More skilled clinical management of COVID-19 patients modified mortality in an intermediate respiratory intensive care unit in Italy.

BACKGROUND: Some studies investigated epidemiological and clinical features of laboratory-confirmed patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the virus causing coronavirus disease 2019 (COVID-19), but limited attention has been paid to the follow-up of hospitalized patients on the basis of clinical setting and the expertise of clinical management. METHODS: In the present single-centered, retrospective, observational study, we reported findings from 87 consecutive laboratory-confirmed COVID-19 patients with moderate-to-severe acute respiratory syndrome hospitalized in an intermediate Respiratory Intensive Care Unit (RICU), subdividing the patients in two groups according to the admission date (before and after March 29, 2020). RESULTS: With improved skills in the clinical management of COVID-19, we observed a significant lower mortality in the T2 group compared with the T1 group and a significantly difference in terms of mortality among the patients transferred in Intensive Care Unit (ICU) from our intermediate RICU (100% in T1 group vs. 33.3% in T2 group). The average length of stay in intermediate RICU of ICU-transferred patients who survived in T1 and T2 was significantly longer than those who died (who died 3.3 ± 2.8 days vs. who survived 6.4 ± 3.3 days). T CONCLUSIONS: The present findings suggested that an intermediate level of hospital care may have the potential to modify survival in COVID-19 patients, particularly in the present phase of a more skilled clinical management of the pandemic.

Rapid Serological Assays and SARS-CoV-2 Real-Time Polymerase Chain Reaction Assays for the Detection of SARS-CoV-2: Comparative Study.

BACKGROUND: Real-time polymerase chain reaction (RT-PCR) testing for the identification of viral nucleic acid is the current standard for the diagnosis of SARS-CoV-2 infection, but technical issues limit its utilization for large-scale screening. Serological immunoglobulin M (IgM)/IgG testing has been proposed as a useful tool for detecting SARS-CoV-2 exposure. OBJECTIVE: The objective of our study was to compare the results of the rapid serological VivaDiag test for SARS-CoV-2-related IgM/IgG detection with those of the standard RT-PCR laboratory test for identifying SARS-CoV-2 nucleic acid. METHODS: We simultaneously performed both serological and molecular tests with a consecutive series of 191 symptomatic patients. The results provided by a new rapid serological colorimetric test for analyzing IgM/IgG expression were compared with those of RT-PCR testing for SARS-CoV-2 detection. RESULTS: Of the 191 subjects, 70 (36.6%) tested positive for SARS-CoV-2 based on RT-PCR results, while 34 (17.3%) tested positive based on serological IgM/IgG expression. Additionally, 13 (6.8%) subjects tested positive based on serological test results, but also tested negative based on RT-PCR results. The rapid serological test had a sensitivity of 30% and a specificity of 89% compared to the standard RT-PCR assay. Interestingly, the performance of both assays improved 8 days after symptom appearance. After 10 days had passed since symptom appearance, the predictive value of the rapid serological test was higher than that of the standard molecular assay (proportion of positive results: 40% vs 20%). Multivariate analysis showed that age >58 years (P<.01) and period of >15 days after symptom onset (P<.02) were significant and independent factors associated with serological test positivity. CONCLUSIONS: The rapid serological test analyzed in this study seems limited in terms of usefulness when diagnosing SARS-CoV-2 infection. However, it may be useful for providing relevant information on people's immunoreaction to COVID-19 exposure.

Hyperacute Hemodynamic Effects of BiPAP Noninvasive Ventilation in Patients With Acute Heart Failure and Left Ventricular Systolic Dysfunction in Emergency Department.

BACKGROUND: Acute heart failure (AHF) is one of the leading causes of admission to emergency department (ED); severe hypoxemic AHF may be treated with noninvasive ventilation (NIV). Despite the demonstrated clinical efficacy of NIV in relieving symptoms of AHF, less is known about the hyperacute effects of bilevel positive airway pressure (BiPAP) ventilation on hemodynamics of patients admitted to ED for AHF. We therefore aimed to assess the effect of BiPAP ventilation on principal hemodynamic, respiratory, pulse oximetry, and microcirculation indexes in patients admitted to ED for AHF, needing NIV. METHODS: Twenty consecutive patients admitted to ED for AHF and left ventricular systolic dysfunction, needing NIV, were enrolled in the study; all patients were treated with NIV in BiPAP mode. The following parameters were measured at admission to ED (T0, baseline before treatment), 3 hours after admission and initiation of BiPAP NIV (T1), and after 6 hours (T2): arterial blood oxygenation (pH, partial pressure of oxygen in the alveoli/fraction of inspired oxygen ratio, Paco2, lactate concentration, HCO3-), hemodynamics (tricuspid annular plane systolic excursion, transpulmonary gradient, transaortic gradient, inferior vena cava diameter, brain natriuretic peptide [BNP] levels), microcirculation perfusion (end-tidal CO2 [etco2], peripheral venous oxygen saturation [SpvO2]). RESULTS: All evaluated indexes significantly improved over time (analysis of variance, P < .001 in quite all cases.). CONCLUSIONS: The BiPAP NIV may rapidly ameliorate several hemodynamic, arterial blood gas, and microcirculation indexes in patients with AHF and left ventricular systolic dysfunction.

Integrated lung ultrasound score for early clinical decision-making in patients with COVID-19: results and implications.

BACKGROUND AND OBJECTIVES: Lung Ultrasound Score (LUS) identifies and monitors pneumonia by assigning increasing scores. However, it does not include parameters, such as inferior vena cava (IVC) diameter and index of collapse, diaphragmatic excursions and search for pleural and pericardial effusions. Therefore, we propose a new improved scoring system, termed "integrated" lung ultrasound score (i-LUS) which incorporates previously mentioned parameters that can help in prediction of disease severity and survival, choice of oxygenation mode/ventilation and assignment to subsequent areas of care in patients with COVID-19 pneumonia. METHODS: Upon admission at the sub-intensive section of the emergency medical department (SEMD), 143 consecutively examined COVID-19 patients underwent i-LUS together with all other routine analysis. A database for anamnestic information, laboratory data, gas analysis and i-LUS parameters was created and analyzed. RESULTS: Of 143 enrolled patients, 59.4% were male (mean age 71 years) and 40.6% female. (mean age 79 years: p = 0.005). Patients that survived at 1 month had i-LUS score of 16, which was lower than that of non-survivors (median 20; p = 0.005). Survivors had a higher PaO2/FiO2 (median 321.5) compared to non-survivors (median 229, p < 0.001). There was a correlation between i-LUS and PaO2/FiO2 ratio (rho:-0.4452; p < 0.001), PaO2/FiO2 and survival status (rho:-0.3452; p < 0.001), as well as i-LUS score and disease outcome (rho:0.24; p = 0.005). In non-survivors, the serum values of different significant COVID indicators were severely expressed. The i-LUS score was higher (median 20) in patients who required non-invasive ventilation (NIV) than in those treated only by oxygen therapy (median 15.42; p = 0.003). The odds ratio for death outcome was 1.08 (confidence interval 1.02-1.15) for each point increased. At 1-month follow-up, 65 patients (45.5%) died and 78 (54.5%) survived. Patients admitted to the high critical ward had higher i-LUS score than those admitted to the low critical one (p < 0.003). CONCLUSIONS: i-LUS could be used as a helpful clinical tool for early decision-making in patients with COVID-19 pneumonia.

A simple prognostic score based on troponin and presepsin for COVID-19 patients admitted to the emergency department: a single-center pilot study.

BACKGROUND: The need to determine prognostic factors that can predict a particularly severe or, conversely, the benign course of COVID-19 is particularly perceived in the Emergency Department (ED), considering the scarcity of resources for a conspicuous mass of patients. The aim of our study was to identify some predictors for 30-day mortality among some clinical, laboratory, and ultrasound variables in a COVID-19 patients population. METHODS: Prospective single-center pilot study conducted in an ED of a University Hospital. A consecutive sample of confirmed COVID-19 patients with acute respiratory failure was enrolled from March 8th to April 15th, 2020. RESULTS: 143 patients were enrolled. Deceased patients (n = 65) were older (81 vs. 61 years, p <0.001), and they had more frequently a history of heart disease, neurological disease, or chronic obstructive pulmonary disease (p-values = 0.026, 0.025, and 0.034, respectively) than survived patients. Troponin I and presepsin had a significant correlation with a worse outcome. Troponin achieved a sensitivity of 77% and a specificity of 82% for a cut-off value of 27.6 ng/L. The presepsin achieved a sensitivity of 54% and a specificity of 92% for a cut-off value of 871 pg/mL. CONCLUSION: In a population of COVID-19 patients with acute respiratory failure in an ED, presepsin and troponin I are accurate predictors of 30-day mortality. Presepsin is highly specific and could permit the early identification of patients who could benefit from more intensive care as soon as they enter the ED. Further validation studies are needed to confirm this result.

Covid-19 Symptomatic Patients with Oral Lesions: Clinical and Histopathological Study on 123 Cases of the University Hospital Policlinic of Bari with a Purpose of a New Classification.

The aim of this study is to report on the oral lesions detected in 123 patients diagnosed at the University Hospital of Bari from October 2020 to December 2020, focusing on the correlation of clinical and pathological features in order to purpose a new classification. METHODS: General and specialistic anamnesis were achieved and oral examination was performed. The following data were collected: age/gender, general symptoms and form of Covid-19, presence and features of taste disorders, day of appearance of the oral lesions, type and features of oral lesions and day of beginning of therapies. If ulcerative lesions did not heal, biopsy was performed. RESULTS: Many types of oral lesions were found and classified into four groups considering the timing of appearance and the start of the therapies. Early lesions in the initial stages of Covid-19 before the start of therapies was observed in 65.9% of the patients. In the histopathological analysis of four early lesions, thrombosis of small and middle size vessels was always noticed with necrosis of superficial tissues. CONCLUSION: The presence of oral lesions in early stages of Covid-19 could represent an initial sign of peripheral thrombosis, a warning sign of possible evolution to severe illness. This suggests that anticoagulant therapies should start as soon as possible.

The Light and Shadow of Rapid Serological Tests for SARS-CoV-2 Infection: Results from a Study in a Large Emergency Department.

A critical point in the management of the SARS-CoV-2 pandemic is the need to promptly identify the greatest number of infected people and to implement strict public health measures. In this study, the performance of a rapid serological test in a clinical setting was evaluated. Samples from 819 consecutive patients (with or without respiratory symptoms) admitted to a large Emergency Department were tested between 23 March and 21 April 2020. Patient samples were tested in a real-time PCR assay and a serological assay. In total, 148/819 patients (18.1%) tested positive for SARS-CoV-2 by real-time PCR. The serological test revealed that 70/819 patients (8.5%) had anti-SARS-CoV-2 IgM and/or IgG. The prevalence of anti-SARS-CoV-2 antibodies was significantly higher in patients with respiratory symptoms lasting for >7 days than in those with respiratory symptoms lasting for 0-7 days (p < 0.001). The serological assay had an overall sensitivity of 35.1% and an overall specificity of 97.3%. A high negative predictive value (96.7%) was reported for patients without respiratory symptoms. The results confirm that rapid serological assays alone are not sufficient for diagnosis of SARS-CoV-2 infection but can be incorporated into large-scale screening programs during periods in which the virus circulation is low.

New Insights in Laboratory Testing for COVID-19 Patients: Looking for the Role and Predictive Value of Human epididymis secretory protein 4 (HE4) and the Innate Immunity of the Oral Cavity and Respiratory Tract.

COVID-19 is a viral pandemic caused by the new coronavirus SARS-CoV-2, an enveloped positive stranded RNA virus. The mechanisms of innate immunity, considered as the first line of antiviral defense, is essential towards viruses. A significant role in host defense of the lung, nasal and oral cavities is played by Human epididymis secretory protein 4 (HE4) HE4 has been demonstrated to be serum inflammatory biomarker and to show a role in natural immunity at the level of oral cavity, nasopharynx and respiratory tract with both antimicrobial/antiviral and anti-inflammatory activity. Several biomarkers like IL-6, presepsin (PSP), procalcitonin (PCT), CRP, D-Dimer have showed a good function as predictor factors for the clinical evolution of COVID-19 patients (mild, severe and critical). The aim of this study was to correlate the blood levels of CRP, IL-6, PSP, PCT, D-Dimer with He4, to identify the predictive values of these biomarkers for the evolution of the disease and to evaluate the possible role of HE4 in the defense mechanisms of innate immunity at the level of oral cavity, nasopharynx and respiratory tract. Of 134 patients admitted at COVID hospital of Policlinico-University of Bari, 86 (58 men age 67.6 ± 12.4 and 28 women age 65.7 ± 15.4) fulfilled the inclusion criteria: in particular, 80 patients (93%) showed prodromal symptoms (smell and/or taste dysfunctions) and other typical clinical manifestations and 19 died (13 men age 73.4 ± 7.7 and 6 women age 74.8 ± 6.7). 48 patients were excluded because 13 finished chemotherapy and 6 radiotherapy recently, 5 presented suspected breast carcinoma, 5 suspected lung carcinoma, 6 suspected ovarian carcinoma or ovary cyst, 1 cystic fibrosis, 3 renal fibrosis and 9 were affected by autoimmune diseases in treatment with monoclonal antibodies. The venous sample was taken for each patient on the admission and during the hospital stay. For each patient, six measurements relating to considered parameters were performed. Significant correlations between He4 and IL-6 levels (r = 0.797), between He4 and PSP (r = 0.621), between He4 and PCT (r = 0.447), between He4 and D-Dimer (r = 0.367), between He4 and RCP (r = 0.327) have been found. ROC curves analysis showed an excellent accuracy for He4 (AUC = 0.92) and IL-6 (AUC = 0.91), a very good accuracy for PSP (AUC = 0.81), a good accuracy for PCT (AUC = 0.701) and D-Dimer (AUC = 0.721) and sufficient accuracy for RCP (AUC = 0.616). These results demonstrated the important correlation between He4, IL6 and PSP, an excellent accuracy of He4 and IL6 and showed a probable role of He4 in the innate immunity in particularly at the level of oral cavity, nasopharynx and respiratory tract. Besides He4 together with IL6 might be involved in the onset of smell and/or taste disorders and it might be used as innovative biomarker to monitor clinical evolution of COVID-19 because He4 could indicate a multi-organ involvement.

Taste and Smell Disorders in COVID-19 Patients: Role of Interleukin-6.

The rapid recovery of smell and taste functions in COVID-19 patients could be attributed to a decrease in interleukin-6 levels rather than central nervous system ischemic injury or viral damage to neuronal cells. To correlate interleukin-6 levels in COVID-19 patients with olfactory or gustatory dysfunctions and to investigate the role of IL-6 in the onset of these disorders, this observational study investigated 67 COVID-19 patients with taste or smell disorders or both, who did not require intensive care admission, admitted at COVID Hospital of Policlinico of Bari from March to May 2020. Interleukin-6 was assayed in COVID-19 patients with taste or smell disturbances at the time of admission and at the time of swab negativization. At the same time, patients have been given a specific survey to evaluate the severity of taste and smell disturbances. Of 125 patients with smell or taste dysfunctions at onset of disease, 67 fulfilled the inclusion criteria, while 58 were excluded because 35 of them required intensive care admission, 5 were unable to answer, 5 died, 7 had finished chemotherapy recently, and 5 refused to participate. The evaluation of taste and smell disorders was carried out using a survey performed at the time of admission and at the time of swab negativization. Sinonasal outcome test 22 (SNOT-22) was used as a reference for olfactory function assessment, and Taste and Smell Questionnaire Section of the US NHANES 2011-2014 protocol (CDC 2013b) was used as reference for gustatory function assessment. A venous blood sample was taken for each patient to measure IL-6 levels upon entry and at swab negativization. Interleukin-6 levels in COVID-19 patients in relation to olfactory or gustatory disorders were correlated from the time of their admission to the time of swab negativization. Statistically significant correlations were obtained between the decrease of interleukin-6 levels and the improvement of smell (p value < 0.05) and taste (p = 0.047) functions at swab negativization. The acquired results demonstrate the key role of interleukin-6 in the pathogenesis of chemosensitive disorders in COVID-19 patients.

Short-Term Variations in Neutrophil-to-Lymphocyte and Urea-to-Creatinine Ratios Anticipate Intensive Care Unit Admission of COVID-19 Patients in the Emergency Department.

Background: Timely assessment of COVID-19 severity is crucial for the rapid provision of appropriate treatments. Definitive criteria for the early identification of severe COVID-19 cases that require intensive care unit admission are lacking. Methods: This was a single-center, retrospective case-control study of 95 consecutive adults admitted to the intensive care unit (cases) or a medical ward (controls) for laboratory-confirmed COVID-19. Clinical data were collected and changes in laboratory test results were calculated between presentation at the emergency department and admission. Univariate and multivariable logistic regression was performed to calculate odds ratios for intensive care unit admission according to changes in laboratory variables. Results: Of the 95 adults with COVID-19, 25 were admitted to intensive care and 70 to a medical ward after a median 6 h stay in the emergency department. During this interval, neutrophil counts increased in cases and decreased in controls (median, 934 vs. -295 × 106/L; P = 0.006), while lymphocyte counts decreased in cases and increased in controls (median, -184 vs. 109 × 106/L; P < 0.001). In cases, the neutrophil-to-lymphocyte ratio increased 6-fold and the urea-to-creatinine ratio increased 20-fold during the emergency department stay, but these ratios did not change in controls (P < 0.001 for both comparisons). By multivariable logistic regression, short-term increases in the neutrophil-to-lymphocyte ratio (OR = 1.43; 95% CI, 1.16-1.76) and urea-to-creatinine ratio (OR = 1.72; 95% CI, 1.20-2.66) were independent predictors of intensive care unit admission. Conclusion: Short-time changes in neutrophil-to-lymphocyte ratio and urea-to-creatinine ratio emerged as stand-alone parameters able to identify patients with aggressive disease at an early stage.

End-tidal arterial CO2 partial pressure gradient in patients with severe hypercapnia undergoing noninvasive ventilation.

BACKGROUND: Patients with severe hypercapnia represent a particularly serious condition in an emergency department (ED), requiring immediate attention. Noninvasive ventilation (NIV) is an integral part of the treatment for acute respiratory failure. The present study aimed to validate the measurement of end-tidal CO2 (EtCO2) as a noninvasive technique to evaluate the effectiveness of NIV in acute hypercapnic respiratory failure. METHODS: Twenty consecutive patients admitted to the ED with severe dyspnea were enrolled in the study. NIV by means of bilevel positive airway pressure, was applied to the patients simultaneously with standard medical therapy and continued for 12 hours; the arterial blood gases and side-stream nasal/oral EtCO2 were measured at subsequent times: T0 (admission to the ED), T1h (after 1 hour), T6h (after 6 hours), and T12h (after 12 hours) during NIV treatment. RESULTS: The arterial CO2 partial pressure (PaCO2)-EtCO2 gradient decreased progressively, reaching at T6h and T12h values lower than baseline (P < 0.001), while arterial pH increased during the observation period (P < 0.001). A positive correlation was found between EtCO2 and PaCO2 values (r = 0.89, P < 0.001) at the end of the observation period. CONCLUSION: In our hypercapnic patients, the effectiveness of the NIV was evidenced by the progressive reduction of the PaCO2-EtCO2 gradient. The measurement of the CO2 gradient could be a reliable method in monitoring the effectiveness of NIV in acute hypercapnic respiratory failure in the ED.