The proposed pulmonary inflammation load score was higher in patients with severe COVID-19 in comparison with patient with mild disease. The optimal inflammation load score threshold for identifying severe patients was 19.5, with 83.3% sensitivity and 94% specificity. Summary statement The chest CT severity score could be used to rapidly identify patients with severe forms of COVID-19. Background: Quantitative and semi-quantitative indicators to evaluate the severity of lung inflammation in Coronavirus Disease 2019 (COVID-19) could provide an objective approach to rapidly identify patients in need of hospital admission. Purpose: To evaluate the value of chest computed tomography severity score (CT-SS) in differentiating clinical forms of COVID-19. Materials and Methods: Inclusion of 102 patients with COVID-19 confirmed by positive real-time reverse transcriptase polymerase chain reaction on throat swabs underwent chest CT (53 men and 49 women, 15-79 years old, 84 cases with mild and 18 cases with severe disease). The CT-SS was defined by summing up individual scores from 20 lung regions; scores of 0, 1, and 2 were respectively assigned for each region if parenchymal opacification involved 0%, less than 50%, or equal or more than 50% of each region (theoretical range of CT-SS from 0 to 40). The clinical and laboratory data were collected, and patients were clinically subdivided according to disease severity by the Chinese National Health Commission guidelines. Results: The posterior segment of upper lobe (left, 68/102; right, 68/102), superior segment of lower lobe (left, 79/102; right, 79/102), lateral basal segment (left, 79/102; right, 70/102) and posterior basal segment of lower lobe (left, 81/102; right, 83/102) were the most frequently involved sites in COVID-19. Lung opacification mainly involved the lower lobes, in comparison with middle-upper lobes. No significant differences in distribution of the disease were seen between right and left lungs. The individual scores of in each lung, as well as the total CT-SS were higher in severe COVID-19 when compared with mild cases (P< 0.05. The optimal CT-SS threshold for identifying severe COVID-19 was 19.5 (area under curve, 0.892), with 83.3% sensitivity and 94% specificity. Conclusion: CT-SS could be used to quickly and objectively evaluate the severity of pulmonary involvement in COVID-19 patients.
Cellular senescence is characterized by stable cell cycle arrest and a secretory program that modulates the tissue microenvironment 1 , 2 . Physiologically, senescence serves as a tumor suppressive mechanism that prevents the expansion of premalignant cells 3 , 4 and plays a beneficial role in wound healing responses 5 , 6 . Pathologically, the aberrant accumulation of senescent cells generates an inflammatory milieu that leads to chronic tissue damage and contributes to diseases such as liver and lung fibrosis, atherosclerosis, diabetes, and osteoarthritis 1 , 7 . Accordingly, elimination of senescent cells from damaged tissues in mice ameliorates symptoms of these pathologies and even promotes longevity 1 , 2 , 8 – 10 . Here we test the therapeutic concept that chimeric antigen receptor (CAR) T cells targeting senescent cells can be effective senolytics. We identify the urokinase plasminogen activator receptor (uPAR) 11 as a cell surface protein broadly induced during senescence and demonstrate that uPAR-specific CAR T cells efficiently ablate senescent cells in vitro and in vivo . uPAR-directed CAR T cells extend the survival of mice harboring lung adenocarcinoma treated with a senescence-inducing drug combination, and restore tissue homeostasis in chemical- or diet-induced liver fibrosis. These results establish the therapeutic potential of senolytic CAR T cells for senescence-associated diseases.
Background: Coronavirus disease 2019 , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), involves multiple organs. Testicular involvement is largely unknown. Objective: To determine the pathological changes and whether SARS-CoV-2 can be detected in the testes of deceased COVID-19 patients. Design, setting, and participants: Postmortem examination of the testes from 12 COVID-19 patients was performed using light and electron microscopy, and immunohistochemistry for lymphocytic and histiocytic markers. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the virus in testicular tissue. Outcome measurements and statistical analysis: Seminiferous tubular injury was assessed as none, mild, moderate, or severe according to the extent of tubular damage. Leydig cells in the interstitium were counted in ten 400Â microscopy fields. Results and limitations: Microscopically, Sertoli cells showed swelling, vacuolation and cytoplasmic rarefaction, detachment from tubular basement membranes, and loss and sloughing into lumens of the intratubular cell mass. Two, five, and four of 11 cases showed mild, moderate, and severe injury, respectively. The mean number of Leydig cells in COVID-19 testes was significantly lower than in the control group (2.2 vs 7.8, p < 0.001). In the interstitium there was edema and mild inflammatory infiltrates composed of T lymphocytes and histiocytes. Transmission EM did not identify viral particles in three cases. RT-PCR detected the virus in one of 12 cases. Conclusions: Testes from COVID-19 patients exhibited significant seminiferous tubular injury, reduced Leydig cells, and mild lymphocytic inflammation. We found no evidence of SARS-CoV-2 virus in the testes in the majority (90%) of the cases by RT-PCR, and in none by electron microscopy. These findings can provide evidence-based guidance for sperm donation and inform management strategies to mitigate the risk of testicular injury during the COVID-19 disease course.
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