Cellular immune profiling of lung and blood compartments in patients with SARS-CoV-2 infection

Background: SARS-CoV-2 related immunopathology may be the driving cause underlying severe COVID-19. Through an immunophenotyping analysis on paired bronchoalveolar lavage fluid (BALF) and blood samples collected from mechanically ventilated patients with COVID-19-associated Acute Respiratory Distress Syndrome (CARDS), this study aimed to evaluate the cellular immune responses in survivors and non-survivors of COVID-19. Methods: A total of 36 paired clinical samples of bronchoalveolar lavage fluid (BALF) mononuclear cells (BALF-MC) and peripheral blood mononuclear cells (PBMC) were collected from 18 SARS-CoV-2-infected subjects admitted to the intensive care unit (ICU) of the Policlinico Umberto I, Sapienza University Hospital in Rome (Italy) for severe interstitial pneumonia. The frequencies of monocytes (total, classical, intermediate and non-classical) and Natural Killer (NK) cell subsets (total, CD56bright and CD56dim), as well as CD4+ and CD8+ T cell subsets [naïve, central memory (TCM) and effector memory (TEM)], and those expressing CD38 and/or HLADR were evaluated by multiparametric flow cytometry. Results: Survivors with CARDS exhibited higher frequencies of classical monocytes in blood compared to non-survivors (p < 0.05), while no differences in the frequencies of the other monocytes, NK cell and T cell subsets were recorded between these two groups of patients (p > 0.05). The only exception was for peripheral naïve CD4+ T cells levels that were reduced in non-survivors (p = 0.04). An increase in the levels of CD56bright (p = 0.012) and a decrease in CD56dim (p = 0.002) NK cell frequencies was also observed in BALF-MC samples compared to PBMC in deceased COVID-19 patients. Total CD4+ and CD8+ T cell levels in the lung compartment were lower compared to blood (p = 0.002 and p < 0.01, respectively) among non-survivors. Moreover, CD38 and HLA-DR were differentially expressed by CD4+ and CD8+ T cell subsets in BALF-MC and in PBMC among SARS-CoV-2-infected patients who died from COVID-19 (p < 0.05). Conclusions: These results show that the immune cellular profile in blood and pulmonary compartments was similar in survivors and non-survivors of COVID-19. T lymphocyte levels were reduced, but resulted highly immune-activated in the lung compartment of patients who faced a fatal outcome

Intraoperative use of extracorporeal CO2 removal (ECCO2R) and emergency ECMO requirement in patients undergoing lung transplant: a case-matched cohort retrospective study

Background: The use of extracorporeal carbon dioxide removal (ECCO2R) is less invasive than extracorporeal membrane oxygenation (ECMO), and intraoperative control of gas exchange could be feasible. The aim of this study in intermediate intraoperative severity patients undergoing LT was to assess the role of intraoperative ECCO2R on emergency ECMO requirement in patients. Methods: Thirty-eight consecutive patients undergoing lung transplantation (LT) with "intermediate" intraoperative severity in the intervals 2007 to 2010 or 2011 to 2014 were analyzed as historical comparison of case-matched cohort retrospective study. The "intermediate" intraoperative severity was defined as the development of intraoperative severe respiratory acidosis with maintained oxygenation function (i.e., pH <7.25, PaCO2 >60 mmHg, and PaO2/FiO2 >150), not associated with hemodynamic instability. Of these 38 patients, twenty-three patients were treated in the 2007-2010 interval by receiving "standard intraoperative treatment," while 15 patients were treated in the 2011-2014 interval by receiving "standard intraoperative treatment + ECCO2R." Results: ECMO requirement was more frequent among patients that received "standard intraoperative treatment" alone than in those treated with "standard intraoperative treatment + ECCO2R" (17/23 vs. 3/15; p = 0.004). The use of ECCO2R improved pH and PaCO2 while mean pulmonary artery pressure (mPAP) decreased. Conclusion: In intermediate intraoperative severity patients, the use of ECCO2R reduces the ECMO requirement

The role of hypothermic machine perfusion in selecting renal grafts with advanced histological score

Background Few studies explored the role of hypothermic machine perfusion (HMP) in the sub-group of non-standard renal grafts with a biopsy-proven advanced histological impairment. This study aimed to investigate the role of HMP in grafts with a Karpinski Score >3 in terms of the need for dialysis, creatinine reduction ratio at day-7 (CRR7), and 3-year graft survival. Methods Twenty-three perfused grafts with Karpinski Score >3 evaluated between November 2017 and December 2018 were retrospectively analyzed and compared with a control group of 32 non-perfused grafts transplanted between January 2014 and October 2017. Results After transplantation, perfused grafts had fewer cases requiring dialysis (8.7% vs. 34.4%; p = 0.051), a better reduction in serum creatinine (median at 7 days: 2.2 vs. 4.3 mg/dl; p = 0.045), and shorter length of hospital stay (median 11 vs. 15 days; p = 0.01). Three-year death-censored graft survival was better in the perfused cases (91.3% vs. 77.0%; p = 0.16). In perfused grafts, initial renal resistance (RR) had the best predictive value for renal function recovery after the first week, as defined by CRR7 <= 70% (AUC = 0.83; p = 0.02). A cut-off value of 0.5 mm Hg/ml/min showed a sensitivity of 82.4%, a specificity of 83.3%, and diagnostic odds ratio = 23.4. After dividing the entire population into a Low-RR (n = 8) and a High-RR Group (n = 15), more cases with CRR7 <= 70% were reported in the latter group (86.7 vs. 13.3%; p = 0.03). Conclusion HMP yielded promising results in kidneys with Karpinski Score >3. Initial RR should be of interest in selecting non-standard organs for single kidney transplantation even in impaired histology