Demographics, clinical variables and outcomes among COVID-19 subjects
We identified 594 hospitalized subjects infected by COVID-19, 53 asymptomatic patients were excluded. 541 cases were recruited in the final analysis. The median age of the recruited subjects was 43 years (IQR, 33–55). Of the 541 subjects, 173 (32.0%) had one or more coexisting medical conditions. Hypertension (14.2%) and diabetes (8.7%) were the most common comorbidities. Respiratory COVID-19 subjects were more likely to be classified into severe and very severe group and had longer hospital days (17 vs 14, p = 0.03) relative to extra-respiratory COVID-19 subjects. All the patients received antiviral therapy. Respiratory COVID-19 subjects received more corticosteroids (26.5 vs 14.6, p = 0.005) and antibiotics (48 vs 36.5, p = 0.02) compared to extra-respiratory COVID-19 subjects. Respiratory COVID-19 subjects also had more secondary bacterial infections (p < 0.001), needed the intensive care unit more (p = 0.005), non-invasive ventilation more (p = 0.004), developed ARDS more (p = 0.001) and needed longer to recover (p = 0.003) compared to predominately extra-respiratory COVID-19 subjects. No extra-respiratory COVID-19 subject required advanced support, including invasive mechanical ventilation, extracorporeal membrane oxygenation, and continuous renal replacement therapies. There were no significant differences of laboratory findings between the two groups. (Table 1)
Table 1
Demographics, clinical variables and outcomes among COVID-19 subjects
Variable | All | Respiratorya | Extra-respiratoryb | pc |
N | 541 | 404 | 137 | |
Age (IQR) | 43.0 (33.0–55.0) | 45.0 (34.0–57.0) | 38.0 (29.0–50.0) | < 0.001 |
Gender: Female (%) | 270 (49.9) | 204 (50.5) | 67 (48.9) | 0.64 |
Body mass index (IQR) | 23.3 (21.3–26.2) | 23.4 (21.3–26.2) | 23.1 (21.3–25.8) | 0.55 |
Contact with confirmed cases (%) | 417 (77.1) | 301 (404) | 116 (84.7) | 0.05 |
Comorbidities, any (%) | 173(32.0) | 144 (35.7) | 29(21.0) | 0.002 |
Diabetes (%) | 47 (8.7) | 38(9.4) | 9 (6.5) | 0.31 |
Hypertension (%) | 77 (14.2) | 67(16.6) | 10(7.2) | 0.007 |
Cardiovascular disease (%) | 23 (4.3) | 21 (5.2) | 2 (1.5) | 0.06 |
Malignancy (%) | 6 (1.1) | 4 (1.0) | 2 (1.5) | 0.65 |
Disease severity at admissiond | 35/436/47/23 | 20/319/44/21 | 15/117/3/2 | < 0.001 |
Illness onset until hospitalization | 4.0 (2.0–7.0) | 5.0(3.0–8.0) | 4.0(2.0–6.0) | 0.16 |
Hospital days (IQR) | 17 (14–21) | 17 (12–24) | 14 (11–20) | 0.03 |
Day to recovery (IQR) | 21 (16–28) | 23(17–28) | 18(14–25) | 0.003 |
Clinical Variables | | | | |
Therapy | | | | |
Antiviral therapy (%)e | 541 (100) | 403(100) | 138 (100) | 1 |
Corticosteroids (%) | 127 (23.5) | 107 (26.5) | 20 (14.6) | 0.005 |
Antibiotics | 244 (45.1) | 194 (48.0) | 50 (36.5) | 0.02 |
Secondary bacterial infection (%) | 36(6.7) | 35 (8.7) | 1(0.7) | < 0.001 |
Support | | | | |
NIV (%) | 31 (5.7) | 30 (7.4) | 1 (0.7) | 0.004 |
IMV (%) | 15 (2.8) | 15 (3.7) | 0 (0.0) | 0.02 |
ECMO (%) | 8 (1.5) | 8 (2.0) | 0 (0.0) | 0.10 |
CRRT(%) | 8 (1.5) | 8 (2.0) | 0 (0.0) | 0.14 |
Outcomes | | | | |
ICU admission (%) | 42 (7.8) | 39 (9.7) | 3 (2.2) | 0.005 |
ARDS (%) | 49 (9.1) | 46 (11.4) | 3 (2.2) | 0.001 |
In-hospital mortality (%) | 4 (0.4%) | 4(0.5) | 0(0.0) | 0.24 |
Laboratory findings |
White blood cell count (× 109/L) | 4.6(3.6–6.1) | 4.7(3.6–6.2) | 4.6(3.7–5.8) | 0.53 |
Neutrophil count (× 109/L) | 2.9(2.2–4.1) | 3.0(2.1–4.2) | 2.9(2.3–3.8) | 0.78 |
Lymphocyte count (× 109/L) | 1.1(0.8–1.6) | 1.1(0.8–1.6) | 1.2(0.9–1.6) | 0.96 |
Hemoglobin (g/L) | 133(121–145) | 132(121–145) | 134(123–144) | 0.68 |
Platelet count (× 109/L) | 190(146–247) | 188(146–246) | 194(147–248) | 0.77 |
D-dimer (mg/L) | 0.3(0.2–0.6) | 0.4(0.2–0.6) | 0.3(0.15–0.53) | 0.11 |
Albumin (g/L) | 40.2(36.2–43.7) | 39.8(35.6–43.4) | 40.7(37.7–44.4) | 0.74 |
Globulin (g/L) | 25.9(23.2–28.6) | 26.2(22.9–29.0) | 25.7(23.3–28.1) | 0.27 |
Creatine kinase (U/L) | 68.7(46.4-109.1) | 69.5(46.8-109.3) | 65.8(45.0-109.1) | 0.34 |
Prothrombin time (s) | 12.2(11.1–12.9) | 12.2(11.1–12.9) | 12.1(11.1–12.8) | 0.77 |
Alanine Aminotransferase (IU/L) | 21.0(14.9–30.6) | 21.0(14.9–31.4) | 21.0(14.7–29.6) | 0.32 |
Aspartate aminotransferase (IU/L) | 24.0(19.2–31.4) | 24.5(19.6–31.3) | 23.4(19.0-32.2) | 0.41 |
Total bilirubin (umol/L) | 12.0(7.7–18.5) | 12.0(7.6–17.4) | 12.0(8.8–21.1) | 0.13 |
Creatinine (umol/L) | 62.7(50.6–76.1) | 63.0(50.6–77.0) | 59.5(49.4–73.0) | 0.16 |
Blood urea nitrogen (mmol/L) | 4.1(3.2–5.1) | 4.1(3.2–5.4) | 3.3.3–4.6) | 0.29 |
Frequencies of initial symptoms and signs of patients with COVID-19 infection
404 of the 541 (74.5%) subjects had initial symptom that were respiratory, while 137 of the 541 (25.5%) subjects had extra-respiratory symptoms. The most common respiratory symptom was dry cough (68.0%), followed by sputum production (30.5%) and dyspnea (16.5%), while the most common extra-respiratory symptom was fever (74.3%), and followed by fatigue (33.1%) and myalgia (12.9%). (Table 2).
Table 2
Frequencies of initial symptoms and signs of patients with COVID-19 infection
Variable | All | Respiratorya | Extra-respiratoryb | pc |
Respiratory only (%) | 103 (19.0) | 103 (25.5) | 0 (0.0) | < 0.001 |
Extra-respiratory only (%) | 137 (25.3) | 0(0.0) | 137(100) | < 0.001 |
Combined (%) | 301 (55.6) | 301 (74.5) | 0(0.0) | < 0.001 |
Initial symptom (respiratory)e | | | | |
Dry cough (%) | 368 (68.0) | 368(91.1) | 0 (0.0) | < 0.001 |
Sputum production (%) | 165 (30.5) | 165(40.8) | 0 (0.0) | < 0.001 |
Dyspnea (%) | 89 (16.5) | 89(22.0) | 0 (0.0) | < 0.001 |
Runny nose (%) | 3 (0.6) | 3(0.7) | 0 (0.0) | 0.31 |
Sore throat (%) | 38 (7.0) | 38 (9.4) | 0 (0.0) | < 0.001 |
Hemoptysis (%) | 26 (4.8) | 26 (6.4) | 0 (0.0) | 0.002 |
Chest tightness (%) | 26 (4.8) | 26 (6.4) | 0 (0.0) | 0.002 |
Nasal congestion (%) | 15 (2.8) | 15 (3.7) | 0 (0.0) | 0.02 |
Initial symptom (extra-respiratory) f | | | | |
Fever (%) | 402 (74.3) | 288(71.3) | 114(83.2) | 0.006 |
Fatigue (%) | 179 (33.1) | 128 (31.7) | 51(37.2) | 0.25 |
Myalgia (%) | 70 (12.9) | 54 (13.4) | 16(11.7) | 0.61 |
Diarrhea (%) | 49 (9.1) | 31(7.7) | 18(13.1) | 0.05 |
Headache (%) | 42 (7.8) | 26 (6.4) | 16 (11.7) | 0.05 |
Palpitation (%) | 3 (0.6) | 3(0.7) | 0 (0.0) | 0.31 |
Nausea (%) | 32 (5.9) | 25 (6.2) | 7 (5.1) | 0.64 |
a Includes COVID-19 subjects with initial symptoms respiratory, b includes COVID-19 subjects with initial symptoms extra-respiratory |
Differences of symptoms between patients developed ARDS and no- ARDS.
Compared with patients who didn’t develop to ARDS, patients who developed ARDS had significantly higher percentage of dyspnea (63.3% vs 11.8%, p < 0.001), fever (93.9% vs 72.4%, p = 0.001) and fatigue (51% vs 31.3%, p = 0.005) (Table 3).
Table 3
Differences of symptoms between patients developed ARDS and no- ARDS.
Variable | ARDS(N = 49) | No-ARDS(N = 492) | p |
Initial symptom (respiratory) | | | |
Dry cough (%) | 38(7.8) | 330(67.1) | 0.13 |
Sputum production (%) | 18(36.7) | 147(29.9) | 0.32 |
Dyspnea (%) | 31(63.3) | 58(11.8) | < 0.001 |
Runny nose (%) | 0(0) | 3 (0.6) | 0.58 |
Sore throat (%) | 2 (4.1) | 36 (7.3) | 0.40 |
Hemoptysis (%) | 5 (10.2) | 21 (4.3) | 0.06 |
Chest tightness (%) | 5 (10.2) | 21 (4.3) | 0.06 |
Nasal congestion (%) | 2 (4.1) | 13 (2.6) | 0.56 |
Initial symptom (extra-respiratory) | | | |
Fever (%) | 46(93.9) | 356(72.4) | 0.001 |
Fatigue (%) | 25(51.0) | 154(31.3) | 0.005 |
Myalgia (%) | 4(8.2) | 66(13.4) | 0.30 |
Diarrhea (%) | 6(12.2) | 43(8.7) | 0.42 |
Headache (%) | 6 (12.2) | 36 (7.3) | 0.22 |
Palpitation (%) | 0(0) | 3 (0.6) | 0.58 |
Nausea (%) | 5 (10.2) | 27 (5.5) | 0.18 |
Risk factors for ARDS incidence.
49 of 541 subjects in the cohort developed ARDS, most coming from the respiratory COVID-19 population. Univariate analysis showed several factors are risk factors for developing ARDS, including age (odds ratio (OR) = 1.05, 95% confidence interval (CI) = 1.03–1.07, p < 0.001), comorbidities (OR = 5.13, 95% CI = 2.74–9.61, p < 0.001), secondary bacterial infection (OR = 50.2, 95% CI = 21.7–116.0, p < 0.001), dry cough(OR = 1.7, 95% CI = 0.85–3.40, p = 0.01), dyspnea (OR = 12.9, 95% CI = 6.78–24.5, p = 0.01), fever ( OR = 5.86, 95% CI = 1.79–19.2, p = 0.003) and fatigue ( OR = 2.27, 95% CI = 1.26–4.11, p = 0.007). The multivariate model showed that age (OR = 1.04, p = 0.01) dyspnea (OR = 4.91, p < 0.001) and secondary bacterial infection (OR = 19.8, p < 0.001) were independently associated with development of ARDS (Table 4).
Table 4
Univariate and stepwise multivariate analysis of risk factors for ARDS development
Variable | Univariate | Multivariate |
| OR | 95% CI | p | OR | 95% CI | p |
Age (years) | 1.05 | 1.03–1.07 | < 0.001 | 1.04 | 1.01–1.06 | 0.01 |
Comorbidities | 5.13 | 2.74–9.61 | < 0.001 | 1.18 | 0.50–2.78 | 0.71 |
Bacterial infection | 50.2 | 21.7–116.0 | < 0.001 | 19.8 | 7.49–52.4 | < 0.001 |
Dry cough | 1.70 | 0.85–3.40 | 0.01 | 0.96 | 0.40–2.33 | 0.93 |
Sputum production | 1.36 | 0.74–2.51 | 0.32 | - | - | - |
Dyspnea | 12.9 | 6.78–24.5 | < 0.001 | 4.91 | 2.21–10.9 | < 0.001 |
Chest tightness | 2.55 | 0.92–7.09 | 0.07 | - | - | - |
Hemoptysis | 2.55 | 0.92–7.09 | 0.07 | - | - | - |
Fever | 5.86 | 1.79–19.2 | 0.003 | 3.76 | 1.01-14.0 | 0.05 |
Headache | 1.78 | 0.71–4.43 | 0.23 | - | - | - |
Fatigue | 2.27 | 1.26–4.11 | 0.007 | 1.67 | 0.77–3.63 | 0.20 |
Myalgia | 0.57 | 0.20–1.65 | 0.30 | - | - | - |
Diarrhea | 1.46 | 0.59–3.62 | 0.42 | - | - | - |
ARDS = acute respiratory distress syndrome, OR = odds ratio, CI = confidence interval. |