Critically-ill COVID-19 Patients Research Articles

COVID-19 associated pulmonary aspergillosis in critically-ill patients: a prospective multicenter study in the era of Delta and Omicron variants

BackgroundDuring the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11–28% of critically ill COVID-19 patients and associated with increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants.MethodsThis is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria.Results566 patients were included over the study period. The prevalence of CAPA was 5.1% [95% CI 3.4–7.3], and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay.ConclusionThis study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients.

Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality

The dysregulated immune response and inflammation resulting in severe COVID-19 are still incompletely understood. Having recently determined that aberrant death-ligand-induced cell death can cause lethal inflammation, we hypothesized that this process might also cause or contribute to inflammatory disease and lung failure following SARS-CoV-2 infection. To test this hypothesis, we developed a novel mouse-adapted SARS-CoV-2 model (MA20) that recapitulates key pathological features of COVID-19. Concomitantly with occurrence of cell death and inflammation, FasL expression was significantly increased on inflammatory monocytic macrophages and NK cells in the lungs of MA20-infected mice. Importantly, therapeutic FasL inhibition markedly increased survival of both, young and old MA20-infected mice coincident with substantially reduced cell death and inflammation in their lungs. Intriguingly, FasL was also increased in the bronchoalveolar lavage fluid of critically-ill COVID-19 patients. Together, these results identify FasL as a crucial host factor driving the immuno-pathology that underlies COVID-19 severity and lethality, and imply that patients with severe COVID-19 may significantly benefit from therapeutic inhibition of FasL.

The use of continuous renal replacement therapy in critically ill patients with COVID-19-related acute kidney injury

Background/Aim. Patients with severe clinical COVID-19 are at higher risk of developing acute kidney injury (AKI). The aim of the study was to analyze the risk factors for AKI/AKI on chronic kidney disease (CKD) and the results of treatment using continuous renal replacement therapy (CRRT) in critically ill COVID-19 patients. Methods. The study included 101 COVID-19 patients with AKI treated with CRRT out of a total of 293 patients with AKI. The study was conducted from March 2020 to July 2021 at the University Clinical Center of Vojvodina, Serbia. Results. The average age of patients was 64.69 ? 9.71 years. Out of the total number of patients, 82.2% were male, of whom 75.2% suffered from hypertension. On invasive mechanical ventilation (IMV) were 93.7% of patients, and 92.1% were on vasopressor therapy. The average length of IMV until the beginning of CRRT was 4.65 ? 4 .57 days. In the first 24 hrs after starting IMV, 60% of patients had to undergo CRRT. Before administering CRRT, the average Simplified Acute Physiology Score II was 39.13 ? 14.45, creatinine 312 ?mol/L [Interquartile Range (IQR) 208.0?437.5], procalcitonin 2.70 ng/L (IQR 0.62?7.20), while 10.9% of patients had SpO2/FiO2 index > 200 and 41.6% had anuria. The mean number of procedures was 2.01 ? 1.36. The most frequent modality was hemodiafiltration in 67.3% of patients, and 46% used the oXiris? membrane. Using binary logistic regression, including demographic parameters, comorbidities, as well as clinical parameters before CRRT, it was found that patients with previous kidney disease were 3.43 times more susceptible to developing AKI, and patients with SpO2/FiO2 index ? 200 were 69% less susceptible to developing AKI/AKI on CKD requiring CRRT in the first 24 hrs from the start of IMV. Conclusion. Determining the risk factors for AKI/AKI on CKD is important for planning the prevention of these conditions that require the application of CRRT with the correct choice of dialysis modality and dose, membrane/filter type, and anticoagulant dose.

A novel multiplex biomarker panel for profiling human acute and chronic kidney disease

Acute and chronic kidney disease continues to confer significant morbidity and mortality in the clinical setting. Despite high prevalence of these conditions, few validated biomarkers exist to predict kidney dysfunction. In this study, we utilized a novel kidney multiplex panel to measure 21 proteins in plasma and urine to characterize the spectrum of biomarker profiles in kidney disease. Blood and urine samples were obtained from age-/sex-matched healthy control subjects (HC), critically-ill COVID-19 patients with acute kidney injury (AKI), and patients with chronic or end-stage kidney disease (CKD/ESKD). Biomarkers were measured with a kidney multiplex panel, and results analyzed with conventional statistics and machine learning. Correlations were examined between biomarkers and patient clinical and laboratory variables. Median AKI subject age was 65.5 (IQR 58.5–73.0) and median CKD/ESKD age was 65.0 (IQR 50.0–71.5). Of the CKD/ESKD patients, 76.1% were on hemodialysis, 14.3% of patients had kidney transplant, and 9.5% had CKD without kidney replacement therapy. In plasma, 19 proteins were significantly different in titer between the HC versus AKI versus CKD/ESKD groups, while NAG and RBP4 were unchanged. TIMP-1 (PPV 1.0, NPV 1.0), best distinguished AKI from HC, and TFF3 (PPV 0.99, NPV 0.89) best distinguished CKD/ESKD from HC. In urine, 18 proteins were significantly different between groups except Calbindin, Osteopontin and TIMP-1. Osteoactivin (PPV 0.95, NPV 0.95) best distinguished AKI from HC, and β2-microglobulin (PPV 0.96, NPV 0.78) best distinguished CKD/ESKD from HC. A variety of correlations were noted between patient variables and either plasma or urine biomarkers. Using a novel kidney multiplex biomarker panel, together with conventional statistics and machine learning, we identified unique biomarker profiles in the plasma and urine of patients with AKI and CKD/ESKD. We demonstrated correlations between biomarker profiles and patient clinical variables. Our exploratory study provides biomarker data for future hypothesis driven research on kidney disease.

Endothelial Biomarkers in Critically Ill COVID-19 Patients: Potential Predictors of the Need for Dialysis.

The aim of this was to evaluate the function of vascular biomarkers to predict the need for hemodialysis in critically ill patients with COVID-19. This is a prospective study with 58 critically ill patients due to COVID-19 infection. Laboratory tests in general and vascular biomarkers, such as VCAM-1, syndecan-1, angiopoietin-1, and angiopoietin-2, were quantified on intensive care unit (ICU) admission. There was a 40% death rate. VCAM and Ang-2/Ang-1 ratio on ICU admission were associated with the need for hemodialysis. Vascular biomarkers (VCAM-1, syndecan-1, angiopoietin-2/angiopoietin-1 ratio) were predictors of death and their cutoff values were useful to stratify patients with a worse prognosis. In the multivariate cox regression analysis with adjusted models, VCAM-1 (OR 1.13 [CI 95%: 1.01-1.27]; p = 0.034) and Ang-2/Ang-1 ratio (OR 4.87 [CI 95%: 1.732-13.719]; p = 0.003) were associated with the need for dialysis. Vascular biomarkers, mostly VCAM-1 and Ang-2/Ang-1 ratio, showed better efficiency to predict the need for hemodialysis in critically ill COVID-19 patients.

Therapeutic plasma exchange in the treatment of COVID-19 induced cytokine storm: the first Moroccan experience

IntroductionCOVID-19 induced cytokine storm is a well-documented phenomena that contributes significantly in the disease’s evolution and prognosis. Therefore, therapies such as therapeutic plasma exchange, constitute a mainstay of therapeutic management especially for critically-ill patients.MethodsWe conducted a monocentric retrospective cohort study in the Resuscitation Department of the Mohammed VI University Hospital of Oujda-Morocco, to evaluate the efficiency of therapeutic plasma exchange on critically-ill COVID-19 patients over a 6 months period.We divided our patients into two groups: patients who received TPE (Therapeutic Plasma Exchange) sessions (TPE group) and patients who only benefited from the standard protocol treatment (non TPE group).ResultsOur study included a total of 165 patients, 34.5% of which benefited from TPE sessions.We observed an improvement of oxygenation parameters (SpO2 and PaO2/FiO2 ratio) and a progressive respiratory weaning, as well as a significant decrease of biomarkers indicative of inflammation (lymphocyte count, CRP (C Reactive Protein), IL-6, Ferritin) and coagulopathy (d-dimers, fibrinogen) in the TPE group after 5 consecutive TPE sessions.In comparison with the non-TPE group, The TPE-group patients had a shorter ICU (Intensive Care Unit) length of stay, required less frequently mechanical ventilation, and we more likely to be extubated. Furthermore, the TPE group had a lower mortality rate.DiscussionMultiple studies have reported the safety and efficiency of therapeutic plasma exchange in the COVID-19 induced cytokine storm. Given the urgent character of the pandemic at the time, each center followed its own protocol in implementing plasma exchange.ConclusionSimilar to the results reported in the literature, our study reports positive results after using TPE specifically in terms of respiratory weaning and an improvement of the cytokine storm biomarkers, and more importantly a lower mortality rate.

Tocilizumab in ICU-admitted COVID-19 Patients: A Retrospective Study.

Severe and critically-ill COVID-19 patients are characterized by a severe inflammatory response. Pharmacologic inhibition of acute-phase inflammatory pathways such as IL-6 receptor inhibitor, Tocilizumab (TCZ) may improve patient outcomes in these cases. Consequently, the therapeutic benefit of TCZ was evaluated in this study. We evaluated intravenous tocilizumab in severe and critically ill adult COVID-19 patients who met pre-defined stringent CRS criteria. A single-center, prospective, observational cohort study was carried out among consecutive adult (≥18 years of age) in-patients with COVID-19 between March 20, 2020 and March 20, 2021. In total, 354 patients were included in our study. Mortality and time to hospital discharge were compared between patients who received tocilizumab treatment (n = 177) and those who did not (n = 177). A total of 354 patients were analyzed whereas 177 patients were included in each group. In those receiving TCZ, all-cause mortality was significantly reduced, corresponding to an adjusted hazard ratio (HR) of 0.57, (95% confidence interval (CI): 0.43-0.76; P < 0.001). Furthermore, time to discharge was significantly improved in the TCZ group (HR: 1.66; 95%CI: 1.17-2.36, P = 0.004). Invasive mechanical ventilation was not statistically different among the study groups after adjusting for confounding variables (HR: 1.38; 95%CI: 0.89-2.14; P = 0.139). Dosing frequency was independent of survival status (P = 0.676). The use of TCZ in ICU-hospitalized patients resulted in improved patient survival and reduced duration of hospitalization. Further studies are needed to confirm the efficacy of TCZ in severe and critical COVID-19 cases.

Abstract #1400698: Performance of a Computerized Insulin Infusion Protocol in 359 Critically Ill Patients with COVID-19

People with diabetes and uncontrolled hyperglycemia are at high risk of COVID-19 complications and as such, many patients admitted to the ICU with COVID-19 have diabetes or stress hyperglycemia. It is suggested that quick and adequate control of hyperglycemia without increasing the risk of hypoglycemia is imperative to improve outcomes in these patients. Control of wide fluctuations of glycemic variances in these patients may often require modifications of existing strategies of glycemic management. Use of a computerized insulin infusion protocol (CIIP) in these settings could be largely beneficial in getting early and sustained glycemic control. We report our experience with the Lalani Insulin Infusion Protocol (LIIP), a novel CIIP with dynamic and adaptive glycemic targets in accordance with the patient’s glycemic state, in critically ill COVID-19 patients with hyperglycemia treated with IV insulin. We conducted a retrospective analysis of 359 critically-ill COVID-19 patients in whom LIIP was used (8/18/2020 to 08/31/2022) at six HonorHealth Hospitals in the Phoenix metropolitan area. Primary endpoints of the analysis included Time to Euglycemia (min), % of time in euglycemia (70-180 mg/dl), % of time in hyperglycemia (>180 mg/dl), and % of time in hypoglycemia (<70 mg/dl). We also report the average length of stay (ALOS) in the hospital and ICU as well as the discharge dispositions of these patients. Of the 359 critically ill COVID-19 patients who received IV insulin directed by LIIP, 167 patients had diabetes, 266 patients were treated with steroids, 226 patients had compromised renal function (eGFR< 60), 40 patients had sepsis, and 5 patients had cardiovascular comorbidities. The following glucometrics were observed: average Time to Euglycemia from baseline glucose values was 278 minutes, average % time in euglycemia was 83.01%, average % time in hyperglycemia was 16.77%, and average % time in hypoglycemia was 0.22%. Of the 359 patients, there were 166 deaths (46.2%), 91 patients were discharged to home (25.4%), and 102 patients were discharged to an interim facility (28.4%). The hospital ALOS was 15.02 days and ICU ALOS was 9.50 days. For HonorHealth hospitals, LIIP was a safe and effective method of quickly achieving and maintaining euglycemia in critically ill patients with COVID-19, while maintaining low hypoglycemia incidence. Herein the patients reported had varying degrees of comorbidities and treatments, including steroids and vasopressors; however, no modifications in glycemic management strategy or nursing workflow were necessary during the use of LIIP due to its adaptive formula which individualizes IV insulin rates for each patient.

Assessment of lung injury severity using ultrasound in critically ill COVID-19 patients in resource limited settings

BackgroundLung ultrasound is a non-invasive tool available at the bedside for the assessment of critically ill patients. The objective of this study was to evaluate the usefulness of lung ultrasound in assessing the severity of SARS-CoV-2 infection in critically-ill patients in a low-income setting.MethodsWe conducted a 12-month observational study in a university hospital intensive care unit (ICU) in Mali, on patients admitted for COVID-19 as diagnosed by a positive polymerase chain reaction for SARS-CoV-2 and/or typical lung computed tomography scan findings.ResultsThe inclusion criteria was met by 156 patients with a median age of 59 years. Almost all patients (96%) had respiratory failure at admission and many needed respiratory support (121/156, 78%). The feasibility of lung ultrasound was very good, with 1802/1872 (96%) quadrants assessed. The reproducibility was good with an intra-class correlation coefficient of elementary patterns of 0.74 (95% CI 0.65, 0.82) and a coefficient of repeatability of lung ultrasound score < 3 for an overall score of 24. Confluent B lines were the most common lesions found in patients (155/156). The overall mean ultrasound score was 23 ± 5.4, and was significantly correlated with oxygen saturation (Pearson correlation coefficient of − 0.38, p < 0.001). More than half of the patients died (86/156, 55.1%). The factors associated with mortality, as shown by multivariable analysis, were: the patients’ age; number of organ failures; therapeutic anticoagulation, and lung ultrasound score.ConclusionLung ultrasound was feasible and contributed to characterize lung injury in critically-ill COVID-19 patients in a low income setting. Lung ultrasound score was associated with oxygenation impairment and mortality.

Resource utilization and preparedness within the COVID-19 pandemic in Tunisian medical intensive care units: A nationwide retrospective multicentre observational study

BackgroundThe worldwide SARS-CoV-2 pandemic represents the most recent global healthcare crisis. While all healthcare systems suffered facing the immense burden of critically-ill COVID-19 patients, the levels of preparedness and adaptability differed highly between countries. Aim: to describe resource mobilization throughout the COVID-19 waves in Tunisian University Medical Intensive Care Units (MICUs) and to identify discrepancies in preparedness between the provided and required resource. MethodsThis is a longitudinal retrospective multicentre observational study conducted between March 2020 and May 2022 analyzing data from eight University MICUs. Data were collected at baseline and at each bed expansion period in relation to the nation’s four COVID-19 waves. Data collected included epidemiological, organizational and management trends and outcomes of COVID-19 and non-COVID-19 admissions. ResultsMICU-beds increased from 66 to a maximum of 117 beds. This was possible thanks to equipping pre-existing non-functional MICU beds (n = 20) and creating surge ICU-beds in medical wards (n = 24). MICU nurses increased from 53 to 200 of which 99 non-ICU nurses, by deployment from other departments and temporary recruitment. The nurse-to-MICU-bed ratio increased from 1:1 to around 1·8:1. Only 55% of beds were single rooms, 80% were equipped with ICU ventilators. These MICUs managed to admit a total of 3368 critically-ill patients (15% of hospital admissions). 33·2% of COVID-19-related intra-hospital deaths occurred within the MICUs. ConclusionDespite a substantial increase in resource mobilization during the COVID-19 pandemic, the current study identified significant persisting discrepancies between supplied and required resource, at least partially explaining the poor overall prognosis of critically-ill COVID-19 patients.

Comparison of Cumulative Corticosteroid Doses in Critically-ill COVID-19 Patients

Comparison of Cumulative Corticosteroid Doses in Critically-ill COVID-19 Patients

EFFECTS OF DIABETES AND FIRST-WEEK HYPERGLYCEMIC EPISODE FREQUENCY ON THE MORTALITY AND INFLAMMATION IN CRITICALLY ILL COVID-19 PATIENTS: A CASE-CONTROL STUDY.

We know that mortality had increased in diabetic patients with COVID-19 pneumonia. The aim of this study was to compare the mortality and inflammation parameters difference in critically ill COVID-19 patients according to their admission HbA1c levels and diabetes mellitus status. Secondary aim was to evaluate the effect of the first week hyperglycemic episode frequency on mortality. Critically ill COVID-19 patients who were tested for HbA1c levels on ICU admission were analyzed retrospectively. Of 218 COVID PCR(+) patients, 139 met the inclusion criteria in study period. The median age was 67 [57-76] years and 55(40%) of them were female. Seventy-six (55%) of the patients required invasive mechanical ventilation (IMV). The IMV requirement was higher in diabetic patients (p=0.01). When the groups were compared in terms of inflammatory parameters no significant difference was found except for admission and first week's highest fibrinogen levels (p=0.02 and p=0.03, respectively). In multivariate analysis, fibrinogen levels were not determined as a risk factor for mortality. Overall ICU mortality was 43% (60/139). In group-1 23 (37%), in group-2 27 (57%), and in group-3 10 (34%) patients had died. There was no statistically significant difference between groups in terms of mortality (p=0.05). Records of 96 (69%) patients revealed there were more than five glucose readings over 180mg/dL during the first week. Mortality was higher in patients with more frequently hyperglycemic recordings (p=0.03). There was no significant mortality and inflammatory parameters difference in patients with and without diabetes. However, more than five glucose readings over 180mg/dL during the first week were found with increased mortality.

Use of high-flow nasal cannula oxygen and risk factors for high-flow nasal cannula oxygen failure in critically-ill patients with COVID-19

BackgroundHigh-flow nasal oxygen therapy (HFNC) may be an attractive first-line ventilatory support in COVID-19 patients. However, HNFC use for the management of COVID-19 patients and risk factors for HFNC failure remain to be determined.MethodsIn this retrospective study, we included all consecutive COVID-19 patients admitted to our intensive care unit (ICU) in the first (Mars-May 2020) and second (August 2020- February 202) French pandemic waves. Patients with limitations for intubation were excluded. HFNC failure was defined as the need for intubation after ICU admission. The impact of HFNC use was analyzed in the whole cohort and after constructing a propensity score. Risk factors for HNFC failure were identified through a landmark time-dependent cause-specific Cox model. The ability of the 6-h ROX index to detect HFNC failure was assessed by generating receiver operating characteristic (ROC) curve.Results200 patients were included: HFNC was used in 114(57%) patients, non-invasive ventilation in 25(12%) patients and 145(72%) patients were intubated with a median delay of 0 (0–2) days after ICU admission. Overall, 78(68%) patients had HFNC failure. Patients with HFNC failure had a higher ICU mortality rate (34 vs. 11%, p = 0.02) than those without. At landmark time of 48 and 72 h, SAPS-2 score, extent of CT-Scan abnormalities > 75% and HFNC duration (cause specific hazard ratio (CSH) = 0.11, 95% CI (0.04–0.28), per + 1 day, p < 0.001 at 48 h and CSH = 0.06, 95% CI (0.02–0.23), per + 1 day, p < 0.001 at 72 h) were associated with HFNC failure. The 6-h ROX index was lower in patients with HFNC failure but could not reliably predicted HFNC failure with an area under ROC curve of 0.65 (95% CI(0.52–0.78), p = 0.02). In the matched cohort, HFNC use was associated with a lower risk of intubation (CSH = 0.32, 95% CI (0.19–0.57), p < 0.001).ConclusionsIn critically-ill COVID-19 patients, while HFNC use as first-line ventilatory support was associated with a lower risk of intubation, more than half of patients had HFNC failure. Risk factors for HFNC failure were SAPS-2 score and extent of CT-Scan abnormalities > 75%. The risk of HFNC failure could not be predicted by the 6-h ROX index but decreased after a 48-h HFNC duration.

Relation between macrophage inflammatory protein-1 and intercellular adhesion molecule-1 and computed tomography findings in critically-ill saudi covid-19 patients

BackgroundSeveral, clinical and biochemical factors were suggested as risk factors for more severe forms of Covid-19. Macrophage inflammatory protein-1 alpha (MIP-1α, CCL3) is a chemokine mainly involved in cell adhesion and migration. Intracellular adhesion molecule 1 (ICAM-1) is an inducible cell adhesion molecule involved in multiple immune processes. The present study aimed to assess the relationship between baseline serum MIP-1α and ICAM-1 level in critically-ill Covid-19 patients and the severity of computed tomography (CT) findings. MethodsThe study included 100 consecutive critically-ill patients with Covid-19 infection. Diagnosis of infection was established on the basis of RT-PCR tests. Serum MIP-1α and ICAM-1 levels were assessed using commercially available ELISA kits. All patients were subjected to a high-resolution computed tomography assessment. ResultsAccording to the computed tomography severity score, patients were classified into those with moderate/severe (n=49) and mild (n = 51) pulmonary involvement. Severe involvement was associated with significantly higher MIP-1α and ICAM-1 level. Correlation analysis identified significant positive correlations between MIP-1α and age, D-dimer, IL6, in contrast, there was an inverse correlation with INF-alpha. Additionally, ICAM-1 showed significant positive correlations with age, D‐Dimer,- TNF—α, IL6,while an inverse correlation with INF-alpha was observed. ConclusionsMIP-1α and ICAM-1 level are related to CT radiological severity in Covid-19 patients. Moreover, these markers are well-correlated with other inflammatory markers suggesting that they can be used as reliable prognostic markers in Covid-19 patients.

Renoprotective Effects of Luteolin: Therapeutic Potential for COVID-19-Associated Acute Kidney Injuries.

Acute kidney injury (AKI) has been increasingly reported in critically-ill COVID-19 patients. Moreover, there was significant positive correlation between COVID-19 deaths and renal disorders in hospitalized COVID-19 patients with underlying comorbidities who required renal replacement therapy. It has suggested that death in COVID-19 patients with AKI is 3-fold higher than in COVID-19 patients without AKI. The pathophysiology of COVID-19-associated AKI could be attributed to unspecific mechanisms, as well as COVID-19-specific mechanisms such as direct cellular injury, an imbalanced renin-angiotensin-aldosterone system, pro-inflammatory cytokines elicited by the viral infection and thrombotic events. To date, there is no specific treatment for COVID-19 and its associated AKI. Luteolin is a natural compound with multiple pharmacological activities, including anticoronavirus, as well as renoprotective activities against kidney injury induced by sepsis, renal ischemia and diverse nephrotoxic agents. Therefore, in this review, we mechanistically discuss the anti-SARS-CoV-2 and renoprotective activities of luteolin, which highlight its therapeutic potential in COVID-19-AKI patients.

Association between Brain Injury Markers and Testosterone in Critically-Ill COVID-19 Male Patients.

Accumulating data suggest that various neurologic manifestations are reported in critically-ill COVID-19 patients. Although low testosterone levels were associated with poor outcomes, the relationship between testosterone levels and indices of brain injury are still poorly understood. Therefore, we aimed to explore whether testosterone levels are associated with glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), biomarkers of brain injury, in patients with a severe form of COVID-19. The present study was conducted on 65 male patients aged 18-65 with severe COVID-19. Blood samples were collected at three time points: upon admission to ICU, 7 days after, and 14 days after. In patients with neurological sequels (n = 20), UCH-L1 serum concentrations at admission were markedly higher than in patients without them (240.0 (155.4-366.4) vs. 146.4 (92.5-243.9) pg/mL, p = 0.022). GFAP concentrations on admission did not differ between the groups (32.2 (24.2-40.1) vs. 29.8 (21.8-39.4) pg/mL, p = 0.372). Unlike GFAP, UCH-L1 serum concentrations exhibited a negative correlation with serum testosterone in all three time points (r = -0.452, p &lt; 0.001; r = -0.430, p &lt; 0.001 and r = -0.476, p = 0.001, respectively). The present study suggests that the traumatic brain injury biomarker UCH-L1 may be associated with neurological impairments seen in severe COVID-19. Moreover, a negative correlation between UCH-L1 and serum testosterone concentrations implies that testosterone may have a role in the development of neurological sequels in critically-ill COVID-19 patients.

Lung ultrasound to predict gas-exchange response to prone positioning in COVID-19 patients: A prospective study in pilot and confirmation cohorts

PurposeTo examine whether lung ultrasound prior to prone positioning can predict the resulting gas-exchange response. Materials and methodsThis is a prospective observational study on critically-ill COVID-19 patients with a pilot and confirmation cohort. Lung ultrasound examinations were performed before prone positioning and gas-exchange parameters were recorded before and after position change. ResultsA total of 79 patients, 36 in the pilot cohort and 43 in the confirmation cohort, were included. In the pilot cohort, a moderate correlation between pre-turn lung ultrasound score index (LUSI) and change in PaO2/FiO2 after prone positioning was found. These findings were corroborated and extended upon in the confirmation cohort. The confirmation cohort found that anterior LUSI had the strongest correlation with follow-up time-points 1, 6, 12, and 24 h after prone positioning, with strength of correlation gradually increasing up to 24 h. In a multivariate model anterior aeration loss (odds ratio 0.035; 95%CI 0.003–0.319 for anterior LUSI >50%) and higher pre-turn PaCO2 (odds ratio 0.479 95% CI 0.235–0.979) were negatively predictive of a PaO2/FiO2 increase ≥20 mmHg. ConclusionsAnterior LUSI, in addition to other clinical parameters, may be used to aid COVID-19 respiratory strategy and a clinician's decision to prone.

Assessment of Admission COVID-19 Associated Hyperinflammation Syndrome Score in Critically-Ill COVID-19 Patients.

PurposeWe aimed to evaluate the relation between admission COVID-19 associated hyperinflammatory syndrome (cHIS) score and intensive care unit (ICU) outcomes.Materials and MethodsPatients with laboratory confirmed COVID-19 admitted to our ICU between 20th March 2020-15th June 2021 were included. Patients who received immunomodulatory treatment except corticosteroids were excluded. Main outcomes were ICU mortality and invasive mechanical ventilation (IMV) requirement after ICU admission.ResultsThree hundred and seventy patients with a median (IQR) age of 66 (56-77) were analyzed. Median admission cHIS score was 3 (2-4). A cHIS score ≥3 was found to be associated with ICU mortality (sensitivity = 0.63, specificity = 0.50; p < 0.01) and IMV requirement after ICU admission (sensitivity = 0.61, specificity = 0.51; p < 0.01). Patients with an admission cHIS score ≥3 (n = 199) had worse median admission APACHEII, SOFA scores and PaO2/FiO2 ratio than others (n = 171) (p < 0.01). IMV requirement after ICU admission (38.5% vs 26.1%;p = 0.03), ICU (36.2% vs 25.1%;p = 0.02), hospital (39.1% vs 26.9%;p = 0.01) and 28th day (28.1% vs 19.1%;p = 0.04) mortality were higher in patients with admission cHIS score ≥3 than others (p < 0.01). Age <65 years, malignancy and higher admission SOFA score were independent variables associated with admission cHIS score ≥3.ConclusionCritically-ill COVID-19 patients with admission cHIS score ≥3 have worse disease severity and outcomes than other patients.

Effect of Tocilizumab in Terms of Hospital Stay and Mortality Pattern Among Patients with Severe Versus Critically-ill COVID-19 Patients: A Comparative Analytic Study

Background and Objectives: Most patients with mild and moderate COVID-19 infection recover with standard care therapy. Mortality in patients with severe illness and those critically ill is high. Tocilizumab acts by blocking interleukin-6 receptors and shows promising results in severe disease. Aim of this study was to assess the effect of Tocilizumab in severe and critically ill COVID-19 patients in terms hospital stay and reducing the risk of death. Methods: In this comparative analytical, single-center study undertaken in DHQ university teaching hospital Gujranwala, forty-four patients were enrolled after an informed consent through non-probability consecutive sampling. The patients were categorized based on oxygen requirement as severe (oxygen requirement 10 L/min) and critically ill patients (oxygen requirement 15 L/min). All patients were treated with injection Tocilizumab (8mg per kg body weight) using criteria based on oxygen requirement (10L/min or more) and increased levels of any two of the laboratory investigations including CRP, D-Dimers, serum ferritin and LDH. Sociodemographic and clinical profile were collected using a semi-structured proforma. Outcome of interest was hospital stay and mortality. Comparison of effect of Tocilizumab was analyzed in regards to age, sex, laboratory investigations and stated outcome using Pearson's Chi-squared test. P-value of ≤0.05 was considered statistically significant. Data were analyzed using SPSS version 24.0. Results: Of 44 COVID-19 patients, 26 (59.1%) had severe disease and 18 (40.9%) were critically ill. We did not observe any statistical difference between these two categories as regards age, sex, hospital stay or presence of co-morbid conditions. However, there were 17 (94%) deaths observed among critically ill patients, while one patient died with severe disease. This mortality difference was found statistically significant (p&lt;0.001). Conclusion: Tocillizumab has shown significant effect to reduce mortality and minimizing hospital stay amongst COVID-19 patients with severe disease only with minimal effect in critically ill patients. Tocilizumab may be introduced early in treatment plan for severe COVID-19 patients.

Prolonged ICU Stay in Severe and Critically-Ill COVID-19 Patients Who Received Convalescent Plasma Therapy.

Background Convalescent plasma administration in severe and critically-ill COVID-19 patients have been proven to not provide improvement in patients' outcome, yet it is still widely used in countries with limited resources due to its high availability and safety. This study aims to investigate its effects on ICU mortality, ICU length of stay (LoS), and improvement of oxygen support requirements. Methods Data of all severe and critically-ill patients in our COVID-19 ICU was collected retrospectively between May and November 2020. We dichotomized the variables and compared outcome data of 48 patients, who received convalescent plasma to 131 patients, receiving standard of care. Data were analyzed using multiple logistic regression to make prediction models of mortality, length of stay, and oxygen support device requirement. Result Overall mortality rate in our COVID-19 ICU was 55.3%, with a median overall length of stay of 8 (4–11) days. Less patients that received convalescent plasma presented with the need for mechanical ventilation on ICU admission (p < 0.001), but with comparable PaO2 to FiO2 (P/F) ratio (p=0.95). Factors that confounded mortality were obesity (aOR = 14.1; 95% CI (1.25, 166.7); p=0.032), mechanical ventilation (aOR = 333; 95% CI (4.5,1,000); p < 0.001), higher neutrophil-to-lymphocyte ratio (NLR) (aOR = 7.32; 95% CI (1.82, 29.4); p=0.005), and lower P/F ratio (aOR = 7.70; 95% CI (2.04, 29.4); p=0.003). ICU LoS was longer in patients, who had prior history of hypertension (aOR = 2.14; 95% CI (1.05, 4.35); p=0.036) and received convalescent plasma (aOR = 3.88; 95% CI (1.77, 8.05); p < 0.001). Deceased patients, who received convalescent plasma, stayed longer in the ICU with a mean length of stay of 12.87 ± 5.7 days versus 8.13 ± 4.8 days with a significant difference (U = 434; p < 0.000). The chance of improved oxygen support requirements was lower in obese patients (aOR = 9.18; 95%CI (2.0, 42.1); p < 0.004), mechanically ventilated patients (aOR = 13.15; 95% CI (3.75, 46.09); p < 0.001), patients with higher NLR (aOR = 2.5; 95% CI (1.07, 5.85); p=0.034), and lower P/F ratio (aOR = 2.76; 95% CI (1.1, 6.91); p=0.031). Conclusion The length of stay of patients in the convalescent plasma group was significantly longer than the control group. There was no effect of convalescent plasma in ICU mortality and no improvement was observed in terms of oxygen support requirements.