key: cord-0833786-ilx9j89c
authors: Bakhoum, M. F.; Ritter, M.; Garg, A.; Chan, A. X.; Bakhoum, C. Y.; Smith, D.
title: Subclinical ocular inflammation in persons recovered from ambulatory COVID-19
date: 2020-09-23
journal: nan
DOI: 10.1101/2020.09.22.20128140
sha: fafc4d57490f6c21db6f83fcac48b78d09605de4
doc_id: 833786
cord_uid: ilx9j89c

Coronavirus disease 2019 (COVID-19) is characterized by striking variability in clinical severity, and a hyperinflammatory response in the lung is associated with high mortality. Little is known about the extent and duration of inflammation in persons recovering from COVID-19. Here, we used spectral domain optical coherence tomography (SD-OCT) to detect the presence of inflammatory cells in the vitreous cavity, an immune-privileged microenvironment, in persons recovered from COVID- 19. Our results provide quasi-histologic evidence that neuroinflammation is present in persons who recovered from COVID-19, only one of whom required hospitalization. Our results also suggest that persons who feel that their recovery is incomplete have evidence of subclinical eye inflammation, which may be a marker of residual inflammation elsewhere as well.

Coronavirus disease 2019 (COVID-19) is characterized by striking variability in clinical severity, and a hyperinflammatory response in the lung is associated with high mortality. Little is known about the extent and duration of inflammation in persons recovering from COVID-19. Here, we used spectral domain optical coherence tomography (SD-OCT) to detect the presence of inflammatory cells in the vitreous cavity, an immune-privileged microenvironment, in persons recovered from COVID-19. Our results provide quasihistologic evidence that neuroinflammation is present in persons who recovered from COVID-19, only one of whom required hospitalization. Our results also suggest that persons who feel that their recovery is incomplete have evidence of subclinical eye inflammation, which may be a marker of residual inflammation elsewhere as well.

Coronavirus disease 2019 (COVID-19) is characterized by striking variability in clinical severity, and a hyperinflammatory response in the lung is associated with high mortality. [1, 2] Little is known about the extent and duration of inflammation in persons recovering from COVID-19. Here, we used spectral domain optical coherence tomography (SD-OCT) to image individual cells in the vitreous cavity, an immune-privileged microenvironment, in persons recovered from COVID-19.

Individuals with history of COVID-19 but no history of uveitis were recruited. A 97-raster SD-OCT scan (Spectralis, Heidelberg) was obtained. Transverse B-scans were reviewed for the presence of cells in the vitreous cavity. [3] Grading of cells in the subhyaloid space was defined as 'rare' < 50 cells, 'few' 50 to 194 cells and 'many' >194 cells (average of more than 1 cell per B-scan). In eyes where a subhyaloid space was not present, 'many cells' were defined as >776 hyperreflective foci (average of more than 4 cells per B-scan).

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted September 23, 2020. . https://doi.org/10.1101/2020.09.22.20128140 doi: medRxiv preprint

Fifteen participants were evaluated (6 women and 9 men). All but one were previously diagnosed with active SARS-CoV-2 infection by polymerase chain reaction (PCR) 58 to 85 days prior to evaluation. One participant had symptoms consistent with COVID-19 and a simultaneous household contact with confirmed COVID-19.

Respiratory symptoms were present in all participants (Table) . Only Participant 14 required hospitalization. All met the criteria of recovery from the active viral phase. [4] Time from recovery ranged from 34 to 60 days (median 50 days). Post-recovery, four persons reported cough, two reported lower extremity weakness and numbness, one reported headaches, and one reported photophobia. On SD-OCT scans, 4 persons had few cells and 3 had many cells (Table and Figure) . Participants 4 and 14 had SD-OCT scans at our institution 6 months and 2 years prior that showed none to rare cells ( Figure, 

Here, we provide quasi-histologic evidence that neuroinflammation is present in persons who recovered from COVID-19, only one of whom required hospitalization. On OCT imaging, presence of numerous cells in the vitreous cavity is abnormal. Cells in the vitreous result from inflammation, hemorrhage or a neoplastic process. [3, 5, 6] Strikingly, in two participants OCT scans prior to their COVID-19 illness showed no evidence of inflammation in the vitreous, while their scans after COVID-19 showed hyperreflective foci, strongly suggesting that even ambulatory COVID-19 may lead to inflammatory cells persisting in the eye up to 1 month after recovery. Persons who felt that their recovery was incomplete had more cells, which likely suggests residual inflammation elsewhere. Our findings are congruent with emerging reports demonstrating that recovery . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted September 23, 2020. . https://doi.org/10.1101/2020.09.22.20128140 doi: medRxiv preprint from COVID-19 may be complicated by post-viral inflammation, and full symptomatic recovery may not occur until weeks after a positive test result, even in younger individuals [7, 8] .

were no molecular or cellular analysis of vitreous biopsies. The specificity of this finding to COVID-19 is unknown, as no similar study to our knowledge has been conducted in persons recovering from other respiratory viral or systemic illnesses. A larger study is needed to determine the true prevalence of vitreous cells in persons recovering from COVID-19, and a longitudinal study is needed to determine its long-term ocular health sequelae.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted September 23, 2020. . https://doi.org/10.1101/2020.09.22.20128140 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Significance was determined using one-way ANOVA (p = 0.01) and student's t test with Tukey's correction. 

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