Pre-existing chronic kidney disease (CDK) was not associated with a severe clinical outcome of hospitalized COVID-19: results of a case-control study in Southern Italy.

The presence of co-morbidities is associated with a poor outcome in patients with COVID-19. The aim of the present study was to investigate the outcomes of patients with SARS-CoV-2 infection and chronic kidney disease (CKD) in order to assess its impact on mortality and severity of disease. We performed a multicenter, observational, 1:2 matched case-control study involving seventeen COVID-19 Units in southern Italy. All the adults hospitalized for SARS-CoV-2 infection and with pre-existing CKD were included (Cases). For each Case, two patients without CKD pair matched for gender, age (+5 years), and number of co-morbidities (excluding CKD) were enrolled (Controls). Of the 2,005 patients with SARS-CoV-2 infection followed during the study period, 146 patients with CKD and 292 patients without were enrolled in the case and control groups, respectively. Between the Case and Control groups, there were no statistically significant differences in the prevalence of moderate (17.1% vs 17.8%, p=0.27) or severe (18.8% and 13.7%, p=0.27) clinical presentation of COVID-19 or deaths (20.9% vs 28.1%, p=0.27). In the Case group, the patients dead during hospitalization were statistically higher in the 89 patients with CKD stage 4-5 compared to 45 patients with stages 1-3 CKD (30.3% vs 13.3%, p=0.03). Our data suggests that only CKD stage 4-5 on admission was associated with an increased risk of in-hospital death.

Lactate dehydrogenase and PaO2/FiO2 ratio at admission helps to predict CT score in patients with COVID-19: An observational study.

INTRODUCTION: Since the beginning of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic an important tool for patients with Coronavirus Disease 2019 (COVID-19) has been the computed tomography (CT) scan, but not always available in some settings The aim was to find a cut-off that can predict worsening in patients with COVID-19 assessed with a computed tomography (CT) scan and to find laboratory, clinical or demographic parameters that may correlate with a higher CT score. METHODS: We performed a multi-center, observational, retrospective study involving seventeen COVID-19 Units in southern Italy, including all 321 adult patients hospitalized with a diagnosis of COVID-19 who underwent at admission a CT evaluated using Pan score. RESULTS: Considering the clinical outcome and Pan score, the best cut-off point to discriminate a severe outcome was 12.5. High lactate dehydrogenase (LDH) serum value and low PaO2/FiO2 ratio (P/F) resulted independently associated with a high CT score. The Area Under Curve (AUC) analysis showed that the best cut-off point for LDH was 367.5 U/L and for P/F 164.5. Moreover, the patients with LDH> 367.5 U/L and P/F < 164.5 showed more frequently a severe CT score than those with LDH< 367.5 U/L and P/F> 164.5, 83.4%, vs 20%, respectively. CONCLUSIONS: A direct correlation was observed between CT score value and outcome of COVID-19, such as CT score and high LDH levels and low P/F ratio at admission. Clinical or laboratory tools that predict the outcome at admission to hospital are useful to avoiding the overload of hospital facilities.

Clinical Characterization of the Three Waves of COVID-19 Occurring in Southern Italy: Results of a Multicenter Cohort Study.

AIMS: To characterize patients hospitalized for COVID-19 in the three waves in Southern Italy. METHODS: We conducted a multicenter observational cohort study involving seventeen COVID-19 Units in Campania, southern Italy: All adult (≥18 years) patients, hospitalized with a diagnosis of SARS-CoV-2 infection from 28 February 2020 to 31 May 2021, were enrolled. RESULTS: Two thousand and fifteen COVID-19 hospitalized patients were enrolled; 392 (19%) in the first wave, 917 (45%) in the second and 706 (35%) in the third wave. Patients showed a less severe clinical outcome in the first wave than in the second and third waves (73%, 65% and 72%, respectively; p = 0.003), but hospitalization expressed in days was longer in the first wave [Median (Q1-Q3): 17 (13-25) v.s. 14 (9-21) and 14 (9-19), respectively, p = 0.001)] and also mortality during hospitalization was higher in the first wave than in the second and third waves: 16.6% v.s. 11.3% and 6.5%, respectively (p = 0.0001). Multivariate analysis showed that older age [OR: 1.069, CI (1046-1092); p = 0.001], a worse Charlson comorbidity index [OR: 1042, CI (1233-1594; p = 0.0001] and enrolment during the first-wave [OR: 1.917, CI (1.054-3.485; p = 0.033] were predictors of mortality in hospitalized patients. CONCLUSIONS: Improved organization of the healthcare facilities and the increase in knowledge of clinical and therapeutic management have contributed to a trend in the reduction in mortality during the three waves of COVID-19.

Prognostic Value of Transaminases and Bilirubin Levels at Admission to Hospital on Disease Progression and Mortality in Patients with COVID-19-An Observational Retrospective Study.

INTRODUCTION: Given the impact of COVID-19 on the world healthcare system, and the efforts of the healthcare community to find prognostic factors for hospitalization, disease progression, and mortality, the aim of the present study was to investigate the prognostic impact of transaminases and bilirubin levels at admission to hospital on disease progression and mortality in COVID-19 patients. METHODS: Using the CoviCamp database, we performed a multicenter, observational, retrospective study involving 17 COVID-19 Units in southern Italy. We included all adult patients hospitalized for SARS-CoV-2 infection with at least one determination at hospital admission of aminotransaminases and/or total bilirubin. RESULTS: Of the 2054 patients included in the CoviCamp database, 1641 were included in our study; 789 patients (48%) were considered to have mild COVID-19, 347 (21%) moderate COVID-19, 354 (22%) severe COVID-19, and 151 patients (9%) died during hospitalization. Older age (odds ratio (OR): 1.02; 95% confidence interval (CI) 1.01-1.03), higher Charlson comorbidity index (CCI) (OR 1.088; 95%CI 1.005-1.18), presence of dementia (OR: 2.20; 95% CI: 1.30-3.73), higher serum AST (OR: 1.002; 95% CI: 1.0001-1.004), and total bilirubin (OR: 1.09; 95% CI: 1.002-1.19) values were associated with a more severe clinical outcome. Instead, the 151 patients who died during hospitalization showed a higher serum bilirubin value at admission (OR 1.1165; 95% CI: 1.017-1.335); the same did not apply for AST. DISCUSSION: Patients with COVID-19 with higher levels of AST and bilirubin had an increased risk of disease progression.

PD-L1 Dysregulation in COVID-19 Patients.

The COVID-19 pandemic has reached direct and indirect medical and social consequences with a subset of patients who rapidly worsen and die from severe-critical manifestations. As a result, there is still an urgent need to identify prognostic biomarkers and effective therapeutic approaches. Severe-critical manifestations of COVID-19 are caused by a dysregulated immune response. Immune checkpoint molecules such as Programmed death-1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1) play an important role in regulating the host immune response and several lines of evidence underly the role of PD-1 modulation in COVID-19. Here, by analyzing blood sample collection from both hospitalized COVID-19 patients and healthy donors, as well as levels of PD-L1 RNA expression in a variety of model systems of SARS-CoV-2, including in vitro tissue cultures, ex-vivo infections of primary epithelial cells and biological samples obtained from tissue biopsies and blood sample collection of COVID-19 and healthy individuals, we demonstrate that serum levels of PD-L1 have a prognostic role in COVID-19 patients and that PD-L1 dysregulation is associated to COVID-19 pathogenesis. Specifically, PD-L1 upregulation is induced by SARS-CoV-2 in infected epithelial cells and is dysregulated in several types of immune cells of COVID-19 patients including monocytes, neutrophils, gamma delta T cells and CD4+ T cells. These results have clinical significance since highlighted the potential role of PD-1/PD-L1 axis in COVID-19, suggest a prognostic role of PD-L1 and provide a further rationale to implement novel clinical studies in COVID-19 patients with PD-1/PD-L1 inhibitors.

More Severe COVID-19 in Patients With Active Cancer: Results of a Multicenter Cohort Study.

BACKGROUND: The aim of the study was to compare coronavirus disease 2019 (COVID-19) severity presentation between oncologic and non-oncologic patients and to evaluate the impact of cancer type and stage on COVID-19 course. METHODS: We performed a multicentre, retrospective study involving 13 COVID-19 Units in Campania region from February to May 2020. We defined as severe COVID-19 presentation the cases that required mechanical ventilation and/or admission to Intensive Care Units (ICU) and/or in case of death. RESULTS: We enrolled 371 COVID-19 patients, of whom 34 (9.2%) had a history or a diagnosis of cancer (24 solid, 6 onco-hematological). Oncologic patients were older (p<0.001), had more comorbidities (p<0.001) and showed a higher rate of severe COVID-19 presentation (p=0.001) and of death (p<0.001). Compared to 12 patients with non-active cancer and to 337 without cancer, the 17 patients with active cancer had more comorbidities and showed a higher rate of severe COVID-19 and of mortality (all p values <0.001). Compared to the 281 non-severe patients, the 90 subjects with a severe presentation of COVID-19 were older (p<0.01), with more comorbidities (p<0.001) and with a higher rate of cancer (p=0.001). At multivariate analysis, age (OR 1.08, 95% CI: 1.04-1.11) and suffering from cancer in an active stage (OR 5.33, 95% CI: 1.77-16.53) were independently associated with severe COVID-19. CONCLUSIONS: Since the higher risk of severe evolution of COVID-19, cancer patients, especially those with an active malignancy, should be candidates for early evaluation of symptoms and early treatment for COVID-19.

Clinical Features of Patients with Home Isolation Sars-Cov-2 Infection: A Multicenter Retrospective Study in Southern Italy.

To describe epidemiological and clinical features of patients confirmed as having SARS-CoV-2 infection and managed in isolation at home. We performed a multicenter retrospective study enrolling all SARS-CoV-2-positive adults evaluated from 28 February to 31 May 2020 at one of nine COVID-19 Units in southern Italy: we included patients receiving care at home and those admitted to hospital. We defined patients with not-severe disease if they were asymptomatic or experienced a mild infection that did not need oxygen (O2) therapy and those with a severe infection if hospitalized and required O2 therapy. We enrolled 415 patients with SARS-CoV-2 infection: 77 were managed in isolation at home, 338 required hospital management. The 77 patients in home isolation were less frequently male than hospitalized patients (55% vs. 64%; <0.01) and were younger (median age 45 years (IQR:19) vs. 62 (IQR 22); p < 0.01), had a lower Charlson comorbidity index (median 0 (IQR2) vs. 6 (IQR 3); p < 0.01), and included fewer subjects with an underlying chronic disease (36% vs. 59%; p < 0.01). According to a binomial logistic regression analysis, a younger age (OR: 0.96 (95% IC: 0.94-0.98), p < 0.01) and a low Charlson comorbidity index (OR: 0.66 (95% IC: 0.54-0.83); p < 0.01) were independent factors associated with at-home management. The identification of subjects with SARS-CoV-2 infection who could be managed in home isolation is useful in clinical practice. A younger age and no comorbidities were identified as factors independently associated with home management.

Combination of Ruxolitinib and Eculizumab for Treatment of Severe SARS-CoV-2-Related Acute Respiratory Distress Syndrome: A Controlled Study.

To date, there are no specific therapeutic strategies for treatment of COVID-19. Based on the hypothesis that complement and coagulation cascades are activated by viral infection, and might trigger an acute respiratory distress syndrome (ARDS), we report clinical outcomes of 17 consecutive cases of SARS-CoV-2-related ARDS treated (N = 7) with the novel combination of ruxolitinib, a JAK1/2 inhibitor, 10 mg/twice daily for 14 days and eculizumab, an anti-C5a complement monoclonal antibody, 900 mg IV/weekly for a maximum of three weeks, or with the best available therapy (N = 10). Patients treated with the combination showed significant improvements in respiratory symptoms and radiographic pulmonary lesions and decrease in circulating D-dimer levels compared to the best available therapy group. Our results support the use of combined ruxolitinib and eculizumab for treatment of severe SARS-CoV-2-related ARDS by simultaneously turning off abnormal innate and adaptive immune responses.