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. 2022 Sep;106(9):1313-1317.
doi: 10.1136/bjophthalmol-2020-318618. Epub 2021 Apr 9.

Detection of SARS-CoV-2 genomic and subgenomic RNA in retina and optic nerve of patients with COVID-19

Maria Casagrande #  1 , Antonia Fitzek #  2 , Martin Spitzer  3 , Klaus Püschel  2 , Markus Glatzel  4 , Susanne Krasemann  4 , Martin Aepfelbacher  5 , Dominik Nörz  5 , Marc Lütgehetmann  5 , Susanne Pfefferle  5 , Maximilian Schultheiss  3
Affiliations

Detection of SARS-CoV-2 genomic and subgenomic RNA in retina and optic nerve of patients with COVID-19

Maria Casagrande et al. Br J Ophthalmol. 2022 Sep.

Erratum in

Abstract

Purpose: Presence of SARS-CoV-2 RNA in human retinal biopsies (RBs) was previously reported by us. In this consecutive study, we analysed RB and optic nerve biopsies (ONBs) in deceased patients with confirmed COVID-19 assessing viral RNA load, possible virus replication and infectivity.

Patients and methods: In this case series, 14 eyes of 14 deceased patients with COVID-19 were enucleated during autopsy. RB and ONB were subjected to molecular detection of viral RNA, virus cultivation and immunohistochemistry. SARS-CoV-2 RNA loads were compared with RNA loads in the respective throat swabs, vitreous humour and blood samples.

Results: SARS-CoV-2 RNA was detected in 7/14 RBs and in 10/13 ONBs. While virus isolation failed and immunohistochemistry of SARS-CoV-2 spike protein was negative, subgenomic RNA (sgRNA) was detectable (40% RB; 60% ONB).

Conclusion: SARS-CoV-2 RNA is detectable in RB and ONB of patients with COVID-19. Presence of sgRNA could point to a SARS-CoV-2 infection of neuronal tissue, but as virus isolation failed and immunohistochemistry of SARS-CoV-2 spike protein was negative, an active infection seems unlikely.

Keywords: COVID-19; microbiology; optic nerve; retina.

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Conflict of interest statement

Competing interests: MS reported receiving grants from Novartis, IDxDR and Boehringer Ingelheim; and personal fees from Bayer, Oxurion, Roche, Allergan, Alcon, Neurogene and GSK outside the submitted work.

Figures

Figure 1
Figure 1
Detection of SARS-CoV-2 RNAs. SARS-CoV-2 RNA loads in eye samples, blood and throat swabs are displayed for each patient (patient number on the x-axis) (A); blank cells reflect SARS-CoV-2 RT-PCR negative samples, and X indicates samples that were not available for analysis. For eye samples, virus-to-cell ratio (B) and levels of sgRNA (C) are illustrated. Mean values are given by horizontal bars. Negative samples are shown below the horizontal bar marked ‘neg’. SARS-CoV-2 infected Vero cells served as positive control, while cell culture supernatants of the respective cultures served as negative control. sgRNA, subgenomic RNA.
Figure 2
Figure 2
Histology and immunohistochemistry: retina and optic nerve. Retinal sections of COVID-19 deceased patients are displayed in figure panels A–D, sections of the optic nerve respectively in figure panels E–H. (A and B) PCR-negative retina. (A) H&E staining, 20× magnification; (B) SARS-CoV-2 spike protein. (C and D) PCR-positive retina. (C) (H&E), 20× magnification; (D) SARS-CoV-2 spike protein. (E and F) PCR-negative optic nerve. (E) H&E staining, 20× magnification; (F) SARS-CoV-2 spike protein. (G and H) PCR-positive optic nerve.
See this image and copyright information in PMC

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