Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 51
Filter
Add filters

Document Type
Year range
1.
Virchows Arch ; 479(1): 97-108, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1574264

ABSTRACT

Between April and June 2020, i.e., during the first wave of pandemic coronavirus disease 2019 (COVID-19), 55 patients underwent long-term treatment in the intensive care unit at the University Hospital of Regensburg. Most of them were transferred from smaller hospitals, often due to the need for an extracorporeal membrane oxygenation system. Autopsy was performed in 8/17 COVID-19-proven patients after long-term treatment (mean: 33.6 days). Autopsy revealed that the typical pathological changes occurring during the early stages of the disease (e.g., thrombosis, endothelitis, capillaritis) are less prevalent at this stage, while severe diffuse alveolar damage and especially coinfection with different fungal species were the most conspicuous finding. In addition, signs of macrophage activation syndrome was detected in 7 of 8 patients. Thus, fungal infections were a leading cause of death in our cohort of severely ill patients and may alter clinical management of patients, particularly in long-term periods of treatment.


Subject(s)
COVID-19/microbiology , Coinfection , Lung Diseases, Fungal/microbiology , Lung/microbiology , Multiple Organ Failure/microbiology , Adult , Aged , COVID-19/drug therapy , COVID-19/mortality , COVID-19/pathology , COVID-19/therapy , Cause of Death , Extracorporeal Membrane Oxygenation , Female , Humans , Intensive Care Units , Lung/pathology , Lung/virology , Lung Diseases, Fungal/mortality , Lung Diseases, Fungal/pathology , Macrophage Activation Syndrome/microbiology , Macrophage Activation Syndrome/pathology , Male , Middle Aged , Multiple Organ Failure/mortality , Multiple Organ Failure/pathology , Multiple Organ Failure/virology , Risk Factors , Time Factors , Treatment Outcome
2.
Immunopharmacol Immunotoxicol ; 43(6): 633-643, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1467231

ABSTRACT

The coronavirus disease-19 (COVID-19), at first, was reported in Wuhan, China, and then rapidly became pandemic throughout the world. Cytokine storm syndrome (CSS) in COVID-19 patients is associated with high levels of cytokines and chemokines that cause multiple organ failure, systemic inflammation, and hemodynamic instabilities. Acute respiratory distress syndrome (ARDS), a common complication of COVID-19, is a consequence of cytokine storm. In this regard, several drugs have been being investigated to suppress this inflammatory condition. Purinergic signaling receptors comprising of P1 adenosine and P2 purinoceptors play a critical role in inflammation. Therefore, activation or inhibition of some subtypes of these kinds of receptors is most likely to be beneficial to attenuate cytokine storm. This article summarizes suggested therapeutic drugs with potential anti-inflammatory effects through purinergic receptors.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Cytokine Release Syndrome/prevention & control , Cytokines/blood , Purinergic Antagonists/therapeutic use , Receptors, Purinergic/drug effects , SARS-CoV-2/drug effects , Animals , Anti-Inflammatory Agents/adverse effects , Biomarkers/blood , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Host-Pathogen Interactions , Humans , Ligands , Molecular Targeted Therapy , Multiple Organ Failure/immunology , Multiple Organ Failure/prevention & control , Multiple Organ Failure/virology , Purinergic Antagonists/adverse effects , Receptors, Purinergic/metabolism , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Signal Transduction
3.
Biomed Pharmacother ; 143: 112158, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1385086

ABSTRACT

COVID-19 (Corona Virus Disease-2019) is an infectious disease caused by a novel coronavirus, known as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This is a highly contagious disease that has already affected more than 220 countries globally, infecting more than 212 million people and resulting in the death of over 4.4 million people. This review aims to highlight the pertinent documentary evidence upon the adverse effects of the SARS-CoV-2 infection on several vital human organs. SARS-CoV-2 primarily targets the lung tissue by causing diffuse alveolar damage and may result in Acute Respiratory Distress Syndrome (ARDS). SARS-CoV-2 infects the cell via cell surface receptor, angiotensin-converting enzyme 2 (ACE2). Besides lungs, SARS-CoV-2 critically damage tissues in other vital human organs such as the heart, kidney, liver, brain, and gastrointestinal tract. The effect on the heart includes muscle dysfunction (acute or protracted heart failure), myocarditis, and cell necrosis. Within hepatic tissue, it alters serum aminotransferase, total bilirubin, and gamma-glutamyl transferase levels. It contributes to acute kidney injury (AKI). Localized infection of the brain can lead to loss or attenuation of olfaction, muscular pain, headaches, encephalopathy, dizziness, dysgeusia, psychomotor disorders, and stroke; while the gastrointestinal symptoms include the disruption of the normal intestinal mucosa, leading to diarrhea and abdominal pain. This review encompassed a topical streak of systemic malfunctions caused by the SARS-CoV-2 infection. As the pandemic is still in progress, more studies will enrich our understanding and analysis of this disease.


Subject(s)
COVID-19 , Multiple Organ Failure , SARS-CoV-2 , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/diagnosis , COVID-19/metabolism , COVID-19/physiopathology , Humans , Multiple Organ Failure/physiopathology , Multiple Organ Failure/virology , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology
4.
Nutrients ; 13(7)2021 Jun 28.
Article in English | MEDLINE | ID: covidwho-1288966

ABSTRACT

SARS-CoV-2 infects the respiratory tract and leads to the disease entity, COVID-19. Accordingly, the lungs bear the greatest pathologic burden with the major cause of death being respiratory failure. However, organs remote from the initial site of infection (e.g., kidney, heart) are not spared, particularly in severe and fatal cases. Emerging evidence indicates that an excessive inflammatory response coupled with a diminished antiviral defense is pivotal in the initiation and development of COVID-19. A common finding in autopsy specimens is the presence of thrombi in the lungs as well as remote organs, indicative of immunothrombosis. Herein, the role of SARS-CoV-2 in lung inflammation and associated sequelae are reviewed with an emphasis on immunothrombosis. In as much as vitamin D is touted as a supplement to conventional therapies of COVID-19, the impact of this vitamin at various junctures of COVID-19 pathogenesis is also addressed.


Subject(s)
COVID-19/drug therapy , COVID-19/immunology , Inflammation/virology , Pneumonia/virology , Vitamin D/therapeutic use , Animals , COVID-19/virology , Extracellular Traps , Humans , Inflammation/drug therapy , Lung/pathology , Mice , Multiple Organ Failure/virology , Pneumonia/drug therapy , Respiratory Distress Syndrome/virology , SARS-CoV-2 , Thrombosis/immunology , Thrombosis/virology , Vitamins/therapeutic use
5.
Crit Care ; 25(1): 224, 2021 06 30.
Article in English | MEDLINE | ID: covidwho-1286832

ABSTRACT

BACKGROUND: Previous studies reporting the causes of death in patients with severe COVID-19 have provided conflicting results. The objective of this study was to describe the causes and timing of death in patients with severe COVID-19 admitted to the intensive care unit (ICU). METHODS: We performed a retrospective study in eight ICUs across seven French hospitals. All consecutive adult patients (aged ≥ 18 years) admitted to the ICU with PCR-confirmed SARS-CoV-2 infection and acute respiratory failure were included in the analysis. The causes and timing of ICU deaths were reported based on medical records. RESULTS: From March 1, 2020, to April 28, 287 patients were admitted to the ICU for SARS-CoV-2 related acute respiratory failure. Among them, 93 patients died in the ICU (32%). COVID-19-related multiple organ dysfunction syndrome (MODS) was the leading cause of death (37%). Secondary infection-related MODS accounted for 26% of ICU deaths, with a majority of ventilator-associated pneumonia. Refractory hypoxemia/pulmonary fibrosis was responsible for death in 19% of the cases. Fatal ischemic events (venous or arterial) occurred in 13% of the cases. The median time from ICU admission to death was 15 days (25th-75th IQR, 7-27 days). COVID-19-related MODS had a median time from ICU admission to death of 14 days (25th-75th IQR: 7-19 days), while only one death had occurred during the first 3 days since ICU admission. CONCLUSIONS: In our multicenter observational study, COVID-19-related MODS and secondary infections were the two leading causes of death, among severe COVID-19 patients admitted to the ICU.


Subject(s)
COVID-19/mortality , Multiple Organ Failure/mortality , Pneumonia, Viral/mortality , Adult , Cause of Death , Female , Hospital Mortality , Humans , Hypoxia/mortality , Hypoxia/virology , Intensive Care Units , Ischemia/mortality , Ischemia/virology , Male , Multiple Organ Failure/virology , Pneumonia, Ventilator-Associated/mortality , Pneumonia, Ventilator-Associated/virology , Pneumonia, Viral/virology , Pulmonary Fibrosis/mortality , Pulmonary Fibrosis/virology , Retrospective Studies , SARS-CoV-2
6.
Arch Argent Pediatr ; 119(3): e252-e255, 2021 06.
Article in English, Spanish | MEDLINE | ID: covidwho-1242314

ABSTRACT

Coronavirus infections (CoV) are common in pediatric patients. In general, they produce a mild clinical presentation consisting of an upper respiratory tract infection that does not usually infect the lungs, with the exception of preterm infants and children with chronic diseases. These infections exceptionally affect other organs (heart, brain, gastrointestinal tract), thus increasing their severity. In relation to the temporal coincidence with the beginning of the current situation of pandemic by the new beta coronavirus SARS-CoV-2 responsible for its associated disease (COVID-19), this study presents a clinical case of a 5-year-old patient showing multiple-organ failure and neurological sequelae due to bulbar injury and vascular thrombosis caused by an alpha coronavirus (CoV-NL63) due to its severity and exceptionality.


Subject(s)
Coronavirus Infections/diagnosis , Coronavirus NL63, Human/isolation & purification , Multiple Organ Failure/virology , Respiratory Tract Infections/diagnosis , COVID-19/diagnosis , Child, Preschool , Coronavirus Infections/complications , Diagnosis, Differential , Humans , Multiple Organ Failure/diagnosis , Respiratory Tract Infections/complications
7.
J Med Virol ; 93(3): 1652-1664, 2021 03.
Article in English | MEDLINE | ID: covidwho-1196493

ABSTRACT

Multiorgan injury has been implicated in patients with coronavirus disease 2019 (COVID-19). We aim to assess the impact of organ injury (OI) on prognosis according to the number of affected organs at admission. This is a retrospective cohort study of patients with confirmed COVID-19 in Wuhan Third Hospital & Tongren Hospital of Wuhan University from February 17 to March 22, 2020. We classified the patients according to the presence and number of damaged organs (heart, liver, and kidney). The percentage of patients with no, one, two, or three organs affected was 59.75%, 30.46%, 8.07%, and 1.72%, respectively. With the increasing number of OI, there is a tendency of gradual increase regarding the white blood cell counts, neutrophil counts, levels of C-reactive protein (CRP), lactate dehydrogenase, D-dimer, and fibrinogen as well as the incidence of most complications. In a Cox regression model, individuals with OI, old age, and an abnormal level of CRP were at a higher risk of death compared with those without. Patients with three organ injuries had the highest mortality rate (57.9%; hazard ratio [HR] with 95% confidence interval [CI] vs. patients without OI: 22.31 [10.42-47.77], those with two [23.6%; HR = 8.68, 95% CI = 4.58-16.48], one [8.6%; HR = 3.1, 95% CI = 1.7-5.7], or no OI [2.6%]; p < .001). The increasing number of OI was associated with a high risk of mortality in COVID-19 infection.


Subject(s)
COVID-19/mortality , Multiple Organ Failure/mortality , Aged , C-Reactive Protein/metabolism , COVID-19/metabolism , COVID-19/virology , Female , Fibrinogen/metabolism , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Incidence , L-Lactate Dehydrogenase/metabolism , Leukocyte Count/methods , Male , Middle Aged , Multiple Organ Failure/metabolism , Multiple Organ Failure/virology , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2/pathogenicity
8.
BMJ Case Rep ; 14(4)2021 Apr 12.
Article in English | MEDLINE | ID: covidwho-1180949

ABSTRACT

Since the emergence of SARS-CoV-2, clinicians have been challenged with a wide spectrum of disease severity. One of the serious complications associated with the virus is multisystem inflammatory syndrome in children (MIS-C). It is characterised by inflammation leading to organ damage, in the setting of positive SARS-CoV-2 infection. MIS-C is thought to be a postviral reaction where most children are negative on PCR testing but are positive for SARS-CoV-2 antibodies. The Centers for Disease Control and Prevention recently defined the same phenomenon occurring in adults as multisystem inflammatory syndrome in adults (MIS-A) and emphasised on the use of antibody testing in this population. Here we describe an adult woman with an exposure to SARS-CoV-2 who presented with unexplained organ failure and shock. Positive antibody testing was the only clue to the diagnosis of MIS-A. We stress the importance of SARS-CoV-2 antibody detection in order to identify these cases.


Subject(s)
COVID-19/complications , Systemic Inflammatory Response Syndrome/virology , Adult , Antibodies, Viral , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19 Serological Testing , Diagnosis, Differential , Female , Humans , Multiple Organ Failure/diagnosis , Multiple Organ Failure/virology , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/drug therapy
9.
Orv Hetil ; 162(16): 602-607, 2021 04 07.
Article in Hungarian | MEDLINE | ID: covidwho-1172895

ABSTRACT

Összefoglaló. Újabb megfigyelések szerint a SARS-CoV-2-fertozést követoen gyermekekben a paediatric inflammatory multisystem syndrome (PIMS) elnevezésu, sokkállapottal szövodött Kawasaki-megbetegedéshez hasonlító, többszervi elégtelenségnek megfelelo tünetegyüttes alakulhat ki. A gyermekek többségében ilyenkor a direkt víruskimutatás már sikertelen, azonban a SARS-CoV-2 ellen képzodött antitest igazolhatja a diagnózist. Dolgozatunk célja az egyik elso hazai eset ismertetése. Egy 15 éves fiú került gyermek intenzív osztályos felvételre több napon át észlelt magas láz, kesztyu-, zokniszeru exanthema, conjunctivitis, többszervi elégtelenség, szeptikus sokk tüneteivel, akut gyulladásra utaló laboratóriumi eltérésekkel és diffúz hasi panaszokkal. Felvételét megelozoen néhány héttel SARS-CoV-2-fertozésen esett át. Felvételekor a direkt víruskimutatás sikertelen volt, ám a SARS-CoV-2 elleni antitest vizsgálata pozitív lett. Komplex intenzív terápia mellett állapota stabilizálódott. Az irodalmi ajánlásoknak megfeleloen immunglobulin-, acetilszalicilsav- és szteroidkezelésben részesítettük, melynek hatására állapota maradványtünetek nélkül rendezodött. A növekvo esetszámú gyermekkori SARS-CoV-2-fertozés mellett egyre gyakrabban várható a SARS-CoV-2-fertozést követo, a Kawasaki-betegség tüneteire emlékezteto PIMS kialakulása. Gyermekekben súlyos szeptikus állapot és többszervi elégtelenség esetén gondolni kell a PIMS lehetoségére, mely esetenként intenzív osztályos ellátást és célzott terápiát igényel. Legjobb tudomásunk szerint a leírásra került beteg a Magyarországon diagnosztizált egyik legkorábbi eset. Orv Hetil. 2021; 162(16): 602-607. Summary. Recently following SARS-CoV-2 infection, a new, multisystem disease (paediatric inflammatory multisystem syndrome, PIMS) with fever was recognized in children with shock and multiorgan failure. On of the first Hungarian cases will be described. A 15-year-old boy was admitted to the Paediatric Intensive Care Unit with persistent high fever, diffuse abdominal pain, septic shock, multiple organ failure, gloves- and socks-shaped cutan exanthema, conjunctivitis and laboratory signs of inflammation. Some weeks preceding his admission, symptoms of mild SARS-CoV-2 infection were revealed. At admission, the SARS-CoV-2 PCR and antigen tests were negative, however, the presence of IgG antibody was shown. Following complex supportive intensive care along with internationally recommended immunoglobulin, aspirin and steroid treatment, the patient was completely cured without any sequalae. In children after SARS-CoV-2 infection, PIMS could occur mimicking Kawasaki syndrome. At this time, in children virus PCR or antigen tests are usually negative already, but the presence of SARS-CoV-2 antibody could prove the preceding disease. Due to the increasing number of SARS-CoV-2 infections, the occurrence of post-SARS-CoV-2 PIMS in childhood is expected to increase. For paediatric patients, in case of severe septic state and multiple organ failure, PIMS should be also considered, which may require intensive care and targeted therapy. As far as we know, the described case is one of the earliest cases of PIMS in Hungary. Orv Hetil. 2021; 162(16): 602-607.


Subject(s)
Abdominal Pain/etiology , COVID-19/diagnosis , Fever/etiology , Immunoglobulin G/blood , Systemic Inflammatory Response Syndrome , Adolescent , COVID-19/blood , COVID-19/virology , Conjunctivitis/virology , Exanthema/virology , Hospitalization , Humans , Hungary , Inflammation/virology , Intensive Care Units, Pediatric , Male , Multiple Organ Failure/virology , SARS-CoV-2 , Shock, Septic/virology , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/virology
10.
Sci Rep ; 11(1): 7163, 2021 03 30.
Article in English | MEDLINE | ID: covidwho-1159799

ABSTRACT

The spread of virus via the blood stream has been suggested to contribute to extra-pulmonary organ failure in Coronavirus disease 2019 (COVID-19). We assessed SARS-CoV-2 RNAemia (RNAemia) and the association between RNAemia and inflammation, organ failure and mortality in critically ill COVID-19 patients. We included all patients with PCR verified COVID-19 and consent admitted to ICU. SARS-CoV-2 RNA copies above 1000/ml measured by PCR in plasma was defined as RNAemia and used as surrogate for viremia. In this cohort of 92 patients 59 (64%) were invasively ventilated. RNAemia was found in 31 patients (34%). Hypertension and corticosteroid treatment was more common in patients with RNAemia. Extra-pulmonary organ failure biomarkers and the extent of organ failure were similar in patients with and without RNAemia, but the former group had more renal replacement therapy and higher mortality (26 vs 16%; 35 vs 16%, respectively, p = 0.04). RNAemia was not an independent predictor of death at 30 days after adjustment for age. SARS-CoV2 RNA copies in plasma is a common finding in ICU patients with COVID-19. Although viremia was not associated with extra pulmonary organ failure it was more common in patients who did not survive to 30 days after ICU admission.Trial registration: ClinicalTrials NCT04316884.


Subject(s)
COVID-19/etiology , COVID-19/mortality , Viremia/etiology , Aged , Biomarkers/blood , COVID-19/therapy , Comorbidity , Critical Illness , Female , Humans , Hypertension/epidemiology , Hypertension/etiology , Interleukin-6/blood , Male , Middle Aged , Multiple Organ Failure/etiology , Multiple Organ Failure/virology , Prospective Studies , RNA, Viral/blood , Renal Replacement Therapy , Respiration, Artificial , Sweden/epidemiology , Viremia/mortality , Viremia/therapy
11.
Expert Rev Proteomics ; 18(2): 105-118, 2021 02.
Article in English | MEDLINE | ID: covidwho-1155738

ABSTRACT

Introduction:The year 2020 was defined by the 29,903 base pairs of RNA that codes for the SARS-CoV-2 genome. SARS-CoV-2 infects humans to cause COVID-19, spreading from patient-to-patient yet impacts patients very divergently.Areas covered: Within this review, we address the known molecular mechanisms and supporting data for COVID-19 clinical course and pathology, clinical risk factors and molecular signatures, therapeutics of severe COVID-19, and reinfection/vaccination. Literature and published datasets were reviewed using PubMed, Google Scholar, and NCBI SRA tools. The combination of exaggerated cytokine signaling, pneumonia, NETosis, pyroptosis, thrombocytopathy, endotheliopathy, multiple organ dysfunction syndrome (MODS), and acute respiratory distress syndrome (ARDS) create a positive feedback loop of severe damage in patients with COVID-19 that impacts the entire body and may persist for months following infection. Understanding the molecular pathways of severe COVID-19 opens the door for novel therapeutic design. We summarize the current insights into pathology, risk factors, secondary infections, genetics, omics, and drugs being tested to treat severe COVID-19.Expert opinion: A growing level of support suggests the need for stronger integration of biomarkers and precision medicine to guide treatment strategies of severe COVID-19, where each patient has unique outcomes and thus require guided treatment.


Subject(s)
COVID-19/genetics , Multiple Organ Failure/genetics , Respiratory Distress Syndrome/genetics , COVID-19/complications , COVID-19/virology , Cytokines/biosynthesis , Cytokines/genetics , Genome, Viral/genetics , Humans , Multiple Organ Failure/complications , Multiple Organ Failure/virology , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/virology , SARS-CoV-2/pathogenicity
13.
Sci Rep ; 11(1): 4263, 2021 02 19.
Article in English | MEDLINE | ID: covidwho-1091460

ABSTRACT

Infection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has been associated with more than two million deaths worldwide. Patients of higher age and with preexisting chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of pre-existing health conditions to death yet is missing, which can be reliably established by autopsy only. We performed full body autopsies on 26 patients that had died after SARS-CoV-2 infection and COVID-19 at the Charité University Hospital Berlin, Germany, or at associated teaching hospitals. We systematically evaluated causes of death and pre-existing health conditions. Additionally, clinical records and death certificates were evaluated. We report findings on causes of death and comorbidities of 26 decedents that had clinically presented with severe COVID-19. We found that septic shock and multi organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. Respiratory failure due to diffuse alveolar damage presented as immediate cause of death in fewer cases. Several comorbidities, such as hypertension, ischemic heart disease, and obesity were present in the vast majority of patients. Our findings reveal that causes of death were directly related to COVID-19 in the majority of decedents, while they appear not to be an immediate result of preexisting health conditions and comorbidities. We therefore suggest that the majority of patients had died of COVID-19 with only contributory implications of preexisting health conditions to the mechanism of death.


Subject(s)
COVID-19/mortality , Cause of Death , Hospital Mortality , Adult , Aged , Aged, 80 and over , Autopsy , Berlin/epidemiology , COVID-19/complications , COVID-19/therapy , COVID-19/virology , Comorbidity , Female , Hospitals, Teaching/statistics & numerical data , Humans , Hypertension/epidemiology , Male , Middle Aged , Multiple Organ Failure/mortality , Multiple Organ Failure/virology , Myocardial Ischemia/epidemiology , Obesity/epidemiology , Prospective Studies , SARS-CoV-2/isolation & purification , Shock, Septic/mortality , Shock, Septic/virology
14.
Med Clin (Barc) ; 155(5): 191-196, 2020 09 11.
Article in English, Spanish | MEDLINE | ID: covidwho-526756

ABSTRACT

OBJECTIVE: The purpose of our study was to assess organ function in 102 patients with severe COVID-19 infections, using retrospective clinical analysis. MATERIAL AND METHODS: A retrospective analysis was conducted on 102 patients with severe COVID-19 infections. The patients were divided into a survival group (n=73) and a non-survival group (n=29) according to their prognosis. The age, sex, underlying diseases, clinical laboratory data within 48h (routine blood tests, ALT, AST, TBIL, ALB, BUN, CR, D-Dimer, PT, APTT, FIB, F VIII:C, CK-MB, CK, and LDH), and ventilation status were collected. The organ functions of these severe COVID-19 patients were assessed by comparing the differences between the two groups. RESULTS: AST, BUN, CR, CK-MB, LDH, and CK in the non-survival group were higher than those in the survival group, and the differences were statistically significant (P<0.05). D-Dimer, PT, FIB, and F VIII:C in the non-survival group were higher than the values observed in the survival group, and the differences were statistically significant (P<0.05). PLT, AST, BUN, CR, D-Dimer, PT, FIB, F VIII:C, CK-MB, CK, and LDH predicted the area under the ROC curve (AUC) of the COVID19 endpoint events and were 0.721, 0.854, 0.867, 0.757, 0.699, 0.679, 0.715, 0.811, 0.935, and 0.802, respectively. CONCLUSION: The results showed that there were different degrees of damage to the liver, kidneys, blood coagulation, and heart function in the non-survival group. In addition, PLT, AST, BUN, CR, D-Dimer, PT, FIB, F VIII:C, CK-MB, CK, and LDH had value in evaluating disease prognosis.


Subject(s)
Betacoronavirus , Coronavirus Infections/physiopathology , Multiple Organ Failure/virology , Pneumonia, Viral/physiopathology , Severity of Illness Index , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19 , COVID-19 Testing , Case-Control Studies , China/epidemiology , Clinical Laboratory Techniques , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Female , Humans , Male , Middle Aged , Multiple Organ Failure/blood , Multiple Organ Failure/diagnosis , Multiple Organ Failure/mortality , Organ Dysfunction Scores , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Prognosis , ROC Curve , Retrospective Studies , SARS-CoV-2
17.
Am J Respir Crit Care Med ; 203(2): 192-201, 2021 01 15.
Article in English | MEDLINE | ID: covidwho-1059843

ABSTRACT

Rationale: In life-threatening coronavirus disease (COVID-19), corticosteroids reduce mortality, suggesting that immune responses have a causal role in death. Whether this deleterious inflammation is primarily a direct reaction to the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or an independent immunopathologic process is unknown.Objectives: To determine SARS-CoV-2 organotropism and organ-specific inflammatory responses and the relationships among viral presence, inflammation, and organ injury.Methods: Tissue was acquired from 11 detailed postmortem examinations. SARS-CoV-2 organotropism was mapped by using multiplex PCR and sequencing, with cellular resolution achieved by in situ viral S (spike) protein detection. Histologic evidence of inflammation was quantified from 37 anatomic sites, and the pulmonary immune response was characterized by using multiplex immunofluorescence.Measurements and Main Results: Multiple aberrant immune responses in fatal COVID-19 were found, principally involving the lung and reticuloendothelial system, and these were not clearly topologically associated with the virus. Inflammation and organ dysfunction did not map to the tissue and cellular distribution of SARS-CoV-2 RNA and protein between or within tissues. An arteritis was identified in the lung, which was further characterized as a monocyte/myeloid-rich vasculitis, and occurred together with an influx of macrophage/monocyte-lineage cells into the pulmonary parenchyma. In addition, stereotyped abnormal reticuloendothelial responses, including excessive reactive plasmacytosis and iron-laden macrophages, were present and dissociated from viral presence in lymphoid tissues.Conclusions: Tissue-specific immunopathology occurs in COVID-19, implicating a significant component of the immune-mediated, virus-independent immunopathologic process as a primary mechanism in severe disease. Our data highlight novel immunopathologic mechanisms and validate ongoing and future efforts to therapeutically target aberrant macrophage and plasma-cell responses as well as promote pathogen tolerance in COVID-19.


Subject(s)
COVID-19/immunology , Inflammation/virology , Lung/immunology , Multiple Organ Failure/virology , SARS-CoV-2/immunology , Aged , Aged, 80 and over , Autopsy , Biopsy , COVID-19/pathology , COVID-19/virology , COVID-19 Nucleic Acid Testing , Female , Fluorescent Antibody Technique , Humans , Inflammation/immunology , Inflammation/pathology , Lung/pathology , Lung/virology , Male , Multiple Organ Failure/immunology , Multiple Organ Failure/pathology , SARS-CoV-2/pathogenicity , Severity of Illness Index
19.
Clin Lab ; 67(1)2021 Jan 01.
Article in English | MEDLINE | ID: covidwho-1045291

ABSTRACT

BACKGROUND: In 2020, the SARS-CoV-2 virus spread worldwide and infected more that 10 million people, causing more than 500,000 deaths worldwide. The infection has systemic effects on the respiratory and cardiovascular systems; thus, patients can present a variety of symptoms from asymptomatic to rapid deaths. In this paper, we present the first case of post-mortem SARS-CoV-2 molecular testing in Western part of Romania in a deceased with disseminated intravascular coagulation (DIC) and elevated D-dimer levels. METHODS: During the autopsy which took place at the Institute of Forensic Medicine from Timisoara, Romania, blood sample was collected in a vacutainer with EDTA and sent to the Laboratory of Forensic Genetics from Victor Babes University of Medicine and Pharmacy, Timisoara, Romania. Viral RNA extraction was performed automated on the Maxwell 48 RSC Extraction System (Promega, USA) using the Maxwell RSC Viral Total Nucleic Acid Purification kit (Promega, USA). After RNA extraction, the samples were amplified on a 7500 real-time PCR (Applied Biosystems, USA) using the genesig® Real-Time PCR Assay (Primer Design, UK). RESULTS: The molecular testing showed a cycle threshold value of 23.4 (1.2 x 106 copies/mL), indicating increased viral loads, which correlated with the laboratory analysis results, especially with D-dimer levels. CONCLUSIONS: In cases of coagulopathy of SARS-CoV-2, patients in hospitals should be monitored closely for thrombosis development. Thus D-dimer can be used as prognostic marker in monitoring the evolution of SARS-CoV-2 infected patients.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Disseminated Intravascular Coagulation/diagnosis , Fibrin Fibrinogen Degradation Products/analysis , Autopsy , Biomarkers/blood , COVID-19/blood , COVID-19/complications , COVID-19/virology , Cause of Death , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/virology , Fatal Outcome , Humans , Multiple Organ Failure/virology , Predictive Value of Tests , Romania , Up-Regulation
20.
J Allergy Clin Immunol Pract ; 9(4): 1442-1448, 2021 04.
Article in English | MEDLINE | ID: covidwho-1039429

ABSTRACT

The year 2020 was a landmark year of a once-in-a-century pandemic of a novel coronavirus, SARS-CoV-2 virus, that led to a rapidly spreading coronavirus disease (COVID-19). The spectrum of disease with SARS-CoV-2 ranges from asymptomatic to mild upper respiratory illness, to moderate to severe disease with respiratory compromise to acute respiratory distress syndrome, multiorgan failure, and death. Early in the pandemic, risk factors were recognized that contributed to more severe disease, but it became evident that individuals and even young people could have severe COVID-19. As we started to understand the immunobiology of COVID-19, it became clearer that the immune responses to SARS-CoV-2 were variable, and in some cases, the excessive inflammatory response contributed to greater morbidity and mortality. In this review, we will explore some of the additional risk factors that appear to contribute to disease severity and enhance our understanding of why some individuals experience more severe COVID-19. Recent advances in genome-wide associations have identified potential candidate genes in certain populations that may modify the host immune responses leading to dysregulated host immunity. Genetic defects of the type I interferon pathway are also linked to a more clinically severe phenotype of COVID-19. Finally, dysregulation of the adaptive immune system may also play a role in the severity and complex clinical course of patients with COVID-19. A better understanding of the host immune responses to SARS-CoV-2 will hopefully lead to new treatment modalities to prevent the poor outcomes of COVID-19 in those individuals with pre-existing risk factors or genetic variants that contribute to the dysregulated host immune responses.


Subject(s)
COVID-19/diagnosis , COVID-19/pathology , Multiple Organ Failure/virology , Respiratory Distress Syndrome/virology , Adaptive Immunity , Genome-Wide Association Study , Humans , Immunity/genetics , Pandemics , Risk Factors
SELECTION OF CITATIONS
SEARCH DETAIL
...