Pulmonary Procoagulant and Innate Immune Responses in Critically Ill COVID-19 Patients

Abstract

RationaleSystemic activation of procoagulant and inflammatory mechanisms has been implicated in the pathogenesis of COVID-19. Knowledge of activation of these host response pathways in the lung compartment of COVID-19 patients is limited.ObjectivesTo evaluate local and systemic activation of coagulation and interconnected inflammatory responses in critically ill COVID-19 patients with persistent acute respiratory distress syndrome.MethodsPaired bronchoalveolar lavage fluid and plasma samples were obtained from 17 patients with COVID-19 related persistent acute respiratory distress syndrome (mechanical ventilation > 7 days) 1 and 2 weeks after start mechanical ventilation and compared with 8 healthy controls. Thirty-four host response biomarkers stratified into five functional domains (coagulation, complement system, cytokines, chemokines and growth factors) were measured.Measurements and Main ResultsIn all patients, all functional domains were activated, especially in the bronchoalveolar compartment, with significantly increased levels of D-dimers, thrombin-antithrombin complexes, soluble tissue factor, C1-inhibitor antigen and activity levels, tissue type plasminogen activator, plasminogen activator inhibitor type I, soluble CD40 ligand and soluble P-selectin (coagulation), next to activation of C3bc and C4bc (complement) and multiple interrelated cytokines, chemokines and growth factors. In 10 patients in whom follow-up samples were obtained between 3 and 4 weeks after start mechanical ventilation many bronchoalveolar and plasma host response biomarkers had declined.ConclusionsCritically ill, ventilated patients with COVID-19 show strong responses relating to coagulation, the complement system, cytokines, chemokines and growth factors in the bronchoalveolar compartment. These results suggest a local pulmonary rather than a systemic procoagulant and inflammatory “storm” in severe COVID-19.

Complement activation in COVID-19 and targeted therapeutic options: A scoping review

“…C5 was only elevated in three studies measuring C5 levels [ 66 , 135 , 136 ]. MBL levels in plasma were in general higher in COVID-19 patients compared with healthy controls [ 134 , 137 , 138 ]. Overactivation of the alternative pathway was observed as well, especially in critically ill COVID-19 patients [ 12 , 16 , 43 , 122 , 139 ].…”

SARS-CoV-2 infection- induced growth factors play differential roles in COVID-19 pathogenesis

“…We found higher levels of both PDGF isoforms in COVID-19, which comply with our recent finding of elevated sCD40L in these patients [45] . These molecules are released by activated platelets and play a role in immune modulation and cell survival [46] , [47] . Interestingly, these factors work in conjunction in COVID-19 patients [37] , indicating their collaborating roles in pathomechanisms of COVID-19.…”

Angiotensin–Converting Enzyme (ACE) 1 Gene Polymorphism and Phenotypic Expression of COVID-19 Symptoms

“…However, as the condition worsened, it is accompanied by not only respiratory damage but also extra-pulmonary multi-organ failure, such as cardiovascular complications [10,11]. Severe COVID-19 is frequently associated with coagulation/fibrinolytic abnormalities characterized by increases in procoagulant factor levels, including fibrinogen, and increases in D-dimers that have been associated with higher mortality [12]. When blood vessels are clogged by blood clots, not only the lungs, but also various parts such as the heart and brain are damaged, and in the worst case, death may occur.…”