Demographic, clinical, functional characteristics and outcomes of patients with pulmonary alveolar proteinosis (PAP) who had COVID-19 (n=34)#
| All | Non-hospitalised | Hospitalised | p-value | |
| Adults | ||||
| Patients | 31 | 20 | 11 | |
| Males | 19 (61.3%) | 12 (60.0%) | 7 (63.6%) | 0.700 |
| Age at inclusion, years, median (IQR) | 47 (35.0–56.0) | 40 (28.5–50.7) | 51 (45.0–56.0) | 0.060 |
| Duration of disease, months, median (IQR) | 57 (36.0–115.0) | 74.5 (38.0–127.5) | 43 (28.0–98.0) | 0.256 |
| Autoimmune PAP¶ | 30 (96.8%) | 19 (95%) | 11 (100%) | 0.451 |
| GM-CSF autoantibody level, μg·mL−1, median (IQR) | 89.5 (52.3–154.7) | 69.01 (21.1–187.7) | 107.6 (62.3–125.2) | 0.625 |
| PAP documented by lung biopsy | 9 (29%) | 3 (15%) | 6 (54.5%) | 0.020 |
| Never-/current/ex-smokers | 38.7%/9.7%/51.6% | 45%/5%/50% | 27.3%/18.2%/54.5% | 0.391 |
| BMI, kg·m−2, median (IQR) | 26.9 (23.5–30.0) | 26.9 (23.4–29.3) | 27 (22.6–34.0) | 0.714 |
| LTOT | 7 (22.6%) | 2 (10%) | 5 (45.5%) | 0.029 |
| Arterial hypertension | 8 (25.8%) | 2 (10%) | 6 (54.5%) | 0.007 |
| History of treatment with WLL | 27 (87.1%) | 18 (90%) | 9 (81.8%) | >0.950 |
| Number of WLLs, median (IQR) | 2 (1–4) | 2 (1–3) | 3 (1–11) | 0.283 |
| History of treatment with iGM-CSF | 15 (48.4%) | 10 (50%) | 5 (45.5%) | 0.809 |
| FVC, % predicted, median (IQR) | 78 (64.3–86.0) | 81.5 (71.0–89.0) | 73 (55.0–81.0) | 0.175 |
| DLCO, % predicted, median (IQR) | 62.9 (48.8–70.7) | 69.4 (53.0–75.5) | 53 (35.5–69.3) | 0.137 |
| SpO2 at rest, median (IQR) | 96.0% (95.5–98%) | 97.0% (94.0–98.0%) | 95.5% (94.5–96.2%) | 0.257 |
| Distance walked in 6MWT, m, median (IQR) | 481 (360–525) | 501 (437.5–560.0) | 407 (333.7–483.3) | 0.060 |
| Fever | 24 (77.4%) | 14 (70%) | 10 (90.9%) | 0.053 |
| Dyspnoea | 19 (61.3%) | 10 (50%) | 9 (81.8%) | 0.032 |
| Fatigue | 18 (58.1%) | 10 (50%) | 8 (72.7%) | 0.114 |
| Cough | 16 (51.6%) | 8 (40%) | 8 (72.7%) | 0.038 |
| Anosmia | 9 (29%) | 6 (30%) | 3 (27.3%) | >0.950 |
| Oxygen therapy or increase of oxygen | 11 (35.5%) | 0 (0%) | 11 (100%) | <0.001 |
| HFNC | 7 (22.6%) | 0 (0%) | 7 (63.6%) | p<0.001 |
| Systemic corticosteroids | 18 (58.1%) | 8 (40%) | 11 (100%) | 0.001 |
| Macrolides | 14 (45.2%) | 6 (30%) | 8 (72.3%) | 0.031 |
| Anticoagulants | 13 (40%) | 4 (20%) | 9 (81.8%) | 0.020 |
| Remdesivir | 2 (6.4%) | 0 (0%) | 2 (18.2%) | 0.118 |
| Other treatment+ | 2 (6.4%) | 0 (0%) | 2 (18.2%) | 0.118 |
| iGM-CSF | 2 (6.4%) | 2 (10%) | 0 (0%) | 0.527 |
| ICU admission | 5 (16.1%) | 0 (0%) | 5 (45.5%) | 0.003 |
| Death or lung transplantation | 3 (9.7%) | 0 (0%) | 3 (27.3%) | 0.037 |
| Children | ||||
| Patients | 7 | 4 | 3 | |
| Males | 4 (57.1%) | 1 (25%) | 3 (100%) | 0.100 |
| Age at inclusion, years, mean (range) | 12 (5–17) | 6 (11–17) | 9 (5–14) | 0.108 |
| Duration of disease, months, mean (range) | 33 (3–36) | 23 (3–26) | 22 (14–36) | 0.154 |
| Autoimmune PAP | 2 (28.6%) | 1 (25%) | 1 (33.3%) | 0.809 |
| Congenital PAP¶ | 5 (71.4%) | 3 (75%) | 2 (66.7%) | 0.809 |
| BMI, kg·m−2, mean (range) | 13.1 (14.4–27.5) | 13.1 (14.4 (27.5) | 7 (14.6–21.6) | 0.724 |
| LTOT | 5 (71.4%) | 3 (75%) | 2 (66.7%) | 0.809 |
| History of treatment with WLL | 5 (71.4%) | 3 (75%) | 2 (66.7%) | 0.809 |
| Number of WLLs, mean (range) | 96 (0–96) | 96 (0–96) | 13 (0–13) | 0.372 |
| History of treatment with iGM-CSF | 1 (14.3%) | 1 (25%) | 0 (0%) | 0.325 |
| Other treatment§ | 5 (71.4%) | 3 (75%) | 2 (66.7%) | >0.950 |
| FVC, % predicted, mean (range) | 47 (35–82) | 19 (39–58) | 47 (35–82) | >0.950 |
| DLCO, % predicted, mean (range) | 61 (31–92) | 18 (31–49) | 0 (92) | 0.221 |
| SpO2 at rest, mean (range) | 22% (75–97%) | 22% (75–97%) | 12% (85–97%) | >0.950 |
| Hospitalisationƒ | 3 (42.9%) | 3 (100%) | ||
| Death or lung transplantation | 0 (0%) | 0 (0%) |
The median (prevalence (interquartile range, IQR) of COVID-19 for European countries participating in the study was calculated taking into consideration the population of each country and the cumulative cases of COVID-19 officially reported for each one as per 7 January 2022 and was found to be 14.8% (11.09–17.15%) (https://www.ecdc.europa.eu/en/covid-19/data): Greece 14.02%, Italy 11.74%, Germany 8.85%, Denmark 15.68%, France 17.14%, Turkey 10.81%, Poland 11.09%, Spain 14.8%, Ireland 18.13%, UK 20.74% and Portugal 15.15%. Regarding adult PAP patients, the prevalence was calculated by COVID-19 patients/active PAP patients followed-up in each centre (Italy 10/50, Greece 3/27, Turkey 3/11, Poland 3/9, Germany 2/38, France 3/38, Spain 2/9, UK 2/50, Denmark 1/10, Ireland 1/4, Portugal 1/2); overall prevalence 31 (12.5%) out of 255. Children included in the study were as follows: four in Germany, one in the UK, one in France and one in Greece; three children (Germany) presented with COVID-19; overall prevalence: 34 out of 255 (13.3%). GM-CSF: granulocyte–macrophage colony-stimulating factor; BMI: body mass index; LTOT: long-term oxygen therapy; WLL: whole-lung lavage; iGM-CSF: inhaled granulocyte–macrophage colony-stimulating factor; FVC: forced vital capacity; DLCO: diffusing capacity of the lung for carbon monoxide; SpO2: oxygen saturation measured by pulse oximetry; 6MWT: 6-min walk test; HFNC: high-flow nasal canula; ICU: intensive care unit. #: 21 out of 31 adult patients had SARS-CoV-2 infection documented by reverse transcriptase (RT)-PCR, only one adult patient had received one dose of the vaccine against SARS-CoV-2 before developing COVID-19 and three out of three children had SARS-CoV-2 infection documented by RT-PCR. ¶: in adults, only one patient had disease related to CSF2RA (GM-CSF receptor subunit α) mutation; in children, one had disease related to CSF2RA mutation, one related to CSF2RB (GM-CSF receptor subunit β) mutation and three to MARS1; out of them, two brothers with MARS1 mutation contracted SARS-CoV-2 infection. +: plasma therapy or bamlanivimab; §: methionine, azithromycin, simvastatin or bromhexine. ƒ: details of treatment upon hospitalisation were available for one child, and included HFNC oxygen treatment, systemic corticosteroids and anticoagulants, but no iGM-CSF. Bold indicates statistically significant p-values (p<0.05).