Emergence of immunosuppressive LOX-1+ PMN-MDSC in septic shock and severe COVID-19 patients with acute respiratory distress syndrome.

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells with immunosuppressive properties. In cancer patients, the expression of lectin-type oxidized LDL receptor 1 (LOX-1) on granulocytic MDSC identifies a subset of MDSC that retains the most potent immunosuppressive properties. The main objective of the present work was to explore the presence of LOX-1+ MDSC in bacterial and viral sepsis. To this end, whole blood LOX-1+ cells were phenotypically, morphologically, and functionally characterized. They were monitored in 39 coronavirus disease-19 (COVID-19, viral sepsis) and 48 septic shock (bacterial sepsis) patients longitudinally sampled five times over a 3 wk period in intensive care units (ICUs). The phenotype, morphology, and immunosuppressive functions of LOX-1+ cells demonstrated that they were polymorphonuclear MDSC. In patients, we observed the significant emergence of LOX-1+ MDSC in both groups. The peak of LOX-1+ MDSC was 1 wk delayed with respect to ICU admission. In COVID-19, their elevation was more pronounced in patients with acute respiratory distress syndrome. The persistence of these cells may contribute to long lasting immunosuppression leaving the patient unable to efficiently resolve infections.

Microcirculatory, Endothelial, and Inflammatory Responses in Critically Ill Patients With COVID-19 Are Distinct From Those Seen in Septic Shock: A Case Control Study.

ABSTRACT: Critically ill patients with COVID-19 infection frequently exhibit a hyperinflammatory response and develop organ failures; however, the underlying mechanisms are unclear. We investigated the microcirculatory, endothelial, and inflammatory responses in critically ill COVID-19 patients and compared them to a group of patients with septic shock in a prospective observational case control study. Thirty critically ill patients with COVID-19 were compared to 33 patients with septic shock.Measurements of sublingual microcirculatory flow using Incident Dark Field video-microscopy and serial measurements of IL-6 and Syndecan-1 levels were performed. COVID-19 patients had significantly less vasoactive drug requirement and lower plasma lactate than those with septic shock. Microcirculatory flow was significantly worse in septic patients than those with COVID-19 (MFI 2.6 vs 2.9 p 0.02, PPV 88 vs 97% P < 0.001). IL-6 was higher in patients with septic shock than COVID-19 (1653 vs 253 pg/mL, P 0.03). IL-6 levels in COVID 19 patients were not elevated compared to healthy controls except on the day of ICU admission. Syndecan-1 levels were not different between the two pathological groups. Compared to patients with undifferentiated septic shock an overt shock state with tissue hypoperfusion does not appear typical of COVID-19 infection. There was no evidence of significant sublingual microcirculatory impairment, widespread endothelial injury or marked inflammatory cytokine release in this group of critically ill COVID-19 patients.

Mesenchymal stromal cells for sepsis and septic shock: Lessons for treatment of COVID-19.

Sepsis is defined as life-threatening organ dysfunction caused by a deregulated immune host response to infection. The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted this multifactorial and complex syndrome. The absence of specific treatment neither against SARS-CoV-2 nor against acute respiratory distress syndrome (ARDS), the most serious stage of this infection, has emphasized the need to find alternative treatments. Several therapeutics are currently being tested, including mesenchymal stromal cells. These cells, already used in preclinical models of ARDS, sepsis, and septic shock and also in a few clinical trials, appear well-tolerated and promising, but many questions remain unanswered.

Possible Cause of Inflammatory Storm and Septic Shock in Patients Diagnosed with (COVID-19).

The novel coronavirus (SARS-CoV-2) infection which has been known as Coronavirus diseases 2019 COVID-19 has become an endemic emergent situation by the World Health Organization. So far, no successful specific treatment has been found for this disease. As has been reported, most of non-survivor patients with COVID-19 (70%) had septic shock which was significantly higher than survived ones. Although the exact pathophysiology of septic shock in these patients is still unclear, it seems to be possible that part of it would be due to the administration of empiric antibiotics with inflammatory properties especially in the absence of bacterial infection. Herein, we have reviewed possible molecular pathways of septic shock in the patients who have received antibiotics with inflammatory properties which mainly is release of interleukin 1ß (IL-1ß), IL-6, and tumor necrosis factor α (TNF- α) through different routes. Altogether, we highly recommend clinicians to look after those antibiotics with anti-inflammatory activity for both empiric antibiotic therapy and reducing the inflammation to prevent septic shock in patients with diagnosed COVID-19.