Clinical and epidemiological factors causing longer SARS-CoV 2 viral shedding: the results from the CoviCamp cohort.

INTRODUCTION: The aim of this study was to investigate how long hospitalized patients stayed positive to the nasopharyngeal swab, and what demographic and clinical factors influence the time-to-negative swab. METHODS: We enrolled in a multicenter, observational, retrospective study involving 17 COVID-19 units in eight cities of the Campania, southern Italy all patients hospitalized from March 2020 to May 2021 diagnosed with Severe Acute Respiratory Distress Syndrome-Coronavirus-2 (SARS-CoV-2) infection for whom time-to-negative swab was available. RESULTS: 963 patients were enrolled. We defined three groups considering time-to-negative swab: the first including patients with time-to-negative swab before the 26th day, the second including patients with time-to-negative swab from day 26 to day 39, and the third including patients with time-to-negative swab > 39 days. 721 (74.9%) patients belonged to the first group, 194 (20.1%) to the second, and 52 (5.4%) belonged to the third group. Belonging to group 2 and 3 seemed to be influenced by age (p value < 0.001), Charlson comorbidity index (p = 0.009), arterial hypertension (p = 0.02), cardiovascular disease (p = 0.017), or chronic kidney disease (CKD) (p = 0.001). The multivariable analysis confers a leading role to CKD, with an odds ratio of 2.3 as factor influencing belonging to the groups showing a longer time-to-negative swab. Patients with CKD and diabetes were more frequently in the third group. DISCUSSION: Our analysis showed that CKD is a factor related to longer time-to-negative swab, probably because of immunosuppression related to this condition.

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

INTRODUCTION: Acute kidney disease and chronic kidney disease are considered conditions that can increase the mortality and severity of COVID-19. However, few studies have investigated the impact of creatinine levels on COVID-19 progression in patients without a history of chronic kidney disease. The aim of the study was to assess the impact of creatinine levels at hospital admission on COVID-19 progression and mortality. METHODS: We performed a multicenter, observational, retrospective study involving seventeen COVID-19 Units in the Campania region in southern Italy. All adult (≥18 years) patients, hospitalized with a diagnosis of SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction on a naso-oropharyngeal swab, from 28 February 2020 to 31 May 2021, were enrolled in the CoviCamp cohort. RESULTS: Evaluating inclusion/exclusion criteria, 1357 patients were included. Considering in-hospital mortality and creatinine value at admission, the best cut-off point to discriminate a death during hospitalization was 1.115 mg/dL. The logistic regression demonstrated that factors independently associated with mortality were age (OR 1.082, CI: 1.054-1.110), Charlson Comorbidity Index (CCI) (OR 1.341, CI: 1.178-1.526), and an abnormal creatinine value at admission, defined as equal to or above 1.12 mg/dL (OR 2.233, CI: 1.373-3.634). DISCUSSION: In conclusion, our study is in line with previous studies confirming that the creatinine serum level can predict mortality in COVID-19 patients and defining that the best cut-off of the creatinine serum level at admission to predict mortality was 1.12 mg/dL.

Prevalence and Epidemiological and Clinical Features of Bacterial Infections in a Large Cohort of Patients Hospitalized for COVID-19 in Southern Italy: A Multicenter Study.

BACKGROUND: The aim of this study was to evaluate the prevalence of bacterial infections and antimicrobial prescriptions in a large cohort of COVID-19 patients and to identify the independent predictors of infection and antibiotic prescription. METHODS: All consecutive patients hospitalized for COVID-19 from March 2020 to May 2021 at 1 of the 17 centers participating in the study were included. All subjects showing a clinical presentation consistent with a bacterial infection with microbiological confirmation (documented infection), and/or a procalcitonin value >1 ng/mL (suspected infection) were considered as having a coinfection (if present at admission) or a superinfection (if acquired after at least 48 h of hospital stay). RESULTS: During the study period, of the 1993 patients, 42 (2.1%) presented with a microbiologically documented infection, including 17 coinfections and 25 superinfections, and 267 (13.2%) a suspected infection. A total of 478 subjects (24.5%) received an antibacterial treatment other than macrolides. No independent predictors of confirmed or suspected bacterial infection were identified. On the contrary, being hospitalized during the second wave of the pandemic (OR 1.35, 95% CI 1.18-1.97, p = 0.001), having a SOFA score ≥3 (OR 2.05, 95% CI 1.53-2.75, p < 0.001), a severe or critical disease (OR 1.66, 95% CI 1.24-2.23, p < 0.001), and a high white blood cell count (OR 1.03, 95% CI 1.004-1.06, p = 0.023) were all independently related to having received an antimicrobial prescription. CONCLUSIONS: Our study reported a high rate of antimicrobial prescriptions despite a limited number of documented or suspected bacterial infections among the large cohort of hospitalized COVID-19 patients.

Obesity as a Risk Factor of Severe Outcome of COVID-19: A Pair-Matched 1:2 Case-Control Study.

BACKGROUND AND AIM: The nature of the association between obesity and poor prognosis of COVID-19 without the evaluation of other co-pathologies associated has not yet been clearly evaluated. The aim of the present pair-matched case-control study was to investigate the outcome of patients with SARS-CoV-2 infection in obese and non-obese patients matched considering gender, age, number of comorbidities, and Charlson Comorbidity Index. METHODS: All the adults hospitalized for SARS-CoV-2 infection and with BMI ≥ 30 kg/m2 were included (Cases). For each Case, two patients with BMI < 30 kg/m2 pair matched for gender, age (±5 years), number of comorbidities (excluding obesity), and Charlson Comorbidity Index (±1) were enrolled (Controls). RESULTS: Of the 1282 patients with SARS-CoV-2 infection followed during the study period, 141 patients with obesity and 282 patients without were enrolled in the case and control groups, respectively. Considering matching variables, there was no statistical difference between the two groups. Patients in the Control group developed more frequently a mild-moderate disease (67% vs. 46.1%, respectively), whereas obese patients were more prone to need intensive care treatment (41.8% vs. 26.6%, respectively; p = 0.001). Moreover, the prevalence of death during hospitalization was higher in the Case group than in the Control group (12.1% vs. 6.4%, p = 0.046). DISCUSSION: We confirmed an association between obesity and severe outcome of patients with COVID-19, also considering other factors associated with a severe outcome of COVID-19. Thus, in the case of SARS-CoV-2 infection, the subjects with BMI ≥ 30 kg/m2 should be evaluated for early antiviral treatment to avoid the development of a severe course.

HIV and Drug-Resistant Subtypes.

Acquired Immunodeficiency Syndrome (AIDS) is a human viral infectious disease caused by the positive-sense single-stranded (ss) RNA Human Immunodeficiency Virus (HIV) (Retroviridae family, Ortervirales order). HIV-1 can be distinguished into various worldwide spread groups and subtypes. HIV-2 also causes human immunodeficiency, which develops slowly and tends to be less aggressive. HIV-2 only partially homologates to HIV-1 despite the similar derivation. Antiretroviral therapy (ART) is the treatment approved to control HIV infection, based on multiple antiretroviral drugs that belong to different classes: (i) NNRTIs, (ii) NRTIs, (iii) PIs, (iv) INSTIs, and (v) entry inhibitors. These drugs, acting on different stages of the HIV life cycle, decrease the patient's total burden of HIV, maintain the function of the immune system, and prevent opportunistic infections. The appearance of several strains resistant to these drugs, however, represents a problem today that needs to be addressed as best as we can. New outbreaks of strains show a widespread geographic distribution and a highly variable mortality rate, even affecting treated patients significantly. Therefore, novel treatment approaches should be explored. The present review discusses updated information on HIV-1- and HIV-2-resistant strains, including details on different mutations responsible for drug resistance.

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.

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.

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.

Infective endocarditis and diabetes mellitus: Results from a single-center study from 1994 to 2017.

BACKGROUND: To evaluate the prognostic impact of diabetes mellitus (DM) in patients with Infective Endocarditis (IE). METHODS AND RESULTS: 375 patients with diagnosis of IE referred to our Hospital between 1994-2017 were retrospectively included; diabetes was reported in 129 (34.4%). Diabetic patients were older than non-diabetic (66±1 vs. 57±2 years, p<0.001) and showed a higher prevalence of comorbidities such as hypertension (75 vs. 54%, p<0.001), coronary artery disease (30 vs. 12%, p<0.001) and history of heart failure (HF; 24 vs. 13%, p = 0.021). Echocardiography showed a higher incidence of paravalvular complications (82 vs. 64%, p<0.001) and a lower left ventricular ejection fraction (LVEF; 52±11 vs. 55±10%, p = 0.001) in diabetic than in non-diabetic patients. In-hospital mortality was higher in diabetic patients (83 vs. 74%; p = 0.030). At logistic regression, history of HF (OR = 3.1, 95%CI: 1.87-5.29, p<0.001) resulted an independent predictor of in-hospital death. At long-term follow-up [median 24(7-84) months], the Kaplan-Meier analysis showed a significantly lower survival free from all-cause death in the group with diabetes (Log-rank<0.001). At the propensity score adjusted Cox multivariable analysis, DM (HR = 1.76, 95%CI: 1.18-2.6, p = 0.005), age (HR = 1.03, 95%CI: 1.02-1.05, p<0.001), intravenous drug users (HR = 5.42, 95%CI: 2.55-11.51, p<0.001) and low LVEF (HR = 0.98, 95%CI: 0.96-0.99, p = 0.013) were independently associated to a higher mortality. CONCLUSION: In patients with IE, DM is associated to a higher prevalence of anatomic complications and a more impaired LVEF. Diabetic patients show a significantly lower survival both in hospital and during follow-up compared to the non-diabetic ones.

Alexithymia in HIV, HCV and coinfections.

Recent studies show that alexithymia, an impairment of emotional processing, plays a role in HIV and HCV infections, although little is known about about alexithymia in HIV/HCV coinfection. This study aimed to assess alexithymia in patients suffering from HIV, HCV or HIV/HCV coinfection and observe major differences. We selected 153 subjects, excluding those with psychiatric diagnosis, cognitive impairment or opportunistic diseases, of whom 70 (46%) had HIV infection, 57 (37%) HCV infection and 26 (17%) HIV/HCV coinfection. For the evaluation of alexithymia, we used the Toronto Alexithymia Scale (TAS-20), a self-report questionnaire which allows the results to be assessed both on a dimensional level and on defined cutoff scores. Data analysis showed significant differences between monoinfected and coinfected subjects. The coinfected group had a mean score of 54.00 ±13.43, higher than HIV (48.11 ± 12.38) and HCV (48.28 ± 10.71) (p <0.05). Furthermore, we found clinically relevant scores (≥51) in 65.38% of coinfected subjects, in 42.85% of HIV and in 40.35% of HCV (p <0.05). Given the medical and behavioral correlates of alexithymia highlighted in the literature, we suggest that further investigations are needed to clarify the relationship between alexithymia and HIV/HCV coinfection.

Kocuria kristinae endocarditis related to diabetic foot infection.

We report an unusual case of endocarditis occurring in a 74-year-old man with a history of systemic hypertension, diabetes mellitus and minor amputation for left forefoot ulcer. The patient was hospitalized for vacuum-assisted closure therapy to aid in wound healing. After the first treatment session, the patient reported abdominal pain with haematemesis and fever (40 °C). Owing to persistent fever, three blood cultures were performed, all positive for Kocuria kristinae. The identification was based on biochemical tests and automated systems. The speciation of the micro-organism was achieved with MALDI-TOF and then confirmed by 16S rRNA gene sequencing. Transthoracic echocardiographic examination showed the presence of a large vegetation (38×20 mm) on the posterior mitral leaflet and moderate mitral regurgitation. Since there are no current guidelines for the treatment of K. kristinae endocarditis, empiric antibiotic therapy with intravenous sulbactam/ampicillin (1.5 g twice daily) and gentamicin (6 mg kg(-1) per day) was started. After 7 days of hospitalization, the patient's condition suddenly worsened because of the occurrence of haemorrhagic stroke. Despite inotropic support and rifampicin infusion, the haemodynamic status progressively deteriorated. After an initial improvement, he worsened again, becoming stuporous, hypotensive and dyspnoeic. In the following days, the patient developed compartment syndrome resulting in right foot ischaemia. Unfortunately, 25 days after hospitalization, the patient died of multiple organ failure from overwhelming sepsis. To the best of our knowledge, this is the first case of K. kristinae endocarditis on a native valve that is not related to a central venous catheter but associated with diabetic foot infection.