CORRELATIVE ASSOCIATION OF OXYGENATION AND SEPSIS PANELS WITH THE USE OF ACE2 INHIBITORS AND WITHOUT IT IN THE CONDITIONS OF SEPTIC SHOCK IN COVID-19-INFECTED AND NON-INFECTED PATIENTS (COHORT STUDY).

Sepsis-associated hyperlactatemia (SAHL), Lactic acidosis, is a common problem in critically ill patients. The prevalence of Lactic acidosis is estimated to be approximately 1% of all hospitalized nonsurgical patients. The purpose of our study was to reveal possible associations between the level of Lactate with sepsis biomarkers: PCT, IL 6, and PO2 in the presence of ACE 2 inhibitors in Covid-19 infected and non-infected patients with Septic Shock. We conducted a cohort study, comparing outcomes of 212 critically ill patients with Septic shock, who were treated in the intensive care unit of First University Clinic of Tbilisi State Medical University during the 2020-2021 years. Inclusion criteria for the study were: Age>40ys; COVID-19 and other respiratory diseases associated with Septic shock, with respiration dysfunctions with prior exposure to ACE2 inhibitors o no history of treatment with the ACE2 inhibitors. Patients enrolled in the study were individuals who were diagnosed with COVID-19 infection and septic shock, and who were undergoing treatment with ACE2 inhibitors/not taking ACE2 inhibitors; patients with septic shock who were not infected with COVID-19, and who were undergoing treatment with ACE2 inhibitors/not taking ACE2 inhibitors. According to lactate level, the studied patients were divided into subgroups: lactate <3 mMol/l, and lactate > 3 mmol/l. In patients with septic shock who were not infected with COVID-19 the main Causative microorganisms were gram-negative bacteria. In patients' blood the Interleukin-6 (IL-6), lactate, procalcitonin (PCT), pO2, and pulmonary pressure were investigated. Results of the study show that the rise in lactate levels in COVID-19-infected and non-infected patients was accompanied by an increase in PCT content and a decrease in pO2 level in blood. Therefore, serum lactate levels can be used as a prognostic marker of the severity of septic shock in COVID-19-infected and noninfected patients. In COVID-19-infected patients together with the increased lactate level, increases the level of IL-6, which indicates the important link between the quality of immunological disorders, inflammation, and COVID-19 infection in patients with ARDS and sepsis. These alterations were not prevented by the prior use of the ACE2 inhibitors. In COVID-19-infected and noninfected patients who didn't use ACE2 inhibitors, high lactate levels were accompanied by decreased pulmonary pressure which was normalized in patients who prior used ACE2 inhibitors.

IMPACT OF THE ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS ON THE COURSE OF THE SEPTIC SHOCK DEVELOPED DURING COVID-19 AND OTHER SEVERE RESPIRATORY INFECTIONS IN PRESENCE OF HYPERFERRITINEMIA.

SARS-CoV-2 can cause sepsis regardless of the presence of secondary bacterial or fungal infections. The virus itself likely causes sepsis through a variety of possible mechanisms, including immune dysregulation, with respiratory dysfunction, which as a result of circulatory dysfunction leads to hypoxemia and metabolic acidosis. We conducted cohort study, comparing outcomes of 212 critically ill patients with Septic shock (134 men (63.3%) and 78 women (36.7%), with a mean age between 40-70 years) were evaluated, who were treated in the intensive care unit of First University Clinic during 2020-2021 years. All four groups had documented Hyperferritinemia (HF). Patients were divided according to ferritin concentrations: moderate HF (ferritin <1500ng/ml) and severe HF (ferritin >1500ng/ml). The study aimed to reveal the impact of the Angiotensin-Converting enzyme -2 (ACE2) inhibitors on the course of the Septic shock developed during COVID-19 and other severe respiratory infections in conditions of hyperferritinemia (HF). Study results show that severe HF in patients with Septic shock is associated with a high risk of mortality and can be considered an indicator of the severity of the disease. The consumption of ACE2 inhibitors plays an important role in the regulation of inflammatory processes in both COVID-19-infected and non-infected patients with Septic shock: ACE2 inhibitors reduce the levels of Ang II and C reactive protein (CRP) in the blood in both COVID-19-infected and non-infected patients with Septic shock in conditions of moderate and severe HF; regulate the activity of leukocytes and the blood pro-coagulation system in both COVID-19-infected and non-infected patients with Septic shock in conditions of moderate HF; reduce the expression of pro-inflammatory cytokines (IL-6), decrease the level of D dimer in СOVID-infected patients in conditions of moderate HF; Procalcitonin levels do not differ between COVID-19 infected and non-infected patients with Septic shock. Based on our study, we can assume that there is the important link between elevated Ang 2 and the quality of immunological disorders and inflammation. The consumption of ACE2 inhibitors plays an important role in the regulation of inflammatory processes in both COVID-19-infected and non-infected patients with Septic shock.

Impact of the Angiotensin-Converting Enzyme (ACE) Inhibitors on the Course of the Acute Respiratory Distress Syndrome (ARDS) Developed During COVID-19 and Other Severe Respiratory Infections Under Hyperferritinemia Conditions: A Cohort Study.

Background: Angiotensin-converting enzyme 2 (ACE2) is not only the entry route of SARS-CoV-2 infection but also triggers a major mechanism of COVID-19 aggravation by promoting a hyperinflammatory state, leading to lung injury, hematological and immunological dysregulation. The impact of ACE2 inhibitors on the course of COVID-19 is still unclear. The effect of ACE2 inhibitors on the course of acute respiratory distress syndrome (ARDS) during COVID-19 and other severe respiratory infections in conditions of hyperferritinemia (HF) was investigated. Methods: A cohort study of critically ill patients with COVID-19 and other respiratory diseases (widespread infection, pneumonia) who underwent treatment in The Critical Care Unit of the First University Clinic (Tbilisi, Georgia) during the 2020-2021 years was conducted. The impact of the ACE2 inhibitors on the course of the ARDS developed during COVID-19 and other severe respiratory infections in conditions of different severity of HF was evaluated. Results: In COVID-19-infected (I) and uninfected (II) patients with ARDS, ACE2 inhibitors reduce the levels of Ang II, C reactive protein (CRP) and D-dimer (I: from 1508.07 ± 26.68 to 48.51 ± 24.35, from 233.92 ± 13.02 to 198.12 ± 11.88, from 7.88 ± 0.47 to 6.28 ± 0.43; II: from 1000.14 ± 149.49 to 46.23 ± 88.21, 226.48 ± 13.81 to 183.52 ± 17.32, from 6.39 ± 0.58 to 5.48 ± 0.69) at moderate HF and Ang II, CRP levels (I: from 1845.89 ± 89.37 to 49.64 ± 51.05, from 209.28 ± 14.41 to 175.37 ± 9.84; II: from 1753.29 ± 65.95 to 49.76 ± 55.74, 287.10 ± 20.50 to 214.71 ± 17.32) at severe HF, reduce interleukin-6 (IL-6) expression at moderate HF (I: from 1977.23 ± 354.66 to 899.36 ± 323.76) and cause reduction of pCO2 index at severe HF (I: from 69.80 ± 3.22 to 60.44 ± 2.20) in COVID-19-infected patients. Conclusion: Study results show that the ACE2 inhibitors play an important role in the regulation of inflammatory processes in both COVID-19-infected and uninfected patients with ARDS. ACE2 inhibitors decrease immunological disorders, inflammation, and lung alveoli dysfunction, especially in COVID-19-infected patients.