Retailoring training programmes in anaesthesia and intensive care after the coronavirus disease 2019 outbreak.

PURPOSE OF REVIEW: In this review, we want to collect all the adaptations that anaesthesiology training has faced because of the health crisis and social distancing measures resulting from coronavirus 2019 disease (COVID-19). We reviewed new teaching tools launched during the COVID-19 outbreak worldwide and particularly those implemented by the European Society of Anaesthesiology and Intensive Care (ESAIC) and the European Association of Cardiothoracic Anaesthesiology and Intensive Care (EACTAIC). RECENT FINDINGS: Globally, COVID-19 has interrupted health services and all aspects of training programmes. These unprecedented changes have led to teaching and trainee support innovation tools, focusing on online learning and simulation programmes. Airway management, critical care and regional anaesthesia, have been enhanced during the pandemic, while there were major obstacles in paediatrics, obstetrics and pain medicine. SUMMARY: The COVID-19 pandemic has altered profoundly the functioning of health systems worldwide. Anaesthesiologists and trainees have fought on the front lines of the battle against COVID-19. As a result, training in anaesthesiology during the last 2 years has focused on managing patients in intensive care. New training programmes have been designed to continue teaching residents of this speciality, focusing on e-learning and advanced simulation. It is necessary to present a review describing the impact that this turbulent period has had on the different subsections of anaesthesiology and to review the innovative measures that have been implemented to address these possible deficits in education and training.

Rapid and sustainable self-questionnaire for large-scale psychological screening in pandemic conditions for healthcare workers.

Background: The pandemic caused by a coronavirus (COVID-19) has shocked healthcare systems worldwide. However, the psychological stressors remain unclear. The objective of this study was to assess the impact of a major pandemic on healthcare workers. We hypothesized that exposure to the virus would be the primary cause of psychological stress perceived by healthcare workers. Methods: A national cross-sectional study conducted via an online questionnaire was distributed between April 9 and April 19, 2020 with a non-probabilistic sample technique. A structural equation model (SEM) was built with the variable "exposure to the virus" and the Psychological Stress and Adaptation at work Score (PSAS). "Exposure to the virus" was defined as the combined factors of 'personal-sphere', "work-related stress" and "hospital characteristics." A generalized linear model (GLM) was also tested. Results: A total of 2,197 participants filled in the questionnaire and were analyzed. The exploratory factor analysis showed statistically significant variables related to the personal-sphere, work-related stress and the hospital's characteristics, although the confirmatory factor analysis showed only the work-related stress factors to be significant. The GLM showed that personal-sphere-related variables (P < .001), stress at work (P < 0.001) and age (P < 0.001) were statistically significant. Conclusion: Physical exposure to the virus is an essential factor that contributes to the psychological impact perceived during the pandemic by healthcare professionals. A combination of personal-sphere variables, work-related stress and hospital characteristics is a significant factor correlating with the degree of stress measured by PSAS, a new and fast instrument to assess stress in healthcare workers.

Airway Management of Patients with Suspected or Confirmed COVID-19: Survey Results from Physicians from 19 Countries in Latin America.

Airway management during the COVID-19 pandemic has been one of the most challenging aspects of care that anesthesiologists and intensivists face. This study was conducted to evaluate the management of tracheal intubation in patients with suspected or confirmed COVID-19 infection. This is a cross-sectional and international multicenter study based on a 37-item questionnaire. The survey was available to physicians who had performed intubations and tracheostomies in patients with suspected or confirmed COVID-19 and had provided informed consent to participate. The primary outcome is the preference to use a specific device for tracheal intubation. Secondary outcomes are clinical practice variables, use of video laryngoscopes, difficult airway management, and safety features to prevent cross-infection. This study included 2411 physicians who performed an average of 11.90 and 20.67 tracheal intubations in patients diagnosed or suspected of having COVID-19 disease, respectively. Physicians were mainly from the specialties of Anesthesiology (61.2%) and Intensive Care (7.4%). COVID-19 infection diagnosed by positive PCR or serology in physicians participating in intubation in this study was 15.1%. Respondents considered preoxygenation for more than three minutes very useful (75.7%). The preferred device for tracheal intubation was the video laryngoscope (64.8%). However, the direct laryngoscope (57.9%) was the most commonly used, followed by the video laryngoscope (37.5%). The preferred device to facilitate intubation was the Eschmann guide (34.2%). Percutaneous tracheostomy was the preferred technique (39.5%) over the open tracheostomy (22%). The predicted or unpredicted difficult airway management in these patients was preferably performed with a video laryngoscope (61.7% or 63.7, respectively). Intubation was mostly performed by two or more expert airway physicians (61.6%). The use of personal protective equipment increased the practitioners' discomfort during intubation maneuvers. The video laryngoscope is the preferred device for intubating patients with COVID-19, combined with the Eschmann guide, flexible stylet within the endotracheal tube, or Frova guide to facilitate intubation. The sub-analysis of the two groups of physicians by the level of intubation experience showed a higher use of the video laryngoscope (63.4%) in the experts group and no significant differences between the two groups in terms of cross-infection rates in physicians, in their preference for the use of the video laryngoscope or in the number of intubations performed in confirmed or suspected COVID-19 patients.

Clinical Characteristics of COVID-19 hospitalised patients associated with mortality: a cohort study in Spain

The heterogeneity of patients with COVID-19 may explain the wide variation of mortality rate due to the population characteristics, presence of comorbidities and clinical manifestations. In this study, we analysed 5,342 patients' recordings and selected a cohort of 177 hospitalised patients with a poor prognosis at an early stage. We assessed during six months their symptomatology, coexisting health conditions, clinical measures and health assistance related to mortality. Multiple Cox proportional hazards models were built to identify the associated factors with mortality risk. We observed that cough and kidney failure triplicate the mortality risk and both bilirubin levels and oncologic condition are shown as the most associated with the demise, increasing in four and ten times the risk, respectively. Other clinical characteristics such as fever, Diabetes Mellitus, breathing frequency, neutrophil-lymphocyte ratio, oxygen saturation and troponin levels, were also related to mortality risk of in-hospital death. The present study shows that some symptomatology, comorbidities and clinical measures could be the target of prevention tools to improve survival rates.

Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Hyperimmune Immunoglobulin Demonstrates Potent Neutralization and Antibody-Dependent Cellular Cytotoxicity and Phagocytosis Through N and S Proteins.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) vaccinations have provided a significant reduction in infections, effective COVID-19 treatments remain an urgent need. METHODS: Functional characterization of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hyperimmune immunoglobulin (hIG) from human convalescent plasma was performed by different virus neutralization methodologies (plaque reduction, virus-induced cytotoxicity, median tissue culture infectious dose [TCID50] reduction, and immunofluorimetry) at different laboratories using geographically different SARS-CoV-2 isolates (USA [1], Italy [1], and Spain [2]; 2 containing the D614G mutation). Neutralization capacity against the original Wuhan SARS-CoV-2 strain and variants (D614G mutant, B.1.1.7, P.1, and B.1.351) was evaluated using a pseudovirus expressing the corresponding spike (S) protein. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) was also evaluated. RESULTS: All SARS-CoV-2 isolates were potently neutralized by hIG as shown by all 4 methodologies. Wild-type SARS-CoV-2 and variants were effectively neutralized using the pseudovirus. The hIG (IgG type) induced ADCC and ADCP against SARS-CoV-2 N and S proteins but not E protein. Very low concentrations (25-100 µg IgG/mL) were required. A potent effect was triggered by antibodies in hIG solutions against the SARS-CoV-2 S and N proteins. CONCLUSIONS: Beyond neutralization, IgG Fc-dependent pathways may play a role in combatting SARS-CoV-2 infections using COVID-19 hIG. This could be especially relevant for the treatment of more neutralization-resistant SARS-CoV-2 variants.

Effective presence of antibodies against common human coronaviruses in immunoglobulin medicinal products.

BACKGROUND: Immunoglobulin products (for intravenous, intramuscular and subcutaneous administration) prepared from geographically diverse plasma pools were tested for activity against common human coronaviruses (HCoVs). Products from plasma obtained from Germany, Czech Republic, Slovak Republic, USA and Spain were tested for antibodies to common HCoVs: 229E, OC43, NL63 and HKU1. As these products are manufactured from pooled plasma from thousands of donors, the antibodies therein are representative of HCoV exposure in the population at large. METHODS: Immunoglobulin products were tested for antibodies to four common HCoVs by enzyme-linked immunosorbent assays (ELISAs). Neutralization assays were conducted using HCoV-229E cultured on to MRC5 cells. RESULTS: ELISAs showed that when expressed as specific activity (anti-HCoV activity/mg immunoglobulin), similar activity against the four common HCoVs was seen across the immunoglobulin products regardless of concentration or geographic origin. Highest anti-HCoV activity was seen against HCoV-229E, followed by HCoV-OC43, HCoV-NL63 and HCoV-HKU1. The neutralization assays showed similar potency for two immunoglobulin products prepared by different processes. CONCLUSIONS: To the authors' knowledge, this is the first demonstration of antibodies to common HCoVs in immunoglobulin products. These results may explain the cross-reactivity seen with pre-pandemic immunoglobulin products and severe acute respiratory syndrome coronavirus-2, and contribute to differences in severity of illness between patients.

Awake Prone Positioning, High-Flow Nasal Oxygen and Non-Invasive Ventilation as Non-Invasive Respiratory Strategies in COVID-19 Acute Respiratory Failure: A Systematic Review and Meta-Analysis.

BACKGROUND: Acute respiratory failure is the most important organ dysfunction of COVID-19 patients. While non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) oxygen are frequently used, efficacy and safety remain uncertain. Benefits and harms of awake prone positioning (APP) in COVID-19 patients are unknown. METHODS: We searched for randomized controlled trials (RCTs) comparing HFNC vs. NIV and APP vs. standard care. We meta-analyzed data for mortality, intubation rate, and safety. RESULTS: Five RCTs (2182 patients) were identified. While it remains uncertain whether HFNC compared to NIV alters mortality (RR: 0.92, 95% CI 0.65-1.33), HFNC may increase rate of intubation or death (composite endpoint; RR 1.22, 1.03-1.45). We do not know if HFNC alters risk for harm. APP compared to standard care probably decreases intubation rate (RR 0.83, 0.71-0.96) but may have little or no effect on mortality (RR: 1.08, 0.51-2.31). CONCLUSIONS: Certainty of evidence is moderate to very low. There is no compelling evidence for either HFNC or NIV, but both carry substantial risk for harm. The use of APP probably has benefits although mortality appears unaffected.

COVID-19 psychological impact in 3109 healthcare workers in Spain: The PSIMCOV group.

BACKGROUND: The current coronavirus disease (COVID-19) has a great impact worldwide. Healthcare workers play an essential role and are one of the most exposed groups. Information about the psychosocial impact on healthcare workers is limited. METHODS: 3109 healthcare workers completed a national, internet-based, cross-sectional 45-item survey between 9 and 19 April 2020. The objective is to assess the psychological impact of the COVID-19 pandemic in Spanish healthcare workers. A Psychological Stress and Adaptation at work Score (PSAS) was defined combining four modified versions of validated psychological assessment tests (A) Healthcare Stressful Test, (B) Coping Strategies Inventory, (C) Font-Roja Questionnaire and (D) Trait Meta-Mood Scale. RESULTS: The highest psychosocial impact was perceived in Respiratory Medicine, the mean (S.D.) PSAS was 48.3 (13.6) and Geriatrics 47.6 (16.4). Higher distress levels were found in the geographical areas with the highest incidence of COVID-19 (>245.5 cases per 100 000 people), PSAS 46.8 (15.2); p < 0.001. The least stress respondents were asymptomatic workers PSAS, 41.3 (15.4); p < 0.001, as well as those above 60 years old, PSAS, 37.6 (16); p < 0.001. Workers who needed psychological therapy and did not receive it, were more stressed PSAS 52.5 (13.6) than those who did not need it PSAS 39.7 (13.9); p < 0.001. CONCLUSIONS: The psychological impact in healthcare workers in Spain during COVID-19 emergency has been studied. The stress perceived is parallel to the number of cases per 100 000 people. Psychotherapy could have a major role to mitigate the experimented stress level.

Impact of COVID-19 Pandemic on Anesthesia and Critical Care Residents in Spain.

BACKGROUND: The pandemic caused by coronavirus disease 2019 (COVID-19) has substantially changed the activity in Spanish healthcare centers. Residents who face pandemics are vulnerable physicians with different knowledge and experience. OBJECTIVES: This study aimed to determine the impact of COVID-19 pandemic on the Anesthesia and Critical Care residents and to establish its formative and personal consequences. METHODS: A 35-question digital survey was developed, and was distributed among Anesthesia and Critical Care residents in Spain. The quantitative variable "Objective Formative Impact Score" (PIOF) was defined, being proportional to the impact on formative routines. RESULTS: Several parameters were associated to a higher formative impact, such as the exposition to patients with COVID-19 (P = 0,020), an increase in the autonomy (P = 0,001), fear to contagion due to lack of protective equipment (P = 0,003), working in higher incidence areas (P < 0,001), being assigned to COVID-19 critical care units (P < 0,001), or to other departments different from Anesthesia and Critical Care. Residents experienced feelings of loneliness from the social distancing or ethical conflicts when working in suboptimal conditions. CONCLUSIONS: COVID-19 pandemic has had a major impact on Anesthesia and Critical Care residents both personally and formatively. The designed parameter PIOF brings an objective value about residents' formation.

Antibiotics for the treatment of COVID-19.

BACKGROUND: The effect of antibiotics with potential antiviral and anti-inflammatory properties are being investigated in clinical trials as treatment for COVID-19. The use of antibiotics follows the intention-to-treat the viral disease and not primarily to treat bacterial co-infections of individuals with COVID-19. A thorough understanding of the current evidence regarding effectiveness and safety of antibiotics as anti-viral treatments for COVID-19 based on randomised controlled trials (RCTs) is required. OBJECTIVES: To assess the efficacy and safety of antibiotics compared to each other, no treatment, standard of care alone, placebo, or any other active intervention with proven efficacy for treatment of COVID-19 outpatients and inpatients.  SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (including MEDLINE, Embase, ClinicalTrials.gov, WHO ICTRP, medRxiv, CENTRAL), Web of Science and WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies to 14 June 2021. SELECTION CRITERIA: RCTs were included that compared antibiotics with each other, no treatment, standard of care alone, placebo, or another proven intervention, for treatment of people with confirmed COVID-19, irrespective of disease severity, treated in the in- or outpatient settings. Co-interventions had to be the same in both study arms. We excluded studies comparing antibiotics to other pharmacological interventions with unproven efficacy. DATA COLLECTION AND ANALYSIS: We assessed risk of bias of primary outcomes using the Cochrane risk of bias tool (ROB 2) for RCTs. We used GRADE to rate the certainty of evidence for the following primary outcomes: 1. to treat inpatients with moderate to severe COVID-19: mortality, clinical worsening defined as new need for intubation or death, clinical improvement defined as being discharged alive, quality of life, adverse and serious adverse events, and cardiac arrhythmias; 2. to treat outpatients with asymptomatic or mild COVID-19: mortality, clinical worsening defined as hospital admission or death, clinical improvement defined as symptom resolution, quality of life, adverse and serious adverse events, and cardiac arrhythmias. MAIN RESULTS: We included 11 studies with 11,281 participants with an average age of 54 years investigating antibiotics compared to placebo, standard of care alone or another antibiotic. No study was found comparing antibiotics to an intervention with proven efficacy. All studies investigated azithromycin, two studies investigated other antibiotics compared to azithromycin. Seven studies investigated inpatients with moderate to severe COVID-19 and four investigated mild COVID-19 cases in outpatient settings. Eight studies had an open-label design, two were blinded with a placebo control, and one did not report on blinding. We identified 19 ongoing and 15 studies awaiting classification pending publication of results or clarification of inconsistencies. Of the 30 study results contributing to primary outcomes by included studies, 17 were assessed as overall low risk and 13 as some concerns of bias. Only studies investigating azithromycin reported data eligible for the prioritised primary outcomes. Azithromycin doses and treatment duration varied among included studies.  Azithromycin for the treatment of COVID-19 compared to placebo or standard of care alone in inpatients We are very certain that azithromycin has little or no effect on all-cause mortality at day 28 compared to standard of care alone (risk ratio (RR) 0.98; 95% confidence interval (CI) 0.90 to 1.06; 8600 participants; 4 studies; high-certainty evidence). Azithromycin probably has little or no effect on clinical worsening or death at day 28 (RR 0.95; 95% CI 0.87 to 1.03; 7311 participants; 1 study; moderate-certainty evidence), on clinical improvement at day 28 (RR 0.96; 95% CI 0.84 to 1.11; 8172 participants; 3 studies; moderate-certainty evidence), on serious adverse events during the study period (RR 1.11; 95% CI 0.89 to 1.40; 794 participants; 4 studies; moderate-certainty evidence), and cardiac arrhythmias during the study period (RR 0.92; 95% CI 0.73 to 1.15; 7865 participants; 4 studies; moderate-certainty evidence) compared to placebo or standard of care alone. Azithromycin may increase any adverse events slightly during the study period (RR 1.20; 95% CI 0.92 to 1.57; 355 participants; 3 studies; low-certainty evidence) compared to standard of care alone. No study reported quality of life up to 28 days. Azithromycin for the treatment of COVID-19 compared to placebo or standard of care alone in outpatients Azithromycin may have little or no effect compared to placebo or standard of care alone on all-cause mortality at day 28 (RR 1.00 ; 95% CI 0.06 to 15.69; 876 participants; 3 studies; low-certainty evidence), on admission to hospital or death within 28 days (RR 0.94 ; 95% CI 0.57 to 1.56; 876 participants; 3 studies; low-certainty evidence), and on symptom resolution at day 14 (RR 1.03; 95% CI 0.95 to 1.12; 138 participants; 1 study; low-certainty evidence). We are uncertain whether azithromycin increases or reduces serious adverse events compared to placebo or standard of care alone (0 participants experienced serious adverse events; 454 participants; 2 studies; very low-certainty evidence). No study reported on adverse events, cardiac arrhythmias during the study period or quality of life up to 28 days. Azithromycin for the treatment of COVID-19 compared to any other antibiotics in inpatients and outpatients One study compared azithromycin to lincomycin in inpatients, but did not report any primary outcome. Another study compared azithromycin to clarithromycin in outpatients, but did not report any relevant outcome for this review. AUTHORS' CONCLUSIONS: We are certain that risk of death in hospitalised COVID-19 patients is not reduced by treatment with azithromycin after 28 days. Further, based on moderate-certainty evidence, patients in the inpatient setting with moderate and severe disease probably do not benefit from azithromycin used as potential antiviral and anti-inflammatory treatment for COVID-19 regarding clinical worsening or improvement. For the outpatient setting, there is currently low-certainty evidence that azithromycin may have no beneficial effect for COVID-19 individuals. There is no evidence from RCTs available for other antibiotics as antiviral and anti-inflammatory treatment of COVID-19. With accordance to the living approach of this review, we will continually update our search and include eligible trials to fill this evidence gap. However, in relation to the evidence for azithromycin and in the context of antimicrobial resistance, antibiotics should not be used for treatment of COVID-19 outside well-designed RCTs.

Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins.

Background: Cross-reactivity against human coronaviruses with Flebogamma® DIF and Gamunex®-C, two available intravenous immunoglobulins (IVIG), has been reported. In this study, these IVIG were tested for neutralization activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). Materials & methods: Neutralization capacity of lots of IVIG manufactured prior to COVID-19 pandemic was assessed against these viruses in cell culture. Infectivity neutralization was quantified by percent reduction in plaque-forming units and/or cytopathic/cytotoxic methods. Results: All IVIG preparations showed neutralization of SARS-CoV-2 isolates. All IVIG lots produced neutralization of SARS-CoV. No IVIG preparation showed significant neutralizing activity against MERS-CoV. Conclusion: The tested IVIG contain antibodies with significant in vitro cross-neutralization capacity against SARS-CoV-2 and SARS-CoV, but not MERS-CoV. These preparations are currently under evaluation as potential therapies for COVID-19.

Currently available intravenous immunoglobulin contains antibodies reacting against severe acute respiratory syndrome coronavirus 2 antigens.

Aim: There is a critical need for effective therapies that are immediately available to control the spread of COVID-19 disease. Material & methods: Gamunex®-C and Flebogamma® DIF (Grifols) intravenous immunoglobulin (IVIG) products were tested using ELISA techniques for antibodies against several antigens of human common betacoronaviruses that may crossreact with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Results: Both IVIGs showed consistent reactivity to components of the tested viruses. Positive crossreactivity was seen in SARS-CoV, middle east respiratory syndrome-CoV and SARS-CoV-2. For SARS-CoV-2, positive reactivity was observed at IVIG concentrations ranging from 100 µg/ml with Gamunex-C to 1 mg/ml with Flebogamma 5% DIF. Conclusion: Gamunex-C and Flebogamma DIF contain antibodies reacting against SARS-CoV-2 antigens. Studies to confirm the utility of IVIG preparations for COVID-19 management may be warranted.

COVID-19 Psychological Impact in 3109 Healthcare workers in Spain: The PSIMCOV Group

Background: The current coronavirus disease (COVID-19) has a great impactworldwide. Healthcare workers have an essential role and are one of the mostexposed groups. Information about the psychosocial impact on healthcare workersis limited.Methods: 3109 healthcare workers completed a national, internet-based, crosssectional 45-item survey between 9 to 19 April, 2020. The objective is to assess thepsychological impact of the SARS-CoV-2 in Spanish healthcare workers. APsychological Stress and Adaptation at work Score (PSAS) was defined combiningfour modified versions of validated psychological assessment tests (A) HealthcareStressful Test, (B) Coping Strategies Inventory, (C) Font-Roja Questionnaire and (D)Trait Meta-Mood Scale.Results: Of the 1671 physicians who completed the survey, the highestpsychosocial impact was perceived in Respiratory medicine, the mean (sd) PSASwas 48.3 (13.6) and Geriatrics 47.6 (16.4). Higher distress levels were found in theareas with the highest incidence of COVID-19 (>245.5 cases per 100,000 people),PSAS 46.8 (15.2);P<0.001. The least stress respondents were asymptomaticworkers PSAS, 41.3 (15.4);P<0.001, as well as those over 60 years old, PSAS,37.6(16);P<0.001. Workers that needed psychological therapy and did not receiveit, were more stressed PSAS 52.5 (13.6) than those who did not need it PSAS39,7(13,9) P<0.001.Conclusions: The psychological impact in healthcare workers in Spain during