Clinicopathologic Features of COVID-19: A Case Report and Value of Forensic Autopsy in Studying SARS-CoV-2 Infection.

ABSTRACT: As of August 23, 2020, the 2019 novel coronavirus disease (COVID-19) has infected more than 23,518,340 people and caused more than 810,492 deaths worldwide including 4,717 deaths in China. We present a case of a 53-year-old woman who was admitted to the hospital because of dry coughs and high fever on January 26, 2020, in Wuhan, China. She was not tested for SARS-CoV-2 RNA until on hospital day 11 (illness day 21) because of a significant shortage of test kits at the local hospital. Then, her test was positive for COVID-19 on hospital day 20. Despite intensive medical treatments, she developed respiratory failure with secondary bacterial infection and expired on hospital day 23 (3 days after she was tested positive for SARS-CoV-2 RNA). A systemic autopsy examination, including immunohistochemistry and ultrastructural studies, demonstrates that SARS-CoV-2 can infect multiple organs with profound adverse effect on the immune system, and the lung pathology is characterized by diffuse alveolar damage. Extrapulmonary SARS-CoV-2 RNA was detected in several organs postmortem. The detailed pathological features are described. In addition, this report highlights the value of forensic autopsy in studying SARS-CoV-2 infection and the importance of clinicopathological correlation in better understanding the pathogenesis of COVID-19.

Death related to epiglottitis.

Although death due to epiglottitis is well-reported in the medical literature, because of vaccines and antibiotics, deaths caused by epiglottitis are rare in the era of modern medicine. This report presents a case of epiglottitis-related death occurring in a middle-aged diabetic man. He initially presented to an emergency department with complaints of a sore throat and bilateral ear pain. Although a quick test for Strep pneumoniae was negative, the work-up was not extensive enough to exclude epiglottitis. He was discharged with a prescription for a decongestant and instructed to drink plenty of fluids. He subsequently collapsed in respiratory distress while waiting to fill his prescription at a pharmacy. He was admitted to the hospital and eventually diagnosed with anoxic brain injury, dying 4 days following his initial presentation. Autopsy disclosed gross and microscopic features of acute epiglottitis, which was considered the underlying cause of death. Awareness of epiglottitis and its risk factors is essential in identifying the proper diagnosis clinically. Characteristic findings at autopsy can confirm the diagnosis.

Accuracy of objective parameters in acute epiglottitis diagnosis: A case-control study.

Lateral neck radiography is often used as a screening tool in emergency departments for suspected acute epiglottitis. The qualitative radiographic signs have been mainly used. The aim of this study was to evaluate the accuracy of objective radiographic parameters to aid diagnosis of acute epiglottitis.Patients who were diagnosed with acute epiglottitis from January 2006 to December 2016 were included in this case-control study. Control subjects with normal lateral neck radiograph findings were included at a 1:4 ratio during the same period. The clinical findings of the patients were assessed from electronic medical records and radiographs were interpreted by a board-certified radiologist and a board-certified emergency medicine physician. The widths of the 3rd cervical vertebral body, epiglottis base (EWB), epiglottis tip (EWT), aryepiglottic fold (AFW), and hypopharynx, as well as the dimensions of the retropharyngeal and retrotracheal soft tissues, were retrospectively measured. The sensitivity, specificity, and receiver operating characteristic (ROC) curves were analyzed for the measured parameters, and cutoff values were determined to predict acute epiglottitis. The predictive cutoff values of radiologic parameters were evaluated using 5-fold cross-validation.A total 260 epiglottitis patients and 1166 controls were included in the study. In the ROC curve analysis, the EWB had an area under the ROC curve (AUROC) of 0.99 for a cutoff value of 5.02 mm (sensitivity, 96.2%; specificity, 98.2%). The EWT had an AUROC of 0.97 for a cutoff value of 4.84 mm (sensitivity, 91.2%; specificity, 97.3%). The AFW had an AUROC of 0.88 for a cutoff value of 6.59 mm (sensitivity, 86.5%; specificity, 78.8%). The 5-fold cross-validation achieved AUROCs of 0.97 for EWB, 0.94 for EWT, and 0.83 for AFW.The objective radiographic parameters in lateral neck radiography may be useful in diagnosing acute epiglottitis. Further prospective studies may be warranted to evaluate the diagnostic performance in actual clinical practice.

Sudden death from acute epiglottitis in a toddler.

The bacterium Haemophilus influenzae type b (Hib) can cause severe and life-threatening infections such as epiglottitis and meningitis. The course of the disease can be very rapid, resulting in sudden death. The incidence of Hib-induced epiglottitis in children has declined since the introduction of vaccinations in countries where such vaccinations are routinely administered. We herein present a case involving a 2.5-year-old boy who died suddenly at home. He had developed acute-onset throat and abdominal pain and a high fever. Despite an emergency cricothyrotomy due to a complicated intubation because of a massively swollen epiglottis, the efforts to resuscitate the child were unsuccessful. He was a previously healthy toddler, but he had not yet been vaccinated. Microbiologic analysis revealed the pathogenic bacterium Hib. The main autopsy finding was acute epiglottitis with swelling and cherry-red coloring of the epiglottis. Postmortem cultures of the cerebrospinal fluid and heart blood also revealed Hib as the pathogenic agent. Acute pneumonia was also diagnosed microscopically. The present report describes a rare case of Hib-induced acute epiglottitis and presents the key findings of forensic investigations in this type of disease.

Sudden Death Due to Acute Epiglottitis in Adults: A Retrospective Review of 11 Postmortem Cases.

We report a retrospective review of fatal acute epiglottitis cases in adults in the province of Ontario, Canada, between 2001 and 2014. Information on demographics, clinical history, gross, microscopic, and laboratory findings were collected and analyzed. Eleven cases, predominantly male (73%), with a mean age of 50 years were identified. Common presenting symptoms included sore throat, dysphagia, and low-grade fever. The predominant postmortem findings included hyperemia and edema of the epiglottis and aryepiglottic folds. Histological features included vascular congestion, stromal edema, and acute inflammation. Five cases (45%) were positive for growth of various bacterial organisms on blood and/or tissue cultures. Acute epiglottitis should be in the differential diagnosis in fatalities presenting with symptoms of upper respiratory tract infection, followed by an episode of acute shortness of breath. History, thorough postmortem examination with close attention to the head and neck structures, histological examination of tissues, and sampling for microbiology will assist in differentiating epiglottitis from other cases of laryngeal swelling leading to death.

An uncommon shape of epiglottis misleading as acute epiglottitis.

We report a case of a 31-year-old Japanese woman with an uncommon shape of epiglottis misleading as acute epiglottitis. She presented with high fever, arthralgia, general fatigue and strong throat pain. Laryngeal fiberscopy showed a markedly swollen epiglottis suggestive of acute epiglottitis, though she had no signs of asphyxia. A careful observation and detailed medical history ruled out acute epiglottitis. However, without clinical discretion, it might have been misinterpreted as acute epiglottitis. She was diagnosed later with Behçet's disease, which is reported to present pharyngeal stenosis. Two years later, a repeat laryngeal fiberscopy showed exactly the same appearance of the epiglottis, suggesting its shape to be permanent. The cause of this misleading shape of the epiglottis in this patient is yet unknown. For similar cases, a possibility of this kind of epiglottis should be considered before diagnosing as acute epiglottitis.

Fatal epiglottic abscess after radiotherapy for laryngeal carcinoma.

Acute epiglottitis is a rare condition, especially in adults, largely owing to the widespread vaccination against Haemophilus influenzae. Traumatic epiglottitis as a result of thermal or caustic insults is documented. Epiglottic abscess formation is described as a sequela of epiglottitis in some cases. The development of epiglottic abscess from epiglottitis secondary to radiotherapy has previously been described in the literature; however, there are no reports of fatalities due to epiglottic abscess after radiotherapy. We present an unusual case of an adult sudden death due to epiglottic abscess formation subsequent to radiotherapy for laryngeal squamous cell carcinoma.

Pathological characteristics of the epiglottis relevant to acute epiglottitis.

OBJECTIVE: The characteristic swelling of acute epiglottitis is thought to be caused by histological factors in the epiglottis. We investigated the relationships between histological findings and the pathology of acute epiglottitis. METHODS: We examined 23 autopsy cases. For 16 of these, histological assessments were performed. In the remaining 7 subjects, physiological saline was injected at the lingual tonsil. RESULTS: These histological findings revealed abundant laryngeal glands on the laryngeal surface compared with the lingual surface. With regard to the blood vessels and lymphatic vessels, more of these vessels tended to be apparent on the lingual surface compared with the laryngeal surface. In each of the physiological saline injected subjects, almost no swelling of the lingual tonsil occurred, but the lingual surface of the epiglottis was swollen, and morphological changes had occurred that resembled those in acute epiglottitis. CONCLUSION: Periepiglottic tissues are rich in lymphatic tissues, and it appears easy for inflammation to spread to the epiglottis itself via the gland's own rich networks of blood and lymphatic vessels. In addition, according to the video observation, it appeared that the liquid ingredient that exudes at the inflamed the lingual tonsil may cause swelling the lingual surface of the epiglottis.

Cutaneous normolipemic plane xanthoma with supraglottic involvement in a patient with hand-Schüller-Christian Disease: a case report.

Normolipemic plane xanthoma (NPX) is a histiocytic disorder characterized by yellow-orange plaques in the periorbital areas, neck, upper trunk, and flexural folds. Association with systemic disease or paraproteinemia has been reported previously, but rarely with Langerhans cell histiocytosis (LCH). We report a case of Hand-Schüller-Christian disease (a type of LCH) in a patient who developed NPX with supraglottic involvement. NPX developed after several courses of chemotherapy and the supraglottic xanthoma occurred about 2 years later. The coexistence of LCH and non-LCH histiocytic lesions in this patient could be a result of chemotherapy-induced changes or may be just coincidental.

Necrotizing epiglottitis in an infant: an unusual first presentation of human immunodeficiency virus infection.

We describe the case of a 4-month-old infant presenting with severe respiratory distress secondary to necrotizing epiglottitis, who was subsequently diagnosed with human immunodeficiency virus infection. Additionally, we review the existing literature on this rare condition with a focus on the potential underlying pathogenesis.

Necrotizing epiglottitis and hemophagocytic lymphohistiocytosis.

With the introduction of vaccination for haemophilus influenza, the epidemiology of epiglottitis in children has changed. Classic childhood epiglottitis is now rare, and unusual forms of the disease may be seen. Nectrotizing epiglottitis is an extremely rare form of epiglottitis. Only four cases of nectrotizing epiglottitis have been previously reported, and all cases were in immunocompromised adult patients. Hemophagocytic lymphohistiocytosis is a rare condition characterized by high fevers, hepatosplenomegaly, and cytopenias caused by an abnormal proliferation and activation of macrophages. We report the first case of a previously healthy 5-year-old male presenting with acute onset of airway distress and pancytopenia. Subsequent airway evaluation led to the diagnosis of nectrotizing epiglottitis, and he was simultaneously diagnosed with infection-induced hemophagocytic lymphohistiocytosis. The patient recovered with intubation and antibiotics. Follow-up direct laryngoscopy revealed an epiglottis remnant with approximately 50% loss of epiglottic tissue. The presentation and pathophysiology of this unusual manifestation of epiglottitis and hemophagocytic lymphohistiocytosis will be reviewed. In the post-haemophilus influenze vaccination era, the pediatric otolaryngologist must be familiar with unusual forms of epiglottitis and its associated manifestations.

[Evaluation of patients with adult acute epiglottitis]. / Akut epiglottitli eriskin olgularin degerlendirilmesi.

OBJECTIVES: We evaluated adult patients who were treated for acute epiglottitis. PATIENTS AND METHODS: The study included five adult patients who were diagnosed as having acute epiglottitis during an eight-month period. All the patients were males with an age range of 38 to 54 years, except for a 77-year-old patient. The Friedman staging system was used to evaluate the severity of dyspnea and symptoms. Treatment was comprised of parenteral steroids and antibiotic therapy. The mean follow-up was one year (range 11 to 17 months). RESULTS: The main presenting symptom was moderate to severe dyspnea in all the patients, which was rated as stage 4 in one patient, stage 3 in two patients, and stage 2 in two patients. Diagnoses were made by laryngoscopic examination and lateral radiograms of the neck, which showed the thumb sign in all the patients. Computed tomography of the neck revealed an epiglottic abscess in one patient. One patient required tracheotomy. All the patients benefited from parenteral steroid and antibiotic treatment, with relief of dyspnea and difficulty in swallowing. The mean hospitalization was 5.6 days (range 3 to 8 days). No recurrences were observed during the follow-up period. CONCLUSION: Acute epiglottitis in adult patients requires a timely and correct diagnosis and prompt appropriate treatment. A tracheotomy should not be avoided when necessary.

[A clinical study of 71 cases of acute epiglottitis].

Acute epiglottitis causes sudden upper airway obstruction that may become lethal, and must be diagnosed and treated quickly and precisely. We review clinical features of 71-cases of acute epiglottitis in 6 years, focusing in cases requiring emergency airway management. Retrospective analysis was done for 1) age and gender, 2) month of onset, 3) symptoms, 4) smoking history, 5) diabetes history, 6) cause and background, 7) first medical institution visit, 8) duration from symptom onset to hospital visit, 9) oropharyngeal findings, 10) laryngendoscopic findings, 11) pharyngeal culture, and 12) deterioration after hospitalization. We found that 2 cases deteriorated in laryngendoscopic findings after hospitalization despite treatment. Even if the first medical findings are mild, it is necessary to respond to patients with the possibility to deterioration in mind. Five cases required emergency airway management-3 with tracheostomy and 2 cases with endotracheal intubation. If symptoms of laryngeal edema, oxygen desaturation, and dyspnea are present, emergency airway management should be prepared soon after hospitalization.

The rising incidence of adult acute epiglottitis and epiglottic abscess.

OBJECTIVE: To examine preliminary observations that the incidence of adult acute epiglottitis has risen between 1986 and 2000. MATERIALS AND METHODS: Demographics, annual and seasonal occurrences, clinical presentation, diagnostic procedures, treatment, airway management, and complications of 116 consecutive adult patients with laryngoscopically confirmed acute epiglottitis are presented. RESULTS: The mean annual incidence of acute epiglottitis per 100,000 adults significantly increased from 0.88 (from 1986-1990) to 2.1 (from 1991-1995) and to 3.1 (from 1996-2000) (P <.001). This rise seems to be unrelated to Haemophilus influenzae type b infection but related to miscellaneous pathogenic bacteria. During these periods, the number of epiglottic abscesses increased concomitantly with the rise in the incidence of acute epiglottitis (from 4/14 episodes [29%], to 8/38 [21%], and to 16/66 [24%], respectively), showing a relatively constant ratio between both phenomena (P =.843). Twenty-five patients (21%) underwent airway intervention, 16 because of objective respiratory distress and 9 because of imminent respiratory obstruction. Stepwise logistic regression showed that drooling, diabetes mellitus, rapid onset of symptoms, and abscess formation were associated with airway obstruction. Diverse origins for the epiglottic abscess, either from coalescent epiglottic infection or from mucopyocele of the tongue base, are suggested. CONCLUSIONS: A rise in the incidence of acute epiglottitis and a concomitant rise in the number of epiglottic abscesses were established. Although the course of acute epiglottitis is often benign and can be safely treated with a conservative management approach, delayed airway obstruction may develop from a few hours to days after admission.

[Epiglottic abscess as a rare reason for airway obstruction in adults]. / Epiglottisabszess als seltene Ursache einer Atemwegsverlegung beim Erwachsenen.

Acute epiglottitis in adults is a potentially life-threatening disease of increasing incidence. Although pharyngitis is the most common cause of sore throat in the adult, acute epiglottitis must be considered in the differential diagnosis when there is unrelenting throat pain and minimal objective signs of pharyngitis. We report the case of a 45-year old man with acute epiglottitis and occlusion of the upper airways due to an epiglottic abscess. A brief discussion of the diagnosis and treatment of adult epiglottitis is presented. Patients with acute painful dysphagia should be considered to have epiglottitis until the diagnosis is proven. Early diagnosis and aggressive airway management can be life saving.