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. 2024 Apr 10;14(1):8395.
doi: 10.1038/s41598-024-56834-4.

Impaired retinal oxygen metabolism and perfusion are accompanied by plasma protein and lipid alterations in recovered COVID-19 patients

Viktoria Pai  1 , Andrea Bileck  2   3 , Nikolaus Hommer  1 , Patrick Janku  1 , Theresa Lindner  1 , Victoria Kauer  1   4 , Benedikt Rumpf  4 , Helmuth Haslacher  5 , Gerhard Hagn  2 , Samuel M Meier-Menches  2   3   6 , Leopold Schmetterer  1   7   8   9   10   11   12 , Doreen Schmidl  1 , Christopher Gerner  13   14 , Gerhard Garhöfer  15
Affiliations

Impaired retinal oxygen metabolism and perfusion are accompanied by plasma protein and lipid alterations in recovered COVID-19 patients

Viktoria Pai et al. Sci Rep. .

Abstract

The aim of the present study was to investigate retinal microcirculatory and functional metabolic changes in patients after they had recovered from a moderate to severe acute COVID-19 infection. Retinal perfusion was quantified using laser speckle flowgraphy. Oxygen saturation and retinal calibers were assessed with a dynamic vessel analyzer. Arterio-venous ratio (AVR) was calculated based on retinal vessel diameter data. Blood plasma samples underwent mass spectrometry-based multi-omics profiling, including proteomics, metabolomics and eicosadomics. A total of 40 subjects were included in the present study, of which 29 had recovered from moderate to severe COVID-19 within 2 to 23 weeks before inclusion and 11 had never had COVID-19, as confirmed by antibody testing. Perfusion in retinal vessels was significantly lower in patients (60.6 ± 16.0 a.u.) than in control subjects (76.2 ± 12.1 a.u., p = 0.006). Arterio-venous (AV) difference in oxygen saturation and AVR was significantly lower in patients compared to healthy controls (p = 0.021 for AVR and p = 0.023 for AV difference in oxygen saturation). Molecular profiles demonstrated down-regulation of cell adhesion molecules, NOTCH3 and fatty acids, and suggested a bisphasic dysregulation of nitric oxide synthesis after COVID-19 infection. The results of this study imply that retinal perfusion and oxygen metabolism is still significantly altered in patients well beyond the acute phase of COVID-19. This is also reflected in the molecular profiling analysis of blood plasma, indicating a down-regulation of nitric oxide-related endothelial and immunological cell functions.Trial Registration: ClinicalTrials.gov ( https://clinicaltrials.gov ) NCT05650905.

Keywords: COVID-19; Metabolomics; Multi-omics analysis; Ocular blood flow; SARS-CoV2.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Arteriovenous ratio in vessel diameter in healthy subjects and patients that had recovered from COVID-19. The top of the box represents the 75th percentile, the bottom of the box represents the 25th percentile, and the line in the middle represents the 50th percentile. The whiskers represent the highest and lowest values. *p < 0.05 between groups.
Figure 2
Figure 2
Arteriovenous difference in oxygen saturation in healthy subjects and patients that had recovered from COVID-19. The top of the box represents the 75th percentile, the bottom of the box represents the 25th percentile, and the line in the middle represents the 50th percentile. The whiskers represent the highest and lowest values. *p < 0.05 between groups.
Figure 3
Figure 3
MV in retinal vessels in healthy subjects and patients that had recovered from COVID-19. The top of the box represents the 75th percentile, the bottom of the box represents the 25th percentile, and the line in the middle represents the 50th percentile. The whiskers represent the highest and lowest values. **p < 0.01 between groups.
Figure 4
Figure 4
Systemic molecular alterations consequent to COVID-19 infection are visualized by volcano plots (left) and principal component analysis (PCA, right). Volcano plots of (A) eicosanoids and fatty acids as well as (B) proteins display significant changes of molecules in red. (C) Volcano plot of metabolites shows no significant changes but a uniform up-regulation of triglycerides marked in red.
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References

    1. Feikin DR, et al. Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: Results of a systematic review and meta-regression. Lancet. 2022;399:924–944. doi: 10.1016/S0140-6736(22)00152-0. - DOI - PMC - PubMed
    1. Michelen M, et al. Characterising long COVID: A living systematic review. BMJ Glob. Health. 2021 doi: 10.1136/bmjgh-2021-005427. - DOI - PMC - PubMed
    1. Tereshchenko LG, et al. Risk of cardiovascular events after COVID-19. Am. J. Cardiol. 2022;179:102–109. doi: 10.1016/j.amjcard.2022.06.023. - DOI - PMC - PubMed
    1. Koyama AK, et al. Risk of cardiovascular disease after COVID-19 diagnosis among adults with and without diabetes. J. Am. Heart Assoc. 2023;12:e029696. doi: 10.1161/jaha.123.029696. - DOI - PMC - PubMed
    1. Salah HM, et al. Post-recovery COVID-19 and incident heart failure in the national COVID cohort collaborative (N3C) study. Nat. Commun. 2022;13:4117. doi: 10.1038/s41467-022-31834-y. - DOI - PMC - PubMed

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