Single-cell analysis of bronchoalveolar cells in inflammatory and fibrotic post-COVID lung disease.

Background: Persistent radiological lung abnormalities are evident in many survivors of acute coronavirus disease 2019 (COVID-19). Consolidation and ground glass opacities are interpreted to indicate subacute inflammation whereas reticulation is thought to reflect fibrosis. We sought to identify differences at molecular and cellular level, in the local immunopathology of post-COVID inflammation and fibrosis. Methods: We compared single-cell transcriptomic profiles and T cell receptor (TCR) repertoires of bronchoalveolar cells obtained from convalescent individuals with each radiological pattern, targeting lung segments affected by the predominant abnormality. Results: CD4 central memory T cells and CD8 effector memory T cells were significantly more abundant in those with inflammatory radiology. Clustering of similar TCRs from multiple donors was a striking feature of both phenotypes, consistent with tissue localised antigen-specific immune responses. There was no enrichment for known SARS-CoV-2-reactive TCRs, raising the possibility of T cell-mediated immunopathology driven by failure in immune self-tolerance. Conclusions: Post-COVID radiological inflammation and fibrosis show evidence of shared antigen-specific T cell responses, suggesting a role for therapies targeting T cells in limiting post-COVID lung damage.

Pediatric preseptal and orbital cellulitis - a 6 year experience from a London tertiary centre.

PURPOSE: This study reports the experience of pediatric preseptal and orbital cellulitis at a London tertiary centre during a 6-year period and highlights the role of orbital surgeons in the management of subperiosteal abscess (SPA). METHODS: A retrospective review was conducted of all pediatric patients hospitalised for preseptal and orbital cellulitis. RESULTS: A total of 201 children including 152 cases of preseptal cellulitis and 49 cases of orbital cellulitis were admitted at a London tertiary centre over the study period. Patients with orbital cellulitis and especially those managed surgically had higher rates of fever, higher presenting white cell count and C-reactive protein level compared to cases of preseptal cellulitis. 77.6% of patients with orbital cellulitis had SPA. 81.6% of SPA had a medial component, while 28.9% had superior component. 61.2% of orbital cellulitis cases were managed surgically. Surgical intervention was carried out by otorhinolaryngologists (ENT) in 76.7% of cases, jointly between ENT and orbital surgeons in 16.7% of cases and by orbital surgeons alone in 6.7% of cases. Of the 11 SPA involving the orbital roof, all were surgically managed and orbital surgeons were involved in 54.5% of cases. When SPA involved the medial wall, orbital surgeons were only involved in 6.5% of cases. CONCLUSIONS: We recommend all patients with superior SPA be treated at a centre with both ENT and orbital surgeons as these may not be amenable to drainage by ENT alone.

Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections.

Effective control of SARS-CoV-2 infection on primary exposure may reveal correlates of protective immunity to future variants, but we lack insights into immune responses before or at the time virus is first detected. We use blood transcriptomics, multiparameter flow cytometry, and T cell receptor (TCR) sequencing spanning the time of incident non-severe infection in unvaccinated virus-naive individuals to identify rapid type 1 interferon (IFN) responses common to other acute respiratory viruses and cell proliferation responses that discriminate SARS-CoV-2 from other viruses. These peak by the time the virus is first detected and sometimes precede virus detection. Cell proliferation is most evident in CD8 T cells and associated with specific expansion of SARS-CoV-2-reactive TCRs, in contrast to virus-specific antibodies, which lag by 1-2 weeks. Our data support a protective role for early type 1 IFN and CD8 T cell responses, with implications for development of universal T cell vaccines.