The intersection of obesity and (long) COVID-19: Hypoxia, thrombotic inflammation, and vascular endothelial injury

Abstract

The role of hypoxia, vascular endothelial injury, and thrombotic inflammation in worsening COVID-19 symptoms has been generally recognized. Damaged vascular endothelium plays a crucial role in forming in situ thrombosis, pulmonary dysfunction, and hypoxemia. Thrombotic inflammation can further aggravate local vascular endothelial injury and affect ventilation and blood flow ratio. According to the results of many studies, obesity is an independent risk factor for a variety of severe respiratory diseases and contributes to high mechanical ventilation rate, high mortality, and slow recovery in COVID-19 patients. This review will explore the mechanisms by which obesity may aggravate the acute phase of COVID-19 and delay long COVID recovery by affecting hypoxia, vascular endothelial injury, and thrombotic inflammation. A systematic search of PubMed database was conducted for papers published since January 2020, using the medical subject headings of “COVID-19” and “long COVID” combined with the following keywords: “obesity,” “thrombosis,” “endothelial injury,” “inflammation,” “hypoxia,” “treatment,” and “anticoagulation.” In patients with obesity, the accumulation of central fat restricts the expansion of alveoli, exacerbating the pulmonary dysfunction caused by SARS-CoV-2 invasion, inflammatory damage, and lung edema. Abnormal fat secretion and immune impairment further aggravate the original tissue damage and inflammation diffusion. Obesity weakens baseline vascular endothelium function leading to an early injury and pre-thrombotic state after infection. Enhanced procoagulant activity and microthrombi promote early obstruction of the vascular. Obesity also prolongs the duration of symptoms and increases the risk of sequelae after hospital discharge. Persistent viral presence, long-term inflammation, microclots, and hypoxia may contribute to the development of persistent symptoms, suggesting that patients with obesity are uniquely susceptible to long COVID. Early interventions, including supplemental oxygen, comprehensive antithrombotic therapy, and anti-inflammatory drugs, show effectiveness in many studies in the prevention of serious hypoxia, thromboembolic events, and systemic inflammation, and are therefore recommended to reduce intensive care unit admission, mortality, and sequelae.

Long-term outcomes of SARS-CoV-2 variants and other respiratory infections: evidence from the Virus Watch prospective cohort in England

“…We developed a directed acyclic graph (DAG) to determine the minimally sufficient adjustment set required to estimate the impact of infection status during each variant period of risk of post-acute sequelae (Supplementary Figure S2); the DAG was considered applicable to all infection status types given that the factors related to exposure to SARS-CoV-2 are relevant to other respiratory infections (vs. no infection). The minimally sufficient adjustment set suggested included age, sex, ethnicity, occupation, deprivation, comorbidities and vaccination status; BMI was also included in the adjustment set in the analyses due to its prominent influence on acute infections and development of long-term symptoms [36,37]. SARS-CoV-2 vaccination status modifies the risk of acquiring SARS-CoV-2 (dependent on the number of doses and waning due to time since recent dose) and consequently may influence infection status overall by altering the likelihood that an individual be included in the other ARI or no infection groups according to our definitions by influencing SARS-CoV-2 infection risk.…”

Cluster Analysis Identifies Long Covid Subtypes in Belgian Patients

“…Cluster 2, characterized by pure neurocognitive disorders (concentration, memory, and phasic disorders), might be a consequence of cerebral hypoxia, as this has been suggested as a pathophysiological mechanism for neurological symptoms associated with long Covid[25] [26]. In this group, an associated inflammatory component may also play a role in the onset of neurocognitive disorders.…”

The demographic, laboratory and genetic factors associated with Long Covid-19 Syndrome: a case-control study

“…The underlying mechanism for this phenomenon has been attributed to mitochondrial dysfunction and the production of reactive oxygen species caused by hyperglycemia in individuals with obesity. These processes lead to the production of pro-in ammatory mediators like leptin (a pro-in ammatory adipokine), TNF-α, IL-1, IL-6, and IL-18 [31]. These mediators can skew the immune response towards a low-grade chronic local in ammatory state, resulting in tissue damage, necrosis, and cellular dysfunction.…”

“…These mediators can skew the immune response towards a low-grade chronic local in ammatory state, resulting in tissue damage, necrosis, and cellular dysfunction. Over time, both innate and adaptive immune responses are systemically affected, rendering obese individuals more vulnerable to viral persistence and secondary infections [31,32].…”