COVID-19 News: Study Validates That SARS-CoV-2 Exhibits Ocular Tropism And Is Able To Cause Vision Issues
: A new study involving researchers from South Korea and Australia has validated that not only does SARS-CoV-2 exhibit ocular tropism and is able to get to the eyes of the host through various ways, but it also causes vision issues.
The study comprised of scientists from the Korea Research Institute of Chemical Technology-Republic of Korea, Korea Research Institute of Bioscience and Biotechnology-Republic of Korea, Griffith University-Australia and the The University of Sydney-Australia.
Despite the fact that past cases reports have covered ocular manifestations in patients with COVID-19, consensus on ocular tropism of SARS-CoV-2 is lacking.
The study team infected K18-hACE2 transgenic mice with SARS-CoV-2 using various routes.
The study team observed ocular manifestation and retinal inflammation with production of pro-inflammatory cytokines in the eyes of intranasally (IN)-infected mice.
Interestingly, intratracheal (IT) infection results in dissemination of the virus from the lungs to the brain and eyes via trigeminal and optic nerves. Ocular and neuronal invasions are confirmed using intracerebral (IC) infection.
Importantly, the eye-dropped (ED) virus does not cause lung infection and becomes undetectable with time.
Ocular and neurotropic distribution of the virus in vivo is evident in fluorescence imaging with an infectious clone of SARS-CoV-2-mCherry. The ocular tropic and neuroinvasive characteristics of SARS-CoV-2 are confirmed in wild-type Syrian hamsters.
The study findings can improve the understanding regarding viral transmission and clinical characteristics of SARS-CoV-2 and help in improving COVID-19 control procedures.
The study findings were published in the peer reviewed journal: Nature Communications.
Thailand Medical News in our various past COVID-19 News
coverages had covered how SARS-CoV-2 could possibly enter the human host via the eyes and also cause various ocular issues.
The South Korean and Australian study team primarily aimed to understand how SARS-CoV-2 affects the eyes and whether it could serve as a virus infection route.
Their study findings found the eyes and the trigeminal nerves are susceptible to the virus and that (in animal models) SARS-CoV-2 can infect the eye through the respiratory tract, via the brain.
Professor Dr Suresh Mahalingam Global Virus Network (GVN) Centre of Excellence in Arboviruses, Griffith University who was the lead researcher told Thailand Medical News
, “The SARS-CoV-2 virus can begin to affect vision when inflammation of the optic nerves, abnormal fluid build-up, and immune cell infiltration cause the retina to get thicker. The virus can infect the eye through nerve tissues at the back of the eye that play a role in the visual aspects of the eye and sending signals for visual purposes. The result of this retinal inflammation was a reduction in depth perception due to blurred vision."
He added that this blurred vision does appear to be symptomatic only, not a permanent degeneration of the eye tissue.
Co -researcher, Griffith University Ph.D. student Mr. Ng Wern Hann said that while a lot of COVID research has been focused on respiratory infection, particularly in the lungs and nasal region, there has not been much focus on the eyes.
He said, "We found the virus can indeed infect the eye through a normal intranasal approach, but also if droplets of the virus make direct contact with the eye. The ACE2 receptor is what the virus attaches to in order to infect a particular cell in a tissue or organ, and this receptor is found in abundance in the lungs, tonsils, nasal cavity, kidneys and heart, which is why a lot of reports have been published for those organs, but we found ACE2 receptors are also present in the eye, therefore facilitating infection."
Past studies have highlighted the neuro-tropism of SARS-CoV-2 and suggested the need to identify the route of viral invasion into the brain3. Olfactory nerves form bundles that provide an anatomical connection between the brain and nasal passage through the foramina in the cribriform plate and synapse on the glomeruli in the olfactory bulb. In addition, branches V1 (ophthalmic) and V2 (maxillary) of trigeminal nerves (TN) innervate both the respiratory and olfactory regions of the nasal passage, connecting the brain.
Though SARS-CoV-2 infection and transmission via the olfactory nerves have been demonstrated by several research groups, those of TN remains to be elucidated.
From data obtained from a patient with COVID-19 who suffered from trigeminal neuralgia, neuronal invasion via TN has been suggested in humans.
The study team demonstrated that TN can be infected by SARS-CoV-2 and used for transmitting the virus to the brain and eyes, along with the optic nerves (ON).
The study team believes that as the nasolacrimal duct provides an anatomical connection between the ocular surface and respiratory tract, the spreading of the virus to the eyes could have occurred via the nasolacrimal duct, and not the neurons.
Though the study team used IT infection to prevent early transmission to the eyes via the nasolacrimal duct, post-inoculation progeny viruses may move toward the eyes via the nasolacrimal duct following viral replication in the lungs, which has not been investigated in this study. Further studies on viral replication in the upper respiratory tract under conditions that stop spreading to the eyes via the nasolacrimal duct are warranted.
The study findings also suggest unidirectionality of the infectious route, from the lungs to the eyes, in animal models where ACE2 was expressed in the corneas of the eyes. In particular, the viral burdens of the eye globes were comparatively low and disappeared with time, suggesting the absence of viral proliferation in the eyes.
The study team concluded that ocular manifestation and retinal inflammation were promoted by SARS-CoV-2 infection in the mouse model, which increased cytokine production. The virus spreads from the lungs to the brain and eyes through a network consisting of TN and ON. This ocular tropism was also observed in wild-type Syrian hamsters. However, the elicitation of ocular inflammation by a viral infection of the eyes and its clinical relevance remains unknown and warrants further investigation. Along with the respiratory system, eyes and TN should be considered SARS-CoV-2-susceptible organ systems. Our data increases awareness regarding ocular and neuronal infection-mediated disorders beyond respiratory diseases, which will assist in designing treatment strategies for patients with COVID-19.
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