Table 1 The influence of the SARS-CoV-2 on the pathophysiology of severe COVID-19 patients and ECMO-related therapeutic effects and complications

Respiratory system

Patients with COVID-19 are mainly predominant by respiratory failure. The pathophysiology of progression to ARDS in COVID-19 patients is very complicated. SARS-CoV-2 directly attacks enough alveoli epithelial cells via the ACE2 receptor to cause pulmonary edema, hyaline membrane formation and collapse of lobular of the lungs. Hypoxic pulmonary vasoconstriction failure, pulmonary embolism and/or pulmonary microcirculation embolism, abnormal immune response may also contribute to the development of ARDS

V-V ECMO mainly provides therapeutic benefits to the respiratory system by improving oxygenation and promoting lung-protective ventilation

Cardiovascular system

It is the second cause of death after respiratory failure in COVID-19 patients. There are several possible mechanisms contributing to cardiac injury: direct injury from viral toxicity; oxygen supply-to-demand mismatch cause damage to myocardial cells; abnormal coagulation, microvascular dysfunction and plaque rupture; systemic inflammatory response and immune system disorders bringing stress to the failing myocardium and leading to further depression in myocardial function

V-A ECMO can support highly selected cases with clear evidence of refractory left ventricle dysfunction. When differential hypoxemia complicating V-A ECMO happens, hybrid V-V/V-A ECMO can be used as a remedial option. A small number of patients using ECMO could bring cardiovascular complications, including atrial thrombosis, fatal arrhythmia, etc

Blood system

Coagulation: COVID-19 patients are characterized by a hypercoagulable state, and associated with a high incidence of thrombosis. The possible mechanism is that the direct impact of SARS-CoV-2 or related excessive inflammatory state leads to the activation of blood coagulation function

Immune response: Higher-risk COVID-19 subgroups tended to have lymphopenia yet with overall leukocytosis and high inflammatory markers (CRP, fibrinogen, ferritin, IL-6). The SARS-CoV-2 attack of cytoplasmic component of the lymphocyte, spleen and lymph nodes, and the intensification in local and systemic inflammation may contribute to lymphopenia

Coagulation: ECMO can cause abnormal blood coagulation function, which can lead to thrombosis and bleeding events. Thrombosis events in COVID-19 patients receiving ECMO treatment is more common

Immune response: On the one hand, ECMO technology have a certain effect of inflammatory activation. On the other hand, ECMO can reduce systemic inflammation indicators by protecting lung ventilation and completely reversing the state of systemic hypoxia

It is worth noting that adequate level of anticoagulant therapy with unfractionated heparin during ECMO is a very huge challenge clinically, because of the COVID-19-related prothrombotic state and the high risk of HIT trigger

Cerebrovascular

The incidence of ischemic stroke in patients with COVID-19 is 10.3%, and most patients have conventional stroke risk factors. Hemorrhagic stroke is relatively rare, with an incidence of 0.9%. The coagulation abnormalities of COVID-19 contributed to this result

The most common ECMO-related cerebrovascular complication is cerebral hemorrhage, with rates up to 21%

Liver

Hepatic dysfunction was seen in 14–53% of COVID-19 patients, particularly in patients hospitalized in ICU (62%), while severe liver failure is rare. SARS-CoV-2 involvement may be related to viral direct damage to liver cells, severe infection, uncontrolled immune response

ECMO is not recommended for patients with severe liver failure

Kidney

The prevalence of AKI among COVID-19 patients ranges from 0.5% to 5.1%, and its severity were highly correlated with poor outcomes. The potential mechanisms may include three aspects: cytokine damage, organ crosstalk and systemic effects

Improvement in kidney oxygenation due to V-V ECMO could be favorable to kidney recovery. Though, ECMO may also aggravate kidney damage by promoting cytokine generation