Lymphopenia is a frequent hematological manifestation, associated with a severe course of COVID-19, with an insufficiently understood pathogenesis. We present molecular genetic immunohistochemical, and electron microscopic data on SARS-CoV-2 dissemination and viral load (VL) in lungs, mediastinum lymph nodes, and the spleen of 36 patients who died from COVID-19. Lymphopenia <1 × 10⁹/L was observed in 23 of 36 (63.8%) patients. In 12 of 36 cases (33%) SARS-CoV-2 was found in lung tissues only with a median VL of 239 copies (range 18–1952) SARS-CoV-2 cDNA per 100 copies of ABL1. Histomorphological changes corresponding to bronchopneumonia and the proliferative phase of DAD were observed in these cases. SARS-CoV-2 dissemination into the lungs, lymph nodes, and spleen was detected in 23 of 36 patients (58.4%) and was associated with the exudative phase of DAD in most of these cases. The median VL in the lungs was 12,116 copies (range 810–250281), lymph nodes—832 copies (range 96–11586), and spleen—71.5 copies (range 0–2899). SARS-CoV-2 in all cases belonged to the 19A strain. A immunohistochemical study revealed SARS-CoV-2 proteins in pneumocytes, alveolar macrophages, and bronchiolar epithelial cells in lung tissue, sinus histiocytes of lymph nodes, as well as cells of the Billroth pulp cords and spleen capsule. SARS-CoV-2 particles were detected by transmission electron microscopy in the cytoplasm of the endothelial cell, macrophages, and lymphocytes. The infection of lymphocytes with SARS-CoV-2 that we discovered for the first time may indicate a possible link between lymphopenia and SARS-CoV-2-mediated cytotoxic effect.

Multi-organ failure is one of the common causes of fatal outcome in COVID-19 patients. However, the pathogenetic association of the SARS-CoV-2 viral load (VL) level with fatal dysfunctions of the lungs, liver, kidneys, heart, spleen and brain, as well as with the risk of death in COVID-19 patients remains poorly understood. SARS-CoV-2 VL in the lungs, heart, liver, kidneys, brain, spleen and lymph nodes have been measured by RT qPCR using the following formula: N^SARS-CoV−2/N^{ABL1 ×} 100. Dissemination of SARS-CoV-2 in 30.5% of cases was mono-organ, and in 63.9% of cases, it was multi-organ. The average SARS-CoV-2 VL in the exudative phase of diffuse alveolar damage (DAD) was 60 times higher than in the proliferative phase. The SARS-CoV-2 VL in the lungs ranged from 0 to 250,281 copies. The “pulmonary factors” of SARS-CoV-2 multi-organ dissemination are the high level of SARS-CoV-2 VL (≥4909) and the exudative phase of DAD. The frequency of SARS-CoV-2 dissemination to lymph nodes was 86.9%, heart–56.5%, spleen–52.2%, liver–47.8%, kidney–26%, and brain–13%. We found no link between the SARS-CoV-2 VL level in the liver, kidneys, and heart and the serum level of CPK, LDH, ALP, ALT, AST and Cr of COVID-19 patients. Isolated detection of SARS-CoV-2 RNA in the myocardium of COVID-19 patients who died from heart failure is possible. The pathogenesis of COVID-19-associated multi-organ failure requires further research in a larger cohort of patients.

Nitric oxide (NO) is a gaseous molecule which plays a key role in wound healing. Previously, we identified the optimal conditions for wound healing strategies using NO donors and an air plasma generator. The aim of this study was to compare the wound healing effects of binuclear dinitrosyl iron complexes with glutathione (B-DNIC-GSH) and NO-containing gas flow (NO-CGF) at their optimal NO doses (0.04 mmol for B-DNIC-GSH and 1.0 mmol for NO-CGF per 1 cm²) in a rat full-thickness wound model over a 3-week period. Excised wound tissues were studied by light and transmission electron microscopy and immunohistochemical, morphometrical and statistical methods. Both treatments had an identical stimulating impact on wound healing, which indicated a higher dosage effectiveness of B-DNIC-GSH compared to the NO-CGF. B-DNIC-GSH spray application reduced inflammation and promoted fibroblast proliferation, angiogenesis and the growth of granulation tissue during the first 4 days after injury. However, prolonged NO spray effects were mild compared to NO-CGF. Future studies should determine the optimal B-DNIC-GSH solution course for a more effective wound healing stimulation.

Telocytes were described in 2010 as a distinct type of interstitial cells involved in the organization of the stroma of various organs. These cells have very long prolongations (telopodes) that can interact with other telocytes to form complex three-dimensional networks within organs. Telocyte networks play an important role in the maintenance of various tissues, in particular by providing a stem cell niche as well as by creating conditions for the differentiation of some cells. The ability to affect cells of different cell types within an organ allows telocyte networks to regulate various histogenetic processes, playing the role of a kind of “system integrators” that unite physically separated cellular components into a single system. This review provides a systematic overview of the current state of knowledge regarding the role of telocyte networks in the organization of specific tissues and their integration into a unified system during both embryonic development and adult state as well as during the development of pathological processes.

Myocarditis (MC) remains a relatively challenging cardiovascular disease to diagnose, often leading to complications, particularly affecting young and middle-aged individuals. Viruses are the most common cause of MC. The COVID-19 pandemic has not only led to an increase in MC cases but also introduced post-vaccination MC following SARS-CoV-2 immunization. Extracellular vesicles, particularly exosomes as key mediators of intercellular communication, have been implicated in the pathogenesis, treatment, and prevention of various cardiovascular diseases. However, data specifically concerning their role in MC remain fragmented. This review offers a comprehensive approach to understanding the diverse roles, functions, and molecular mechanisms of various exosome types in viral MC. A new approach to viral MC-associated exosomes classification is proposed: it is based on their functional features and differences in actions. Separately, data on mitochondrial vesicles as mediators of inter-organelle and intercellular signaling during inflammation and viral infection are presented. Terms “masking” and “protective” exosomes are used for the first time. Furthermore, definitions are provided, and the antagonistic features between virus-induced and “protective” exosomes in the infectious process are demonstrated. The striking similarity in the biogenesis of exosomes and certain viruses has provided a pathway for viral dissemination throughout the host organism and enabled immune evasion through “masking” or mimetic exosomes. This resemblance also offers researchers wide prospects for discovering novel antiviral defense strategies; however, it simultaneously necessitates a reconsideration of the safety aspects and future applications of mRNA vaccines due to the potential adverse consequences of MC development.