Distinct clinical phenotypes of critically ill COVID-19 patients: a cohort observational study

Introduction: COVID-19 presents a complex pathophysiology and evidence collected points towards an intricated interaction of viraldependent and individual immunological mechanisms. The identification of phenotypes, through clinical and biological markers, may provide a better understanding of the subjacent mechanisms and an early patient-tailored characterization of illness severity. Method(s): Multicenter prospective cohort study performed in 5 hospitals of Portugal and Brazil, during one year, between 2020-2021. All adult patients with an Intensive Care Unit admission with SARS-CoV-2 pneumonia were eligible. COVID-19 was diagnosed using clinical and radiologic criteria with a SARS-CoV-2 positive RT-PCR test. A two-step hierarchical cluster analysis was made using several class-defining variables. Result(s): 814 patients were included. The cluster analysis revealed a three-class model, allowing for the definition of three distinct COVID- 19 phenotypes: 244 patients in phenotype A, 163 patients in phenotype B, and 407 patients in phenotype C. Patients included in the phenotype C were significantly older, with higher baseline inflammatory biomarkers profile, and significantly higher requirement of organ support and mortality rate (Table 1 ( P062)). Phenotypes A and B demonstrated some overlapping clinical characteristics but different outcomes. Phenotype B patients presented a lower mortality rate, with consistently lower C-reactive protein, but higher procalcitonin and interleukin-6 serum levels, describing an immunological profile significantly different from phenotype A (Table 1). Conclusion(s): Severe COVID-19 patients exhibit three different clinical phenotypes with distinct profiles and outcomes. Their identification could have an impact in patients' care, justifying different therapy responses and inconsistencies identified across different randomized control trials results.

What changed between the peak and plateau periods of the first COVID-19 pandemic wave? A multicentric Portuguese cohort study in intensive care

Objective: To analyze and compare COVID-19 patient characteristics, clinical management and outcomes between the peak and plateau periods of the first pandemic wave in Portugal. Methods: This was a multicentric ambispective cohort study including consecutive severe COVID-19 patients between March and August 2020 from 16 Portuguese intensive care units. The peak and plateau periods, respectively, weeks 10 - 16 and 17 - 34, were defined. Results: Five hundred forty-one adult patients with a median age of 65 [57 - 74] years, mostly male (71.2%), were included. There were no significant differences in median age (p = 0.3), Simplified Acute Physiology Score II (40 versus 39;p = 0.8), partial arterial oxygen pressure/fraction of inspired oxygen ratio (139 versus 136;p = 0.6), antibiotic therapy (57% versus 64%;p = 0.2) at admission, or 28-day mortality (24.4% versus 22.8%;p = 0.7) between the peak and plateau periods. During the peak period, patients had fewer comorbidities (1 [0 - 3] versus 2 [0 - 5];p = 0.002) and presented a higher use of vasopressors (47% versus 36%;p < 0.001) and invasive mechanical ventilation (58.1 versus 49.2%;p < 0.001) at admission, prone positioning (45% versus 36%;p = 0.04), and hydroxychloroquine (59% versus 10%;p < 0.001) and lopinavir/ ritonavir (41% versus 10%;p < 0.001) prescriptions. However, a greater use of high-flow nasal cannulas (5% versus 16%, p < 0.001) on admission, remdesivir (0.3% versus 15%;p < 0.001) and corticosteroid (29% versus 52%, p < 0.001) therapy, and a shorter ICU length of stay (12 days versus 8, p < 0.001) were observed during the plateau. Conclusion: There were significant changes in patient comorbidities, intensive care unit therapies and length of stay between the peak and plateau periods of the first COVID-19 wave. © 2023 Associacao de Medicina Intensiva Brasileira - AMIB. All rights reserved.

MiniVent: A low-cost pressure-controlled ventilator system for emergency use

Objective: To address the issue of ventilator shortages due to the COVID-19 pandemic, our group developed the proof-of-concept of a low-cost and rapidly scalable open-source mechanical ventilator system for emergency use. Method(s): A simplified architecture of MiniVent was designed to meet the low-cost and easy-to-produce pre-established properties of our device. To carry out such an approach, we decided to use only components commonly available in the market or components of easy production with usual manufacturing techniques, such as 3D printing. The design of MiniVent comprises a pneumatic unit that controls the quality of the air and oxygen mixture and maintains the pressure on the patient's lungs at the desired preset value, along the respiratory cycle. The control unit was programmed on a microcontroller and is responsible for ensuring the respiratory rate and the inspiratory-expiratory ratio, selected by the user. To ensure the fulfilment of all the security and specification requirements of pandemic ventilators, we followed the mandatory specifications presented in the document - Rapidly Manufactured Ventilator System (RMVS) - published by the Medicines & Healthcare products Regulatory Agency (MHRA). A set of tests was performed using different ventilatory parameters for instrumental verification of MiniVent's physical and biological performance. A stability test was also carried out during 35 hours of uninterrupted operation to analyse whether the expected dynamics of the output pressure were maintained over this time. Result(s): The ventilator system developed allows prescribing different breathing rates, fractions inspired of oxygen (FiO2), inspiratory-expiratory ratios (I: E), positive inspiratory pressures (PIP) and positive end-expiratory pressures (PEEP), which can be easily adjustable to the patient's condition. The results of a set of tests assured the reliability of all the ventilatory parameters set by the user. Furthermore, MiniVent showed a good performance over 35 hours of uninterrupted operation, which pointed out the stability of this device. In addition, the device was tested in a porcine model showing good mechanical performance and adequate arterial blood gas throughout all test periods. When compared with commercial ventilators, MiniVent exhibited a similar performance of ventilation. Conclusion(s): MiniVent could be a reliable solution to overcome the shortage of commercial ventilators in emergencies, such as the recent COVID-19 pandemic. This device presents a production cost of under 1000 and does not need specialized technical assistance so it might be a viable solution even in lowerincome countries.

Septic shock 3.0 in severe COVID19 patients: Are we missing something clinically important?

Introduction/Purpose: COVID19 can be associated with life-threatening organ dysfunction due to septic shock, frequently requiring ICU admission, respiratory and vasopressor support. Therefore, clear clinical criteria are pivotal to early recognition of patients more likely to have poor outcomes, needing prompt organ support. Although most patients with severe COVID19 meet the Sepsis-3.0 criteria for septic shock, it has been increasingly recognized that, in this population, hyperlactatemia is frequently absent, possibly leading to an underestimation of illness severity and mortality risk. Purpose: This study aimed to identify the proportion of patients with COVID19 with hypotension despite adequate volume resuscitation, needing vasopressors to have a MAP>65mmHg, with and without hyperlactatemia, in ICU, and describe its clinical outcomes and mortality rate. Methods: We performed a single-center retrospective cohort study. All adult patients admitted to ICU with COVID19 were eligible and were further divided in 3 groups according to hyperlactatemia (lactate >2mmol/L) and persistent hypotension with vasopressor therapy requirement: (1) sepsis group (without both criteria), (2) vasoplegic shock (with persistent hypotension with vasopressor therapy requirement without hyperlactatemia) and (3) septic shock 3.0 (with both criteria). COVID19 was diagnosed using clinical and radiologic criteria with a SARS-CoV-2 positive RT-PCR test. Qui-square test was used for categorical variables and Kruskal-Wallis and logistic regression were used on continuous variables for statistical assessment of outcomes between groups. Kaplan-Meier survival curve and logrank test were also obtained. Results: 103 patients (mean age 62 years, 71% males) were included in the analysis (N=45 sepsis, N=25 vasoplegic shock;N=33 septic shock 3.0). SOFA score at ICU admission and ICU length of stay were different between groups (p<0.001). Ventilator-free days and vasopressor-free days were also different between sepsis vs vasoplegic shock and septic shock 3.0 groups (both p<0.001 and p<0.001, respectively), and similar in vasoplegic vs septic shock 3.0 groups (p=0.387 and p=0.193, respectively). Mortality was significantly higher in vasoplegic shock and septic shock 3.0 when compared with sepsis group (p<0.001) without difference between the former two groups (p=0.595). Log rank test of Kaplan-Meier survival curves were also different (p=0.07). Logistic regression identified the maximum dose of vasopressor therapy used (OR 1.065;CI 95%: 1.023-1.108, p=0.02) and serum lactate level (OR 1.543;CI 95%: 1.069-2.23, p=0.02) as the major explanatory variables of mortality rates. Conclusions: In severe COVID19 patients, the Sepsis 3 criteria of septic shock may exclude patients with a similarly high risk of poor outcomes and mortality rate, that should be equally approached. (Table Presented).