key: cord-1047201-c8dz0eif
authors: Kumaran, Neruban; Sekhawat, Vivek; Mahadeva, Ula; Green, Anna; Douthwaite, Sam; Wong, Roger
title: Absence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in ocular post-mortem studies
date: 2020-10-20
journal: Can J Ophthalmol
DOI: 10.1016/j.jcjo.2020.10.009
sha: 6054461d07600362109c1e157e89e10406325cc5
doc_id: 1047201
cord_uid: c8dz0eif

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the Coronavirus disease 2019 (COVID-19), has infected over 15 million people and caused over 600,000 deaths globally, as of the 26 th July 2020. 1 Interestingly, the pooled prevalence of ocular manifestations among COVID-19 patients is thought to be as low as 5.5% 2 with conjunctivitis accounting for the majority. Alongside this there has been considerable interest as to whether Ophthalmic surgery can generate aerosols and ultimately whether such surgery can result in possible transmission. 3 Little however is known regarding the presence of SARS-Cov-2 in intraocular tissues with only one post-mortem study to date, to the authors' knowledge. 4 In this study, Bayyoud et al. demonstrate the absence of SARS-Cov-2 in multiple ocular sites (including conjunctiva, cornea, aqueous, vitreous sclera and optic nerve) of one patient.

Further to this, we too describe the absence of SARS-Cov-2 in ocular post mortem studies of three patients with known SARS-Cov-2 (Table 1) . Notably, none of the patients displayed signs of conjunctivitis. Furthermore, none of the patients received remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, which has been used by some for those with SARS-Cov-2. Ocular post mortem samples were taken in conjunction with samples from other non-ocular sites with no chemical sprays used. Conjunctival swabs were taken without excessive force being applied. Aqueous and vitreous biopsies of as greater volume as possible, were taken. Samples were taken from both eyes. Aqueous samples from each eye were combined for analysis with the same procedure for vitreous samples.

Given the relatively smaller volume of the anterior chamber and vitreous cavity, these ocular samples were less than that of other non-ocular samples. In our study we used two different PCR assays. The AusDiagnostics PCR assay was used locally, at St Thomas' Hospital, London, to test for multiple respiratory pathogens and has been identified to have a sensitivity of 98.4% for SARS-Cov-2. 5 In comparison, samples sent to the Respiratory Virus Unit Laboratory, Public Health England, London, UK were analysed using a real-time reverse transcription (RT) PCR assay using primers and probe sequences made public by CDC China. 6 This targeted a conserved region of the open reading frame (ORF1ab) gene of SARS CoV-2, alongside an internal control to monitor the extraction and RT-PCR processes, with a specificity thought to be greater than 95% (personal communication).

We note the limitation of the small number of patients in our study and its post-mortem nature. However, this also highlights the benefit of future studies investigating the presence of SARS-Cov-2 from ocular samples of live subjects. Additionally, as future therapies become available for the treatment of SARS-Cov-2, it will be useful to know more about associated ocular penetration, of which there is little in the literature to date.

Interestingly, our study demonstrates the presence of SARS-Cov-2 in similar non-ocular sites to other studies performed in a similar time frame, highlighting that SARS-Cov-2 can be detected up to at least 9 days. 7 Interestingly, much controversy exists regarding the ability of SARS-Cov-2 to infect ocular structures. 8 It is understood that cellular infection with SARS-Cov-2 is reliant on SARS-Cov-2 S protein / Angiotensin-Converting-Enzyme-2 (ACE-2) receptor interaction, with limited evidence of such protein expression in the eye. 9 Though, understandably, adequate personal protection is recommended for those in an Ophthalmic outpatient and surgical setting.

Further to the above, we feel our results support suggestions that the risk of transmitting SARS-Cov-2 via ocular tissues and fluid to be minimal, especially in patients who have no attributable ocular symptoms. 

COVID-19) Dashboard. World Health Organization

The prevalence of ophthalmic manifestations in COVID-19 and the diagnostic value of ocular tissue/fluid. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie

Part 2 model eye simulation: aerosol generating procedures in intraocular surgery

Absence of Severe Acute Respiratory Syndrome-Coronavirus-2 RNA in ocular tissues

Clinical evaluation of AusDiagnostics SARS-CoV-2 multiplex tandem PCR assay

Novel coronavirus nucleic acid detection primers and probe sequences (Specific primers and probes for detection 2019 novel coronavirus)

Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study

Coronavirus disease 2019 (SARS-CoV-2) and colonization of ocular tissues and secretions: a systematic review

Mechanism of the action between the SARS-CoV S240 protein and the ACE2 receptor in eyes