Procalcitonin Values Fail to Track the Presence of Secondary Bacterial Infections in COVID-19 ICU Patients.

The development of secondary bacterial infections in COVID-19 patients has been associated with increased mortality and worse clinical outcomes. Consequently, many patients have received empirical antibiotic therapies with the potential to further exacerbate an ongoing antimicrobial resistance crisis. The pandemic has seen a rise in the use of procalcitonin testing to guide antimicrobial prescribing, although its value remains elusive. This single-centre retrospective study sought to analyse the efficacy of procalcitonin in identifying secondary infections in COVID-19 patients and evaluate the proportion of patients prescribed antibiotics to those with confirmed secondary infection. Inclusion criteria comprised patients admitted to the Grange University Hospital intensive care unit with SARS-CoV-2 infection throughout the second and third waves of the pandemic. Data collected included daily inflammatory biomarkers, antimicrobial prescriptions, and microbiologically proven secondary infections. There was no statistically significant difference between PCT, WBC, or CRP values in those with an infection versus those without. A total of 57.02% of patients had a confirmed secondary infection, with 80.2% prescribed antibiotics in Wave 2, compared to 44.07% with confirmed infection and 52.1% prescribed antibiotics in Wave 3. In conclusion, procalcitonin values failed to indicate the emergence of critical care-acquired infection in COVID-19 patients.

Awake Prone Positioning for Non-Intubated COVID-19 Patients with Acute Respiratory Failure: A Meta-Analysis of Randomised Controlled Trials.

INTRODUCTION: Awake prone positioning (APP) has been widely applied in non-intubated patients with COVID-19-related acute hypoxemic respiratory failure. However, the results from randomised controlled trials (RCTs) are inconsistent. We performed a meta-analysis to assess the efficacy and safety of APP and to identify the subpopulations that may benefit the most from it. METHODS: We searched five electronic databases from inception to August 2022 (PROSPERO registration: CRD42022342426). We included only RCTs comparing APP with supine positioning or standard of care with no prone positioning. Our primary outcomes were the risk of intubation and all-cause mortality. Secondary outcomes included the need for escalating respiratory support, length of ICU and hospital stay, ventilation-free days, and adverse events. RESULTS: We included 11 RCTs and showed that APP reduced the risk of requiring intubation in the overall population (RR 0.84, 95% CI: 0.74-0.95; moderate certainty). Following the subgroup analyses, a greater benefit was observed in two patient cohorts: those receiving a higher level of respiratory support (compared with those receiving conventional oxygen therapy) and those in intensive care unit (ICU) settings (compared to patients in non-ICU settings). APP did not decrease the risk of mortality (RR 0.93, 95% CI: 0.77-1.11; moderate certainty) and did not increase the risk of adverse events. CONCLUSIONS: In patients with COVID-19-related acute hypoxemic respiratory failure, APP likely reduced the risk of requiring intubation, but failed to demonstrate a reduction in overall mortality risk. The benefits of APP are most noticeable in those requiring a higher level of respiratory support in an ICU environment.

Procalcitonin Evaluation of Antibiotic Use in COVID-19 Hospitalised Patients (PEACH): Protocol for a Retrospective Observational Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is a viral illness, many patients admitted to hospital are prescribed antibiotics, based on concerns that COVID-19 patients may experience secondary bacterial infections, and the assumption that they may respond well to antibiotic therapy. This has led to an increase in antibiotic use for some hospitalised patients at a time when accumulating antibiotic resistance is a major global threat to health. Procalcitonin (PCT) is an inflammatory marker measured in blood samples and widely recommended to help diagnose bacterial infections and guide antibiotic treatment. The PEACH study will compare patient outcomes from English and Welsh hospitals that used PCT testing during the first wave of the COVID-19 pandemic with those from hospitals not using PCT. It will help to determine whether, and how, PCT testing should be used in the NHS in future waves of COVID-19 to protect patients from antibiotic overuse. PEACH is a retrospective observational cohort study using patient-level clinical data from acute hospital Trusts and Health Boards in England and Wales. The primary objective is to measure the difference in antibiotic use between COVID-19 patients who did or did not have PCT testing at the time of diagnosis. Secondary objectives include measuring differences in length of stay, mortality, intensive care unit admission, and resistant bacterial infections between these groups.

SARS-CoV-2 infection risk among 77,587 healthcare workers: a national observational longitudinal cohort study in Wales, United Kingdom, April to November 2020.

OBJECTIVES: To better understand the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers, leading to recommendations for the prioritisation of personal protective equipment, testing, training and vaccination. DESIGN: Observational, longitudinal, national cohort study. SETTING: Our cohort were secondary care (hospital-based) healthcare workers employed by NHS Wales (United Kingdom) organisations from 1 April 2020 to 30 November 2020. PARTICIPANTS: We included 577,756 monthly observations among 77,587 healthcare workers. Using linked anonymised datasets, participants were grouped into 20 staff roles. Additionally, each role was deemed either patient-facing, non-patient-facing or undetermined. This was linked to individual demographic details and dates of positive SARS-CoV-2 PCR tests. MAIN OUTCOME MEASURES: We used univariable and multivariable logistic regression models to determine odds ratios (ORs) for the risk of a positive SARS-CoV-2 PCR test. RESULTS: Patient-facing healthcare workers were at the highest risk of SARS-CoV-2 infection with an adjusted OR (95% confidence interval [CI]) of 2.28 (95% CI 2.10-2.47). We found that after adjustment, foundation year doctors (OR 1.83 [95% CI 1.47-2.27]), healthcare support workers [OR 1.36 [95% CI 1.20-1.54]) and hospital nurses (OR 1.27 [95% CI 1.12-1.44]) were at the highest risk of infection among all staff groups. Younger healthcare workers and those living in more deprived areas were at a higher risk of infection. We also observed that infection rates varied over time and by organisation. CONCLUSIONS: These findings have important policy implications for the prioritisation of vaccination, testing, training and personal protective equipment provision for patient-facing roles and the higher risk staff groups.

The PANDORA Study: Prevalence and Outcome of Acute Hypoxemic Respiratory Failure in the Pre-COVID-19 Era.

OBJECTIVES: To establish the epidemiological characteristics, ventilator management, and outcomes in patients with acute hypoxemic respiratory failure (AHRF), with or without acute respiratory distress syndrome (ARDS), in the era of lung-protective mechanical ventilation (MV). DESIGN: A 6-month prospective, epidemiological, observational study. SETTING: A network of 22 multidisciplinary ICUs in Spain. PATIENTS: Consecutive mechanically ventilated patients with AHRF (defined as Pao2/Fio2 ≤ 300 mm Hg on positive end-expiratory pressure [PEEP] ≥ 5 cm H2O and Fio2 ≥ 0.3) and followed-up until hospital discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were prevalence of AHRF and ICU mortality. Secondary outcomes included prevalence of ARDS, ventilatory management, and use of adjunctive therapies. During the study period, 9,803 patients were admitted: 4,456 (45.5%) received MV, 1,271 (13%) met AHRF criteria (1,241 were included into the study: 333 [26.8%] met Berlin ARDS criteria and 908 [73.2%] did not). At baseline, tidal volume was 6.9 ± 1.1 mL/kg predicted body weight, PEEP 8.4 ± 3.1 cm H2O, Fio2 0.63 ± 0.22, and plateau pressure 21.5 ± 5.4 cm H2O. ARDS patients received higher Fio2 and PEEP than non-ARDS (0.75 ± 0.22 vs 0.59 ± 0.20 cm H2O and 10.3 ± 3.4 vs 7.7 ± 2.6 cm H2O, respectively [p < 0.0001]). Adjunctive therapies were rarely used in non-ARDS patients. Patients without ARDS had higher ventilator-free days than ARDS (12.2 ± 11.6 vs 9.3 ± 9.7 d; p < 0.001). All-cause ICU mortality was similar in AHRF with or without ARDS (34.8% [95% CI, 29.7-40.2] vs 35.5% [95% CI, 32.3-38.7]; p = 0.837). CONCLUSIONS: AHRF without ARDS is a very common syndrome in the ICU with a high mortality that requires specific studies into its epidemiology and ventilatory management. We found that the prevalence of ARDS was much lower than reported in recent observational studies.

Procalcitonin evaluation of antibiotic use in COVID-19 hospitalized patients during the first wave of COVID-19: the PEACH study

Background A minority of patients presenting to hospital with COVID-19 have bacterial coinfection. Procalcitonin testing may help identify patients for whom antibiotics should be prescribed or withheld. The PEACH study describes the use of procalcitonin in English and Welsh hospitals during the first wave of the COVID-19 pandemic to help diagnose bacterial infections and guide antibiotic treatment. There is a lack of clear evidence to support its use in lung infections, which means in some hospitals, clinicians have used the procalcitonin test to guide antibiotic decisions in COVID-19, whilst in other hospitals, they have not. Our study is analysing data from hospitals that did and did not use procalcitonin testing during the first wave of the COVID-19 pandemic. It will determine whether and how procalcitonin testing should be used in the NHS in future waves of COVID-19 to protect patients from antibiotic overuse. Methods To assess whether the use of PCT testing, to guide antibiotic prescribing, safely reduced antibiotic use among patients who were hospitalized with COVID-19 during the first wave of the pandemic, we are answering this question through three different, and complimentary, work streams (WS), each with discrete work packages (WP): (i) Work Stream 1: utilization of PCT testing to guide antibiotic prescribing during the first wave of COVID-19 pandemic;(ii) Work Stream 2: patient-level impact of PCT testing on antibiotic exposure and clinical outcome (main work stream currently in analysis);and (iii) Work Stream 3: health economics analysis of PCT testing to guide antibiotics in COVID-19. Results Our first publication from Work Stream 1 (Antibiotics 2021, 10: 516) used a web-based survey to gather data from antimicrobial leads about the use of procalcitonin testing. Responses were received from 148/151 (98%) eligible hospitals. During the first wave of the COVID-19 pandemic, there was widespread introduction and expansion of PCT use in NHS hospitals. The number of hospitals using PCT in emergency/acute admissions rose from 17 (11%) to 74/146 (50.7%) and use in ICU increased from 70 (47.6%) to 124/147 (84.4%). This increase happened predominantly in March and April 2020, preceding NICE guidance. Approximately half of hospitals used PCT as a single test to guide decisions to discontinue antibiotics and half used repeated measurements. There was marked variation in the thresholds used for empirical antibiotic cessation and guidance about interpretation of values. Conclusions Procalcitonin testing has been widely adopted in the NHS during the COVID-19 pandemic in an unevidenced, heterogeneous way and in conflict with relevant NICE guidance. Further research is needed urgently that assesses the impact of this change on antibiotic prescribing and patient safety. Work Stream 2 is ongoing, and results will be published once available.

PROCALCITONIN KINETICS MAY INDICATE PRESENCE OF SECONDARY BACTERIAL INFECTIONS IN COVID-19 ARDS

PCT rise was observed in 35 (53.8%) of patients, CRP rise in 42 (67.4%) and WCC rise in 52 (80%) of the patients. VAP was the most common ICU-acquired infection, occurring in 28/65 (43.1%) patients, of whom 8/65 (12.3%) suffered both VAP and BSI during their ICU stay. B Introduction: b Secondary bacterial infection in Covid-19 is associated with increased mortality and disproportionately affects critically ill patients. [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Procalcitonin Increase Is Associated with the Development of Critical Care-Acquired Infections in COVID-19 ARDS.

Secondary bacterial infection in COVID-19 patients is associated with increased mortality and disproportionately affects critically ill patients. This single-centre retrospective observational study investigates the comparative efficacy of change in procalcitonin (PCT) and other commonly available biomarkers in revealing or predicting microbiologically proven secondary infection in critical COVID-19 patients. Adult patients admitted to an intensive care unit (ICU) with confirmed SARS-CoV-2 infection between 9 March 2020 and 5 June 2020 were recruited to the study. For daily biomarker and secondary infection, laboratory-confirmed bloodstream infection (LCBI) and ventilator-associated pneumonia/tracheobronchitis (VAP/VAT) data were collected. We observed a PCT rise in 53 (81.5%) of the patients, a C-reactive protein (CRP) rise in 55 (84.6%) and a white blood cell count (WBC) rise in 61 (93.8%). Secondary infection was confirmed in 33 (50.8%) of the patients. A PCT rise was present in 97.0% of patients with at least one confirmed VAP/VAT and/or LCBI event. CRP and WBC rises occurred in 93.9% and 97.0% of patients with confirmed VAP/VAT and/or LCBI, respectively. Logistic regression analysis found that, when including all biomarkers in the same model, there was a significant association between PCT rise and the occurrence of LCBI and/or VAP/VAT (OR = 14.86 95%CI: 2.20, 342.53; p = 0.021). Conversely, no statistically significant relationship was found between either a CRP rise (p = 0.167) or a WBC rise (p = 0.855) and the occurrence of VAP/VAT and/or LCBI. These findings provide a promising insight into the usefulness of PCT measurement in predicting the emergence of secondary bacterial infection in ICU.

The role of rotational thromboelastometry in understanding the coagulation problems in COVID-19 associated critical illness.

In critically ill patients with COVID-19, concomitant abnormalities of coagulation have been seen with an unusually high incidence, often despite seemingly appropriate prophylactic anti-coagulation. It appears that standard coagulation tests are limited in their ability to accurately reflect the severity of the prothrombotic phenotype observed in severe COVID-19 infections. In this narrative review we consider the role of a global haemostatic assay, rotational thromboelastometry (ROTEM), as a near bedside test allowing a more comprehensive assessment of haemostatic function in the context of COVID-19 infection. A comprehensive literature search was conducted on PubMed using the keywords "COVID-19" OR "SARS-CoV-2" AND "Rotational thromboelastometry". Sixteen original articles were included for analysis and two existing literature reviews were considered. Whilst not the perfect substitute for in vivo coagulation, studies utilising rotational thromboelastometry assays in COVID-19 patients have demonstrated increased maximum clot firmness (consistent with hypercoagulability) and reduced maximum lysis (consistent with "fibrinolytic shutdown"). There is a possible association with disease severity and degree of hypercoagulability and hypofibrinolysis as a possible tool for risk stratification and the potential modulation of fibrinogen-dependent maximum clot firmness with enhanced anticoagulation strategies. Precisely how these coagulation abnormalities can be modified by optimum, individualised medical interventions to improve clinical outcomes, however, remains unclear.

Do ventilatory parameters influence outcome in patients with severe acute respiratory infection? Secondary analysis of an international, multicentre14-day inception cohort study.

PURPOSE: To investigate the possible association between ventilatory settings on the first day of invasive mechanical ventilation (IMV) and mortality in patients admitted to the intensive care unit (ICU) with severe acute respiratory infection (SARI). MATERIALS AND METHODS: In this pre-planned sub-study of a prospective, multicentre observational study, 441 patients with SARI who received controlled IMV during the ICU stay were included in the analysis. RESULTS: ICU and hospital mortality rates were 23.1 and 28.1%, respectively. In multivariable analysis, tidal volume and respiratory rate on the first day of IMV were not associated with an increased risk of death; however, higher driving pressure (DP: odds ratio (OR) 1.05; 95% confidence interval (CI): 1.01-1.1, p = 0.011), plateau pressure (Pplat) (OR 1.08; 95% CI: 1.04-1.13, p < 0.001) and positive end-expiratory pressure (PEEP) (OR 1.13; 95% CI: 1.03-1.24, p = 0.006) were independently associated with in-hospital mortality. In subgroup analysis, in hypoxemic patients and in patients with acute respiratory distress syndrome (ARDS), higher DP, Pplat, and PEEP were associated with increased risk of in-hospital death. CONCLUSIONS: In patients with SARI receiving IMV, higher DP, Pplat and PEEP, and not tidal volume, were associated with a higher risk of in-hospital death, especially in those with hypoxemia or ARDS.

Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure: The REST Randomized Clinical Trial.

Importance: In patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes. Objective: To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. Design, Setting, and Participants: This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020. Interventions: Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210). Main Outcomes and Measures: The primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates. Results: Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, -7.6% to 11.5%]; P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, -2.1 [95% CI, -3.8 to -0.3]; P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device. Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT02654327.

Differences in Inflammatory Marker Kinetics between the First and Second Wave of COVID-19 Patients Admitted to the ICU: A Retrospective, Single-Center Study.

BACKGROUND: We sought to determine if there was a difference in the longitudinal inflammatory response measured by white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), and ferritin levels between the first and the second COVID-19 wave of ICU patients. METHODS: In a single-center retrospective observational study, ICU patients were enrolled during the first and second waves of the COVID-19 pandemic. Data were collected on patient demographics, comorbidities, laboratory results, management strategies, and complications during the ICU stay. The inflammatory response was evaluated using WBC count, CRP, PCT, and Ferritin levels on the day of admission until Day 28, respectively. Organ dysfunction was measured by the SOFA score. RESULTS: 65 patients were admitted during the first and 113 patients during the second wave. WBC and ferritin levels were higher in the second wave. CRP and PCT showed markedly different longitudinal kinetics up until day 28 of ICU stay between the first and second wave, with significantly lower levels in the second wave. Steroid and immunomodulatory therapy use was significantly greater in the second wave. Mortality was similar in both waves. CONCLUSIONS: We found that there was a significantly reduced inflammatory response in the second wave, which is likely to be attributable to the more widespread use of immunomodulatory therapies.

Use of Procalcitonin during the First Wave of COVID-19 in the Acute NHS Hospitals: A Retrospective Observational Study.

A minority of patients presenting to hospital with COVID-19 have bacterial co-infection. Procalcitonin testing may help identify patients for whom antibiotics should be prescribed or withheld. This study describes the use of procalcitonin in English and Welsh hospitals during the first wave of the COVID-19 pandemic. A web-based survey of antimicrobial leads gathered data about the use of procalcitonin testing. Responses were received from 148/151 (98%) eligible hospitals. During the first wave of the COVID-19 pandemic, there was widespread introduction and expansion of PCT use in NHS hospitals. The number of hospitals using PCT in emergency/acute admissions rose from 17 (11%) to 74/146 (50.7%) and use in Intensive Care Units (ICU) increased from 70 (47.6%) to 124/147 (84.4%). This increase happened predominantly in March and April 2020, preceding NICE guidance. Approximately half of hospitals used PCT as a single test to guide decisions to discontinue antibiotics and half used repeated measurements. There was marked variation in the thresholds used for empiric antibiotic cessation and guidance about interpretation of values. Procalcitonin testing has been widely adopted in the NHS during the COVID-19 pandemic in an unevidenced, heterogeneous way and in conflict with relevant NICE guidance. Further research is needed urgently that assesses the impact of this change on antibiotic prescribing and patient safety.

Clinical Risk Prediction Scores in Coronavirus Disease 2019: Beware of Low Validity and Clinical Utility.

Several risk stratification tools were developed to predict disease progression in coronavirus disease 2019, with no external validation to date. We attempted to validate three previously published risk-stratification tools in a multicenter study. Primary outcome was a composite outcome of development of severe coronavirus disease 2019 disease leading to ICU admission or death censored at hospital discharge or 30 days. We collected data from 169 patients. Patients were 73 years old (59-82 yr old), 66 of 169 (39.1%) were female, 57 (33.7%) had one comorbidity, and 80 (47.3%) had two or more comorbidities. Area under the receiver operating characteristic curve (95% CI) for the COVID-GRAM score was 0.636 (0.550-0.722), for the CALL score 0.500 (0.411-0.589), and for the nomogram 0.628 (0.543-0.714).

Epidemiology of the First Wave of COVID-19 ICU Admissions in South Wales-The Interplay Between Ethnicity and Deprivation.

On the 9th March 2020, the first patient with COVID-19 was admitted to ICU in the Royal Gwent Hospital (RGH), Newport, Wales. We prospectively recorded the rate of ICU admissions of 52 patients with COVID-19 over 60 days, focusing on the epidemiology of ethnicity and deprivation because these factors have emerged as significant risk factors. Patients were 65% (34 of 52) male and had a median (IQR) age of 55 (48-62) years. Prevalent comorbidities included obesity (52%); diabetes (33%), and asthma (23%). COVID-19 hospital and ICU inpatient numbers peaked on days 23 and 39, respectively-a lag of 16 days. The ICU mortality rate was 33% (17 of 52). People of black, Asian, and minority ethnic descent (BAME group) represented 35% of ICU COVID-19 admissions (18 of 52) and 35% of deaths (6 of 17). Amongst the BAME group, 72% (13 of 18) of patients were found to reside in geographical areas representing the 20% most deprived in Wales, vs. 27% of patients in the Caucasian group (9 of 33). Less than 5% of the population within the area covered by RGH are of BAME descent, yet this group had a disproportionately high ICU admission and mortality rate from COVID-19. The interplay between ethnicity and deprivation, which is complex, may be a factor in our findings. This in turn could be related to an increased prevalence of co-morbidities; higher community exposure; larger proportion of lower band key worker roles; or genetic polymorphisms.