The systemic capillary leak syndrome following COVID-19 vaccine

"Abstract

... With the extensive application of COVID-19 vaccines, rare but serious adverse reactions have gradually emerged, among which systemic capillary leak syndrome (SCLS) deserves our attention. SCLS is difficult to diagnose. Not only can it exacerbate various diseases, but also can lead to pulmonary edema, kidney failure, and even death. We summarized and discussed case reports of SCLS induced by COVID-19 vaccines to raise awareness of COVID-19 vaccine-associated rare diseases. We conducted a comprehensive search in Web of Science, PubMed and Embase and collected case reports of SCLS induced by COVID-19 vaccine before February 19, 2024. We identified and analyzed 12 articles, encompassing 15 cases. We synthesized the data to summarize possible mechanisms of SCLS, clinical manifestations, differential diagnoses, and therapeutic approaches.  Most SCLS occurred after vaccination with the Pfe-Biontech [Pfizer-Biontech] mRNA vaccine (9/15) and following the second vaccination (10/15). Almost all patients experienced hypotension (13/15) and tachycardia (11/15)... 4 patients died. Inflammation and endothelial cell damage may be linked to SCLS and COVID-19 vaccines. These findings highlight the necessity of focusing on serious adverse reactions of COVID-19 vaccines and the urgency to reconsider the safety of COVID-19 vaccines...

Discussion

... The specific mechanism of SCLS induced by COVID-19 vaccines is not completely clear, but literature suggests that both viral vector and mRNA COVID-19 vaccines induce strong activation of CD8+ T cells and CD4+ T cells, as well as the production of TNF-α, IFN-γ, and IL-210. Elevated IL-2 plays an important role in the inflammatory response and cytokine storm in COVID-19 patients. At the same time, IL-2 can enhance the production of nitric oxide synthase (NOS) and induce the production of NO, which directly or indirectly damages capillaries and leads to fluid leakage. Lim WC et al. showed that the expression of IL-6, G-CSF and GM-CSF in endothelial cells increased significantly under the synergistic effect of TNF-α and IFN-γ. In addition, Karki R et al. showed that the synergistic effect of TNF-α and IFN-γ could directly cause endothelial cell injury. IL-6 directly affects vascular endothelial cells, produces multiple types of cytokines and chemokines, and activates the coagulation cascade, resulting in endothelial dysregulation characterized by coagulation disorders and vascular leakage, while triggering cytokine storms. Cytokine storms will activate more immune cells, further aggravating endothelial cell injury and SCLS, forming a vicious cycle."