Pulmonary pathology of the new coronavirus disease (COVID-19). The preliminary analysis of post-mortem findings

Background. Currently, the patho- and morphogenesis of the new coronavirus infection (COVID-19) is being studied in depth. A comparative analysis of the morphological changes in the lungs of deceased patients is of importance, for various time periods after the onset of the first clinical symptoms. The clinical and morphological comparison should help to increase the qualified medical care for patients in the resuscitation profile and reduce the hospital mortality. The aim of the study was to formulate a working hypothesis for a conceptual scheme of clinical and morphological phases of development of the new coronavirus infection (COVID-19). Methods. An analysis of 80 fatal cases was carried out in the COVID-center of the Federal Research Clinical Center of FMBA of Russia. Along with the assessment of macro- and microscopic changes in the respiratory tract, additional histochemical van Gieson staining was applied and immunohistochemical studies were performed to assess the condition of the COVID-19-affected lungs. Results. The revealed features of diffuse alveolar damage in the case of the new coronavirus infection (COVID-19) made it possible to present a working hypothesis of the pathomorphogenesis of COVID-19 interstitial pneumonia. It proceeds through 3 phases: fulminant, persistent and fibrotic. Each phase is conditionally limited by certain time parameters and is characterized by certain morphological signs Dysregulatory activation of monocytic phagocytes, development of generalized microthrombosis, persistent signs of the exudative phase, pathological repair, progressive intraalveolar and interstitial fibrosis are the main links in the pathomorphogenesis of COVID-19 interstitial pneumonia. In response to the penetration of SARS-CoV-2, the T-cell immunity reactions prevail at the exudative and proliferative stages. At the fibrotic stage, the overall number of T-lymphocytes is drastically decreased, the cells of humoral immunity are not revealed. The CD8+ T-lymphocytes prevailing over CD4+ T-lymphocyte helpers is probably related to the autoimmune damage mechanisms. Conclusions. Damage to the lungs with the development of COVID-19 interstitial pneumonia is the main cause of the severe course of the disease and deaths. The revealed features of the pathomorphogenesis of the clinical and morphological phases of COVID-19 interstitial pneumonia will improve the quality of diagnosis and treatment of a new coronavirus infection (COVID-19)

Возможности метода зондовой конфокальной лазерной эндомикроскопии в диагностике холангиокарцином

Method probe confocal laser endomicroscopy can be crucial in case of inefficiency or a small informative other methods of diagnosis in diseases of the pancreato-biliary area. The article presents clinical observation of various diseases of the bile ducts, including cholangiocarcinoma, developed on the background of chronic diseases of the pancreato-biliary area. Reflects the complexity of instrumental diagnosis at an early stage of the disease. For the first time in this pathology diagnostic purpose method applied scanning probe confocal laser endomicroscopy, allowing in all cases to Refine and verify the diagnosis. The method of research, its results are compared with other diagnostic methods.Метод зондовой конфокальной лазерной эндомикроскопии может иметь решающее значение при неэффективности или малой информативности других методов диагностики при заболеваниях органов панкреатобилиарной зоны. В статье приведены клинические наблюдения различных заболеваний желчных протоков, в том числе и холангиокарциномы, развившихся на фоне хронических заболеваний органов панкреатобилиарной зоны. Отражены сложности инструментальной диагностики на ранней стадии заболевания. Впервые при данной патологии с диагностической целью применен метод зондовой конфокальной лазерной эндомикроскопии, позволивший во всех случаях уточнить и верифицировать диагноз. Описана методика исследования, ее результаты сопоставлены с другими методами диагностики

The case of diagnostics of invasive pulmonary aspergillosis by in vivo probe-based confocal laser endomicroscopy of central and distal airways

We present a case of 41-year-old patient with invasive pulmonary aspergillosis (IPA) in which probe-based confocal laser endomicroscopy (pCLE) imaging of central and distal airways was first performed in vivo. pCLE imaging showed the signs of complete or partial destruction of elastin network of alveolar wall with fibrillar branching fluorescent structures in the zone with typical IPA changes on HRCT

Oncolytic therapy with recombinant vaccinia viruses targeting the interleukin-15 pathway elicits a synergistic response

We developed recombinant variants of oncolytic vaccinia virus LIVP strain expressing interleukin-15 (IL-15) or its receptor subunit alpha (IL-15Rα) to stimulate IL-15-dependent immune cells. We evaluated their oncolytic activity either alone or in combination with each other in vitro and in vivo using the murine CT26 colon carcinoma and 4T1 breast carcinoma models. We demonstrated that the admixture of these recombinant variants could promote the generation of the IL-15/IL-15Rα complex. In vitro studies indicated that 4T1 breast cancer cells were more susceptible to the developed recombinant viruses. In vivo studies showed significant survival benefits and tumor regression in 4T1 breast cancer syngeneic mice that received a combination of LIVP-IL15-RFP with LIVP-IL15Ra-RFP. Histological analysis showed recruited lymphocytes at the tumor region, while no harmful effects to the liver or spleen of the animals were detected. Evaluating tumor-infiltrated lymphocytes represented profound activation of cytotoxic T cells and macrophages in mice receiving combination therapy. Thus, our experiments showed superior oncolytic effectiveness of simultaneous injection of LIVP-IL15-RFP and LIVP-IL15Ra-RFP in breast cancer-bearing mice. The combined therapy by these recombinant variants represents a potent and versatile approach for developing new immunotherapies for breast cancer