A novel coronavirus was identified in China in late 2019 with similarity to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and was classified as SARS-CoV-2. This virus causes Coronavirus Disease-2019 (COVID-19) pneumonia which may progress to acute respiratory distress syndrome (ARDS) as well as several extrapulmonary manifestations. The spread of SARS-CoV-2 has caused a worldwide pandemic resulting in unmeasurable global devastation.
Since the beginning of the SARS-CoV-2 pandemic, there has been a sharp rise in the number of patients who have required mechanical ventilation. The number of days that patients with COVID-19 pneumonia have required mechanical ventilation has been longer compared to similarly matched patients with other diseases requiring mechanical ventilation, averaging 28.5 days in a Spanish study by Mata-Castro et al. [4]. Patients with COVID-19 pneumonia have required higher positive end expiratory pressures (PEEP) for extended periods of time, which may explain the prolonged duration of intubation in SARS-CoV-2 patients. However, the number of patients with tracheal damage in SARS-CoV-2 infection has been disproportionally high. In a cohort study of 98 patients with COVID-19 pneumonia and severe respiratory failure, Fiaccini et al. [5] observed tracheal damage in nearly half (48%) of COVID-19 pneumonia patients requiring prolonged mechanical ventilation compared to 2% in similarly matched non-SARS-CoV-2 patients.
Acquired tracheal stenosis typically results from trauma or ischemic changes such as prolonged intubation with overinflated balloons, or endoscopic damage to the trachea, with histology showing scar formation and ossific metaplasia [6]. In a study of 20 patients undergoing surgery for tracheal stenosis of benign etiology, Zagalo et al. [7] identified the common findings of hypertrophied submucosa with regions absent of ciliated cells with congestion, hemorrhage, and neovascularization frequently observed, with fibrosis alternating with layers of plasma cell infiltration. Literature review did not identify any published examples of multinucleated syncytial cells as a characteristic of tracheal stenosis in non-SARS-CoV-2 patients.
In the lungs, the viral destruction of pulmonary parenchyma appears to be diffuse alveolar damage (DAD). Xu et al. [3] further showed the presence of multinucleated syncytial cells with prominent nucleoli in specimens from patients with COVID-19 pneumonia. Additional case reports have come to similar conclusions regarding the hallmark histologic characteristics for SARS-CoV-2 infection [2]. Wehzhong and Hualan [8] reported in their recent paper the presumed mechanism of the CaMKII-like system of S protein stimulated membrane fusion by which the syncytia are thought to form. This would indicate that multinucleated syncytial cells are a fundamental histologic characteristic of SARS-CoV-2 infection.
Fiacchini et al. proposed possible etiologies for the increased incidence of tracheal stenosis in patients with COVID-19 pneumonia, citing decreased arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio resulting in hypoxic damage to the trachea, prothrombotic state resulting in microvascular injury and necrosis to the tracheal mucosa, increased use of proning of patients, and high viral replication in the tracheal mucosa [5]. However, our patient in case 1 did not require a period of prolonged intubation which would eliminate most of these other possible etiologies. Given the similarity of the histology on the pathology specimens from case 1 and 2 with that of known SARS-CoV-2 pathologic changes seen in infected tissues, and lack of other possible etiologies for the tracheal stenosis, SARS-CoV-2 may therefore play a direct role in the pathogenesis of the tracheal stenosis in these patients.