key: cord-0796767-qu4oi570
authors: Liu, Zhe; Sun, Chuan‐bin
title: Conjunctiva is not a preferred gateway of entry for SARS‐CoV‐2 to infect respiratory tract
date: 2020-04-10
journal: J Med Virol
DOI: 10.1002/jmv.25859
sha: 89393077806bc98bfd698752ae2367e3baa02b2f
doc_id: 796767
cord_uid: qu4oi570

The conjunctival mucosa is directly exposed to infectious droplets expelled by patients during close contact and fomites when the eye is touched by contaminated hands.(2, 3) More over, the mucosa of the conjunctiva and upper respiratory tract is connected by nasolacrimal duct, and share the same entry receptor of SARS‐CoV‐2, angiotensin‐converting enzyme 2 (ACE2), on host cell membranes.(2, 3) Hence, it is reasonable to postulate that the conjunctiva may be easily involved in SARS‐CoV‐2 infection, and may even act as a route of transmission during SARS‐CoV‐2 infection. This article is protected by copyright. All rights reserved.

transmitted via the conjunctiva route. The conjunctiva is neither a preferred tissue for SARS-CoV-2 infection, nor is a preferred gateway of entry for SARS-CoV-2 to infect respiratory tract, based on previous clinical and experimental investigations including the findings of Xia et al.

The conjunctival mucosa is directly exposed to infectious droplets expelled by patients during close contact and fomites when the eye is touched by contaminated hands. 2, 3 More over, the mucosa of the conjunctiva and upper respiratory tract is connected by nasolacrimal duct, and share the same entry receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), on host cell membranes. 2, 3 Hence, it is reasonable to postulate that the conjunctiva may be easily involved in SARS-CoV-2 infection, and may even act as a route of transmission during SARS-CoV-2 infection. However, until now, viral conjunctivitis has been reported in literature only in 5 cases with COVID-19, whereas in 0 and 4 cases infected by SARS-CoV and human coronavirus -NL63 which share the same entry receptor (i.e., ACE 2) with SARS-CoV-2, respectively (Table 1) (Table 1) . 1, 2 Taken together, recent clinical evidence and laboratory test results suggest that the conjunctiva is rarely involved in SARS-CoV-2 infection, and that the conjunctiva is neither a preferred tissue for SARS-CoV-2 infection, nor is a preferred gateway of entry for SARS-CoV-2 to infect respiratory tract. 2 We agree with Zhou et al 4 that the premise for transmission through conjunctiva must be based on that SARS-CoV-2 can replicate, and cytopathic changes and viral particles could be identified in conjunctival epithelial cells.

The rarity of viral conjunctivitis in SARS-CoV-2 infection may exist in three interpretations: firstly, the expression of ACE 2 protein on conjunctival epithelial cell membranes is much less than that in human lung and kidney tissues. 2, 5, 6 Secondly, the binding capability of ACE2 protein on conjunctival epithelial cells This article is protected by copyright. All rights reserved.

to SARS-CoV spike protein is much lower than that in lung tissues. 2, 7 Thirdly, the protective effect of the antimicrobial agents in tears including lactoferrin and secretory IgA, and constant tear rinsing on ocular surface which could eliminate the viruses dropped onto ocular surface into nasal cavity through nasolacrimal duct. 2, 8 Previous investigations have revealed that the binding of SARS-CoV to its entry receptor, ACE2 protein, depends on the assistance of an attachment receptor, heparan sulfate proteoglycans, on host cell membranes. 9 Lactoferrin can inhibit the binding of SARS-CoV to ACE2 protein by preventing the attachment of SARS-CoV to heparan sulfate proteoglycans. 2, 8, 9 The extremely low positive rate of SARS-CoV-2 tested by RT-PCR in tears and conjunctival secretions from patients with COVID-19 may be interpreted as follows: Firstly, current RT-PCR test for SARS-CoV-2 RNA is not sensitive enough, its sensitivity generally ranges from 50% to 60%. 2 

throat swabs from 1 to 7 day after conjunctival inoculation. This finding suggested that the virus load in the mucosa of nasal cavity and throat was much higher than that in conjunctiva. Hence, it is more likely that SARS-CoV-2 infection is transmitted via the nose and throat route than via the conjunctiva route in this animal model. SARS-CoV-2 exposed to the ocular surface might first be 

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Is novel coronavirus disease (COVID-19) transmitted through conjunctiva?

Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis

Expression of SARS coronavirus S proteinfunctional receptor-angiotensin-converting enzyme 2 in human cornea and conjunctiva

This article is protected by copyright. All rights reserved