung lobes seen on axial 1 mm-thick CT (a) and 10 mm-thick minimum intensity projection (mIP) slices, 1 mm-thick CT (c) and 10 mm-thick minimum intensity projection (mIP) sagittal reformats (d) in lung windowing. This combines classical features of lung fibrosis with architectural distortion, reticulations, honeycombing (arrowhead in A) and traction bronchiectasis (orange arrows in a−d), as well as sharply demarcated areas of low attenuation in both lungs (orange circles in a−d). Clusters of contiguous hypoattenuating lobules and traction bronchiectasis are better visualised on mIP images with narrow window settings (b and d). Note the bulging of the interlobular septae (b and d, blue curved arrows) as well as the subpleural pneumatocele in c and d.
Tables
- TABLE 1
Baseline characteristics and follow-up findings in patients with severe/critical and mild /moderate COVID-19
COVID-19 survivors Severe/critical disease (n=66) Mild/moderate disease (n=47) Number (%), mean (sd), median (IQR) p-value# CHARACTERSTICS AT BASELINE Gender, men/women 40/26 27/20 0.89 Age, years 60.3 (12.0) 52.9 (10.9) <0.001 Ever smokers %¶ 56% 37% 0.16 Body mass index, kg/m2 29.8 (5.7) 25.5 (4.7) 0.02 D-Dimers, µg/L+ 1011 (366–1989) 387 (1–658) 0.26 Mechanical ventilation# 71% – – Duration of mechanical ventilation, days# 11.9 (9.5–18) – – COMORBIDITIES Interstitial lung disease 6% 3% 0.58 COPD 12% 3% 0.18 Asthma 9% 19% 0.32 Arterial hypertension 55% 8% 0.003 Diabetes 35% 0% 0.04 GERD 10% 9% 1 Sleep apnea 16% 3% 0.09 Chronic heart failure 10% 9% 1 Chronic renal failure 19% 0% 0.009 Cancer 6% 5% 1 Depression or antiety 12% 7% 0.66 PULMONARY FUNCTION AT FOLLOW-UP (n=72) FEV/FVC, % 94.7 (13.7) 84.2 (14.3) <0.001 TLC, L 5.22 (1.5) 6.5 (1.6) 0.050 TLC, % predicted 86.0 (20.0) 102.0 (19.3) 0.047 FVC, L 3.28 (1.01) 4.12 (1.2) <0.001 FVC, % predicted 86.6 (20.1) 95.6 (17.9) 0.02 FEV1, L 2.64 (0.8) 3.34 (1.1) <0.001 FEV1, % predicted 89.4 (20.7) 94.0 (15.6) 0.19 DLCO, % predicted 73.2 (18.4) 95.3 (20.6) 0.003 PImax, kPa 10.3 (8.8) 8.1 (2.6) 0.14 PEmax, kPa 8.7 (3.3) 10.3 (4.1) 0.20 OXYGENATION AT FOLLOW-UP (n=72) paO2, mmHg 79.0 (12.2) 87.5 (9.0) 0.0002 6-MWD, meters 456 (105) 576 (78) 0.001 O2 nadir on 6MWT 90 (4.5) 93 (3.1) 0.001 O2 desaturation 6MWT 5.6 (3.8) 2.6 (3.1) 0.02 #p-values from two-sample t-tests, Wilcoxon Rank Sum test, chi square test, or Fisher's Exact Test.
¶38 missing,.
+59 missing, *11 missing.
Abbreviations: COPD: chronic obstructive pulmonary disease; CT: computed tomography DLCO: diffusing capacity of the lung for carbon monoxide; FEV1: forced vital capacity in 1 min; FVC: forced vital capacity; GERD: gastroesophageal reflux disease; paO2: arterial partial pressure of oxygen; PImax: maximal inspiratory pressure; PEmax: maximal expiratory pressure; TLC: total lung capacity; 6MWD: 6-min walk distance; 6MWT: 6-min walk test.
- TABLE 2
Complete clinical multivariable model for severe/critical disease
OR (95% CI) p-value* DLCO, 10%-pred. 0.59 (0.37–0.87) 0.01 Age, year 0.98 (0.92–1.05) 0.62 Sex, men 1.98 (0.50–8.56) 0.34 BMI, kg/m2 1.19 (1.03–1.41) 0.02 6MWD, 10 m 0.88 (0.67–0.95) 0.01 Min. SpO2, % 0.80 (0.44–0.95) 0.07 Effect estimates indicate the associations of the variables with severe/critical disease in the context of the complete multivariable model. E.g. for every 10 meters increase in 6MWD the odds for severe/critical disease decreases by 12% adjusting for age, sex, BMI, DLCO, and minimal SpO2. The overall area under the receiver operating curve (AUC) of the multivariable model including DLCO, age, sex, BMI, 6MWD, and minimal SpO2 was 0.95 (95% CI 0.88–1.00).
Abbreviations: AUC: area under the receiver operating curve; BMI: body mass index; CI: confidence interval; DLCO: diffusing capacity of the lung for carbon monoxide; OR: odds ratio; 6MWD: 6-min walk distance; min. SpO2: minimal oxygen saturation on 6-min walk test.
- TABLE 3
Unadjusted and adjusted association of radiological features with previous severe/critical COVID-19
Radiological sign Unadjusted Adjusted for age and sex OR (95% CI) p# OR (95% CI) p# Hypoattenuation 13.5 (2.1–265) 0.02 11.7 (1.7–239) 0.03 Reticulations 10.1 (1.6–198) 0.04 8.73 (1.3–174) 0.06 #p-value for the radiological sign.
Odds ratios indicate the associations of the radiological variables at follow-up with severe/critical disease. E.g. the odds of severe/critical disease is 11.7 times higher for a patient with than for a patient without hypoattenuation, adjusting for age and sex.
Abbreviations: CI: confidence interval; COVID-19: coronavirus disease 2019; DLCO: diffusing capacity of the lung for carbon monoxide, OR: odds ratio.
