LAUSR

We read the letter by Agarwal R et al. very carefully and appreciate them for nicely addressing the issues; however, we have some concerns. The authors have expressed their concern about presence of the virus in ocular secretions; however, although the prevalence is low, the presence of SARSCoV-2 in ocular fluid is well-established. Even some patients have showed strong positivity for the virus in ocular fluid [1]. In a study, around 31.6% of the patients showed ophthalmologic manifestations similar to conjunctivitis and 16% of the patients showed SARS-CoV-2 positivity in ocular fluid [2]. A systematic review and meta-analysis have already established this issue [3]. The low prevalence of ocular fluid positivity for SARS-CoV-2 may be due to many reasons. The timing of sample collection is very important in this regard [1]. Many authors report that viral secretion can be seen only during the early phases [1, 4]. Again, sample collection may be inadequate and ocular surface swab samples collected few exfoliated cells which had a low chance of detecting the virus [1]. Again, low sensitivity of the RT-PCR-based diagnostic kits can also contribute to the low detection rate [1]. Agarwal R et al. also mentioned their concern regarding uncertainty about the ability of the virus into the systematic circulation through that through accidental hand-eye contact. Although we do not have data regarding occurrence of COVID-19 from accidental hand eye exposure, however there is a report of occupational ocular exposure to SARS-CoV-2 (owing to dislodged eye goggles) that led to development of COVID-19 in a nurse who used a dislodged eye goggles [5]. However, we have data from rhesus macao [6], which proves that ocular inoculation may lead to establishment of an infection. In animals with conjunctival inoculation, high concentration of SARS-CoV-2 was noted in the nasolacrimal duct (NLD). Establishment of systemic infection was noted with both the route of inoculation (intra-tracheal and conjunctival inoculation) [6]. Again, the authors have expressed their concern regarding the doubtful presence of and action of ACE2 receptor in corneal and conjunctival epithelium. We all know that both ACE2 and TMPRSS2 are required for a successful establishment of a human infection [7–9]. A study by Ma et al. 2020 raised concern against the expression of TMPRSS2 in conjunctival cells and commented that conjunctiva is less likely to be infected with the virus (data generated in mouse cornea and human primary conjunctival and pterygium cell lines) [8]. Another point to be considered is that mRNA expression level differs between in vivo state and in culture [10, 11]. In human cell lines, although ACE2 was present in the conjunctival cell lines, however, they could not locate the expression of TMPRSS2 in the conjunctival cells [8]. Another study has supported these findings [12]. However, many of the other studies report in the opposite. One of the studies published from John Hopkins University School of medicine has confirmed the expression of ACE2 in cornea, limbus, and conjunctiva in surgical and postmortem specimen using immunohistochemistry (IHC). Notably, prominent staining was noted in the epithelial surface of cornea and superficial conjunctival surface. In their study, TMPRSS2 expression was noted in conjunctival specimens. These findings were further validated in western blot analysis [13]. Other studies also confirmed the presence of ACE2 receptor expression in conjunctival tissue [14, 15]. These studies summarized that COVID-19 may spread through conjunctiva [14]. Another possible route of * Anusuya Bhattacharyya [email protected]