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1.
Critical Care Medicine ; 50:71-71, 2022.
Article in English | Academic Search Complete | ID: covidwho-1597408

ABSTRACT

Most patients had persistently elevated CCL23 levels, with the stroke patient cohort having the highest values (p=0.018). Serum levels of neurodegeneration markers proved complex, therefore possibly suggesting a more dynamic relationship to the neural abnormalities seen in COVID-19 patients. The IL-6 levels of stroke patients were significantly higher compared to their non-stroke counterparts one week after admission (p=0.001), while IL-8 levels fluctuated before declining (p< 0.001). [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

2.
Critical Care Medicine ; 50:74-74, 2022.
Article in English | Academic Search Complete | ID: covidwho-1596582

ABSTRACT

B Background: b In the past, few studies have utilized urine to assess the state of the immune system. Here, we hypothesize that urine biomarkers can assess immune activation and the effect of antiviral treatment in patients infected with COVID-19. With regards to treatments, Remdesivir had a more profound impact on the urine biomarkers than steroids. [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

5.
Immunity ; 54(11): 2632-2649.e6, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1549842

ABSTRACT

The incidence and severity of sepsis is higher among individuals of African versus European ancestry. We found that genetic risk variants (RVs) in the trypanolytic factor apolipoprotein L1 (APOL1), present only in individuals of African ancestry, were associated with increased sepsis incidence and severity. Serum APOL1 levels correlated with sepsis and COVID-19 severity, and single-cell sequencing in human kidneys revealed high expression of APOL1 in endothelial cells. Analysis of mice with endothelial-specific expression of RV APOL1 and in vitro studies demonstrated that RV APOL1 interfered with mitophagy, leading to cytosolic release of mitochondrial DNA and activation of the inflammasome (NLRP3) and the cytosolic nucleotide sensing pathways (STING). Genetic deletion or pharmacological inhibition of NLRP3 and STING protected mice from RV APOL1-induced permeability defects and proinflammatory endothelial changes in sepsis. Our studies identify the inflammasome and STING pathways as potential targets to reduce APOL1-associated health disparities in sepsis and COVID-19.


Subject(s)
Apolipoprotein L1/genetics , COVID-19/genetics , Genetic Predisposition to Disease/genetics , Sepsis/genetics , Animals , Apolipoprotein L1/blood , COVID-19/pathology , DNA, Mitochondrial/metabolism , Endothelial Cells/metabolism , Humans , Inflammation/genetics , Inflammation/pathology , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice , Mice, Knockout , Mitophagy/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Risk Factors , Sepsis/pathology , Severity of Illness Index , /statistics & numerical data
6.
Biomedicines ; 9(12)2021 Nov 29.
Article in English | MEDLINE | ID: covidwho-1542416

ABSTRACT

The balance between neurodegeneration, neuroinflammation, neuroprotection, and COVID-19-directed therapy may underly the heterogeneity of SARS-CoV-2's neurological outcomes. A total of 105 patients hospitalized with a diagnosis of COVID-19 had serum collected over a 6 month period to assess neuroinflammatory (MIF, CCL23, MCP-1), neuro-injury (NFL, NCAM-1), neurodegenerative (KLK6, τ, phospho τ, amyloids, TDP43, YKL40), and neuroprotective (clusterin, fetuin, TREM-2) proteins. These were compared to markers of nonspecific inflammatory responses (IL-6, D-dimer, CRP) and of the overall viral burden (spike protein). Data regarding treatment (steroids, convalescent plasma, remdasavir), pre-existing conditions, and incidences of strokes were collected. Amyloid ß42, TDP43, NF-L, and KLK6 serum levels declined 2-3 days post-admission, yet recovered to admission baseline levels by 7 days. YKL-40 and NCAM-1 levels remained elevated over time, with clusters of differential responses identified among TREM-2, TDP43, and YKL40. Fetuin was elevated after the onset of COVID-19 while TREM-2 initially declined before significantly increasing over time. MIF serum level was increased 3-7 days after admission. Ferritin correlated with TDP-43 and KLK6. No treatment with remdesivir coincided with elevations in Amyloid-ß40. A lack of convalescent plasma resulted in increased NCAM-1 and total tau, and steroidal treatments did not significantly affect any markers. A total of 11 incidences of stroke were registered up to six months after initial admission for COVID-19. Elevated D-dimer, platelet counts, IL-6, and leukopenia were observed. Variable MIF serum levels differentiated patients with CVA from those who did not have a stroke during the acute phase of COVID-19. This study demonstrated concomitant and opposite changes in neurodegenerative and neuroprotective markers persisting well into recovery.

7.
Int J Mol Sci ; 22(19)2021 Sep 29.
Article in English | MEDLINE | ID: covidwho-1463705

ABSTRACT

(1) Background: Sepsis is one of the most common critical care illnesses with increasing survivorship. The quality of life in sepsis survivors is adversely affected by several co-morbidities, including increased incidence of dementia, stroke, cardiac disease and at least temporary deterioration in cognitive dysfunction. One of the potential explanations for their progression is the persistence of lipid profile abnormalities induced during acute sepsis into recovery, resulting in acceleration of atherosclerosis. (2) Methods: This is a targeted review of the abnormalities in the long-term lipid profile abnormalities after sepsis; (3) Results: There is a well-established body of evidence demonstrating acute alteration in lipid profile (HDL-c ↓↓, LDL-C -c ↓↓). In contrast, a limited number of studies demonstrated depression of HDL-c levels with a concomitant increase in LDL-C -c in the wake of sepsis. VLDL-C -c and Lp(a) remained unaltered in few studies as well. Apolipoprotein A1 was altered in survivors suggesting abnormalities in lipoprotein metabolism concomitant to overall lipoprotein abnormalities. However, most of the studies were limited to a four-month follow-up and patient groups were relatively small. Only one study looked at the atherosclerosis progression in sepsis survivors using clinical correlates, demonstrating an acceleration of plaque formation in the aorta, and a large metanalysis suggested an increase in the risk of stroke or acute coronary event between 3% to 9% in sepsis survivors. (4) Conclusions: The limited evidence suggests an emergence and persistence of the proatherogenic lipid profile in sepsis survivors that potentially contributes, along with other factors, to the clinical sequel of atherosclerosis.


Subject(s)
Atherosclerosis/metabolism , Cholesterol/metabolism , Lipoproteins/metabolism , Sepsis/metabolism , Apolipoproteins/metabolism , Atherosclerosis/complications , Cholesterol, HDL/metabolism , Cholesterol, LDL/metabolism , Disease Progression , Humans , Sepsis/complications , Triglycerides/metabolism
8.
Sci Rep ; 11(1): 19675, 2021 10 04.
Article in English | MEDLINE | ID: covidwho-1450292

ABSTRACT

Kidney function is affected in COVID-19, while kidney itself modulates the immune response. Here, hypothesize if COVID-19 urine biomarkers level can assess immune activation vs. clinical trajectory. Considering the kidney's critical role in modulating the immune response, we sought to analyze activation markers in patients with pre-existing dysfunction. This was a cross-sectional study of 68 patients. Blood and urine were collected within 48 h of hospital admission (H1), followed by 96 h (H2), seven days (H3), and up to 25 days (H4) from admission. Serum level ferritin, procalcitonin, IL-6 assessed immune activation overall, while the response to viral burden was gauged with serum level of spike protein and αspike IgM and IgG. 39 markers correlated highly between urine and blood. Age and race, and to a lesser extend gender, differentiated several urine markers. The burden of pre-existing conditions correlated with urine DCN, CAIX and PTN, but inversely with IL-5 or MCP-4. Higher urinary IL-12 and lower CAIX, CCL23, IL-15, IL-18, MCP-1, MCP-3, MUC-16, PD-L1, TNFRS12A, and TNFRS21 signified non-survivors. APACHE correlated with urine TNFRS12, PGF, CAIX, DCN, CXCL6, and EGF. Admission urine LAG-3 and IL-2 predicted death. Pre-existing kidney disease had a unique pattern of urinary inflammatory markers. Acute kidney injury was associated, and to a certain degree, predicted by IFNg, TWEAK, MMP7, and MUC-16. Remdesavir had a more profound effect on the urine biomarkers than steroids. Urinary biomarkers correlated with clinical status, kidney function, markers of the immune system activation, and probability of demise in COVID-19.


Subject(s)
Acute Kidney Injury/pathology , Biomarkers/urine , COVID-19/immunology , Renal Insufficiency, Chronic/pathology , Acute Kidney Injury/complications , Adult , Aged , Antigens, CD/urine , Biomarkers/blood , CA-125 Antigen/urine , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Chemokines, CC/blood , Cross-Sectional Studies , Female , Humans , Interleukin-12/urine , Interleukin-6/blood , Male , Membrane Proteins/urine , Middle Aged , Procalcitonin/blood , Renal Insufficiency, Chronic/complications , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Severity of Illness Index , Spike Glycoprotein, Coronavirus/blood
9.
BioMed ; 1(1):80-92, 2021.
Article in English | MDPI | ID: covidwho-1408447

ABSTRACT

Coronavirus disease 2019 (COVID-19) interacts with the nervous system directly and indirectly by affecting the activation of the immune system. Guillain–Barré syndrome (GBS) is triggered by an inappropriate immune system activation that overlaps with the neurotoxic mechanism of an invading pathogen. Here, we discuss the complexity of an abnormal immune system response leading to the generation of autoimmunity in the setting of acute viral infection. A 67-year-old male patient with COVID-19 developed a sensory motor acute polyneuropathy with respiratory failure. Several serum inflammatory and neurodegeneration markers were collected during hospital days 1, 3, 8, and 67 and compared to healthy individuals. Neural cell adhesion molecule 1 (NCAM-1) and neurofilament light chain (NfL) values were highly variable when compared to healthy individuals, but not to the reference COVID-19 group. We focused our attention on NCAM-1 as a possible target for antibodies directed at COVID-19 in silico.

10.
Adv Biol Regul ; 81: 100818, 2021 08.
Article in English | MEDLINE | ID: covidwho-1313202

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by a wide spectrum of symptom severity, which is manifested at different phases of infection and demands different levels of care. Viral load, host innate-immune response to SARS-CoV-2, and comorbidities have a direct impact on the clinical outcomes of COVID-19 patients and determine the diverse disease trajectories. The initial SARS-CoV-2 penetrance and replication in the host causes death of infected cells, determining the viral response. SARS-CoV-2 replication in the host triggers the activation of host antiviral immune mechanisms, determining the inflammatory response. While a healthy immune response is essential to eliminate infected cells and prevent spread of the virus, a dysfunctional immune response can result in a cytokine storm and hyperinflammation, contributing to disease progression. Current therapies for COVID-19 target the virus and/or the host immune system and may be complicated in their efficacy by comorbidities. Here we review the evidence for use of two classes of anti-inflammatory drugs, glucocorticoids and nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of COVID-19. We consider the clinical evidence regarding the timing and efficacy of their use, their potential limitations, current recommendations and the prospect of future studies by these and related therapies.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , COVID-19/drug therapy , Glucocorticoids/therapeutic use , SARS-CoV-2/physiology , Virus Replication/drug effects , COVID-19/epidemiology , COVID-19/immunology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/immunology , Humans , Viral Load/drug effects , Viral Load/immunology , Virus Replication/immunology
11.
Front Immunol ; 12: 650465, 2021.
Article in English | MEDLINE | ID: covidwho-1285288

ABSTRACT

Identification of novel immune biomarkers to gauge the underlying pathology and severity of COVID-19 has been difficult due to the lack of longitudinal studies. Here, we analyzed serum collected upon COVID-19 admission (t1), 48 hours (t2), and seven days later (t3) using Olink proteomics and correlated to clinical, demographics, and therapeutic data. Older age positively correlated with decorin, pleiotrophin, and TNFRS21 but inversely correlated with chemokine (both C-C and C-X-C type) ligands, monocyte attractant proteins (MCP) and TNFRS14. The burden of pre-existing conditions was positively correlated with MCP-4, CAIX, TWEAK, TNFRS12A, and PD-L2 levels. Individuals with COVID-19 demonstrated increased expression of several chemokines, most notably from the C-C and C-X-C family, as well as MCP-1 and MCP-3 early in the course of the disease. Similarly, deceased individuals had elevated MCP-1 and MCP-3 as well as Gal-9 serum levels. LAMP3, GZMB, and LAG3 at admission correlated with mortality. Only CX3CL13 and MCP-4 correlated positively with APACHE score and length of stay, while decorin, MUC-16 and TNFRSF21 with being admitted to the ICU. We also identified several organ-failure-specific immunological markers, including those for respiratory (IL-18, IL-15, Gal-9) or kidney failure (CD28, VEGF). Treatment with hydroxychloroquine, remdesivir, convalescent plasma, and steroids had a very limited effect on the serum variation of biomarkers. Our study identified several potential targets related to COVID-19 heterogeneity (MCP-1, MCP-3, MCP-4, TNFR superfamily members, and programmed death-ligand), suggesting a potential role of these molecules in the pathology of COVID-19.


Subject(s)
Biomarkers/blood , COVID-19/immunology , Chemokines, CC/blood , Monocyte Chemoattractant Proteins/blood , SARS-CoV-2/physiology , Adult , Aged , Aged, 80 and over , B7-H1 Antigen/metabolism , COVID-19/drug therapy , COVID-19/epidemiology , Female , Humans , Immune Sera , Immune System , Male , Middle Aged , Socioeconomic Factors , United States/epidemiology , Young Adult
12.
Crit Care Explor ; 3(4): e0380, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1174967

ABSTRACT

Objectives: Coronavirus disease 2019 pandemic exercised a significant demand on healthcare workers. We aimed to characterize the toll of caring for coronavirus disease 2019 patients by registered nurses. Design: An observational study of two registered nurses cohorts. Setting: ICUs in a large academic center. Subjects: Thirty-nine ICU registered nurses assigned to coronavirus disease 2019 versus noncoronavirus disease 2019 patients. Interventions: None. Measurements and Main Results: Skin temperature (t [°C]), galvanic skin stress response (GalvStress), blood pulse wave, energy expenditure (Energy [cal]), number of steps (hr-1), heart rate (min-1), and respiratory rate (min-1) were collected using biosensors during the shift. National Aeronautics and Space Administration Task Loading Index measured the subjective perception of an assignment load. Elevated skin temperatures during coronavirus disease 2019 shifts were recorded (ΔtCOVID vs tnon-COVID = +1.3 [°C]; 95% CI, 0.1-2.5). Registered nurses staffing coronavirus disease patients self-reported elevated effort (ΔEffortCOVID vs Effortnon-COVID = +28.6; 95% CI, 13.3-43.9) concomitant with higher energy expenditure (ΔEnergyCOVID vs Energynon-COVID = +21.5 [cal/s]; 95% CI, 4.2-38.7). Galvanic skin stress responses were more frequent among coronavirus disease registered nurse (ΔGalStressCOVID vs GalvStressnon-COVID = +10.7 [burst/hr]; 95% CI, 2.6-18.7) and correlated with self-reported increased mental burden (ΔTLXMentalCOVID vs ΔTLXMentalnon-COVID = +15.3; 95% CI, 1.0-29.6). Conclusions: There are indications that registered nurses providing care for coronavirus disease 2019 in the ICU reported increased thermal discomfort coinciding with elevated energy expenditure and a more pronounced self-perception of effort, stress, and mental demand.

13.
Healthcare (Basel) ; 9(3)2021 Mar 18.
Article in English | MEDLINE | ID: covidwho-1158372

ABSTRACT

Biosensors represent one of the numerous promising technologies envisioned to extend healthcare delivery. In perioperative care, the healthcare delivery system can use biosensors to remotely supervise patients who would otherwise be admitted to a hospital. This novel technology has gained a foothold in healthcare with significant acceleration due to the COVID-19 pandemic. However, few studies have attempted to narrate, or systematically analyze, the process of their implementation. We performed an observational study of biosensor implementation. The data accuracy provided by the commercially available biosensors was compared to those offered by standard clinical monitoring on patients admitted to the intensive care unit/perioperative unit. Surveys were also conducted to examine the acceptance of technology by patients and medical staff. We demonstrated a significant difference in vital signs between sensors and standard monitoring which was very dependent on the measured variables. Sensors seemed to integrate into the workflow relatively quickly, with almost no reported problems. The acceptance of the biosensors was high by patients and slightly less by nurses directly involved in the patients' care. The staff forecast a broad implementation of biosensors in approximately three to five years, yet are eager to learn more about them. Reliability considerations proved particularly troublesome in our implementation trial. Careful evaluation of sensor readiness is most likely necessary prior to system-wide implementation by each hospital to assess for data accuracy and acceptance by the staff.

14.
Healthcare (Basel) ; 9(1)2021 Jan 14.
Article in English | MEDLINE | ID: covidwho-1028823

ABSTRACT

The COVID-19 pandemic has accelerated the demand for virtual healthcare delivery and highlighted the scarcity of telehealth medical student curricula, particularly tele-critical care. In partnership with the Penn E-lert program and the Department of Anesthesiology and Critical Care, the Perelman School of Medicine (PSOM) established a tele-ICU rotation to support the care of patients diagnosed with COVID-19 in the Intensive Care Unit (ICU). The four-week course had seven elements: (1) 60 h of clinical engagement; (2) multiple-choice pretest; (3) faculty-supervised, student-led case and topic presentations; (4) faculty-led debriefing sessions; (5) evidence-based-medicine discussion forum; (6) multiple-choice post-test; and (7) final reflection. Five third- and fourth-year medical students completed 300 h of supervised clinical engagement, following 16 patients over three weeks and documenting 70 clinical interventions. Knowledge of critical care and telehealth was demonstrated through improvement between pre-test and post-test scores. Professional development was demonstrated through post-course preceptor and learner feedback. This tele-ICU rotation allowed students to gain telemedicine exposure and participate in the care of COVID patients in a safe environment.

15.
Healthcare (Basel) ; 8(4)2020 Dec 01.
Article in English | MEDLINE | ID: covidwho-1024558

ABSTRACT

The COVID-19 pandemic put significant strain on societies and their resources, with the healthcare system and workers being particularly affected. Artificial Intelligence (AI) offers the unique possibility of improving the response to a pandemic as it emerges and evolves. Here, we utilize the WHO framework of a pandemic evolution to analyze the various AI applications. Specifically, we analyzed AI from the perspective of all five domains of the WHO pandemic response. To effectively review the current scattered literature, we organized a sample of relevant literature from various professional and popular resources. The article concludes with a consideration of AI's weaknesses as key factors affecting AI in future pandemic preparedness and response.

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