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2.
N Engl J Med ; 384(22): 2092-2101, 2021 06 03.
Article in English | MEDLINE | ID: covidwho-2283980

ABSTRACT

BACKGROUND: Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder. METHODS: We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19. We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)-heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions. Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4-heparin immunoassay. RESULTS: Of the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49). Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage. Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died. Five patients had disseminated intravascular coagulation. None of the patients had received heparin before symptom onset. All 28 patients who tested positive for antibodies against PF4-heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin. Platelet activation was inhibited by high levels of heparin, Fc receptor-blocking monoclonal antibody, and immune globulin (10 mg per milliliter). Additional studies with PF4 or PF4-heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation. CONCLUSIONS: Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.).


Subject(s)
Autoantibodies/blood , COVID-19 Vaccines/adverse effects , Platelet Factor 4/immunology , Thrombocytopenia/etiology , Thrombosis/etiology , Adult , Autoimmune Diseases/etiology , Blood Chemical Analysis , ChAdOx1 nCoV-19 , Disseminated Intravascular Coagulation/etiology , Enzyme-Linked Immunosorbent Assay , Fatal Outcome , Female , Humans , Intracranial Hemorrhages/etiology , Male , Middle Aged , Platelet Activation , Thrombocytopenia/immunology , Thrombosis/immunology , Young Adult
3.
J Korean Med Sci ; 38(10): e78, 2023 Mar 13.
Article in English | MEDLINE | ID: covidwho-2264614

ABSTRACT

We present an autopsy case of a 19-year-old man with a history of epilepsy whose unwitnessed sudden death occurred unexpectedly in the night. About 4 years before death, he was diagnosed with unilateral optic neuritis (ON). Demyelinating disease was suspected, but he was lost to follow up after the recovery. Six months before death, he received a second dose of mRNA coronavirus disease 2019 (COVID-19) vaccine. Three months before death, he experienced epileptic seizures for the first time. Seventeen days before death, he was infected with COVID-19, which showed self-limited course under home isolation. Several days before death, he complained of seizures again at night. Autopsy revealed multifocal gray-tan discoloration in the cerebrum. Histologically, the lesions consisted of active and inactive demyelinated plaques in the perivenous area of the white matter. Perivascular lymphocytic infiltration and microglial cell proliferation were observed in both white matter and cortex. The other major organs including heart and lung were unremarkable. Based on the antemortem history and postmortem findings, the cause of death was determined to be multiple sclerosis with suspected exacerbation. The direct or indirect involvement of cortex and deep gray matter by exacerbated multiple sclerosis may explain the occurrence of seizures. Considering the absence of other structural abnormalities except the inflammatory demyelination of the cerebrum, fatal arrhythmia or laryngospasm in the terminal epileptic seizure may explain his sudden unexpected death in the benign circumstances. In this case, the onset of seizure was preceded by COVID-19 vaccination, and the exacerbation of seizure was preceded by COVID-19 infection, respectively. Literature reporting first manifestation or relapse of multiple sclerosis temporally associated with COVID-19 vaccination or infection are reviewed.


Subject(s)
COVID-19 , Epilepsy , Multiple Sclerosis , Humans , Male , Young Adult , COVID-19/complications , COVID-19 Vaccines/adverse effects , Death, Sudden/etiology , Epilepsy/complications , Multiple Sclerosis/complications , Seizures/complications , Vaccination/adverse effects , Fatal Outcome
7.
J Investig Med High Impact Case Rep ; 10: 23247096221111760, 2022.
Article in English | MEDLINE | ID: covidwho-1938261

ABSTRACT

A case of massive muscular bleeding of iliopsoas resulting in lethal exsanguination is presented. The intramuscular bleeding occurred spontaneously in an old man with heart failure, presented to the emergency department after the acute onset of shortness of breath, and treated with therapeutic doses of antiplatelets and heparin to prevent thrombosis. On the sixth day of recovery, pain in the left lumbar region develops while there was a decrease in hemoglobin level. Computed tomography (CT) scan revealed a 10 × 3 cm hematoma of the left iliac muscle. The treatment was immediately stopped, but within 6 hours, the death was confirmed. The autopsy revealed that the hematoma, and its increased size since the latest imaging assessment, was the leading cause of death. Particularly in older patients with comorbidity, even in those with clotting parameters in the therapeutic range, the potential for fatal result of iliopsoas muscle bleeding should be considered. Identifying potential patience with increased risk of this complication could be important, especially in pandemic time of COVID-19, when the use of anticoagulant therapy-both for treatment and for prevention of severe disease-has become massive and addressed also to people without previous and specific pathologies.


Subject(s)
COVID-19 , Psoas Muscles , Aged , Autopsy , COVID-19/complications , Fatal Outcome , Hematoma/etiology , Hemorrhage/pathology , Humans , Male , Psoas Muscles/diagnostic imaging , Psoas Muscles/pathology
9.
J Pediatr ; 243: 214-218.e5, 2022 04.
Article in English | MEDLINE | ID: covidwho-1757591

ABSTRACT

A previously healthy 12-year-old boy had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related multisystem inflammatory syndrome (MIS-C) that was rapidly fatal. Autopsy revealed the presence of a large intracardiac thrombus. SARS-CoV-2 spike protein was detected in intestinal cells, supporting the hypothesis that viral presence in the gut may be related to the immunologic response of MIS-C.


Subject(s)
COVID-19 , Intestines , Spike Glycoprotein, Coronavirus , COVID-19/complications , COVID-19/pathology , Child , Fatal Outcome , Humans , Intestines/virology , Male , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
10.
N Engl J Med ; 386(9): 861-868, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1721753

ABSTRACT

Melioidosis, caused by the bacterium Burkholderia pseudomallei, is an uncommon infection that is typically associated with exposure to soil and water in tropical and subtropical environments. It is rarely diagnosed in the continental United States. Patients with melioidosis in the United States commonly report travel to regions where melioidosis is endemic. We report a cluster of four non-travel-associated cases of melioidosis in Georgia, Kansas, Minnesota, and Texas. These cases were caused by the same strain of B. pseudomallei that was linked to an aromatherapy spray product imported from a melioidosis-endemic area.


Subject(s)
Aromatherapy/adverse effects , Burkholderia pseudomallei/isolation & purification , Disease Outbreaks , Melioidosis/epidemiology , Aerosols , Brain/microbiology , Brain/pathology , Burkholderia pseudomallei/genetics , COVID-19/complications , Child, Preschool , Fatal Outcome , Female , Genome, Bacterial , Humans , Lung/microbiology , Lung/pathology , Male , Melioidosis/complications , Middle Aged , Phylogeny , Shock, Septic/microbiology , United States/epidemiology
11.
Ann Neurol ; 91(4): 568-574, 2022 04.
Article in English | MEDLINE | ID: covidwho-1680263

ABSTRACT

Coronavirus disease 2019 (COVID-19) severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2 infection) can lead to intensive care unit (ICU) admission and critical illness myopathy (CIM). We examined 3 ICU patients with COVID-19 who required mechanical ventilation for pneumonia and developed CIM. Pathological examination of the skeletal muscle biopsies revealed myopathic changes consistent with CIM, variable inflammation with autophagic vacuoles, SARS-CoV immunostaining + fibers/granules, and electron microscopy findings of mitochondrial abnormalities and coronavirus-like particles. Although mitochondrial dysfunction with compromised energy production is a critical pathogenic mechanism of non-COVID-19-associated CIM, in our series of COVID-19-associated CIM, myopathic changes including prominent mitochondrial damage suggest a similar mechanism and association with direct SARS-CoV-2 muscle infection. ANN NEUROL 2022;91:568-574.


Subject(s)
COVID-19/complications , COVID-19/virology , Critical Illness , Muscular Diseases/etiology , Muscular Diseases/virology , SARS-CoV-2 , Adult , Aged , Autophagy , Fatal Outcome , Female , Humans , Inflammation/pathology , Intensive Care Units , Male , Middle Aged , Mitochondria/pathology , Muscle, Skeletal/pathology , Vacuoles/pathology
12.
Pediatr Infect Dis J ; 41(2): 148-150, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1677331

ABSTRACT

Group-B Enteroviruses, such as Echoviruses, are a common cause of infections in neonates but fatal myocarditis during Echovirus-induced sepsis have been rarely reported. We report on 2 cases of neonatal Echovirus-related sepsis with myocarditis. Fatal cardiorespiratory failure occurred in both cases. Autopsies and thorough histologic and microbiologic investigations evidenced Echoviruses 5- and 11-induced myocarditis as the cause of death.


Subject(s)
Echovirus Infections , Myocarditis , Sepsis , Enterovirus B, Human , Fatal Outcome , Humans , Infant, Newborn , Male , Respiratory Insufficiency
13.
Dermatol Online J ; 27(11)2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1675050

ABSTRACT

Vaccine development for COVID-19 has progressed expeditiously. To date, the Food and Drug Administration (FDA) has authorized the Moderna/mRNA-1273, Pfizer-BioNTech (BNT162b2), and Johnson & Johnson's Janssen (JNJ-78436735) vaccines for use in the United States. Immediate side effects have included myalgia fatigue, chills, fever, and headache. We report an elderly patient with a history of lung cancer and no prior history of autoimmune disease who developed cutaneous lupus erythematosus two ½ months after the second dose of the Pfizer-BioNTech COVID-19 vaccine.


Subject(s)
BNT162 Vaccine/adverse effects , Lung Neoplasms , Lupus Erythematosus, Cutaneous/etiology , Aged , BNT162 Vaccine/administration & dosage , Fatal Outcome , Humans , Immunization, Secondary/adverse effects , Lung Neoplasms/complications , Lupus Erythematosus, Cutaneous/pathology , Male
14.
Pathol Res Pract ; 231: 153796, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1665390

ABSTRACT

This case report describes a fatal case of a young woman with superior sagittal, transverse and sigmoid sinus thrombosis after administration of the ChAdOx1 nCov-19 vaccination. Eleven days post-vaccination she was found unconscious and transferred to the Emergency Department. Blood parameters showed low platelets, and a CT scan showed an extensive left intracranial hemorrhage and the presence of an occlusive thrombus of the superior sagittal sinus. She under-went a craniectomy, but after the intervention, she remained in a comatose state. After a few days, her clinical conditions worsened, and she died. A complete autopsy was performed which showed a thrombosis of the cerebral venous district, of the upper and lower limbs. A blood sample was also performed to carry out a gene study about the predisposition to thrombosis. The organ samples were studied through light microscope both in hematoxylin-eosin and immunohistochemical examination, and showed a strong inflammatory response in all samples and at the site of thrombosis. Our study aims to provide a proper autopsy technique to study the entire cerebral venous system through a multidisciplinary approach (anatomical dissection and neurosurgery) in post-vaccine venous thrombosis.


Subject(s)
ChAdOx1 nCoV-19/adverse effects , Sinus Thrombosis, Intracranial/etiology , Thrombocytopenia/etiology , Adult , COVID-19/prevention & control , Fatal Outcome , Female , Humans
16.
J Infect Dev Ctries ; 15(12): 1808-1812, 2021 12 31.
Article in English | MEDLINE | ID: covidwho-1639503

ABSTRACT

Beginning in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly resulted in a worldwide pandemic. Many patients with coronavirus disease-19 (COVID-19) require invasive ventilation due to severe respiratory failure. However, many medical hospitals experienced shortages of personal protective equipment, increasing the risk of healthcare workers contracting an infection. However, we report a case of acute respiratory distress syndrome during the early stage of COVID-19 treated at a university hospital outside of Wuhan, China. We described the optimization of healthcare worker personal protection and a procedure for airway management in the context of insufficient personal protective equipment. This report may provide a reference for resource-limited settings in low- and middle-income countries, even countries where healthcare systems have been overwhelmed by the pandemic.


Subject(s)
COVID-19/transmission , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Personal Protective Equipment/supply & distribution , COVID-19/epidemiology , China/epidemiology , Fatal Outcome , Humans , Intubation, Intratracheal/adverse effects , Male , Middle Aged , Pandemics , Respiratory Aerosols and Droplets , SARS-CoV-2
18.
Pediatr Neurol ; 127: 1-5, 2022 02.
Article in English | MEDLINE | ID: covidwho-1636569

ABSTRACT

BACKGROUND: We report the clinical, radiological, laboratory, and neuropathological findings in support of the first diagnosis of lethal, small-vessel cerebral vasculitis triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric patient. PATIENT DESCRIPTION: A previously healthy, eight-year-old Hispanic girl presented with subacute left-sided weakness two weeks after a mild febrile illness. SARS-CoV-2 nasopharyngeal swab was positive. Magnetic resonance imaging revealed an enhancing right frontal lobe lesion with significant vasogenic edema. Two brain biopsies of the lesion showed perivascular and intraluminal lymphohistiocytic inflammatory infiltrate consistent with vasculitis. Despite extensive treatment with immunomodulatory therapies targeting primary angiitis of the central nervous system, she experienced neurological decline and died 93 days after presentation. SARS-CoV-2 testing revealed positive serum IgG and positive cerebrospinal fluid IgM. Comprehensive infectious, rheumatologic, hematologic/oncologic, and genetic evaluation did not identify an alternative etiology. Postmortem brain autopsy remained consistent with vasculitis. CONCLUSION: This is the first pediatric presentation to suggest that SARS-CoV-2 can lead to a fatal, postinfectious, inflammatory small-vessel cerebral vasculitis. Our patient uniquely included supportive cerebrospinal fluid and postmortem tissue analysis. While most children recover from the neurological complications of SARS-CoV-2, we emphasize the potential mortality in a child with no risk factors for severe disease.


Subject(s)
COVID-19/blood , COVID-19/diagnostic imaging , SARS-CoV-2/isolation & purification , Vasculitis, Central Nervous System/blood , Vasculitis, Central Nervous System/diagnostic imaging , COVID-19/complications , Child , Fatal Outcome , Female , Humans , Vasculitis, Central Nervous System/etiology
20.
Chest ; 161(1): e5-e11, 2022 01.
Article in English | MEDLINE | ID: covidwho-1595933

ABSTRACT

CASE PRESENTATION: A 67-year-old obese man (BMI 38.0) with type 2 diabetes mellitus (DM), chronic atrial fibrillation, and chronic lymphocytic leukemia stage II, stable for 8 years after chemotherapy, and a history of smoking presented to the ED with progressive dyspnea and fever due to SARS-CoV-2 infection. He was admitted to a general ward and treated with dexamethasone (6 mg IV once daily) and oxygen. On day 3 of hospital admission, he became progressively hypoxemic and was admitted to the ICU for invasive mechanical ventilation. Dexamethasone treatment was continued, and a single dose of tocilizumab (800 mg) was administered. On day 9 of ICU admission, voriconazole treatment was initiated after tracheal white plaques at bronchoscopy, suggestive of invasive Aspergillus tracheobronchitis, were noticed. However, his medical situation dramatically deteriorated.


Subject(s)
Acute Kidney Injury/virology , Antifungal Agents/therapeutic use , COVID-19/complications , Mucormycosis/diagnosis , Mucormycosis/drug therapy , Pulmonary Aspergillosis/diagnosis , Pulmonary Aspergillosis/drug therapy , Aged , Amphotericin B/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Atrial Fibrillation/complications , Bronchoscopy , Dexamethasone/therapeutic use , Diabetes Mellitus, Type 2/complications , Fatal Outcome , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Male , Nitriles/therapeutic use , Obesity/complications , Oxygen Inhalation Therapy , Pyridines/therapeutic use , Respiration, Artificial , SARS-CoV-2 , Smoking/adverse effects , Tomography, X-Ray Computed , Triazoles/therapeutic use , Voriconazole/therapeutic use
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