AUTHOR=Hohberger Bettina , Ganslmayer Marion , Lucio Marianna , Kruse Friedrich , Hoffmanns Jakob , Moritz Michael , Rogge Lennart , Heltmann Felix , Szewczykowski Charlotte , Fürst Julia , Raftis Maximilian , Bergua Antonio , Zenkel Matthias , Gießl Andreas , Schlötzer-Schrehardt Ursula , Lehmann Paul , Strauß Richard , Mardin Christian , Herrmann Martin 

TITLE=Retinal Microcirculation as a Correlate of a Systemic Capillary Impairment After Severe Acute Respiratory Syndrome Coronavirus 2 Infection

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.676554

DOI=10.3389/fmed.2021.676554

ISSN=2296-858X

ABSTRACT=<p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), affects the pulmonary systems via angiotensin-converting enzyme-2 (ACE-2) receptor, being an entry to systemic infection. As COVID-19 disease features ACE-2 deficiency, a link to microcirculation is proposed. Optical coherence tomography angiography (OCT-A) enables non-invasive analysis of retinal microvasculature. Thus, an impaired systemic microcirculation might be mapped on retinal capillary system. As recent OCT-A studies, analyzing microcirculation in two subdivided layers, yielded contrary results, an increased subdivision of retinal microvasculature might offer an even more fine analysis. The aim of the study was to investigate retinal microcirculation by OCT-A after COVID-19 infection in three subdivided layers (I). In addition, short-term retinal affections were monitored during COVID-19 disease (II). Considering (I), a prospective study (33 patients<sub>post−COVID</sub> and 28 controls) was done. Macula and peripapillary vessel density (VD) were scanned with the Spectralis II. Macula VD was measured in three layers: superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Analysis was done by the EA-Tool, including an Anatomical Positioning System and an analysis of peripapillary VD by implementing Bruch's membrane opening (BMO) landmarks. Overall, circular (c<sub>1</sub>, c<sub>2</sub>, and c<sub>3</sub>) and sectorial VD (s<sub>1</sub>-s<sub>12</sub>) was analyzed. Considering (II), in a retrospective study, 29 patients with severe complications of COVID-19 infection, hospitalized at the intensive care unit, were monitored for retinal findings at bedside during hospitalization. (I) Overall (<italic>p</italic> = 0.0133) and circular (c<sub>1</sub>, <italic>p</italic> = 0.00257; c<sub>2</sub>, <italic>p</italic> = 0.0067; and c<sub>3</sub>, <italic>p</italic> = 0.0345). VD of the ICP was significantly reduced between patients<sub>post−COVID</sub> and controls, respectively. Overall (<italic>p</italic> = 0.0179) and circular (c<sub>1</sub>, <italic>p</italic> = 0.0189) peripapillary VD was significantly reduced between both groups. Subgroup analysis of hospitalized vs. non-hospitalized patients<sub>post−COVID</sub> yielded a significantly reduced VD of adjacent layers (DCP and SVP) with increased severity of COVID-19 disease. Clinical severity parameters showed a negative correlation with VD (ICP) and peripapillary VD. (II) Funduscopy yielded retinal hemorrhages and cotton wool spots in 17% of patients during SARS-CoV-2 infection. As VD of the ICP and peripapillary regions was significantly reduced after COVID-19 disease and showed a link to clinical severity markers, we assume that the severity of capillary impairment after COVID-19 infection is mapped on retinal microcirculation, visualized by non-invasive OCT-A.</p>