ABSTRACT
SARS-CoV-2 is assumed to use angiotensin-converting enzyme 2 (ACE2) and other auxiliary proteins for cell entry. Recent studies have described conjunctival congestion in 0.8% of patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and there has been speculation that SARS-CoV-2 can be transmitted through the conjunctiva. However, it is currently unclear whether conjunctival epithelial cells express ACE2 and its cofactors. In this study, a total of 38 conjunctival samples from 38 patients, including 12 healthy conjunctivas, 12 melanomas, seven squamous cell carcinomas, and seven papilloma samples, were analyzed using high-throughput RNA sequencing to assess messenger RNA (mRNA) expression of the SARS-CoV-2 receptor ACE2 and its cofactors including TMPRSS2, ANPEP, DPP4, and ENPEP. ACE2 protein expression was assessed in eight healthy conjunctival samples using immunohistochemistry. Our results show that the SARS-CoV-2 receptor ACE2 is not substantially expressed in conjunctival samples on the mRNA (median: 0.0 transcripts per million [TPM], min: 0.0 TPM, max: 1.7 TPM) and protein levels. Similar results were obtained for the transcription of other auxiliary molecules. In conclusion, this study finds no evidence for a significant expression of ACE2 and its auxiliary mediators for cell entry in conjunctival samples, making conjunctival infection with SARS-CoV-2 via these mediators unlikely.
Subject(s)
COVID-19/virology , Carcinoma, Squamous Cell/virology , Eye Neoplasms/virology , Melanoma/virology , Papilloma/virology , Receptors, Virus/genetics , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/complications , COVID-19/pathology , COVID-19/surgery , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Case-Control Studies , Conjunctiva/pathology , Conjunctiva/surgery , Dipeptidyl Peptidase 4/genetics , Dipeptidyl Peptidase 4/metabolism , Eye Neoplasms/complications , Eye Neoplasms/pathology , Eye Neoplasms/surgery , Gene Expression , Glutamyl Aminopeptidase/genetics , Glutamyl Aminopeptidase/metabolism , Humans , Immunohistochemistry , Male , Melanoma/complications , Melanoma/pathology , Melanoma/surgery , Middle Aged , Papilloma/complications , Papilloma/pathology , Papilloma/surgery , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Virus/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolismABSTRACT
Recent studies have described conjunctivitis in approximately 1% of COVID-19 patients and speculated that SARS-CoV2 can be transmitted via the conjunctiva. In this article we recapitulate the molecular mechanisms of host cell entry of SARS-CoV2 and discuss the current evidence for a potential conjunctival transmission of SARS-CoV2. The current body of evidence indicates that SARS-CoV2 requires the membrane-bound angiotensin-converting enzyme 2 (ACE2) and the membrane-bound serine protease TMPRSS2 to enter cells. Recent studies suggest that COVID-19 patients rarely exhibit viral RNA in tear film and conjunctival smears and that, ACE2 and TMPRSS2 are only expressed in small amounts in the conjunctiva, making conjunctival infection with SARS-CoV2 via these mediators unlikely. Nevertheless, we consider the current evidence to be still too limited to provide a conclusive statement and recommend appropriate protective measures for healthcare personnel who are in close contact with suspected and confirmed COVID-19 patients.
Subject(s)
COVID-19 , SARS-CoV-2 , Conjunctiva , HumansABSTRACT
Recent studies have described conjunctivitis in approximately 1% of COVID-19 patients and speculated that SARS-CoV2 can be transmitted via the conjunctiva. In this article we recapitulate the molecular mechanisms of host cell entry of SARS-CoV2 and discuss the current evidence for a potential conjunctival transmission of SARS-CoV2. The current body of evidence indicates that SARS-CoV2 requires the membrane-bound angiotensin-converting enzyme 2 (ACE2) and the membrane-bound serine protease TMPRSS2 to enter cells. Recent studies suggest that COVID-19 patients rarely exhibit viral RNA in tear film and conjunctival smears and that, ACE2 and TMPRSS2 are only expressed in very small amounts in the conjunctiva, making conjunctival infection with SARS-CoV2 via these mediators unlikely. Nevertheless, we consider the current evidence to be still too limited to provide a conclusive statement and recommend appropriate protective measures for healthcare personnel who are in close contact with suspected and confirmed COVID-19 patients.