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1.
Int J Mol Sci ; 23(9)2022 Apr 20.
Article in English | MEDLINE | ID: covidwho-1792658

ABSTRACT

In the beginning of the third year of the fight against COVID-19, the virus remains at least still one step ahead in the pandemic "war". The key reasons are evolving lineages and mutations, resulting in an increase of transmissibility and ability to evade immune system. However, from the immunologic point of view, the cytokine storm (CS) remains a poorly understood and difficult to combat culprit of the extended number of in-hospital admissions and deaths. It is not fully clear whether the cytokine release is a harmful result of suppression of the immune system or a positive reaction necessary to clear the virus. To develop methods of appropriate treatment and therefore decrease the mortality of the so-called COVID-19-CS, we need to look deeply inside its pathogenesis, which is the purpose of this review.


Subject(s)
COVID-19 , Cytokine Release Syndrome , Cytokines , Humans , Pandemics , SARS-CoV-2
2.
Pharmaceuticals (Basel) ; 15(2)2022 Feb 05.
Article in English | MEDLINE | ID: covidwho-1690192

ABSTRACT

In December 2019 the SARS-CoV-2 virus appeared in the world, mainly presenting as an acute infection of the lower respiratory tract, namely pneumonia. Nearly 10% of all patients show significant pulmonary fibrotic changes after the infection. The aim of this study was to evaluate the effectiveness and safety of potassium canrenoate in the treatment of COVID-19-associated pneumonia and pulmonary fibrosis. We performed a randomized clinical trial (RCT) of potassium canrenoate vs placebo. A total of 55 patients were randomized and 49 were included in the final analysis (24 allocated to the intervention group and 25 allocated to the control group). Patients were assessed by physical examination, lung ultrasound, CT imaging and blood samples that underwent biochemical analysis. This RCT has shown that the administration of potassium canrenoate to patients with COVID-19 induced pneumonia was not associated with shorter mechanical ventilation time, shorter passive oxygenation, shorter length of hospitalization or less fibrotic changes on CT imaging. The overall mortality rate was not significantly different between the two groups. Adverse events recorded in this study were not significantly increased by the administration of potassium canrenoate. The negative outcome of the study may be associated with the relatively small number of patients included. Any possible benefits from the use of potassium canrenoate as an antifibrotic drug in COVID-19 patients require further investigation.

3.
Cells ; 10(7)2021 07 19.
Article in English | MEDLINE | ID: covidwho-1323130

ABSTRACT

Since the end of 2019, a new, dangerous virus has caused the deaths of more than 3 million people. Efforts to fight the disease remain multifaceted and include prophylactic strategies (vaccines), the development of antiviral drugs targeting replication, and the mitigation of the damage associated with exacerbated immune responses (e.g., interleukin-6-receptor inhibitors). However, numerous uncertainties remain, making it difficult to lower the mortality rate, especially among critically ill patients. While looking for a new means of understanding the pathomechanisms of the disease, we asked a question-is our immunity key to resolving these uncertainties? In this review, we attempt to answer this question, and summarize, interpret, and discuss the available knowledge concerning the interplay between neutrophils, neutrophil extracellular traps (NETs), and T-cells in COVID-19. These are considered to be the first line of defense against pathogens and, thus, we chose to emphasize their role in SARS-CoV-2 infection. Although immunologic alterations are the subject of constant research, they are poorly understood and often underestimated. This review provides background information for the expansion of research on the novel, immunity-oriented approach to diagnostic and treatment possibilities.


Subject(s)
COVID-19/immunology , Extracellular Traps/immunology , Neutrophils/immunology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Animals , COVID-19/diagnosis , COVID-19/pathology , COVID-19/therapy , Humans , Immunity, Innate , Neutrophils/pathology , T-Lymphocytes/pathology
4.
Int J Mol Sci ; 22(13)2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1288908

ABSTRACT

The continually evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in a vast number of either acute or chronic medical impairments of a pathophysiology that is not yet fully understood. SARS-CoV-2 tropism for the organs is associated with bilateral organ cross-talks as well as targeted dysfunctions, among which acute kidney injury (AKI) seems to be highly prevalent in infected patients. The need for efficient management of COVID-related AKI patients is an aspect that is still being investigated by nephrologists; however, another reason for concern is a disturbingly high proportion of various types of kidney dysfunctions in patients who have recovered from COVID-19. Even though the clinical picture of AKI and COVID-related AKI seems to be quite similar, it must be considered that regarding the latter, little is known about both the optimal management and long-term consequences. These discrepancies raise an urgent need for further research aimed at evaluating the molecular mechanisms associated with SARS-CoV-2-induced kidney damage as well as standardized management of COVID-related AKI patients. The following review presents a comprehensive and most-recent insight into the pathophysiology, clinical manifestations, recommended patient management, treatment strategies, and post-mortem findings in patients with COVID-related AKI.


Subject(s)
Acute Kidney Injury/diagnosis , COVID-19/pathology , Acute Kidney Injury/etiology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Biomarkers/metabolism , COVID-19/complications , COVID-19/drug therapy , COVID-19/virology , Glomerular Filtration Rate , Humans , Interleukin-6/metabolism , Renin-Angiotensin System , Rhabdomyolysis/etiology , SARS-CoV-2/isolation & purification
5.
Cells ; 9(11)2020 11 02.
Article in English | MEDLINE | ID: covidwho-1256431

ABSTRACT

Secondary immunodeficiency is observed in all patients with chronic lymphocytic leukemia (CLL) in varying degrees. The aim of the study was to review the available literature data on patients with CLL, with particular regard to the pathogenesis of the disease and the impact of humoral immunity deficiency on the clinical and therapeutic approach. A systematic literature review was carried out by two independent authors who searched PubMed databases for studies published up to January 2020. Additionally, Google Scholar was used to evaluate search results and support manual research. The search resulted in 240 articles eligible for analysis. After all criteria and filters were applied, 22 studies were finally applied to the analysis. The data analysis showed that the clinical heterogeneity of CLL patients correlates with the diversity of molecular abnormalities determining the clinical picture of the disease, the analysis of which enables setting therapeutic targets. Additionally, in improving the therapeutic method, it is worth introducing supportive therapies with the use of vaccines, antibiotics and/or immunoglobins. Moreover, humoral immunodeficiency in CLL has a strong influence on the risk of infection in patients for whom infections are a major cause of morbidity and mortality.


Subject(s)
Immunity, Humoral , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Prognosis
6.
Pharmaceuticals (Basel) ; 14(1)2021 Jan 17.
Article in English | MEDLINE | ID: covidwho-1031152

ABSTRACT

In March 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared a global pandemic by the World Health Organization (WHO). The clinical course of the disease is unpredictable but may lead to severe acute respiratory infection (SARI) and pneumonia leading to acute respiratory distress syndrome (ARDS). It has been shown that pulmonary fibrosis may be one of the major long-term complications of COVID-19. In animal models, the use of spironolactone was proven to be an important drug in the prevention of pulmonary fibrosis. Through its dual action as a mineralocorticoid receptor (MR) antagonist and an androgenic inhibitor, spironolactone can provide significant benefits concerning COVID-19 infection. The primary effect of spironolactone in reducing pulmonary edema may also be beneficial in COVID-19 ARDS. Spironolactone is a well-known, widely used and safe anti-hypertensive and antiandrogenic medication. It has potassium-sparing diuretic action by antagonizing mineralocorticoid receptors (MRs). Spironolactone and potassium canrenoate, exerting combined pleiotropic action, may provide a therapeutic benefit to patients with COVID-19 pneumonia through antiandrogen, MR blocking, antifibrotic and anti-hyperinflammatory action. It has been proposed that spironolactone may prevent acute lung injury in COVID-19 infection due to its pleiotropic effects with favorable renin-angiotensin-aldosterone system (RAAS) and ACE2 expression, reduction in transmembrane serine protease 2 (TMPRSS2) activity and antiandrogenic action, and therefore it may prove to act as additional protection for patients at highest risk of severe pneumonia. Future prospective clinical trials are warranted to evaluate its therapeutic potential.

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