Introduction
Methods
Study design, setting, and participants
Study procedures and data collection
Outcome measures
Statistical analysis
Results
n = 90 | Severe disease requiring ICU admission n = 21 (23%) | Moderate severity (Hospitalization- non-ICU) n = 51 (57%) | Mild severity (Outpatient) n = 18 (20%) | p value* | |
---|---|---|---|---|---|
Age (years)a | 55 (49–63) | 55 (54–62) | 57 (51–69) | 48 (39–54) | 0.003 |
Sex (female)c | 35 (39) | 5 (24) | 19 (37) | 11 (61) | 0.055 |
Ethnicity; Caucasianc | 90 (100) | 21 (100) | 51 (100) | 18 (100) | – |
Body mass index (SI)a | 26 (24–29) | 25 (24–28) | 27 (25–30) | 25 (21–27) | 0.046 |
Current smokingc | 2 (2) | 0 (0) | 2 (4) | 0 (0) | 0.457 |
Ex-smokingc | 54 (40) | 5 (24) | 25 (49) | 4 (22) | 0.042 |
Pack yearsb | 7 ± 14 | 4 ± 7 | 11 ± 17 | 1 ± 3 | 0.009 |
Premedical history | |||||
Cardiovascular diseasec | 32 (36) | 12 (57) | 20 (39) | 0 (0) | 0.001 |
Arterial hypertensionc | 23 (26) | 10 (48) | 13 (26) | 0 (0) | 0.003 |
Pulmonary diseasec | 17 (19) | 4 (19) | 11 (22) | 2 (11) | 0.622 |
Endocrinological diseasec | 41 (46) | 12 (57) | 27 (53) | 2 (11) | 0.004 |
Hypercholesterolemiac | 17 (19) | 4 (19) | 13 (26) | 0 (0) | 0.060 |
Diabetes mellitus IIc | 14 (16) | 4 (19) | 10 (20) | 0 (0) | 0.126 |
Malignancyc | 12 (13) | 3 (14) | 8 (16) | 1 (6) | 0.548 |
Immunological deficiencyc | 5 (6) | 4 (19) | 0 (0) | 1 (6) | 0.006 |
Pre-existing neurological diseases | |||||
Nonec | 69 (77) | 17 (81) | 38 (75) | 14 (78) | 0.835 |
Strokec | 0 (0) | 0 (0) | 0 (0) | 0 (0) | – |
Parkinsonismc | 0 (0) | 0 (0) | 0 (0) | 0 (0) | – |
Multiple sclerosisc | 0 (0) | 0 (0) | 0 (0) | 0 (0) | – |
Motor neuron diseasec | 0 (0) | 0 (0) | 0 (0) | 0 (0) | – |
(Poly)-Neuropathyc | 5 (6) | 1 (5) | 4 (8) | 0 (0) | 0.451 |
Traumatic brain injuryc | 1 (1) | 0 (0) | 1 (2) | 0 (0) | 0.679 |
Restless legs syndromec | 2 (2) | 1 (5) | 0 (0) | 1 (6) | 0.259 |
Essential tremorc | 2 (2) | 1 (5) | 1 (2) | 0 (0) | 0.592 |
Migrainec | 3 (3) | 1 (5) | 1 (2) | 1 (6) | 0.702 |
Neuromuscular diseasec | 0 (0) | 0 (0) | 0 (0) | 0 (0) | – |
Epilepsyc | 0 (0) | 0 (0) | 0 (0) | 0 (0) | – |
Otherc | 10 (11) | 1 (5) | 7 (14) | 2 (11) | 0.546 |
Pre-existing psychiatric diseases | |||||
Depression (treated) c | 6 (7) | 3 (14) | 3 (6) | 0 (0) | 0.193 |
Treatment and hospital course | |||||
Oxygen requirementc | 49 (55) | 21 (100) | 28 (55) | 0 (0) | < 0.001 |
Mechanical ventilationc | 20 (22) | 20 (95) | 0 (0) | 0 (0) | < 0.001 |
Steroid treatmentc | 15 (17) | 7 (33) | 8 (16) | 0 (0) | 0.023 |
Length of hospital stay (days)a | 10 (5–19) | 28 (19–38) | 8 (5–11) | – | < 0.001 |
Early rehabilitationc | 18 (20) | 15 (71) | 3 (6) | 0 (0) | < 0.001 |
Length of rehabilitation (days)a | 21 (21–27) | 21 (21–27) | 19–21 | – | < 0.001 |
Three-month prevalence of impaired HR-quality of life
Mental health and SF-36 at the 3-month follow-up
Physical symptom burden and SF-36 at the 3-month follow-up
Factors associated with impaired quality of life at the 3-month follow-up
SF-36 ≥ 40 | SF-36 < 40 | p value* | MCS ≥ 40 | MCS < 40 | p value* | PCS ≥ 40 | PCS < 40 | p value* | |
---|---|---|---|---|---|---|---|---|---|
n | 61 | 28 | 67 | 22 | 76 | 12 | |||
Demographics | |||||||||
Age | 57.1 (12.6) | 53.5 (11.9) | 0.22 | 57.3 (12.4) | 52.0 (11.8) | 0.08 | 56.13 (12.4) | 55.00 (13.8) | 0.77 |
Body mass index | 26.7 (5.2) | 26.6 (4.7) | 0.95 | 26.4 (5.1) | 27.4 (4.6) | 0.40 | 27.1 (5.0) | 24.35 (4.0) | 0.08 |
Male sex | 36 (59.0) | 19 (67.9) | 0.57 | 39 (58.2) | 16 (72.7) | 0.34 | 49 (64.5) | 6 (50.0) | 0.52 |
Current smoker | 0 (0.0) | 2 (7.1) | 0.18 | 1 (1.5) | 1 (4.5) | 0.99 | 0 (0.0) | 2 (16.7) | 0.01 |
Premedical history | |||||||||
Cardiovascular disease | 21 (34.4) | 11 (39.3) | 0.84 | 24 (35.8) | 8 (36.4) | 1.00 | 27 (35.5) | 5 (41.7) | 0.93 |
Pulmonary disease | 11 (18.0) | 6 (21.4) | 0.93 | 11 (16.4) | 6 (27.3) | 0.42 | 13 (17.1) | 3 (25.0) | 0.80 |
Diabetes mellitus II | 8 (13.1) | 6 (21.4) | 0.49 | 9 (13.4) | 5 (22.7) | 0.48 | 12 (15.8) | 2 (16.7) | 1.00 |
Malignancy | 9 (14.8) | 3 (10.7) | 0.85 | 10 (14.9) | 2 (9.1) | 0.74 | 11 (14.5) | 1 (8.3) | 0.90 |
Neurological disease | 14 (22.6) | 7 (25.0) | 0.79 | 15 (22.1) | 6 (27.3) | 0.77 | 17 (22.1) | 4 (33.3) | 0.45 |
Treatment and hospital course | |||||||||
Risk category | 0.25 | 0.51 | 0.24 | ||||||
Mild (Outpatient) | 14 (23.0) | 3 (10.7) | 14 (20.9) | 3 (13.6) | 15 (19.7) | 2 (16.7) | |||
Moderate (Hospitalized) | 35 (57.4) | 16 (57.1) | 39 (58.2) | 12 (54.5) | 46 (60.5) | 5 (41.7) | |||
Severe (ICU) | 12 (19.7) | 9 (32.1) | 14 (20.9) | 7 (31.8) | 15 (19.7) | 5 (41.7) | |||
Risk category (WHO) | 0.35 | 0.28 | 0.18 | ||||||
Mild | 14 (23.0) | 3 (10.7) | 14 (20.9) | 3 (13.6) | 15 (19.7) | 2 (16.7) | |||
Moderate | 17 (27.9) | 6 (21.4) | 20 (29.9) | 3 (13.6) | 19 (25.0) | 4 (33.3) | |||
Severe | 18 (29.5) | 10 (35.7) | 19 (28.4) | 9 (40.9) | 27 (35.5) | 1 (8.3) | |||
Critical | 12 (19.7) | 9 (32.1) | 14 (20.9) | 7 (31.8) | 15 (19.7) | 5 (41.7) | |||
Mechanical ventilation | 11 (18.0) | 9 (32.1) | 0.23 | 13 (19.4) | 7 (31.8) | 0.36 | 14 (18.4) | 5 (41.7) | 0.15 |
Steroid use | 7 (11.5) | 8 (28.6) | 0.09 | 9 (13.4) | 6 (27.3) | 0.24 | 11 (14.5) | 4 (33.3) | 0.23 |
Length of hospital stay (days)** | 9.8 (10.4) | 16.5 (17.5) | 0.03 | 10.9 (12.1) | 14.8 (16.4) | 0.24 | 10.0 (9.9) | 23.7 (23.7) | 0.00 |
ICU days | 3.2 (7.4) | 6.2 (11.9) | 0.14 | 3.6 (7.8) | 5.9 (12.2) | 0.29 | 2.8 (6.9) | 11.8 (16.1) | 0.00 |
Mental health and cognition at 3 months | |||||||||
HADS-A | 3.1 (2.4) | 7.64 (4.1) | 0.00 | 3.3 (2.6) | 8.4 (4.0) | 0.00 | 4.0 (3.1) | 7.8 (5.4) | 0.00 |
HADS-A > 7 | 4 (6.9) | 15 (53.6) | 0.00 | 5 (7.8) | 14 (63.6) | 0.00 | 13 (17.8) | 5 (41.7) | 0.14 |
HADS-D | 1.7 (1.7) | 5.4 (3.9) | 0.00 | 1.8 (1.7) | 6.3 (3.9) | 0.00 | 2.5 (2.6) | 5.3 (5.0) | 0.01 |
HADS-D > 7 | 1 (1.7) | 9 (32.1) | 0.00 | 1 (1.6) | 9 (40.9) | 0.00 | 6 (8.2) | 4 (33.3) | 0.04 |
PCL-5 > 32 | 1 (1.7) | 8 (28.6) | 0.00 | 1 (1.6) | 8 (36.4) | 0.00 | 4 (5.5) | 4 (33.3) | 0.01 |
Any mental health disorder | 6 (10.3) | 19 (67.9) | 0.00 | 7 (10.9) | 18 (81.8) | 0.00 | 17 (23.3) | 7 (58.3) | 0.03 |
Fatigue | 10 (16.4) | 12 (44.4) | 0.01 | 13 (19.7) | 9 (40.9) | 0.09 | 12 (15.8) | 9 (81.8) | 0.00 |
Sleep disturbance | 11 (18.0) | 19 (67.9) | 0.00 | 15 (22.4) | 15 (68.2) | 0.00 | 19 (25.0) | 10 (83.3) | 0.00 |
Impaired concentration | 7 (11.5) | 11 (42.3) | 0.00 | 8 (12.1) | 10 (47.6) | 0.00 | 14 (18.7) | 3 (27.3) | 0.79 |
MOCA | 27.8 (2.0) | 26.9 (2.6) | 0.11 | 27.9 (2.0) | 26.5 (2.6) | 0.01 | 27.4 (2.3) | 28.1 (1.5) | 0.36 |
MOCA < 26 | 9 (15.5) | 7 (26.9) | 0.35 | 9 (14.5) | 7 (31.8) | 0.14 | 15 (20.5) | 1 (10.0) | 0.72 |
Neurological signs and diseases at 3 months | |||||||||
Any new neurological disease | 7 (11.5) | 4 (14.3) | 0.98 | 9 (13.4) | 2 (9.1) | 0.87 | 7 (9.2) | 4 (33.3) | 0.06 |
New peripheral neuromyopathy | 6 (9.8) | 3 (10.7) | 1.00 | 7 (10.4) | 2 (9.1) | 1.00 | 6 (7.9) | 3 (25.0) | 0.19 |
CIP/CIM | 0 (0.0) | 3 (10.7) | 0.05 | 1 (1.5) | 2 (9.1) | 0.30 | 0 (0.0) | 3 (25.0) | 0.00 |
Any neurological sign | 33 (54.1) | 17 (60.7) | 0.72 | 38 (56.7) | 12 (54.5) | 1.00 | 41 (53.9) | 9 (75.0) | 0.29 |
Objective hyposmia (SS-16 ≤ 12) | 21 (36.2) | 14 (51.9) | 0.26 | 25 (39.7) | 10 (45.5) | 0.82 | 27 (37.0) | 8 (72.7) | 0.06 |
Subjective hyposmia | 11 (18.0) | 3 (10.7) | 0.57 | 13 (19.4) | 1 (4.5) | 0.19 | 12 (15.8) | 2 (16.7) | 1.00 |
Subjective hypogeusia | 6 (9.8) | 4 (14.3) | 0.80 | 8 (11.9) | 2 (9.1) | 1.00 | 7 (9.2) | 3 (25.0) | 0.27 |
New headache | 2 (3.3) | 2 (7.1) | 0.79 | 2 (3.0) | 2 (9.1) | 0.54 | 2 (2.6) | 1 (8.3) | 0.88 |
Vertigo | 2 (3.3) | 4 (14.3) | 0.14 | 3 (4.5) | 3 (13.6) | 0.32 | 2 (2.6) | 3 (25.0) | 0.02 |
Self-reported numbness | 8 (13.8) | 11 (44.0) | 0.01 | 10 (15.6) | 9 (47.4) | 0.01 | 14 (19.4) | 4 (40.0) | 0.29 |
Gait abnormality | 1 (1.6) | 3 (10.7) | 0.17 | 3 (4.5) | 1 (4.5) | 1.00 | 2 (2.6) | 2 (16.7) | 0.16 |
Myalgia | 4 (6.6) | 4 (14.3) | 0.43 | 7 (10.4) | 1 (4.5) | 0.68 | 4 (5.3) | 4 (33.3) | 0.01 |
Tremors | 5 (8.2) | 2 (7.1) | 1.00 | 5 (7.5) | 2 (9.1) | 1.00 | 7 (9.2) | 0 (0.0) | 0.60 |
Muscle atrophy | 1 (1.6) | 2 (7.1) | 0.48 | 2 (3.0) | 1 (4.5) | 1.00 | 1 (1.3) | 2 (16.7) | 0.06 |
Paresis | 2 (3.3) | 3 (10.7) | 0.36 | 4 (6.0) | 1 (4.5) | 1.00 | 3 (3.9) | 2 (16.7) | 0.27 |
Cardio-pulmonary health at 3 months | |||||||||
CT pathology | 36 (61.0) | 19 (70.4) | 0.55 | 40 (62.5) | 15 (68.2) | 0.83 | 47 (63.5) | 7 (63.6) | 1.00 |
CT abnormalities > 5 | 15 (25.0) | 9 (33.3) | 0.59 | 18 (27.7) | 6 (27.3) | 1.00 | 18 (24.0) | 6 (54.5) | 0.08 |
CT abnormalities > 10 | 5 (8.3) | 5 (18.5) | 0.31 | 5 (7.7) | 5 (22.7) | 0.13 | 7 (9.3) | 3 (27.3) | 0.22 |
Reduced DLCO | 9 (15.0) | 5 (18.5) | 0.92 | 12 (18.2) | 2 (9.5) | 0.55 | 10 (13.3) | 4 (36.4) | 0.14 |
Impaired lung function | 21 (35.0) | 11 (39.3) | 0.88 | 25 (37.9) | 7 (31.8) | 0.80 | 23 (30.7) | 8 (66.7) | 0.04 |
Diastolic dysfunction | 34 (56.7) | 16 (59.3) | 1.00 | 37 (56.9) | 13 (59.1) | 1.00 | 43 (57.3) | 6 (54.5) | 1.00 |
Persistent dyspnoa | 18 (30.0) | 13 (48.1) | 0.16 | 22 (33.8) | 9 (40.9) | 0.73 | 23 (30.7) | 8 (72.7) | 0.02 |
Dyspnoea, mMRC | 0.19 | 0.39 | 0.00 | ||||||
0 | 42 (70.0) | 13 (50.0) | 43 (66.2) | 12 (57.1) | 52 (69.3) | 2 (20.0) | |||
1 | 16 (26.7) | 9 (34.6) | 19 (29.2) | 6 (28.6) | 21 (28.0) | 4 (40.0) | |||
2 | 1 (1.7) | 2 (7.7) | 2 (3.1) | 1 (4.8) | 1 (1.3) | 2 (20.0) | |||
3 | 1 (1.7) | 1 (3.8) | 1 (1.5) | 1 (4.8) | 1 (1.3) | 1 (10.0) | |||
4 | 0 (0.0) | 1 (3.8) | 0 (0.0) | 1 (4.8) | 0 (0.0) | 1 (10.0) | |||
Persistent cough | 8 (13.3) | 6 (22.2) | 0.47 | 9 (13.8) | 5 (22.7) | 0.52 | 10 (13.3) | 4 (36.4) | 0.14 |
Laboratory parameters at 3 months | |||||||||
Hyperferrtinemia | 10 (16.7) | 6 (22.2) | 0.75 | 12 (18.5) | 4 (18.2) | 1.00 | 13 (17.3) | 3 (27.3) | 0.71 |
HbA1c | 0.47 | 0.54 | 0.99 | ||||||
< 5.7% | 40 (66.7) | 17 (63.0) | 42 (64.6) | 15 (68.2) | 49 (65.3) | 7 (63.6) | |||
≥ 5.7% and < 6.5% | 16 (26.7) | 6 (22.2) | 18 (27.7) | 4 (18.2) | 19 (25.3) | 3 (27.3) | |||
≥ 6.5% | 4 (6.7) | 4 (14.8) | 5 (7.7) | 3 (13.6) | 7 (9.3) | 1 (9.1) | |||
NT elevated | 15 (25.9) | 6 (22.2) | 0.93 | 16 (25.4) | 5 (22.7) | 1.00 | 17 (23.3) | 4 (36.4) | 0.58 |
D dimer elevated | 14 (23.7) | 5 (18.5) | 0.79 | 17 (26.6) | 2 (9.1) | 0.16 | 15 (20.3) | 4 (36.4) | 0.42 |
CRP levels elevated | 5 (8.3) | 3 (11.1) | 0.99 | 5 (7.7) | 3 (13.6) | 0.68 | 7 (9.3) | 1 (9.1) | 1.00 |
IL6 elevated | 4 (6.7) | 1 (3.7) | 0.96 | 5 (7.7) | 0 (0.0) | 0.42 | 4 (5.3) | 1 (9.1) | 1.00 |
Functional outcome at 3 months | |||||||||
GOSE | 0.07 | 0.37 | 0.00 | ||||||
5 | 0 (0.0) | 1 (3.6) | 1 (1.5) | 0 (0.0) | 0 (0.0) | 1 (8.3) | |||
6 | 2 (3.3) | 3 (10.7) | 3 (4.5) | 2 (9.1) | 2 (2.6) | 3 (25.0) | |||
7 | 18 (29.5) | 12 (42.9) | 20 (29.9) | 10 (45.5) | 23 (30.3) | 6 (50.0) | |||
8 | 41 (67.2) | 12 (42.9) | 43 (64.2) | 10 (45.5) | 51 (67.1) | 2 (16.7) | |||
mRS | 0.01 | 0.14 | 0.00 | ||||||
0 | 37 (60.7) | 10 (35.7) | 39 (58.2) | 8 (36.4) | 45 (59.2) | 2 (16.7) | |||
1 | 21 (34.4) | 10 (35.7) | 22 (32.8) | 9 (40.9) | 27 (35.5) | 3 (25.0) | |||
2 | 3 (4.9) | 7 (25.0) | 5 (7.5) | 5 (22.7) | 4 (5.3) | 6 (50.0) | |||
4 | 0 (0.0) | 1 (3.6) | 1 (1.5) | 0 (0.0) | 0 (0.0) | 1 (8.3) |