Objectives Aim of our study was to describe the incidence and predictive factors of secondary infections in patients with COVID-19. Methods Cohort study on patients hospitalized with COVID-19 at IRCCS San Raffaele Hospital between February 25 th and April 6th, 2020 (NCT04318366). We considered secondary bloodstream (BSIs) or possible lower respiratory tract infections (pLRTIs) occurred after 48 hours since hospital admission until death or discharge. We calculated multivariable Fine-Gray models, to assess factors associated with risk of secondary infections. Results Among 731 patients, a secondary infection was diagnosed in 68 patients (9.3%): 58/731 patients (7.9%) had at least one BSI and 22/731 patients (3.0%) at least one pLRTI. Overall 28-day cumulative incidence was 16.4% (95% CI 12.4% - 21.0%). The majority of BSIs was due to gram-positive pathogens (76/106 isolates, 71.7%), specifically coagulase-negative staphylococci (53/76, 69.7%), while among gram-negatives (23/106, 21.7%) Acinetobacter baumanii (7/23, 30.4%) and Escherichia coli (5/23, 21.7%) predominated. pLRTIs were mainly caused by gram-negative pathogens (14/26, 53.8%). Eleven patients were diagnosed with putative invasive aspergillosis. At multivariable analysis, factors associated with secondary infections were low baseline lymphocyte count ( < 0.7 vs >0.7 per 10 9 /L: subdistribution hazard ratios (sdHRs) 1.93 [95% CI 1.11-3.35]), baseline PaO 2 /FiO 2 (per 100-points lower: sdHRs 1.56 [95% CI 1.21-2.04]), and intensive-care unit (ICU) admission in the first 48 hours (sdHR 2.51 [95% CI 1.04-6.05]). Conclusions Patients hospitalized with COVID-19 had a high incidence of secondary infections. At multivariable analysis, early need for ICU, respiratory failure, and severe lymphopenia, were identified as risk factors for secondary infections.

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The aim of this study was to evaluate the impact of early treatment with corticosteroids on SARS-CoV-2 clearance in hospitalized COVID-19 patients. Retrospective analysis on patients admitted to the San Raffaele Hospital (Milan, Italy) with moderate/severe COVID-19 and availability of at least two nasopharyngeal swabs. The primary outcome was the time to nasopharyngeal swab negativization. A multivariable Cox model was fitted to determine factors associated with nasopharyngeal swab negativization. Of 280 patients included, 59 (21.1%) patients were treated with steroids. Differences observed between steroid users and non-users included the proportion of patients with a baseline PaO2/FiO2 ≤ 200 mmHg (45.8% vs 34.4% in steroids and non-steroids users, respectively; p = 0.023) or ≤ 100 mmHg (16.9% vs 12.7%; p = 0.027), and length of hospitalization (20 vs 14 days; p < 0.001). Time to negativization of nasopharyngeal swabs was similar in steroid and non-steroid users (p = 0.985). According to multivariate analysis, SARS-CoV-2 clearance was associated with age ≤ 70 years, a shorter duration of symptoms at admission, a baseline PaO2/FiO2 > 200 mmHg, and a lymphocyte count at admission > 1.0 × 109/L. SARS-CoV-2 clearance was not associated with corticosteroid use. Our study shows that delayed SARS-CoV-2 clearance in moderate/severe COVID-19 is associated with older age and a more severe disease, but not with an early use of corticosteroids.

Background: cerebral microcirculation might reveal important prognostic information for acute ischemic stroke. Time-Domain Near-Infrared Spectroscopy (TD-NIRS) is an advanced optical technique that estimates quantitatively and non-invasively the oxygenation in microcirculation of cerebral outer layers at the bedside of the patient. We aimed to measure hemoglobin species and tissue oxygen saturation in acute ischemic stroke patients comparing them to controls according to brain areas and large vessel recanalization status. Methods: TD-NIRS measurements within 24 h of stroke onset (1 st time point) and after 24 h (2 nd time point) were performed on anterior circulation stroke patients classified as lacunar and recanalized or non-recanalized partial/total anterior circulation syndrome. Fiducial markers categorized the brain region below each TD-NIRS probe as ischemic or non-stroke areas. We evaluated the concentration of deoxyhemoglobin (HbR), oxyhemoglobin (HbO), total hemoglobin (HbT) and tissue oxygen saturation (StO 2 ) and assessed differences compared to control subjects and according to large vessel occlusion. Results: TD-NIRS measurements were performed on 47 acute ischemic stroke patients. At 1 st time point the ischemic area had higher HbR and HbT compared to controls in both recanalized (p=8.2·10 -4 ; p=0.03) and non-recanalized patients (p=4.9·10 -3 , p=0.03), but lower StO 2 only in recanalized patients (p=0.015). The ischemic area of recanalized patients had higher concentration of HbR, HbO, HbT compared to the ipsilateral non-stroke area (p=0.01; p=3.6·10 -3 ; p=2.0·10 -3 ). The same pattern was observed at 2 nd time point. Recanalized patients had lower mean StO 2 in the ipsilateral hemisphere compared to non-recanalized patients at both time points (p=0.016, p=0.011). Conclusions: TD-NIRS can be performed during routine Stroke Unit activity and it is able to detect significant differences in hemoglobin species in large vessels ischemic stroke patients compared to controls. Data suggest that StO 2 could serve as surrogate functional marker of the metabolic activity of the rescued brain tissue.

Large vessel occlusion (LVO) stroke might cause different degrees of hemodynamic impairment that affects microcirculation and contributes to metabolic derangement. Time-domain near-infrared spectroscopy (TD-NIRS) estimates the oxygenation of microcirculation of cerebral outer layers. We measure hemoglobin species and tissue oxygen saturation (StO 2) of anterior circulation stroke patients, classified as LVO or lacunar, and assess the differences compared with controls and according to LVO recanalization status. Fiducial markers categorize the brain region below each TD-NIRS probe as ischemic or nonstroke areas. The study includes 47 consecutive acute ischemic stroke patients and 35 controls. The ischemic area has significantly higher deoxy-hemoglobin (HbR) and total hemoglobin (HbT) compared with controls in both recanalized and nonrecanalized patients but lower StO 2 only in recanalized patients. Recanalized patients have significantly lower mean StO 2 in the ipsilateral hemisphere compared with nonrecanalized patients. This is the first study to report TD-NIRS measurements in acute ischemic stroke patients. TD-NIRS is able to detect significant differences in hemoglobin species in LVO stroke compared with controls and according to recanalization status. This preliminary data might suggest that StO 2 can serve as a surrogate functional marker of the metabolic activity of rescued brain tissue.