OBJECTIVE: To assess the correlation of dead space fraction (VD/VT) measured through time capnography, corrected minute volume (CMV) and ventilation ratio (VR) with clinical outcomes in COVID-19 patients requiring invasive mechanical ventilation.
METHODS: Observational study of a historical cohort.
METHODS: University hospital in Medellin, Colombia.
METHODS: Patients aged 15 and above with a confirmed COVID-19 diagnosis admitted to the ICU and requiring mechanical ventilation.
METHODS: Measurement of VD/VT, CMV, and VR in COVID-19 patients.
METHODS: VD/VT, CMV, VR, demographic data, oxygenation indices and ventilatory parameters.
RESULTS: During the study period, 1047 COVID-19 patients on mechanical ventilation were analyzed, of whom 446 (42%) died. Deceased patients exhibited a higher prevalence of advanced age and obesity, elevated Charlson index, higher APACHE II and SOFA scores, as well as an increase in VD/VT ratio (0.27 in survivors and 0.31 in deceased) and minute ventilation volume on the first day of mechanical ventilation. The multivariate analysis revealed independent associations to in-hospital mortality, higher VD/VT (HR 1.24; 95%CI 1.003-1.525; p = 0.046), age (HR 1.024; 95%CI 1.014-1.034; p < 0.001), and SOFA score at onset (HR: 1.036; 95%CI: 1.001-1.07; p = 0.017).
CONCLUSIONS: VD/VT demonstrated an association with mortality in COVID-19 patients with ARDS on mechanical ventilation. These findings suggest that VD/VT measurement may serve as a severity marker for the disease.

Persistent sinus tachycardia (pST) has been associated with adverse cardiovascular events in critically ill patients. Pharmacological control of heart rate with negative inotropic agents has proven to be safe but could be potentially dangerous in patients with concomitant right ventricular (RV) dysfunction. Ivabradine, a medication devoid of negative inotropy, could be a potentially safe solution for this patient population when adequate heart rate control is desired. A 17-year-old male with a history of vaping developed acute respiratory distress syndrome (ARDS) and RV dysfunction, requiring extra corporal life support (ECLS). He suffered from pST. Given his RV dysfunction, a beta-blocker was avoided, and ivabradine was used safely with improvement of his pST. This case demonstrates the efficacy of ivabradine to reduce heart rate and avoid the use of beta-blockers for patients with RV dysfunction, which could be detrimental. Ivabradine was shown to lower the heart rate without altering hemodynamic parameters.

Coronavirus disease 2019 (COVID-19) often presents with a wide range of complications, including respiratory distress, acute respiratory distress syndrome (ARDS), and hypercoagulable states with resultant cerebrovascular incidents. Intra- and extra-pulmonological shunts can further complicate patient courses, leading to persistent hypoxemia and paradoxical emboli, resulting in potentially life-threatening consequences, necessitating a comprehensive, multidisciplinary approach to patient care. Here we present the case of a 73-year-old male who experienced severe persistent hypoxemic respiratory failure, superimposed methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, and stroke with a previously undiagnosed patent foramen ovale (PFO) contributing to his clinical presentation.

Background Pulmonary thrombosis and thromboembolism play a significant role in the physiologic derangements seen in COVID-19 acute respiratory failure. The effect of thrombolysis with tenecteplase on patient outcomes is unknown. Methods We conducted a randomized, controlled, double-blind, phase II trial comparing tenecteplase versus placebo in patients with COVID-19 acute respiratory failure (NCT04505592). Patients with COVID-19 acute respiratory failure were randomized to tenecteplase 0.25 mg/kg or placebo in a 2:1 proportion. Both groups received therapeutic heparin for at least 72 hours. Results Thirteen patients were included in the trial. Eight patients were randomized to tenecteplase and five were randomized to placebo. At 28 days, 63% (n = 5) of patients assigned to the treatment group were alive and free from respiratory failure compared to 40% (n = 2) in the placebo arm (p = 0.43). Mortality at 28 days was 25% (n = 2) in the treatment arm and 20% (n = 1) in the control arm (p = 1.0). No patients in the treatment arm developed renal failure by 28 days compared to 60% (n = 3) in the placebo arm (p = 0.07). Major bleeding occurred in 25% (n = 2) of the treatment arm and 20% (n = 1) in the placebo arm; however, no patients in either arm experienced intracranial hemorrhage. Conclusions Tenecteplase with concomitant heparin may improve patient outcomes in patients with COVID-19 respiratory failure. As this study was limited by a small sample size, larger confirmatory studies are needed.

Acute respiratory distress syndrome (ARDS) is a severe lung disease associated with a high mortality rate. Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy for severe ARDS patients who do not respond to conventional treatments. Nevertheless, the optimal management of ARDS patients undergoing ECMO and their mortality rates remain subjects of controversy. Thus, this systematic review aims to assess mortality rates in ARDS patients on ECMO and identify associated factors. The review adhered to the Preferred Reporting Items for Systemic Review and Meta-Analysis (PRISMA) 2020 guidelines. A comprehensive literature search was conducted on PubMed, PubMed Central (PMC), Medline, and Embase. In accordance with our inclusion and exclusion criteria, filters, and key terms, we proceeded to screen the articles. After assessing the relevance of each article to our topic, further screening was carried out. Quality assessment of the articles was conducted, resulting in the inclusion of a total of 12 articles for the review. The primary outcome focused on mortality rates among ARDS patients undergoing ECMO. Secondary outcomes explored potential contributors to mortality, including patient age, underlying cause of ARDS, and Sequential Organ Failure Assessment (SOFA) scores at the initiation of ECMO. Mortality rates exhibited significant variation, ranging from 22% to 62.6%. Several factors emerged as potential predictors of mortality, encompassing patient age, comorbidities, complications during ECMO therapy, and treatment-related variables. This systematic review offers valuable insights into the intricate factors influencing mortality rates among ARDS patients on ECMO. A comprehension of these factors is essential to steer clinical practice and enhance patient outcomes. While ECMO serves as a restorative avenue for ARDS patients, future research is warranted to further elucidate these complex interactions and refine ECMO therapy protocols.

SARS-CoV-2 infection causes COVID-19, which has emerged as a health emergency worldwide. SARS-CoV-2 infects cells by binding to ACE2 receptors and enters into the cytoplasm following its escape from endolysosomes. Once in the cytoplasm, the virus replicates and eventually causes various pathological conditions including acute respiratory distress syndrome (ARDS) that is caused by pro-inflammatory cytokine storms. Thus, endolysosomes and cytokine storms are important therapeutic targets to suppress SARS-CoV-2 infection and COVID-19. Here, we discuss therapeutic targets of SARS-CoV-2 infection and available drugs that could be helpful in the suppression of the SARS-CoV-2 infection and pathological condition COVID-19. The urgency of the COVID-19 pandemic precludes the development of new drugs and increased focus on drug repurposing might provide the quickest way to finding effective medicines.

COVID-19 is a severe respiratory disease caused by SARS-CoV-2, a novel human coronavirus. Patients infected with SARS-CoV-2 exhibit heterogeneous symptoms that pose pragmatic hurdles for implementing appropriate therapy and management of the COVID-19 patients and their post-COVID complications. Thus, understanding the impact of infection severity at the molecular level in the host is vital to understand the host response and accordingly it\'s precise management. In the current study, we performed a comparative transcriptomics analysis of publicly available seven asymptomatic and eight severe COVID-19 patients. Exploratory data analysis employing Principal Component Analysis (PCA) showed the distinct clusters of asymptomatic and severe patients. Subsequently, the differential gene expression analysis using DESeq2 identified 1224 significantly upregulated genes (logFC≥ 1.5, p-adjusted value <0.05) and 268 significantly downregulated genes (logFC≤ -1.5, p-adjusted value <0.05) in severe samples in comparison to asymptomatic samples. Eventually, Gene Set Enrichment Analysis (GSEA) revealed the upregulation of anti-viral and anti-inflammatory pathways, secondary infections, Iron homeostasis, anemia, cardiac-related, etc.; while, downregulation of lipid metabolism, adaptive immune response, translation, recurrent respiratory infections, heme-biosynthetic pathways, etc. Conclusively, these findings provide insight into the enhanced susceptibility of severe COVID-19 patients to other health comorbidities including non-viral pathogenic infections, atherosclerosis, autoinflammatory diseases, anemia, male infertility, etc. owing to the activation of biological processes, pathways and molecular functions associated with them. We anticipate this study will facilitate the researchers in finding efficient therapeutic targets and eventually the clinicians in management of COVID-19 patients and post-COVID-19 effects in them.

UNASSIGNED: Sepsis is associated with endothelial cell (EC) dysfunction, increased vascular permeability and organ injury, which may lead to mortality, acute respiratory distress syndrome (ARDS) and acute renal failure (ARF). There are no reliable biomarkers to predict these sepsis complications at present. Recent evidence suggests that circulating extracellular vesicles (EVs) and their content caspase-1 and miR-126 may play a critical role in modulating vascular injury in sepsis; however, the association between circulating EVs and sepsis outcomes remains largely unknown.
UNASSIGNED: We obtained plasma samples from septic patients (n=96) within 24 hours of hospital admission and from healthy controls (n=45). Total, monocyte- or EC-derived EVs were isolated from the plasma samples. Transendothelial electrical resistance (TEER) was used as an indicator of EC dysfunction. Caspase-1 activity in EVs was detected and their association with sepsis outcomes including mortality, ARDS and ARF was analyzed. In another set of experiments, total EVs were isolated from plasma samples of 12 septic patients and 12 non-septic critical illness controls on days 1, and 3 after hospital admission. RNAs were isolated from these EVs and Next-generation sequencing was performed. The association between miR-126 levels and sepsis outcomes such as mortality, ARDS and ARF was analyzed.
UNASSIGNED: Septic patients with circulating EVs that induced EC injury (lower transendothelial electrical resistance) were more likely to experience ARDS (p<0.05). Higher caspase-1 activity in total EVs, monocyte- or EC-derived EVs was significantly associated with the development of ARDS (p<0.05). MiR-126-3p levels in EC EVs were significantly decreased in ARDS patients compared with healthy controls (p<0.05). Moreover, a decline in miR-126-5p levels from day 1 to day 3 was associated with increased mortality, ARDS and ARF; while decline in miR-126-3p levels from day 1 to day 3 was associated with ARDS development.
UNASSIGNED: Enhanced caspase-1 activity and declining miR-126 levels in circulating EVs are associated with sepsis-related organ failure and mortality. Extracellular vesicular contents may serve as novel prognostic biomarkers and/or targets for future therapeutic approaches in sepsis.

BACKGROUND: Acute kidney injury (AKI) is frequently reported in the setting of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection. The aim of our work is to evaluate the impact of acute dialysis use on mortality in patients with AKI during the coronavirus disease 2019 (COVID-19) pandemic.
METHODS: This is a retrospective study conducted in the Hassan II University Hospital of Fez, Morocco. From July 2020 to December 2021, we included all patients admitted to a COVID-19 unit with acute kidney injury defined according to Kidney Disease Improvement Global Outcomes 2012 (KDIGO 2012) criteria. Our patients were older than 18 years, and SARS-CoV-2 infection was confirmed by a positive RT-PCR test or thoracic CT scan imaging. Patients with end-stage renal disease (ESRD) and pregnant women were excluded from our study.
RESULTS: The total number of patients hospitalized in the COVID-19 unit during the study period was 2560, including 206 in an intensive care setting. We included 61 patients with AKI, with an incidence in the intensive care unit (ICU) setting of 15.5%. Eighty percent of patients had respiratory distress on admission, which was the main reason for consultation. Stage 1 AKI was found in 1.6% of patients, 25.8% had stage II AKI, and 72.6% had KDIGO stage 3 AKI. The main etiology of AKI was acute tubular necrosis. Lung involvement secondary to infection was severe in 18 patients; 21 had moderate involvement. In our study, twenty-one of our patients (34.4%) were hospitalized in an ICU. Thirteen of our patients were intubated (21.1%). Twenty-one (34.4%) patients were hemodynamically unstable and were put on vasoactive drugs. Twenty-three (37.7%) of our patients received at least one session of conventional acute hemodialysis with an average duration of 2.1 hours ± 0.9 (1-3.5). The indication was overload (27%), severe metabolic acidosis (1.6%), threatening hyperkalemia (1.6%), and symptomatic hyperuremia (62%). The evolution was marked by a return to baseline renal function in two patients, partial improvement in 35 of them at discharge, and no improvement in 24 patients. We recorded a death rate of 34.4% (n=21). In a univariate analysis, we compared the demographic, clinical, paraclinical, and dialytic characteristics of the dialysis and non-dialysis groups. There was a significant difference between unstable, intubated patients and those hospitalized in the ICU in the dialysis group, with respective p-values of p=0.0001, p=0.0001, and p=0.01. We noticed there were more deaths in the dialysis group than in the non-dialysis group; this difference was statistically significant with a p-value of 0.005. In multivariate analysis, a logistic regression model was performed to test the relationship between dialysis and COVID-19 mortality while adjusting for other co-factors. The final model did not show a significant association between dialysis and mortality (p = 0.150, OR: 2.578 [0.710-9.364]). The only factor that remained independently significant was admission to the intensive care unit (p = 0.004, OR: 6.732 [1.847-24.540]).
CONCLUSIONS: AKI is a frequently encountered complication in patients with COVID-19, especially those hospitalized in the ICU. In the context of the SARS-CoV-2 infection, the use of at least one dialysis session seems to represent an excess risk of mortality related to AKI.

COVID-19 causes morbid pathological changes in different organs including lungs, kidneys, liver, and so on, especially in those who succumb. Though clinical outcomes in those with comorbidities are known to be different from those without-not much is known about the differences at the histopathological level. To compare the morbid histopathological changes in COVID-19 patients between those who were immunocompromised (Gr 1), had a malignancy (Gr 2), or had cardiometabolic conditions (hypertension, diabetes, or coronary artery disease) (Gr 3), postmortem tissue sampling (minimally invasive tissue sampling [MITS]) was done from the lungs, kidney, heart, and liver using a biopsy gun within 2 hours of death. Routine (hematoxylin and eosin) and special staining (acid fast bacilli, silver methanamine, periodic acid schiff) was done besides immunohistochemistry. A total of 100 patients underwent MITS and data of 92 patients were included (immunocompromised: 27, malignancy: 18, cardiometabolic conditions: 71). In lung histopathology, capillary congestion was more in those with malignancy, while others like diffuse alveolar damage, microthrombi, pneumocyte hyperplasia, and so on, were equally distributed. In liver histopathology, architectural distortion was significantly different in immunocompromised; while steatosis, portal inflammation, Kupffer cell hypertrophy, and confluent necrosis were equally distributed. There was a trend towards higher acute tubular injury in those with cardiometabolic conditions as compared to the other groups. No significant histopathological difference in the heart was discerned. Certain histopathological features were markedly different in different groups (Gr 1, 2, and 3) of COVID-19 patients with fatal outcomes.