[en] Infectious diseases of the conjunctiva and cornea usually leave behind both broad local and systemic immunity. Case reports of SARS-CoV-2-positive conjunctivitis with subsequent systemic immunity suggest a new route of immunization preventing the primary infection of the airways. Material and Methods: A total of 24 Syrian field hamsters were treated. In systematic animal experiments, we infected the eyes of n = 8 animals (group 1) and the airways of another n = 8 animals (group 2) with SARS-CoV-2 (Wuhan type); n = 8 hamsters served as controls (group 3). The weight development of the animals was recorded. After two weeks of observation of disease symptoms, all animals were re-exposed to SARS-CoV-2 in the respiratory tract (challenge) to determine whether immunity to the virus had been achieved. Results: The epi-ocularly infected animals (group 1) showed no clinically visible disease during the ocular infection phase. At most, there was a slightly reduced weight gain compared to the control group (group 3), while the respiratory infected animals (group 2) all lost weight, became lethargic, and slowly recovered after two weeks. After the challenge, none of the animals in groups 1 and 2 became ill again. The animals in the negative control (group 3) all became ill. Cytotoxic antibodies were detectable in the blood of the infected groups before and after challenge, with higher titers in the epi-ocularly infected animals. Conclusion: By epi-ocular infection with SARS-CoV-2, the development of systemic immunity with formation of cytotoxic antibodies without severe general disease could be observed in the experimental animals, which did not induce any more disease upon a second infection in the respiratory tract. Therefore, it can be concluded that a purely epi-ocular infection with SARS-CoV2 only induces a weak disease pattern followed by systemic immunity.
Disciplines :
Immunology & infectious disease
Author, co-author :
Schrage, Norbert ; ACTO e.V., Aachen, Germany
Blomet, Joel; Laboratoires Prevor, Moulin de Verville, Valmondois, France
Funding: This research was funded by Laboratoires Prevor, Moulin de Verville; F-95670 Valmondois, France and Ursapharm Arzneimittel GmbH Industriestraße 35, 66129 Saarbrücken, Germany.
WHO Coronavirus (COVID-19) Dashboard. Available online: https://covid19.who.int/Overview (accessed on 5 June 2022).
da Silva Torres, M.K.; Bichara, C.D.A.; Vallinoto, M.C.; Queiroz, M.A.F.; Vallinoto, I.M.V.C.; Dos Santos, E.J.M.; de Carvalho, C.A.M.; Vallinoto, A.C.R. The complexity of SARS-CoV-2 infection and the COVID-19 pandemic. Front. Microbiol. 2022, 13, 789882. [CrossRef]
Richardson, J.R.; Götz, R.; Mayr, V.; Lohse, M.J.; Holthoff, H.-P.; Ungerer, M. SARS-CoV2 wild type and mutant specific humoral and T cell immunity is superior after vaccination than after natural infection. PLoS ONE 2022, 17, e0266701. [CrossRef] [PubMed]
Gebert, A.; Pabst, R. M cells at locations outside the gut. Semin. Immunol. 1999, 11, 165–170. [CrossRef] [PubMed]
Jonas, R.A.; Ung, L.; Rajaiya, J.; Chodosh, J. Mystery eye: Human adenovirus and the enigma of epidemic keratoconjunctivitis. Prog. Retin. Eye Res. 2020, 76, 100826. [CrossRef] [PubMed]
Alrawashdeh, H.M.; Al Zubi, K.; Abdulmannan, D.M.; Al-Habahbeh, O.; Abu-Ismail, L. Conjunctivitis as the only sign and symptom of COVID-19: A case report and review of literature. Qatar Med. J. 2021, 2021, 31.
Sirakaya, E.; Sahiner, M.; Sirakaya, H.A. A patient with bilateral conjunctivitis positive for SARS-CoV-2 RNA in a conjunctival sample. Cornea 2021, 40, 383–386. [CrossRef] [PubMed]
Tisi, A.; Zerti, D.; Genitti, G.; Vicentini, M.T.; Baccante, M.; Flati, V.; Maccarone, R. Characterization of SARS-CoV-2 Entry Factors’ Expression in Corneal and Limbal Tissues of Adult Human Donors Aged from 58 to 85. J. Ocul. Pharmacol. Ther. 2022, 38, 56–65. [CrossRef] [PubMed]
Seo, K.Y.; Han, S.J.; Cha, H.-R.; Seo, S.-U.; Song, J.-H.; Chung, S.-H.; Kweon, M.-N. Eye mucosa: An efficient vaccine delivery route for inducing protective immunity. J. Immunol. 2010, 185, 3610–3619. [CrossRef] [PubMed]
Kim, E.-D.; Han, S.J.; Byun, Y.-H.; Yoon, S.C.; Choi, K.S.; Seong, B.L.; Seo, K.Y. Inactivated eyedrop influenza vaccine adjuvanted with poly (I:C) Is safe and effective for inducing protective systemic and mucosal immunity. PLoS ONE 2015, 10, e0137608. [CrossRef]
Deng, W.; Bao, L.; Gao, H.; Xiang, Z.; Qu, Y.; Song, Z.; Gong, S.; Liu, J.; Liu, J.; Yu, P.; et al. Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 in rhesus macaques. Nat. Commun. 2020, 11, 1–7. [CrossRef]
Selvaraj, P.; Lien, C.Z.; Liu, S.; Stauft, C.B.; Nunez, I.A.; Hernandez, M.; Nimako, E.; Ortega, M.A.; Starost, M.F.; Dennis, J.U.; et al. SARS-CoV-2 infection induces protective immunity and limits transmission in Syrian hamsters. Life Sci. Alliance 2021, 4, e202000886. [CrossRef] [PubMed]
Misset, B.; Hoste, E.; Donneau, A.-F.; Grimaldi, D.; Meyfroidt, G.; Moutschen, M.; Compernolle, V.; Gothot, A.; Desmecht, D.; Garigliany, M.; et al. A multicenter randomized trial to assess the efficacy of CONvalescent plasma therapy in patients with Invasive COVID-19 and acute respiratory failure treated with mechanical ventilation: The CONFIDENT trial protocol. BMC Pulm. Med. 2020, 20, 317. [CrossRef] [PubMed]
Hamelmann, E.; Schwarze, J.; Takeda, K.; Oshiba, A.; Larsen, G.L.; Irvin, C.G.; Gelfand, E.W. Noninvasive Measurement of Airway Responsiveness in Allergic Mice Using Barometric Plethysmography. Am. J. Respir. Crit. Care Med. 1997, 156, 766–775. [CrossRef] [PubMed]
Schwarze, J.; Hamelmann, E.; Bradley, K.L.; Takeda, K.; Gelfand, E.W. Respiratory syncytial virus infection results in airway hyperresponsiveness and enhanced airway sensitization to allergen. J. Clin. Investig. 1997, 100, 226–233. [CrossRef] [PubMed]
Nuñez, I.A.; Lien, C.Z.; Selvaraj, P.; Stauft, C.B.; Liu, S.; Starost, M.F.; Wang, T.T. SARS-CoV-2 B.1.1.7 Infection of Syrian Hamster Does Not Cause More Severe Disease, and Naturally Acquired Immunity Confers Protection. mSphere 2021, 6, e0050721. [CrossRef] [PubMed]
Salz, A.; Acharya, M.; Hofmann, N.; Wittmershaus, I.; Sangwan, V.; Börgel, M.; Mathur, U. Risk of SARS-CoV-2 virus transmission from donor corneal tissue: A review. Indian J. Ophthalmol. 2021, 69, 1592–1597. [CrossRef] [PubMed]
Brdovčak, M.C.; Materljan, J.; Šustić, M.; Ravlić, S.; Ružić, T.; Lisnić, B.; Miklić, K.; Brizić, I.; Matešić, M.P.; Lisnić, V.J.; et al. ChAdOx1-S adenoviral vector vaccine applied intranasally elicits superior mucosal immunity compared to the intramuscular route of vaccination. Eur. J. Immunol. 2022, 52, 936–945. [CrossRef] [PubMed]