Bronchoalveolar lavage fluid characteristics and outcomes of invasively mechanically ventilated patients with COVID-19 pneumonia in Genoa, Italy.

BACKGROUND: The primary objective of the study is to describe the cellular characteristics of bronchoalveolar lavage fluid (BALF) of COVID-19 patients requiring invasive mechanical ventilation; the secondary outcome is to describe BALF findings between survivors vs non-survivors. MATERIALS AND METHODS: Patients positive for SARS-CoV-2 RT PCR, admitted to ICU between March and April 2020 were enrolled. At ICU admission, BALF were analyzed by flow cytometry. Univariate, multivariate and Spearman correlation analyses were performed. RESULTS: Sixty-four patients were enrolled, median age of 64 years (IQR 58-69). The majority cells in the BALF were neutrophils (70%, IQR 37.5-90.5) and macrophages (27%, IQR 7-49) while a minority were lymphocytes, 1%, TCD3+ 92% (IQR 82-95). The ICU mortality was 32.8%. Non-survivors had a significantly older age (p = 0.033) and peripheral lymphocytes (p = 0.012) were lower compared to the survivors. At multivariate analysis the percentage of macrophages in the BALF correlated with poor outcome (OR 1.336, CI95% 1.014-1.759, p = 0.039). CONCLUSIONS: In critically ill patients, BALF cellularity is mainly composed of neutrophils and macrophages. The macrophages percentage in the BALF at ICU admittance correlated with higher ICU mortality. The lack of lymphocytes in BALF could partly explain a reduced anti-viral response.

Isolation of Candida auris from invasive and non-invasive samples of a patient suffering from vascular disease, Italy, July 2019.

We recently isolated Candida auris from a blood culture and cutaneous swabs of a patient in her mid-70s. Our routine phenotypic methods failed to identify the microorganism, but it was identified by molecular tests and MALDI-TOF MS analysis. Our report, the first from Italy, further underlines the geographically wide distribution of C. auris and the need to confirm species identification of any suspicious colony as soon as possible to stop its spread.

Pharmacokinetics of high-dose extended-infusion meropenem during pulmonary exacerbation in adult cystic fibrosis patients: a case series.

This case series explored the pharmacokinetic/pharmacodynamic (PK/PD) characteristics of meropenem (MEM) in adult cystic fibrosis (CF) patients hospitalized for a pulmonary exacerbation. From January 2015 to June 2016, all adult patients with cystic fibrosis (CF) and chronic pulmonary infection due to meropenem (MEM)-susceptible/intermediate Pseudomonas aeruginosa who received at least 48 h of MEM as an extended 3-hour infusion for treating a pulmonary exacerbation were enrolled. MEM plasma concentrations were determined by high-performance liquid chromatography. Six adult CF patients with a median age of 47 years were included in the study. MEM showed a high Vd (mean 45.98 L, standard deviation [SD] ±34.45). A minimal PK/PD target of 40% T > minimum inhibitory concentration (MIC) with respect to the MEM MIC of P. aeruginosa strains isolated from sputum during exacerbation was achieved in 5/6 patients (83%). MEM failed to achieve this target only in one patient, whose strain showed the highest MEM MIC in our cohort (8 mg/L). In all patients, MEM was well tolerated, and no adverse events were reported. In conclusion, high-dose, extended-infusion MEM during pulmonary exacerbation showed a high Vd in six adult CF patients with high median age, and was well tolerated.

First report of chronic pulmonary infection by KPC-3-producing and colistin-resistant Klebsiella pneumoniae sequence type 258 (ST258) in an adult patient with cystic fibrosis.

The spread of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae continues to increase, and the possible development of KPC-producing K. pneumoniae infections in cystic fibrosis (CF) patients is a matter of concern. Here, we describe the establishment of a chronic lung infection due to a colistin-resistant KPC-producing K. pneumoniae isolate in an Italian CF patient.

Nasal monkeypox virus infection successfully treated with cidofovir in a patient newly diagnosed with HIV.

Monkeypox (MPXV) usually causes a mild and self-limited infection. To date there are no data about cidofovir for the treatment for MPXV in humans. We report a case of a 25 years-old Brazilian man with a concurrent diagnosis of acute HIV (human immunodeficiency virus) infection, primary syphilis and MPXV infection with a nasal lesion successfully treated with intravenous cidofovir.

Kaposi-Juliusberg Varicelliform Eruption complicating Darier disease: May cannabinoid abuse be an underestimated risk factor?

Cannabinoid abuse may facilitate disseminated skin infection by herpes viruses in predisposed patients. These patients should be counselled about that.

The Longest Persistence of Viable SARS-CoV-2 With Recurrence of Viremia and Relapsing Symptomatic COVID-19 in an Immunocompromised Patient-A Case Study.

BACKGROUND: Immunocompromised patients show prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal swabs. We report a case of prolonged persistence of viable SARS-CoV-2 associated with clinical relapses of coronavirus disease 2019 (COVID-19) in a patient with mantle cell lymphoma who underwent treatment with rituximab, bendamustine, cytarabine with consequent lymphopenia and hypogammaglobulinemia. METHODS: Nasopharyngeal swabs and blood samples were tested for SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR). On 5 positive nasopharyngeal swabs, we performed viral culture and next-generation sequencing. We analyzed the patient's adaptive and innate immunity to characterize T- and NK-cell subsets. RESULTS: SARS-CoV-2 RT-PCR on nasopharyngeal swabs samples remained positive for 268 days. All 5 performed viral cultures were positive, and genomic analysis confirmed a persistent infection with the same strain. Viremia resulted positive in 3 out of 4 COVID-19 clinical relapses and cleared each time after remdesivir treatment. The T- and NK-cell dynamic was different in aviremic and viremic samples, and no SARS-CoV-2-specific antibodies were detected throughout the disease course. CONCLUSIONS: In our patient, SARS-CoV-2 persisted with proven infectivity for >8 months. Viremia was associated with COVID-19 relapses, and remdesivir treatment was effective in viremia clearance and symptom remission, although it was unable to clear the virus from the upper respiratory airways. During the viremic phase, we observed a low frequency of terminal effector CD8+ T lymphocytes in peripheral blood; these are probably recruited in inflammatory tissue for viral eradication. In addition, we found a high level of NK-cell repertoire perturbation with relevant involvement during SARS-CoV-2 viremia.

Higher Mortality and Intensive Care Unit Admissions in COVID-19 Patients with Liver Enzyme Elevations.

The aim of the present study is to evaluate if an independent association exists between liver enzyme elevations (LEE) and the risk of mortality or intensive care unit (ICU) admissions in patients with COVID-19. This was a single-center observational study, recruiting all consecutive adults with COVID-19. The elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) to the highest level between COVID-19 diagnosis and hospital discharge was categorized according to a standardized toxicity grade scale. In total, 799 patients were included in this study, 39% of which were female, with a mean age of 69.9 (±16.0) years. Of these patients, 225 (28.1%) developed LEE of grade ≥2 after a median of three days (interquartile range (IQR): 0-8 days) from the diagnosis of COVID-19, and they were estimated to have a higher hazard of death or ICU admission (adjusted hazard ratio (aHR): 1.46, 95% confidence interval (CI): 1.14-1.88). The clinical and laboratory variables associated with the development of LEE were male sex, higher respiratory rate, higher gamma glutamyl transpeptidase (GGT) and lower albumin levels at baseline. Among the analyzed treatments, steroids, tocilizumab and darunavir/ritonavir correlated with LEE. In conclusion, LEE were associated with mortality and ICU admission among COVID-19 patients. While the origin of LEE is probably multifactorial, LEE evaluation could add information to the clinical and laboratory variables that are commonly evaluated during the course of COVID-19.

Clinical characteristics, management and in-hospital mortality of patients with coronavirus disease 2019 in Genoa, Italy.

OBJECTIVES: To describe clinical characteristics, management and outcome of individuals with coronavirus disease 2019 (COVID-19); and to evaluate risk factors for all-cause in-hospital mortality. METHODS: This retrospective study from a University tertiary care hospital in northern Italy, included hospitalized adult patients with a diagnosis of COVID-19 between 25 February 2020 and 25 March 2020. RESULTS: Overall, 317 individuals were enrolled. Their median age was 71 years and 67.2% were male (213/317). The most common underlying diseases were hypertension (149/317; 47.0%), cardiovascular disease (63/317; 19.9%) and diabetes (49/317; 15.5%). Common symptoms at the time of COVID-19 diagnosis included fever (285/317; 89.9%), shortness of breath (167/317; 52.7%) and dry cough (156/317; 49.2%). An 'atypical' presentation including at least one among mental confusion, diarrhoea or nausea and vomiting was observed in 53/317 patients (16.7%). Hypokalaemia occurred in 25.8% (78/302) and 18.5% (56/303) had acute kidney injury. During hospitalization, 111/317 patients (35.0%) received non-invasive respiratory support, 65/317 (20.5%) were admitted to the intensive care unit (ICU) and 60/317 (18.5%) required invasive mechanical ventilation. All-cause in-hospital mortality, assessed in 275 patients, was 43.6% (120/275). On multivariable analysis, age (per-year increase OR 1.07; 95% CI 1.04-1.10; p < 0.001), cardiovascular disease (OR 2.58; 95% CI 1.07-6.25; p 0.03), and C-reactive protein levels (per-point increase OR 1.009; 95% CI 1.004-1.014; p 0.001) were independent risk factors for all-cause in-hospital mortality. CONCLUSIONS: COVID-19 mainly affected elderly patients with predisposing conditions and caused severe illness, frequently requiring non-invasive respiratory support or ICU admission. Despite supportive care, COVID-19 remains associated with a substantial risk of all-cause in-hospital mortality.

Tocilizumab and steroid treatment in patients with COVID-19 pneumonia.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome. METHODS: This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. SOC consisted of hydroxychloroquine 400mg bid plus, in those admitted before March 24th, also darunavir/ritonavir. Anti-inflammatory treatment consisted of either tocilizumab (8mg/kg intravenously or 162mg subcutaneously) or methylprednisolone 1 mg/kg for 5 days or both. Failure was defined as intubation or death, and the endpoints were failure-free survival (primary endpoint) and overall survival (secondary) at day 30. Difference between the groups was estimated as Hazard Ratio by a propensity score weighted Cox regression analysis (HROW). RESULTS: Overall, 196 adults were included in the analyses. They were mainly male (67.4%), with comorbidities (78.1%) and severe COVID-19 pneumonia (83.7%). Median age was 67.9 years (range, 30-100) and median PaO2/FiO2 200 mmHg (IQR 133-289). Among them, 130 received early anti-inflammatory treatment with: tocilizumab (n = 29, 22.3%), methylprednisolone (n = 45, 34.6%), or both (n = 56, 43.1%). The adjusted failure-free survival among tocilizumab/methylprednisolone/SOC treated patients vs. SOC was 80.8% (95%CI, 72.8-86.7) vs. 64.1% (95%CI, 51.3-74.0), HROW 0.48, 95%CI, 0.23-0.99; p = 0.049. The overall survival among tocilizumab/methylprednisolone/SOC patients vs. SOC was 85.9% (95%CI, 80.7-92.6) vs. 71.9% (95%CI, 46-73), HROW 0.41, 95%CI: 0.19-0.89, p = 0.025. CONCLUSION: Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients with COVID-19 pneumonia.

Respiratory Fungal Diseases in Adult Patients With Cystic Fibrosis.

Clinical manifestations of respiratory fungal diseases in adult cystic fibrosis (CF) patients are very heterogeneous, ranging from asymptomatic colonization to chronic infections, allergic disorders, or invasive diseases in immunosuppressed CF patients after lung transplantation. In this narrative review, mainly addressed to clinicians without expertise in CF who may nonetheless encounter adult CF patients presenting with acute and chronic respiratory syndromes, we briefly summarize the most representative clinical aspects of respiratory fungal diseases in adult CF patients.

Clinical performance of the (1,3)-ß-D-glucan assay in early diagnosis of nosocomial Candida bloodstream infections.

Microbiological diagnosis of nosocomial candidemia is negatively affected by suboptimal culture yield. Alternative methods are not fully reliable as an aid in candidemia diagnosis. Recently, the detection of (1,3)-ß-D-glucan (BG) has been shown to be very promising in this setting. We carried out a prospective study on the clinical usefulness of BG detection in early diagnosis of candidemia. BG detection was performed in patients with fever unresponsive to antibacterial agents and risk factors for candidemia. BG detection was done with the Fungitell test. A total of 152 patients were included in the study; 53 were proven to have candidemia, while in 52 patients candidemia was excluded on microbiological and clinical bases. The remaining 47 patients were considered to have possible candidemia. In summary, 41 of 53 candidemia patients (77.3%), 9 of 52 patients without candidemia (17.3%), and 38 of 47 patients with possible candidemia (80.8%) were positive in the BG assay. With these results, the sensitivity and the specificity of the assay were 77% and 83%, respectively. BG levels of >160 pg/ml were highly predictive of candidemia. In 36 of 41 patients with candidemia and positive BG testing, the BG assay was performed within 48 h from when the first Candida-positive blood sample for culture was drawn, thus allowing a possible earlier start of antifungal therapy. Based on these results, the BG assay may be used as an aid in the diagnosis of nosocomial candidemia. The timing of assay performance is critical for collecting clinically useful information. However, the test results should be associated with clinical data.

Clinical evaluation of a (1,3)-beta-D-glucan assay for presumptive diagnosis of Pneumocystis jiroveci pneumonia in immunocompromised patients.

(1,3)-beta-d-Glucan (BG) is a component of the Pneumocystis jiroveci cell wall. Thirty-one immunocompromised patients with pneumonia (16 with presumptive pneumocystis pneumonia [PCP] and 15 with non-PCP) were evaluated for serum BG levels. Serum from all 16 presumptive PCP patients and from 2/15 patients with non-PCP was positive for BG. Results indicate that BG is a reliable marker for diagnosing PCP.