Evaluation of the implementation of WHO infection prevention and control core components in Turkish health care facilities: results from a WHO infection prevention and control assessment framework (IPCAF)-based survey.

BACKGROUND: The core components (CCs) of infection prevention and control (IPC) from World Health Organization (WHO) are crucial for the safety and quality of health care. Our objective was to examine the level of implementation of WHO infection prevention and control core components (IPC CC) in a developing country. We also aimed to evaluate health care-associated infections (HAIs) and antimicrobial resistance (AMR) in intensive care units (ICUs) in association with implemented IPC CCs. METHODS: Members of the Turkish Infectious Diseases and Clinical Microbiology Specialization Association (EKMUD) were invited to the study via e-mail. Volunteer members of any healt care facilities (HCFs) participated in the study. The investigating doctor of each HCF filled out a questionnaire to collect data on IPC implementations, including the Infection Prevention and Control Assessment Framework (IPCAF) and HAIs/AMR in ICUs in 2021. RESULTS: A total of 68 HCFs from seven regions in Türkiye and the Turkish Republic of Northern Cyprus participated while 85% of these were tertiary care hospitals. Fifty (73.5%) HCFs had advanced IPC level, whereas 16 (23.5%) of the 68 hospitals had intermediate IPC levels. The hospitals' median (IQR) IPCAF score was 668.8 (125.0) points. Workload, staffing and occupancy (CC7; median 70 points) and multimodal strategies (CC5; median 75 points) had the lowest scores. The limited number of nurses were the most important problems. Hospitals with a bed capacity of > 1000 beds had higher rates of HAIs. Certified IPC specialists, frequent feedback, and enough nurses reduced HAIs. The most common HAIs were central line-associated blood stream infections. Most HAIs were caused by gram negative bacteria, which have a high AMR. CONCLUSIONS: Most HCFs had an advanced level of IPC implementation, for which staffing was an important driver. To further improve care quality and ensure everyone has access to safe care, it is a key element to have enough staff, the availability of certified IPC specialists, and frequent feedback. Although there is a significant decrease in HAI rates compared to previous years, HAI rates are still high and AMR is an important problem. Increasing nurses and reducing workload can prevent HAIs and AMR. Nationwide "Antibiotic Stewardship Programme" should be initiated.

Major adverse cardiovascular events (MACE) in patients with severe COVID-19 registered in the ISARIC WHO clinical characterization protocol: A prospective, multinational, observational study.

PURPOSE: To determine its cumulative incidence, identify the risk factors associated with Major Adverse Cardiovascular Events (MACE) development, and its impact clinical outcomes. MATERIALS AND METHODS: This multinational, multicentre, prospective cohort study from the ISARIC database. We used bivariate and multivariate logistic regressions to explore the risk factors related to MACE development and determine its impact on 28-day and 90-day mortality. RESULTS: 49,479 patients were included. Most were male 63.5% (31,441/49,479) and from high-income countries (84.4% [42,774/49,479]); however, >6000 patients were registered in low-and-middle-income countries. MACE cumulative incidence during their hospital stay was 17.8% (8829/49,479). The main risk factors independently associated with the development of MACE were older age, chronic kidney disease or cardiovascular disease, smoking history, and requirement of vasopressors or invasive mechanical ventilation at admission. The overall 28-day and 90-day mortality were higher among patients who developed MACE than those who did not (63.1% [5573/8829] vs. 35.6% [14,487/40,650] p < 0.001; 69.9% [6169/8829] vs. 37.8% [15,372/40,650] p < 0.001, respectively). After adjusting for confounders, MACE remained independently associated with higher 28-day and 90-day mortality (Odds Ratio [95% CI], 1.36 [1.33-1.39];1.47 [1.43-1.50], respectively). CONCLUSIONS: Patients with severe COVID-19 frequently develop MACE, which is independently associated with worse clinical outcomes.

Management of hypoxemia in SARS-CoV-2 infection: Lessons learned from one year of experience, with a special focus on silent hypoxemia.

Silent hypoxemia is common in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this article, the possible pathophysiological mechanisms underlying respiratory symptoms have been reviewed, and the presence of hypoxemia without hypoxia is also discussed. The experience we have gained since the start of the Coronavirus disease 19 (COVID-19) pandemic has changed our point of view about which patients with respiratory involvement should be admitted to the intensive care unit/high-dependency unit for mechanical ventilation and monitoring. In patients with clinically well-tolerated mild to moderate hypoxemia (silent hypoxemia), regardless of the extent of pulmonary opacities found in radiological studies, the administration of supplemental oxygen therapy may increase the risk of endothelial damage. The risk of sudden respiratory arrest during emergency intubation, which could expose healthcare workers to infection, should be considered along with the risks of premature intubation. Criteria for intubation need to be revisited based on updated evidence showing that many patients with severe hypoxemia do not show increased work of breathing. This has implications in patient management and may explain in part reports of broad differences in outcomes among intubated patients.

COVID-19-Associated Pulmonary Aspergillosis (CAPA).

Invasive Pulmonary Aspergillosis (IPA) has been recognized as a possible secondary infection complicating Coronavirus disease 2019 (COVID-19) and increasing mortality. The aim of this review was to report and summarize the available data in the literature concerning the incidence, pathophysiology, diagnosis, and treatment of COVID-19-Associated Pulmonary Aspergillosis (CAPA). Currently, the incidence of CAPA is unclear due to different definitions and diagnostic criteria used among the studies. It was estimated that approximately 8.6% (206/2383) of mechanically ventilated patients were diagnosed with either proven, probable, or putative CAPA. Classical host factors of invasive aspergillosis are rarely recognized in patients with CAPA, who are mainly immuno-competent presenting with comorbidities, while the role of steroids warrants further investigation. Direct epithelial injury and diffuse pulmonary micro thrombi in combination with immune dysregulation, hyper inflammatory response, and immunosuppressive treatment may be implicated. Discrimination between two forms of CAPA (e.g., tracheobronchial and parenchymal) is required, whereas radiological signs of aspergillosis are not typically evident in patients with severe COVID-19 pneumonia. In previous studies, the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria, a clinical algorithm to diagnose Invasive Pulmonary Aspergillosis in intensive care unit patients (AspICU algorithm), and influenza-associated pulmonary aspergillosis (IAPA) criteria were used for the diagnosis of proven/probable and putative CAPA, as well as the differentiation from colonization, which can be challenging. Aspergillus fumigatus is the most commonly isolated pathogen in respiratory cultures. Bronchoalveolar lavage (BAL) and serum galactomannan (GM), ß-d-glucan (with limited specificity), polymerase chain reaction (PCR), and Aspergillus-specific lateral-flow device test can be included in the diagnostic work-up; however, these approaches are characterized by low sensitivity. Early treatment of CAPA is necessary, and 71.4% (135/189) of patients received antifungal therapy, mainly with voriconazole, isavuconazole, and liposomal amphotericin B . Given the high mortality rate among patients with Aspergillus infection, the administration of prophylactic treatment is debated. In conclusion, different diagnostic strategies are necessary to differentiate colonization from bronchial or parenchymal infection in intubated COVID-19 patients with Aspergillus spp. in their respiratory specimens vs. those not infected with severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Following confirmation, voriconazole or isavuconazole should be used for the treatment of CAPA.

Clinical Phenotypes of COVID-19 Associated Mucormycosis (CAM): A Comprehensive Review.

A mucormycosis surge was reported during the COVID-19 pandemic in India. A literature search until 14 July 2022, with the aim of updating COVID-19-associated mucormycosis (CAM), identified 663 studies and 88 met inclusion criteria (8727 patients). India reported 8388 patients, Egypt 208 and Europe 40. Rhino-orbito-cerebral mucormycosis (ROCM) was identified among 8082 (98.3%) patients, followed by 98 (1.2%) with pulmonary. In India, 82.6% of patients had diabetes mellitus, with 82% receiving corticosteroids. In Europe, 75% presented pulmonary CAM, 32.5% had diabetes and 40% were immunocompromised. CAM was identified at a median of 17.4 days (IQR 7.5 days) post COVID-19 diagnosis, and PCR was performed in five studies. Rhino-orbital invasion is clinically obvious, while cerebral involvement presents with cavernous sinus thrombosis, meningitis and cerebrovascular disease. Symptoms of pulmonary CAM usually overlap with severe COVID-19 pneumonia. High-dose liposomal Amphotericin B (and early surgical debridement in ROCM) are the mainstay of therapy. The median mortality rate was estimated to be 21.4% (IQR 31.9%), increased by the presence of pulmonary (80% (IQR 50%) or cerebral involvement (50% (IQR 63.9%). In summary, different CAM clinical phenotypes need to be distinguished, influenced by geographical presentation. Opportunities exist for diagnosis and therapy optimization, based on earlier high-dose antifungal therapy, early source control, strict glycemic control and restriction of steroids to COVID-19 patients with oxygen requirements.

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study.

BACKGROUND: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). METHODS: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. RESULTS: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). CONCLUSIONS: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

Varicella-Zoster virus reactivation following severe acute respiratory syndrome coronavirus 2 vaccination or infection: New insights.

INTRODUCTION: Varicella zoster virus (VZV) reactivation has been reported following vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the real extent remains unknown. METHODS: We conducted a systematic review to summarize evidence of VZV reactivation or infection following SARS-CoV-2 vaccination. Episodes after coronavirus disease-2019 (COVID-19) were also identified. Related articles were identified in PubMed and EMBASE databases till December 31, 2021 using the terms "varicella zoster" and "COVID-19″. PROSPERO Register Number: CRD42021289399. RESULTS: The search revealed 314 articles, of which 55 met the inclusion criteria. VZV manifestations were documented in 179 (82.1%) subjects following SARS-CoV-2 vaccination and in 39 (17.9%) patients with COVID-19. Among the vaccinated, median (IQR) age was 56.5 (42-70) years, and 56.8% were female. Twenty-one (16.8%) were immunosuppressed. The median (IQR) latency time after vaccination was 6 (3-10) days, and 84.4% received mRNA vaccines. VZV reactivation occurred following a first dose (68.2%), a second dose (12.8%) or a booster (0.6%). The most important VZV manifestation was dermatome herpes zoster rash, which accounted for 86.4% of events in vaccinated subjects. Twenty patients (11.3%) presented serious VZV events after vaccination, with Herpes Zoster ophthalmicus (5.6%) and post-herpetic neuralgia (3.4%) predominating. No VZV pneumonia or deaths were recorded. Antiviral prescriptions were made in 96.2% of vaccinated subjects. No significant differences between vaccinated and infected subjects were found. CONCLUSION: This study indicates that the occurrence of VZV reactivation is clinically relevant. However, our findings suggest that COVID-19 vaccination is safe, and remains strongly recommended.

Positive airway pressure longer than 24 h is associated with histopathological volutrauma in severe COVID-19 pneumonia-an ESGFOR based narrative case-control review.

Background and Objective: A thorough understanding of the pathogenic mechanisms elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still requires further research. Until recently, only a restricted number of autopsies have been performed, therefore limiting the accurate knowledge of the lung injury associated with SARS-CoV-2. A multidisciplinary European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group of Forensic and Post-mortem Microbiology-ESGFOR team conducted a non-systematic narrative literature review among coronavirus 2019 disease (COVID-19) pneumonia cases assessing the histopathological (HP) effects of positive airways pressure. HP lung features were recorded and compared between mechanically ventilated (>24 hours) and control (ventilation <24 hours) patients. A logistic regression analysis was performed to identify associations between mechanical ventilation (MV) and HP findings. Methods: A PubMed and MEDLINE search was conducted in order to identify studies published between March 1st 2020 and June 30th 2021. Key Content and Findings: Seventy patients (median age: 69 years) from 24 studies were analysed, among whom 38 (54.2%) underwent MV longer than 24 hours. Overall, main HP features were: diffuse alveolar damage (DAD) in 53 (75.7%), fibrosis (interstitial/intra-alveolar) in 43 (61.4%), vascular damage-including thrombosis/emboli- in 41 (58.5%), and endotheliitis in only 8 (11.4%) patients. Association of DAD, fibrosis and vascular damage was detected in 30 (42.8%) patients. Multivariate analysis, adjusted by age and gender, identified MV >24 hours as an independent variable associated with DAD (OR =5.40, 95% CI: 1.48-19.62), fibrosis (OR =3.88, 95% CI: 1.25-12.08), vascular damage (OR =5.49, 95% CI: 1.78-16.95) and association of DAD plus fibrosis plus vascular damage (OR =6.99, 95% CI: 2.04-23.97). Conclusions: We identified that patients mechanically ventilated >24 hours had a significantly higher rate of pulmonary injury on histopathology independently of age and gender. Our findings emphasize the importance of maintaining a protective ventilator strategy when subjects with COVID-19 pneumonia undergo intubation.

Effect of High Altitude on the Survival of COVID-19 Patients in Intensive Care Unit: A Cohort Study.

Purpose: The effect of high altitude ( ≥ 1500 m) and its potential association with mortality by COVID-19 remains controversial. We assessed the effect of high altitude on the survival/discharge of COVID-19 patients requiring intensive care unit (ICU) admission for mechanical ventilation compared to individuals treated at sea level. Methods: A retrospective cohort multi-center study of consecutive adults patients with a positive RT-PCR test for COVID-19 who were mechanically ventilated between March and November 2020. Data were collected from two sea-level hospitals and four high-altitude hospitals in Ecuador. The primary outcome was ICU and hospital survival/discharge. Survival analysis was conducted using semi-parametric Cox proportional hazards models. Results: Of the study population (n = 670), 35.2% were female with a mean age of 58.3 ± 12.6 years. On admission, high-altitude patients were more likely to be younger (57.2 vs. 60.5 years old), presented with less comorbidities such as hypertension (25.9% vs. 54.9% with p-value <.001) and diabetes mellitus (20.5% vs. 37.2% with p-value <.001), less probability of having a capillary refill time > 3 sec (13.7% vs. 30.1%, p-value <.001), and less severity-of-illness condition (APACHE II score, 17.5 ± 8.1 vs. 20 ± 8.2, p < .01). After adjusting for key confounders high altitude is associated with significant higher probabilities of ICU survival/discharge (HR: 1.74 [95% CI: 1.46-2.08]) and hospital survival/discharge (HR: 1.35 [95% CI: 1.18-1.55]) than patients treated at sea level. Conclusions: Patients treated at high altitude at any time point during the study period were 74% more likely to experience ICU survival/discharge and 35% more likely to experience hospital survival/discharge than to the sea-level group. Possible reasons for these findings are genetic and physiological adaptations due to exposure to chronic hypoxia.

Healthcare-associated infections in adult intensive care unit patients: Changes in epidemiology, diagnosis, prevention and contributions of new technologies.

Patients in intensive care units (ICUs) are at high risk for healthcare-acquired infections (HAI) due to the high prevalence of invasive procedures and devices, induced immunosuppression, comorbidity, frailty and increased age. Over the past decade we have seen a successful reduction in the incidence of HAI related to invasive procedures and devices. However, the rate of ICU-acquired infections remains high. Within this context, the ongoing emergence of new pathogens, further complicates treatment and threatens patient outcomes. Additionally, the SARS-CoV-2 (COVID-19) pandemic highlighted the challenge that an emerging pathogen provides in adapting prevention measures regarding both the risk of exposure to caregivers and the need to maintain quality of care. ICU nurses hold a special place in the prevention and management of HAI as they are involved in basic hygienic care, steering and implementing quality improvement initiatives, correct microbiological sampling, and aspects antibiotic stewardship. The emergence of more sensitive microbiological techniques and our increased knowledge about interactions between critically ill patients and their microbiota are leading us to rethink how we define HAIs and best strategies to diagnose, treat and prevent these infections in the ICU. This multidisciplinary expert review, focused on the ICU setting, will summarise the recent epidemiology of ICU-HAI, discuss the place of modern microbiological techniques in their diagnosis, review operational and epidemiological definitions and redefine the place of several controversial preventive measures including antimicrobial-impregnated medical devices, chlorhexidine-impregnated washcloths, catheter dressings and chlorhexidine-based mouthwashes. Finally, general guidance is suggested that may reduce HAI incidence and especially outbreaks in ICUs.

Solid organ transplantation from donors with recent or current SARS-CoV-2 infection: A systematic review.

BACKGROUND: Solid-organ transplantation (SOT) from SARS-CoV-2 positive donors could be a life-saving opportunity worth grasping. We perform a systematic review to evaluate the recipient outcomes of SOT from donors with recent or current SARS-CoV-2 infection. METHODS: Search strategy was performed in PubMed, Cochrane COVID-19 Study Register, and Web of Science databases from the 1st of January 2019 to the 31st of December 2021. SOT adult recipients from a donor with past or current SARS-CoV-2 infection were elegible for inclusion. Outcomes were viral transmission, COVID-19 symptoms, mortality, hospital stay, and complications. PROSPERO Register Number: CRD42022303242 FINDINGS: Sixty-nine recipients received 48 kidneys, 18 livers and 3 hearts from 57 donors. Six additional transplants from positive lungs were identified. IgG+ anti-SARS-CoV-2 titers were detected among 10/16 recipients; only 4% (3/69) recipients were vaccinated. Non-lung transplant recipients received organs from 10/57 (17.5%) donors with persistent COVID-19. In 18/57 donors, SARS-CoV-2 RNA was detected (median 32 Cycle threshold [Ct]) at procurement. Among non-lung transplant recipients, SARS-CoV-2 viral transmission was not documented. Four patients presented delayed graft dysfunction, two patients acute rejection, and two patients died of septic shock. The median (IQR) hospital stay was 18 (11-28) days in recipients from symptomatic donors. Viral transmission occurred from three lung donors to their recipients, who developed COVID-19 symptoms. One of the recipients subsequently died. CONCLUSION: Use of non-lung (kidney, liver and heart) organs from SARS-CoV-2 positive donors seem to be a safe practice, with a low risk of transmission irrespective of the presence of symptoms at the time of procurement. Low viral replication (Ct > 30) was safe among non-lung donors, even if persistently symptomatic at procurement.

Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the International Severe Acute Respiratory and Emerging Infection Consortium WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study.

Due to the large number of patients with severe coronavirus disease 2019 (COVID-19), many were treated outside the traditional walls of the intensive care unit (ICU), and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the International Severe Acute Respiratory and Emerging Infection Consortium World Health Organization COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or noninvasive mechanical ventilation, high-flow nasal cannula, inotropes or vasopressors. A logistic generalised additive model was used to compare clinical outcomes among patients admitted or not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median (interquartile range (IQR), 67 (55-78) years), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 (5-19) days and was longer in patients admitted to an ICU than in those who were cared for outside the ICU (12 (6-23) days versus 8 (4-15) days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% (5797 out of 18 831) versus 39.0% (7532 out of 19 295), p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR 0.70, 95% CI 0.65-0.75; p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside an ICU.

The COVID-19 vaccination acceptance/hesitancy rate and its determinants among healthcare workers of 91 Countries: A multicenter cross-sectional study.

The aim of this study was to investigate the COVID-19 vaccination acceptance rate and its determinants among healthcare workers in a multicenter study. This was a cross-sectional multi-center survey conducted from February 5 to April 29, 2021. The questionnaire consisted of 26 items in 6 subscales. The English version of the questionnaire was translated into seven languages and distributed through Google Forms using snowball sampling; a colleague in each country was responsible for the forward and backward translation, and also the distribution of the questionnaire. A forward stepwise logistic regression was utilized to explore the variables and questionnaire factors tied to the intention to COVID-19 vaccination. 4630 participants from 91 countries completed the questionnaire. According to the United Nations Development Program 2020, 43.6 % of participants were from low Human Development Index (HDI) regions, 48.3 % high and very high, and 8.1 % from medium. The overall vaccination hesitancy rate was 37 %. Three out of six factors of the questionnaire were significantly related to intention to the vaccination. While 'Perceived benefits of the COVID-19 vaccination' (OR: 3.82, p-value<0.001) and 'Prosocial norms' (OR: 5.18, p-value<0.001) were associated with vaccination acceptance, 'The vaccine safety/cost concerns' with OR: 3.52, p-value<0.001 was tied to vaccination hesitancy. Medical doctors and pharmacists were more willing to take the vaccine in comparison to others. Importantly, HDI with OR: 12.28, 95 % CI: 6.10-24.72 was a strong positive determinant of COVID-19 vaccination acceptance. This study highlighted the vaccination hesitancy rate of 37 % in our sample among HCWs. Increasing awareness regarding vaccination benefits, confronting the misinformation, and strengthening the prosocial norms would be the primary domains for maximizing the vaccination coverage. The study also showed that the HDI is strongly associated with the vaccination acceptance/hesitancy, in a way that those living in low HDI contexts are more hesitant to receive the vaccine.

Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the ISARIC WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study

Due to the large number of patients with severe COVID-19, many were treated outside of the traditional walls of the ICU, and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside of the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the ISARIC WHO COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or non-invasive mechanical ventilation, high-flow nasal cannula, inotropes, and vasopressors. A logistic Generalised Additive Model was used to compare clinical outcomes among patients admitted and not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median [IQR], 67 years [55, 78]), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 days (5–19) and was longer in patients admitted to an ICU than in those that were cared for outside of ICU (12 [6–23] versus 8 [4–15] days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% [5797/18831] versus 39.0% [7532/19295], p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR:0.70, 95%CI: 0.65-0.75, p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside of an ICU.

Single-Breath Counting Test Predicts Non-Invasive Respiratory Support Requirements in Patients with COVID-19 Pneumonia.

The use of non-invasive respiratory strategies (NIRS) is crucial to improve oxygenation in COVID-19 patients with hypoxemia refractory to conventional oxygen therapy. However, the absence of respiratory symptoms may delay the start of NIRS. The aim of this study was to determine whether a simple bedside test such as single-breath counting test (SBCT) can predict the need for NIRS in the 24 h following the access to Emergency Department (ED). We performed a prospective observational study on 120 patients with COVID-19 pneumonia. ROC curves were used to analyze factors which might predict NIRS requirement. We found that 36% of patients had normal respiratory rate and did not experience dyspnea at rest. 65% of study population required NIRS in the 24 h following the access to ED. NIRS-requiring group presented lower PaO2/FiO2 (235.09 vs. 299.02), SpO2/FiO2 ratio (357.83 vs. 431.07), PaCO2 (35.12 vs. 40.08), and SBCT (24.46 vs. 30.36) and showed higher incidence of dyspnea at rest (57.7% vs. 28.6%). Furthermore, SBCT predicted NIRS requirement even in the subgroup of patients without respiratory symptoms (AUC = 0.882, cut-off = 30). SBCT might be a valuable tool for bedside assessment of respiratory function in patients with COVID-19 pneumonia and might be considered as an early clinical sign of impending respiratory deterioration.

Beneficial and harmful outcomes of tocilizumab in severe COVID-19: A systematic review and meta-analysis.

INTRODUCTION: The results of studies of tocilizumab (TCZ) in COVID-19 are contradictory. Our study aims to update medical evidence from controlled observational studies and randomized clinical trials (RCTs) on the use of TCZ in hospitalized patients with COVID-19. METHODS: We searched the following databases from January 1, 2020 to April 13, 2021 (date of the last search): MEDLINE database through the PubMed search engine and Scopus, using the terms ("COVID-19" [Supplementary Concept]) AND "tocilizumab" [Supplementary Concept]). RESULTS: Sixty four studies were included in the present study: 54 were controlled observational studies (50 retrospective and 4 prospective) and 10 were RCTs. The overall results provided data from 20,616 hospitalized patients with COVID-19: 7668 patients received TCZ in addition to standard of care (SOC) (including 1915 patients admitted to intensive care units (ICU) with reported mortality) and 12,948 patients only receiving SOC (including 4410 patients admitted to the ICU with reported mortality). After applying the random-effects model, the hospital-wide (including ICU) pooled mortality odds ratio (OR) of patients with COVID-19 treated with TCZ was 0.73 (95% confidence interval (CI) = 0.56-0.93). The pooled hospital-wide mortality OR was 1.25 (95% CI = 0.74-2.18) in patients admitted at conventional wards versus 0.66 (95% CI = 0.59-0.76) in patients admitted to the ICU. The pooled OR of hospital-wide mortality (including ICU) of COVID-19 patients treated with TCZ plus corticosteroids (CS) was 0.67 (95% CI = 0.54-0.84). The pooled in-hospital mortality OR was 0.71 (95% CI = 0.35-1.42) when TCZ was early administered (≤10 days from symptom onset) versus 0.83 (95% CI 0.48-1.45) for late administration (>10 days from symptom onset). The meta-analysis did not find significantly higher risk for secondary infections in COVID-19 patients treated with TCZ. CONCLUSIONS: TCZ prevented mortality in patients hospitalized for COVID-19. This benefit was seen to a greater extent in patients receiving concomitant CS and when TCZ administration occurred within the first 10 days after symptom onset.

Ventilator-Associated Events: Definitions and Uses

The use of specific care bundles to control infection has been demonstrated to be effective, including ventilator-associated pneumonia (VAP). However, the proposal of VAP rates as a quality indicator has generated debate due a lack of a gold standard definition. In 2013, the Centers for Disease Control and Prevention (CDC) replaced surveillance definitions from VAP to other preventable conditions related to mechanical ventilation (ventilator-associated events: VAE), which may predict outcomes. This represents a new opportunity to overcome many of the weaknesses of traditional VAP surveillance and broadens the focus of surveillance encompassing other preventable conditions related to mechanical ventilation.