ABSTRACT
The rapid emergence and subsequent global dissemination of SARS-CoV-2 disease (COVID-19) has resulted in over 4 million cases worldwide. The disease has a marked predilection for adults, and children are relatively spared. Understanding the age-based differences in pathophysiological pathways and processes relevant to the onset and progression of disease both in the clinical course and in experimental disease models may hold the key to the identification of therapeutic targets. The differences in the clinical course are highlighted by the lack of progression of the SARS-CoV-2 infection beyond mild symptoms in a majority of children, whereas in adults the disease progresses to acute lung injury and an acute respiratory distress syndrome (ARDS)-like phenotype with high mortality. The pathophysiological mechanisms leading to decreased lung injury in children may involve the decreased expression of the mediators necessary for viral entry into the respiratory epithelium and differences in the immune system responses in children. Specifically, decreased expression of proteins, including angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) in the airway epithelium in children may prevent viral entry. The immune system differences may include a relative preponderance of CD4+ T cells, decreased neutrophil infiltration, decreased production of proinflammatory cytokines, and increased production of immunomodulatory cytokines in children compared with adults. Notably, the developing lung in children may have a greater capacity to recover and repair after viral infection. Understanding the relative contributions of the above processes to the protective phenotype in the developing lung can guide the trial of the appropriate therapies in adults.
Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/drug therapy , Adult , Age Distribution , Angiotensin-Converting Enzyme 2 , COVID-19 , Child , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Cytokines/blood , Humans , Pandemics , Peptidyl-Dipeptidase A/immunology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , SARS-CoV-2 , Serine Endopeptidases/metabolismABSTRACT
BACKGROUND: Primary graft dysfunction (PGD) is a frequent complication after cardiac transplantation and remains one of the leading causes of mortality in these patients. The objective of this case-control study is to identify donor and surgical procedure's factors associated with PGD, and further guide possible strategies to prevent PGD. METHODS: Retrospective analysis of the medical records of patients who underwent cardiac transplantation at Memorial Hermann Hospital at Texas Medical Center between October 2012 and February 2015. RESULTS: The study population included 99 patients, of which 18 developed PGD. Univariate analysis of donor characteristics revealed opioid use (P = .049) and death owing to anoxia (P = .021) were associated with PGD. The recipient/donor blood type match AB/A was significantly associated with PGD (P = .031). Time from brain death to aortic cross clamp (TBDACC) of ≥3 and ≥5 days were also found to be associated with PGD (P = .0011 and .0003, respectively). Multivariate analysis confirmed that patients with a time from brain death to aortic cross clamp ≥3 and ≥5 days had lesser odds of developing PGD (odds ratio, 0.098 [P = .0026] and OR, 0.092 [P = .0017], respectively]. CONCLUSIONS: Our study showed that a longer time from brain death to aortic cross clamp was associated with lower odds of developing PGD. Therefore, postponing heart procurement for a few days after brain death seems to be beneficial in preventing PGD.
