Mitochondria-induced formation of neutrophil extracellular traps is enhanced in the elderly via Toll-like receptor 9.

Neutrophil extracellular traps are potent antimicrobial weapons; however, their formation during sterile inflammation is detrimental, and the mechanism of induction is still unclear. Since advanced age is the primary clinical risk factor for poor outcomes in inflammatory diseases, we hypothesized that sterile stimuli, represented by mitochondria, would induce neutrophil extracellular trap formation in an age-dependent manner. Therefore, we analyzed induction of neutrophil extracellular traps in patients grouped according to age or immune status and observed that neutrophils from elderly patients responded to the presence of mitochondria with enhanced neutrophil extracellular trap formation. These neutrophil extracellular traps were also found to be more oxidized and exhibited higher resistance to DNase I degradation. Additionally, a higher concentration of residual neutrophil extracellular traps was detected in the plasma of the elderly. This plasma was capable of priming neutrophils through TLR9-mediated signaling, leading to further neutrophil extracellular trap formation, which was successfully inhibited with chloroquine. Finally, in a mouse model of mitochondria-induced acute lung injury, we observed that neutrophils from aged mice displayed impaired chemotactic activity but exhibited a trend of higher neutrophil extracellular trap formation. Thus, we propose that residual neutrophil extracellular traps circulating in the elderly preactivate neutrophils, making them more prone to enhanced neutrophil extracellular trap formation when exposed to mitochondria during sterile inflammation. Further investigation is needed to determine whether this vicious circle could be a suitable therapeutic target.

On the Origin of Neutrophil Extracellular Traps in COVID-19.

Despite ongoing vaccination COVID-19 is a global healthcare problem because of the lack of an effective targeted therapy. In severe COVID-19 manifesting as acute respiratory distress syndrome, uncontrolled innate immune system activation results in cytokine deregulation, damage-associated molecular patterns release upon tissue damage and high occurrence of thrombotic events. These pathomechanisms are linked to neutrophil function and dysfunction, particularly increased formation of neutrophil extracellular traps (NETs). While the association of NETs and severity of COVID-19 has been shown and proved, the causes of NETs formation are unclear. The aim of this review is to summarize potential inducers of NETs formation in severe COVID-19 and to discuss potential treatment options targeting NETs formation of removal.

Polymorbidity in seniors hospitalized for COVID-19.

BACKGROUND: The health of seniors is usually characterized by polymorbidity. With regard to quoad vitam prognosis, COVID-19 is extremely risky for seniors. The data on polymorbidity in seniors with COVID-19 are scarce. OBJECTIVE: To investigate comorbidity in seniors diagnosed with COVID-19 and requiring hospitalization. METHODS: In a retrospective observational study, we analyzed patients aged 65 years or older and hospitalized primarily for COVID-19 from November 1, 2020, to April 30, 2021 (n=155; mean age 82 years). We monitored the presence of 48 diseases accompanying COVID-19. RESULTS: The mean (minimal - maximal) number of acute, chronic and all comorbidities were 1.8 (0‒5), 11.3 (2‒20) and 13.1 (4‒22), respectively. Excessive comorbidity (>10 diseases) was present in 72.3 %. Comorbid arterial hypertension was diagnosed in 86 %, chronic kidney disease in 86 %, hepatopathy in 82 %, coronary artery disease in 79 %, dehydration in 46 %, and urinary infections in 30 %. Twenty-six chronic comorbidities had a prevalence of >10 %. Residents of social care facilities (SCF) had significantly higher polymorbidity than home-living seniors (on average by 3.5 more diseases, their OR for excessive polymorbidity was 11.8). The prevalence of overall, chronic and excess polymorbidity increased up to the age of 84 years. Nine out of ten seniors aged 80 years or older had 11 or more comorbidities. CONCLUSION: The burden of accompanying diseases in seniors with severe COVID-19 is very high. Seniors living in SCF are particularly at risk (Tab. 5, Fig. 8, Ref. 58).

24-hours mortality in seniors hospitalised with medical conditions.

AIM: Mortality is the hardest outcome characterising the severity of diseases and the result of the health care. It is connected mainly with elderly patients (pts.). Information on 24-hours hospital mortality (M24) in seniors admitted to nonsurgical departments is scarce. PATIENTS AND METHODS: In a retrospective observational study, we investigated M24 in pts. of 65 years of age and older, who were discharged from an university geriatric department in years 2016-2018. The identification of diseases which primarily led to M24 and their classification was independently performed by authors from geriatric and internal medicine departments. RESULTS: We proved that M24 is rather frequent (2.3 % out of all hospitalised pts.). There was a 2.4-fold M24 incidence increase from the age 65-69 years up to 90 years (from 1.4 to 3.3 %). The average age of deceased M24 pts. (n = 101) was 80.8 years and was not different from the age of those who deceased later. The majority of M24 (58.4 %) occurred during the first 12 hours after the admission to the hospital. There were many diseases (n = 25) that primarily led to M24 with dominating cardiovascular pathologies (39.6 %), followed closely by infective diseases (33.7 %). Therapeutically irreversible advanced chronic diseases led to M24 in 15.8 %. There was a higher frequency of acute diseases therapeutically irreversibly decompensating pre-existing diseases (43.6 %) than that of acute diseases incompatible with survival (33.7 %).