Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 in Rhesus macaques

Abstract

19 The outbreak of Corona Virus Disease 2019 caused by the severe acute respiratory 20 syndrome coronavirus (SARS-CoV-2) is highly transmitted. The potential 21 extra-respiratory transmission routes remain uncertain. Five rhesus macaques were 22 inoculated with 1×10 6 TCID50 of SARS-CoV-2 via conjunctival (CJ), intratracheal 23 (IT), and intragastric (IG) routes, respectively. Remarkably, the CJ 24 inoculated-macaques developed mild interstitial pneumonia and viral load was 25 detectable in the conjunctival swabs at 1 days post-inoculation (dpi). Only via IT 26 inoculation, viral load was detected in the anal swab at 1-7 dpi and macaque showed 27 weight loss. However, viral load was undetectable after IG inoculation. Comparatively, 28 viral load was higher in the nasolacrimal system but lesions of lung were relatively 29 mild and local via CJ inoculation compared with that via IT inoculation, 30 demonstrating distinct characteristics of virus dispersion. Both the two routes affected 31 the alimentary tract. Therefore the clinicians need to protect eye while working with 32 patients. 33 34

The prevalence of ophthalmic manifestations in COVID-19 and the diagnostic value of ocular tissue/fluid

“…Although the main mode of SARS-CoV-2 transmission is predominantly respiratory, several studies have suggested that exposure of unprotected eyes to the virus may also cause novel coronavirus pneumonia (NCP) [1,2]. In agreement, a recent animal study also confirmed that macaque's conjunctiva inoculated with SARS-CoV-2 lead to the development of mild interstitial pneumonia [3], implying that ocular tissues and fluid may be a potential alternative mode of SARS-CoV-2 transmission. So far, there have been varying reports regarding the prevalence of ocular manifestations among COVID-19-infected patients [2,[4][5][6][7][8][9].…”

Molecular Detection of SARS-CoV-2 in Formalin Fixed Paraffin Embedded Specimens

“…At the time of writing, there are no animal models that truly mimic the disease spectrum and pathogenesis of COVID-19. However, small animals (e.g., human ACE2 transgenic laboratory mice (19), cats (20), domestic ferrets (20, 21), golden hamsters (22)), and nonhuman primates (e.g., rhesus monkeys (23, 24), crab-eating macaques (25)), are used to study SARS-CoV-2 infection as alveolar damage, interstitial inflammation, and viral shedding occur in these animal models to various degree. It is hoped that further development of these and other animal models will help overcome the current roadblock to evaluating the efficacy of candidate medical countermeasures (MCMs) against and the pathogenesis of COVID-19.…”

The ocular surface, coronaviruses and COVID‐19

“…However, an as yet non-peer-reviewed paper has been made available that directly compares inoculation of SARS-CoV-2 of rhesus macaque monkeys via their conjunctiva, trachea or stomach. 51 While the one monkey that received SARS-CoV-2 via their trachea had weight loss, the two monkeys that were inoculated via their conjunctiva had no weight loss. SARS-CoV-2 RNA was transiently found in the conjunctiva after one day only, and only in conjunctivainfected monkeys.…”

“…The authors concluded that conjunctival inoculation resulted in a mild lung infection compared to the trachea inoculation. 51 Unfortunately, no histology was performed on the eye during the infection, and given…”