COVID-19

SARS-CoV-2 infection is characterized by its high contagiousness and unusual potential lethality. Microscopically, diffuse alveolar damage is the main histologic lung injury dominated by alveolar destruction. At the early stage, the authors note non-specific lesions similar to lesions of diffuse alveolar damage. In particular, the alveoli dilated and filled with exudative fibromyxoid material, the thickening of the interalveolar partitions by edema and an essentially mononuclear inflammatory infiltrate with eosinophilic hyaline membranes covering the alveoli. Viral inclusions are not generally found, and at an advanced stage, the installation of pulmonary fibrosis is noted. The place of non-invasive and/or invasive ventilation is undetermined in hypoxemic respiratory failure secondary to SARS-Cov-2 pneumonia, whereas in the most severe cases of COVID-19, the use of oxygenation by extracorporeal membrane is immediate. The cytokine storm in the lungs prompted clinicians to administer immunomodulators, the results of which was a reduction in hospital mortality.

Liver Histopathological Analysis of 24 Postmortem Findings of Patients With COVID-19 in China

Although the pathologic investigation of liver injury was observed in a couple of cases in China, the detailed description of liver histopathologic and ultrastructural changes in a relatively larger series of liver tissues from COVID-19 patients is lacking. Samples from the liver were obtained from 24 COVID-19 cases from February 1 to April 1, 2020. Light microscopy showed that all liver sections had different degrees of liver injury manifested as swelling of the hepatocytes, hepatocellular necrosis, steatosis, lobular inflammation, portal inflammation, dilatation of sinusoids, and so on. SARS-CoV-2 induced liver injury might be independent of pre-existing Schistosoma infection or obstructive cholestasis. Patients combined with respiratory failure had more severe hepatocellular necrosis and male patients were more susceptible to liver injury. Although coronavirus particles or viral inclusions were not detected in the liver tissues for all cases, vacuolar degenerations in hepatocytes, edematous of mitochondria with the disruption of cristae, and expansions of the endoplasmic reticulum were observed. In conclusion, pathologic changes of liver tissues provide us a further understanding of liver injury in COVID-19 patients. Changes in the liver seem to be related to the underlying diseases/conditions.

Parvoviral enteritis and salmonellosis in raccoons with sudden death

Eight of 9 juvenile raccoons at a rehabilitation center died without obvious prior clinical signs. Gross changes were unremarkable except for mildly distended intestines. Microscopically, crypt loss, distension, necrosis, and regeneration with intranuclear viral inclusions were observed in the small intestine, with marked lymphoid depletion and necrosis in Peyer patches and mesenteric lymph nodes. Immunohistochemistry with a canine parvovirus antibody showed intensive signals of parvoviral antigens in the crypts and lymphoid germinal centers. Metagenomic sequencing allowed assembly of a complete parvoviral genome with >99% identity to canine parvovirus 2a, as well as Salmonella enterica subsp. enterica. Also, S. enterica subsp. enterica serovar Thompson with multiple antimicrobial resistance was isolated from the intestinal contents. Concurrent infection with parvovirus and Salmonella should be included as a differential diagnosis in raccoons with sudden death.

Histologic lesions of experimental infection with Lymantria dispar multicapsid nucleopolyhedrovirus and Lymantria dispar cytoplasmic polyhedrosis virus in European gypsy moth caterpillars (Lymantria dispar dispar)

European gypsy moths ( Lymantria dispar dispar) are an invasive species in North America, and are listed by the International Union for the Conservation of Nature as one of the 100 most destructive invasive species worldwide. They have several known viruses, some of which are used as biological control agents. However, there are no detailed descriptions of many entomopathogenic viral infections, including in European gypsy moths, using bright-field microscopy. In this study, 11 European gypsy moth caterpillars were evaluated histologically: 4 were experimentally infected with Lymantria dispar multicapsid nucleopolyhedrovirus (LdMNPV; Baculoviridae); 4 were experimentally infected with Lymantria dispar cytoplasmic polyhedrosis virus (LdCPV; Reoviridae); 3 control animals were uninfected. A complete tissue set was evaluated in all animals from all groups using bright-field microscopy, including epidermis, cuticle, striated muscle, tracheae, foregut, midgut, hindgut, Malpighian tubules, hemocytes, fat body, and nervous system. LdMNPV-infected caterpillars had marked karyomegaly and intranuclear viral inclusions in cells of the epidermis, tracheae, fat body, and hemocytes. LdMNPV-infected caterpillars also had hyperplasia and hypertrophy of epidermal and tracheal epithelial cells. LdCPV-infected caterpillars had numerous granular eosinophilic intracytoplasmic viral inclusions in midgut epithelial cells. Both LdMNPV-infected and LdCPV-infected caterpillars had atrophy of fat body adipocytes; this change was more pronounced in LdCPV-infected caterpillars. This work provides the first detailed descriptions of these viral infections in European gypsy moth caterpillars using bright-field light microscopy and provides images of normal histology from control caterpillars.

Routine immunohistochemistry study for polyomavirus BK nephropathy in transplanted kidney biopsies, is it recommended?

Background Early diagnosis and treatment of Polyomavirus BK Nephropathy (PVBKN) is a challenging issue in the management of patients with kidney transplantation. Currently, histopathologic diagnosis is the gold standard method for diagnosis of PVBKN. However, typical viral inclusions may not be found in early stages of the PVBKN and should, instead, be diagnosed using immunohistochemistry (IHC) study. There is no clear consensus about routine IHC tests in the pathologic evaluation of transplanted kidney biopsy samples. Material and methods The current study was conducted on transplanted kidney biopsy samples, since 2016 to 2019. The patients who have presented with new onset of allograft dysfunction, at least 2 weeks after transplantation surgery, were included in our study. All these biopsy samples were evaluated with routine renal biopsy stains as well as IHC for SV40 (Simvian Virus 40) antigen. The identification of typical nuclear virus inclusion body and any nuclear positive staining on IHC (≥1+ positive result) were considered as definite evidence of PVBKN. Sensitivity, specificity, Positive Predictive and Negative Predictive Values (PPV and NPV) of histopathologic assessment without IHC study were evaluated. Results Among 275 included cases, 18 (6.5%) patients with PVBKN were diagnosed. In patients with PVBKN, typical viral inclusions were detected in 14 samples (77.7%), on primary histopathological examination. However, virus-infected cells were identified just after IHC study in 4 (22.2%) of patients. Sensitivity, Specifity, PPV and NPV of morphologic histopathological assay without IHC for detection of PVBKN was 77.7, 100, 100 and 98.4% respectively. Conclusion Routine IHC study for SV40 in all transplanted kidney biopsy samples with new onset of allograft dysfunction, will enhance the diagnostic sensitivity of early stage disease detection.

Features Of Non-Specific Protection Factors And Cytokine Status In Inflammatory Diseases Of The Paranasal Sinuses In Twin Children

The Aim of this work was to study the functional activity of monocytes, neutrophils and cytokines in twin children with Inflammatory diseases of the paranasal sinuses in comparison with non-twins. It was found that with various rhinosinusitis in children, phagocytic activity of monocytes in blood decrease, which causes the development of a chronic purulent focus and is characterized by an increase in monocytes with viral inclusions. In patients with Inflammatory diseases of the paranasal sinuses, the activity of non-specific protective factors of the body is significantly reduced, which is expressed in a decrease phagocytic activity of monocytes and an increase monocyte with viral inclusions, which is more evidently in twin children than in non-twin children. Serum cytokines in children with Inflammatory diseases of the paranasal sinuses were significantly increased in relation to the data of healthy children. In children-twins and non - twins, the parameters of anti-inflammatory cytokines changed in different directions.

Bronchoscopy in COVID19 ARDS patients on mechanical ventilation – a prospective study

BackgroundBronchoscopy has been done sparingly in COVID19 patients due to the risk of aerosol generation, with few reports describing its clinical utility. We describe a study on bronchoscopy in mechanically ventilated (MV) COVID-19 patients outlining the procedural, clinical, utilitarian and safety aspects.MethodsBedside bronchoscopy was performed in suspected or confirmed COVID-19 cases on MV; only positive cases were included in the study. Demographic, clinical, bronchoscopic and laboratory findings were noted and analysed.Results98 procedures were performed on 61 patients, mean age of 62.1 years, 51 (83.6%) males. 42 patients (69%) had at least 1 co-morbidity. Major indications for bronchoscopy were new radiographic infiltrates with clinical deterioration, increased endotracheal tube (ETT) secretions and haemorrhagic secretions/hemoptysis. Common findings were copious secretions in 87 (88.8%), purulent in 61%, mucoid in 18%, haemorrhagic in 7% and frothy in 14% cases. Morphologically, hyperaemic airways were seen in 85 (86.7%) cases, ranging from mild (61%) to moderate-severe (39%). On the management front, antibiotics were changed in 31 (31.6%) cases based on bronchoscopic findings. Other significant changes included reduction or stopping of steroids and anticoagulation, fluid, and diuretic adjustment and ETT repositioning. The incidence of bacterial superinfection was also high (54% culture positivity for various bacteria), a significant number (94%) with multi-drug resistant organisms. Fungi were seen in 7 cases (7.1%). Pneumocystis jiroveci was not seen and cytology did not show any viral inclusions. Therapeutic mucus plug removal was done in 30 cases (30.6%), and hemoptysis control in 4% cases. The procedures were safe with no complications, and none of the HCW developed any COVID19 infection.ConclusionBronchoscopy in critically ill MV COVID-19 patients contributes on both diagnostic and therapeutic fronts and can significantly influence management decisions. With adequate precautions and standard protocols, it is safe for both HCW and patients.

Massive Perivillous Fibrin Deposition in Congenital Cytomegalovirus Infection: A Case Report

Cytomegalovirus (CMV) infection is one of the most common congenital viral infections. Classically associated placental findings include chronic villitis with plasma cells, stromal hemosiderin deposition, and identification of viral inclusions in villous endothelial and stromal cells. We present a case of confirmed congenital CMV infection that lacked these classical findings, but demonstrated massive perivillous fibrin deposition (MPVFD). This is the first report of CMV associated with MPVFD. MPVFD is an uncommon placental lesion associated with adverse fetal outcomes and a high risk of recurrence. However, the recurrence risk in patients with an infectious cause may be lower in than patients with other associated clinical conditions.

A modified lysosomal organelle mediates nonlytic egress of reovirus

Mammalian orthoreoviruses (reoviruses) are nonenveloped viruses that replicate in cytoplasmic membranous organelles called viral inclusions (VIs) where progeny virions are assembled. To better understand cellular routes of nonlytic reovirus exit, we imaged sites of virus egress in infected, nonpolarized human brain microvascular endothelial cells (HBMECs) and observed one or two distinct egress zones per cell at the basal surface. Transmission electron microscopy and 3D electron tomography (ET) of the egress zones revealed clusters of virions within membrane-bound structures, which we term membranous carriers (MCs), approaching and fusing with the plasma membrane. These virion-containing MCs emerged from larger, LAMP-1–positive membranous organelles that are morphologically compatible with lysosomes. We call these structures sorting organelles (SOs). Reovirus infection induces an increase in the number and size of lysosomes and modifies the pH of these organelles from ∼4.5–5 to ∼6.1 after recruitment to VIs and before incorporation of virions. ET of VI–SO–MC interfaces demonstrated that these compartments are connected by membrane-fusion points, through which mature virions are transported. Collectively, our results show that reovirus uses a previously undescribed, membrane-engaged, nonlytic egress mechanism and highlights a potential new target for therapeutic intervention.

COVID-19 Autopsies, Oklahoma, USA

Objectives To report the methods and findings of two complete autopsies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive individuals who died in Oklahoma (United States) in March 2020. Methods Complete postmortem examinations were performed according to standard procedures in a negative-pressure autopsy suite/isolation room using personal protective equipment, including N95 masks, eye protection, and gowns. The diagnosis of coronavirus disease 2019 (COVID-19) was confirmed by real-time reverse transcriptase polymerase chain reaction testing on postmortem swabs. Results A 77-year-old obese man with a history of hypertension, splenectomy, and 6 days of fever and chills died while being transported for medical care. He tested positive for SARS-CoV-2 on postmortem nasopharyngeal and lung parenchymal swabs. Autopsy revealed diffuse alveolar damage and chronic inflammation and edema in the bronchial mucosa. A 42-year-old obese man with a history of myotonic dystrophy developed abdominal pain followed by fever, shortness of breath, and cough. Postmortem nasopharyngeal swab was positive for SARS-CoV-2; lung parenchymal swabs were negative. Autopsy showed acute bronchopneumonia with evidence of aspiration. Neither autopsy revealed viral inclusions, mucus plugging in airways, eosinophils, or myocarditis. Conclusions SARS-CoV-2 testing can be performed at autopsy. Autopsy findings such as diffuse alveolar damage and airway inflammation reflect true virus-related pathology; other findings represent superimposed or unrelated processes.