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Comment & Response
July 29, 2021

Live and Replication-Competent SARS-CoV-2 in Ocular Fluids

Author Affiliations
  • 1National Institute for Infectious Diseases Lazzaro Spallanzani, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
JAMA Ophthalmol. 2021;139(9):1041. doi:10.1001/jamaophthalmol.2021.2681

To the Editor We read with great interest the research by Azzolini and colleagues.1 From the virologic perspective, the authors showed that SARS-CoV-2 RNA was found on the ocular surface in 52 of 91 patients with COVID-19 (57.1%; 95% CI, 46.3-67.5), and 10 of 41 patients with nasopharyngeal swab results available the same day or within 2 days had positive results with conjunctival swab and negative results with nasopharyngeal swab. We believe it is useful to elucidate the role of the ocular apparatus and lacrimal secretions in COVID-19 pathogenesis, both in the interest of infection control and diagnosis. To this end, more in-depth bibliographic research may be of help as the scientific interest on ocular involvement in COVID-19 and its route of transmission has been high since the beginning of the pandemic.2 As shown by Roehrich et al,3 among others, both corneal and conjunctival epithelium specimens obtained from cornea donors express ACE2, DC-SIGN or DC-SIGNR, and TMPRSS2, which are recognized cell receptors for SARS-CoV-2. This evidence points to the SARS-CoV-2 tropism for ocular apparatus. In addition, the viral replication competence in conjunctival mucosa has been demonstrated in ex vivo and in vitro cultures,4 suggesting that the conjunctiva is a potential virus reservoir for SARS-CoV-2 infection and may represent an additional portal of infection with implications for both transmission and contagion.

We have previously reported5 that live and replication-competent virus was isolated directly from the ocular fluid collected from 1 of the COVID-19 patients in Italy who was admitted to the National Institute for Infectious Diseases Lazzaro Spallanzani in Rome, Italy, at the end of January 2020. The presence of infectious virus and the prolonged detection of SARS-CoV-2 RNA in longitudinal ocular samples (when viral RNA was at lower levels or even undetectable in nasal swabs) suggest a sustained viral replication in the ocular compartment. Overall, these data corroborate the conclusions of Azzolini and colleagues1 that SARS-CoV-2 transmission may be mediated by ocular fluids and that attention should be given to the possibility of ocular disease in patients with suspected COVID-19 infection.

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Article Information

Corresponding Author: Concetta Castilletti, PhD, Emerging Viruses Operative Unit, Laboratory of Virology, National Institute for Infectious Diseases Lazzarro Spallanzani, Istituto di Ricovero e Cura a Carattere Scientifico, Via Portuense 292, 00149 Rome, Italy (concetta.castilletti@gmail.com).

Published Online: July 29, 2021. doi:10.1001/jamaophthalmol.2021.2681

Conflict of Interest Disclosures: None reported.

Azzolini  C, Donati  S, Premi  E,  et al.  SARS-CoV-2 on ocular surfaces in a cohort of patients with COVID-19 from the Lombardy region, Italy.   JAMA Ophthalmol. Published online March 4, 2021. doi:10.1001/jamaophthalmol.2020.5464 PubMedGoogle Scholar
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Roehrich  H, Yuan  C, Hou  JH.  Immunohistochemical study of SARS-CoV-2 viral entry factors in the cornea and ocular surface.   Cornea. 2020;39(12):1556-1562. doi:10.1097/ICO.0000000000002509PubMedGoogle ScholarCrossref
Hui  KPY, Cheung  M-C, Perera  RAPM,  et al.  Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures.   Lancet Respir Med. 2020;8(7):687-695. doi:10.1016/S2213-2600(20)30193-4PubMedGoogle ScholarCrossref
Colavita  F, Lapa  D, Carletti  F,  et al.  SARS-CoV-2 isolation from ocular secretions of a patient with COVID-19 in Italy with prolonged viral RNA detection.   Ann Intern Med. 2020;173(3):242-243. doi:10.7326/M20-1176PubMedGoogle ScholarCrossref