Participants
From 1st May to 31st August 2021, 421 confirmed COVID-19 patients were identified, of these, 170 were excluded due to prior treatment from other hospitals (101), and referral (70) (Fig. 1). Of the 250 patients who were eligible for the study, 122 patients were received respiratory support whilst 128 patients did not. Among these 250 patients, 50 (20%), 95 (38%), and 105 (42%) were admitted to ICU, intermediate ICU and cohort infectious disease ward, respectively.
Descriptive data
The patients who required respiratory support were significant older (57.1 vs 46.6, p < 0.001), had chronic kidney disease (83.3 vs 16.7, p 0.008), higher respiratory rate (23.0 vs 20.6, p < 0.001), less oxygen saturation (92.8% vs 97.1%, p < 0.001) and higher SOFA score on admission (3.4 vs 0.4, p < 0.001) compare with those without respiratory support. Severe and critical COVID-19 infection were received more respiratory support. Clinical characteristics and demographic data are summarized in Table 1.
Table 1
Patient baseline characteristics. BMI; body mass index, SOFA; sequential organ failure assessment.
Characteristic | Respiratory support (N = 122) n (%) | Non-respiratory support (N = 128) n (%) | p-value |
Male | 76 (62.3) | 70 (54.7) | 0.171 |
Age, mean (± SD) (years) | 57.1 (± 16.8) | 46.6 (± 16.5) | < 0.001 |
BMI ≥ 25 (kg/m2) | 87 (71.3) | 88 (68.6) | 0.721 |
Comorbidity | |
Hypertension | 52 (46.7) | 39 (30.5) | 0.036 |
Diabetes mellitus | 31 (25.4) | 22 (17.2) | 0.178 |
Obesity (BMI ≥ 30) | 37 (30.3) | 31 (24.2) | 0.380 |
Lung disease | 7 (5.7) | 3 (2.3) | 0.164 |
Chronic kidney diseases | 10 (8.2) | 2 (1.6) | 0.008 |
Dyslipidemia | 24 (19.7) | 28 (21.9) | 0.716 |
Vital signs: | |
Body temperature, mean (± SD) (ºC) | 37.6 (0.9) | 37.4 (0.9) | 0.098 |
Respiratory rate, mean (± SD) (/min) | 23.0 (4.5) | 20.6 (2.9) | < 0.001 |
Mean arterial pressure, mean (± SD) (mmHg) | 98.5 (13.1) | 96.8 (13.5) | 0.324 |
Pulse rate, mean (± SD) (beat per min) | 95.1 (15.5) | 92.0 (13.9) | 0.099 |
Oxygen saturation, mean (± SD) (%) | 92.8 (7.6) | 97.1 (2.2) | < 0.001 |
SOFA score at admission, mean (± SD) | 3.4 (2.6) | 0.6 (1.2) | < 0.001 |
Classification of COVID-19 | | | < 0.001 |
Mild | 4 (3.2) | 127 (99.2) | |
Severe | 76 (62.3) | 1 (0.8) | |
Critical | 42 (34.4) | 0 (0) | |
The MDW and CRP values were significantly higher in the respiratory support group: 27.2 ± 4.6 vs 23.6 ± 4.1, p < 0.001) and (78.2 vs 25.5, p < 0.001), respectively. Among all CBC parameters, neutrophil count, lymphocyte count, platelets, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were significant different between the two groups as were the mean ferritin and procalcitonin levels. By contrast, serum lactate, D-dimer, and interleukin-6 were not different between the two groups (p = 0.062 and p = 0.676, respectively). Additional laboratory parameters are presented in Table 2.
Table 2
Laboratory parameters at admission. IQR; interquartile range, CRP; C-reactive protein, LDH; lactate dehydrogenase, NT-proBNP; N-terminal pro b-type natriuretic peptide.
Laboratory | Respiratory support (N = 122) | Non- RS support (N = 128) | p-value |
Mean | ±SD | Mean | ±SD | |
Complete blood count and coagulogram | | | | | |
Monocyte distributive width day 1 (Unit) | 27.2 | 4.6 | 23.6 | 4.1 | < 0.001 |
Hemoglobin (g/dl) | 13.8 | 1.8 | 13.4 | 1.8 | 0.110 |
White blood cell count (median; IQR) (103/uL) | 6.5 | 4.9, 8.5 | 6 | 4.7, 7.6 | 0.215 |
Neutrophil count (median; IQR) (cells/mm3) | 4617 | 3120, 6873 | 3469 | 2562, 4900 | < 0.001 |
Lymphocyte count (median; IQR) (cells/mm3) | 999 | 666,1470 | 1540 | 1196,1890 | < 0.001 |
Platelets (103 /uL) | 202.1 | 82.8 | 237.9 | 88.8 | < 0.001 |
Neutrophil-to-lymphocyte ratio (median; IQR) | 4.42 | 2.54, 7.94 | 2.22 | 1.42, 3.58 | < 0.001 |
Platelets-to-lymphocyte ratio (median; IQR) | 184.6 | 113.8, 291.9 | 139.7 | 103.2, 195.9 | 0.001 |
Blood chemistry | | | | | |
Creatinine (median; IQR) (mg/dL) | 1.01 | 0.7, 1.3 | 0.85 | 0.69, 1.04 | 0.002 |
Lactate (median; IQR) (mmol/L) (n = 91) | 2.9 | 1.8, 3.8 | 2.3 | 1.64, 2.6 | 0.062 |
CRP (median; IQR) (mg/dL) (n = 180) | 78.21 | 42.3, 87.52 | 25.5 | 8.42, 68.35 | < 0.001 |
Interleukein-6 (median; IQR) (pg/ml) (n = 24) | 19.8 | 13.4, 45.82 | 27.48 | 4.77, 50.19 | 0.676 |
D-dimer (median; IQR) (ng/ml) (n = 96) | 666 | 395, 1980 | 672 | 365, 1101 | 0.511 |
Ferritin (median; IQR) (ng/ml) (n = 9) | 881 | 430, 1124 | 27.5 | 12, 43 | 0.040 |
Procalcitonin (median; IQR) (ug/L) (n = 125) | 0.17 | 0.09, 0.37 | 0.11 | 0.07, 0.22 | 0.019 |
Cardiac troponin (median; IQR) (ng/ml) (n = 24) | 0.04 | 0.009, 0.165 | 0.01 | 0.004, 0.095 | 0.260 |
NT-proBNP (median; IQR) (pg/mL) (n = 16) | 1724.5 | 572, 3766 | 20 | 39, 201 | 0.080 |
LDH (median; IQR) (U/L) (n = 60) | 420 | 293, 554 | 353 | 233, 437 | 0.022 |
Outcome data
122/250 (48.8%) patients received respiratory support that consisted mostly high-flow nasal cannula, followed by invasive mechanical ventilation, non-invasive ventilation, and oxygen mask with a bag: 113 (45.2%), 41 (16.4%), 20 (8%), and 17(6.8%), respectively, whilst 132 received conventional oxygen cannula. Vasopressor and renal replacement therapy were also significantly higher in the respiratory support group: 25/122 (20.5%) vs. 1/128 (0.7%, p < 0.001) and 9/122 (7.4%) vs 1/128 (0.7%), p = 0.008). COVID-19 patients who required respiratory support had a lower rate of survival (74.8% vs 100%, p < 0.001). A longer mean length of hospital stay was also found in the respiratory support group 17.5 vs 7.8 days (p < 0.001). In addition, the mortality rate at 7,14, and 28 days were significantly higher in the respiratory support group. The longer length of stay was also found in patients who require respiratory support (17.5 days vs 7.8 days, p < 0.001). The treatments and results are shown in Table 3.
Table 3
| N (%) |
Received Respiratory support (N = 122) | |
Oxygen mask with bag | 20 (16.4) |
Non-invasive ventilation | 17 (13.9) |
High-flow nasal cannula | 113 (92.6) |
Mechanical ventilation | 41 (33.6) |
Treatment |
| Respiratory support (N = 122) n (%) | Non-respiratory support (N = 128) n (%) | p-value |
Vasopressor requirement | 25 (20.5) | 1 (0.7) | < 0.001 |
Renal replacement therapy | 9 (7.4) | 1 (0.7) | 0.008 |
Result | | |
7-day mortality | 5 (4.1) | 0 (0) | 0.025 |
14-day mortality | 20 (16.4) | 0 (0) | < 0.001 |
28-day mortality | 26 (21.3) | 0 (0) | < 0.001 |
Length of stay mean (± SD) (day) | 17.5 (10.1) | 7.8 (4.9) | < 0.001 |
Survival to discharge | 90 (74.8) | 128 (100) | < 0.001 |
Compared to the non-support group, the respiratory support group had significantly higher complication rates (Table 4). Almost all patients in respiratory support group developed respiratory failure [118 (96%)], ARDS [40 (32.7%)] and required invasive mechanical ventilation [41 (34%)]. Hospital acquired pneumonia, sepsis, septic shock, acute kidney injury and cardiac arrest were more frequent in the respiratory support group (Table 4).
Table 4
Complication | Respiratory support (N = 122) n (%) | Non-respiratory support (N = 128) n (%) | p-value |
Hypotension | 32 (26.2) | 1 (0.7) | < 0.001 |
Arrhythmia | 22 (18) | 3 (2.3) | < 0.001 |
Cardiac arrest | 32 (26.2) | 0 (0) | < 0.001 |
Respiratory failure | 118 (96.7) | 1 (0.7) | < 0.001 |
Acute respiratory distress syndrome (ARDS) | 40 (32.8) | 1 (0.7) | < 0.001 |
Hospital-acquired pneumonia | 54 (44.3) | 4 (3.1) | < 0.001 |
Sepsis | 49 (40.2) | 1 (0.7) | < 0.001 |
Septic shock | 28 (23) | 0 (0) | < 0.001 |
Acute kidney injury | 41 (33.6) | 7 (5.5) | < 0.001 |
Gastrointestinal bleeding | 10 (8.2) | 1 (0.7) | 0.004 |
Received blood transfusion | 11 (9.0) | 0 (0) | < 0.001 |
Pulmonary embolism | 4 (3.3) | 0 (0) | 0.053 |
Transaminitis | 24 (19.7) | 14 (10.9) | 0.048 |
We identified a MDW value of ≥ 25 as best cutoff for predicting the need for respiratory support in COVID-19 patients. The AuROC was 0.70 [95% confidence interval (CI); 0.64–0.76, sensitivity 71.9, specificity 68.2, positive likelihood ratio 2.26] (Table 5). By logistic regression analyses, the independent factors associated with need respiratory support were a MDW ≥ 25, increasing age, increasing respiratory rate, and a lower oxygen saturation (Table 6).
Table 5
Cut point of MDW in COVID-19 patients with respiratory support requirement. 95% CI; 95% confidence interval, LR+; likelihood ratio of positive, LR-; likelihood ratio of negative.
Cut point | AuROC | Sensitivity, % (95% CI) | Specificity, % (95% CI) | LR+ | LR- |
(≥ 20) | 0.572 | 96.7 (91.8–99.1) | 17.8 (11.7–25.5) | 1.18 | 0.19 |
(≥ 21) | 0.618 | 95.9 (90.6–98.6) | 27.9 (20.4–36.5) | 1.33 | 0.15 |
(≥ 22) | 0.645 | 94.2 (88.4–97.6) | 34.9 (26.7–43.8) | 1.45 | 0.17 |
(≥ 23) | 0.674 | 86.8 (79.4–92.2) | 48.1 (39.2–57.0) | 1.67 | 0.28 |
(≥ 24) | 0.671 | 76.9 (68.3–84.0) | 57.4 (48.4–66.0) | 1.80 | 0.40 |
(≥ 25) | 0.700 | 71.9 (63.0-79.7) | 68.2 (59.4–76.1) | 2.26 | 0.41 |
(≥ 26) | 0.657 | 56.2 (46.9–65.2) | 75.2 (66.8–82.4) | 2.27 | 0.58 |
(≥ 27) | 0.630 | 46.3 (37.2–55.6) | 79.8 (71.9–86.4) | 2.30 | 0.67 |
(≥ 28) | 0.582 | 28.9 (21.0-37.9) | 87.6 (80.6–92.7) | 2.33 | 0.81 |
(≥ 29) | 0.581 | 24.0 (16.7–32.6) | 92.2 (86.2–96.2) | 3.09 | 0.82 |
(≥ 30) | 0.564 | 19.0 (12.4–27.1) | 93.8 (88.1–97.3) | 3.07 | 0.86 |
Table 6
Logistic regression of monocyte distribution width (MDW) ≥ 25 for respiratory support.
Respiratory support | Odd ratio | 95% CI | p-value |
MDW ≥ 25 | 3.42 | 1.85–6.33 | < 0.001 |
Age | 1.03 | 1.01–1.05 | < 0.001 |
Respiratory rate | 1.11 | 1.00–1.21 | 0.041 |
Oxygen saturation (SpO2) | 0.81 | 0.72–0.91 | < 0.001 |
*adjusted for age, respiratory rate, and oxygen saturation. |
The AuROC of clinical features (age, RR, and oxygen saturation), CRP, MDW ≥ 25, and MDW ≥ 25 plus clinical features for predicting respiratory support requirement are shown in Table 7; clinical features plus a MDW ≥ 25 gave the best result and this was significantly better (p < 0.001) than clinical features alone.
Table 7
The area under receiver operative curve (AUROC) of clinical features, CRP, MDW ≥ 25, and MDW ≥ 25 with clinical features as predictors of respiratory support and 28-day mortality in COVID-19 patients. RR; respiratory rate, CRP; c-reactive protein, MDW; monocyte distribution width.
Predictor | AuROC | 95%CI | p-value |
Respiratory support | | | |
Clinical features only (age + RR + SpO2) | 0.82 | 0.76–0.87 | Ref |
CRP | 0.72 | 0.65–0.80 | < 0.001 |
MDW ≥ 25 | 0.70 | 0.65–0.76 | < 0.001 |
MDW ≥ 25 + clinical features* | 0.84 | 0.79–0.88 | < 0.001 |
28-day mortality | | | |
Clinical features only (age + RR + SpO2) | 0.87 | 0.80–0.93 | Ref |
CRP | 0.73 | 0.63–0.83 | 0.144 |
MDW ≥ 25 | 0.64 | 0.55–0.73 | < 0.001 |
MDW ≥ 25 + clinical features* | 0.87 | 0.79–0.94 | 1.000 |
*Reference with clinical features (age, respiratory rate, and oxygen saturation), |