COVID-19 and Life Threatening Cardiac and Cerebellar Thromboembolic Events in Cardiac Operations

There are several reported cases that have showed that COVID-19 is a highly thrombogenic disease. The release of cytokines during cardiopulmonary bypass plus COVID 19 related thrombogenic factors can trigger life-threatening thromboembolic events as we have experienced with these two young patients.

Myocarditis was rare in COVID-19 in an autopsy population of 277 subjects; however, COVID-19-related cardiovascular histopathologic findings, such as macro or microvascular thrombi were reported in nearly half of the cases 11. There was no definitive evidence of direct myocardial infection detected in a detailed histopathologic, immune-histochemical, ultrastructural, and molecular cardiac series; however, COVID-19 cases frequently have cardiac fibrin micro-thrombi 12. SARS-CoV-2 stimulates extracellular neutrophils traps (NETs) in a process called NETosis in association with increased levels of intracellular Reactive Oxygen Species (ROS) in neutrophils; the ROS-NET pathway plays a role in thrombosis formation 13. The SARS-CoV2 virus directly infects immune cells and dysregulates the immune system. It also infects endothelial cells and damages them, activates leukocytes to potentiate pro-coagulant states via the release of intravascular tissue factor, platelet activation, NETo sis, and inhibition of anticoagulant mechanisms 14. The presence of SARS-CoV-2 virus within the endothelial cells suggests that direct viral infection induces inflammation of the endothelium as well as host inflammatory response which may further contribute to endothelial injury 15,16.

Fatal COVID-19 is characterized as a cytokine release syndrome (CRS) that is induced by a cytokine storm with high mortality 17. Cytokines are the mediators of inflammation and immunity. Cytokines modulate the recruitment and activation of leukocytes, activate platelet aggregation, bind to endothelial cells, immobilize leukocytes resulting in vascular occlusion, and thrombosis 18. The raised CRP of these patients could be an indicator of the severity of illness due to COVID-19 19,20 or just a response of recent surgery. Even patients with mild forms of COVID-19 remain at risk for COVID-19-associated coronary and cerebral thrombosis, and coagulopathy 21. Arterial thromboembolic events were also noticed in 9.6% of admitted patients with severe COVID-19 infection 23.
Additionally, both patients were asymptomatic prior to the operation and had negative upper respiratory tract COVID 19 swabs. SARS-CoV-2 RNA was detected in postoperative Broncho-alveolar Lavage by PCR 1. They remained stable during the initial postoperative period, then developed major life-threatening thromboembolic events. The question arises whether bronchioalveolar lavage to test for SARS-CoV-2 immediately post intubation should be routinely carried out, for those patients who had recent negative swabs? If the result is positive and available prior to start of the operation, surgeons can postpone non-urgent/emergency operations. However, if a positive result is obtained during/after the operation, the aim should be to keep a hypo-coagulable status. Combination therapy with antiplatelet and treatment dose anticoagulation should be considered at very early postoperative hours in SARS-CoV-2 positive patients. Furthermore, these anticoagulant therapies can also be considered in adjuvant to other therapies in severe COVID 19 infections. A randomized clinical trial called DICER is testing dipyridamole in patients with confirmed coronavirus (SARS-CoV)-2 infections, to assess if it is effective in reducing excessive blood clots 24.

Acknowledgements

Thank you to Dr Hakeem Oluwatoyin Yusuff, Dr Meenal Rana, Dr Patricia Romero Palomino and Professor Sanjay Agrawal for their contribution in the management.

References

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