Severe SARS-CoV-2 infections are characterized by lymphopenia, but the mechanisms involved are still elusive. Based on our knowledge of HIV pathophysiology, we hypothesized that SARS-CoV-2 infection-mediated lymphopenia could also be related to T cell apoptosis. By comparing intensive care unit (ICU) and non-ICU COVID-19 patients with age-matched healthy donors, we found a strong positive correlation between plasma levels of soluble FasL (sFasL) and T cell surface expression of Fas/CD95 with the propensity of T cells to die and CD4 T cell counts. Plasma levels of sFasL and T cell death are correlated with CXCL10 which is part of the signature of 4 biomarkers of disease severity (ROC, 0.98). We also found that members of the Bcl-2 family had modulated in the T cells of COVID-19 patients. More importantly, we demonstrated that the pan-caspase inhibitor, Q-VD, prevents T cell death by apoptosis and enhances Th1 transcripts. Altogether, our results are compatible with a model in which T-cell apoptosis accounts for T lymphopenia in individuals with severe COVID-19. Therefore, a strategy aimed at blocking caspase activation could be beneficial for preventing immunodeficiency in COVID-19 patients.

High resolution computed tomography (HRCT) scans are increasingly used in hypersensitivity pneumonitis (HP). This study looked at HRCT findings at different phases of farmer's lung (FL), a common form of HP.A cross sectional analysis of 95 HRCT scans of FL cases (20 acute, 75 with a history of FL, 48 still in contact (Ex +) (dairy farm), and 27 who had ceased contact (Ex-)) was made. All scans were read independently by two, and if needed by three, radiologists blinded to the category. The lungs were divided into six regions (fives lobes + lingula), and read for attenuation/mosaic, ground-glass, micronodules, fibrosis, and emphysema. A score of 0±3 was given for each region and each variable: 0 = absence, 1 =<25% of the surface, 2 = 25±50%, 3 =>50%. Mediastinal lymphadenopathy was also noted.Ground glass, predominating in the lower lobes, was the most frequent feature in the acute and Ex+ cases. Other abnormalities had no preferential distribution. Ex+ had more ground-glass than the Ex-(p=0.0025). Emphysema was more frequently seen than interstitial fibrosis (p=0.004). Mediastinal lymphadenopathy was present in 26 cases (9 acute, 10 Ex+ and 7 Ex-).In conclusion, in farmer's lung: 1) ground-glass predominates in the lower lobes while the other abnormalities have no anatomic predilection; 2) contact avoidance allows a better resolution of computed tomography abnormalities than continued exposure; 3) emphysema is a more frequent finding than interstitial fibrosis; and 4) the presence of mediastinal lymphadenopathy has no negative diagnostic value. Eur Respir J 2000; 16: 56±60.

Follicular T helper cells (Tfh), a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs) during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs) during the acute phase of infection, which persists thereafter. This profound loss is associated with lack of sustained expression of the Tfh-defining transcription factors, Bcl-6 and c-Maf but with higher expression of the repressors KLF2 and Foxo1. In this context of Tfh abortive differentiation and loss, we found decreased percentages of memory B cell subsets and lower titers of SIV-specific IgG. We further demonstrate a drastic remodeling of the lymphoid architecture of the spleen and LNs, which disrupts the crucial cell-cell interactions necessary to maintain memory B cells and Tfh cells. Finally, our data demonstrated the early infection of Tfh cells. Paradoxically, the frequencies of SIV DNA were higher in splenic Tfh cells of RMs progressing more slowly suggesting sanctuaries for SIV in the spleen. Our findings provide important information regarding the impact of HIV/SIV infection on Tfh cells, and provide new clues for future vaccine strategies.

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