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2.
Microscopy and Microanalysis ; 28(S1):1374, 2022.
Article in English | ProQuest Central | ID: covidwho-1947161
3.
Vet Pathol ; 59(4): 681-695, 2022 07.
Article in English | MEDLINE | ID: covidwho-1714567

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease in mink similar to human COVID-19. We characterized the pathological findings in 72 mink from US farms with SARS-CoV-2 outbreaks, localized SARS-CoV-2 and its host cellular receptor angiotensin-converting enzyme 2 (ACE2) in mink respiratory tissues, and evaluated the utility of various test methods and specimens for SARS-CoV-2 detection in necropsy tissues. Of SARS-CoV-2-positive animals found dead, 74% had bronchiolitis and diffuse alveolar damage (DAD). Of euthanized SARS-CoV-2-positive animals, 72% had only mild interstitial pneumonia or minimal nonspecific lung changes (congestion, edema, macrophages); similar findings were seen in SARS-CoV-2-negative animals. Suppurative rhinitis, lymphocytic perivascular inflammation in the lungs, and lymphocytic infiltrates in other tissues were common in both SARS-CoV-2-positive and SARS-CoV-2-negative animals. In formalin-fixed paraffin-embedded (FFPE) upper respiratory tract (URT) specimens, conventional reverse transcription-polymerase chain reaction (cRT-PCR) was more sensitive than in situ hybridization (ISH) or immunohistochemistry (IHC) for detection of SARS-CoV-2. FFPE lung specimens yielded less detection of virus than FFPE URT specimens by all test methods. By IHC and ISH, virus localized extensively to epithelial cells in the nasal turbinates, and prominently within intact epithelium; olfactory mucosa was mostly spared. The SARS-CoV-2 receptor ACE2 was extensively detected by IHC within turbinate epithelium, with decreased detection in lower respiratory tract epithelium and alveolar macrophages. This study expands on the knowledge of the pathology and pathogenesis of natural SARS-CoV-2 infection in mink and supports their further investigation as a potential animal model of SARS-CoV-2 infection in humans.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Mink , SARS-CoV-2 , Animals , COVID-19/veterinary , Epithelial Cells , Lung , Macrophages, Alveolar , SARS-CoV-2/physiology , Virus Internalization
4.
Emerg Infect Dis ; 28(3): 510-517, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1686417

ABSTRACT

Severe coronavirus disease in neonates is rare. We analyzed clinical, laboratory, and autopsy findings from a neonate in the United States who was delivered at 25 weeks of gestation and died 4 days after birth; the mother had asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and preeclampsia. We observed severe diffuse alveolar damage and localized SARS-CoV-2 by immunohistochemistry, in situ hybridization, and electron microscopy of the lungs of the neonate. We localized SARS-CoV-2 RNA in neonatal heart and liver vascular endothelium by using in situ hybridization and detected SARS-CoV-2 RNA in neonatal and placental tissues by using reverse transcription PCR. Subgenomic reverse transcription PCR suggested viral replication in lung/airway, heart, and liver. These findings indicate that in utero SARS-CoV-2 transmission contributed to this neonatal death.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Autopsy , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Lung , Placenta , Pregnancy , RNA, Viral/genetics , SARS-CoV-2
5.
Sci Rep ; 11(1): 9682, 2021 05 06.
Article in English | MEDLINE | ID: covidwho-1219072

ABSTRACT

The need for high-affinity, SARS-CoV-2-specific monoclonal antibodies (mAbs) is critical in the face of the global COVID-19 pandemic, as such reagents can have important diagnostic, research, and therapeutic applications. Of greatest interest is the ~ 300 amino acid receptor binding domain (RBD) within the S1 subunit of the spike protein because of its key interaction with the human angiotensin converting enzyme 2 (hACE2) receptor present on many cell types, especially lung epithelial cells. We report here the development and functional characterization of 29 nM-affinity mouse SARS-CoV-2 mAbs created by an accelerated immunization and hybridoma screening process. Differing functions, including binding of diverse protein epitopes, viral neutralization, impact on RBD-hACE2 binding, and immunohistochemical staining of infected lung tissue, were correlated with variable gene usage and sequence.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Animals , COVID-19/diagnosis , COVID-19 Serological Testing , Epitopes/immunology , Female , Humans , Immunization , Mice , Mice, Inbred BALB C , Models, Molecular , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/immunology
6.
Emerg Infect Dis ; 27(5): 1517-1519, 2021 May.
Article in English | MEDLINE | ID: covidwho-1127972

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shares common clinicopathologic features with other severe pulmonary illnesses. Hantavirus pulmonary syndrome was diagnosed in 2 patients in Arizona, USA, suspected of dying from infection with SARS-CoV-2. Differential diagnoses and possible co-infections should be considered for cases of respiratory distress during the SARS-CoV-2 pandemic.


Subject(s)
COVID-19 , Communicable Diseases, Emerging , Hantavirus Pulmonary Syndrome , Arizona , Communicable Diseases, Emerging/epidemiology , Humans , SARS-CoV-2
7.
J Infect Dis ; 223(5): 752-764, 2021 03 03.
Article in English | MEDLINE | ID: covidwho-1117027

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to produce substantial morbidity and mortality. To understand the reasons for the wide-spectrum complications and severe outcomes of COVID-19, we aimed to identify cellular targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tropism and replication in various tissues. METHODS: We evaluated RNA extracted from formalin-fixed, paraffin-embedded autopsy tissues from 64 case patients (age range, 1 month to 84 years; 21 COVID-19 confirmed, 43 suspected COVID-19) by SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR). For cellular localization of SARS-CoV-2 RNA and viral characterization, we performed in situ hybridization (ISH), subgenomic RNA RT-PCR, and whole-genome sequencing. RESULTS: SARS-CoV-2 was identified by RT-PCR in 32 case patients (21 COVID-19 confirmed, 11 suspected). ISH was positive in 20 and subgenomic RNA RT-PCR was positive in 17 of 32 RT-PCR-positive case patients. SARS-CoV-2 RNA was localized by ISH in hyaline membranes, pneumocytes, and macrophages of lungs; epithelial cells of airways; and endothelial cells and vessel walls of brain stem, leptomeninges, lung, heart, liver, kidney, and pancreas. The D614G variant was detected in 9 RT-PCR-positive case patients. CONCLUSIONS: We identified cellular targets of SARS-CoV-2 tropism and replication in the lungs and airways and demonstrated its direct infection in vascular endothelium. This work provides important insights into COVID-19 pathogenesis and mechanisms of severe outcomes.


Subject(s)
COVID-19/virology , Endothelium, Vascular/virology , Respiratory System/virology , SARS-CoV-2/physiology , Virus Replication , Adolescent , Adult , Aged , Aged, 80 and over , Autopsy , COVID-19/complications , COVID-19 Nucleic Acid Testing , Child , Child, Preschool , Female , Humans , In Situ Hybridization , Infant , Lung/virology , Male , Middle Aged , RNA, Viral/isolation & purification , Real-Time Polymerase Chain Reaction , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Viral Tropism , Whole Genome Sequencing , Young Adult
8.
Emerg Infect Dis ; 27(4): 1023-1031, 2021 04.
Article in English | MEDLINE | ID: covidwho-1088897

ABSTRACT

Efforts to combat the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have placed a renewed focus on the use of transmission electron microscopy for identifying coronavirus in tissues. In attempts to attribute pathology of COVID-19 patients directly to tissue damage caused by SARS-CoV-2, investigators have inaccurately reported subcellular structures, including coated vesicles, multivesicular bodies, and vesiculating rough endoplasmic reticulum, as coronavirus particles. We describe morphologic features of coronavirus that distinguish it from subcellular structures, including particle size range (60-140 nm), intracellular particle location within membrane-bound vacuoles, and a nucleocapsid appearing in cross section as dense dots (6-12 nm) within the particles. In addition, although the characteristic spikes of coronaviruses may be visible on the virus surface, especially on extracellular particles, they are less evident in thin sections than in negative stain preparations.


Subject(s)
COVID-19 , Cellular Structures , SARS-CoV-2 , Biopsy/methods , COVID-19/pathology , COVID-19/virology , Cellular Structures/classification , Cellular Structures/ultrastructure , Humans , Microscopy, Electron/methods , SARS-CoV-2/isolation & purification , SARS-CoV-2/ultrastructure
9.
Emerg Infect Dis ; 26(9): 2005-2015, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-326269

ABSTRACT

An ongoing pandemic of coronavirus disease (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Characterization of the histopathology and cellular localization of SARS-CoV-2 in the tissues of patients with fatal COVID-19 is critical to further understand its pathogenesis and transmission and for public health prevention measures. We report clinicopathologic, immunohistochemical, and electron microscopic findings in tissues from 8 fatal laboratory-confirmed cases of SARS-CoV-2 infection in the United States. All cases except 1 were in residents of long-term care facilities. In these patients, SARS-CoV-2 infected epithelium of the upper and lower airways with diffuse alveolar damage as the predominant pulmonary pathology. SARS-CoV-2 was detectable by immunohistochemistry and electron microscopy in conducting airways, pneumocytes, alveolar macrophages, and a hilar lymph node but was not identified in other extrapulmonary tissues. Respiratory viral co-infections were identified in 3 cases; 3 cases had evidence of bacterial co-infection.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Aged , COVID-19 , Coronavirus Infections/virology , Female , Humans , Immunohistochemistry , Lung/pathology , Lung/virology , Male , Microscopy, Electron , Middle Aged , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , United States/epidemiology
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