The Effects of GCSF Primary Prophylaxis on Survival Outcomes and Toxicity in Patients with Advanced Non-Small Cell Lung Cancer on First-Line Chemoimmunotherapy: A Sub-Analysis of the Spinnaker Study.

GCSF prophylaxis is recommended in patients on chemotherapy with a >20% risk of febrile neutropenia and is to be considered if there is an intermediate risk of 10−20%. GCSF has been suggested as a possible adjunct to immunotherapy due to increased peripheral neutrophil recruitment and PD-L1 expression on neutrophils with GCSF use and greater tumour volume decrease with higher tumour GCSF expression. However, its potential to increase neutrophil counts and, thus, NLR values, could subsequently confer poorer prognoses on patients with advanced NSCLC. This analysis follows on from the retrospective multicentre observational cohort Spinnaker study on advanced NSCLC patients. The primary endpoints were OS and PFS. The secondary endpoints were the frequency and severity of AEs and irAEs. Patient information, including GCSF use and NLR values, was collected. A secondary comparison with matched follow-up duration was also undertaken. Three hundred and eight patients were included. Median OS was 13.4 months in patients given GCSF and 12.6 months in those not (p = 0.948). Median PFS was 7.3 months in patients given GCSF and 8.4 months in those not (p = 0.369). A total of 56% of patients receiving GCSF had Grade 1−2 AEs compared to 35% who did not receive GCSF (p = 0.004). Following an assessment with matched follow-up, 41% of patients given GCSF experienced Grade 1−2 irAEs compared to 23% of those not given GCSF (p = 0.023). GCSF prophylaxis use did not significantly affect overall or progression-free survival. Patients given GCSF prophylaxis were more likely to experience Grade 1−2 adverse effects and Grade 1−2 immunotherapy-related adverse effects.

External validation of unsupervised COVID-19 clinical phenotypes and their prognostic impact.

BACKGROUND: Hospitalized patients with coronavirus disease 2019 (COVID-19) can be classified into different clinical phenotypes based on their demographic, clinical, radiology, and laboratory features. We aimed to validate in an external cohort of hospitalized COVID-19 patients the prognostic value of a previously described phenotyping system (FEN-COVID-19) and to assess the reproducibility of phenotypes development as a secondary analysis. METHODS: Patients were classified in phenotypes A, B or C according to the severity of oxygenation impairment, inflammatory response, hemodynamic and laboratory tests according to the FEN-COVID-19 method. RESULTS: Overall, 992 patients were included in the study, and 181 (18%), 757 (76%) and 54 (6%) of them were assigned to the FEN-COVID-19 phenotypes A, B, and C, respectively. An association with mortality was observed for phenotype C vs. A (hazard ratio [HR] 3.10, 95% confidence interval [CI] 1.81-5.30, p < 0.001) and for phenotype C vs. B (HR 2.20, 95% CI 1.50-3.23, p < 0.001). A non-statistically significant trend towards higher mortality was also observed for phenotype B vs. A (HR 1.41; 95% CI 0.92-2.15, p = 0.115). By means of cluster analysis, three different phenotypes were also identified in our cohort, with an overall similar gradient in terms of prognostic impact to that observed when patients were assigned to FEN-COVID-19 phenotypes. CONCLUSIONS: The prognostic impact of FEN-COVID-19 phenotypes was confirmed in our external cohort, although with less difference in mortality between phenotypes A and B than in the original study.

Hospitalized patients with COVID-19 can be classified into different clinical phenotypes based on their demographic, clinical, radiology, and laboratory featuresIn this study, we externally confirmed the prognostic impact of clinical phenotypes previously identified by Gutierrez-Gutierrez and colleagues in a Spanish cohort of hospitalized patients with COVID-19, and the usefulness of their simplified probabilistic model for phenotypes assignmentThis could indirectly support the validity of both phenotype's development and their extrapolation to other hospitals and countries for management decisions during other possible future viral pandemics.

Role of Renal Parenchyma Attenuation and Perirenal Fat Stranding in Chest CT of Hospitalized Patients with COVID-19.

BACKGROUND: Chest CT on coronavirus disease (COVID-19) has been extensively investigated. Acute kidney injury (AKI) has been widely described among COVID patients, but the role of kidney imaging has been poorly explored. The aim of this study is to clarify the role of opportunistic kidney assessment on non-enhanced chest CT. METHODS: We collected data on patients with COVID-19 consecutively admitted to our institution who underwent chest CT (including the upper parts of kidneys as per protocol). Three ROIs of 0.5-0.7 cm2 were positioned in every kidney. The values of renal parenchyma attenuation (RPA) and the presence of perirenal fat stranding (PFS) were analyzed. The primary and secondary outcomes were the occurrence of AKI and death. RESULTS: 86 patients with COVID-19 and unenhanced chest CT were analyzed. The cohort was split into CT RPA quartiles. Patients with a CT RPA <24 HU were more likely to develop AKI when compared with other patients (χ2 = 2.77, p = 0.014): at multivariate logistic regression analysis, being in the first quartile of CT RPA was independently associated with a four times higher risk of AKI (HR 4.56 [95% CI 1.27-16.44, p = 0.020). Within a mean 22 ± 15 days from admission, 32 patients died (37.2%). Patients with PFS were more likely to die as compared to patients without it (HR 3.90 [95% CI 1.12-13.48], p = 0.031). CONCLUSIONS: Detection of low RPA values and of PFS in COVID-19 patients independently predicts, respectively, the occurrence of AKI and an increased risk for mortality. Therefore, opportunistic kidney assessment during chest CT could help physicians in defining diagnostic and therapeutic strategies.

Management of the Medico-Legal Dispute of Healthcare-Related SARS-CoV-2 Infections: Evaluation Criteria and Case Study in a Large University Hospital in Northwest Italy from 2020 to 2021.

Healthcare-related SARS-CoV-2 infection is an issue of particular concern during the pandemic. It has important repercussions on the National Health System, which represents a source of medical-legal health disputes. In the healthcare context, there are reports of negative screening at hospital admission (via nasopharyngeal swabs) and subsequent diagnosis of SARS-CoV-2 infection during hospitalization. Such cases cannot be considered a priori of healthcare-related infections but require extensive in-depth evaluation. In this study, we propose an empirical classification to frame cases of SARS-CoV-2 infection diagnosed in the hospital (first negative admission swab, with subsequent positive test during hospitalization). The classification is based on five categories: nosocomial, probably nosocomial, indeterminate, probably community, and community cases. We analyzed patients who died after testing positive for SARS-CoV-2 during hospitalization (with initial negative screening) in the largest hospital in Northwest Italy from February 2020 to 31 December 2021. A total of 383 cases were tracked and are listed as follows: 41 cases (11%) were classified as nosocomial (i.e., 3.2% of COVID-19 deaths). In contrast, 71 cases (19%) were classified as probably nosocomial, 69 (18%) were indeterminate (i.e., the clinical, radiological, and laboratory characteristics did not provide information on the genesis of the infection), 166 (43%) were classified as probably community cases, and 36 (9%) were defined as community cases. Deceased patients with nosocomial SARS-CoV-2 infection constituted the following: 3.23% (41/1266) with respect to the total number of COVID-19 deaths, 1.1% (41/3789) with respect to those who entered the hospital with a negative swab and 0.82% (41/4672) with respect to the total of deaths from any cause of death. In this paper we discuss the topic and issues of nosocomial COVID-19 in hospitalized patients and address the medicolegal implications.

Healthcare Worker Study Cohort to Determine the Level and Durability of Cellular and Humoral Immune Responses after Two Doses of SARS-CoV-2 Vaccination.

We prospectively studied immunological response against SARS-CoV-2 after vaccination among healthcare workers without (group A) and with previous infection (group B). The analyses were collected at T0 (before the BNT162b2), T1 (before the second dose), T2 and T6 (1 and 6 months after the second dose). For cellular immune response, the activation-induced cell marker assay was performed with CD4 and CD8 Spike peptide megapools expressed as Stimulation Index. For humoral immune response, we determined antibodies to Spike-1 and nucleocapsid protein. The linear mixed model compared specific times to T0. The CD4+ Spike response overall rate of change was significant at T1 (p = 0.038) and at T2 (p < 0.001), while decreasing at T6. For CD8+ Spike reactivity, the interaction between the time and group was significant (p = 0.0265), and the p value for group comparison was significant at the baseline (p = 0.0030) with higher SI in previously infected subjects. Overall, the anti-S Abs significantly increased from T1 to T6 compared to T0. The group B at T6 retained high anti-S titer (p < 0.001). At T6, in both groups we found a persistent humoral response and a high CD4+ T cell response able to cross recognize SARS-COV-2 variants including epsilon, even if not a circulating virus at that time.

AKI and Renal Parenchyma Attenuation in Hospitalized Patients With COVID-19

BACKGROUND AND AIMS Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a worldwide spread since early 2020 and a lot of studies concerning the diagnostic and prognostic role of chest computed tomography (CT) on coronavirus disease (COVID-19) has been published. Renal involvement might be present in up to 75% of cases, significantly impacting on the prognosis. The aim of this study is to clarify the role of opportunistic kidney assessment on non-enhanced chest CT and to evaluate if radiological findings could be associated with relevant clinical information regarding kidney function and patient's prognosis in hospitalized patients with COVID-19. METHOD 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 who underwent chest CT. The standard chest CT-scan acquired in full inspiration include large part of both kidneys as per protocol. Three regions of interest (ROI) of 0.5–0.7 cm2 were positioned in every kidney, right and left to include both the cortex and the medulla. The mean values of attenuation of kidney regions were analysed. The primary and secondary outcomes were the occurrence of acute kidney injury (AKI), in-hospital and 9 months of death for all causes. RESULTS A total of 86 patients with COVID-19 and unenhanced chest CT were analyzed splitting the cohort into CT renal parenchyma attenuation (RPA) quartiles. Patients with a CT RPA below 24 Hounsfield unit (HU) were more likely to develop AKI when compared with other patients (×2 = 2.77, P = .014). An AKI-specific cut-off point of RPA was identified by performing a survival receiver operating characteristic (ROC) curve. At multivariate logistic regression analysis, being in the first quartile of CT RPA was associated with a four-times higher risk of AKI (Table 1) after adjustment for age, gender, hypertension, kidney function at admission and other comorbidities. During a mean 22 ± 15 days of admission, 32 patients died (37.2%). Patients with lower values of RPA at CT (first quartile, <24 HU) were not at a higher risk of death compared with patients with RPA ≥ 24 HU, as shown by Kaplan Maier curve (Fig. 1) and by multivariate Cox regression analysis [HR 1.84 (95% CI 0.82–4.13);P = .14].Figure 1: Data patients, grouped by AKI situation (without AKI, AKI on arrival or AKI during admission). CONCLUSION The association between AKI and RPA < 24 HU was independent of age, gender, creatinine and comorbidities. RPA values seemed to be predictive of AKI development in COVID-19 patients who underwent chest CT, suggesting RPA values could significantly improve patients’ care. The opportunistic measure of RPA could help physicians identifying patients with a higher risk of AKI, and this increased awareness could guide choices for diagnostic and therapeutic procedures.

Prognostic Impact of Bronchoalveolar Lavage Fluid Galactomannan and Aspergillus Culture Results on Survival in COVID-19 Intensive Care Unit Patients: a Post Hoc Analysis from the European Confederation of Medical Mycology (ECMM) COVID-19-Associated Pulmonary Aspergillosis Study.

Critically ill patients with coronavirus disease 2019 (COVID-19) may develop COVID-19-associated pulmonary aspergillosis (CAPA), which impacts their chances of survival. Whether positive bronchoalveolar lavage fluid (BALF) mycological tests can be used as a survival proxy remains unknown. We conducted a post hoc analysis of a previous multicenter, multinational observational study with the aim of assessing the differential prognostic impact of BALF mycological tests, namely, positive (optical density index of ≥1.0) BALF galactomannan (GM) and positive BALF Aspergillus culture alone or in combination for critically ill patients with COVID-19. Of the 592 critically ill patients with COVID-19 enrolled in the main study, 218 were included in this post hoc analysis, as they had both test results available. CAPA was diagnosed in 56/218 patients (26%). Most cases were probable CAPA (51/56 [91%]) and fewer were proven CAPA (5/56 [9%]). In the final multivariable model adjusted for between-center heterogeneity, an independent association with 90-day mortality was observed for the combination of positive BALF GM and positive BALF Aspergillus culture in comparison with both tests negative (hazard ratio, 2.53; 95% CI confidence interval [CI], 1.28 to 5.02; P = 0.008). The other independent predictors of 90-day mortality were increasing age and active malignant disease. In conclusion, the combination of positive BALF GM and positive BALF Aspergillus culture was associated with increased 90-day mortality in critically ill patients with COVID-19. Additional study is needed to explore the possible prognostic value of other BALF markers.

Investigating SARS-CoV-2 transmission among co-workers in a University of Northern Italy during COVID-19 pandemic: an observational study.

BACKGROUND: This study aimed to investigate SARS-CoV-2 transmission among co-workers at the University of Genoa, Italy, during the second COVID-19 pandemic wave. METHODS: A cross-sectional study was carried out in October 2020 - March 2021: RT-PCR confirmed cases of COVID-19 notified to the Occupational Health Service were included in the analysis. RESULTS: Among the n = 201 notified cases, contact tracing of n = 53 individuals identified n = 346 close contacts. The household setting (IRR = 36.8; 95% CI: 4.9-276.8; p < 0.001) and sharing eating areas (IRR = 19.5; 95% CI: 2.5-153.9; p = 0.005) showed the highest Secondary Attack Rates (SARs) compared to the office setting. Fatigue (IRR= 17.1; 95% CI: 5.2-55.8; p < 0.001), gastrointestinal symptoms (IRR= 6.6; 95% CI: 2.9-15.2; p< 0.001) and cough (IRR= 8.2; 95% CI: 3.7-18.2; p= p< 0.001) were associated with transmission of infection. Polysymptomatic cases (IRR= 23.1; 95% CI: 3.1-169.2; p = 0.02) were more likely to transmit the infection. Among COVID-19 index cases aged >60 years (OR = 7.7; 95% CI: 1.9-31.9; p = 0.0046) SARs were higher than in other age groups. Wearing respiratory protections by both the case and the close contact resulted an effective measure compared with no use (IRR = 0.08; 95% CI: 0.03-0.2; p = < 0.0001). CONCLUSIONS: Accurate infection monitoring and contact tracing was useful to identify the main situations Conclusions: Accurate infection monitoring and contact tracing was useful to identify the main situations of SARS-CoV-2 transmission in the workplace, and hence for risk assessment and prevention programs.

Severe outcomes of COVID-19 among patients with multiple sclerosis under anti-CD-20 therapies: A systematic review and meta-analysis.

BACKGROUND: COVID-19 may spread through various ways ranging from asymptomatic to severe forms, until respiratory failure, critical conditions and death occurs. There is a particular concern for patients affected by multiple sclerosis, especially for those under disease-modifying treatments. Some studies have found an association between anti-CD20 therapies (especially rituximab) and severe COVID-19. However, results were not always clear and thus a systematic review was helpful. METHODS: A systematic literature search was performed independently by two authors on the main search tools considering as key inclusion criterion the presence of data on patients under ocrelizumab or rituximab positive to COVID-19. The quality of the included studies was evaluated based on a modified version of the Dutch Cochrane center critical review checklist proposed by MOOSE and in case of missing data an email was sent to the corresponding authors asking for missing information. After excluding case-reports, a random effects meta-analysis of proportions was conducted using the continuity correction and the I2statistic was calculated to measure heterogeneity. RESULTS: 29 articles were included in the analysis and the median quality of the articles reached 4/5 after having integrated the additional details provided by the authors. The articles included 5173 patients, of whom 770 (14.8%) and 455 (8.8%) were, respectively, under ocrelizumab and rituximab. Pooled estimates of hospitalization, pneumonia and intensive care unit admission were 18.1%, 14.8% and 3.3%, respectively, while pooled estimate for death was 1.8% overall and 1.6% and 4.5%, respectively, for patients under ocrelizumab and rituximab. CONCLUSION: Patients treated with rituximab seem to be at higher risk of severe COVID-19 outcomes compared to patients under other treatments.

Patterns of Comorbidity and In-Hospital Mortality in Older Patients With COVID-19 Infection.

Introduction: Older adults are more susceptible to severe COVID-19, with increased all-cause mortality. This has been attributed to their multimorbidity and disability. However, it remains to be established which clinical features of older adults are associated with severe COVID-19 and mortality. This information would aid in an accurate prognosis and appropriate care planning. Here, we aimed to identify the chronic clinical conditions and the comorbidity clusters associated with in-hospital mortality in a cohort of older COVID-19 patients who were admitted to the IRCCS Policlinico San Martino Hospital, Genoa, Italy, between January and April 2020. Methods: This was a retrospective cohort study including 219 consecutive patients aged 70 years or older and is part of the GECOVID-19 study group. During the study period, upon hospital admission, demographic information (age, sex) and underlying chronic medical conditions (multimorbidity) were recorded from the medical records at the time of COVID-19 diagnosis before any antiviral or antibiotic treatment was administered. The primary outcome measure was in-hospital mortality. Results: The vast majority of the patients (90%) were >80 years; the mean patient age was 83 ± 6.2 years, and 57.5% were men. Hypertension and cardiovascular disease, along with dementia, cerebrovascular diseases, and vascular diseases were the most prevalent clinical conditions. Multimorbidity was assessed with the Cumulative Illness Rating Scale. The risk of in-hospital mortality due to COVID-19 was higher for males, for older patients, and for patients with dementia or cerebral-vascular disease. We clustered patients into three groups based on their comorbidity pattern: the Metabolic-renal-cancer cluster, the Neurocognitive cluster and the Unspecified cluster. The Neurocognitive and Metabolic-renal-cancer clusters had a higher mortality compared with the Unspecified cluster, independent of age and sex. Conclusion: We defined patterns of comorbidity that accurately identified older adults who are at higher risk of death from COVID-19. These associations were independent of chronological age, and we suggest that the identification of comorbidity clusters that have a common pathophysiology may aid in the early assessment of COVID-19 patients with frailty to promote timely interventions that, in turn, may result in a significantly improved prognosis.

Clinical Management of Adult Patients with COVID-19 Outside Intensive Care Units: Guidelines from the Italian Society of Anti-Infective Therapy (SITA) and the Italian Society of Pulmonology (SIP).

INTRODUCTION: The Italian Society of Anti-Infective Therapy (SITA) and the Italian Society of Pulmonology (SIP) constituted an expert panel for developing evidence-based guidance for the clinical management of adult patients with coronavirus disease 2019 (COVID-19) outside intensive care units. METHODS: Ten systematic literature searches were performed to answer ten different key questions. The retrieved evidence was graded according to the Grading of Recommendations Assessment, Development, and Evaluation methodology (GRADE). RESULTS AND CONCLUSION: The literature searches mostly assessed the available evidence on the management of COVID-19 patients in terms of antiviral, anticoagulant, anti-inflammatory, immunomodulatory, and continuous positive airway pressure (CPAP)/non-invasive ventilation (NIV) treatment. Most evidence was deemed as of low certainty, and in some cases, recommendations could not be developed according to the GRADE system (best practice recommendations were provided in similar situations). The use of neutralizing monoclonal antibodies may be considered for outpatients at risk of disease progression. For inpatients, favorable recommendations were provided for anticoagulant prophylaxis and systemic steroids administration, although with low certainty of evidence. Favorable recommendations, with very low/low certainty of evidence, were also provided for, in specific situations, remdesivir, alone or in combination with baricitinib, and tocilizumab. The presence of many best practice recommendations testified to the need for further investigations by means of randomized controlled trials, whenever possible, with some possible future research directions stemming from the results of the ten systematic reviews.

Tracheostomy Timing and Outcome in Severe COVID-19: The WeanTrach Multicenter Study.

BACKGROUND: Tracheostomy can be performed safely in patients with coronavirus disease 2019 (COVID-19). However, little is known about the optimal timing, effects on outcome, and complications. METHODS: A multicenter, retrospective, observational study. This study included 153 tracheostomized COVID-19 patients from 11 intensive care units (ICUs). The primary endpoint was the median time to tracheostomy in critically ill COVID-19 patients. Secondary endpoints were survival rate, length of ICU stay, and post-tracheostomy complications, stratified by tracheostomy timing (early versus late) and technique (surgical versus percutaneous). RESULTS: The median time to tracheostomy was 15 (1-64) days. There was no significant difference in survival between critically ill COVID-19 patients who received tracheostomy before versus after day 15, nor between surgical and percutaneous techniques. ICU length of stay was shorter with early compared to late tracheostomy (p < 0.001) and percutaneous compared to surgical tracheostomy (p = 0.050). The rate of lower respiratory tract infections was higher with surgical versus percutaneous technique (p = 0.007). CONCLUSIONS: Among critically ill patients with COVID-19, neither early nor percutaneous tracheostomy improved outcomes, but did shorten ICU stay. Infectious complications were less frequent with percutaneous than surgical tracheostomy.

Efficacy of early anti-inflammatory treatment with high doses of intravenous anakinra with or without glucocorticoids in patients with severe COVID-19 pneumonia.

BACKGROUND: IL-1 plays a pivotal role in the inflammatory response during cytokine storm syndromes. OBJECTIVE: Our aim was to analyze the efficacy and safety of early anti-inflammatory treatment (AIT) with intravenous anakinra with or without glucocorticoids in coronavirus disease 2019 (COVID-19) pneumonia. METHODS: We performed a retrospective single-center cohort study of patients admitted for COVID-19 pneumonia from February 26 to April 29, 2020, to assess the efficacy of early AIT with intravenous anakinra (100 mg every 8 hours for 3 days, with tapering) alone or in combination with a glucocorticoid (intravenous methylprednisolone, 1-2 mg/kg daily, with tapering). The standard of care (SOC) treatment was hydroxychloroquine and/or azithromycin with or without antivirals and anticoagulants. Late rescue AIT with anakinra or tocilizumab was also evaluated. Treatment effect on overall survival was assessed by a propensity score-adjusted Cox model. RESULTS: A total of 128 patients were analyzed; 63 patients received early AIT (30 received anakinra alone and 33 received anakinra plus a glucocorticoid) at admission, and 65 patients did not receive early AIT and were used as controls; of the latter 65 patients, 44 received the SOC treatment alone and 21 received the SOC treatment plus late rescue AIT. After adjustment for all the unbalanced baseline covariates, early AIT reduced the hazard of mortality by 74% (adjusted hazard ratio [HR] = 0.26; P < .001). The effect was similar in patients receiving anakinra alone (adjusted HR = 0.28; P = .04) and anakinra plus a glucocorticoid (adjusted HR = 0.33; P = .07). Late rescue treatment did not show a significant advantage over SOC treatment alone (adjusted HR = 0.82; P = .70). CONCLUSIONS: This study suggests, on a larger series of patients with COVID-19 pneumonia, the potential efficacy and safety of the early use of high doses of intravenous anakinra with or without glucocorticoids.

Prevalence of Antibodies to SARS-CoV-2 in Italian Adults and Associated Risk Factors.

We aimed to assess the prevalence of and factors associated with anti- severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positivity in a large population of adult volunteers from five administrative departments of the Liguria and Lombardia regions. A total of 3609 individuals were included in this analysis. Participants were tested for anti-SARS-CoV-2 antibodies [Immunoglobulin G (IgG) and M (IgM) class antibodies] at three private laboratories (Istituto Diganostico Varelli, Medical Center, and Casa della Salute di Genova). Demographic data, occupational or private exposure to SARS-CoV-2-infected patients, and prior medical history consistent with SARS-CoV-2 infection were collected according to a preplanned analysis. The overall seroprevalence of anti-SARS-CoV-2 antibodies (IgG and/or IgM) was 11.0% [398/3609; confidence interval (CI) 10.0%-12.1%]. Seroprevalence was higher in female inmates than in male inmates (12.5% vs. 9.2%, respectively, p = 0.002), with the highest rate observed among adults aged >55 years (13.2%). A generalized estimating equations model showed that the main risk factors associated with SARS-CoV-2 seroprevalence were the following: an occupational exposure to the virus [Odd ratio (OR) = 2.36; 95% CI 1.59-3.50, p = 0.001], being a long-term care facility resident (OR = 4.53; 95% CI 3.19-6.45, p = 0.001), and reporting previous symptoms of influenza-like illness (OR = 4.86; 95% CI 3.75-6.30, p = 0.001) or loss of sense of smell or taste (OR = 41.00; 95% CI 18.94-88.71, p = 0.001). In conclusion, we found a high prevalence (11.0%) of SARS-CoV-2 infection that is significantly associated with residing in long-term care facilities or occupational exposure to the virus. These findings warrant further investigation into SARS-CoV-2 antibody prevalence among the Italian population.

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.

Bloodstream infections in critically ill patients with COVID-19.

BACKGROUND: Little is known about the incidence and risk of intensive care unit (ICU)-acquired bloodstream infections (BSI) in critically ill patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: This retrospective, single-centre study was conducted in Northern Italy. The primary study objectives were as follows: (a) to assess the incidence rate of ICU-acquired BSI and (b) to assess the cumulative risk of developing ICU-acquired BSI. RESULTS: Overall, 78 critically ill patients with COVID-19 were included in the study. Forty-five episodes of ICU-acquired BSI were registered in 31 patients, with an incidence rate of 47 episodes (95% confidence interval [CI] 35-63) per 1000 patient-days at risk. The estimated cumulative risk of developing at least one BSI episode was of almost 25% after 15 days at risk and possibly surpassing 50% after 30 days at risk. In multivariable analysis, anti-inflammatory treatment was independently associated with the development of BSI (cause-specific hazard ratio [csHR] 1.07 with 95% CI 0.38-3.04 for tocilizumab, csHR 3.95 with 95% CI 1.20-13.03 for methylprednisolone and csHR 10.69 with 95% CI 2.71-42.17 for methylprednisolone plus tocilizumab, with no anti-inflammatory treatment as the reference group; overall P for the dummy variable = 0.003). CONCLUSIONS: The incidence rate of BSI was high, and the cumulative risk of developing BSI increased with ICU stay. Further study will clarify if the increased risk of BSI we detected in COVID-19 patients treated with anti-inflammatory drugs is outweighed by the benefits of reducing any possible pro-inflammatory dysregulation induced by SARS-CoV-2.