Applicability of the CURB-65 pneumonia severity score for outpatient treatment of COVID-19

Abstract

Dear editor, Tomlins and colleagues recently reported in this journal the clinical features of 95 sequential hospitalised patients with novel coronavirus 2019 disease (COVID-19) in the first UK cohort. 1 Interestingly, consistent with evidence supporting the use of CURB-65 as a predictor of mortality secondary to community acquired pneumonia (CAP), non-survivors had a significantly higher median CURB-65 score versus survivors (2.5 versus 1 respectively). The CURB-65 is a severity score for CAP, comprising 5 variables, attributing 1 point for each item: new onset confusion; urea >7 mmol/L; respiratory rate ≥30/minute, systolic blood pressure <90 mmHg and/or diastolic blood pressure ≤60 mmHg; and age ≥65 years. 2 It has been extensively validated to predict 30-day mortality in CAP, 3 and divides patients into 3 groups: score 0–1: low risk of 30–day mortality (0.7–3.2%); score 2: intermediate risk (13%) and score 3–5: high risk of 30–day mortality (17–57%). The Infectious Diseases Society of America / American Thoracic Society and the British Thoracic Society guidelines suggest that patients with CURB-65 scores of 0–1 are at low risk of death and thus may be managed as outpatients. 4 , 5 However, whether CURB-65 can be applicable to COVID-19 patients for the decision outpatient treatment is still unknown. Here, we describe a retrospective single-centre study assessing the performance of the CURB-65 to predict the risk of unfavourable outcome. Hospitalized patients aged 18 or over diagnosed with COVID-19, based on positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on nasal swabs, and/or typical abnormalities on chest computed tomography (CT) were included in the study. Patients were excluded if they were directly admitted to ICU. Their baseline demographics, co-morbidities, clinical symptoms, vital signs, and laboratory results on admission were retrospectively collected. CURB-65 scores were calculated retrospectively. A poor outcome was defined as the time until transfer to the intensive care unit (ICU) for non-invasive ventilation (NIV) and/or high flow nasal cannula (HFNC) and/or invasive mechanical ventilation and/or death, whichever occurred first, within the 14 days following admission. The association between the CURB-65 and the outcome was assessed by a univariable Cox proportional hazard regression model to calculate hazard ratios (HR) and their 95% confidence intervals (95%CI). The study was approved by the local institutional review board (IRB 00006477). A total of 279 patients hospitalized between March 15th and April 14th, 2020 were included in this study. Their baseline characteristics at admission are described in Table 1 . According to the CURB-65, 171 (61.3%) patients were considered at low risk (CURB-65 0–1), 66 (23.7%) at intermediate risk (CURB-65=2), and 42 (15.1%) had high risk of 30-day mortality (CURB-65 3–5). During the study period, 88 (31.5%) patients had poor outcome: 48 (17.2%) were admitted to ICU (28 had NIV and/or HFNC, 27 had mechanical ventilation, following NIV and/or HFNC for 7, and 11 patients died within the 14 days) and 40 (14.3%) patients died without being admitted to ICU, leading to 51 (18.3%) deaths within the 14 days following admission. Table 1 Baseline characteristics and outcomes of the study population according to the CURB 65 (N=279) Table 1 Overall (N=279) CURB-65 P 0–1 N=171 2 N=66 3–5 (N=42) Age, mean (SD) 64.8 (16.1) 57.3 (14.4) 75.6 (11.6) 78.2 (9.5) <0.001 Male sex 183 (65.6) 107 (62.6) 45 (68.2) 31 (73.8) 0.342 Diabetes 77 (27.6) 39 (22.8) 22 (33.3) 16 (38.1) 0.068 Hypertension 131 (47.0) 61 (35.7) 39 (59.1) 31 (73.8) <0.001 CURB-65 features  Confusion 23 (8.2) 0 (0) 8 (12.1) 15 (35.7) <0.001  Urea >7 mmol/L 103 (36.9) 10 (5.8) 52 (78.8) 41 (97.6) <0.001  Respiratory rate>30/min 59 (21.1) 25 (14.6) 9 (13.6) 25 (59.5) <0.001  Hypotension 22 (7.9) 3 (1.8) 6 (9.1) 13 (31.0) <0.001  Age >65 years 145 (52.0) 47 (27.5) 57 (86.4) 41 (97.6) <0.001 Other clinical features Time from symptom onset to admission, (days) 6.76 (4.80) 7.3 (5.0) 6.9 (4.5) 3.4 (3.4) 0.001  Respiratory rate (/minute) 26.2 (6.7) 25.2 (6.1) 25.1 (6.0) 31.5 (7.8) <0.001  Body temperature >38°C 110 (39.4) 71 (41.5) 23 (34.8) 16 (38.1) 0.630  Cough 190 (68.1) 129 (73.7) 39 (59.1) 22 (52.4) 0.003  Dyspnoea 198 (71.0) 126 (37.7) 39 (59.1) 33 (78.6) 0.043  Myalgia 58 (20.8) 43 (25.1) 8 (12.1) 7 (16.7) 0.067  Diarrhoea 55 (19.7) 41 (24.0) 9 (13.6) 5 (11.9) 0.077 Biological features  Lymphocytes count (G/L) 1.2 (1.0) 0.7 (2.5) 1.0 (0.6) 1.0 (0.7) 0.038  C-reactive protein (mg/L) 126.3 (91.11) 117.0 (86.1) 126.1 (94.2) 164.2 (98.1) 0.013  Creatinine level (µmol/L) 108.2 (75.7) 84.1 (41.6) 134.7 (105.2) 164.1 (95.1) <0.001  SGOT (U/L) 71.2 (101.9) 65.6 (49.4) 58.7 (38.6) 108.4 (224.5) 0.033  SPOT (U/L) 45.8 (59.1) 47.0 (43.5) 32.79 (24.6) 59.73 (114.1) 0.078  D-dimers (mg/L) 3421.5 (7303.8) 3229.8 (7209.2) 3662.21 (7544.5) 3737.0 (7639.4) 0.945  Us Troponin I (ng/L) 72.7 (421.9) 21.5 (43.8) 46.3 (63.1) 301.3 (1016.1) 0.009  Ferritin (mg/L) 1465.3 (1584.2) 1485.8 (1836.6) 1309.3 (1115.2) 1585.3 (1303.5) 0.824 Outcome  Favourable 191 (68.5) 135 (78.9) 42 (63.6) 14 (33.3) <0.001  Unfavourable 88 (31.5) 36 (21.1) 24 (36.4) 28 (66.7) <0.001   HFNC or NVI 28 (10.0) 13 (11.4) 10 (29.4) 5 (26.3) 0.024   Mechanical ventilation 27 (39.1) 19 (16.2) 5 (14.7) 3 (15.8) 0.977   Deceased 51 (18.3) 15 (8.9) 15 (24.2) 21 (53.8) <0.001 Results are expressed as count (%) for categorical variables and as mean (standard deviation) for quantitative variables. *SGOT and SPOT were available for 244 (87.5%), us troponin I levels for 157 (56.3%) patients, and ferritin for 112 (29.6%) patients. Abbreviations: AST: aspartate aminotransferase; ALT: alanine aminotransferase; HFNC: high flow nasal cannula; NVI: non-invasive ventilation. In the Cox proportional hazard model, the CURB-65 was strongly associated with a poor outcome (HR 1.84, 95%CI 1.10–3.09, P=0.020 for a CURB-65 of 2 compared to 0–1; and HR 4.18, 95% CI 2.54–6.86, p<0.001 for a CURB-65 of 3–5 compared to 0–1; P for linear trend <0.001). However, among patients with a CURB-65 of 0–1, thus considered at low risk, 36/171 (21.1%) had a poor outcome: 27 (15.8%) were transferred for ICU for HFNC and/or NIV (N=13), and/or invasive mechanical ventilation (N=19), and 15 (8.8%) patients died within the 14 days following admission (Figure 1 ). Figure 1 Description of the outcome according to the CURB-65 (N=279). Figure 1 Our results showed that the CURB-65 is associated with an unfavourable outcome, and thus its application as a severity score for COVID-19 might be promising. However, while the majority of our patients would have been considered at low risk of 30-day mortality according to this severity score, more than 20% of them had a poor outcome. Our study suggests that the applicability of CURB-65 to guide the decision of inpatient or outpatient care is scarce, as it does not safely identify patients who could be managed as outpatients. In studies of CURB-65 in the clinical practice of CAP, many patients with low CURB-65 scores are not suitable for outpatient treatment because many factors are not incorporated in the score, including hypoxemia requiring oxygen therapy, unmet social needs 6 . In addition, this score also appears to underestimate severity in young patients with CAP. Those limitations might also apply to COVID-19, whose epidemiology and severity also differ from CAP. COVID-19 is a systemic disease, and its severity might be due to virus-activated “cytokine storm syndrome”, exacerbated inflammatory responses. 7 Many known risk factors, such as cardiovascular history, D-dimers, Interleukin-6, but also the myocardial involvement of COVID-19 might not be captured by the CURB-65 8, 9, 10. Thus, we express our concerns regarding the use of the CURB-65 to guide the decision of inpatient or outpatient care for COVID-19. There is an unmet need to have easy-to-use scores to detect COVID-19 patients at risk, and to guide this decision. Declaration of Competing Interest None of the authors declared any competing interest in link with the present study.