Project description:Coronavirus disease 2019 (COVID-19) can lead to multiorgan damage and fatal outcomes. MicroRNAs (miRNAs) are detectable in blood, reflecting cell activation and tissue injury. We performed small RNA-Seq in healthy controls (N=11), non-severe (N=18) and severe (N=16) COVID-19 patients
Project description:ObjectivesTo describe the clinical characteristics of paediatric patients admitted to a single paediatric intensive care unit (PICU) in Iran with COVID-19.MethodsA cross-sectional study of paediatric patients who were admitted to a COVID-19-dedicated PICU from 16 March 2020 to 21 April 2020 with COVID-19.ResultsSix children had confirmed COVID-19 and four had suspected COVID-19. Six had pre-existing chronic medical conditions. Nine had respiratory failure and needed ventilation. Five children, of whom four had chronic medical conditions, died. Four had cardiac arrhythmias. Clinical presentation included fever and cough.ConclusionCOVID-19 can be fatal in paediatric patients, especially in those with a chronic medical condition.
Project description:Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Comprehensively capturing the host physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index and APACHE II score were poor predictors of survival. Instead, using plasma proteomes quantifying 302 plasma protein groups at 387 timepoints in 57 critically ill patients on invasive mechanical ventilation, we found 14 proteins that showed trajectories different between survivors and non-survivors. A proteomic predictor trained on single samples obtained at the first time point at maximum treatment level (i.e. WHO grade 7) and weeks before the outcome, achieved accurate classification of survivors (AUROC 0.81, n=49). We tested the established predictor on an independent validation cohort (AUROC of 1.0, n=24). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that predictors derived from plasma protein levels have the potential to substantially outperform current prognostic markers in intensive care.
Project description:PurposeThe objective of the present study was to provide a detailed histopathological description of fatal coronavirus disease 2019 (COVID 19), and compare the lesions in Intensive Care Unit (ICU) and non-ICU patients.MethodsIn this prospective study we included adult patients who died in hospital after presenting with confirmed COVID-19. Multiorgan biopsies were performed. Data generated with light microscopy, transmission electron microscopy (TEM) and RT-PCR assays were reviewed.Results20 patients were enrolled in the study and the main pulmonary finding was alveolar damage, which was focal in 11 patients and diffuse in 8 patients. Chronic fibrotic and inflammatory lesions were observed in 18 cases, with acute inflammatory lesions in 12 cases. Diffuse lesions, collapsed alveoli and dystrophic pneumocytes were more frequent in the ICU group (62.5%, vs. 25%; 63%, vs. 55%; 87.5%, vs. 54%). Acute lesions (82%, vs. 37.5%; p = 0.07) with neutrophilic alveolitis (63.6% vs. 0%, respectively; p = 0.01) were observed more frequently in the non-ICU group. Viral RNA was detected in 12 lung biopsies (60%) up to 56 days after disease upset. TEM detected viral particles in the lung and kidney biopsy samples up to 27 days after disease upset. Furthermore, abundant networks of double-membrane vesicles (DMVs, a hallmark of viral replication) were observed in proximal tubular epithelial cells.ConclusionLung injury was different in ICU and non-ICU patients. Extrapulmonary damage consisting in kidney and myocardial injury were more frequent in ICU patients. Our TEM experiments provided the first description of SARS-CoV-2-induced DMVs in kidney biopsy samples-a sign of intense viral replication in this organ.
Project description:COVID-19 has impacted millions of patients across the world. Molecular testing occurring now identifies the presence of the virus at the sampling site: nasopharynx, nares, or oral cavity. RNA sequencing has the potential to establish both the presence of the virus and define the host's response in COVID-19. Single center, prospective study of patients with COVID-19 admitted to the intensive care unit where deep RNA sequencing (> 100 million reads) of peripheral blood with computational biology analysis was done. All patients had positive SARS-CoV-2 PCR. Clinical data was prospectively collected. We enrolled fifteen patients at a single hospital. Patients were critically ill with a mortality of 47% and 67% were on a ventilator. All the patients had the SARS-CoV-2 RNA identified in the blood in addition to RNA from other viruses, bacteria, and archaea. The expression of many immune modulating genes, including PD-L1 and PD-L2, were significantly different in patients who died from COVID-19. Some proteins were influenced by alternative transcription and splicing events, as seen in HLA-C, HLA-E, NRP1 and NRP2. Entropy calculated from alternative RNA splicing and transcription start/end predicted mortality in these patients. Current upper respiratory tract testing for COVID-19 only determines if the virus is present. Deep RNA sequencing with appropriate computational biology may provide important prognostic information and point to therapeutic foci to be precisely targeted in future studies.
Project description:ObjectivesCOVID-19 associated arterial thrombosis has been attributed to multiple inflammation and coagulation mechanisms. The aim of this study was to report the experience of a tertiary center on COVID-19 patients managed for acute peripheral arterial thrombosis.MethodsA single-center case series was conducted, including retrospectively collected data from all COVID-19 patients presenting arterial thrombosis, from March 2020 to February 2022. Intensive care unit (ICU) and non-ICU cases were included. The primary outcomes were mortality, successful revascularization, and amputation at 30 days.ResultsTwenty patients presented peripheral arterial thrombosis (90% males, mean age 65 years (16-82 years)). Eighteen were diagnosed with the Delta variant and none was previously vaccinated. All cases presented acute lower limb ischemia; in 20% with bilateral involvement. Nine patients were hospitalized in the ward while 11 in the ICU. From the non-ICU cases, five presented Rutherford IIb and four cases, Rutherford's IIa ischemia. Six cases underwent revascularization (67%). Two of them were finally amputated (33%) and two died during hospitalization (33%). Two revascularizations were considered successful (33%). The ICU group presented mainly with Rutherford's III ischemia (54.5%). The mortality in the ICU cohort was 72.7%. Only one patient underwent successful revascularization and two were amputated in this subgroup. Early mortality was 50% for the total cohort while the type of management was not related to mortality.ConclusionsCovid-19 related arterial thrombosis in non-vaccinated population is associated with 50% early mortality; increased up to 72% in the ICU patients. The amputation rate was 20% while only 40% of the revascularizations were considered successful.
Project description:Coronavirus disease 2019 (COVID-19) has a wide spectrum of disease severity from mild upper respiratory symptoms to respiratory failure. The role of neutralizing antibody (NAb) response in disease progression remains elusive. This study determined the seroprevalence of 733 non-COVID-19 individuals from April 2018 to February 2020 in the Hong Kong Special Administrative Region and compared the neutralizing antibody (NAb) responses of eight COVID-19 patients admitted to the intensive care unit (ICU) with those of 42 patients not admitted to the ICU. We found that NAb against SARS-CoV-2 was not detectable in any of the anonymous serum specimens from the 733 non-COVID-19 individuals. The peak serum geometric mean NAb titer was significantly higher among the eight ICU patients than the 42 non-ICU patients (7280 [95% confidence interval (CI) 1468-36099]) vs (671 [95% CI, 368-1223]). Furthermore, NAb titer increased significantly at earlier infection stages among ICU patients than among non-ICU patients. The median number of days to reach the peak Nab titers after symptoms onset was shorter among the ICU patients (17.6) than that of the non-ICU patients (20.1). Multivariate analysis showed that oxygen requirement and fever during admission were the only clinical factors independently associated with higher NAb titers. Our data suggested that SARS-CoV-2 was unlikely to have silently spread before the COVID-19 emergence in Hong Kong. ICU patients had an accelerated and augmented NAb response compared to non-ICU patients, which was associated with disease severity. Further studies are required to understand the relationship between high NAb response and disease severity.
Project description:Trends in routine laboratory tests, such as high white blood cell and low platelet counts, correlate with COVID-19-related intensive care unit (ICU) admissions. Other related biomarkers include elevated troponin, alanine aminotransferase, and aspartate transaminase levels (liver function tests). To this end, the aim of this study was to investigate the effect of changes in laboratory test parameters on ward-based and ICU COVID-19 patients. A total of 280 COVID-19 patients were included in the study and were divided based on admission status into ICU (37) or ward (243) patients. ICU admission correlated significantly with higher levels of several tested parameters, including lactate dehydrogenase, creatinine, D-dimer, creatine kinase, white blood cell count, and neutrophil count. In conclusion, routine laboratory tests offer an indication of which COVID-19 patients are most likely to be admitted to the ICU. These associations can assist healthcare providers in addressing the needs of patients who are at risk of COVID-19 complications.