Project description:BackgroundAKI is common among hospitalized patients with coronavirus disease 2019 (COVID-19) and is an independent risk factor for mortality. Although there are numerous potential mechanisms underlying COVID-19-associated AKI, our current knowledge of kidney pathologic findings in COVID-19 is limited.MethodsWe examined the postmortem kidneys from 42 patients who died of COVID-19. We reviewed light microscopy findings in all autopsies and performed immunofluorescence, electron microscopy, and in situ hybridization studies for SARS-CoV-2 on a subset of samples.ResultsThe cohort had a median age of 71.5 years (range, 38-97 years); 69% were men, 57% were Hispanic, and 73% had a history of hypertension. Among patients with available data, AKI developed in 31 of 33 patients (94%), including 6 with AKI stage 1, 9 with stage 2, and 16 with stage 3. The predominant finding correlating with AKI was acute tubular injury. However, the degree of acute tubular injury was often less severe than predicted for the degree of AKI, suggesting a role for hemodynamic factors, such as aggressive fluid management. Background changes of hypertensive arterionephrosclerosis and diabetic glomerulosclerosis were frequent but typically mild. We identified focal kidney fibrin thrombi in 6 of 42 (14%) autopsies. A single Black patient had collapsing FSGS. Immunofluorescence and electron microscopy were largely unrevealing, and in situ hybridization for SARS-CoV-2 showed no definitive positivity.ConclusionsAmong a cohort of 42 patients dying with COVID-19, autopsy histologic evaluation revealed acute tubular injury, which was typically mild relative to the degree of creatinine elevation. These findings suggest potential for reversibility upon resolution of SARS-CoV-2 infection.
Project description:Infections caused by SARS-CoV-2 may cause a severe disease, termed COVID-19, with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms, and their modulation is the only therapeutic strategy that has shown a mortality benefit. Herein, we used peripheral blood transcriptomes of critically-ill COVID-19 patients obtained at admission in an Intensive Care Unit, to identify two clusters that, in spite of no major clinical differences, have different gene expression profiles that reveal different underlying pathogenetic mechanisms and ultimately have different ICU outcome. A transcriptomic signature was used to identify these clusters in an external validation cohort, yielding a similar result. These results illustrate the potential of transcriptomic profiles to identify patient endotypes and point to relevant pathogenetic mechanisms in COVID-19.
Project description:Infections caused by SARS-CoV-2 may cause a severe disease, termed COVID-19, with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms, and their modulation is the only therapeutic strategy that has shown a mortality benefit. Herein, we used peripheral blood transcriptomes of critically-ill COVID-19 patients obtained at admission in an Intensive Care Unit, to identify two clusters that, in spite of no major clinical differences, have different gene expression profiles that reveal different underlying pathogenetic mechanisms and ultimately have different ICU outcome. A transcriptomic signature was used to identify these clusters in an external validation cohort, yielding a similar result. These results illustrate the potential of transcriptomic profiles to identify patient endotypes and point to relevant pathogenetic mechanisms in COVID-19.
Project description:Infections caused by SARS-CoV-2 may cause a severe disease, termed COVID-19, with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms, and their modulation is the only therapeutic strategy that has shown a mortality benefit. Herein, we used peripheral blood transcriptomes of critically-ill COVID-19 patients obtained at admission in an Intensive Care Unit, to identify two clusters that, in spite of no major clinical differences, have different gene expression profiles that reveal different underlying pathogenetic mechanisms and ultimately have different ICU outcome. A transcriptomic signature was used to identify these clusters in an external validation cohort, yielding a similar result. These results illustrate the potential of transcriptomic profiles to identify patient endotypes and point to relevant pathogenetic mechanisms in COVID-19.
Project description:Total plasma IgA glycosylation was compared between healthy volunteers and volunteers suffering fromo infections with either the influenza A virus or the severe acute respiratory syndrome corona virus 2. Data from functional assays of the same plasma samples, such as neutrophil extracellular trap formation is also available.
Project description:ObjectivesThe objective of this study was to investigate the clinical features and laboratory findings of patients with and without critical COVID-19 pneumonia and identify predictors for the critical form of the disease.MethodsDemographic, clinical, and laboratory data of 63 COVID-19 pneumonia patients were retrospectively reviewed. Laboratory parameters were also collected within 3-5 days, 7-9 days, and 11-14 days of hospitalization. Outcomes were followed up until March 12, 2020.ResultsTwenty-two patients developed critically ill pneumonia; one of them died. Upon admission, older patients with critical illness were more likely to report cough and dyspnoea with higher respiration rates and had a greater possibility of abnormal laboratory parameters than patients without critical illness. When compared with the non-critically ill patients, patients with serious illness had a lower discharge rate and longer hospital stays, with a trend towards higher mortality. The interleukin-6 level in patients upon hospital admission was important in predicting disease severity and was associated with the length of hospitalization.ConclusionsMany differences in clinical features and laboratory findings were observed between patients exhibiting non-critically ill and critically ill COVID-19 pneumonia. Non-critically ill COVID-19 pneumonia also needs aggressive treatments. Interleukin-6 was a superior predictor of disease severity.
Project description:Single-cell RNA-sequencing reveals a shift from focused IFN alpha-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 – a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention.
Project description:The majority of populations in developing countries are living in areas of no access or limited access to prehospital emergency medical services (EMS). In Addis Ababa, the reported prehospital EMS utilization were ranging from zero to thirty-eight percent. However, there is limited research on reasons for the low utilization of prehospital resources in Ethiopia. This study aimed to assess factors associated with prehospital EMS utilization among critically ill COVID-19 patients in Addis Ababa, Ethiopia. A hospital-based cross-sectional study was conducted to collect primary data from 421 COVID-19 patients in Addis Ababa between May and July 2021. Logistic regression was used to identify factors associated with prehospital service utilization. Andersen’s Behavioral Model was implemented to address independent variables, including predisposing, enabling, need, and health behaviors-related variables. The level of prehospital care utilization was 87.6%. Being married [AOR 2.6(95%; CI:1.24–5.58)], belief that self-transport is quicker than the ambulance [AOR 0.13(95%; CI: 0.05–0.34)], and perceptions that ambulance provides transportation service only [AOR 0.14(95%; CI:0.04–0.45)] were predisposing factors associated with prehospital service utilization while the source of referrals [AOR 6.9(95%; CI: 2.78–17.30)], and prior knowledge on the availability of toll-free ambulance calling numbers [AOR 0.14(95%; CI: 0.04–0.45)] were identified as enabling factors. Substantial proportions of critically ill COVID-19 patients used prehospital services to access treatment centers. Prehospital EMS utilization in this study varies by predisposing and enabling factors, particularly: marital status, source of referral, prior knowledge on the availability of toll-free ambulances, belief that self-transport is quicker than ambulances, and perceptions that ambulance provides transportation service only. Our findings call for further actions to be taken by policymakers including physical and media campaigns focusing on the identified factors.
Project description:Background Cardiac function of critically ill patients with COVID-19 generally has been reported from clinically obtained data. Echocardiographic deformation imaging can identify ventricular dysfunction missed by traditional echocardiographic assessment. Research Question What is the prevalence of ventricular dysfunction and what are its implications for the natural history of critical COVID-19? Study Design and Methods This is a multicenter prospective cohort of critically ill patients with COVID-19. We performed serial echocardiography and lower extremity vascular ultrasound on hospitalization days 1, 3, and 8. We defined left ventricular (LV) dysfunction as the absolute value of longitudinal strain of < 17% or left ventricle ejection fraction (LVEF) of < 50%. Primary clinical outcome was inpatient survival. Results We enrolled 110 patients. Thirty-nine (35.5%) died before hospital discharge. LV dysfunction was present at admission in 38 patients (34.5%) and in 21 patients (36.2%) on day 8 (P = .59). Median baseline LVEF was 62% (interquartile range [IQR], 52%-69%), whereas median absolute value of baseline LV strain was 16% (IQR, 14%-19%). Survivors and nonsurvivors did not differ statistically significantly with respect to day 1 LV strain (17.9% vs 14.4%; P = .12) or day 1 LVEF (60.5% vs 65%; P = .06). Nonsurvivors showed worse day 1 right ventricle (RV) strain than survivors (16.3% vs 21.2%; P = .04). Interpretation Among patients with critical COVID-19, LV and RV dysfunction is common, frequently identified only through deformation imaging, and early (day 1) RV dysfunction may be associated with clinical outcome.