An emerging marker predicting the severity of COVID-19: Neutrophil-Lymphocyte Count Ratio (preprint)

Background: To analyze clinical features and laboratory indicators and identify the markers of exacerbation in COVID-19. Methods: We reviewed clinical histories of 177 patients with confirmed COVID-19. The patients were categorized into mild group (153 patients) and severe group (24 patients). The baseline demographic and laboratory indicators of all patients were collected, including the neutrophil-lymphocyte count ratio (NLCR) and C-reactive protein to albumin ratio (CAR). Receiver operating characteristic curve (ROC) analysis was performed to search for indicators predicting exacerbation in COVID-19 patients, and acquiring the area under the curves (AUCs), sensitivity, specificity and cut-off value. Results: The age of the severe group were significantly older than those of the mild group (P <0.01). Fever was the typical symptom in all COVID-19 patients. Cough and fatigue were manifested in mild group, yet severe patients were more prominent in dyspnea. The laboratory indicators showing that the mild group mainly had an elevated C-reactive protein; the severe group had a decreased lymphocyte count and lymphocyte ratio. WBC, neutrophil count, neutrophil ratio, D-dimer, AST, ALT, LDH,  BUN, CRP levels increased. Furthermore, compared to mild group, WBC, neutrophil count, neutrophil ratio (Neut%), D-dimer, total bilirubin, albumin, AST, ALT, LDH, BUN, creatine kinase, CRP, CAR, NLCR were significantly higher, the lymphocyte count, lymphocyte ratio, and APTT were significantly lower  in  severe group (P<0.05). The ROC indicating that NLCR, Neut%, CAR, CRP, and LDH were better at distinguishing mild and severe patients. The AUCs of NLCR was larger than others (NLCR>Neut%>CAR>CRP>LDH: 0.939>0.925>0.908>0.895>0.873), which suggested that NLCR was the optimal maker; a cut-off value for NLCR of  6.15  had 87.5% sensitivity and 97.6% specificity for predicting exacerbation in COVID-19 patients. Conclusions: The different types of COVID-19 had significant differences in age, clinical symptoms and laboratory indicators, and severe patients might be easier to suffer from the multiple organ damage. An elevated NLCR may indicate that the disease was progressing towards exacerbation. It was essential to dynamically monitor the serum NLCR levels which contributed to evaluate the patient's condition and efficacy. NLCR could be used as a novel, highly specific and sensitive marker for predicting severity of COVID-19 patients.

The Use of Adjuvant Therapy in Preventing Progression to Severe Pneumonia in Patients with Coronavirus Disease 2019: A Multicenter Data Analysis (preprint)

ABSTRACT IMPORTANCE Coronavirus disease 2019 (COVID-19) is a global pandemic associated with high mortality and effective treatment to prevent clinical deterioration to severe pneumonia has not yet been well clarified. OBJECTIVE To investigate the role of several adjuvant treatments in preventing severe pneumonia in patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS Multicenter, retrospective cohort study of 564 consecutively hospitalized patients with confirmed COVID-19 at Third Xiangya Hospital of Central South University, Changsha Public Health Treatment Center, First Hospital of Yueyang, Junshan People's Hospital of Yueyang, Central Hospital of Shaoyang, Central Hospital of Xiangtan, Second Hospital of Changde, Central Hospital of Loudi, and First Affiliated Hospital of University of South China in Hunan province from January 17, 2020 to February 28, 2020; The final date of follow-up was March 15, 2020. EXPOSURES Nonspecific antivirals (arbidol, lopinavir/ritonavir, and interferon ), antihypertensives, and chloroquine. MAIN OUTCOMES AND MEASURES The development of severe COVID-19 pneumonia; Demographic, epidemiological, clinical, laboratory, radiological, and treatment data were collected and analyzed. RESULTS Of 564 patients, the median age was 47 years (interquartile range, 36-58 years), and 284 (50.4%) patients were men. Sixty-nine patients (12.2%) developed severe pneumonia. Patients who developed severe pneumonia were older (median age of 59 and 45 years, respectively), and more patients had comorbidities including hypertension (30.4% and 12.3%, respectively), diabetes (17.4% and 6.7%, respectively), and cardiovascular disease (8.7% and 3.2%, respectively) and presented with fever (84.1% and 60.4%, respectively) and shortness of breath (10.1% and 3.8%, respectively) compared with those who did not. Nonspecific antiviral therapy did not prevent clinical progression to severe pneumonia, although fewer hypertensive patients on angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (ACEI/ARB) therapy developed severe pneumonia in contrast with those on non-ACEI/ARB antihypertensive therapy (1 of 16 [6.3%] patients and 16 of 49 [32.7%] patients, respectively [difference, 26.4%; 95% CI, 1.5% to 41.3%]). Multivariate logistic regression analysis showed that hypertension without receiving ACEI/ARB therapy was an independent risk factor (odds ratio [OR], 2.07; 95% CI, 1.07 to 4.00) for developing severe pneumonia irrespective of age. Besides, none of patients treated with chloroquine developed severe pneumonia, though without significance (difference, 12.0%; 95% CI, -3.5% to 30.0%) by propensity score matching. CONCLUSIONS AND RELEVANCE Hypertensive patients on ACEI or ARB may be protective from severe pneumonia in COVID-19 and hence these therapies should not be ceased unless there is a strong indication or further epidemiological evidence. Though none of the current antiviral and immunoregulation therapy showed benefit in preventing COVID-19 progression, chloroquine deserved further investigation.

COVID-19 discharged patients in Hunan, China: correlation between early features and prognosis (preprint)

Purpose      To describe the correlation between the clinical, laboratory and radiological findings with hospitalization days in Coronavirus Infected Disease-19 (COVID-19) discharged patients. Method In this multicenter study, we retrospectively identified 153 discharged patients with COVID-19 pneumonia from Jan 16, 2020 to Feb 26, 2020 in Hunan province. Patients were grouped based on the hospitalization days: Group 1 (hospitalization days≦12 days) and Group 2((hospitalization days> 12days). Demographic, clinical characteristics and laboratory findings on admission and the imaging features of the first Chest CT on admission were analyzed. The differences between groups were analyzed using univariate logistic regression to find the impact factors. Results The cohort included 153 discharged patients (85 males and 68 females, with the mean age of 42.32±14.03 years old). 90(58.8%) patients had hospitalization days≦12 and 63(41.2%) patients had hospitalization days>12. 44(48.9%) patients in Group1 and 28(44.4%) in Group 2 had been to Wuhan. In both Group1 and Group2, most common symptoms at onset were fever (62.2%, 60.3%) and cough (33.3%, 50.8%). Cough was occurred more common in Group 2(50.8%) than Group 1(33.3%) with a significant difference (p=0.03). 6(6.7%) patients in Group1 and 10(15.9%) in Group2 had admitting diagnosis as non-pneumonia (p=0.07), some of them occurred mild pneumonia during hospital stay. White blood cell (2.2%, 9.5%) and neutrophil (9.5%) count above normal were more common on in Group 2 (p=0.04, p=0.04). Patients in Group 2 had higher concentration of aspartate aminotransferase (P=0.04) than Group 1. Most of patients had multiple lesions (75.6%, 69.8%) with bilateral distribution (73.3%, 58.7%) in both groups. Mixed ground-glass opacity (GGO) and consolidation appearance were seen in most patients. GGO components > consolidation appearance were more common in Group 1(31.1%) than in Group 2(8.0%) with a significant difference between groups (P<0.01). Patients had cough at onset disease (OR, 0.47; 95%CI, 0.23 to 0.96, p=0.04) and CT represented as GGO components more than consolidation (OR, 4.84; 95%CI, 1.80 to 13.04, p<0.01) were associated with hospitalization days. Conclusions COVID-19 non-pneumonia patients with longer hospitalization days might have the persistent symptoms or pneumonia occurrence after admission. Chest CT could help prompt diagnosis and monitor disease progression, GGO/consolidation >1 in mixed lesions was associated with shorter hospitalization days. Special attention should be paid to the role of radiological features in monitoring disease prognosis.

Early Prediction of Disease Progression in 2019 Novel Coronavirus Pneumonia Patients Outside Wuhan with CT and Clinical Characteristics (preprint)

Objective: To determine the predictive value of CT and clinical characteristics for short-term disease progression in patients with 2019 novel coronavirus pneumonia (NCP). Materials and Methods: 224 patients with confirmed 2019 novel coronavirus (COVID-19) infection outside Wuhan who had chest CT examinations were retrospectively screened. Clinical data were obtained from electronic medical records. CT images were reviewed and scored for lesion distribution, lobe and segment involvement, ground-glass opacities, consolidation, and interstitial thickening. All included patients with moderate NCP were observed for at least 14 days from admission to determine whether they exacerbated to severe NCP (progressive group) or not (stable group). CT and clinical characteristics between the two groups were compared, and multivariate logistic regression and sensitivity analyses were performed to identify the risk factors for developing severe NCP. Results: A total of 141 patients with moderate NCP were included, of which 15 (10.6%) patients developed severe NCP during hospitalization and assigned to the progressive group. Multivariate logistic regression analysis showed that higher neutrophil-to-lymphocyte ratio (NLR) (odds ratio [OR] and 95% confidence interval [CI], 1.26 [1.04-1.53]; P = 0.018) and CT severity score (OR and 95% CI, 1.25 [1.08-1.46]; P = 0.004) on admission were independent predictors for progression to severe NCP, and sensitivity analysis confirmed the consistent results in nonimported patients but not in imported patients. However, no significant difference in lung involvement was found on CT between imported and nonimported patients (all P > 0.05). Patients who were admitted more than 4 days from symptom onset tended to have more severe lung involvement. Spearman correlation analysis showed the close association between CT severity score and inflammatory indexes (r = 0.17~0.47, all P < 0.05). Conclusion: CT severity score was associated with inflammatory levels and higher NLR and CT severity score on admission were independent risk factors for short-term progression in patients with NCP outside Wuhan. Furthermore, early admission and surveillance by CT should be recommended to improve clinical outcomes.