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Current COVID-19 vaccines induce suboptimal respiratory mucosal immunity even after mRNA boosters (Declercq et al. and Lasrado et al., this issue). [ABSTRACT FROM AUTHOR]

Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) represent an urgent public health challenge and are estimated to affect more than 60 million individuals globally. Although a growing body of evidence suggests that dysregulated immune reactions may be linked with PASC symptoms, most investigations have primarily centered around blood-based studies, with few focusing on samples derived from affected tissues. Furthermore, clinical studies alone often provide correlative insights rather than causal mechanisms. Thus, it is essential to compare clinical samples with relevant animal models and conduct functional experiments to understand the etiology of PASC. In this study, we comprehensively compared bronchoalveolar lavage fluid single-cell RNA sequencing data derived from clinical PASC samples and a mouse model of PASC. This revealed a pro-fibrotic monocyte-derived macrophage response in respiratory PASC, as well as abnormal interactions between pulmonary macrophages and respiratory resident T cells, in both humans and mice. Interferon-γ (IFN-γ) emerged as a key node mediating the immune anomalies in respiratory PASC. Neutralizing IFN-γ after the resolution of acute SARS-CoV-2 infection reduced lung inflammation and tissue fibrosis in mice. Together, our study underscores the importance of performing comparative analysis to understand the cause of PASC and suggests that the IFN-γ signaling axis might represent a therapeutic target. Editor's summary: The term "Long Covid" covers a myriad of symptoms that a person may experience after an acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is also referred to as postacute sequelae of SARS-CoV-2 (PASC). The specific drivers of these symptoms are unclear, complicating the development of therapeutics for those suffering from this condition. Here, Li et al. used comparative analysis to interrogate a potential driver of respiratory PASC, one of the most debilitating types of PASC. The authors found that humans with respiratory PASC had evidence of an enhanced monocyte-derived macrophage response in their bronchoalveolar lavage fluid. A similar phenotype was observed in aged C57BL/6 mice infected with mouse-adapted SARS-CoV-2. This phenotype in mice could be reduced by anti–interferon-γ (anti–IFN-γ) treatment initiated after the resolution of acute disease, suggesting that the IFN-γ signaling pathway may represent a potential therapeutic target for humans. —Courtney Malo [ABSTRACT FROM AUTHOR]

In recent years, the areas damaged by the East Asia migratory locust plagues (Locusta migratoria manilensis) have enlarged geographically in China. Some outbreaks in parts of the Dagang region, in the east coast of China, have caused drastic reductions in the yield of agricultural reeds and have created a severe threat to local and regional agriculture. Currently, the monitoring system for this species depends on field observations conducted by sparsely distributed observing stations established in the 1950s. This observation network was. in the past, successfully operated to identify major locust outbreaks. However, due lo the expansion of infestation areas and the increase of locust density, spatial information technology was needed to establish a satellite sensor-based monitoring system for the East Asia migratory locust plagues. This Letter outlines the preliminary experimental work conducted in 2001 for a feasibility study in establishing a sensor-based locust monitoring system. In this experiment, sample statistics of biomass and leaf area index (LAI) from the affected and non-affected areas by locusts were calculated, and the spectra of field reed samples from both areas were also evaluated together with synchronous Landsat Enhanced Thematic Mapper (ETM+) multi-spectral data. The study showed that satellite sensors may be used operationally to monitor locust damage. [ABSTRACT FROM AUTHOR]

The long-term physiological consequences of SARS-CoV-2, termed Post-Acute Sequelae of COVID-19 (PASC), are rapidly evolving into a major public health concern. The underlying cellular and molecular etiology remain poorly defined but growing evidence links PASC to abnormal immune responses and/or poor organ recovery post-infection. Yet, the precise mechanisms driving non-resolving inflammation and impaired tissue repair in the context of PASC remain unclear. With insights from three independent clinical cohorts of PASC patients with abnormal lung function and/or viral infection-mediated pulmonary fibrosis, we established a clinically relevant mouse model of post-viral lung sequelae to investigate the pathophysiology of respiratory PASC. By employing a combination of spatial transcriptomics and imaging, we identified dysregulated proximal interactions between immune cells and epithelial progenitors unique to the fibroproliferation in respiratory PASC but not acute COVID-19 or idiopathic pulmonary fibrosis (IPF). Specifically, we found a central role for lung-resident CD8 + T cell-macrophage interactions in maintaining Krt8 hi transitional and ectopic Krt5 + basal cell progenitors, thus impairing alveolar regeneration and driving fibrotic sequelae after acute viral pneumonia. Mechanistically, CD8 + T cell derived IFN-γ and TNF stimulated lung macrophages to chronically release IL-1β, resulting in the abnormal accumulation of dysplastic epithelial progenitors and fibrosis. Notably, therapeutic neutralization of IFN-γ and TNF, or IL-1β after the resolution of acute infection resulted in markedly improved alveolar regeneration and restoration of pulmonary function. Together, our findings implicate a dysregulated immune-epithelial progenitor niche in driving respiratory PASC. Moreover, in contrast to other approaches requiring early intervention, we highlight therapeutic strategies to rescue fibrotic disease in the aftermath of respiratory viral infections, addressing the current unmet need in the clinical management of PASC and post-viral disease.