Transfusion practice in patients receiving VV ECMO (PROTECMO): a prospective, multicentre, observational study.

BACKGROUND: In patients receiving venovenous (VV) extracorporeal membrane oxygenation (ECMO) packed red blood cell (PRBC) transfusion thresholds are usually higher than in other patients who are critically ill. Available guidelines suggest a restrictive approach, but do not provide specific recommendations on the topic. The main aim of this study was, in a short timeframe, to describe the actual values of haemoglobin and the rate and the thresholds for transfusion of PRBC during VV ECMO. METHODS: PROTECMO was a multicentre, prospective, cohort study done in 41 ECMO centres in Europe, North America, Asia, and Australia. Consecutive adult patients with acute respiratory distress syndrome (ARDS) who were receiving VV ECMO were eligible for inclusion. Patients younger than 18 years, those who were not able to provide informed consent when required, and patients with an ECMO stay of less than 24 h were excluded. Our main aim was to monitor the daily haemoglobin concentration and the value at the point of PRBC transfusion, as well as the rate of transfusions. The practice in different centres was stratified by continent location and case volume per year. Adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for baseline and time varying confounding. FINDINGS: Between Dec 1, 2018, and Feb 22, 2021, 604 patients were enrolled (431 [71%] men, 173 [29%] women; mean age 50 years [SD 13·6]; and mean haemoglobin concentration at cannulation 10·9 g/dL [2·4]). Over 7944 ECMO days, mean haemoglobin concentration was 9·1 g/dL (1·2), with lower concentrations in North America and high-volume centres. PRBC were transfused on 2432 (31%) of days on ECMO, and 504 (83%) patients received at least one PRBC unit. Overall, mean pretransfusion haemoglobin concentration was 8·1 g/dL (1·1), but varied according to the clinical rationale for transfusion. In a time-dependent Cox model, haemoglobin concentration of less than 7 g/dL was consistently associated with higher risk of death in the intensive care unit compared with other higher haemoglobin concentrations (hazard ratio [HR] 2·99 [95% CI 1·95-4·60]); PRBC transfusion was associated with lower risk of death only when transfused when haemoglobin concentration was less than 7 g/dL (HR 0·15 [0·03-0·74]), although no significant effect in reducing mortality was reported for transfusions for other haemoglobin classes (7·0-7·9 g/dL, 8·0-9·9 g/dL, or higher than 10 g/dL). INTERPRETATION: During VV ECMO, there was no universally accepted threshold for transfusion, but PRBC transfusion was invariably associated with lower mortality only when done with haemoglobin concentration of less than 7 g/dL. FUNDING: Extracorporeal Life Support Organization.

Persistence of spike-specific immune responses in BNT162b2-vaccinated donors and generation of rapid ex-vivo T cells expansion protocol for adoptive immunotherapy: A pilot study.

Introduction: The BNT162b2 mRNA-based vaccine has shown high efficacy in preventing COVID-19 infection but there are limited data on the types and persistence of the humoral and T cell responses to such a vaccine. Methods: Here, we dissect the vaccine-induced humoral and cellular responses in a cohort of six healthy recipients of two doses of this vaccine. Results and discussion: Overall, there was heterogeneity in the spike-specific humoral and cellular responses among vaccinated individuals. Interestingly, we demonstrated that anti-spike antibody levels detected by a novel simple automated assay (Jess) were strongly correlated (r=0.863, P<0.0001) with neutralizing activity; thus, providing a potential surrogate for neutralizing cell-based assays. The spike-specific T cell response was measured with a newly modified T-spot assay in which the high-homology peptide-sequences cross-reactive with other coronaviruses were removed. This response was induced in 4/6 participants after the first dose, and all six participants after the second dose, and remained detectable in 4/6 participants five months post-vaccination. We have also shown for the first time, that BNT162b2 vaccine enhanced T cell responses also against known human common viruses. In addition, we demonstrated the efficacy of a rapid ex-vivo T cell expansion protocol for spike-specific T cell expansion to be potentially used for adoptive-cell therapy in severe COVID-19, immunocompromised individuals, and other high-risk groups. There was a 9 to 13.7-fold increase in the number of expanded T cells with a significant increase of anti-spike specific response showing higher frequencies of both activation and cytotoxic markers. Interestingly, effector memory T cells were dominant in all four participants' CD8+ expanded memory T cells; CD4+ T cells were dominated by effector memory in 2/4 participants and by central memory in the remaining two participants. Moreover, we found that high frequencies of CD4+ terminally differentiated memory T cells were associated with a greater reduction of spike-specific activated CD4+ T cells. Finally, we showed that participants who had a CD4+ central memory T cell dominance expressed a high CD69 activation marker in the CD4+ activated T cells.

Bleeding Hazard of Percutaneous Tracheostomy in COVID-19 Patients Supported With Venovenous Extracorporeal Membrane Oxygenation: A Case Series.

OBJECTIVES: Tracheostomy usually is performed to aid weaning from mechanical ventilation and facilitate rehabilitation and secretion clearance. Little is known about the safety of percutaneous tracheostomy in patients with severe COVID-19 supported on venovenous extracorporeal membrane oxygenation (VV-ECMO). This study aimed to investigate the bleeding risk of bedside percutaneous tracheostomy in patients with COVID-19 infection supported with VV-ECMO. DESIGN: A Retrospective review of electronic data for routine care of patients on ECMO. SETTING: Tertiary, university-affiliated national ECMO center. PARTICIPANTS: Patients with COVID-19 who underwent percutaneous tracheostomy while on VV-ECMO support. INTERVENTIONS: No intervention was conducted during this study. MEASUREMENTS AND MAIN RESULTS: Electronic medical records of 16 confirmed patients with COVID-19 who underwent percutaneous tracheostomy while on VV-ECMO support, including patient demographics, severity of illness, clinical variables, procedural complications, and outcomes, were compared with 16 non-COVID-19 patients. The SPSS statistical software was used for statistical analysis. The demographic data were compared using the chi-square test, and normality assumption was tested using the Shapiro-Wilk test. The indications for tracheostomy in all the patients were prolonged mechanical ventilation and sedation management. None of the patients suffered a life-threatening procedural complication within 48 hours. Moderate-to-severe bleeding was similar in both groups. There was no difference in 30- and 90-days mortality between both groups. As per routine screening results, none of the staff involved contracted COVID-19 infection. CONCLUSIONS: In this case series, percutaneous tracheostomy during VV-ECMO in patients with COVID-19 appeared to be safe and did not pose additional risks to patients or healthcare workers.

IoT-based mock oxygenator for extracorporeal membrane oxygenation simulator.

BACKGROUND: Training is an essential aspect of providing high-quality treatment and ensuring patient safety in any medical practice. Because extracorporeal membrane oxygenation (ECMO) is a complicated operation with various elements, variables, and irregular situations, doctors must be experienced and knowledgeable about all conventional protocols and emergency procedures. The conventional simulation approach has a number of limitations. The approach is intrinsically costly since it relies on disposable medical equipment (i.e., oxygenators, heat exchangers, and pumps) that must be replaced regularly due to the damage caused by the liquid used to simulate blood. The oxygenator, which oxygenates the blood through a tailored membrane in ECMO, acts as a replacement for the patient's natural lung. For the context of simulation-based training (SBT) oxygenators are often expensive and cannot be recycled owing to contamination issues. METHODS: Consequently, it is advised that the training process include a simulated version of oxygenators to optimize reusability and decrease training expenses. Toward this goal, this article demonstrates a mock oxygenator for ECMO SBT, designed to precisely replicate the real machine structure and operation. RESULTS: The initial model was reproduced using 3D modeling and printing. Additionally, the mock oxygenator could mimic frequent events such as pump noise and clotting. Furthermore, the oxygenator is integrated with the modular ECMO simulator using cloud-based communication technology that goes in hand with the internet of things technology to provide remote control via an instructor tablet application. CONCLUSIONS: The final 3D modeled oxygenator body was tested and integrated with the other simulation modules at Hamad Medical Corporation with several participants to evaluate the effectiveness of the training session.

Bleeding Hazard of Percutaneous Tracheostomy in COVID-19 Patients Supported with Veno-venous Extracorporeal Membrane Oxygenation: A Case Series

Objectives Tracheostomy is usually performed to aid weaning from mechanical ventilation and facilitate rehabilitation and secretion clearance. Little is known about the safety of percutaneous tracheostomy in patients with severe COVID-19 supported on veno-venous extracorporeal membrane oxygenation (VV-ECMO). This study aims to investigate the bleeding risk of bedside percutaneous tracheostomy in patients with COVID-19 infection supported with VV-ECMO. Design A Retrospective review of electronic data for routine care of patients on ECMO. Setting Tertiary, university affiliated national ECMO centre. Participants COVID-19 patients who underwent percutaneous tracheostomy while on VV-ECMO support. Interventions No intervention was conducted during this study. Measurements and Main Results: Electronic medical records of 16 confirmed COVID-19 patients who underwent percutaneous tracheostomy while on VV-ECMO support, including patient demographics, severity of illness, clinical variables, procedural complications, and outcome were compared with 16 non-COVID-19 cases. SPSS statistical software was used for statistical analysis. Demographic data were compared using the chi-square test and normality assumption was test using Shapiro-Wilk test. The indications for tracheostomy in all the cases were prolonged mechanical ventilation and sedation management. None of the patients suffered a life-threatening procedural complication within 48 hours. Moderate to severe bleeding was similar in both groups. There was no difference in 30 and 90-days mortality between both groups. As per routine screening results, none of the staff involved contracted COVID-19 infection. Conclusions In this case series percutaneous tracheostomy during VV-ECMO in COVID-19 patients appeared to be safe and did not pose additional risks to patients or healthcare workers.

Association of periodontal therapy, with inflammatory biomarkers and complications in COVID-19 patients: a case control study.

BACKGROUND: In previous studies, COVID-19 complications were reported to be associated with periodontitis. Accordingly, this study was designed to test the hypothesis that a history of periodontal therapy could be associated with lower risk of COVID-19 complications. METHODS: A case-control study was performed using the medical health records of COVID-19 patients in the State of Qatar between March 2020 and February 2021 and dental records between January 2017 and December 2021. Cases were defined as COVID-19 patients who suffered complications (death, ICU admissions and/or mechanical ventilation); controls were COVID-19 patients who recovered without major complications. Associations between a history of periodontal therapy and COVID-19 complications were analysed using logistic regression models adjusted for demographic and medical factors. Blood parameters were compared using Kruskal-Wallis test. RESULTS: In total, 1,325 patients were included. Adjusted odds ratio (AOR) analysis revealed that non-treated periodontitis was associated with significant risk of need for mechanical ventilation (AOR = 3.91, 95% CI 1.21-12.57, p = 0.022) compared to periodontally healthy patients, while treated periodontitis was not (AOR = 1.28, 95% CI 0.25-6.58, p = 0.768). Blood analyses revealed that periodontitis patients with a history of periodontal therapy had significantly lower levels of D-dimer and Ferritin than non-treated periodontitis patients. CONCLUSION: Among COVID-19 patients with periodontal bone loss, only those that have not received periodontal therapy had higher risk of need for assisted ventilation. COVID-19 patients with a history of periodontal therapy were associated with significantly lower D-dimer levels than those without recent records of periodontal therapy. CLINICAL RELEVANCE: The fact that patients with treated periodontitis were less likely to suffer COVID-19 complications than non-treated ones further strengthen the hypothesis linking periodontitis to COVID-19 complications and suggests that managing periodontitis could help reduce the risk for COVID-19 complications, although future research is needed to verify this.

Prognostic tools and candidate drugs based on plasma proteomics of patients with severe COVID-19 complications.

COVID-19 complications still present a huge burden on healthcare systems and warrant predictive risk models to triage patients and inform early intervention. Here, we profile 893 plasma proteins from 50 severe and 50 mild-moderate COVID-19 patients, and 50 healthy controls, and show that 375 proteins are differentially expressed in the plasma of severe COVID-19 patients. These differentially expressed plasma proteins are implicated in the pathogenesis of COVID-19 and present targets for candidate drugs to prevent or treat severe complications. Based on the plasma proteomics and clinical lab tests, we also report a 12-plasma protein signature and a model of seven routine clinical tests that validate in an independent cohort as early risk predictors of COVID-19 severity and patient survival. The risk predictors and candidate drugs described in our study can be used and developed for personalized management of SARS-CoV-2 infected patients.

Emerging COVID-19 variants and their impact on SARS-CoV-2 diagnosis, therapeutics and vaccines.

The emergence of novel and evolving variants of SARS-CoV-2 has fostered the need for change in the form of newer and more adaptive diagnostic methods for the detection of SARS-CoV-2 infections. On the other hand, developing rapid and sensitive diagnostic technologies is now more challenging due to emerging variants and varying symptoms exhibited among the infected individuals. In addition to this, vaccines remain the major mainstay of prevention and protection against infection. Novel vaccines and drugs are constantly being developed to unleash an immune response for the robust targeting of SARS-CoV-2 and its associated variants. In this review, we provide an updated perspective on the current challenges posed by the emergence of novel SARS-CoV-2 mutants/variants and the evolution of diagnostic techniques to enable their detection. In addition, we also discuss the development, formulation, working mechanisms, advantages, and drawbacks of some of the most used vaccines/therapeutic drugs and their subsequent immunological impact.Key messageThe emergence of novel variants of the SARS-CoV-2 in the past couple of months, highlights one of the primary challenges in the diagnostics, treatment, as well as vaccine development against the virus.Advancements in SARS-CoV-2 detection include nucleic acid based, antigen and immuno- assay-based and antibody-based detection methodologies for efficient, robust, and quick testing; while advancements in COVID-19 preventive and therapeutic strategies include novel antiviral and immunomodulatory drugs and SARS-CoV-2 targeted vaccines.The varied COVID-19 vaccine platforms and the immune responses induced by each one of them as well as their ability to battle post-vaccination infections have all been discussed in this review.

Mortality Prediction Utilizing Blood Biomarkers to Predict the Severity of COVID-19 Using Machine Learning Technique.

Healthcare researchers have been working on mortality prediction for COVID-19 patients with differing levels of severity. A rapid and reliable clinical evaluation of disease intensity will assist in the allocation and prioritization of mortality mitigation resources. The novelty of the work proposed in this paper is an early prediction model of high mortality risk for both COVID-19 and non-COVID-19 patients, which provides state-of-the-art performance, in an external validation cohort from a different population. Retrospective research was performed on two separate hospital datasets from two different countries for model development and validation. In the first dataset, COVID-19 and non-COVID-19 patients were admitted to the emergency department in Boston (24 March 2020 to 30 April 2020), and in the second dataset, 375 COVID-19 patients were admitted to Tongji Hospital in China (10 January 2020 to 18 February 2020). The key parameters to predict the risk of mortality for COVID-19 and non-COVID-19 patients were identified and a nomogram-based scoring technique was developed using the top-ranked five parameters. Age, Lymphocyte count, D-dimer, CRP, and Creatinine (ALDCC), information acquired at hospital admission, were identified by the logistic regression model as the primary predictors of hospital death. For the development cohort, and internal and external validation cohorts, the area under the curves (AUCs) were 0.987, 0.999, and 0.992, respectively. All the patients are categorized into three groups using ALDCC score and death probability: Low (probability < 5%), Moderate (5% < probability < 50%), and High (probability > 50%) risk groups. The prognostic model, nomogram, and ALDCC score will be able to assist in the early identification of both COVID-19 and non-COVID-19 patients with high mortality risk, helping physicians to improve patient management.

Association between periodontitis and severity of COVID-19 infection: A case-control study.

AIM: COVID-19 is associated with an exacerbated inflammatory response that can result in fatal outcomes. Systemic inflammation is also a main characteristic of periodontitis. Therefore, we investigated the association of periodontitis with COVID-19 complications. MATERIALS AND METHODS: A case-control study was performed using the national electronic health records of the State of Qatar between February and July 2020. Cases were defined as patients who suffered COVID-19 complications (death, ICU admissions or assisted ventilation), and controls were COVID-19 patients discharged without major complications. Periodontal conditions were assessed using dental radiographs from the same database. Associations between periodontitis and COVID 19 complications were analysed using logistic regression models adjusted for demographic, medical and behaviour factors. RESULTS: In total, 568 patients were included. After adjusting for potential confounders, periodontitis was associated with COVID-19 complication including death (OR = 8.81, 95% CI 1.00-77.7), ICU admission (OR = 3.54, 95% CI 1.39-9.05) and need for assisted ventilation (OR = 4.57, 95% CI 1.19-17.4). Similarly, blood levels of white blood cells, D-dimer and C Reactive Protein were significantly higher in COVID-19 patients with periodontitis. CONCLUSION: Periodontitis was associated with higher risk of ICU admission, need for assisted ventilation and death of COVID-19 patients, and with increased blood levels of biomarkers linked to worse disease outcomes.

Performance evaluation of five ELISA kits for detecting anti-SARS-COV-2 IgG antibodies.

OBJECTIVES: To evaluate and compare the performances of five commercial ELISA assays (EDI, AnshLabs, Dia.Pro, NovaTec, and Lionex) for detecting anti-SARS-CoV-2 IgG. METHODS: Seventy negative control samples (collected before the COVID-19 pandemic) and samples from 101 RT-PCR-confirmed SARS-CoV-2 patients (collected at different time points from symptom onset: ≤7, 8-14 and >14 days) were used to compare the sensitivity, specificity, agreement, and positive and negative predictive values of each assay with RT-PCR. A concordance assessment between the five assays was also conducted. Cross-reactivity with other HCoV, non-HCoV respiratory viruses, non-respiratory viruses, and nuclear antigens was investigated. RESULTS: Lionex showed the highest specificity (98.6%; 95% CI 92.3-99.8), followed by EDI and Dia.Pro (97.1%; 95% CI 90.2-99.2), NovaTec (85.7%; 95% CI 75.7-92.1), then AnshLabs (75.7%; 95% CI 64.5-84.2). All ELISA kits cross-reacted with one anti-MERS IgG-positive sample, except Lionex. The sensitivity was low during the early stages of the disease but improved over time. After 14 days from symptom onset, Lionex and NovaTec showed the highest sensitivity at 87.9% (95% CI 72.7-95.2) and 86.4% (95% CI 78.5-91.7), respectively. The agreement with RT-PCR results based on Cohen's kappa was as follows: Lionex (0.89) > NovaTec (0.70) > Dia.Pro (0.69) > AnshLabs (0.63) > EDI (0.55). CONCLUSION: The Lionex and NovaLisa IgG ELISA kits, demonstrated the best overall performance.