Abstract
Background
The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown.
Methods
Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group.
Results
A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p<0.001), had higher burden of anxiety (29.1% versus 22.0%, p=0.002), depression (31.2% versus 24.7%, p=0.006), higher percentage of impaired mobility using short physical performance battery ≤10 (57.4% versus 45.2%, p<0.001) and 27% had a new disability (assessed by the Washington Group Short Set on Functioning) versus 16.6%, p=0.014. HRQoL assessed using EQ-5D-5L Utility Index was lower in the airways group (mean±SD 0.64±0.27 versus 0.73±0.25, p<0.001). Burden of breathlessness, fatigue and cough measured using a study-specific tool was higher in the airways group.
Conclusion
Individuals with pre-existing airway diseases hospitalised due to COVID-19 were less likely to feel fully recovered, had lower physiological performance measurements, more burden of symptoms and reduced HRQoL up to 1 year post-hospital discharge.
Shareable abstract
Following hospitalisation with COVID-19, individuals with pre-existing airway diseases were less likely to feel fully recovered, had more burden of symptoms and reduced health-related quality of life compared to those without pre-existing airway diseases https://bit.ly/3VfUhcM
Introduction
Early in the COVID-19 pandemic, the prevalence of asthma and COPD in hospitalised patients with COVID-19 was low, raising the possibility that pre-existing airway diseases or inhaled corticosteroid (ICS) therapy might play a protective role against contracting SARS-CoV-2 infection or severe outcomes [1, 2]. However, later reports found no evidence to support these theories [3, 4], and the number of hospitalised patients with pre-existing airway diseases increased, likely due to relaxation in social distancing [5]. Patients with COPD who were hospitalised were at increased risk of severe COVID-19 illness or death, likely due to factors such as older age, increased number of comorbidities and reduced physiological reserve to survive critical illness [6–9]. Worse clinical outcomes in hospitalised patients with pre-existing asthma were mainly observed in those with severe asthma or those who required multiple courses of oral corticosteroids in the preceding year [10, 11]. Results from a large UK hospitalised cohort found that patients with asthma were more likely to receive critical care than those without asthma [12]. Little is known about the impact of SARS-CoV-2 in patients with pre-existing bronchiectasis largely due to the scarce literature, but there is a suggestion that individuals with pre-existing bronchiectasis had increased risk of worse clinical outcomes after COVID-19 infection [13, 14].
The long-term sequelae following COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. An international consensus exercise to determine research priorities in patients with pre-existing airway diseases following COVID-19 hospitalisation identified the need to determine the short- and medium-term effects of COVID-19 infection in this group [15]. Here we report on the results from a large UK-based multicentre cohort study of hospitalised COVID-19 survivors (Post-hospitalisation COVID-19 study (PHOSP-COVID) study).
Materials and methods
Study design and participants
The PHOSP-COVID is a UK national multicentre prospective longitudinal cohort study. The PHOSP-COVID study methods have been described in detail elsewhere [16]. Participants were invited to attend two research visits: the first visit between 2 and 7 months; and the second visit between 10 and 14 months post-hospital discharge. Participants were included in the airways group if they self-reported a history of asthma, COPD or bronchiectasis prior to their initial hospitalisation with COVID-19. A small number of the participants indicated a history of combined pre-existing asthma and COPD or bronchiectasis and COPD. Clinical characteristics of this group revealed significant smoking history and older mean age; therefore, these individuals were assigned to the COPD group. Written informed consent was obtained from all participants. The study was approved by the Leeds West Research Ethics Committee (20/YH/0225) and registered on the ISRCTN Registry (ISRCTN10980107).
Data collection and procedures
Details about the participants' hospital admission were retrospectively collected from the medical records. Research data collected from the two research visits included: patient reported outcome measures (PROMs), health-related quality of life (HRQoL) questionnaires, physiological assessments, routine and research sampling, and pulmonary function tests depending on the local arrangement for aerosol-generating procedures (see supplementary material SM1). HRQoL was measured using EQ-5D-5L Utility Index (UI) and EQ-5D-5L Visual Analogue Scale (VAS).
The Patient Symptom Questionnaire (PSQ) was a study-specific tool used to assess the participants’ perceived full recovery by asking them to answer the question “Do you feel fully recovered from COVID-19?” using the options “Yes”, “No” or “Not sure” at each research visit. The PSQ also assessed the burden of breathlessness, cough, fatigue, sleep disturbance and pain symptoms using a numerical scale ranging from 0 to 10, where 10 represents the highest burden of the symptom. The participants were asked to provide pre-COVID estimates of EQ-5D-5L UI, EQ-5D-5L VAS and burden of symptoms using the PSQ scale.
Statistical analysis
Descriptive statistics were used to describe participant characteristics. Continuous variables are presented as mean±SD, or medians and interquartile ranges, as appropriate. Binary and categorical variables are presented as counts and percentages of available data. No imputation was performed for the missing data. Results were not adjusted for multiple testing. t-test, analysis of variance (ANOVA F-test) and Kruskal–Wallis H-test were used to compare parametric and non-parametric continuous data as appropriate. Chi-squared test was used to compare categorical data. We did not adjust for cofounders. To examine the predictors of recovery at the second research visit, the participants with pre-existing airway diseases were dichotomised into: “recovered” group for those who answered “Yes” to the perceived full recovery question or “not recovered” group including those who answered “No” or “Not sure” using the PSQ tool. Univariable and multivariable logistic regression were reported to identify predictors of recovery. Only explanatory variables available at hospital discharge were used in the multivariable logistic model comprising: age as a factor, sex at birth, ethnicity, Index of Multiple Deprivation, body mass index (BMI), number of comorbidities, admission duration, severity of acute illness using World Health Organization (WHO) Clinical Progression Scale, history of pre-existing neuropsychiatric disease and the use of systemic steroids during acute admission. R (version 3.6.3) and Stata (version 16.0) were used for all data analysis.
Results
Between 10 August 2020 and 31 March 2022, 2697 participants were recruited to the PHOSP-COVID study and attended at least one research visit. A total of 615 (22.8%) reported a history of pre-existing airway diseases prior to COVID-19 hospitalisation (figure 1, table 1). This included 443 (72.0%) who had a history of asthma, 141 (22.9%) with COPD and 31 (5.1%) with bronchiectasis.
FIGURE 1.
Flow diagram of the participants.
TABLE 1.
Patient characteristic
| n | Pre-existing airway disease# | n | No pre-existing airway disease¶ | p-value | |
|---|---|---|---|---|---|
| Age years | 615 | 58.7±12.9 | 2081 | 57.8±12.5 | 0.148 |
| Sex at birth | 615 | 2081 | 0.000 | ||
| Male | 317 (51.5) | 1341 (64.4) | |||
| Female | 298 (48.5) | 740 (35.6) | |||
| Ethnicity | 608 | 2070 | 0.000 | ||
| White | 499 (82.1) | 1508 (72.9) | |||
| South Asian | 54 (8.9) | 251 (12.1) | |||
| Black | 33 (5.4) | 160 (7.7) | |||
| Mixed | 10 (1.6) | 45 (2.2) | |||
| Other | 12 (2.0) | 106 (5.1) | |||
| Smoking | 539 | 1774 | 0.002 | ||
| Current smoker | 23 (4.3) | 55 (3.1) | |||
| Ex-smoker | 234 (43.4) | 641 (36.1) | |||
| Nonsmoker | 282 (52.3) | 1078 (60.8) | |||
| Index of multiple deprivation index (IMD) | 612 | 2065 | 0.018 | ||
| 1 – most deprived | 162 (26.5) | 456 (22.1) | |||
| 2 | 147 (24.0) | 475 (23.0) | |||
| 3 | 95 (15.5) | 368 (17.8) | |||
| 4 | 86 (14.1) | 386 (18.7) | |||
| 5 – least deprived | 122 (19.9) | 380 (18.4) | |||
| BMI kg·m−2 | 432 | 1441 | |||
| Median (IQR) | 31.9 (28.2–37.4) | 30.9 (27.5–35.3) | 0.001 | ||
| <30 kg·m−2 | 154 (35.7) | 641 (44.6) | |||
| ≥30 kg·m−2 | 278 (64.3) | 796 (55.4) | |||
| Comorbidities + | 65 | 2082 | |||
| Median (IQR) | 2 (1–4) | 1 (0–3) | 0.000 | ||
| 0 | 138 (22.4) | 667 (32.0) | 0.000 | ||
| 1 | 104 (16.9) | 433 (20.8) | |||
| ≥2 | 373 (60.7) | 982 (47.2) | |||
| Cardiovascular | 615 | 297 (48.3) | 2082 | 942 (45.2) | 0.183 |
| Type 2 diabetes | 614 | 121 (19.7) | 2077 | 416 (20.0) | 0.972 |
| Neuropsychiatric | 615 | 184 (29.9) | 2082 | 378 (18.2) | 0.000 |
| Renal and endocrine | 615 | 85 (13.8) | 2082 | 202 (9.7) | 0.004 |
| Hospital admission details | |||||
| Admission duration days | 615 | 13.7±16.8 | 2082 | 14.2±18.3 | 0.540 |
| Positive SARS-CoV-2 PCR | 570 | 535 (93.9) | 1887 | 1748 (92.6) | 0.317 |
| WHO clinical progression scale | 615 | 2082 | 0.041 | ||
| WHO class 3–4 | 101 (16.4) | 346 (16.6) | |||
| WHO class 5 | 278 (45.2) | 857 (41.2) | |||
| WHO class 6 | 149 (24.2) | 484 (23.2) | |||
| WHO class 7–9 | 87 (14.2) | 395 (19.0) | |||
| Systemic steroids | 583 | 369 (63.3) | 1978 | 1079 (54.6) | 0.000 |
| Antibiotic therapy | 602 | 484 (80.4) | 2030 | 1591 (78.4) | 0.286 |
| Anticoagulants | 579 | 248 (42.8) | 1986 | 925 (46.6) | 0.112 |
Data are presented as n (%), mean±sd or median (IQR). Percentages are calculated by category after exclusion of missing data for that variable. World Health Organization (WHO) classes are as follows: 3–4=no continuous supplemental oxygen needed; 5=continuous supplemental oxygen only; 6=continuous or bi-level positive airway pressure ventilation or high-flow nasal oxygen; and 7–9=invasive mechanical ventilation or other organ support. BMI: body mass index; SARS-CoV-2 PCR: severe acute respiratory syndrome coronavirus 2 polymerase chain reaction. #: n=615; ¶: n=2082; +: the total number of comorbidities in the airways group does not include the airway diseases.
Comparison of the participants’ characteristics showed the airways group to have: more females (48.5% versus 35.6%, p<0.001), more from a White ethnic background (82.1% versus 72.9%, p<0.001), a higher prevalence of pre-existing neuropsychiatric comorbidity (29.9% versus 18.2%, p<0.001), higher BMI (median 31.9 versus 30.9 kg·m−2, p=0.001) and more likely to have received systemic steroids during hospital admission (63.3% versus 54.6%, p=0.001) compared to the non-airways group. There was no difference in age, length of hospital admission or treatment with antibiotics or anticoagulants between the two groups. The level of organ support during acute admission was comparable between the two groups with the exception that receiving invasive mechanical ventilation and other organ support (WHO class 7–9) was lower in the airways group (10.0% versus 14.2%, p=0.041). At hospital discharge, 63.9% of the airways group were prescribed a form of ICS therapy and 27.2% were on antidepressant medications compared to 1.9% and 16.9% in the non-airways group, respectively. The breakdown of the different classes of prescribed medications upon discharge and additional reported changes at 5-month and 1-year visits are listed in supplementary table S1.
Results from the 5-month visit
The first research visit was attended by 2570 participants at a median of 5.5 months (IQR 4.1–6.4) from hospital discharge, labelled here as “5-month” visit. A total of 595 out of 2570 (23.2%) participants reported a history of pre-existing airway disease prior to hospital admission (table 2). Assessments at the 5-month visit revealed that the airways group participants were more likely to have symptoms consistent with anxiety (34.4% versus 22.8%, p<0.001), depression (44.2% versus 26.5%, p<0.001), post-traumatic stress disorder (PTSD) (19.4% versus 11.6%, p<0.001) and greater breathlessness measured using the Dyspnoea-12 questionnaire (mean±sd 10.2±9.7 versus 5.3±7.4, p<0.001). The airways group participants had a higher percentage of impaired mobility measured using short physical performance battery ≤10 (59.6% versus 48.5%, p<0.001) and a lower percentage of predicted incremental shuttle walk test distance (52.4% versus 58.7%, p=0.001). They were more likely to be frail using the Rockwood Clinical Frailty score without features of cognitive impairment. Pulmonary function tests revealed lower spirometry measurements in the airways group but no difference in gas transfer measurements between the two groups. The airways group had higher levels of blood neutrophils, eosinophils and higher numbers with systemic inflammation measured by C-reactive protein (CRP) of more than 5 mg·L−1 (table 2).
TABLE 2.
Patient characteristics at the 5-month and 1-year research visits stratified by the presence of pre-existing airway diseases
| 5-month visit | 1-year visit | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| n | Pre-existing airway disease# | n | No pre-existing airway disease¶ | p-value | n | Pre-existing airway disease+ | n | No pre-existing airway disease§ | p-value | |
| PROMS | ||||||||||
| GAD-7 total score | 552 | 6.7±6.1 | 1856 | 4.9±5.5 | 0.000 | 447 | 5.9±6.0 | 1503 | 4.8±5.5 | 0.001 |
| Anxiety (GAD-7 >8) | 552 | 190 (34.4) | 1856 | 424 (22.8) | 0.000 | 447 | 130 (29.1) | 1503 | 331 (22.0) | 0.002 |
| PHQ-9 total score | 550 | 9.0±6.9 | 1856 | 6.5±6.3 | 0.000 | 443 | 7.4±6.6 | 1504 | 6.1±6.3 | 0.000 |
| Depression (PHQ-9 ≥10) | 550 | 243 (44.2) | 1856 | 491 (26.5) | 0.000 | 443 | 138 (31.2) | 1504 | 371 (24.7) | 0.006 |
| PCL-5 total score | 552 | 20.2±18.9 | 1851 | 14.6±16.5 | 0.000 | 440 | 17.5±18.4 | 1497 | 13.3±16.2 | 0.000 |
| PTSD (PCL-5 ≥38) | 552 | 107 (19.4) | 1851 | 214 (11.6) | 0.000 | 440 | 74 (16.8) | 1497 | 147 (9.8) | 0.000 |
| Dyspnoea-12 | 540 | 10.2±9.7 | 1821 | 5.3±7.4 | 0.000 | 430 | 8.5±8.8 | 1462 | 4.9±7.2 | 0.000 |
| FACIT fatigue subscale score | 535 | 29.7±13.6 | 1791 | 36.1±12.6 | 0.000 | 402 | 32.7±13.2 | 1400 | 36.7±12.4 | 0.000 |
| Physical performance | ||||||||||
| SPPB total score | 539 | 9.2±2.7 | 1803 | 10.0±2.2 | 0.000 | 397 | 9.4±2.5 | 1397 | 10.2±2.1 | 0.000 |
| SPPB ≤10 (impaired mobility) | 539 | 321 (59.6) | 1803 | 875 (48.5) | 0.000 | 397 | 228 (57.4) | 1397 | 632 (45.2) | 0.000 |
| ISWT distance m | 422 | 364±249 | 1467 | 441±267 | 0.000 | 295 | 393±257 | 1104 | 456±267 | 0.000 |
| ISWT % predicted | 305 | 52.4±30.3 | 1032 | 58.7±30.0 | 0.001 | 226 | 54.0±30.8 | 796 | 60.8±30.3 | 0.003 |
| Frailty and cognition | ||||||||||
| Rockwood CFS score ≥5 | 541 | 65 (12.0) | 1743 | 70 (4.0) | 0.000 | 422 | 45 (10.7) | 1463 | 59 (4.0) | 0.000 |
| SARC-F total score | 541 | 2.8±2.5 | 1785 | 1.7±2.1 | 0.000 | 403 | 2.5±2.5 | 1405 | 1.7±2.1 | 0.000 |
| MoCA total score | 482 | 25.4±3.8 | 1616 | 25.7±3.4 | 0.074 | 379 | 26.3±3.3 | 1303 | 26.3±3.4 | 0.708 |
| Corrected MoCA total score | 482 | 25.8±3.8 | 1616 | 26.1±3.4 | 0.126 | 379 | 26.7±3.2 | 1303 | 26.6±3.3 | 0.443 |
| MoCA <23 | 482 | 85 (17.6) | 1616 | 236 (14.6) | 0.105 | 379 | 47 (12.4) | 1303 | 152 (11.7) | 0.696 |
| Corrected MoCA <23 | 482 | 74 (15.4) | 1616 | 205 (12.7) | 0.130 | 379 | 39 (10.3) | 1303 | 139 (10.7) | 0.833 |
| Lung physiology | ||||||||||
| FEV1 L | 366 | 2.47±0.77 | 1150 | 2.85±0.79 | 0.000 | 241 | 2.52±0.81 | 840 | 2.89±0.80 | 0.000 |
| FEV1 % predicted | 341 | 84.5±19.4 | 1098 | 91.7±17.8 | 0.000 | 231 | 86.5±21.2 | 820 | 93.2±17.4 | 0.000 |
| FEV1 % predicted <80% | 341 | 135 (39.6) | 1098 | 255 (23.2) | 0.000 | 231 | 84 (36.4) | 820 | 173 (21.1) | 0.000 |
| FVC L | 366 | 3.24±0.94 | 1150 | 3.55±1.03 | 0.000 | 241 | 3.33±0.98 | 840 | 3.61±1.01 | 0.000 |
| FVC % predicted | 341 | 87.2±17.3 | 1098 | 89.7±19.0 | 0.029 | 231 | 89.7±20.4 | 820 | 91.2±17.8 | 0.289 |
| FVC % predicted <80% | 341 | 116 (34.0) | 1098 | 311 (28.3) | 0.043 | 231 | 78 (33.8) | 820 | 188 (22.8) | 0.001 |
| FEV1/FVC | 366 | 0.77±0.12 | 1150 | 0.81±0.09 | 0.000 | 241 | 0.77±0.19 | 840 | 0.81±0.11 | 0.000 |
| FEV1/FVC <0.7 | 341 | 80 (23.5) | 1098 | 83 (7.6) | 0.000 | 241 | 55 (22.8) | 840 | 63 (7.5) | 0.000 |
| T LCO | 122 | 7.08±2.13 | 389 | 7.53±2.38 | 0.062 | 76 | 7.62±2.33 | 264 | 7.69±2.36 | 0.832 |
| TLCO % predicted | 121 | 90.7±26.8 | 378 | 91.9±32.5 | 0.718 | 76 | 96.8±28.1 | 261 | 95.0±29.7 | 0.628 |
| TLCO % predicted <80% | 121 | 45 (37.2) | 378 | 130 (34.4) | 0.574 | 76 | 18 (23.7) | 261 | 60 (23.0) | 0.899 |
| K CO | 127 | 1.49±0.28) | 393 | 1.45±0.32) | 0.214 | 80 | 1.46±0.28) | 273 | 1.44±0.27) | 0.454 |
| KCO % predicted | 127 | 102.3±18.0 | 380 | 100.5±20.9 | 0.387 | 80 | 101.9±18.2 | 270 | 100.0±17.3 | 0.405 |
| KCO % predicted <80% | 127 | 9 (7.1) | 380 | 36 (9.5) | 0.413 | 80 | 9 (11.3) | 270 | 24 (8.9) | 0.526 |
| Biochemical tests | ||||||||||
| Haemoglobin | 501 | 139.6±15.0 | 1640 | 141.5±15.4 | 0.012 | 383 | 139.6±15.7 | 1280 | 141.6±14.8 | 0.024 |
| Neutrophils | 500 | 4.5±1.8 | 1635 | 4.0±1.5 | 0.000 | 381 | 4.6±2.2 | 1275 | 4.0±1.5 | 0.000 |
| Eosinophils | 495 | 0.23±0.22 | 1626 | 0.18±0.17 | 0.000 | 381 | 0.22±0.18 | 1275 | 0.19±0.18 | 0.001 |
| BNP/Pro-NT-BNP above threshold | 378 | 25 (6.6) | 1197 | 76 (6.4) | 0.867 | 237 | 23 (9.7) | 824 | 68 (8.3) | 0.482 |
| HbA1C ≥6.0 | 394 | 150 (38.1) | 1236 | 427 (34.6) | 0.203 | 279 | 107 (38.4) | 1008 | 355 (35.2) | 0.334 |
| eGFR <60 (mL/min/1.73 m2) | 488 | 57 (11.7) | 1581 | 155 (9.8) | 0.232 | 358 | 46 (12.9) | 1227 | 153 (12.5) | 0.853 |
| Systemic inflammation | ||||||||||
| CRP mg·L−1 | 472 | 6.2±9.4 | 1580 | 5.2±11.2 | 0.074 | 374 | 5.8±6.4 | 1260 | 4.9±7.0 | 0.021 |
| CRP >5 mg·L−1 | 472 | 146 (30.9) | 1580 | 348 (22.0) | 0.000 | 374 | 114 (30.5) | 1260 | 278 (22.1) | 0.001 |
| CRP ≥10 mg·L−1 | 472 | 73 (15.5) | 1580 | 155 (9.8) | 0.001 | 374 | 53 (14.2) | 1260 | 120 (9.5) | 0.011 |
Data are presented as n (%) or mean±sd. Percentages are calculated by category after exclusion of missing data for that variable. Threshold of BNP ≥100 ng·L−1 or NT-BNP ≥400 ng·L−1. Corrected MoCA adjusted for level of education. One was subtracted from the total number of comorbidities in the airways group. See Table SM1 for further descriptions of variables. PROMs: patient reported outcome measures; GAD7: Generalised Anxiety Disorder 7-item scale; PHQ-9: Patient Health Questionnaire-9; PCL-5: Post-Traumatic Stress Disorder (PTSD) Checklist; FACIT fatigue: Functional Assessment of Chronic Illness Therapy Fatigue Scale; SPPB: short physical performance battery; ISWT: incremental shuttle walk test; CFS: Clinical Frailty Scale; MoCA: Montreal Cognitive Assessment; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; TLCO: transfer capacity of the lung for carbon monoxide; KCO: carbon monoxide transfer coefficient; BNP: brain natriuretic peptide; NT-BNP: N-terminal BNP; HbA1C: glycated haemoglobin; eGFR: estimated glomerular filtration rate; CRP: C-reactive protein. #: n=595; ¶: n=1975; +: n=479; §: n=1621.
The perceived recovery question demonstrated a lower proportion of participants in the airways group reporting “full recovery” (19.7% versus 27.6%, p=0.005) (table 3). The participants who attended the 5-month visit were assigned one of the previously identified four cluster memberships of recovery phenotypes [17]: very severe, severe, moderate with cognitive impairment, and mild mental and physical impairment (see supplementary material SM1). Recovery cluster assignment was different between the airways and non-airways groups with a higher proportion of those with pre-existing airway diseases assigned to the very severe mental and physical impairment cluster (32.5% versus 17.5%) and a smaller proportion assigned to the mild cluster (21.1% versus 32.7%), p<0.001 (figure 2, supplementary table S2).
TABLE 3.
Recovery, health-related quality of life and symptoms burden at the 5-month and 1-year research visits stratified by the presence of pre-existing airway diseases
| 5-month visit | 1-year visit | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| n | Pre-existing airway disease# | n | No pre-existing airway disease¶ | p-value | n | Pre-existing airway disease+ | n | No pre-existing airway disease§ | p-value | |
| Fully recovered from COVID-19? | 509 | 1693 | 0.002 | 403 | 1384 | 0.000 | ||||
| Yes | 100 (19.7) | 467 (27.6) | 82 (20.4) | 459 (33.2) | ||||||
| No | 303 (59.5) | 912 (53.9) | 225 (55.8) | 638 (46.1) | ||||||
| Not sure | 106 (20.8) | 314 (18.5) | 96 (23.8) | 287 (20.7) | ||||||
| EQ-5D-5L Utility Index pre-COVID estimate | 503 | 0.74±0.27 | 1667 | 0.84±0.21 | 0.000 | 422 | 0.74±0.27 | 1399 | 0.84±0.21 | 0.000 |
| EQ-5D-5L Utility Index at the visit | 487 | 0.62±0.28 | 1626 | 0.73±0.24 | 0.000 | 390 | 0.64±0.27 | 1350 | 0.73±0.25 | 0.000 |
| EQ-5D-5L Utility Index delta change | 404 | −0.12±0.26 | 1353 | −0.11±0.21 | 0.451 | 338 | −0.10±0.24 | 1160 | −0.11±0.22 | 0.351 |
| EQ5D-5L VAS pre-COVID estimate | 491 | 73.7±18.5 | 1604 | 81.3±16.8 | 0.000 | 410 | 74.6±18.9 | 1342 | 81.1±16.6 | 0.000 |
| EQ5D-5L VAS at the visit | 488 | 63.4±21.3 | 1618 | 72.2±19.2 | 0.000 | 384 | 67.3±21.2 | 1347 | 71.3±20.4 | 0.001 |
| EQ5D-5L VAS delta change | 397 | −10.6±21.3 | 1300 | −9.7±18.8 | 0.441 | 323 | −8.5±20.2 | 1112 | −10.2±19.7 | 0.168 |
| WG-SS-SCo | 508 | 176±34.7 | 1700 | 356±20.9 | 0.000 | 407 | 130±31.9 | 1386 | 259±18.7 | 0.000 |
| WG-SS-SCo new disability | 384 | 94 (24.5) | 1275 | 223 (17.5) | 0.002 | 111 | 30 (27.0) | 380 | 63 (16.6) | 0.014 |
| PSQ Breathlessness pre-COVID estimate | 493 | 2.6±2.6 | 1669 | 0.8±1.7 | 0.000 | 256 | 2.6±2.4 | 837 | 0.8±1.6 | 0.000 |
| PSQ Breathlessness at the visit | 496 | 4.9±2.8 | 1697 | 3.7±2.9 | 0.000 | 398 | 3.7±2.7 | 1372 | 2.4±2.5 | 0.000 |
| PSQ Breathlessness delta change | 481 | 2.3±3.1 | 1628 | 2.9±3.0 | 0.000 | 243 | 1.2±2.7 | 805 | 1.9±2.7 | 0.000 |
| PSQ Cough pre-COVID estimate | 489 | 1.7±2.4 | 1664 | 0.6±1.5 | 0.000 | 256 | 1.5±2.2 | 836 | 0.6±1.5 | 0.000 |
| PSQ Cough at the visit | 491 | 2.9±2.9 | 1693 | 1.9±2.6 | 0.000 | 395 | 2.1±2.5 | 1368 | 1.3±2.1 | 0.000 |
| PSQ Cough delta change | 476 | 1.3±3.0 | 1622 | 1.3±2.7 | 0.643 | 241 | 0.6±2.4 | 801 | 0.9±2.3 | 0.100 |
| PSQ Fatigue pre-COVID estimate | 488 | 2.2±2.6 | 1664 | 1.4±2.2 | 0.000 | 256 | 2.1±2.4 | 831 | 1.3±2.0 | 0.000 |
| PSQ Fatigue at the visit | 490 | 5.7±2.9 | 1693 | 4.5±3.0 | 0.000 | 396 | 4.3±3.0 | 1369 | 3.3±2.9 | 0.000 |
| PSQ Fatigue delta change | 474 | 3.5±3.3 | 1621 | 3.1±3.2 | 0.060 | 243 | 2.5±2.0 | 799 | 2.4±2.2 | 0.979 |
| PSQ Sleep Disturbance pre-COVID estimate | 488 | 2.8±2.7 | 1663 | 1.9±2.5 | 0.000 | 255 | 2.5±2.7 | 836 | 1.8±2.4 | 0.000 |
| PSQ Sleep Disturbance at the visit | 491 | 4.9±3.0 | 1686 | 3.8±3.1 | 0.000 | 398 | 3.9±3.1 | 1368 | 3.3±3.0 | 0.000 |
| PSQ Sleep Disturbance delta change | 473 | 2.1±3.0 | 1616 | 1.9±3.1 | 0.136 | 243 | 1.5±2.9 | 805 | 1.6±2.9 | 0.739 |
| PSQ Pain pre-COVID estimate | 489 | 2.3±2.9 | 1649 | 1.4±2.4 | 0.000 | 253 | 2.3±2.8 | 836 | 1.4±2.3 | 0.000 |
| PSQ Pain at the visit | 492 | 4.0±3.4 | 1677 | 3.0±3.1 | 0.000 | 396 | 3.3±3.1 | 1363 | 2.5±2.8 | 0.000 |
| PSQ Pain delta change | 477 | 1.7±2.9 | 1601 | 1.6±2.8 | 0.320 | 239 | 1.2±2.7 | 800 | 1.3±2.6 | 0.653 |
Data are presented as n (%) or mean±sd. Missing not included in %. Delta change at each visit was calculated from the pre-COVID estimates. EQ-5D-5L VAS: Euroqol five level visual analogue scale 0–100; WG-SS-SCo: Washington Group Short Set of Functioning Severity Continuum; PSQ: Patient Symptoms Questionnaires. See supplementary table SM1 for further descriptions of variables. #: n=595; ¶: n=1975; +: n=479; §: n=1621.
FIGURE 2.
Recovery cluster membership assignment at 5-month visit stratified by the underlying class of airway disease. The four clusters are: very severe mental and physical impairment, severe mental and physical impairment, moderate mental and physical impairment with cognitive impairment, and mild.
HRQoL assessed using EQ-5D-5L UI and EQ-5D-5L VAS showed lower estimated pre-hospitalisation levels in the airways group (0.74±0.27 versus 0.84±0.21 and 73.7±18.5 versus 81.3±16.8, all p<0.001), respectively. The participants in the airways group reported a drop in the EQ-5D-5L UI of 0.12±0.26 units similar to the non-airways group (0.11±0.21 units, p=0.451). A higher proportion of the airways group reached the threshold for a new disability using the Washington Group Short Set on Functioning (WG-SS), 24.5% versus 17.5%, p=0.002. In the airways group, the burden of breathlessness, cough, fatigue, sleep disturbance and pain measured using the PSQ scale was higher both at pre-COVID estimate and at the 5-month visit (table 3, figure 3). However, delta difference between pre-COVID level and the 5-month visit was smaller in the case of breathlessness (2.3 versus 2.9, p<0.001) in the airways group compared to the non-airways group but similar in cough, fatigue, sleep disturbance and pain.
FIGURE 3.
Symptoms over time. Symptoms change measured using Patient Symptoms Questionnaire (PSQ) from pre-COVID, to 5-month and 1-year visits stratified by presence or absence of pre-existing airway diseases: a) breathlessness, b) cough and c) fatigue. ***p<0.001.
The differences in clinical characteristics of the participants attending the 5-month visit stratified by the underlying class of airway disease are included in supplementary tables S3 and S4. The COPD group were older, had more male participants, were mainly from a White background, were less likely to have received invasive ventilation, had more comorbidities and were more likely to be assigned to the moderate mental and physical impairment with cognitive impairment cluster. The COPD group at the 5-month visit were frailer, had a higher percentage of impaired mobility, more evidence of cognitive impairment and showed features of anxiety and depression in over 30% of the group. They also had the lowest spirometry measurements but comparable gas transfer readings. Blood tests revealed higher levels of neutrophils, eosinophils, CRP and higher proportion of participants with heart failure or renal impairment. The COPD group had the smallest drop in EQ-5D-5L UI and VAS measurements despite having the lowest estimates pre-COVID (figure 4). They also had minimal increase in the burden of breathlessness, cough and fatigue measured using PSQ despite having higher levels of baseline burden (figure 3).
FIGURE 4.
Change in health-related quality of life (HRQoL) measured using EQ-5D-5L Utility Index from pre-COVID to 5-month and 1-year visit by presence or absence of pre-existing airway diseases. COPD: chronic obstructive pulmonary disease. p-values calculated using t-test: ***p<0.001.
The participants with underlying asthma were characterised by: younger age, more females, higher BMI, more likely to report “not recovered” and more than a third were assigned to the very severe cluster. The asthma group had the largest drop in EQ-5D-5L UI and VAS and the highest increase in burden of fatigue (supplementary table S4, figure 3). The change in breathlessness and cough in the asthma group was similar to those without pre-existing airway diseases (figure 3).
Results from the 1-year visit
A total of 2100 participants attended a second research visit at “1 year” at a median of 12.6 months (IQR 11.8–13.4) from hospital discharge. A total of 479 (22.8%) participants had a history of pre-existing airway diseases (figure 1). At 1-year visit, the airways group participants remained less likely to report full recovery compared to the non-airways group (20.4% versus 33.2%, p<0.001) and were more likely to have features consistent with anxiety, depression, PTSD, increased frailty, reduced physical performance and higher CRP levels (table 2). HRQoL measurements at 1 year in the airways group were lower than in the non-airways group and showed no improvement from the 5-month levels with no recovery to pre-COVID estimates (figure 4). A higher proportion of the airways group reached the threshold for a new disability using the WG-SS (27% versus 16.6%, p=0.014).
In the airways group there was some improvement in the burden of symptoms between the 5-month and 1-year visit: anxiety (34.4% to 29.1%), depression (44.2% to 31.1%), cognitive impairment (15.4% to 10.3%) and breathlessness measured using Dyspnoea-12 (mean 10.2 to 8.5), table 2. Despite the participants in the airways group having a higher burden of the symptoms measured using PSQ compared to the non-airways group at 1 year, there was a trend towards improvement from the 5-month levels (figure 3). Clinical characteristics of the participants who attended the 1-year visit stratified by the underlying class of airway diseases are available in supplementary tables S5 and S6.
Factors predicting recovery at 1 year
At the 1-year visit, data about perceived recovery were available in 403 out of 479 (84.1%) of the airways group and 1384 out of 1621 (85.3%) of the non-airways group. The characteristics of the recovered participants in the airways group are listed in supplementary table S7. The multivariable logistic regression model did not identify any statistically significant features to predict recovery at 1 year post discharge in the airways group; however, non-White ethnicity, age ≥70 years and receiving noninvasive respiratory support during initial admission were associated with increased likelihood of recovery (supplementary table S8, figure SF1). In contrast, female sex, history of neuropsychiatric comorbidity, increased level of deprivation, having one or more comorbidity, and receiving invasive ventilation/organ support were suggestive of reduced likelihood of full recovery. These predicting factors were similar in the non-airways group with the features of female, non-White ethnicity and pre-existing neuropsychiatric comorbidity reaching statistical significance (supplementary table S9 and figure SF2).
Discussion
To our knowledge, this is the first report to focus on the long-term impact of COVID-19 hospitalisation on individuals with pre-existing airway diseases using results from a large multicentre prospective longitudinal UK cohort study. Around a quarter of the PHOSP-COVID cohort had a history of pre-existing airway diseases with the majority of those reporting asthma. Individuals with pre-existing airway diseases were less likely to feel fully recovered at 5-month and at 1-year post-hospital discharge and they had a significant burden of anxiety, depression, PTSD, breathlessness, cough and fatigue compared to the non-airways group. There was evidence of reduced physiological performance, lower spirometry measurements, reduced level of HRQoL both pre-COVID and at the follow-up visits with raised neutrophils, eosinophils and systemic inflammation measured using CRP in the airways group.
Although the prevalence of airway diseases in our cohort might seem high, it is comparable to reports from the large ISARIC study and to the prevalence of asthma in the age group of 55–64 years in the UK [12]. Furthermore, around two-thirds of the airways group were prescribed inhaled bronchodilators or ICS therapy. The results from this cohort study support previous findings from smaller studies including a UK-wide survey where patients with pre-existing lung diseases were more likely to report “breathing complications” after contracting COVID-19 [18]. Another UK-based online survey among patients with underlying asthma revealed that more than half of the participants experienced features of “long COVID” that were not related to personal characteristics such as age, sex, ethnicity or household income [19]. A cohort study of 2649 participants from Russia revealed that patients with chronic pulmonary diseases were more likely to report respiratory symptoms and chronic fatigue [20]. Numerous reports identified breathlessness as one of the commonest persistent symptoms post-COVID in the general population [21–23]. In our study, people with pre-existing airway disease had a higher burden of breathlessness measured using the Dyspnoea-12 questionnaire and PSQ breathlessness scale at both visits. However, the non-airways group had the largest increase in breathlessness from pre-COVID levels measured using the PSQ scale. As expected, spirometry results were lower in the airways group, but we observed no difference in gas transfer measurements between the two groups. Despite the smaller number of participants who completed these procedures (due to the restrictions around aerosol-generating procedures), the latter finding suggests that a pre-existing airway disease is not necessarily a major risk factor for further lung function impairment post-COVID-19 hospitalisation and the pathophysiology of persistent breathlessness is likely to be multifactorial [24].
Other symptoms of cough, sleep disturbance and pain were higher in the airways group at pre-COVID baseline but increased in similar proportion to the non-airways group, resulting in an overall higher burden of these symptoms at both visits in those with pre-existing airway disease. Fatigue is highly prevalent in patients with airway diseases [25, 26], and the COPD group in our cohort had double the level of fatigue burden pre-COVID compared to the non-airways group. Interestingly, the asthma group, which was dominated by female participants, demonstrated the highest increase in fatigue burden compared to the COPD and the non-airways groups. Multiple reports have identified female sex as an independent risk factor for developing chronic fatigue post-COVID-19 [22, 27, 28].
Patients with pre-existing airway diseases are known to have reduced HRQoL compared to controls [29–31]. In our study, HRQoL in the airways group was reduced both at pre-COVID estimates and at both follow-up visits, with minimal improvement between 5 months and 1 year post discharge. This was similar to the results of 1-year follow-up of 1276 COVID-19 survivors from Wuhan, China [21] and a German study of COVID-19 survivors who required intensive care unit admission [32], where HRQoL remained reduced at 1 year after hospital discharge. Interestingly, in our cohort the magnitude of decline in HRQoL from pre-COVID estimates to the research visits was similar in both groups, suggesting that patients with pre-existing airway diseases are not at increased risk of significant deterioration of HRQoL compared to those without airway diseases. There was a general trend of improvement in the burden of symptoms between the 5-month and 1-year visit in the overall cohort and more specifically in the airways group. This was similar to the findings from the Wuhan study [21].
Owing to the small number of the bronchiectasis cases in this cohort, reaching robust conclusions about the long-term sequelae of COVID-19 in this disease is challenging, but our results support earlier indications that pre-existing bronchiectasis is associated with increased morbidity after COVID-19 [13, 14].
The multivariable logistic regression suggested that in both airways and non-airways groups, being female, more severe acute illness, increased number of comorbidities and history of pre-existing neuropsychiatric diseases were all associated with reduced likelihood of reporting full recovery at 1 year post discharge. These identified risk factors were consistent with previously published systematic reviews and meta-analyses exploring the risk factors of prolonged symptoms post-COVID in hospitalised individuals [21, 33–35].
Results from this cohort study are important for policy decisions and clinical practice as they highlight the significant burden of symptoms and morbidity in an already vulnerable group [36]. The challenges facing healthcare providers globally will likely worsen the clinical outcomes of individuals with pre-existing airway diseases unless healthcare provision is prioritised in this group in the form of offering pulmonary rehabilitation, reviews of inhaler technique, delivery of vaccinations, clinical monitoring and self-management plan implementation [37, 38]. The high prevalence of anxiety, depression and PTSD in this group highlights the rising need to improve access to mental health and counselling services [39, 40].
The strengths of this cohort analysis include reporting the findings from a large multicentre study with in-depth assessments using validated and novel tools to measure recovery, burden of symptoms and HRQoL in hospitalised COVID-19 individuals with pre-existing airway diseases. Our study had several limitations. First, the high prevalence of symptoms across the whole of the PHOSP-COVID study participants raises the possibility of selection bias where individuals with high burden of symptoms choose to participate in the study. Second, we relied on the recall of certain measurements by the participants including the history of pre-existing illness and the pre-COVID estimates of HRQoL and burden of symptoms. This includes the use of the study-specific PSQ, which is not externally validated but supports results from other validated tools, e.g., Dyspnoea-12, FACIT fatigue subscale scores. Although a large proportion of the airways group individuals were prescribed inhaled therapy on hospital discharge, which supports the self-reported diagnosis of pre-existing airway disease, this observation alone cannot confirm a pre-existing diagnosis due to discrepancy between prescribing inhaled therapy and the prevalence of diagnosed asthma and COPD [41, 42]. Third, the lack of a control group of participants with pre-existing airway diseases who were not hospitalised for COVID-19 infection is also a limitation; however, the overall design of the PHOSP-COVID study did not include a control group of non-hospitalised individuals. Fourth, it is not clear how much of the reported burden of symptoms up to 1 year post discharge can be attributed to the pre-existing airway diseases versus emergent impaired health status. Fifth, no data were collected regarding the frequency or severity of exacerbations of pre-existing airway diseases nor the use of rescue medications. Sixth, the participants in this cohort were mainly individuals who were hospitalised during the first wave of the pandemic in the UK prior to the widespread use of in-hospital COVID-19 therapeutic interventions and the uptake of vaccination, therefore limiting the generalisability of these findings to the overall population.
In conclusion, individuals with pre-existing airway diseases who were hospitalised due to COVID-19 were less likely to feel fully recovered and had greater burden of symptoms and reduced HRQoL up to 1 year post discharge. Prioritisation of clinical care provision in this group is essential to minimise further decline in health status in an already premorbid population.
Supplementary material
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Supplementary material 00982-2023.SUPPLEMENT (1.6MB, pdf)
Acknowledgement
This study would not be possible without all the participants who have given their time and support. We thank all the participants and their families. We thank the many research administrators, healthcare and social care professionals who contributed to setting up and delivering the study at all of the 65 National Health Service trusts/health boards and 25 research institutions across the UK, as well as all the supporting staff at the National Institute for Health Research (NIHR) Clinical Research Network, Health Research Authority, Research Ethics Committee, Department of Health and Social Care, Public Health Scotland, and Public Health England, and support from the ISARIC Coronavirus Clinical Characterisation Consortium. We thank Kate Holmes at the NIHR Office for Clinical Research Infrastructure (NOCRI) for her support in coordinating the charities group. The PHOSP-COVID industry framework was formed to provide advice and support in commercial discussions, and we thank the Association of the British Pharmaceutical Industry as well NOCRI for coordinating this. We are very grateful to all the charities that have provided insight to the study: Action Pulmonary Fibrosis, Alzheimer's Research UK, Asthma+Lung UK, British Heart Foundation, Diabetes UK, Cystic Fibrosis Trust, Kidney Research UK, MQ Mental Health, Muscular Dystrophy UK, Stroke Association, Blood Cancer UK, McPin Foundations, Versus Arthritis and The Wolfson Foundation. We thank the NIHR Leicester Biomedical Research Centre patient and public involvement group, and Long Covid Support. We thank Martha McIlvenny (Wellcome Wolfson Institute for Experimental Medicine, Belfast) for her administration support of the project.
Provenance: Submitted article, peer reviewed.
Ethics statement: The study was approved by the Leeds West Research Ethics Committee (20/YH/0225) and registered on the ISRCTN Registry (ISRCTN10980107).
The PHOSP-COVID Study Collaborative Group: J.K. Baillie (Roslin Institute, University of Edinburgh, and Intensive Care Unit, Royal Infirmary of Edinburgh, Edinburgh, UK); N.I. Lone (Usher Institute, University of Edinburgh, and Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, UK); E. Pairo-Castineira, N. Avramidis and K. Rawlik (Baillie Gifford Pandemic Science Hub, Centre for Inflammation Research and The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK); S Jones (Action for Pulmonary Fibrosis, Peterborough, UK); L. Armstrong, B. Hairsine, H. Henson, C. Kurasz, A. Shaw and L. Shenton (Airedale NHS Foundation Trust, Keighley, UK); H. Dobson (Alzheimer's Research UK, Cambridge, UK); A. Dell, S. Fairbairn, N. Hawkings, J. Haworth, M. Hoare, V. Lewis, A. Lucey, G. Mallison, H. Nassa, C. Pennington, A. Price, C. Price, A. Storrie, G. Willis and S. Young (Aneurin Bevan University Health Board, Newport, UK); K. Poinasamy, S. Walker and I. Jarrold (Asthma+Lung UK); A. Sanderson (Barnsley Hospital NHS Foundation Trust, Barnsley, UK); K. Chong-James, C. David, W.Y. James, P. Pfeffer and O. Zongo (Barts Health NHS Trust, London, UK); A. Martineau (Barts Health NHS Trust and Queen Mary University of London, London, UK); C. Manisty (Barts Heart Centre, London, UK); C. Armour, V. Brown, J. Busby, B. Connolly, T. Craig, S. Drain, L.G. Heaney, B. King, N. Magee, E. Major, D. McAulay, L. McGarvey, J. McGinness, T. Peto and R. Stone (Belfast Health and Social Care Trust and Queen's University Belfast, Belfast, UK); A. Bolger, F. Davies, A. Haggar, J. Lewis, A. Lloyd, R. Manley, E. McIvor, D. Menzies, K. Roberts, W. Saxon, D. Southern, C. Subbe and V. Whitehead (Betsi Cadwallader University Health Board, St Asaph, UK); A. Bularga (BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK); N.L. Mills (BHF Centre for Cardiovascular Science, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK); J. Dawson, H. El-Taweel and L. Robinson (Borders General Hospital, NHS Borders, Melrose, UK); L. Brear, K. Regan, D. Saralaya and K. Storton (Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK); S. Amoils (British Heart Foundation, London, UK); A. Bermperi, I. Cruz, K. Dempsey, A. Elmer, J. Fuld, H. Jones, S. Jose, S. Marciniak, M. Parkes, C. Ribeiro, J. Taylor, M. Toshner, L. Watson and J. Worsley (Cambridge University Hospitals NHS Foundation Trust, NIHR Cambridge Clinical Research Facility and University of Cambridge, Cambridge, UK); L. Broad, T. Evans, M. Haynes, L. Jones, L. Knibbs, A. McQueen, C. Oliver, K. Paradowski, R. Sabit and J. Williams (Cardiff and Vale University Health Board, Cardiff, UK); I. Jones (Cardiff University, National Centre for Mental Health, Cardiff, UK); L. Milligan (MQ Mental Health Research, London, UK); E. Harris and C. Sampson (Chesterfield Royal Hospital NHS Trust, Chesterfield, UK); E. Davies, C. Evenden, A. Hancock, K. Hancock, C. Lynch, M. Rees, L. Roche, N. Stroud and T. Thomas-Woods (Cwm Taf Morgannwg University Health Board, Pontypridd, UK); S. Heller (Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK); T. Chalder (Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK); K. Shah (Diabetes UK, London, UK); E. Robertson (Diabetes UK, University of Glasgow, Glasgow, UK); B. Young (DUK | NHS Digital, Salford Royal Foundation Trust, Salford, UK); M. Babores, M. Holland, N. Keenan, S. Shashaa and H. Wassall (East Cheshire NHS Trust, Macclesfield, UK); L. Austin, E. Beranova, T. Cosier, J. Deery, T. Hazelton, C. Price, H. Ramos, R. Solly, S. Turney and H. Weston (East Kent Hospitals University NHS Foundation Trust, Canterbury, UK); M. Ralser (Francis Crick Institute, London, UK); L. Pearce, S. Pugmire, W. Stoker, A. Wilson and W. McCormick (Gateshead NHS Trust, Gateshead, UK); E. Fraile and J. Ugoji (Great Western Hospital Foundation Trust, Swindon, UK); L. Aguilar Jimenez, G. Arbane, S. Betts, K. Bisnauthsing, A. Dewar, N. Hart, G. Kaltsakas, H. Kerslake, M.M. Magtoto, P. Marino, L.M. Martinez, M. Ostermann, J. Rossdale and T.S. Solano (Guy's and St Thomas' NHS Foundation Trust, London, UK); M. Alvarez Corral, A. Arias, E. Bevan, D. Griffin, J. Martin, J. Owen, S. Payne, A. Prabhu, A. Reed, W. Storrar, N. Williams and C. Wrey Brown (Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK); T. Burdett, J. Featherstone, C. Lawson, A. Layton, C. Mills and L. Stephenson (Harrogate and District NHS Foundation Trust); Y. Ellis (Health and Care Research Wales, Castlebridge, UK); P. Atkin, K. Brindle, M.G. Crooks, K. Drury, N. Easom, R. Flockton, L. Holdsworth, A. Richards, D.L. Sykes, S. Thackray-Nocera and C. Wright (Hull University Teaching Hospitals NHS Trust and University of Hull, Hull, UK); S. Coetzee, K. Davies, R. Hughes, R. Loosley, H. McGuinness, A. Mohamed, L. O'Brien, Z. Omar, E. Perkins, J. Phipps, G. Ross, A. Taylor, H. Tench and R. Wolf-Roberts (Hywel Dda University Health Board, Haverfordwest, UK); L. Burden, E. Calvelo, B. Card, C. Carr, E.R. Chilvers, D. Copeland, P. Cullinan, P. Daly, L. Evison, T. Fayzan, H. Gordon, S. Haq, R.G. Jenkins, C. King, O. Kon, K. March, M. Mariveles, L. McLeavey, N. Mohamed, S. Moriera, U. Munawar, J. Nunag, U. Nwanguma, L. Orriss-Dib, A. Ross, M. Roy, E. Russell, K. Samuel, J. Schronce, N. Simpson, L. Tarusan, D.C. Thomas, C. Wood and N. Yasmin (Imperial College Healthcare NHS Trust and Imperial College London, London, UK); D. Altmann, L.S. Howard, D. Johnston, A. Lingford-Hughes, W.D-C. Man, J. Mitchell, P.L. Molyneaux, C. Nicolaou, D.P. O'Regan, L. Price, J. Quint, D. Smith, R.S. Thwaites, J. Valabhji, S. Walsh, C.M. Efstathiou, F. Liew, A. Frankel, L. Lightstone, S. McAdoo, M. Wilkins and M. Willicombe (Imperial College London, London, UK); R. Touyz (Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovoascular Research Centre, University of Glasgow, Glasgow, UK); A-M. Guerdette, M. Hewitt, R. Reddy, K. Warwick and S. White (Kettering General Hospital NHS Trust, Kettering, UK); A. McMahon (Kidney Research UK, Peterborough, UK); M. Malim (King's College Hospital NHS Foundation Trust and King's College London, London, UK); K. Bramham, M. Brown, K. Ismail, T. Nicholson, C. Pariante, C. Sharpe, S. Wessely and J. Whitney (King's College London, London, UK); O. Adeyemi, R. Adrego, H. Assefa-Kebede, J. Breeze, S. Byrne, P. Dulawan, A. Hoare, C.J. Jolley, A. Knighton, S. Patale, I. Peralta, N. Powell, A. Ramos, K. Shevket, F. Speranza and A. Te (King's College Hospital NHS Foundation Trust and King's College London, London, UK); A. Shah (King's College London, British Heart Foundation Centre, and King's College Hospital NHS Foundation Trust, London, UK); A. Chiribiri and C. O'Brien (King's College Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK); A. Hayday (King's College Hospital NHS Foundation Trust and King's College London, UK); A. Ashworth, P. Beirne, J. Clarke, C. Coupland, M. Dalton, C. Favager, J. Glossop, J. Greenwood, L. Hall, T. Hardy, A. Humphries, J. Murira, D. Peckham, S. Plein, J. Rangeley, G. Saalmink, A.L. Tan, E. Wade, B. Whittam, N. Window and J. Woods (Leeds Teaching Hospitals and University of Leeds, Leeds, UK); G. Coakley (Lewisham and Greenwich NHS Trust, London, UK); L. Turtle, L. Allerton, A.M. Allt, M. Beadsworth, A. Berridge, J. Brown, S. Cooper, A. Cross, S. Defres, S.L. Dobson, J. Earley, N. French, W. Greenhalf, K. Hainey, H.E. Hardwick, J. Hawkes, V. Highett, S. Kaprowska, A.L. Key, L. Lavelle-Langham, N. Lewis-Burke, G. Madzamba, F. Malein, S. Marsh, C. Mears, L. Melling, M.J. Noonan, L. Poll, J. Pratt, E. Richardson, A. Rowe, M.G. Semple, V. Shaw, K.A. Tripp, L.O. Wajero, S.A. Williams-Howard, D.G. Wootton and J. Wyles (Liverpool University Hospitals NHS Foundation Trust and University of Liverpool, Liverpool, UK); S.N. Diwanji, S. Gurram, P. Papineni, S. Quaid, G.F. Tiongson and E. Watson (London North West University Healthcare NHS Trust, London, UK); A. Briggs and M. Marks (London School of Hygiene and Tropical Medicine, London, UK); C. Hastie, N. Rogers and N. Smith (Long Covid Support, London, UK); D. Stensel and L. Bishop (Loughborough University, Loughborough, UK); K. McIvor (Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Salford, UK); P. Rivera-Ortega (Manchester University NHS Foundation Trust, Manchester, UK); B. Al-Sheklly, C. Avram, J. Blaikely, M. Buch, N. Choudhury, D. Faluyi, T. Felton, T. Gorsuch, N.A. Hanley, A. Horsley, T. Hussell, Z. Kausar, N. Odell, R. Osbourne, K. Piper Hanley, K. Radhakrishnan and S. Stockdale (Manchester University NHS Foundation Trust and University of Manchester, Manchester, UK); T. Kabir (McPin Foundation, London, UK); J.T. Scott (MRC University of Glasgow Centre for Virus Research, Glasgow, UK); P.J.M. Openshaw and I.D. Stewart (National Heart and Lung Institute, Imperial College London, London, UK); D. Burn (Newcastle University and NIHR Dementia TRC, Newcastle upon Tyne, UK); A. Ayoub, J. Brown, G. Burns, G. Davies, A. De Soyza, C. Echevarria, H. Fisher, C. Francis, A. Greenhalgh, P. Hogarth, J. Hughes, K. Jiwa, G. Jones, G. MacGowan, D. Price, A. Sayer, J. Simpson, H. Tedd, S. Thomas, S. West, M. Witham, S. Wright and A. Young (Newcastle upon Tyne Hospitals NHS Foundation Trust and University of Newcastle, Newcastle upon Tyne, UK); M.J. McMahon and P. Neill (NHS Dumfries and Galloway, Dumfries, UK); D. Anderson,; N. Basu, H. Bayes, A. Brown, A. Dougherty, K. Fallon, L. Gilmour, D. Grieve, K. Mangion, A. Morrow, R. Sykes, C. Berry, I.B. McInnes and K. Scott (NHS Greater Glasgow and Clyde Health Board, and University of Glasgow, Glasgow, UK); F. Barrett, A. Donaldson and E.K. Sage (NHS Highland, Inverness, UK); D. Bell, A. Brown, M. Brown, R. Hamil, K. Leitch, L. Macliver, M. Patel, J. Quigley, A. Smith and B. Welsh (NHS Lanarkshire, Bothwell, UK); G. Choudhury, S. Clohisey, A. Deans, A.B. Docherty, J. Furniss, E.M. Harrison, S. Kelly and A. Sheikh (NHS Lothian and University of Edinburgh, Edinburgh, UK); J.D. Chalmers, D. Connell, C. Deas, A. Elliott, J. George, S. Mohammed, J. Rowland, A.R. Solstice, D. Sutherland and C.J. Tee (NHS Tayside and University of Dundee, Dundee, UK); J. Bunker, R. Gill and R. Nathu (NIHR Leicester Biomedical Research Centre, Respiratory Patient and Public Involvement Group, Leicester, UK); K. Holmes (NIHR Office for Clinical Research Infrastructure); H. Adamali, D. Arnold, S. Barratt, A. Dipper, S. Dunn, N. Maskell, A. Morley, L. Morrison, L. Stadon, S. Waterson and H. Welch (North Bristol NHS Trust and University of Bristol, Bristol, UK); B. Jayaraman and T. Light (North Middlesex University Hospital NHS Trust, London, UK); I. Vogiatzis (Northumbria University, Newcastle upon Tyne, UK); P. Almeida, C.E. Bolton, A. Hosseini, L. Matthews, R. Needham, K. Shaw, A.K. Thomas, J. Bonnington, M. Chrystal, C. Dupont, P.L. Greenhaff, A. Gupta, W. Jang, S. Linford, A. Nikolaidis and S. Prosper (Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK); A. Burns and N. Kanellakis (Oxford University Hospitals NHS Foundation Trust, Oxford, UK); V.M. Ferreira, C. Nikolaidou, C. Xie, M. Ainsworth, A. Alamoudi, A. Bloss, P. Carter, M. Cassar, J. Chen, F. Conneh, T. Dong, R.I. Evans, E. Fraser, J.R. Geddes, F. Gleeson, P. Harrison, M. Havinden-Williams, L.P. Ho, P. Jezzard, I. Koychev, P. Kurupati, H. McShane, C. Megson, S. Neubauer, D. Nicoll, G. Ogg, E. Pacpaco, M. Pavlides, Y. Peng, N. Petousi, J. Pimm, N.M. Rahman, B. Raman, M.J. Rowland, K. Saunders, M. Sharpe, N. Talbot and E.M. Tunnicliffe (Oxford University Hospitals NHS Foundation Trust and University of Oxford, Oxford, UK); A. Korszun (Queen Mary University of London, London, UK); S. Kerr (Roslin Institute, The University of Edinburgh, Edinburgh, UK); R.E. Barker, D. Cristiano, N. Dormand, P. George, M. Gummadi, S. Kon, K. Liyanage, C.M. Nolan, B. Patel, S. Patel, O. Polgar, L. Price, P. Shah, S. Singh and J.A. Walsh (Royal Brompton and Harefield Clinical Group, Guy's and St Thomas' NHS Foundation Trust, London, UK); M. Gibbons (Royal Devon and Exeter NHS Trust, Exeter, UK); S. Ahmad, S. Brill, J. Hurst, H. Jarvis, L. Lim, S. Mandal, D. Matila, O. Olaosebikan, C. Singh and C. Laing (Royal Free London NHS Foundation Trust, London, UK); H. Baxendale, L. Garner, C. Johnson, J. Mackie, A. Michael, J. Newman, J. Pack, K. Paques, H. Parfrey, J. Parmar and A. Reddy (Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK); M. Halling-Brown (Royal Surrey NHS Foundation Trust, Guildford, UK); P. Dark, N. Diar-Bakerly, D. Evans, E. Hardy, A. Harvey, D. Holgate, S. Knight, N. Mairs, N. Majeed, L. McMorrow, J. Oxton, J. Pendlebury, C. Summersgill, R. Ugwuoke and S. Whittaker (Salford Royal NHS Foundation Trust, Salford, UK); W. Matimba-Mupaya and S. Strong-Sheldrake (Salisbury NHS Foundation Trust, Salisbury, UK); P. Chowienczyk (School of Cardiovascular Medicine and Sciences, King's College London, London, UK); J. Bagshaw, M. Begum, K. Birchall, R. Butcher, H. Carborn, F. Chan, K. Chapman, Y. Cheng, L. Chetham, C. Clark, Z. Coburn, J. Cole, M. Dixon, A. Fairman, J. Finnigan, H. Foot, D. Foote, A. Ford, R. Gregory, K. Harrington, L. Haslam, L. Hesselden, J. Hockridge, A. Holbourn, B. Holroyd-Hind, L. Holt, A. Howell, E. Hurditch, F. Ilyas, C. Jarman, A. Lawrie, J-H. Lee, E. Lee, R. Lenagh, A. Lye, I. Macharia, M. Marshall, A. Mbuyisa, J. McNeill, S. Megson, J. Meiring, L. Milner, S. Misra, H. Newell, T. Newman, C. Norman, L. Nwafor, D. Pattenadk, M. Plowright, J. Porter, P. Ravencroft, C. Roddis, J. Rodger, S.L. Rowland-Jones, P. Saunders, J. Sidebottom, J. Smith, L. Smith, N. Steele, G. Stephens, R. Stimpson, B. Thamu, A.A.R. Thompson, N. Tinker, K. Turner, H. Turton, P. Wade, S. Walker, J. Watson, I. Wilson and A. Zawia (Sheffield Teaching NHS Foundation Trust and University of Sheffield, Sheffield, UK); L. Allsop, K. Bennett, P. Buckley, M. Flynn, M. Gill, C. Goodwin, M. Greatorex, H. Gregory, C. Heeley, L. Holloway, M. Holmes, J. Hutchinson, J. Kirk, W. Lovegrove, T.A. Sewell, S. Shelton, D. Sissons, K. Slack, S. Smith, D. Sowter, S. Turner, V. Whitworth and I. Wynter (Sherwood Forest Hospitals NHS Foundation Trust, Mansfield, UK); J. Tomlinson, L. Warburton and S. Painter (Shropshire Community Health NHS Trust, Shrewsbury, UK); S. Palmer, D. Redwood, J. Tilley, C. Vickers and T. Wainwright (Somerset NHS Foundation Trust, Taunton, UK); G. Breen and M. Hotopf (South London and Maudsley NHS Foundation Trust, and King's College London, London, UK); R. Aul, D. Forton, M. Ali, A. Dunleavy, M. Mencias, N. Msimanga, T. Samakomva, S. Siddique, V. Tavoukjian and J. Teixeira (St George's University Hospitals NHS Foundation Trust, London, UK); R. Ahmed and R. Francis (Stroke Association, London, UK); L. Connor, A. Cook, G.A. Davies, T. Rees, F. Thaivalappil and C. Thomas (Swansea Bay University Health Board, Swansea, UK); M. McNarry (Swansea University, Swansea, UK); N. Williams (Swansea University and Swansea Welsh Network, Swansea, UK); K.E. Lewis (Swansea University, Swansea Welsh Network and Hywel Dda University Health Board, Swansea, UK); M. Coulding, H. Jones, S. Kilroy, J. McCormick, J. McIntosh, V. Turner, J. Vere, A. Butt and H. Savill (Tameside and Glossop Integrated Care NHS Foundation Trust, Ashton under Lyne, UK); S.S. Kon, G. Landers, H. Lota, S. Portukhay and M. Nasseri (The Hillingdon Hospitals NHS Foundation Trust, Uxbridge, UK); A. Daniels, A. Hormis, J. Ingham and L. Zeidan (The Rotherham NHS Foundation Trust, Rotherham, UK); M. Chablani and L. Osborne (United Lincolnshire Hospitals NHS Trust, Grantham, UK); S. Aslani, A. Banerjee, R. Batterham, G. Baxter, R. Bell, A. David, E. Denneny, A.D. Hughes, W. Lilaonitkul, P. Mehta, A. Pakzad, B. Rangelov, B. Williams, J. Willoughby and M. Xu (University College London, London, UK); N. Ahwireng, D. Bang, D. Basire, J.S. Brown, R.C. Chambers, A. Checkley, R. Evans, M. Heightman, T. Hillman, J. Jacob, R. Jastrub, M. Lipman, S. Logan, D. Lomas, M. Merida Morillas, H. Plant, J.C. Porter, K. Roy and E. Wall (University College London Hospital and University College London, London, UK); T. Treibel (University College London NHS Foundation Trust, London and Barts Health NHS Trust, London, UK); N. Ahmad Haider, C. Atkin, R. Baggott, M. Bates, A. Botkai, A. Casey, B. Cooper, J. Dasgin, C. Dawson, K. Draxlbauer, N. Gautam, J. Hazeldine, T. Hiwot, S. Holden, K. Isaacs, T. Jackson, V. Kamwa, D. Lewis, J.M. Lord, S. Madathil, C. McGhee, K. McGee, A. Neal, A. Newton-Cox, J. Nyaboko, D. Parekh, Z. Peterkin, H. Qureshi, L. Ratcliffe, E. Sapey, J. Short, T. Soulsby, J. Stockley, Z. Suleiman, T. Thompson, M. Ventura, S. Walder, C. Welch, D. Wilson, S. Yasmin and K.P. Yip (University Hospital Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK); N. Chaudhuri (University Hospital of South Manchester NHS Foundation Trust, Manchester, UK); C. Childs, R. Djukanovic, S. Fletcher, M. Harvey, M.G. Jones, E. Marouzet, B. Marshall, R. Samuel, T. Sass, T. Wallis and H. Wheeler (University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, UK); R. Steeds (University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK); P. Beckett, C. Dickens and U. Nanda (University Hospitals of Derby and Burton, Derby, UK); M. Aljaroof, N. Armstrong, H. Arnold, H. Aung, M. Bakali, M. Bakau, E. Baldry, M. Baldwin, C. Bourne, M. Bourne, C.E. Brightling, N. Brunskill, P. Cairns, L. Carr, A. Charalambou, C. Christie, M.J. Davies, E. Daynes, S. Diver, R. Dowling, S. Edwards, C. Edwardson, O. Elneima, H. Evans, R.A. Evans, J. Finch, S. Finney, S. Glover, N. Goodman, B. Gooptu, N.J. Greening, K. Hadley, P. Haldar, B. Hargadon, V.C. Harris, L. Houchen-Wolloff, W. Ibrahim, L. Ingram, K. Khunti, A. Lea, D. Lee, H.J.C. McAuley, G.P. McCann, P. McCourt, T. McNally, G. Mills, W. Monteiro, M. Pareek, S. Parker, A. Prickett, I.N. Qureshi, A. Rowland, R. Russell, M. Sereno, A. Shikotra, S. Siddiqui, A. Singapuri, S.J. Singh, J. Skeemer, M. Soares, E. Stringer, S. Terry, T. Thornton, M. Tobin, T.J.C. Ward, F. Woodhead, T. Yates and A.J. Yousuf (University Hospitals of Leicester NHS Trust and University of Leicester, Leicester, UK); B. Guillen Guiio, O.C. Leavy and L.V. Wain (Department of Population Health Sciences, University of Leicester, Leicester, UK); M. Broome, P. McArdle, D. Thickett, R. Upthegrove, D. Wilkinson, P. Moss and D. Wraith (University of Birmingham, Birmingham, UK); J. Evans (University of Bristol, Bristol, UK); E. Bullmore, J.L. Heeney, C. Langenberg, W. Schwaeble, C. Summers and J. Weir McCall (University of Cambridge, Cambridge, UK); D. Adeloye, D.E. Newby, R. Pius, I. Rudan, M. Shankar-Hari, C.L. Sudlow, M. Thorpe, S. Walmsley and B. Zheng (University of Edinburgh, Edinburgh, UK); L. Allan, C. Ballard and A. McGovern (University of Exeter, Exeter, UK); J. Dennis (University of Exeter Medical School, Exeter, UK); J. Cavanagh, S. MacDonald, K. O'Donnell, J. Petrie, N. Sattar and M. Spears (University of Glasgow, Glasgow, UK); E. Guthrie and M. Henderson (University of Leeds, Leeds, UK); R.J. Allen, M. Bingham, T. Brugha, R. Free, D. Jones, C. Lawson, L. Gardiner, A.J. Moss, E. Mukaetova-Ladinska, P. Novotny, C. Overton, J.E. Pearl, T. Plekhanova, M. Richardson, N. Samani, J. Sargent, M. Sharma, M. Steiner, C. Taylor, C. Tong, E. Turner, J. Wormleighton, B. Zhao, K. Ntotsis, R.M. Saunders and D. Lozano-Rojas (University of Leicester, Leicester, UK); D. Cuthbertson, G. Kemp, A. McArdle, B. Michael, W. Reynolds, L.G. Spencer, B. Vinson and M. Ashworth (University of Liverpool, Liverpool, UK); K. Abel, H. Chinoy, B. Deakin, M. Harvie, C.A. Miller, S. Stanel, P. Barran and D. Trivedi (University of Manchester, Manchester, UK); H. McAllister-Williams, S. Paddick, A. Rostron and J.P. Taylor (University of Newcastle, Newcastle upon Tyne, UK); D. Baguley, C. Coleman, E. Cox, L. Fabbri, S. Francis, I. Hall, E. Hufton, S. Johnson, F. Khan, P. Kitterick, R. Morriss, N. Selby and L. Wright (University of Nottingham, Nottingham, UK); C. Antoniades, A. Bates, M. Beggs, K. Bhui, K. Breeze, K.M. Channon, D. Clark, X. Fu, M. Husain, X. Li, E. Lukaschuk, C. McCracken, K. McGlynn, R. Menke, K. Motohashi, T.E. Nichols, G. Ogbole, S. Piechnik, I. Propescu, J. Propescu, A.A. Samat, Z.B. Sanders, L. Sigfrid, M. Webster, L. Kingham, P. Klenerman and H. Lamlum (University of Oxford, Oxford, UK); G. Carson (University of Oxford, Nuffield Department of Medicine, Oxford, UK); M. Taquet (University of Oxford and Oxford Health NHS Foundation Trust, Oxford, UK); L. Finnigan, L.C. Saunders and J.M. Wild (University of Sheffield, Sheffield, UK); P.C. Calder, N. Huneke, G. Simons and D. Baldwin (University of Southampton, Southampton, UK); S. Bain (University of Swansea, Swansea, UK); L. Daines (Usher Institute, University of Edinburgh, Edinburgh, UK); E. Bright, P. Crisp, R. Dharmagunawardena and M. Stern (Whittington Health NHS Trust, London, UK); L. Bailey, A. Reddington and A. Wight (Wirral University Teaching Hospital, Birkenhead, UK); A. Ashish, J. Cooper and E. Robinson (Wrightington Wigan and Leigh NHS Trust, Wigan, UK); A. Broadley (Yeovil District Hospital NHS Foundation Trust, Yeovil, UK); and L. Barman, C. Brookes, K. Elliott, L. Griffiths, Z. Guy, K. Howard, D. Ionita, H. Redfearn, C. Sarginson and A. Turnbull (York and Scarborough NHS Foundation Trust, York, UK).
Author contributions: The manuscript was initially drafted by O. Elneima and C.E. Brightling, and further developed by the writing committee. C.E. Brightling, R.A. Evans, L.V. Wain, J.D. Chalmers, L-P. Ho, A. Horsley, M. Marks, K. Poinasamy, B. Raman, O. Elneima, H.J.C. McAuley, A. Shikotra, A. Singapuri, M. Sereno, L. Houchen-Wolloff and A. Sheikh made substantial contributions to the conception and design of the work. All authors contributed to data interpretation, critical review and revision of the manuscript. O. Elneima and C.E. Brightling have accessed and verified the underlying data. O. Elneima, C.E. Brightling, A. De Soyza and L.G. Heaney were responsible for the decision to submit the manuscript, and are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Conflict of interest: J.R. Hurst has received support to attend meetings, research grants, and personal payment and payment to his employer from pharmaceutical companies that make medicines to treat airways diseases. J.K. Quint reports grants from Industrial Strategy Challenge Fund, the Medical Research Council, Health Data Research, GlaxoSmithKline (GSK), Boehringer Ingelheim (BI), Asthma+Lung UK and AstraZeneca (AZ), and consulting fees from GSK, Evidera, Chiesi, AZ and Insmed outside the submitted work. P.E. Pfeffer reports grants from NIHR and GSK, Honoraria payments for lectures from AZ, GSK, Sanofi and Chiesi and travel fees from AZ, GSK, Sanofi outside the submitted work. N.J. Greening reports grants from GSK and BioAge, and personal fees and travel grants from Genentech, Roche, Chiesi, AZ, GSK, Pulmonx and Chiesi outside the submitted work. J.D. Chalmers is an associate editor of this journal. A. Horsley reports grants from UKRI, NIHR and NIHR Manchester BRC during the conduct of this study and unenumerated role as the chair of NIHR Translational Research Collaboration. A. Sheikh has served on AZ's thrombotic thrombocytopenic taskforce, and on a number of UK and Scottish Government COVID-19 advisory bodies; all these roles were unremunerated. B. Raman reports grant from BHF Oxford CRE and speaker fees from Axcella Therapeutics. R.A. Evans reports grants from UKRI/MRC, DHSC/NIHR, Wolfson Foundation and Genentec/Roche during the conduct of this study, travel and speaker fees from AZ/Evidera, Boehringer Ingelheim (BI), Moderna and Chiesi, and unremunerated leadership roles in ERS/ATS outside the submitted work. C.E. Brightling declares that their institute was awarded a grant from UKRI/NIHR to complete this work; the author reports grants from GSK, AZ, Sanofi, Regeneron, BI, Chiesi, Novartis, Roche, Genentech, Mologic and 4DPharma; and consultancy fees paid to their institution from GSK, AZ, Sanofi, BI, Chiesi, Novartis, Roche, Genentech, Mologic, 4DPharma and Areteia. A. De Soyza declares receiving personal consulting fees and travel grants from AZ, Bayer, GSK, Chiesi, Novartis, Pfizer, Insmed, Gilead and 30T outside the submitted work. All other authors declare no competing interests.
Support statement: This work is independent research jointly funded by the National Institute for Health and Care Research (NIHR) and UK Research and Innovation (UKRI) (PHOSP-COVID – Post-hospitalisation COVID-19 study: a national consortium to understand and improve long-term health outcomes; grant references: MR/V027859/1 and COV0319). The views expressed in this publication are those of the author(s) and not necessarily those of NIHR, The Department of Health and Social Care or UKRI.
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