The current study investigated the association between airway bleeding events and SARS-CoV-2 infection in patients receiving tracheostomies. We found that although the upper and lower airways were anatomically separated after temporary or permanent tracheostomies, positive SARS-CoV-2 RNA test results were still reported for oropharyngeal swabs. The finding indicates that in addition to respiratory droplet transmission, SARS-CoV-2 may infect the oropharyngeal epithelium by airborne and close contact transmission, which is consistent with a previous study [12]. As these patients do not manifest clinical symptoms such as fever, nasal congestion, runny nose, and sore throat, it is advisable for patients receiving temporary or permanent tracheostomy to wear surgical masks to cover the mouth, nose, and tracheostoma. Furthermore, after tracheostomies, positive SARS-CoV-2 RNA test results were reported not only for the oropharyngeal swabs but also for tracheal swab samples, with a lower Ct value in the tracheal swabs than in the oropharyngeal swabs. The tracheal swabs were still tested positive even when SARS-CoV-2 RNA test results of the oropharyngeal swabs were negative. These results suggest that even after tracheostomies, the trachea still may have a higher viral load and longer infection time than the oropharynx, which is consistent with the previous study [13]. For patients who received total laryngectomy and permanent tracheostomy while infected with SARS-CoV-2, no statistical difference in Ct values was evident between oropharyngeal and tracheal swabs, which may be attributed to the small sample size. As SARS-CoV-2 RNA detection in the trachea and oropharynx can be discordant and the trachea may have a higher viral load, tracheal swab can be a more reliable specimen for SARS-CoV-2 detection in patients after temporary or permanent tracheostomy.

Previous studies have documented that SARS-CoV-2 infection can induce a severe procoagulant state despite prophylactic anticoagulation, with many adults developing myocardial infarction, cerebral infarction, and venous thromboembolism (VTE) [14, 15]. Additionally, it can incur rare but serious hemorrhagic conditions, including gastrointestinal bleeding [16], spontaneous cerebral hemorrhage [5], and spontaneous bleeding from the nasal and oral mucosa [17]. However, so far, bleeding events in patients who were infected with SARS-CoV-2 after tracheostomies are even more rarely reported. In this study, 11 of 29 SARS-CoV-2 infected patients (37.9%) reported airway bleeding events after receiving tracheostomies, which included bloody sputum, hemoptysis, and massive endotracheal crust formation.

To date, the mechanism of airway bleeding is not fully elucidated and various explanations have been proposed, including the status of tracheostomies, the virus itself, the viral inflammation, etc. In patients receiving temporary or permanent tracheostomy, the nasal mucociliary clearance of pathogens and particles is compromised [18], which may increase the risk of SARS-CoV-2 infection during the epidemic [19]. Meanwhile, the mucosal production decreases and the viscosity of secretion increases in the trachea, making it easier to form sputum crusts in the airway [8], which often triggers severe cough and aggravates airway bleeding. Besides, according to the genetic data from the Global Initiative of Sharing All Influenza Data (GISAID) international database (https://gisaid.org/phylodynamics/china-cn/), from December 2022 to February 2023, Omicron variants were the dominant strains in Fujian, China. Compared with SASR-CoV-2 wild-type (WT) or other variants, the Omicron variant of SARS-CoV-2 mainly infects cells in the upper airway, bronchi, and trachea by binding the spike (S) protein to the main receptor, angiotensin-converting enzyme 2 (ACE2), and entering host cells via the endosomal route with the aid of ACE2 and cathepsin L [4, 20]. The single-cell sequencing shows that cells co-expressing ACE2 and cathepsin L are more abundant in the pharynx, trachea, and trachea than in alveolar epithelium [4]. The in vitro experiment shows that compared with the WT and Delta variants, the Omicron variant of the SARS-CoV-2 displays a higher replication competence in bronchial tissues and lower replication competence in lung parenchymal tissues at 37 °C [21]. The reduced capacity of Omicron has also been observed in a polarized human lung epithelial cell model [22]. Omicron infection can cause damage, necrosis, and exfoliation of epithelium cells, leading to airway bleeding. In our study, we found patients infected with SARS-CoV-2 showed no obvious clinical symptoms of pneumonia and extremely mild lesions in the lungs by the computed tomography (CT), which is consistent with the characteristics of Omicron infection [20]. In addition, SARS-CoV-2 infection inhibits the interferon signaling pathway but elevates chemokine expression. As a result, when the virus multiplies exponentially, a large number of inflammatory cells are recruited to the site of infection by chemokines, leading to a cytokine storm that stimulates a serious inflammatory response, causing organ damage and airway bleeding [23, 24]. Chemokine can also cause activation, injury, and dysfunction of vascular endothelial cells, leading to bleeding or thrombotic events [18]. In our study, the HE staining of sputum crusts reported a large amount of mucus, necrosis, inflammatory exudate containing neutrophils and eosinophils, and a small amount of squamous epithelial cells, indicating airway inflammation.

After SARS-CoV-2 infection, patients receiving temporary or permanent tracheostomy are more susceptible to airway bleeding and sputum crust formation. Therefore, when addressing a SARS-COV-2-infected patient, head and neck surgeons should take heed of the potential airway bleeding and adopt proper airway management. For patients receiving tracheostomies, more careful airway management should be prescribed, such as humidification, timely suction, and anticoagulant suspension when a bleeding tendency is evident.

Some limitations remain in this study. First, this was a single-center study that had a limited sample size. It will be necessary to evaluate airway bleeding events in a larger population. Second, no record has been made of the duration from virus infection to the airway bleeding and that of airway bleeding, which may be related to the viral load. However, for patients receiving temporary or permanent tracheostomy, our study provides important data on airway bleeding after SARS-CoV-2 infection, which is useful in airway management during the epidemic.