Figures
- FIGURE 1
Flow diagram of study enrolment.
- FIGURE 2
Patient-reported outcomes and pulmonary function measurements at 3 and 6 months after coronavirus disease 2019 (COVID-19) symptom onset. Each circle represents a patient, and the box represents the median and interquartile range. The y-axis shows the complete range of possible scores, and areas shaded in grey represent the normal range based on population adjusted norms where available. DLCO: diffusing capacity of the lung for carbon monoxide; EQ-5D: EuroQol- 5 Dimension; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; PHQ-9: Patient Health Questionnaire-9; PSQI: Pittsburgh Sleep Quality Index; QoL: quality of life; UCSD: University of California, San Diego shortness of breath questionnaire; VAS: visual analogue scale.
- FIGURE 3
The effect of time on the association between radiological abnormalities and diffusing capacity of the lung for carbon monoxide (DLCO) at 3 and 6 months after coronavirus disease 2019 (COVID-19) symptom onset. The x-axis represents the log of each radiological score. This figure demonstrates the association between 3-month computed tomography (CT) scores (ground glass, reticulation and total CT scores) and DLCO % predicted. In each case, there is a negative relationship between the radiological abnormalities and DLCO % predicted. However, this negative relationship is attenuated over time, as demonstrated by the shallower slopes at 6 months compared to 3 months.
Tables
- TABLE 1
Clinical characteristics and pulmonary function tests of patients hospitalised with coronavirus disease 2019 (COVID-19), 6 months after symptom onset
Features Overall cohort Patients with dyspnoea at 6 months p-value Unexplained dyspnoea Dyspnoea Subjects n 73 13 15 Demographics Age years 65 (53–72) 49 (34–67) 66 (59–76) 0.02 Male sex n (%) 44 (60) 4 (31) 9 (60) 0.12 Ever-smoker n (%) 23 (32) 2 (15) 8 (53) 0.06 Comorbidities n (%) Hypertension 27 (37) 5 (39) 8 (53) 0.43 Diabetes 19 (26) 3 (23) 5 (33) 0.69 Chronic pulmonary disease# 10 (14) 0 4 (27) 0.10 Coronary heart disease 7 (10) 0 3 (20) 0.23 Malignancy 8 (11) 1 (8) 1 (7) 1.00 Chronic kidney disease 6 (8) 1 (8) 2 (13) 1.00 Respiratory symptoms UCSD dyspnoea score 9 (3–31) 31 (17–40) 35 (23–46) 0.27 Cough VAS mm 20 (10–37) 10 (9–10) 30 (16–44) 0.07 Patient-reported outcome measures EQ-5D health utility 0.9 (0.8–0.9) 0.83 (0.77–0.87) 0.83 (0.76–0.87) 0.79 EQ-5D VAS 80 (75–90) 75 (70–90) 75 (65–85) 0.50 PSQI 5 (2–9)
(n=72)9 (6–12)
(n=12)7 (5–9) 0.28 PHQ-9 1 (0–6) 6 (2–10) 5 (1–7) 0.39 Pulmonary function tests FEV1 % predicted 91±15
(n=72)88±14 83±14 0.31 FVC % predicted 93±16
(n=72)93±11 81±15 0.03 FEV1/FVC % 84±12
(n=72)84±13 84±11 0.88 TLC % predicted 87±13
(n=64)86±11
(n=12)77±13
(n=14)0.09 DLCO % predicted 79±18
(n=70)88±9 63±14 <0.001 Transthoracic echocardiogram (n=72) LVEF % 60 (60–65) 60 (60–64) 65 (60–65) 0.29 PASP mmHg 27 (23–30) 19 (23–34) 27 (23–30) 0.77 Data are shown as mean±sd or median (IQR) unless otherwise stated. Data denoted in bold indicate p-value <0.05. Patients with dyspnoea (n=31) have been categorised into those with unexplained dyspnoea (i.e. UCSD >10 with DLCO ≥80% predicted) and those with dyspnoea (i.e. UCSD >10 with DLCO <80% predicted). There were three patients who did not have DLCO measurements and could not be categorised. Echocardiogram data are from 3 months after symptom onset. UCSD: University of California, San Diego shortness of breath questionnaire; VAS: visual analogue scale; EQ-5D: EuroQol- 5 Dimension; PSQI: Pittsburgh Sleep Quality Index; PHQ-9: Patient Health Questionnaire-9; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; TLC: total lung capacity; DLCO: diffusing capacity of the lung for carbon monoxide; LVEF: left ventricular ejection fraction; PASP: pulmonary artery systolic pressure. #: asthma (n=3), COPD (n=4), interstitial lung disease (n=2) or previous pulmonary embolism (n=1).
- TABLE 2
Respiratory symptoms, patient-reported outcome measures and pulmonary function at 3 and 6 months after coronavirus disease 2019 (COVID-19) symptom onset
3 months 6 months Mean or median difference 95% CI p-value Respiratory symptoms UCSD dyspnoea score 11 (3–26) 9 (3–31) −1.0 −4.0–2.0 0.53 Cough VAS 28 (8–60) 20 (10–35) −4.6 −18.7–8.4 0.41 Patient-reported outcome measures PHQ-9 2 (1–6) 1 (0–6) 0.5 0–1.5 0.16 PSQI 5 (3–8) 5 (2–9) 0 −1.0–1.5 0.81 EQ-5D utility 0.87 (0.79–0.95) 0.90 (0.81–0.95) −0.022 −0.1–0.003 0.12 EQ-5D VAS 75 (68–90) 80 (75–90) 6.3 5.0–9.5 <0.001 Pulmonary function, % predicted FEV1 89±16 91±16 1.3 −0.8–3.4 0.21 FVC 90±17 93±17 3.3 1.3–5.2 0.001 FEV1/FVC 87±12 84±12 −2.9 −4.5– −1.3 0.001 TLC 83±14 87±13 3.8 2.2–5.5 <0.001 DLCO 74±17 80±17 5.7 3.6–7.8 <0.001 Data for 3 and 6 months are shown as mean±sd or median (IQR). Data denoted in bold indicate p-value <0.05. A paired t-test or Wilcoxon signed rank test were used to compare values between 3 and 6 months. UCSD: University of California, San Diego shortness of breath questionnaire; VAS: visual analogue scale; PHQ-9: Patient Health Questionnaire-9; PSQI: Pittsburgh Sleep Quality Index; EQ-5D: EuroQol- 5 Dimension; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; TLC: total lung capacity; DLCO: diffusing capacity of the lung for carbon monoxide.
- TABLE 3
Predictors of change in respiratory outcomes and QoL between 3 and 6 months after coronavirus disease 2019 (COVID-19) symptom onset
Model Outcome Predictor (at 3 months) Coefficient 95% CI p-value Prespecified covariates 1a DLCO % predicted Ground glass score −2.2 −5.9–1.4 0.23 Sex, age, smoking pack-years Time 0.8 −0.5–2.0 0.21 Ground glass score*Time 0.6 0.05–1.2 0.03 1b DLCO % predicted Reticulation score −8.7 −12.1– −5.4 <0.001 Sex, age, smoking pack-years Time 1.2 0.1–2.2 0.03 Reticulation score*Time 0.6 −0.01–1.25 0.05 1c DLCO % predicted Total CT score −5.3 −8.7– −1.8 0.003 Sex, age, smoking pack-years Time 0.8 −0.5–2.2 0.23 Total CT score*Time 0.5 −0.04–1.05 0.07 2a UCSD Ground glass score 0.8 −3.4–5.0 0.69 Sex, age, smoking pack-years Time −0.2 −2.9–2.5 0.88 Ground glass score*Time −0.1 −1.4–1.1 0.87 2b QoL Ground glass score −0.003 −0.05–0.04 0.89 Sex, age, smoking pack-years Time −0.003 −0.02–0.02 0.77 Ground glass score*Time 0.01 −0.002–0.02 0.15 3a UCSD Unexplained dyspnoea 5.16 −7.95–18.3 0.43 Sex, age, smoking pack-years Time −0.45 −1.98–1.08 0.56 Unexplained dyspnoea*Time 1.01 −2.98–5.01 0.61 3b QoL Unexplained dyspnoea 0.01 −0.11–0.13 0.88 Sex, age, smoking pack-years Time 0.01 −0.001–0.02 0.07 Unexplained Dyspnoea*Time −0.01 −0.04–0.01 0.33 Time was categorised as 3 months (reference) and 6 months from symptom onset. Ground glass, reticulation and total CT scores were continuous variables that were log-transformed to make them normally distributed and to meet model assumptions. Unexplained dyspnoea at 3 months (defined as the presence of a UCSD dyspnoea score >10 with DLCO % predicted ≥80%) was categorical (present or absent). Time was included as an interaction term to evaluate whether time modified the effect of the primary predictor on the outcome. The primary predictor variables are denoted in bold. Example of Model 1a interpretation: the coefficient of −2.2 for ground glass score indicates that each 1% increase in ground glass score is associated with a 2.2% decrease in DLCO % predicted. This association is modified by time. At 6 months, for each 1% increase in ground glass, the coefficient will increase by 1.4 (0.8+0.6), which means there will be a 0.8% (−2.2+1.4) decrease in DLCO % predicted at 6 months compared to a 2.2% decrease at 3 months. DLCO : diffusing capacity of the lung for carbon monoxide; UCSD: University of California, San Diego shortness of breath questionnaire; QoL: quality of life. Asterisks (*) signify interaction terms.
Supplementary Material
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Supplementary material 00243-2021.SUPPLEMENT
