COVID-19 ve Endotelyal Disfonksiyon: Moleküler Yaklaşım
Özet
COVID-19, SARS-CoV-2 virüsünün yol açtığı, dünya genelinde hızla yayılarak küresel halk sağlığını tehdit eden ve çoklu organ yetmezliğine neden olabilen multisistemik bir hastalıktır. Virüs, konakçı hücreye yüzeyindeki ACE2 reseptörüne bağlanarak giriş yapar; bu reseptörün farklı dokularda bulunması hastalığın multisistemik etkilerini ve bireyler arası seyir farklılıklarını açıklar. Klinik seyir hafif, orta, ciddi ve kritik olarak sınıflandırılmakta, ağır vakalarda hiperinflamasyonla karakterize sitokin salınımı sendromu (sitokin fırtınası) gelişmektedir. Son kanıtlar, şiddetli COVID-19 patofizyolojisinde endotel disfonksiyonunun ve sistemik endotelitin merkezi bir rol oynadığını; derin ven trombozu, pulmoner emboli ve mikrovasküler tromboz gibi jeneralize trombotik mikroanjiyopati tablolarının ortak paydası olduğunu göstermektedir. Ayrıca ileri yaş, hipertansiyon, diyabet ve obezite gibi kardiyovasküler risk faktörlerine sahip bireylerde endotel hasarı nedeniyle hastalığın daha şiddetli seyrettiği bildirilmiştir. Hastalığın takibinde ve kötü prognozun belirlenmesinde D-dimer, von Willebrand Faktör (vWF), PAI-1, Endotelin-1, sICAM-1, ADMA ve CRP gibi endotel disfonksiyonu biyobelirteçleri kritik öneme sahiptir. Vasküler homeostazı düzenleyen eNOS kaynaklı nitrik oksit (NO) düzeyindeki azalma ise oksidatif stresi artırarak endotel hasarını ve viral duyarlılığı şiddetlendirmektedir.
COVID-19 is a multisystemic disease caused by the SARS-CoV-2 virus, which has rapidly spread worldwide, threatening global public health and potentially causing multi-organ failure. The virus enters the host cell by binding to the ACE2 receptor on the cell surface; the presence of this receptor in various tissues explains the multisystemic effects and the variance in clinical course among individuals. The clinical course is classified as mild, moderate, severe, and critical, with heavy cases developing cytokine release syndrome (cytokine storm) characterized by hyperinflammation. Recent evidence indicates that endothelial dysfunction and systemic endotheliitis play a central role in severe COVID-19 pathophysiology, serving as the common denominator for generalized thrombotic microangiopathy conditions such as deep vein thrombosis, pulmonary embolism, and microvascular thrombosis. Furthermore, it has been reported that the disease progresses more severely in individuals with cardiovascular risk factors like advanced age, hypertension, diabetes, and obesity due to endothelial injury. Endothelial dysfunction biomarkers, including D-dimer, von Willebrand Factor (vWF), PAI-1, Endothelin-1, sICAM-1, ADMA, and CRP, are of critical importance in tracking the disease and determining poor prognosis. Conversely, the decrease in eNOS-derived nitric oxide (NO) levels, which regulates vascular homeostasis, increases oxidative stress, thereby exacerbating endothelial damage and viral susceptibility.
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