Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination.

SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether it elicits effective immune responses in the respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared the SARS-CoV-2 S-specific total and neutralizing antibody responses, and B and T cell immunity, in the bronchoalveolar lavage fluid (BAL) and blood of COVID-19-vaccinated individuals and hospitalized patients. Vaccinated individuals had significantly lower levels of neutralizing antibody against D614G, Delta (B.1.617.2), and Omicron BA.1.1 in the BAL compared with COVID-19 convalescents despite robust S-specific antibody responses in the blood. Furthermore, mRNA vaccination induced circulating S-specific B and T cell immunity, but in contrast to COVID-19 convalescents, these responses were absent in the BAL of vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic mRNA vaccination alone induced weak respiratory mucosal neutralizing antibody responses, especially against SARS-CoV-2 Omicron BA.1.1 in mice; however, a combination of systemic mRNA vaccination plus mucosal adenovirus-S immunization induced strong neutralizing antibody responses not only against the ancestral virus but also the Omicron BA.1.1 variant. Together, our study supports the contention that the current COVID-19 vaccines are highly effective against severe disease development, likely through recruiting circulating B and T cell responses during reinfection, but offer limited protection against breakthrough infection, especially by the Omicron sublineage. Hence, mucosal booster vaccination is needed to establish robust sterilizing immunity in the respiratory tract against SARS-CoV-2, including infection by the Omicron sublineage and future VOCs.

Use of flexible bronchoscopy in pediatric patients receiving extracorporeal membrane oxygenation (ECMO) support.

INTRODUCTION: Critically ill children treated with extracorporeal membrane oxygenation (ECMO) support frequently have respiratory complications amenable to evaluation by flexible bronchoscopy (FB). The safety and efficacy of FB in this setting has not been well described in children. METHODS: Retrospective analysis of 153 FBs in 79 children treated with ECMO at a single institution from 2000 to 2008. Demographic data, clinical findings, and complications were obtained. Chest radiographs reports were evaluated prior to and following FB. Physiologic variables were compared prior to and following FB. RESULTS: Seventy-nine patients underwent FB on ECMO [58 veno-venous (VV) and 21 veno-arterial (VA) ECMO], with 153 total FBs performed. Indications for FB included clearance of tenacious airway secretions (n = 118, 77%), or evaluation of suspected secondary infections with bronchoalveolar lavage (n = 26, 17%). Two patients also had surfactant instillation following secretion removal. FB was performed a median 5 days following cannulation for ECMO (range 2-14 days). Most common findings included thick secretions (n = 77, 50.3%), mucoid secretions (n = 15, 9.8%), and mucopurulent secretions (n = 28, 18.3%). No deterioration in radiographic lung findings was described post-FB. FB was not associated with any significant change in heart rate, systemic blood pressure, or temperature. No significant changes in ECMO pump flow rate or sweep gas flow was seen during or after FB. Cannula dislodgement, inadvertent extubation, fever, pneumothorax, or intraprocedural hypoxemia was not reported. Fifty-three FBs (35%) resulted in blood-tinged secretions from the endotracheal tube post-FB, which resolved spontaneously. Three patients received high frequency oscillatory ventilation (HFOV) following FB in association with mild hemorrhage. CONCLUSIONS: FB is a well-tolerated and safe procedure in critically ill pediatric patients on ECMO. FB may have a diagnostic as well as therapeutic benefit in such patients.