The Novel Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) Directly Decimates Human Spleens and Lymph Nodes

While lymphocytopenia is a common characteristic of patients infected by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the mechanisms responsible for this depletion are unclear. Through careful inspection of the spleens and lymph nodes (LNs) from six cases with postmortem examinations, we observed that SARS-CoV-2 could directly infect secondary lymphoid organs to induce cell death. Immunohistochemistry demonstrated ACE2 (angiotensin-converting enzyme 2), the potential receptor of SARS-CoV-2, expresses on tissue-resident CD169+ macrophages in spleens and LNs. Immunofluorescent staining confirmed that viral nucleocaspid protein (NP) can be found in ACE2+ cells, CD169+ macrophages, but not in CD3+ T cells or B220+ B cells in spleens and LNs. SARS-CoV-2 infection induces severe tissue damage including lymph follicle depletion, splenic nodule atrophy, histiocyte hyperplasia and lymphocyte reductions. Moreover, in situ TUNEL staining illustrated that viral infection leads to severe lymphocyte apoptosis, which might be mediated by viral antigens inducing Fas upregulation. Furthermore, SARS-CoV-2 also triggers macrophages to produce IL-6, a proinflammatory cytokine that directly promotes lymphocyte necrosis. Collectively, these results demonstrate that SARS-CoV-2 directly neutralizes human spleens and LNs through infecting tissue-resident CD169+ macrophages.

Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection

BACKGROUNDThe outbreak of a novel coronavirus (SARS-CoV-2, previously provisionally named 2019 novel coronavirus or 2019-nCoV) since December 2019 in Wuhan, China, has become an emergency of major international concern. Apart from the respiratory system, it is unclear whether SARS-CoV-2 can also directly infect other tissues such as the kidney or induce acute renal failure. METHODSWe conducted a retrospective analysis of estimated glomerular filtration rate (eGFR) along with other clinical parameters from 85 patients with laboratory-confirmed COVID-19 admitted to a hospital in Wuhan from January 17, 2020 to March 3, 2020. Kidney tissues from six patients with postmortem examinations were analyzed by Hematoxylin and Eosin (H&E) and in situ expression of viral nucleocaspid protein (NP) antigen, immune cell markers (CD8, CD68 and CD56) and the complement C5b-9 was detected by immunohistochemistry. Moreover, the viral particles in kidneys were also investigated by transmission electronic microscope (EM). RESULTS27.06% (23/85) patients exhibited acute renal failure (ARF). The eldery patients and cases with comorbidities such as hypertension and heart failure more easily developed ARF (65.22% vs 24.19%, p< 0.001; 69.57% vs 11.29%, p< 0.001, respectively). H&E staining demonstrated kidney tissues from postmortems have severe acute tubular necrosis and lymphocyte infiltration. Immunohistochemistry showed that SARS-CoV-2 NP antigen was accumulated in kidney tubules. EM observation also demonstrated that viruses-like particles are visible in the kidneys. Viral infection not only induces CD68+ macrophages infiltrated into tubulointerstitium, but also enhances complement C5b-9 deposition on tubules. CONCLUSIONSSARS-CoV-2 induces ARF in COVID-19 patients. Viruses directly infect human kidney tubules to induce acute tubular damage. The viruses not only have direct cytotoxicity, but also initiate CD68+ macrophage together with complement C5b-9 deposition to mediate tubular pathogenesis.

Reduction and Functional Exhaustion of T Cells in Patients with Coronavirus Disease 2019 (COVID-19)

BACKGROUNDThe outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health, which has been declared a public health emergency of international concern (PHEIC) by the WHO. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. METHODSWe retrospectively reviewed the counts of total T cells, CD4+, CD8+ T cell subsets, and serum cytokine concentration from inpatient data of 522 patients with laboratory-confirmed COVID-19, admitted into two hospitals in Wuhan from December 2019 to January 2020, and 40 healthy controls, who came to the hospitals for routine physical examination. In addition, the expression of T cell exhaustion markers PD-1 and Tim-3 were measured by flow cytometry in the peripheral blood of 14 COVID-19 cases. RESULTSThe number of total T cells, CD4+ and CD8+ T cells were dramatically reduced in COVID-19 patients, especially among elderly patients ([>=]60 years of age) and in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8+T cells or CD4+T cells lower than 800/L, 300/L, or 400/L, respectively, are negatively correlated with patient survival. Statistical analysis demonstrated that T cell numbers are negatively correlated to serum IL-6, IL-10 and TNF- concentration, with patients in decline period showing reduced IL-6, IL-10 and TNF- concentrations and restored T cell counts. Finally, T cells from COVID-19 patients have significantly higher levels of the exhausted marker PD-1 as compared to health controls. Moreover, increasing PD-1 and Tim-3 expression on T cells could be seen as patients progressed from prodromal to overtly symptomatic stages, further indicative of T cell exhaustion. CONCLUSIONST cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients, with total T cells, CD8+T cells CD4+T cells counts lower than 800/L, 300/L, and 400/L, respectively, may still require aggressive intervention even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.

Establishment of a Carrying System for Space Cellular Experiment on Shenzhou-6 Spacecraft / 航天医学与医学工程

Objective To establish a carrying system for space cellular experiment suitable for astronaut to carry out cellular experiments on Shenzhou-6 mission.Methods The cell carrying sample bag,sample box and sample box integrated package were designed.Primary cardiomyocytes and osteoblasts culture and ground model experiment in the simulated environment of space cabin were performed.With man-tended,the cellular experiment was carried out on the orbit.Results After 5 d space flight,the returned cell samples were analyzed.The results demonstrated that the system was of good safety,reliability and applicability,as well as satisfied the demands of analyzed samples.Conclusion After Shenzhou-6 space flight,it is showed that this system fits for small loading,multi-cells and man-tended carrying mission,and can satisfy the demand of the first man-tended space cellular experiments carried out on the Shenzhou-6 spacecraft.

Application of Equipment in Mobile Medical Service Corps and Construction of Maintaining SOP / 医疗卫生装备

The reason for the construction of standard operation process(SOP) in equipment application and maintenance is expatiated.The content and how to construct the system are also discussed.Many problems in equipment application and management are solved.The efficiency of all kinds of equipment in the construction of mobile medical service corps are enhanced.

Clinical observation on treatment of thoracolumbar fractures using anti-rotation reduction internal fixators, atlas fixator and Dick screw / 中华创伤杂志

Objective To compare the treatment effects of self-designed anti-rotation reduction internal fixators (ARRIF), atlas fixator (AF) and Dick screw in reduction and fixation of different thoracolumbar spinal fractures. Methods Reduction effect, operation time, bleeding volume during operation and complications were observed and compared after ARRIF, AF and Dick screw were used to treat 90 cases of thoracolumbar spinal fractures. Results Compared with AF and Dick screw, the operation time of ARRIF was shorter with less bleeding volume during operation as well as less complications like broken or pulled-out screw or broken rod. Conclusions All three fixation methods can attain the reduction and fixation of various kinds of thoracolumbar spinal fractures. However, ARRIF is the most valuable transpedicular internal fixator and can more conveniently reduce and fixate the different spinal fractures and AF places the second.

MECHANICAL EVALUATION OF SPINAL FIXATION STABILITY PROVIDED BY THREE INTERNAL FIXATION DE- VICES FOR THROACOLUMBAR SPINE FRACTURES / 解放军医学杂志

By mechanical comparison study of ARRIF,Dick and AF ,their reliable basis for further clinical application was evaluated. Models of spinal fracture were made using fresh cadavers. According to the Latin squre experimental designing principle, the fracture specimens were fixed with ARRIF,Dick and AF separately. The shift and angle changes were observed under different loads,and the analysis of variance was performed to all the data with the SPSS software . The single spinal compression fracture model showed no significant shift and the mechanical features were similar when it was fixed by ARRIF,Dick and AF. The model of spinal compression fracture with three spinal damages showed significant differences among these three fixings when axial torsion load was given. ARRIF and AF were clearly superior to Dick. The histological observation of ARRIF recorded no significant changes in the bone trabecula around the nail pass and the structure kept normal. The mechanical feature of ARRIF was basically similar to that of AF and Dick. Our conclusion is that because of the characteristics of its designing, the anti-axial torsion ability of ARRIF is outstanding and it can be easily fixed in application, thus it holds certain value in clinical practice.