key: cord-032268-oj94e8wo authors: Kaeuffer, Charlotte; Ruch, Yvon; Fabacher, Thibaut; Hinschberger, Olivier; Mootien, Joy; Eyriey, Magali; Greigert, Valentin; Meyer, icolas; Fafi-Kremer, Samira; Lefebvre, Nicolas; Hansmann, Yves; Martinot, Martin; Danion, François title: The BAS²IC score: a useful tool to identify patients at high risk of early progression to severe COVID-19 date: 2020-09-01 journal: Open Forum Infect Dis DOI: 10.1093/ofid/ofaa405 sha: doc_id: 32268 cord_uid: oj94e8wo We developed a score, based on easily accessible data (age, sex, BMI, dyspnea and inflammatory parameters), to predict the risk of rapid progression to severe disease in hospitalized patients with COVID-19. Using a cut-off of >6 points, the negative and positive predictive values were 87% and 49%, respectively. The coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO) on 13 March 2020 [1] . On an average, less than 3% of infected individuals are hospitalized, among which 20% require intensive care. Overall, 0.5% of patients with COVID-19 died [2] . Rapid identification of patients at a high risk of developing severe COVID-19 appeared to be crucial to help clinicians closely monitor such patients and for triage. In a previous multicenter study involving 1,045 hospitalized patients with confirmed COVID-19, we identified several independent risk factors, such as advanced age, obesity and inflammation, associated with the early development of severe disease [3] . In the present study, we aimed to develop a practical score for estimating the risk of rapid progression to severe disease in a cohort of patients hospitalized for COVID-19. We used data collected from a prospective non-interventional cohort study, which included adult patients with confirmed COVID-19 hospitalized in March 2020 in Strasbourg University and Mulhouse hospitals (France) [3] . Severe disease was defined as admission to the intensive care unit (ICU) or death within 7 days after admission. Overweight and obesity were defined according to the WHO as a body mass index (BMI) of ≥25 kg/m² and ≥30 kg/m², respectively. Dyspnea was defined as a score >0 according to the modified Medical Research Council breathlessness scale. We chose an early time-point at day 7 as majority of ICU transfers or deaths occurred within the first week of hospitalization. In the derivation cohort, we have performed a Bayesian logistic regression to identify risk factors for severe COVID-19. All demographic, clinical and biological variables with a Pr(diff>0) <0.025 or a Pr(diff>0) >0.975 in the univariate analysis, or of clinical relevance, were included in the multivariate model. Variables collected were: age, sex, BMI, comorbidities (hypertension, diabetes, chronic lung disease, immunosuppression, chronic kidney disease, chronic heart failure, chronic hepatic failure, cancer, hematological malignancy, active smoking), pregnancy, symptoms at admission (fever, dyspnea, headache, chills, cough, fatigue, myalgia, chest pain, diarrhea, abdominal pain, confusion, anosmia or ageusia, oxygen level at admission), biological markers (C-reactive protein, neutrophil count, lymphocyte count, aspartate aminotransferase, alanine aminotransferase, hemoglobin level, platelet count, serum creatinine, serum sodium, lactate), radiological findings (chest computed tomography (CT) described as typical, bilateral involvement, ground-glass opacities, micronodules), treatments in the previous month (non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, angiotensin-2 receptor antagonists, insulin, corticosteroids, hydroxychloroquine), antibiotic in the seven days prior to admission (betalactam, macrolide). [3] . To build the score, these coefficients have been multiplied by 4 and rounded to the nearest half-integer. The score was evaluated (positive predictive value [PPV], negative predictive value [NPV] , sensitivity, specificity) on the derivation cohort and clinically relevant cut offs (NPV >85% and PPV >60%) were determined. Missing data were imputed using prior distributions derived from the observed data. The performance of this score was validated using an external cohort of 153 patients hospitalized for COVID-19 during the same period in Colmar Hospital, France. The study was approved by the Ethics Committee of the University Hospital of Strasbourg (N°CE-2020-51). Written consent was waived in the context of an emerging infection. The patients who refused to participate in this study were not included. In the derivation cohort of 1,045 patients, the mean age was 66 years (standard deviation [SD], 16), and 612 patients (58.6%) were men (supplementary Table 1 Based on previously identified prognostic factors [3] , we then defined a prognostic BAS²IC score including BMI, age, sex, shortness of breath and inflammatory parameters to screen patients at a risk of developing early severe disease (Table 1 ). In the receiver-operating characteristics analysis, the area under the curve was 0.76 (0.73-0.79) (Figure 1 ). Using a cut-off >6 points, the NPV and PPV were 87% and 49%, respectively, with a sensitivity of 93% and a specificity of 32%. Using a cut-off >14 points, the NPV was 66%, the PPV was 66%, sensitivity was 33% and specificity of 88%. In the validation cohort, including 153 adult patients, the mean age was 72 years (SD, 13). Among them, 97 (63.4%) were men and 103 (67.3%) were overweight. In this cohort, 45 (29%) patients have developed severe disease. Using a cut-off >6 points, the NPV, PPV, sensitivity and specificity were 88%, 38%, 87% and 40%, respectively (Figure 1 ). Using a cut-off >14 points, the NPV, PPV, sensitivity and specificity were 73%, 58%, 16% and 95%, respectively. A suggestion on management was proposed depending of these cut offs (Table 1b ). In this study, we established a new practical score, the BAS²IC score, to easily evaluate the risk of developing early severe COVID-19 among patients hospitalized due to severe COVID-19. The score was validated on an external cohort, providing a similar performance. Patients with a score ≤6 points could be considered at a low risk of developing severe disease, with a NPV of 87%; hence, this score may help to decide which patients can be discharged. On the contrary, those with score >14 were considered to have a high risk, requiring rapid implementation of appropriate measures, such as hospitalization and consideration of specific therapeutics (e.g. dexamethasone, remdesivir) [4, 5] . The BAS²IC score has several advantages over previously published scores [4] [5] [6] . This score was based on a large multicenter prospective cohort. It can predict the development of early complications, and it relies on clinical and laboratory parameters, all of which are simple, inexpensive and easily accessible. This score could be easily implemented in routine clinical practice to help clinicians classify patients at low risk and those at high risk, who should be closely monitored and thus, might benefit quickly from the relevant therapy. This is particularly important in the context of a rapid increase in the number of cases saturating health care facilities and in cases where identifying patients at high risk of developing a severe disease might help optimize medical resources. Moreover, this score includes overweight parameter and certain inflammatory parameters, two important risk factors that have not been taken into account in previously published scores [6, 7] . The use of inflammatory parameters is of particular relevance in terms of the results of dexamethasone administration for COVID-19 treatment [5] . However, the BAS²IC score has some limits. First, the performance level of this score is not very high. Some risk factors, such as high levels of D-dimer and interleukine-6, which are associated with a poor outcome, were not taken into account when elaborating our score [8, 9] . The efficacy of the score would probably have been even better if these parameters had been included. However, we believe that since these parameters are not tested for in routine clinical practice, adding them to the BAS²IC score would have rendered the score difficult to use for clinicians. The etiology of death or admission to the ICU among the elderly is multifactorial and often linked to the decompensation of underlying diseases. Comorbidities, such as diabetes, immunosuppression and chronic kidney disease, were not associated with severe disease in our previous analysis but were associated with death alone [3] . As this study was conducted in March 2020, the beginning of the outbreak in France, very few patients benefited from specific therapy, such as corticosteroids or immunomodulatory treatments. This could have had an impact on the number of patients with severe disease. Finally, this score is a helpful tool for clinicians, but it should not replace common clinical sense for deciding whether the patients require hospitalization or specific therapy. Other parameters, such as the duration of symptoms, decompensation of comorbidities, need for oxygen, extension of lesions on computed tomography, and others, may be taken into account. Further studies are needed to confirm the performance of the BAS²IC score and validate our proposal for COVID-19 management depending on the score. We developed the predictive BAS²IC score, which is easy to implement and use in routine clinical practice, to help clinicians identify patients at high risk of developing early severe COVID-19. This simple score may be useful for triage of patients with COVID-19 and to identify those who should be closely monitored. WHO Director-General's opening remarks at the media briefing on COVID-19 -13 Estimating the burden of SARS-CoV-2 in France Risk Factors Associated with Severe COVID-19 in Eastern France: Analysis of 1045 Cases Remdesivir for the Treatment of Covid-19 -Preliminary Report Dexamethasone in Hospitalized Patients with Covid-19 -Preliminary Report Development and Validation of a Clinical Risk Score to Predict the Occurrence of Critical Illness in Hospitalized Patients With COVID-19 Prediction for Progression Risk in Patients with COVID-19 Pneumonia: the CALL Score Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19 The authors would like to thank Enago (www.enago.com) for the English language review. The authors declare no conflict of interest.