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Background Few small studies have described hospital-acquired infections (HAIs) during COVID-19. Research Question What patient characteristics in critically ill patients with COVID-19 are associated with HAIs and how do HAIs associate with outcomes in these patients? Study Design and Methods Multicenter retrospective analysis of prospectively collected data including adult patients with severe COVID-19, admitted to 8 Italian hub hospitals from February 20, 2020, to May 20, 2020. Descriptive statistics, univariable and multivariable Weibull regression models were used to assess incidence, microbial etiology, resistance patterns, risk factors (i.e., demographics, comorbidities, exposure to medication), and impact on outcomes (i.e., ICU survival, length of ICU and hospital stay and duration of mechanical ventilation) of microbiologically-confirmed HAIs. Results Of the 774 included patients, 359 (46%) patients developed 759 HAIs (44.7 infections/1000 ICU patient-days, 35% multi-drug resistant (MDR) bacteria). Ventilator-associated pneumonia (VAP) (389, 50%), bloodstream infections (183, 34%), and catheter related blood stream infections (74, 10%) were the most frequent HAIs, with 26.0 (23.6-28.8) VAPs/1000 patient intubation-days, 11.7(10.1-13.5) BSIs/1000 ICU patient-days, and 4.7 (3.8-5.9) CRBSIs/1000 patient-days. Gram-negative bacteria (especially Enterobacterales ) and Staphylococcus aureus caused 64% and 28% of VAPs. Variables independently associated with infection were age, PEEP and treatment with broad-spectrum antibiotic at admission. 234 patients (30%) died in ICU (15.3 deaths/1000 ICU patient-days). Patients with HAIs complicated by septic shock had almost doubled mortality (52% vs. 29%), while non-complicated infections did not affect mortality. HAIs prolonged mechanical ventilation (24(14-39) vs. 9(5-13) days; p<0.001), ICU and hospital stay (24(16-41) vs. 9(6-14) days, p=0.003; and (42(25-59) vs. 23(13-34) days, p<0.001). Interpretation Critically-ill COVID-19 patients are at high risk for HAIs, especially VAPs and BSIs due to MDR organisms. HAIs prolong mechanical ventilation and hospitalization, and HAIs complicated by septic-shock almost doubled mortality.

Objectives: The management of healthcare workers (HCWs) exposed to confirmed cases of coronavirus disease 2019 (COVID-19) is still a matter of debate. We aimed to assess in this group the attack rate of asymptomatic carriers and the symptoms most frequently associated with infection. Methods: Occupational and clinical characteristics of HCWs who underwent nasopharyngeal swab testing for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a university hospital from 24 February 2020 to 31 March 2020 were collected. For those who tested positive and for those who tested positive but who were asymptomatic, we checked the laboratory and clinical data as of 22 May to calculate the time necessary for HCWs to then test negative and to verify whether symptoms developed thereafter. Frequencies of positive tests were compared according to selected variables using multivariable logistic regression models. Results: There were 139 positive tests (8.8%) among 1573 HCWs (95% confidence interval, 7.5e10.3), with a marked difference between symptomatic (122/503, 24.2%) and asymptomatic (17/1070, 1.6%) workers (p < 0.001). Physicians were the group with the highest frequency of positive tests (61/582, 10.5%), whereas clerical workers and technicians had the lowest frequency (5/137, 3.6%). The likelihood of testing positive for COVID-19 increased with the number of reported symptoms; the strongest predictors of test positivity were taste and smell alterations (odds ratio ¼ 76.9) and fever (odds ratio ¼ 9.12). The median time from first positive test to a negative test was 27 days (95% confidence interval, 24e30). Conclusions: HCWs can be infected with SARS-CoV-2 without displaying any symptoms. Among symptomatic HCWs, the key symptoms to guide diagnosis are taste and smell alterations and fever. A median of almost 4 weeks is necessary before nasopharyngeal swab test results are negative.

Background: Immunomodulants have been proposed to mitigate severe acute respiratory syndrome coronavirus 2-induced cytokine storm, which drives acute respiratory distress syndrome in coronavirus disease 2019 . Objective: We sought to determine efficacy and safety of the association of IL-1 receptor antagonist anakinra plus methylprednisolone in severe COVID-19 pneumonia with hyperinflammation. Methods: A secondary analysis of prospective observational cohort studies was carried out at an Italian tertiary health care facility. COVID-19 patients consecutively hospitalized (February 25, 2020, to March 30, 2020 with hyperinflammation (ferritin > _1000 ng/mL and/or C-reactive protein >10 mg/dL) and respiratory failure (oxygen therapy from 0.4 FiO 2 Venturi mask to invasive mechanical ventilation) were evaluated to investigate the effect of high-dose anakinra plus methylprednisolone on survival. Patients were followed from study inclusion to day 28 or death. Crude and adjusted (sex, age, baseline PaO 2 :FiO 2 ratio, Charlson index, baseline mechanical ventilation, hospitalization to inclusion lapse) risks were calculated (Cox proportional regression model). Results: A total of 120 COVID-19 patients with hyperinflammation (median age, 62 years; 80.0% males; median PaO 2 :FiO 2 ratio, 151; 32.5% on mechanical ventilation) were evaluated. Of these, 65 were treated with anakinra and methylprednisolone and 55 were untreated historical controls. At 28 days, mortality was 13.9% in treated patients and 35.6% in controls (Kaplan-Meier plots, P 5 .005). Unadjusted and adjusted risk of death was significantly lower for treated patients compared with controls (hazard ratio, 0.33, 95% CI, 0.15-0.74, P 5 .007, and HR, 0.18, 95% CI, 0.07-0.50, P 5 .001, respectively). No significant differences in bloodstream infections or laboratory alterations were registered. Conclusions: Treatment with anakinra plus methylprednisolone may be a valid therapeutic option in COVID-19 patients with hyperinflammation and respiratory failure, also on mechanical ventilation. Randomized controlled trials including the use of either agent alone are needed to confirm these results. (J Allergy Clin Immunol 2021;147:561-6.)