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 24 th , 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

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.

Objectives: To investigate the first Italian outbreak of bloodstream infections caused by multidrugresistant (MDR) Klebsiella pneumoniae producing metallo-b-lactamase (MBL), which occurred in three wards of one large tertiary-care hospital in Genoa, Italy, from September 2004 to March 2005.Methods: MBL production was screened by an imipenem-EDTA disc synergy test and confirmed by a conventional hydrolysis test. Antibiotic susceptibility was determined by broth microdilution or disc diffusion. PFGE was used to study the genetic relatedness of isolates. PCR and sequencing were carried out to identify the b-lactamase genes and to analyse the genetic context of the MBL gene. Outer membrane protein (OMP) profiles were analysed by SDS-PAGE.Results: Nine cases of bloodstream infections caused by an MDR strain of K. pneumoniae producing the VIM-1 MBL and the SHV-5 extended-spectrum b-lactamase (ESBL) were identified. The isolates exhibited various carbapenem resistance levels (imipenem MICs ranged from 4 to 64 mg/L) and were resistant to other b-lactams, fluoroquinolones, trimethoprim/sulfamethoxazole and chloramphenicol. The isolate with the highest imipenem MIC also lacked the k36 OMP. The bla VIM-1 gene cassette was part of the variable region of a class 1 integron that also included an aac(6 0 )-IIc cassette. The ESBL and MBL genes were transferable by conjugation.Conclusions: This is the first report on the emergence of an MDR strain of K. pneumoniae producing the VIM-1 MBL, causing an outbreak of bloodstream infections in an Italian hospital. The strain evolved through OMP alterations generating a mutant with increased carbapenem resistance.

Background The prevalence of kidney involvement during SARS-CoV-2 infection has been reported to be high. Nevertheless, data are lacking about the determinants of acute kidney injury (AKI) and the combined effect of chronic kidney disease (CKD) and AKI in COVID-19 patients. Methods We collected data on patient demographics, comorbidities, chronic medications, vital signs, baseline laboratory test results and in-hospital treatment in patients with COVID-19 consecutively admitted to our Institution. Chronic kidney disease was defined as eGFR < 60 mL/min per 1.73 m2 or proteinuria at urinalysis within 180 days prior to hospital admission. AKI was defined according to KDIGO criteria. The primary and secondary outcomes were the development of AKI and death. Results Of 777 patients eligible for the study, acute kidney injury developed in 176 (22.6%). Of these, 79 (45%) showed an acute worsening of a preexisting CKD, and 21 (12%) required kidney replacement therapy. Independent associates of AKI were chronic kidney disease, C-reactive protein (CRP) and ventilation support. Among patients with acute kidney injury, 111 died (63%) and its occurrence increased the risk of death by 60% (HR 1.60 [95% IC 1.21–2.49] p = 0.002) independently of potential confounding factors including hypertension, preexisting kidney damage, and comorbidities. Patients with AKI showed a significantly higher rate of deaths attributed to bleeding compared to CKD and the whole population (7.5 vs 1.5 vs 3.5%, respectively). Conclusion Awareness of kidney function, both preexisting CKD and development of acute kidney injury, may help to identify those patients at increased risk of death.

Correlates for the initiation of Mycobacterium tuberculosis hominis (Mth) replication from latency are needed in order to improve Mth control. In order to analyze if perturbations of peripheral NK cells may be associated with exit from Mth latency, sequential patients with newly diagnosed lung tuberculosis (TB) were studied. Peripheral NK cells were analyzed by cytofluorometry, in vitro culture and functional assays. At the onset of lung TB, imbalances in NK cell subsets were evident. Decreased CD56(bright)CD16(+/-) subsets with significantly compromised NKp30 and NKp46 expression and with specifically decreased gamma-IFN production upon triggering were evident. These features were not completely restored when purified NK cells were cultured in vitro. Culture supplementation with alpha-IFN increased only NKp30 expression in TB and healthy donors. Extensive peripheral NK cell triggering was evident in these patients, as shown by the expression of NK cell activation markers and of the lymph node-homing chemokine receptor CCR7 on CD16(+) CD56(dull) cells. Significant persistence of decreased NKp30 and NKp46 after successful treatment with a standard four-drug regimen was detected after full recovery. NK cell function is deeply affected in patients at the onset of pulmonary TB. The involvement of multiple activatory receptors may provide a relevant contribution to the spread of mycobacteria exiting from latency.