No abstract

Intramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable “sterilizing immunity” at the mucosal level. Our study uncovers a strong temporary neutralizing mucosal component of immunity, emanating from intramuscular administration of an mRNA vaccine. We show that saliva of BNT162b2 vaccinees contains temporary IgA targeting the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus-2 spike protein and demonstrate that these IgAs mediate neutralization. RBD-targeting IgAs were found to associate with the secretory component, indicating their bona fide transcytotic origin and their polymeric multivalent nature. The mechanistic understanding of the high neutralizing activity provided by mucosal IgA, acting at the first line of defense, will advance vaccination design and surveillance principles and may point to novel treatment approaches and new routes of vaccine administration and boosting.

Intramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable 'sterilizing immunity' at the mucosal level. Our study uncovers, strong neutralizing mucosal component (NT50 ≤ 50pM), emanating from intramuscular administration of an mRNA vaccine. We show that saliva of BNT162b2 vaccinees contains temporary IgA targeting the Receptor-Binding-Domain (RBD) of SARS-CoV-2 spike protein and demonstrate that these IgAs are key mediators of potent neutralization. RBD-targeting IgAs were found to associate with the Secretory Component, indicating their bona-fide transcytotic origin and their dimeric tetravalent nature. The mechanistic understanding of the exceptionally high neutralizing activity provided by mucosal IgA, acting at the first line of defence, will advance vaccination design and surveillance principles, pointing to novel treatment approaches, and to new routes of vaccine administration and boosting.

Symptoms following acute COVID-19 infection are common, but their relationship to initial COVID-19 severity is unclear. We hypothesize that residual symptoms are related to disease severity, and severe acute COVID-19 infection is more likely to cause residual pulmonary damage. This study aims to evaluate symptoms, lung function, and abnormal imaging within 3 months following COVID-19 infection, and to determine whether they are related to initial disease severity. A cross-sectional study was carried out at a designated post-COVID clinic in Hadassah Medical Center, Jerusalem, Israel. Patients with PCR-confirmed SARS-CoV-2 infection were evaluated within 12 weeks following infection and included both admitted and non-admitted subjects. All study participants underwent assessment of symptoms, quality of life (SGRQ), pulmonary function tests, and imaging. A total of 208 patients (age 49.3 ± 16 years) were included in the study. Initial disease severity was mild in 86, moderate in 49, and severe in 73 patients. At the time of follow-up, there were no differences in frequency of residual symptoms or in SGRQ score between groups. Patients with severe COVID-19 were more likely to have residual dyspnea ( p = 0.04), lower oxygen saturation ( p < 0.01), lower FVC and TLC ( p < 0.001, p = 0.03 respectively), abnormal CXR ( p < 0.01), and abnormal CT scan ( p < 0.01) compared to other groups.Frequency of symptoms and impairment of quality of life at 12 week follow-up are common and are not related to severity of initial COVID-19 disease. In contrast, reduced lung function and abnormal pulmonary imaging are more common in patients with more severe acute COVID-19 infection.