Respiratory immune characteristics associated withCoronavirus Disease 2019 (COVID-19) severity are currently unclear. We characterized bronchoalveolar lavage fluid immune cells from patients with varying severity of COVID-19 and from healthy people by using single-cell RNA sequencing. Proinflammatory monocyte-derived macrophages were abundant in the bronchoalveolar lavage fluid from patients with severe COVID-9. Moderate cases were characterized by the presence of highly clonally expanded CD8 + T cells. This atlas of the bronchoalveolar immune microenvironment suggests potential mechanisms underlying pathogenesis and recovery in COVID-19.

1 BackgroundThe outbreak of novel coronavirus pneumonia (NCP) caused by

The global pandemic of Coronavirus Disease 2019 (COVID-19) is now ongoing. Rapid and accurate detection of the causative virus SARS-CoV-2 is vital for the treatment and control of COVID-19. In this study, the comparative sensitivity of different respiratory specimens were retrospectively analyzed using 3552 clinical samples from 410 Guangdong CDC (Center for Disease Control and Prevention) confirmed COVID-19 patients. Except for BALF, the sputum possessed the highest positive rate (73.4%∼87.5%), followed by nasal swabs (53.1%∼85.3%) for both severe and mild cases during the first 14 days after illness onset (d.a.o). Viral RNA could be detected in all BALF from the severe group collected as early as 4 days after illness onset (d.a.o) and lasted up to 46 d.a.o., while none of BALF samples from mild group. Moreover, although viral RNA was negative in the upper respiratory samples, it was also positive in BALF samples in most cases from severe group during treatment. Despite of typical ground-glass opacity observed via computed tomographic (CT) scans, no viral RNA was detected in the first 3 or all upper respiratory tract specimens from some COVID-19 patients. In conclusion, sputum is most sensitive for routine laboratory diagnosis of COVID-19, followed by nasal swabs. Detection of viral RNAs in BLAF improves diagnostic accuracy in severe COVID-19 patients.

Loss of IL-27R on T cells results in increased protection from Mycobacterium tuberculosis. Torrado et al. demonstrate that IL-27R−/− T cells show improved fitness that is associated with decreased expression of cell death molecules, maintenance of IL-2 production, and preferential accumulation in the lung parenchyma and around infected macrophages.

Our results demonstrate that reduced Th17 responses were associated with the clinical outcome of M. tuberculosis infection. Suppression of Th17 response through down-regulation of IL-6R expression may be an important mechanism in the development of active TB.

Mycobacterium tuberculosis infection is associated with a spectrum of clinical outcomes, from long-term latent infection to different manifestations of progressive disease. Pro-inflammatory pathways, such as those controlled by IL-1β, have the contrasting potential both to prevent disease by restricting bacterial replication, and to promote disease by inflicting tissue damage. Thus, the ultimate contribution of individual inflammatory pathways to the outcome of M. tuberculosis infection remains ambiguous. In this study, we identified a naturally-occurring polymorphism in the human IL1B promoter region, which alters the association of the C/EBPβ and PU.1 transcription factors and controls Mtb-induced IL-1β production. The high-IL-1β expressing genotype was associated with the development of active tuberculosis, the severity of pulmonary disease and poor treatment outcome in TB patients. Higher IL-1β expression did not suppress the activity of IFN-γ-producing T cells, but instead correlated with neutrophil accumulation in the lung. These observations support a specific role for IL-1β and granulocytic inflammation as a driver of TB disease progression in humans, and suggest novel strategies for the prevention and treatment of tuberculosis.

Gamma interferon (IFN-␥) release assays have been proven to be useful in the diagnosis of 5%). In conclusion, the IFN-␥ ELISPOT assay is a useful adjunct to current tests for diagnosis of active TB in China. The ELISPOT assay is more accurate than TST in identifying TB infections.Tuberculosis (TB) is a leading cause of morbidity and mortality throughout the world, with 95% of cases and 97% of all deaths occurring in high-prevalence countries, such as China, where the prevalence of active TB is as high as 367/100,000 population (10). For the effective and efficient control of TB in these countries, rapid diagnosis and treatment for active-TB patients are the mainstays of the TB control program. However, the current widely used tests, including acid-fast staining of sputum, mycobacterial culture, and antibody test, are not satisfactory for this purpose (4).Recently, commercial immunodiagnostic tests for TB infection have been introduced. These tests are based on the Mycobacterium tuberculosis-specific antigens early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10

e Diagnosis of tuberculous pleurisy remains a challenge in the clinic. In this study, we evaluated the usefulness of a previously developed Mycobacterium tuberculosis antigen-specific gamma interferon enzyme-linked immunospot (ELISPOT) assay in the diagnosis of tuberculous pleurisy by testing a cohort of 352 patients with pleural effusion. We found that M. tuberculosis antigen-specific gamma interferon-producing cells were enriched four to five times in pleural fluid compared with their levels in peripheral blood from patients with tuberuclous pleurisy assayed in parallel. The sensitivity, specificity, positive predictive value, and negative predictive value of the pleural fluid mononuclear cell ELISPOT assay for the diagnosis of tuberculous pleurisy were 95.7%, 100%, 100%, and 81.0%, respectively. In comparison, the sensitivity and specificity of the ELISPOT assay using peripheral blood mononuclear cells were 78.3% and 86.3%, respectively. The sensitivity and specificity of the pleural fluid adenosine deaminase activity test were 55.5% and 86.3%, respectively. These results demonstrate that the M. tuberculosis antigen-specific ELISPOT assay performed on pleural fluid mononuclear cells provides an accurate, rapid diagnosis of tuberculous pleurisy.T uberculosis (TB) is a leading cause of morbidity and mortality throughout the world, with 95% of cases and 97% of all deaths occurring in high-prevalence countries such as China, where the prevalence of active TB is as high as 367/100,000 population (1). Tuberculous pleurisy (TBP) is a common clinical manifestation of active TB disease and may account for up to 50% of all pleural effusions in areas with a high incidence of TB (2). Standard diagnostic assays for TBP, including microbiological examination, adenosine deaminase (ADA) levels, cell infiltrate profile, and certain other biochemical tests, do not provide satisfactory sensitivity and specificity (3). As an example, ADA determination has been recognized as a relatively sensitive diagnostic test for TBP; increased ADA levels are observed in a number of other diseases, such as parapneumonic effusions and noninfectious inflammatory diseases (4). High pleural fluid ADA levels do not necessarily indicate the presence of TBP, especially when pleural fluid potassium levels exceed 5.0 mEq/liter (5).Infection with Mycobacterium tuberculosis elicits a strong antigen-specific gamma interferon (IFN-␥) response from host T cells, which is used as an indicator to diagnose latent M. tuberculosis infection in clinical practice (6, 7). In addition, we and others have applied the M. tuberculosis antigen-specific IFN-␥ enzymelinked immunosorbent spot (ELISPOT) assay to peripheral blood mononuclear cells (PBMC) to diagnose active TB (8, 9). Although the sensitivity of the peripheral blood ELISPOT assay for the diagnosis of active pulmonary TB is significantly higher than those of routine tests such as sputum M. tuberculosis culture, the specificity is not satisfactory, mostly due to its inability to discriminate active TB disease ...