COVID-19: A Possible Contribution of the MAPK Pathway.

BACKGROUND: COVID-19 is characterized by an uncontrolled inflammatory response with high pro-inflammatory cytokine production through the activation of intracellular pathways, such as mitogen-activated protein kinase (MAPK). Viruses are able to exploit the MAPK pathway to their advantage; this pathway relevance to severe COVID-19 is poorly described. The aim of this study was to quantify biomarkers involved in the MAPK pathway and to clarify its possible role in affecting some COVID-19-related clinical features. METHODS: H-RAS, C-RAF, MAPK1, MAPK2, and ERK were quantified through ELISA, and genetic polymorphisms were evaluated through real-time PCR. RESULTS: We prospectively recruited 201 individuals (158 positive and 43 negative for SARS-CoV-2): 35 were male, and their median age was 65 years. MAPK-related biomarker levels were increased in SARS-CoV-2-positive participants (n = 89) compared to negative ones (n = 29). Dyspnea was reported by 48%; this symptom was associated with PBMC C-RAF levels in positive participants (p = 0.022) and type of ventilation (p = 0.031). The highest degree of ventilation was used by 8% for invasive ventilation and 41% for continuous positive airway pressure (CPAP). CONCLUSIONS: This is the first study that showed a possible contribution of MAPK-related biomarkers in affecting COVID-19 clinical features, and this may be relevant for identifying COVID-19 positive participants at risk of serious complications.

Effectiveness of mid-regional pro-adrenomedullin, compared to other biomarkers (including lymphocyte subpopulations and immunoglobulins), as a prognostic biomarker in COVID-19 critically ill patients: New evidence from a 15-month observational prospective study.

Background: Mid-regional pro-adrenomedullin (MR-proADM), an endothelium-related peptide, is a predictor of death and multi-organ failure in respiratory infections and sepsis and seems to be effective in identifying COVID-19 severe forms. The study aims to evaluate the effectiveness of MR-proADM in comparison to routine inflammatory biomarkers, lymphocyte subpopulations, and immunoglobulin (Ig) at an intensive care unit (ICU) admission and over time in predicting mortality in patients with severe COVID-19. Methods: All adult patients with COVID-19 pneumonia admitted between March 2020 and June 2021 in the ICUs of a university hospital in Italy were enrolled. MR-proADM, lymphocyte subpopulations, Ig, and routine laboratory tests were measured within 48 h and on days 3 and 7. The log-rank test was used to compare survival curves with MR-proADM cutoff value of >1.5 nmol/L. Predictive ability was compared using the area under the curve (AUC) and 95% confidence interval (CI) of different receiver-operating characteristic curves. Results: A total of 209 patients, with high clinical severity [SOFA 7, IQR 4-9; SAPS II 52, IQR 41-59; median viral pneumonia mortality score (MuLBSTA)-11, IQR 9-13] were enrolled. ICU and overall mortality were 55.5 and 60.8%, respectively. Procalcitonin, lactate dehydrogenase, D-dimer, the N-terminal prohormone of brain natriuretic peptide, myoglobin, troponin, neutrophil count, lymphocyte count, and natural killer lymphocyte count were significantly different between survivors and non-survivors, while lymphocyte subpopulations and Ig were not different in the two groups. MR-proADM was significantly higher in non-survivors (1.17 ± 0.73 vs. 2.31 ± 2.63, p < 0.0001). A value of >1.5 nmol/L was an independent risk factor for mortality at day 28 [odds ratio of 1.9 (95% CI: 1.220-3.060)] after adjusting for age, lactate at admission, SOFA, MuLBSTA, superinfections, cardiovascular disease, and respiratory disease. On days 3 and 7 of the ICU stay, the MR-proADM trend evaluated within 48 h of admission maintained a correlation with mortality (p < 0.0001). Compared to all other biomarkers considered, the MR-proADM value within 48 h had the best accuracy in predicting mortality at day 28 [AUC = 0.695 (95% CI: 0.624-0.759)]. Conclusion: MR-proADM seems to be the best biomarker for the stratification of mortality risk in critically ill patients with COVID-19. The Ig levels and lymphocyte subpopulations (except for natural killers) seem not to be correlated with mortality. Larger, multicentric studies are needed to confirm these findings.

Ceftazidime-Avibactam (C/A) Resistant, Meropenem Sensitive KPC-Producing Klebsiella pneumoniae in ICU Setting: We Are What We Are Treated with?

The continuous spread of carbapenem-resistant Klebsiella pneumoniae (CP-Kp) strains presents a severe challenge to the healthcare system due to limited therapeutic options and high mortality. Since its availability, ceftazidime/avibactam (C/A) has become a first-line option against KPC-Kp, but C/A-resistant strains have been reported increasingly, especially with pneumonia or prior suboptimal blood exposure to C/A treatment. A retrospective, observational study was conducted with all patients admitted to the Intensive Care Unit (ICU) dedicated to COVID-19 patients at the City of Health & Sciences in Turin, between 1 May 2021 and 31 January 2022, with the primary endpoint to study strains with resistance to C/A, and secondly to describe the characteristics of this population, with or without previous exposure to C/A. Seventeen patients with colonization or invasive infection due to Klebsiella pneumoniae, C/A resistance, and susceptibility to meropenem (MIC = 2 µg/L) were included;the blaKPC genotype was detected in all isolates revealing D179Y mutation in the blaKPC-2 (blaKPC-33) gene. Cluster analysis showed that 16 out of the 17 C/A-resistant KPC-Kp isolates belonged to a single clone. Thirteen strains (76.5%) were isolated in a 60-day period. Only some patients had a previous infection with non-mutant KPC at other sites (5;29.4%). Eight patients (47.1%) underwent previous large-spectrum antibiotic treatment, and four patients (23.5%) had prior treatment with C/A. The secondary spread of the D179Y mutation in the blaKPC-2 during the COVID-19 pandemic needs to be addressed constantly by an interdisciplinary interaction between microbiologists, infection control personnel, clinicians, and infectious diseases consultants to properly diagnose and treat patients.

Evaluating the Protective Effect of Intravesical Bacillus Calmette-Guerin against SARS-CoV-2 in Non-Muscle Invasive Bladder Cancer Patients: A Multicenter Observational Trial

Simple Summary The transurethral resection of bladder tumors followed by intravesical Bacillus Calmette-Guerin (BCG) instillations represents the standard treatment for high-risk and selected intermediate-risk non-muscle invasive bladder cancer (NMIBC) patients. We hypothesized that intravesical BCG might be protective against symptomatic SARS-CoV-2 infection, especially in those patients who experienced systemic adverse events during BCG treatment. We tested our hypothesis in a large multicenter cohort of NMIBC patients treated with adjuvant intravesical BCG in the year preceding the first and second waves of the SARS-CoV-2 pandemic at two tertiary urological centers in Northern Italy. We aim to evaluate the potential protective role of intravesical Bacillus Calmette-Guerin (BCG) against SARS-CoV-2 in patients with non-muscle invasive bladder cancer (NMIBC). Patients treated with intravesical adjuvant therapy for NMIBC between January 2018 and December 2019 at two Italian referral centers were divided into two groups based on the received intravesical treatment regimen (BCG vs. chemotherapy). The study's primary endpoint was evaluating SARS-CoV-2 disease incidence and severity among patients treated with intravesical BCG compared to the control group. The study's secondary endpoint was the evaluation of SARS-CoV-2 infection (estimated with serology testing) in the study groups. Overall, 340 patients treated with BCG and 166 treated with intravesical chemotherapy were included in the study. Among patients treated with BCG, 165 (49%) experienced BCG-related adverse events, and serious adverse events occurred in 33 (10%) patients. Receiving BCG or experiencing systemic BCG-related adverse events were not associated with symptomatic proven SARS-CoV-2 infection (p = 0.9) nor with a positive serology test (p = 0.5). The main limitations are related to the retrospective nature of the study. In this multicenter observational trial, a protective role of intravesical BCG against SARS-CoV-2 could not be demonstrated. These results may be used for decision-making regarding ongoing and future trials.

Evaluating the Protective Effect of Intravesical Bacillus Calmette-Guerin against SARS-CoV-2 in Non-Muscle Invasive Bladder Cancer Patients: A Multicenter Observational Trial.

We aim to evaluate the potential protective role of intravesical Bacillus Calmette-Guerin (BCG) against SARS-CoV-2 in patients with non-muscle invasive bladder cancer (NMIBC). Patients treated with intravesical adjuvant therapy for NMIBC between January 2018 and December 2019 at two Italian referral centers were divided into two groups based on the received intravesical treatment regimen (BCG vs. chemotherapy). The study's primary endpoint was evaluating SARS-CoV-2 disease incidence and severity among patients treated with intravesical BCG compared to the control group. The study's secondary endpoint was the evaluation of SARS-CoV-2 infection (estimated with serology testing) in the study groups. Overall, 340 patients treated with BCG and 166 treated with intravesical chemotherapy were included in the study. Among patients treated with BCG, 165 (49%) experienced BCG-related adverse events, and serious adverse events occurred in 33 (10%) patients. Receiving BCG or experiencing systemic BCG-related adverse events were not associated with symptomatic proven SARS-CoV-2 infection (p = 0.9) nor with a positive serology test (p = 0.5). The main limitations are related to the retrospective nature of the study. In this multicenter observational trial, a protective role of intravesical BCG against SARS-CoV-2 could not be demonstrated. These results may be used for decision-making regarding ongoing and future trials.

Ceftazidime-Avibactam (C/A) Resistant, Meropenem Sensitive KPC-Producing Klebsiella pneumoniae in ICU Setting: We Are What We Are Treated with?

The continuous spread of carbapenem-resistant Klebsiella pneumoniae (CP-Kp) strains presents a severe challenge to the healthcare system due to limited therapeutic options and high mortality. Since its availability, ceftazidime/avibactam (C/A) has become a first-line option against KPC-Kp, but C/A-resistant strains have been reported increasingly, especially with pneumonia or prior suboptimal blood exposure to C/A treatment. A retrospective, observational study was conducted with all patients admitted to the Intensive Care Unit (ICU) dedicated to COVID-19 patients at the City of Health & Sciences in Turin, between 1 May 2021 and 31 January 2022, with the primary endpoint to study strains with resistance to C/A, and secondly to describe the characteristics of this population, with or without previous exposure to C/A. Seventeen patients with colonization or invasive infection due to Klebsiella pneumoniae, C/A resistance, and susceptibility to meropenem (MIC = 2 µg/L) were included; the blaKPC genotype was detected in all isolates revealing D179Y mutation in the blaKPC-2 (blaKPC-33) gene. Cluster analysis showed that 16 out of the 17 C/A-resistant KPC-Kp isolates belonged to a single clone. Thirteen strains (76.5%) were isolated in a 60-day period. Only some patients had a previous infection with non-mutant KPC at other sites (5; 29.4%). Eight patients (47.1%) underwent previous large-spectrum antibiotic treatment, and four patients (23.5%) had prior treatment with C/A. The secondary spread of the D179Y mutation in the blaKPC-2 during the COVID-19 pandemic needs to be addressed constantly by an interdisciplinary interaction between microbiologists, infection control personnel, clinicians, and infectious diseases consultants to properly diagnose and treat patients.

Ventilatory associated barotrauma in COVID-19 patients: A multicenter observational case control study (COVI-MIX-study).

BACKGROUND: The risk of barotrauma associated with different types of ventilatory support is unclear in COVID-19 patients. The primary aim of this study was to evaluate the effect of the different respiratory support strategies on barotrauma occurrence; we also sought to determine the frequency of barotrauma and the clinical characteristics of the patients who experienced this complication. METHODS: This multicentre retrospective case-control study from 1 March 2020 to 28 February 2021 included COVID-19 patients who experienced barotrauma during hospital stay. They were matched with controls in a 1:1 ratio for the same admission period in the same ward of treatment. Univariable and multivariable logistic regression (OR) were performed to explore which factors were associated with barotrauma and in-hospital death. RESULTS: We included 200 cases and 200 controls. Invasive mechanical ventilation was used in 39.3% of patients in the barotrauma group, and in 20.1% of controls (p<0.001). Receiving non-invasive ventilation (C-PAP/PSV) instead of conventional oxygen therapy (COT) increased the risk of barotrauma (OR 5.04, 95% CI 2.30 - 11.08, p<0.001), similarly for invasive mechanical ventilation (OR 6.24, 95% CI 2.86-13.60, p<0.001). High Flow Nasal Oxygen (HFNO), compared with COT, did not significantly increase the risk of barotrauma. Barotrauma frequency occurred in 1.00% [95% CI 0.88-1.16] of patients; these were older (p=0.022) and more frequently immunosuppressed (p=0.013). Barotrauma was shown to be an independent risk for death (OR 5.32, 95% CI 2.82-10.03, p<0.001). CONCLUSIONS: C-PAP/PSV compared with COT or HFNO increased the risk of barotrauma; otherwise HFNO did not. Barotrauma was recorded in 1.00% of patients, affecting mainly patients with more severe COVID-19 disease. Barotrauma was independently associated with mortality. TRIAL REGISTRATION: this case-control study was prospectively registered in clinicaltrial.gov as NCT04897152 (on 21 May 2021).

Predictors of mortality in patients with COVID-19 infection in different health-care settings: A retrospective analysis from a CORACLE study group.

BACKGROUND: Despite the large number of hospitalized patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, few data are available about risk factors and mortality in subjects with nosocomially acquired respiratory infection of Coronavirus Disease 2019 (COVID-19). METHODS: We retrospectively evaluated in a multicentric study -during the pre-vaccination era-all patients admitted with confirmed diagnosis of nosocomial COVID-19 (NC). Patients were classified according to provenance: hospital-acquired NC or long-term care (LTC) facilities. RESULTS: Among overall 1047 patients evaluated with COVID-19, 137 had a confirmed diagnosis of NC (13%). 78 (56.9%) patients had hospital-acquired NC and 59 (43%) had LTC NC. Overall mortality was 35.8%, in hospital-acquired NC 24.4%, in LTC NC 50.8% (p < 0.001) (Log Rank test: p = 0.001). Timing of diagnosis was significantly different between hospital acquired and LTC NC (3.5 vs 10 days, p < 0.001). In multivariate analysis age, intensive-care unit admission, LTC provenance and sepsis were significant predictors of mortality in patients with NC infection. CONCLUSION: Patients with NC are at higher risk of mortality (especially for LTC NC) and required preventive strategies, early diagnosis, and treatment to avoid COVID-19 cluster.

Prognostic evaluation of Acinetobacter baumannii ventilator-associated pneumonia in COVID-19.

Background: Since the emergence of the pandemic of SARS-CoV-2, a high reported incidence of VAP in COVID-19 sustained by carbapenem resistant Acinetobacter baumannii (CRAB) has been observed, but data are scarce to date. Materials and methods: We retrospectively collected COVID-19 patients who developed CRAB-VAP - defined according to Center for Diseases Control (CDC) 2020 criteria and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) or Infectious Diseases Society of America (IDSA) guidelines - to describe characteristics and outcome. Results: Among 21 patients with CRAB-VAP in COVID-19, median age was 66 years (IQR 41-80). Median time of VAP-onset was 7 days (IQR 0-28 days) from ICU - admission and 76.2% had septic shock. Treatment regimens were all colistin-based, in 28% (n=6) including ampicillin/sulbactam and rifampicin. In three cases, cefiderocol was started as rescue. Survival rate at 28-days was 35% (n=7). Conclusion: Non-fermenting Gram-negative bacteria are an emerging aetiology of VAP in COVID-19 patients. This underscores the urgent need for proper microbiological identification to address therapies and infection control protocols.

A Regional Observational Study on COVID-19-Associated Pulmonary Aspergillosis (CAPA) within Intensive Care Unit: Trying to Break the Mold.

The reported incidence of COVID-19-associated pulmonary aspergillosis (CAPA) ranges between 2.4% and 35% in intensive care unit (ICU) patients, and awareness in the medical community is rising. We performed a regional retrospective observational study including patients diagnosed with CAPA defined according to the Modified AspICU Dutch/Belgian Mycosis Study Group and CAPA-EECMM, from five different ICUs, admitted between March, 2020 and September, 2021. Forty-five patients were included. The median age was 64 (IQR 60-72), mostly (73%) males. At ICU admission, the median Charlson comorbidity index was 3 (2-5), and the simplified acute physiology score (SAPS)-II score was 42 (31-56). The main underlying diseases were hypertension (46%), diabetes (36%) and pulmonary diseases (15%). CAPA was diagnosed within a median of 17 days (IQR 10-21.75) after symptoms onset and 9 days (IQR 3-11) after ICU admission. The overall 28-day mortality rate was 58%, and at univariate analysis, it was significantly associated with older age (p = 0.009) and SAPS-II score at admission (p = 0.032). The use of immunomodulatory agents, p = 0.061; broad-spectrum antibiotics, p = 0.091; positive culture for Aspergillus on BAL, p = 0.065; and hypertension, p = 0.083, were near reaching statistical significance. None of them were confirmed in multivariate analysis. In critically ill COVID-19 patients, CAPA acquired clinical relevance in terms of incidence and reported mortality. However, the risk between underdiagnosis-in the absence of specific invasive investigations, and with a consequent possible increase in mortality-and over-diagnosis (case identification with galactomannan on broncho-alveolar fluid alone) might be considered. Realistic incidence rates, based on local, real-life epidemiological data, might be helpful in guiding clinicians.

Real-Life Experience of Molnupiravir in Hospitalized Patients Who Developed SARS-CoV2-Infection: Preliminary Results from CORACLE Registry.

Real-life experience of molnupiravir treatment is lacking, especially in people hospitalized for underlying diseases not related to COVID-19. We conducted a retrospective analysis regarding molnupiravir therapy in patients with SARS-CoV-2 infection admitted for underlying diseases not associated with COVID-19. Forty-four patients were included. The median age was 79 years (interquartile range [IQR]: 51-93 years), and most males were 57,4%. The median Charlson Comorbidity Index and 4C score were, respectively, 5 (IQR: 3-10) and 9.9 (IQR: 4-12). Moreover, 77.5% of the patients had at least two doses of the anti-SARS-CoV-2 vaccine, although 10.6% had not received any SARS-CoV-2 vaccine. Frequent comorbidities were cardiovascular diseases (68.1%), and diabetes (31.9%), and most admissions were for the acute chronic heart (20.4%) or liver (8.5%) failure. After molnupiravir started, 8 (18.1%) patients developed acute respiratory failure, and five (11.4%) patients died during hospitalisation. Moreover, molnupiravir treatment does not result in a statistically significant change in laboratory markers except for an increase in the monocyte count (p = 0.048, Z = 1.978). Molnupiravir treatment in our analysis was safe and well tolerated. In addition, no patients' characteristics were found significantly related to hospital mortality or an increase in oxygen support. The efficacy of the molecule remains controversial in large clinical studies, and further studies, including larger populations, are required to fill the gap in this issue.

The Burden of Carbapenem-Resistant Acinetobacter baumannii in ICU COVID-19 Patients: A Regional Experience.

Since the beginning of the COVID-19 pandemic, the impact of superinfections in intensive care units (ICUs) has progressively increased, especially carbapenem-resistant Acinetobacter baumannii (CR-Ab). This observational, multicenter, retrospective study was designed to investigate the characteristics of COVID-19 ICU patients developing CR-Ab colonization/infection during an ICU stay and evaluate mortality risk factors in a regional ICU network. A total of 913 COVID-19 patients were admitted to the participating ICUs; 19% became positive for CR-Ab, either colonization or infection (n = 176). The ICU mortality rate in CR-Ab patients was 64.7%. On average, patients developed colonization or infection within 10 ± 8.4 days from ICU admission. Scores of SAPS II and SOFA were significantly higher in the deceased patients (43.8 ± 13.5, p = 0.006 and 9.5 ± 3.6, p < 0.001, respectively). The mortality rate was significantly higher in patients with extracorporeal membrane oxygenation (12; 7%, p = 0.03), septic shock (61; 35%, p < 0.001), and in elders (66 ± 10, p < 0.001). Among the 176 patients, 129 (73%) had invasive infection with CR-Ab: 105 (60.7%) Ventilator-Associated Pneumonia (VAP), and 46 (26.6%) Bloodstream Infections (BSIs). In 22 cases (6.5%), VAP was associated with concomitant BSI. Colonization was reported in 165 patients (93.7%). Mortality was significantly higher in patients with VAP (p = 0.009). Colonized patients who did not develop invasive infections had a higher survival rate (p < 0.001). Being colonized by CR-Ab was associated with a higher risk of developing invasive infections (p < 0.001). In a multivariate analysis, risk factors significantly associated with mortality were age (OR = 1.070; 95% CI (1.028-1.115) p = 0.001) and CR-Ab colonization (OR = 5.463 IC95% 1.572-18.988, p = 0.008). Constant infection-control measures are necessary to stop the spread of A. baumannii in the hospital environment, especially at this time of the SARS-CoV-2 pandemic, with active surveillance cultures and the efficient performance of a multidisciplinary team.

Pregnancy and COVID-19: The Possible Contribution of Vitamin D.

BACKGROUND: Vitamin D deficiency has been associated with the severity of COVID-19. The role of vitamin D in pregnant women with COVID-19 has been poorly investigated to date. The aim of this study was to evaluate the influence of vitamin D in affecting some clinical features in pregnancy between SARS-CoV-2 positive and negative patients. METHODS: Vitamin D pathway related polymorphisms and 25-hydroxyvitamin D levels were quantified in pregnant women followed from the first to the third trimester of pregnancy. Vitamin D deficiency was considered with values ≤ 30 ng/mL. RESULTS: In total, 160 women were enrolled: 23 resulted positive for at least one SARS-CoV-2 related test (molecular swab or antibody tests). Vitamin D-associated polymorphisms were able to affect vitamin D levels in SARS-CoV-2 negative and positive subjects: remarkably, all the VDR TaqICC genotype patients were negative for SARS-CoV-2. In a sub-population (118 patients), vitamin D levels correlated with pregnancy-related factors, such as alpha-fetoprotein levels. Third-trimester vitamin D levels were lower in preterm births compared to full-term pregnancy: this trend was highlighted for SARS-CoV-2 positive patients. CONCLUSIONS: This is the first study demonstrating a role of vitamin D in affecting the clinical characteristics of pregnant women during the COVID-19 era. Further studies in larger and different cohorts of patients are required to confirm these findings.

First Cases of Candida auris in a Referral Intensive Care Unit in Piedmont Region, Italy.

Candida auris is an emerging healthcare-associated infection that can easily cause dissemination in hospitals through colonizing the skin and contaminating environmental surfaces, especially in Intensive Care Units (ICU). Difficulties with identification of this organism, uncertainty about routes of transmission and antifungals resistance have impacted significantly outbreak detection and management. Here, we describe our experience with colonization/infection of C. auris among critically ill patients, admitted to a referral ICU of a University Hospital, in a transitional period (July 2021-March 2022) between management of non-COVID-19 and COVID-19 patients due to the reconversion of the ICU between two waves. A total of 8 patients presented colonization from C. auris, and two of them developed invasive infection from C. auris. The fungal pathogen was cultured from different sites: the skin (7 isolates), urine (2), respiratory tract (1), blood (1). The median time from admission to first detection is 24 days with 100% of patients requiring mechanical ventilation. All 8 patients received broad-spectrum antibiotic therapy for bacterial infections before identification of C. auris; 62.5% of the patients had prior antifungal exposure; 87.5% received steroids; 37.5% patients used immunomodulatory; and 75% had severe COVID-19 illness prior to C. auris identification. Only two cases (25%) were treated with antifungals as C. auris infections (1 patient for suspected UTI; 1 patient with candidemia). Infection control measures, including rapid microbiological identification, contact isolation, screening of contacts, antisepsis of colonized patients, dedicated equipment, cleaning and disinfection of the environment and subsequent follow-up sampling, remain essential in critically ill patients. Our experience highlights the importance of establishing a multidisciplinary model and bundling of practices for preventing C. auris' spread.

An Observational Study of MDR Hospital-Acquired Infections and Antibiotic Use during COVID-19 Pandemic: A Call for Antimicrobial Stewardship Programs.

The pandemic caused by the COVID-19 virus has required major adjustments to healthcare systems, especially to infection control and antimicrobial stewardship. The objective of this study was to describe the incidence of multidrug-resistant (MDR) hospital-acquired infections (HAIs) and antibiotic consumption during the three waves of COVID-19 and to compare it to the period before the outbreak at Molinette Hospital, located in the City of Health and Sciences, a 1200-bed teaching hospital with surgical, medical, and intensive care units. We demonstrated an increase in MDR infections: particularly in K. pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp), A. baumannii, and MRSA. Fluoroquinolone use showed a significant increasing trend in the pre-COVID period but saw a significant reduction in the COVID period. The use of fourth- and fifth-generation cephalosporins and piperacillin-tazobactam increased at the beginning of the COVID period. Our findings support the need for restoring stewardship and infection control practices, specifically source control, hygiene, and management of invasive devices. In addition, our data reveal the need for improved microbiological diagnosis to guide appropriate treatment and prompt infection control during pandemics. Despite the infection control practices in place during the COVID-19 pandemic, invasive procedures in critically ill patients and poor source control still increase the risk of HAIs caused by MDR organisms.

Inpatient Mortality According to Level of Respiratory Support Received for Severe Acute Respiratory Syndrome Coronavirus 2 (Coronavirus Disease 2019) Infection: A Prospective Multicenter Study.

OBJECTIVES: To describe patients according to the maximum degree of respiratory support received and report their inpatient mortality due to coronavirus disease 2019. DESIGN: Analysis of patients in the Coracle registry from February 22, 2020, to April 1, 2020. SETTING: Hospitals in the Piedmont, Lombardy, Tuscany, and Lazio regions of Italy. PATIENTS: Nine-hundred forty-eight patients hospitalized for coronavirus disease 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 948 patients, 122 (12.87%) received invasive ventilation, 637 (67.19%) received supplemental oxygen only, and 189 (19.94%) received no respiratory support. The median (quartile 1-quartile 3) age was 65 years (54-76.59 yr), and there was evidence of differential respiratory treatment by decade of life (p = 0.0046); patients greater than 80 years old were generally not intubated. There were 606 men (63.9%) in this study, and they were more likely to receive respiratory support than women (p < 0.0001). The rate of in-hospital death for invasive ventilation recipients was 22.95%, 12.87% for supplemental oxygen recipients, and 7.41% for those who received neither (p = 0.0004). A sensitivity analysis of the 770 patients less than 80 years old revealed a lower, but similar mortality trend (18.02%, 8.10%, 5.23%; p = 0.0008) among the 14.42%, 65.71%, and 19.87% of patients treated with mechanical ventilation, supplemental oxygen only, or neither. Overall, invasive ventilation recipients who died were significantly older than those who survived (median age: 68.5 yr [60-81.36 yr] vs 62.5 yr [55.52-71 yr]; p = 0.0145). CONCLUSIONS: Among patients hospitalized for coronavirus disease 2019, 13% received mechanical ventilation, which was associated with a mortality rate of 23%.

Liver involvement and mortality in COVID-19: A retrospective analysis from the CORACLE study group.

Introduction: liver abnormalities are common in COVID-19 patients and associated with higher morbidity and mortality. We aimed to investigate clinical significance and effect on the mortality of abnormal liver function tests (ALFTs) in COVID-19 patients. Methods: we retrospectively evaluated in a multicentre study all patients admitted with confirmed diagnosis of COVID-19. Results: 434 patients were included in this analysis. Among overall patients, 311 (71.6%) had normal baseline ALT levels. 123 patients showed overall abnormal liver function tests (ALFTs) at baseline [101 ALFTs <2x UNL and 22 ≥2 UNL]. Overall in-hospital mortality was 14% and mean duration of hospitalization was 10.5 days. Hypertension (50.5%), cardiovascular diseases (39.6%), diabetes (23%) were frequent comorbidities and 53.7% of patients had ARDS. At multivariate analysis, the presence of ARDS at baseline (OR=6.11; 95% CI: 3.03-12.32; p<0.000); cardiovascular diseases (OR=4; 95% CI: 2.05-7.81; p<0.000); dementia (OR=3.93; 95%CI:1.87-8.26; p<0.000) and no smoking (OR=4.6; 95% CI: 1.45-14.61; p=0.010) resulted significantly predictive of in-hospital mortality. The presence of ALFTs at baseline was not significantly associated with mortality (OR=3.44; 95% CI=0.81-14.58; p=0.094). Conclusion: ALFTs was frequently observed in COVID-19 patients, but the overall in-hospital mortality was mainly determined by the severity of illness, comorbidities and presence of ARDS.

Disseminated Cryptococcosis Complicating Severe SARS-CoV-2 Infection

Opportunistic invasive fungal infections (IFI) have been described in severe SARS-CoV-2 infection. COVID-19-related cytokine storm, immune dysregulation and lymphopenia may increase IFI susceptibility in comorbid patients. We described the case of a 64-year-old man with respiratory failure due to SARS-CoV-2 infection complicated with disseminated cryptococosis. We analyzed the role played by the SARS-CoV-2-associated lymphopenia and the cumulative risk factors that lead to secondary infection by Cryptococcus neoformans, and its part in the dysregulation of the immunity response.

Vaccine development and technology for SARS-CoV-2: Current insight.

Severe acute respiratory syndrome coronavirus 2 is associated with a severe respiratory disease in China, that rapidly spread across continents. Since the beginning of the pandemic, available data suggested the asymptomatic transmission and patients were treated with specific drugs with efficacy and safety data not always satisfactory. The aim of this review is to describe the vaccines developed by three companies, Pfizer-BioNTech, Moderna, and University of Oxford/AstraZeneca, in terms of both technological and pharmaceutical formulation, safety, efficacy, and immunogenicity. A critical analysis of Phases 1, 2, and 3 clinical trial results available was conducted, comparing the three vaccine candidates, underlining their similarities and differences. All candidates showed consistent efficacy and tolerability; although some differences can be noted, such as their technological formulation, temperature storage, which will be related to logistics and costs. Further studies will be necessary to evaluate long-term effects and to assess the vaccine safety and efficacy in the general population.