Innate immune deficiencies are associated with severity and poor prognosis in patients with COVID-19

COVID-19 can cause acute respiratory distress syndrome, leading to death in many individuals. Evidence of a deleterious role of the innate immune system is accumulating, but the precise mechanisms involved remain unclear. In this study, we investigated the links between circulating innate phagocytes and severity in COVID-19 patients. We performed in-depth phenotyping of neutrophil and monocyte subpopulations and measured soluble activation markers in plasma. Additionally, anti-microbial functions (phagocytosis, oxidative burst, and NETosis) were evaluated on fresh cells from patients. Neutrophils and monocytes had a strikingly disturbed phenotype, and elevated concentrations of activation markers (calprotectin, myeloperoxidase, and neutrophil extracellular traps) were measured in plasma. Critical patients had increased CD13low immature neutrophils, LOX-1 + and CCR5 + immunosuppressive neutrophils, and HLA-DRlow downregulated monocytes. Markers of immature and immunosuppressive neutrophils were strongly associated with severity. Moreover, neutrophils and monocytes of critical patients had impaired antimicrobial functions, which correlated with organ dysfunction, severe infections, and mortality. Together, our results strongly argue in favor of a pivotal role of innate immunity in COVID-19 severe infections and pleads for targeted therapeutic options.

Biomarker candidates for progression and clinical management of COVID-19 associated pneumonia at time of admission

COVID-19 pathophysiology is currently not fully understood, reliable prognostic factors remain elusive, and few specific therapeutic strategies have been proposed. In this scenario, availability of biomarkers is a priority. MS-based Proteomics techniques were used to profile the proteome of 81 plasma samples extracted in four consecutive days from 23 hospitalized COVID-19 associated pneumonia patients. Samples from 10 subjects that reached a critical condition during their hospital stay and 10 matched non-severe controls were drawn before the administration of any COVID-19 specific treatment and used to identify potential biomarkers of COVID-19 prognosis. Additionally, we compared the proteome of five patients before and after glucocorticoids and tocilizumab treatment, to assess the changes induced by the therapy on our selected candidates. Forty-two proteins were differentially expressed between patients' evolution groups at 10% FDR. Twelve proteins showed lower levels in critical patients (fold-changes 1.20–3.58), of which OAS3 and COG5 found their expression increased after COVID-19 specific therapy. Most of the 30 proteins over-expressed in critical patients (fold-changes 1.17–4.43) were linked to inflammation, coagulation, lipids metabolism, complement or immunoglobulins, and a third of them decreased their expression after treatment. We propose a set of candidate proteins for biomarkers of COVID-19 prognosis at the time of hospital admission. The study design employed is distinctive from previous works and aimed to optimize the chances of the candidates to be validated in confirmatory studies and, eventually, to play a useful role in the clinical practice.

What impact have Covid-19 pandemic on number of death occurring at the Emergency Department: A Retrospective Analysis of Mortality in India from January 2019 to May 2021

BackgroundAcute treatment in emergency case management is required for survival and stabilization of critical patients, followed by a shifting to the relevant medical department for further care. However, for the seriously ill critical patients, i.e., when the care provided by the Emergency Department (ED) of the hospital is not enough to enable transfer, death may occur while treatment in the emergency department. This aspect of emergency management is often overlooked, and very few researcher and government is really serious regarding who dies in the ED. Aim and ObjectiveThe aim of my study was to determine the total Mortality occurring in India from 1st January 2019 to 31st May 2021(limitation here due to data availability is limited from accredited source) of emergency department admissions of public and private health facilities. The objective is to find out if there is increase or decrease in mortality of emergency department admissions during the covid-19 pandemic era by comparing average mortality of ED per month of public, private, rural, urban health facilities before the pandemic from 1st and 2nd year of pandemic i.e. 2020 and 2021 respectively MethodsThis research study is a cross sectional retrospective analysis of the mortality occurring at the emergency department of public and private, rural, urban hospitals from 1st January 2019 to May31st 2021 with aim to find out impact of covid-19. Electronic patient records from HMIS (health management information system) of MoHFW (ministry of health and family welfare) , Government of India is collected, observed, analyzed, compared for all patients deaths occurring at Emergency Department (ED) of public and private, rural, urban health facilities (n = 452102) during the period January 2019 to May 2021. ResultsThe study results found that largest total number of death occurred in the ED during may 2021 whereas the least number of deaths occurred in February 2019 (limitation is data availability up to May 2021 from accredited sources). During the first year of the pandemic, average mortality per month (Jan2020-Dec2020) in the emergency department (ED) of rural, urban, public and private hospitals in India was 16067per month whereas before the pandemic it was 12542 per month while during second year of pandemic i.e. 2021 the average mortality increased to 21758 per month (up to May 2021).DiscussionRecently a new strain omicron has again disrupted the normal life and lockdown and other measures are being implemented by different countries to save lives. The mortality at ED are having various etiologies, clinical severity at time of admission has a direct correlation with mortality, which requires the necessity of advanced triage system. There exists a lack of proper knowledge and advanced directives in the beginning i.e. December 2019 of the covid-19 pandemic era.Conclusions Due to novel disease majority of clinicians have challenging situation as well as Emergency Medicine (EM) teams faced a sudden increase in the number of cases with limited resources. Furthermore, a lack of proper knowledge and directives may have hindered access to proper care, as witnessed in many part of the world and available in various literatures. The authors hope that this study will help global researchers as well as policy makers to promote further research and discussion into preparation methods for such pandemics to reduce patient’s risk of death in the ED. KeywordsEmergency department, Death, Covid-19, Pandemic, Health facilities,

Regulatory T-cells are central hubs for age-, sex- and severity-associated cellular networks during COVID-19

Using single-cell proteomics by mass cytometry, we investigate changes to a broad selection of over 10,000,000 immune cells in a cohort of moderate, severe, and critical Japanese COVID-19 patients and healthy controls with a particular focus on regulatory T-cells (Tregs). We find significant disruption within all compartments of the immune system and the emergence of atypical CTLA-4high CD4 T-cells and proliferating HLA-DRlowCD38high Tregs associated with critical patients. We also observed disrupted regulation of humoral immunity in COVID-19, with a loss of circulating T follicular regulatory T cells (Tfr) and altered T follicular helper (Tfh)/Tfr and plasma cell/Tfr ratios, all of which are significantly lower in male patients. Shifting ratios of CXCR4 and CXCR5 expression in B-cells provides further evidence of an autoimmune phenotype and dysregulated humoral immunity. These results suggest that Tregs are central to the changing cellular networks of a wide range of cells in COVID-19 and that sex specific differences to the balance of Tfr, Tfh and plasma cells may have important implications for the specificity of the humoral immune response to SARS-CoV-2.

The Casualty Stabilization–Transportation Problem in a Large-Scale Disaster

We address the problem of picking up, stabilizing, and transporting casualties in response to mass-injury disasters. Our proposed methodology establishes the itinerary for collecting, on-site stabilization, and transporting victims considering capacitated vehicles and medical care centers. Unlike previous works, we minimize the time required to achieve on-site stabilization of each victim according to his age and level of severity of the injuries for their subsequent transfer to specialized medical centers. Thus, more critical patients will be the first to be stabilized, maximizing their chances of survival. In our methodology, the victims’ age, the injuries’ severity level, and their deterioration over time are considered critical factors in prioritizing care for each victim. We tested our approach using simulated earthquake scenarios in the city of Iquique, Chile, with multiple injuries. The results show that explicitly considering the on-site stabilization of the vital functions of the prioritized victims as an objective, before their transfer to a specialized medical center, allows treating and stabilizing patients earlier than with traditional objectives.

Đánh giá một số chỉ số huyết học và chuyển hóa liên quan đến kết cục điều trị của bệnh nhân Covid-19

TÓM TẮT Mục tiêu: Đánh giá các chỉ số huyết học, chuyển hóa và số yếu tố liên quan đến kết cục điều trị của bệnh nhân COVID-19 tại trung tâm hồi sức COVID-19 bệnh viện Trung ương Huế. Đối tượng và phương pháp: Chúng tôi tiến hành một nghiên cứu mô tả cắt ngang tiến hành trên 225 bệnh nhân COVID-19 nặng và nguy kịch điều trị tại Trung tâm Hồi sức COVID-19, Bệnh viện Trung ương Huế từ tháng 9 đến tháng 11 năm 2021. Kết quả: Có sự liên quan giữa tuổi cao và tỷ lệ tử vong do COVID-19, nhóm tuổi trên 60 có nguy cơ tử vong cao gấp 2,0 lần nhóm từ 60 tuổi trở xuống. Các chỉ số huyết học về bạch cầu, tiểu cầu có sự khác biệt mang ý nghĩa thống kê giữa nhóm tử vong và nhóm ra viện. Số lượng bạch cầu ở nhóm tử vong cao hơn nhóm ra viện, 17,5 (13,4 - 25,3) ngàn/mm3 so với 9,4 (6,4 - 13,6) ngàn/mm3, p < 0,001. Tỷ lệ bạch cầu đa nhân trung tính ở nhóm tử vong cao hơn nhóm ra viện nhưng tỷ lệ bạch cầu Lympho lại thấp hơn. Chỉ số NLR có sự khác biệt đáng kể giữa nhóm tử vong và nhóm ra viện, 37,5 (20,1 - 52,8) so với 11,8 (4,4 - 22,6), NLR có khả năng dự đoán khá tốt tử vong do COVID-19 với AUC = 0,78. Khi sử dụng điểm cắt 22,25, NLR có độ nhạy/độ đặc hiệu trong dự đoán tử vong do COVID-19 là 74,2% và 74.5%. Có sự khác biệt mang ý nghĩa thống kê về số lượng tiểu cầu ở nhóm tử vong và nhóm ra viện, 166 (106 - 289) triệu/mm3 so với 236 (183 - 338) mm3. ABSTRACT ASSESSMENT OF HEMATOLOGIC AND METABOLIC INDICATORS CONTRIBUTING TO TREATMENT OUTCOMES OF COVID-19 PATIENTS Objectives: To evaluate hematological features and metabolic characteristics; and determine the contributing factors to the treatment outcome of COVID-19 patients. Methods: We conducted a cross-sectional descriptive study on 225 severe and critical COVID-19 patients treated at this COVID-19 Resuscitation Center from September 2021 to November 2021. Results: There was an association between age and mortality caused by COVID-19, the age group over 60 has a 2.0 times higher risk of death than the group aged 60 and under. The hematological indices of leukocytes and platelets had statistically significant differences between the mortality group and the group of hospital discharge. The number of white blood cells in the mortality group was higher than the hospital discharge group, 17.5 (13.4 - 25.3) thousand/mm3 compared with 9.4 (6.4 - 13.6 thousand/mm3, p < 0.001). The rate of neutrophils in the mortality group was higher than in the discharge group, but the rate of lymphocytes was lower. The NLR index had a significant difference between the mortality group and the discharge group, 37.5 (20.1 - 52.8) compared with 11.8 (4.4 - 22.6), NLR could well mortality - predictdue to COVID-19 with AUC = 0.78. Using the 22.25 cut - off, the NLR had a sensitivity/specificity in predicting COVID-19 mortality of 74.2% and 74.5%, respectively. There was a statistically significant difference in platelet counts in the mortality and discharge groups, 166 (106 - 289) million/mm3 versus 236 (183 - 338) mm3. Keywords: COVID-19, severe and critical patients, NRL, leukocytes, platelets, mortality

In-hospital mortality in the emergency department: clinical and etiological differences between early and late deaths among patients awaiting admission

Objective Given that there are no studies on diseases that occur by waiting for hospitalization, we aimed to evaluate the main causes of death in the emergency room (ER) and their relationship with overcrowding.Methods Patients who died in the ER in the past 2 years (pediatrics and trauma victims excluded) were divided into two groups: patients who died within 6 hours of arrival (emergency department [ED] group) and patients who died later (LD group). We compared the causes of death, total vital signs, diagnostic tests performed, and therapy between the groups. We assessed for possible correlation between the number of monthly deaths per group and four variables of overcrowding: number of patients treated per month, waiting time before medical visit (W-Time), mean intervention time (I-Time), and number of patients admitted to the ward per month (NPA).Results During the two years, 175 patients had died in our ER (52% in ED group and 48% in LD group). The total time spent in the ER was, respectively, 2.9±0.2 hours for ED group and 17.9± 1.5 hours for LD group. The more frequent cause of death was cardiovascular syndrome (30%) in ED group and sepsis (27%) and acute respiratory failure (27%) in LD group. Positive correlations between number of monthly deaths and W-Time (R2 0.51, P<0.001), I-Time (R2 0.73, P< 0.0001), and NPA (R2 0.37, P<0.01) were found only in LD group.Conclusion Patients with sepsis and acute respiratory failure die after a long stay in the ER, and the risk increases with overcrowding. A fast-track pathway should be considered for hospital admission of critical patients.

Pathophysiology of Acute Respiratory Failure by CoV-2 Infection: Role of Oxidative Stress, Endothelial Dysfunction and Obesity

Coronavirus disease 2019 (COVID-19) due to CoV-2 (coronavirus type 2) virus possess a particular risk of developing acute respiratory distress syndrome (ARDS) or SARS (severe acute respiratory syndrome coronavirus 2)-CoV2 in people with pre-existing conditions related to endothelial dysfunction and increased pro-inflammatory and pro-oxidant state. In between these conditions, chronic systemic inflammation related to obese patients is associated with the development of atherosclerosis, type 2 diabetes, and hypertension, comorbidities that adversely affect the clinical outcome in critical patients with COVID-19. Obesity affects up to 40% of the general population in the USA and more than 30% of the adult population in Chile. Until April 2021, 1,019,478 people have been infected, with 23,524 deaths. Given the coexistence of this worldwide obesity epidemic, COVID-19 negative outcomes are seriously enhanced in the current scenario. On the other hand, obesity is characterized by endothelial dysfunction observed in different vascular beds, an alteration which can be associated with impaired vasodilation, oxidative stress, and inflammatory events. Emerging evidence shows that obesity-related conditions such as endothelial dysfunction are associated with detrimental outcomes for COVID-19 evolution, especially if the patient derives to Intensive Care Units (ICU). This implies the need to understand the pathophysiology of the infection in the obese population, in order to propose therapeutic alternatives and public health policies, especially if the virus remains in the population. In this review, we summarize evidence about the pathogeny of Cov-2 infection in obese individuals and discuss how obesity-associated inflammatory and prooxidant status increase the severity of COVID-19.

POCT errors can lead to false potassium results

Point-of-care-testing (POCT) facilitates rapid availability of results that allows prompt clinical decision making. These results must be reliable and the whole process must not compromise its quality. Blood gas analyzers are one of the most used methods for POCT tests in Emergency Departments (ED) and in critical patients. Whole blood is the preferred sample, and we must be aware that hemolysis can occur. These devices cannot detect the presence of hemolysis in the sample, and because of the characteristics of the sample, we cannot visually detect it either. Hemolysis can alter the result of different parameters, including potassium with abnormal high results or masking low levels (hypokalemia) when reporting normal concentrations. Severe hyperkalemia is associated with the risk of potentially fatal cardiac arrhythmia and demands emergency clinical intervention. Hemolysis can be considered the most frequent cause of pseudohyperkalemia (spurious hyperkalemia) or pseudonormokalemia and can be accompanied by a wrong diagnosis and an ensuing inappropriate clinical decision making. A complete review of the potential causes of falsely elevated potassium concentrations in blood is presented in this article. POCT programs properly led and organized by the clinical laboratory can help to prevent errors and their impact on patient care.

Use of exogenic phosphocreatine in ICU rehabilitation of patients with COVID-19 (pilot study)

The objective: to establish the possible effectiveness of exogenous phosphocreatine as a component of pharmacological support during the resuscitation stage of rehabilitation measures in critically ill patients with COVID-19.Subjects and Methods. Within a randomized study, 21 patients diagnosed with COVID-19 were divided into two groups: Group 1 (patients received the infusion of exogenous phosphocreatine as part of intensive care) and Group 2 (patients received standard intensive care) against the background of rehabilitation measures. Patients were assessed for muscle strength using the MRC scale, exercise tolerance by Borg rating, oxygenation parameters, routine clinical laboratory blood tests, dependence on respiratory support, outcome on day 10 of therapy, and hospital outcome.Results. The effectiveness of the use of the exogenous phosphocreatine as a component of pharmacological support during the resuscitation stage of rehabilitation measures in critical patients has been confirmed by positive dynamics: an increase in muscle strength (the MRC score in the group receiving exogenous phosphocreatine on day 10 was 0.5 points higher) and an increase in exercise tolerance (Borg rating in the group receiving exogenous phosphocreatine on day 10 was 1.5 points higher), significant increase in oxygenation based on arterial blood saturation data, and significant increase in lymphocyte count by 25% in the group receiving exogenous phosphocreatine.Conclusion. Exogenous phosphocreatine is a candidate drug for pharmacological support during resuscitation stage of rehabilitation of critical patients with COVID-19.