Dear Editor,
We read the recent published paper by Chen and colleagues in journal of Infection with great interest, which described the clinical progression of patients with COVID-19 in Shanghai, China.1 Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) emerged in Wuhan, China and spread globally to become a public health emergency of international concern.2 Patients with COVID-19 tend to progress after onset of symptoms within 7 days1 and severe type may rapidly progress to acute respiratory distress syndrome (ARDS) or end-organ failure.3 , 4 Therefore, early and simple identification of patients who require intensive respiratory or vasopressor support (IRVS) would be of considerable value during the outbreak of the COVID-19 crisis. Thus far, there are no effective severity assessment tools for patients with COVID-19.
Here, we performed a retrospective single-center study to compare the performance of simple score systems such as quick sepsis-related organ failure assessment (qSOFA), the CURB-65 score adopted by the British Thoracic Society, and its simpler versions (CRB and CRB-65) to predict the need for IRVS in patients with COVID-2019. Patients with confirmed COVID-19 and age ≥18 years hospitalized between February 7, 2020 and February 17, 2020 in Renmin Hospital of Wuhan University were screened in this study. Patients were excluded if they died within 48 h of admission, were pregnant, or had a Do Not Resuscitate (DNR) order. Baseline demographics, co-morbidities, clinical symptoms or signs, vital signs, laboratory results on admission, and outcomes were collected. The CRB, CRB-65, CURB-65 and qSOFA scores were calculated on basis of demographic and clinical characteristics of each patient.
A total of 116 patients were eventually included for this study. The baseline characteristics are presented in Table 1 . The median age of this cohort was 63[IQR 51 to 72] and 47.4% patients were males. The most common symptom was fever (86.2%), followed by fatigue (85.3%) and cough (69.0%). On admission, the median scores of CRB, CRB-65, CURB-65, and qSOFA were 0[0,1], [0,1], 1[0,2] and 1[0,1], respectively. A total of 25 (21.6%) patients needed IRVS during the period of hospital stay. Patients with IRVS had higher CRB (1[0,2] vs. 0[0,0], P<0.001), CRB-65 (2[1,3] vs. 1[0,1], P<0.001), CURB-65 (3[2,3] vs. 1[0,1], P<0.001), and qSOFA scores (1[1,2] vs. 1[0,1], P=0.001) than non-IRVS patients. The hospital mortality rate in this cohort was 7.8%. The median length of hospital stay was 29 [18,36] days.
Table 1.
Clinical characteristics of COVID-19 patients.
| Entire cohort | No need for IRVS | Need for IRVS | P value | |
|---|---|---|---|---|
| Number of patients | 116 | 91 | 25 | |
| Age (years) | 63[51, 72] | 61[48,69] | 72[63,81] | <0.001 |
| Gender (male), n (%) | 55(47.4) | 42(46.2) | 13(52) | 0.66 |
| Smoking history, n (%) | 10(8.6) | 9(9.9) | 1(4) | 0.69 |
| Comorbidities | ||||
| Hypertension, n (%) | 38(32.8) | 25(27.5) | 13(52) | 0.03 |
| Diabetes mellitus, n (%) | 20(17.2) | 15(16.5) | 5(20) | 0.77 |
| CAD, n (%) | 12(10.3) | 9(9.9) | 3(12) | 0.72 |
| COPD, n (%) | 2(1.7) | 0(0) | 2(8) | 0.05 |
| Cerebrovascular disease, n (%) | 2(1.7) | 1(1.1) | 1(4) | 0.39 |
| Chronic renal disease, n (%) | 4(3.4) | 3(3.3) | 1(4) | 1.00 |
| Signs and symptoms | ||||
| Fever, n (%) | 100(86.2) | 76(83.6) | 24(96) | 0.19 |
| Cough, n (%) | 80(69.0) | 62(68.1) | 18(72) | 0.81 |
| Sputum production, n (%) | 15(12.9) | 11(12.1) | 4(16) | 0.74 |
| Fatigue, n (%) | 99(85.3) | 76(83.5) | 23(92) | 0.36 |
| Headache, n (%) | 6(5.2) | 6(6.6) | 0(0) | 0.34 |
| Dyspnea, n (%) | 66(56.9) | 44(48.4) | 22(88) | <0.001 |
| Nausea or vomiting, n (%) | 25(21.6) | 18(19.8) | 7(28) | 0.41 |
| Diarrhea, n (%) | 23(19.8) | 18(19.8) | 5(20) | 1.00 |
| Anorexia, n (%) | 8(6.9) | 2(2.2) | 6(24) | 0.001 |
| Myalgia or arthralgia, n (%) | 10(8.6) | 8(8.8) | 2(8) | 1.00 |
| Onset of symptom to hospital admission | 12[9,16] | 12[9,17] | 10[7,16] | 0.08 |
| Vital signs at hospital admission | ||||
| Altered mental status, n (%) | 6(5.2) | 0(0) | 6(24) | <0.001 |
| Heart rate, beats/minute | 90[79, 102] | 86[78,100] | 96[86,107] | 0.02 |
| Respiratory rate, breaths/minute | 23[20,29] | 22[20,25] | 32[22,35] | <0.001 |
| Systolic blood pressure, mm Hg | 132[122,145] | 131[122, 144] | 137[121,152] | 0.38 |
| Diastolic blood pressure, mm Hg | 78[68,84] | 79[69,84] | 74[66,91] | 0.98 |
| Severity of illness scores at hospital admission | ||||
| CRB | 0[0,1] | 0[0,0] | 1[0,2] | <0.001 |
| CRB-65 | 1[0,1] | 1[0,1] | 2[1,3] | <0.001 |
| CURB-65 | 1[0,2] | 1[0,1] | 3[2,3] | <0.001 |
| qSOFA | 1[0,1] | 1[0,1] | 1[1,2] | 0.001 |
| Blood urea nitrogen, mmol/L | 4.85[3.91, 6.30] | 4.67[3.69,5.84] | 7.35[4.85,9.28] | <0.001 |
| Respiratory support | ||||
| High flow nasal cannula, n (%) | 24(20.7) | 0(0) | 24(96) | <0.001 |
| Non-invasive mechanical ventilation, n (%) | 5(4.3) | 0(0) | 5(20) | <0.001 |
| Invasive mechanical ventilation, n (%) | 8(6.9) | 0(0) | 8(32) | <0.001 |
| Renal replacement therapy, n (%) | 3(2.6) | 2(2.2) | 1(4) | 0.52 |
| Extracorporeal membrane oxygenation, n (%) | 1(0.9) | 0(0) | 1(4) | 0.22 |
| Need for vasopressor support, n (%) | 9(7.8) | 0(0) | 9(36) | <0.001 |
| Need for IRVS, n (%) | 25(21.6) | 0(0) | 25(100) | <0.001 |
| Hospital mortality, n (%) | 9(7.8) | 0(0) | 9(36) | <0.001 |
| Hospital length of stay, days | 29[18,36] | 28[18,33] | 38[8,49] | 0.18 |
Continuous variables are shown as the mean ± SD or median [IQR], as appropriate. Categorical variables are shown as number (%).
COVID-19, coronavirus disease 2019; BUN, blood urea nitrogen; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; CRB, confusion, respiratory rate, and blood pressure; CRB-65, confusion, respiratory rate, blood pressure and age ≥65 years; CURB-65, confusion, urea nitrogen, respiratory rate, blood pressure and age ≥65 years; SOFA, Sepsis-related Organ Failure Assessment; qSOFA, quick Sepsis-related Organ Failure Assessment; IRVS, intensive respiratory or vasopressor support.
ROC curve analyses were performed to evaluate the performance of four simple score systems to predict the need for IRVS. The AUC, optimal cut-off value, sensitivity, specificity, and positive and negative predictive values of each score system were shown in Table 2 . The optimal cut-off score of CRB-65 for prediction of IRVS was 2, which provided sensitivity of 64% and specificity of 93.4%. The AUC values of the CRB-65 score in predicting the need for IRVS were much higher than those for the qSOFA score (0.81 ± 0.05 vs. 0.70 ± 0.06, P=0.02). The CRB-65 had higher AUC values than CRB score for IRVS prediction, however, the difference was not statistically significant (0.81 ± 0.05 vs. 0.77 ± 0.05, P=0.22). The AUC values were comparable between CRB-65 and CURB-65 for IRVS prediction (0.81 ± 0.05 vs. 0.85 ± 0.05, P=0.08).
Table 2.
Performance of variables in predicting clinical outcomes.
| Outcomes | Predictors | AU ROC | 95% CI | P | Cut-off | Sensitivity (%) | Specificity (%) | PPV | NPV | LR+ | LR- |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Need for IRVS | CRB | 0.77 ± 0.05 | 0.69-0.85 | <0.001 | 1 | 72 | 79.1 | 48.6 | 91.1 | 3.45 | 0.35 |
| CRB | 2 | 28 | 96.7 | 70 | 83 | 8.49 | 0.74 | ||||
| CRB-65 | 0.81 ± 0.05 | 0.73-0.88 | <0.001 | 1 | 88 | 45.1 | 30.6 | 93.2 | 1.6 | 0.27 | |
| CRB-65 | 2 | 64 | 93.4 | 72.7 | 90.4 | 9.71 | 0.39 | ||||
| CRB-65 | 3 | 24 | 97.8 | 75 | 82.4 | 10.92 | 0.78 | ||||
| CURB-65 | 0.85 ± 0.05 | 0.77-0.91 | <0.001 | 1 | 88 | 42.9 | 29.7 | 92.9 | 1.54 | 0.28 | |
| CURB-65 | 2 | 80 | 87.9 | 64.5 | 94.1 | 6.62 | 0.23 | ||||
| CURB-65 | 3 | 52 | 96.7 | 81.2 | 88 | 15.77 | 0.5 | ||||
| CURB-65 | 4 | 12 | 98.9 | 75 | 80.4 | 10.92 | 0.89 | ||||
| qSOFA | 0.70 ± 0.06 | 0.60-0.78 | <0.001 | 1 | 80 | 47.3 | 29.4 | 89.6 | 1.52 | 0.42 | |
| qSOFA | 2 | 24 | 98.9 | 85.7 | 82.6 | 21.84 | 0.77 |
Abbreviations: AUROC, area under the receiver operating characteristic curve; CI, confidence interval; LR, likelihood ratio; PPV, positive predictive values; NPV, negative predictive value; CRB, confusion, respiratory rate, and blood pressure; CRB-65, confusion, respiratory rate, blood pressure and age ≥65 years; CURB-65, confusion, urea nitrogen, respiratory rate, blood pressure and age ≥65 years; qSOFA, quick Sepsis-related Organ Failure Assessment; IRVS, intensive respiratory or vasopressor support. Bold: the optimal cut-off values according to Youden index.
AUC comparisons
CRB-65 vs. qSOFA, P=0.02; CRB-65 vs. CRB, P=0.22; CRB-65 vs. CURB-65, P=0.08; CRB vs. qSOFA, P=0.09.
To the best of our knowledge, the present study is the first to investigate the predictive performance of simple score systems in patients with COVID-19. In this study, the CRB-65 score could better identify patients with COVID-19 at risk for IRVS than the qSOFA score. The CRB score contains the same three clinical parameters used in qSOFA score (confusion, respiratory rate, and blood pressure). However, the thresholds for tachypnea and hypotension in CRB were stricter than the qSOFA score (respiratory rate ≥ 30/min in CRB vs. ≥ 22/min in qSOFA; blood pressure: systolic blood pressure ≤ 100 mmHg in qSOFA vs. < 90 mmHgsys or ≤ 60 mmHgdias in CRB). It seems that qSOFA is more accurate than the CRB score for predicting IRVS. However, in this study, the AUC values of CRB and qSOFA scores were comparable without statistically significant differences. After including the parameter of age, the CRB-65 score performed better than the qSOFA score in predicting requirement of IRVS. As age ≥ 65 years was included in the CRB-65 score, it provided additional predictive performance compared with the CRB score. This result was supported by previous reports, which showed that age was an independent risk factor for mortality in patients with COVID-19.5 , 6
The CRB-65 score has been reported to have a similar predictive performance to that of the CURB-65 and PSI scores in predicting the severity of CAP.7, 8, 9 In our study, the CRB-65 and CURB-65 scores also had a similar prognostic value in predicting the receipt of IRVS. The CRB-65 score makes it easy to assess the severity of COVID-19 without the limit of laboratory data for blood urea nitrogen especially in the pandemic of COVID-19, thereby allowing earlier triage decisions.
In conclusion, the CRB-65 score could better identify patients with COVID-19 at risk for IRVS than the qSOFA score. The CRB-65 may be a useful score tool for COVID-19 because of its simplicity in application especially in emergent and complicated conditions.
Declaration of Competing Interest
The authors declare that they have no competing interests.
Acknowledgments
Funding
This article was supported by grants from the Research Funds of Zhongshan Hospital (2019ZSQN13 and XYYX201922) and the Research Fund of Shanghai Municipal Health Commission (2019ZB0105).
Acknowledgements
The authors appreciate the great sacrifice and contribution of people from Wuhan, Hubei province, China.
References
- 1.Chen J., Qi T., Liu L., Ling Y., Qian Z., Li T. Clinical progression of patients with COVID-19 in Shanghai, China. J Infect. 2020;80:e1–e6. doi: 10.1016/j.jinf.2020.03.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Tu H., Tu S., Gao S., Shao A., Sheng J. The epidemiological and clinical features of COVID-19 and lessons from this global infectious public health event. J Infect. 2020 doi: 10.1016/j.jinf.2020.04.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507–513. doi: 10.1016/S0140-6736(20)30211-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 doi: 10.1016/S0140-6736(20)30566-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Fu L., Wang B., Yuan T., Chen X., Ao Y., Fitzpatrick T. Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: A systematic review and meta-analysis. J Infect. 2020 doi: 10.1016/j.jinf.2020.03.041. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Liu K., Chen Y., Lin R., Han K. Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients. J Infect. 2020 doi: 10.1016/j.jinf.2020.03.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Morris A., ACP Journal Club Review: CURB65, CRB65, and Pneumonia Severity Index similarly predict mortality in community-acquired pneumonia. Ann Intern Med. 2011;154:C4–13. doi: 10.7326/0003-4819-154-8-201104190-02013. [DOI] [PubMed] [Google Scholar]
- 8.Chalmers J.D., Singanayagam A., Akram A.R., Mandal P., Short P.M., Choudhury G. Severity assessment tools for predicting mortality in hospitalised patients with community-acquired pneumonia. Systematic review and meta-analysis. Thorax. 2010;65:878–883. doi: 10.1136/thx.2009.133280. [DOI] [PubMed] [Google Scholar]
- 9.Su Y., Ju M.J., Ma J.F., Tu G.W., He H.Y., Gu Z.Y. Lactate dehydrogenase as a prognostic marker of renal transplant recipients with severe community-acquired pneumonia: a 10-year retrospective study. Ann Transl Med. 2019;7:660. doi: 10.21037/atm.2019.10.75. [DOI] [PMC free article] [PubMed] [Google Scholar]