Assessment of Admission COVID-19 Associated Hyperinflammation Syndrome Score in Critically-Ill COVID-19 Patients

Abstract

Purpose We aimed to evaluate the relation between admission COVID-19 associated hyperinflammatory syndrome (cHIS) score and intensive care unit (ICU) outcomes. Materials and Methods Patients with laboratory confirmed COVID-19 admitted to our ICU between 20th March 2020-15th June 2021 were included. Patients who received immunomodulatory treatment except corticosteroids were excluded. Main outcomes were ICU mortality and invasive mechanical ventilation (IMV) requirement after ICU admission. Results Three hundred and seventy patients with a median (IQR) age of 66 (56-77) were analyzed. Median admission cHIS score was 3 (2-4). A cHIS score ≥3 was found to be associated with ICU mortality (sensitivity = 0.63, specificity = 0.50; p < 0.01) and IMV requirement after ICU admission (sensitivity = 0.61, specificity = 0.51; p < 0.01). Patients with an admission cHIS score ≥3 (n = 199) had worse median admission APACHEII, SOFA scores and PaO2/FiO2 ratio than others (n = 171) (p < 0.01). IMV requirement after ICU admission (38.5% vs 26.1%;p = 0.03), ICU (36.2% vs 25.1%;p = 0.02), hospital (39.1% vs 26.9%;p = 0.01) and 28th day (28.1% vs 19.1%;p = 0.04) mortality were higher in patients with admission cHIS score ≥3 than others (p < 0.01). Age <65 years, malignancy and higher admission SOFA score were independent variables associated with admission cHIS score ≥3. Conclusion Critically-ill COVID-19 patients with admission cHIS score ≥3 have worse disease severity and outcomes than other patients.

Investigational Use of Mesenchymal Stem/Stromal Cells and Their Secretome as Add-On Therapy in Severe Respiratory Virus Infections: Challenges and Perspectives

“…Tissue factor and hemocompatibility assessment [ 105 ] to be included for the evaluation of the product suitability for intravenous use MSC-derived extracellular vesicles isolated according to the guidelines of the International Society for Extracellular Vesicles [ 92 ] MSC-derived conditioned medium characterized for the presence of extracellular vesicles and for the contents of soluble biologically active factors [ 92 , 93 ]. Optimization of formulation and manufacturing [ 120 ] Scalable production according to the current Good Clinical Manufacturing guidelines Evaluation of the potency of the product (e.g., immunomodulatory/immunosuppressive properties assessed by mixed lymphocyte reaction) Dose estimated on the basis of preclinical studies or previous pilot clinical studies Characteristic of the clinical trials Prospective, randomized, double-blind, or open-label placebo-controlled two-arm studies in hospitalized patients with severe and critical COVID-19 and influenza Concomitant therapies with antivirals, glucocorticoids, and other immunomodulators and antiinflammatory agents according to current guidelines Sample size calculated to detect significant differences for the selected primary efficacy outcome Functional and biochemical parameters indicating the need for add-on therapy Patients showing rapidly increasing oxygen needs and systemic inflammation despite treatment with antivirals, immunomodulators, and antiinflammatory agents according to current guidelines Use of the Hyperinflammation Syndrome score at enrollment [ 113 , 114 ] Recording and monitoring of C-reactive protein, D-dimers, interleukin-6, serum ferritin concentrations, soluble urokinase plasminogen activator receptor, and leukocyte counts [ 106 , 110 – 112 ] Main outcome measures All-cause mortality at day 28 and at hospital discharge Clinical progression assessed daily by using the WHO Clinical Progression Scale [ 106 ] Secondary outcomes Length of stay in ICU Need for intubation Length of stay in the hospital Changes in biochemical parameters (C-reactive protein, D-dimers, interleukin-6, serum ferritin concentrations, soluble urokinase plasminogen activator receptor, leukocyte counts) Organ dysfunction score Pulmonary function at 1, 6, 12 months Radiological findings Tolerability and adverse events Viral burden assessed by quantitative real-time polymerase chain reaction Clinical data recording and reporting According to the Good Clinical practice guidelines Data for economic analysis …”

“…Finally, it should be considered that the high costs of MSC-based therapy would still represent an obstacle to its clinical acceptance [ 114 ], even if its effectiveness at reducing the healthcare expenditures associated with the prolonged hospitalizations of critically ill patients were conclusively demonstrated. The costs of obtaining clinical-grade allogeneic MSCs varies depending on the MSC source [ 114 ], and the use of cell-free MSC-derived products, such as exosomes and other extracellular vesicles, can greatly increase these costs.…”

“…Finally, it should be considered that the high costs of MSC-based therapy would still represent an obstacle to its clinical acceptance [ 114 ], even if its effectiveness at reducing the healthcare expenditures associated with the prolonged hospitalizations of critically ill patients were conclusively demonstrated. The costs of obtaining clinical-grade allogeneic MSCs varies depending on the MSC source [ 114 ], and the use of cell-free MSC-derived products, such as exosomes and other extracellular vesicles, can greatly increase these costs. The use of properly isolated MSC-derived exosomes would render the costs of the MSC-based therapy particularly high because of the expensive isolation procedure and the necessity to produce a huge number of clinical-grade vesicles to overcome problems with the biodistribution of these nanoparticles after intravenous infusion [ 108 , 115 ].…”

“…Tissue factor and hemocompatibility assessment [105] to be included for the evaluation of the product suitability for intravenous use MSC-derived extracellular vesicles isolated according to the guidelines of the International Society for Extracellular Vesicles [92] MSC-derived conditioned medium characterized for the presence of extracellular vesicles and for the contents of soluble biologically active factors [92,93]. Optimization of formulation and manufacturing [120] Scalable production according to the current Good Clinical Use of the Hyperinflammation Syndrome score at enrollment [113,114] Recording and monitoring of C-reactive protein, D-dimers, interleukin-6, serum ferritin concentrations, soluble urokinase plasminogen activator receptor, and leukocyte counts [106,[110][111][112] Main outcome measures All-cause mortality at day 28 and at hospital discharge Clinical progression assessed daily by using the WHO Clinical Progression Scale [106] immune activation, the elevated level of plasma soluble urokinase plasminogen activator receptor, which has been found to predict disease progression in hospitalized patients with COVID-19 and other viral pneumonia more accurately than other inflammatory parameters [109][110][111]. Alternatively, or concomitantly, a composite score such as the COVID-19-associated Hyperinflammation Syndrome score [112,113] may be introduced to evaluate the risk of further disease progression in critically ill patients already receiving the recommended immunomodulatory/antiinflammatory regimen (Table 7), although this score system still needs to be fully validated.…”