Distinct Type 1 Immune Networks Underlie the Severity of Restrictive Lung Disease after COVID-19.

The variable etiology of persistent breathlessness after COVID-19 have confounded efforts to decipher the immunopathology of lung sequelae. Here, we analyzed hundreds of cellular and molecular features in the context of discrete pulmonary phenotypes to define the systemic immune landscape of post-COVID lung disease. Cluster analysis of lung physiology measures highlighted two phenotypes of restrictive lung disease that differed by their impaired diffusion and severity of fibrosis. Machine learning revealed marked CCR5+CD95+ CD8+ T-cell perturbations in mild-to-moderate lung disease, but attenuated T-cell responses hallmarked by elevated CXCL13 in more severe disease. Distinct sets of cells, mediators, and autoantibodies distinguished each restrictive phenotype, and differed from those of patients without significant lung involvement. These differences were reflected in divergent T-cell-based type 1 networks according to severity of lung disease. Our findings, which provide an immunological basis for active lung injury versus advanced disease after COVID-19, might offer new targets for treatment.

T-cell responses in asthma exacerbations.

OBJECTIVE: Asthma is a chronic lung disease comprising multiple endotypes and characterized by periodic exacerbations. A diverse array of T cells has been found to contribute to all endotypes of asthma in pathogenic and regulatory roles. Here, we review the contributions of CD4+, CD8+, and unconventional T cells in allergic and nonallergic asthma. DATA SOURCES: Review of published literature pertaining to conventional and unconventional T-cell types in asthma. STUDY SELECTIONS: Recent peer-reviewed articles pertaining to T cells in asthma, with additional peer-reviewed studies for context. RESULTS: Much research in asthma has focused on the roles of CD4+ TH cells. Roles for TH2 cells in promoting allergic asthma pathogenesis have been well-described, and the recent description of pathogenic TH2A cells provides additional insight into these responses. Other TH types, notably TH1 and TH17, have been linked to neutrophilic and steroid-resistant asthma phenotypes. Beyond CD4+ T cells, CD8+ Tc2 cells are also strongly associated with allergic asthma. An emerging area for study is unconventional T-cell types, including γδT, invariant natural killer T, and mucosal-associated invariant T cells. Although data in asthma remain limited for these cells, their ability to bridge innate and adaptive responses likely makes them key players in asthma. A number of asthma therapies target T-cell responses, and, although data are limited, they seem to modulate T-cell populations. CONCLUSION: Given the diversity and heterogeneity of asthma and T-cell responses, there remain many rich avenues for research to better understand the pathogenesis of asthma. Despite the breadth of T cells in asthma, approved therapeutics remain limited to TH2 networks.

Herpes simplex serious neurological disease in young children: incidence and long-term outcome.

OBJECTIVE: To determine the contribution of herpes simplex virus (HSV) to serious neurological disease. SETTING AND PATIENTS: A 3-year prospective survey of children aged 2-23 months in Britain and Ireland. RESULTS: 19 children had HSV central nervous system (CNS) infection; 13 aged 2-11 months had focal neuroimaging abnormalities and 11 long-term neurological sequelae. Of six aged 12-35 months, one had abnormal neuroimaging and three long-term neurological sequelae. 17 of the 19 had serious neurological disease. HSV CNS infection accounted for 23% of serious neurological disease in children aged 2-11 months and 4.5% in older children. CONCLUSIONS: The incidence of HSV-induced serious neurological disease in the UK was estimated at 1 in 64 000/year in younger children and 1 in 230 000 in older children. HSV CNS infection has clinical effects ranging from frank encephalitis to severe illness with fever and convulsions to milder disease lacking encephalopathy.

Analysis of yellow fever vaccination practice in England.

BACKGROUND: Prior to initiation of a program of registration, training, standards, and audit for yellow fever vaccination centers (YFVCs) in England, the National Travel Health Network and Centre (NaTHNaC) assessed the current practice and resource needs of these centers. METHODS: A questionnaire was sent to all YFVCs on the English Department of Health (DH) database in November 2004. It surveyed type of practice, administration of travel vaccines, training and duties of staff, vaccine storage and record keeping, access to travel health information, and resource and training needs. RESULTS: The questionnaire was completed by 69% (2,933 of 4,242) of YFVCs on the DH database. Nearly all (94%) YFVCs were part of general practice; centers were widely distributed throughout England. A median number of 35 doses of yellow fever vaccine (YFV) were given every year, with 75% of centers giving less than one dose per week. Nurses administered YFV more frequently than physicians (96% of nurses vs 49% of physicians, p < 0.0001). More nurses in YFVCs had received travel health training compared with physicians (95% vs 57%, p < 0.0001). Study days run by pharmaceutical companies were the most frequent source of training. Most YFVCs properly refrigerated vaccine and maintained vaccination records. Of the centers that reported using Internet resources for every patient, the Travax (Health Protection Scotland) (64%) and DH (England) (48%) Web sites were most frequently accessed. YFVCs cited training opportunities, information for travelers, and specific travel medicine advice as resources that would be most helpful to them. CONCLUSIONS: The NaTHNaC program of registration, training, standards, and audit should help to meet important needs in practice settings and contribute to an improvement in travel health.

Risk of serious neurologic disease after immunization of young children in Britain and Ireland.

OBJECTIVE: We sought to investigate the risk of serious neurologic disease after immunization in early childhood. METHODS: The results of a 3-year prospective study of children (2-35 months old) in Britain and Ireland with encephalitis and/or severe illness with convulsions and fever were linked to each child's vaccine history. Cases were reported via the British Paediatric Surveillance Unit's network. The self-controlled case-series method was used to investigate associations between immunization and acute potential adverse events. The risk periods investigated were 0 to 3 and 0 to 7 days post-diphtheria, tetanus, whole cell pertussis, Haemophilus influenzae type b or meningococcal C conjugate vaccine and 6 to 11 and 15 to 35 days post-measles, mumps, rubella vaccine. RESULTS: A total of 157 disease episodes from 155 children met the analytical case definition. There were 11 cases of herpes simplex encephalitis and 23 cases of primary human herpesvirus 6 and/or 7 infection. There was no evidence of a raised relative incidence of serious neurologic disease in any of the specified risk periods with the exception of a raised relative incidence of 5.68 in the 6-11 days after measles, mumps, rubella vaccine. Based on this relative incidence, between 3 and 6 of the 6 cases in this period were estimated to be attributable to the vaccine with a best estimate of 5. The 6 cases all had fever with convulsions lasting >30 minutes; in all but 1, there was complete recovery by discharge from hospital. Of the 5 patients who recovered, 1 had a concurrent primary human herpesvirus 6 infection and one a primary human herpesvirus 7. CONCLUSIONS: Six to 11 days after measles, mumps, rubella vaccine there is an increased risk of fever and convulsions lasting >30 minutes. All 6 of the episodes temporally related to immunization met the criteria for complex febrile convulsions. The estimated attributable risk of serious neurological disease was similar to that previously found for measles vaccine.

Scrub typhus serologic testing with the indirect immunofluorescence method as a diagnostic gold standard: a lack of consensus leads to a lot of confusion.

A review was performed to determine the evidence base for scrub typhus indirect immunofluorescence assay (IFA) methodologies and the criteria for positive results. This review included a total of 109 publications, which comprised 123 eligible studies for analysis (14 publications included 2 substudies). There was considerable underreporting of the IFA methodology and seropositivity criteria used, with most studies using a defined cutoff titer rather than an increase in the titer in paired samples. The choice of positivity cutoff titer varied by country and purpose of the IFA test. This variation limits the comparability of seroprevalence rates between studies and, more seriously, raises questions about the appropriateness of the cutoffs for positive IFA results chosen for diagnosis of acute scrub typhus infection. We suggest that the diagnosis of scrub typhus using IFA should be based on a > or =4-fold increase in the titer in paired serum samples and should only be based on a single sample titer when there is an adequate local evidence base.