Arterial Stiffness and Oxidized LDL Independently Associated With Post-Acute Sequalae of SARS-CoV-2

Abstract:

Objective: COVID-19 survivors can experience lingering symptoms known as post-acute sequelae of SARS-CoV-2 (PASC) that appear in different phenotypes, and its etiology remains elusive. We assessed the relationship of endothelial dysfunction with having COVID and PASC.

Methods: Data was collected from a prospectively enrolled cohort (n=379) of COVID-negative and COVID-positive participants with and without PASC. Primary outcomes, endothelial function (measured by reactive hyperemic index [RHI]), and arterial elasticity (measured by augmentation index standardized at 75 bpm [AI]), were measured using the FDA approved EndoPAT. Patient characteristics, labs, metabolic measures, markers of inflammation, and oxidized LDL (ox-LDL) were collected at each study visit, and PASC symptoms were categorized into 3 non-exclusive phenotypes: cardiopulmonary, neurocognitive, and general. COVID-negative controls were propensity score matched to COVID-negative-infected cases using the greedy nearest neighbor method.

Results: There were 14.3% of participants who were fully recovered COVID positive and 28.5% who were COVID positive with PASC, averaging 8.64 ± 6.26 total number of symptoms. The mean RHI was similar across the cohort and having COVID or PASC was not associated with endothelial function (P=0.33). Age (P<0.0001), female sex (P<0.0001), and CRP P=0.04) were positively associated with arterial stiffness, and COVID positive PASC positive with neurological and/or cardiopulmonary phenotypes had the worst arterial elasticity (highest AI). Values for AI (P=0.002) and ox-LDL (P<0.0001) were independently and positively associated with an increased likelihood of having PASC.

Conclusion: There is evidence of an independent association between PASC, ox-LDL, and arterial stiffness with neurological and/or cardiopulmonary phenotypes having the worst arterial elasticity. Future studies should continue investigating the role of oxidative stress in the pathophysiology of PASC.

Source: Zisis SN, Durieux JC, Mouchati C, Funderburg N, Ailstock K, Chong M, Labbato D, McComsey GA. Arterial Stiffness and Oxidized LDL Independently Associated With Post-Acute Sequalae of SARS-CoV-2. Pathog Immun. 2023 Dec 20;8(2):1-15. doi: 10.20411/pai.v8i2.634. PMID: 38156116; PMCID: PMC10753933. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10753933/ (Full text)

Increase in gut permeability and oxidized ldl is associated with post-acute sequelae of SARS-CoV-2

Abstract:

Background: Post-acute sequelae of SARS-CoV-2 (PASC) is marked by persistent or newly developing symptoms beyond 4 weeks of infection. Investigating gut integrity, oxidized lipids and inflammatory markers is important for understanding PASC pathogenesis.

Methods: A cross-sectional study including COVID+ with PASC, COVID+ without PASC, and COVID-negative (COVID-) participants. We measured plasma markers by enzyme-linked immunosorbent assay to assess intestinal permeability (ZONULIN), microbial translocation (lipopolysaccharide-binding protein or LBP), systemic inflammation (high-sensitivity C-reactive protein or hs-CRP), and oxidized low-density lipoprotein (Ox-LDL).

Results: 415 participants were enrolled in this study; 37.83% (n=157) had prior COVID diagnosis and among COVID+, 54% (n=85) had PASC. The median zonulin among COVID- was 3.37 (IQR: 2.13, 4.91) mg/mL, 3.43 (IQR: 1.65, 5.25) mg/mL among COVID+ no PASC, and highest [4.76 (IQR: 3.2, 7.35) mg/mL] among COVID+ PASC+ (p<.0001). The median ox-LDL among COVID- was 47.02 (IQR: 35.52, 62.77) U/L, 57.24 (IQR: 40.7, 75.37) U/L among COVID+ No PASC, and the highest [76.75 (IQR: 59.95, 103.28) U/L] among COVID+ PASC+ (p<.0001). COVID+ PASC+ was positively associated with zonulin (p=0.0002) and ox-LDL (p<.0001), and COVID- was negatively associated with ox-LDL (p=0.01), compared to COVID+ No PASC. Every unit increase in zonulin was associated with 44% higher predicted odds of having PASC [aOR: 1.44 (95%CI: 1.1, 1.9)] and every one-unit increase in ox-LDL was associated with more than four-fold increased odds of having PASC [aOR: 2.44 (95%CI: 1.67, 3.55)].

Conclusions: PASC is associated with increased gut permeability and oxidized lipids. Further studies are needed to clarify whether these relationships are causal which could lead to targeted therapeutics.

Source: Mouchati C, Durieux JC, Zisis SN, Labbato D, Rodgers MA, Ailstock K, Reinert BL, Funderburg NT, McComsey GA. Increase in gut permeability and oxidized ldl is associated with post-acute sequelae of SARS-CoV-2. Front Immunol. 2023 May 12;14:1182544. doi: 10.3389/fimmu.2023.1182544. PMID: 37251403; PMCID: PMC10217362. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10217362/ (Full text)