Potential long-term effects of SARS-CoV-2 infection on the pulmonary vasculature: Multilayered cross-talks in the setting of coinfections and comorbidities

Abstract

The Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its sublineages pose a new challenge to healthcare systems worldwide due to its ability to efficiently spread in immunized populations and its resistance to currently available therapies. COVID-19, although targeting primarily the respiratory system, is also now well established that later affects every organ in the body. Most importantly, despite the available therapy and vaccine-elicited protection, the long-term consequences of viral infection in breakthrough and asymptomatic individuals are areas of concern. In the past two years, investigators accumulated evidence on how the virus triggers our immune system and the molecular signals involved in the cross-talk between immune cells and structural cells in the pulmonary vasculature to drive pathological lung complications such as endothelial dysfunction and thrombosis. In the review, we emphasize recent updates on the pathophysiological inflammatory and immune responses associated with SARS-CoV-2 infection and their potential long-term consequences that may consequently lead to the development of pulmonary vascular diseases.

Exploring the incidence of peripheral arterial occlusive disease following COVID‐19 infection: A retrospective cohort study

“…The prolonged COVID-19 infection could increase the inflammatory response and damage to vasculature in the human body. 15,25 In previous studies, the incidence of coronary heart disease and CVDs also elevated even months after the COVID-19 infection. 10,26 The cumulative probability analysis of our study further supported the findings of the previous publication.…”

“…On the other hand, the incidence of PAOD in the COVID‐19 group was significantly higher than the non‐COVID‐19 group in all time points and the cumulative probability of PAOD episode increased significantly in the COVID‐19 group than the non‐COVID‐19 group. The prolonged COVID‐19 infection could increase the inflammatory response and damage to vasculature in the human body 15,25 . In previous studies, the incidence of coronary heart disease and CVDs also elevated even months after the COVID‐19 infection 10,26 .…”

Extracorporeal membrane oxygenation support for balloon atrial septostomy in a BMPR2 variant‐associated pulmonary arterial hypertension

“…4 The epigenetic mechanism may also contribute to the genetic bases for the etiopathogenesis of PAH, because the COVID-19 pandemic is known to be associated with PAH. 5 Tian et al 6 proposed the 2-hit model of the development of PAH, where 5-lipoxygenase-expressing adenovirus working through TGF-β pathway activation provoked the severe lung inflammation in BMPR2 +/− rats. The 5-lipoxygenase and TGF-β signaling drive the inflammatory process in association with virus infection.…”

CCR5/CXCR3 antagonist TAK-779 prevents diffuse alveolar damage of the lung in the murine model of the acute respiratory distress syndrome

“…Activation of the type I interferon (IFN I) response induces the recruitment of macrophages, NK cells, and neutrophils to the virus penetration site ( Tamir et al, 2022 ). It is believed that resident alveolar macrophages are the first defensive line to fight the virus ( Kumar et al, 2023 ), and neutrophils may undergo TNF-dependent necroptosis among seriously ill patients ( Schweizer et al, 2021 ; Mairpady Shambat et al, 2022 ). During the adaptive immune response stage, CD4 + and CD8 + T cells spread and hyperactivate, which may lead to a lack of reactivity or cell death ( Alberca and Baddour, 2021 ).…”