Convergence insufficiencyCentral mini-plication of medial rectusDiplopiaConsecutive esotropiaSurgical overcorrection / Detection of anti-SARS-CoV-2 antibodies in tears: Ocular surface immunity to COVID-19

Objetivos Evaluar la presencia de anticuerpos IgA e IgG específicos del SARS-CoV-2 en lágrima de sujetos no vacunados y vacunados contra la COVID-19 con antecedentes de infección SARS-CoV-2. Correlacionar los resultados en lágrima con los de saliva y sangre, datos clínicos y regímenes de vacunación. Métodos Estudio transversal que incluyó a sujetos con antecedentes de infección SARS-CoV-2, tanto no vacunados como vacunados contra la COVID-19. Se recogieron 3muestras: lágrima, saliva y sangre. Se analizaron IgA e IgG frente a S-1 SARS-CoV-2 con ELISA semicuantitativo. Resultados Treinta sujetos, con una edad media 36,4±10, varones 13/30 (43,3%) con historia de infección SARS-CoV-2 leve; 13/30 (43,3%) habían recibido un régimen de 2 dosis y 13/30 (43,3%) un régimen de 3 dosis de vacunación anti-COVID-19, 4/30 (13,3%) no estaban vacunados. Todos los sujetos con vacunación completa presentaron IgA detectable en los 3biofluidos. Entre los no vacunados, se detectó IgA en 3/4 sujetos en lágrima y saliva, mientras que no se detectó IgG. No se observaron diferencias entre la pauta de vacunación de 2 y 3 dosis según los títulos IgA-IgG. Conclusiones Anticuerpos IgA e IgG del SARS-CoV-2 están presentes en lágrimas de pacientes con antecedentes de COVID-19 leve, lo que destaca el papel de la superficie ocular como primera línea de defensa frente a la infección. La mayoría de los sujetos no vacunados presentaron IgA a largo plazo en lágrima y saliva. La inmunización híbrida (infección natural más vacunación) parece potenciar las respuestas IgG mucosas y sistémicas. No se observaron diferencias entre la pauta de 2 y 3 dosis (AU)

Purpose To evaluate the presence of SARS-CoV-2 specific IgA and IgG antibodies in tears of unvaccinated and anti-COVID-19 vaccinated subjects with previous history of SARS-CoV-2 infection. To compare results in tears with those in saliva and serum and correlate with clinical data and vaccination regimens. Methods Cross-sectional study including subjects with a previous history of SARS-CoV-2 infection, both unvaccinated and vaccinated against COVID-19. Three samples were collected: tears, saliva and serum. IgA and IgG antibodies against S-1 protein of SARS-CoV-2 were analyzed with a semi-quantitative ELISA. Results Thirty subjects, mean age 36.4±10, males 13/30 (43.3%) with history of mild SARS-CoV-2 infection were included. 13/30 (43.3%) subjects had received a 2-dose regimen and 13/30 (43.3%) a 3-dose regimen of anti-COVID-19 vaccine, 4/30 (13.3%) subjects were unvaccinated. All the participants with full anti-COVID-19 vaccination (2-or 3-doses) presented detectable anti-S1 specific IgA in all 3biofluids, tears, saliva and serum. Among unvaccinated subjects, specific IgA was detected in 3/4 subjects in tears and saliva, whereas IgG was not detected. Considering IgA and IgG antibodies titers, no differences were observed between the 2- and 3-dose vaccination regimen. Conclusions SARS-CoV-2-specific IgA and IgG antibodies were detected in tears after mild COVID-19, highlighting the role of the ocular surface as a first line of defense against infection. Most naturally infected unvaccinated individuals exhibit long-term specific IgA in tears and saliva. Hybrid immunization (natural infection plus vaccination) appears to enhance mucosal and systemic IgG responses. However, no differences were observed between the 2- and 3-dose vaccination schedule (AU)

SARS-COV-2 viral load in tears of patients with COVID-19 in the early symptomatic stages: comparison of two different tear sampling methods.

PURPOSE: To evaluate the presence of SARS-CoV-2 virus in tears of patients with COVID-19 in the early symptomatic stages and to compare two different sampling methods. MATERIALS AND METHOD: In this cross-sectional study, tears sampling was performed in COVID-19 patients admitted within the first 7 days of symptom onset. The samples were collected with both conjunctival swabs and Schirmer strips. Each specimen was analyzed via RT-PCR. The viral load was evaluated in terms of the cycle threshold value. Ocular and systemic symptoms and comorbidities of the patients were also recorded. RESULTS: Forty patients were included. The average time from the initiation of symptoms was 3.15 days. Unilateral conjunctivitis has been observed in 5% of patients and foreign body sensation in 7.5% of patients. No viral RNA was detected in the tear samples of the patients with ocular findings. The positivity rate for SARS-CoV-2 in tears was 2.5% (n = 1). None of the samples collected by Schirmer test strips yielded positive polymerase chain reaction result for SARS-COV-2. The Ct value of the positive conjunctival swab was 36.03 and the nasopharyngeal Ct value of the same patient was 25.68. CONCLUSION: The SARS-CoV-2 viral shedding rate has been determined as 2.5% in the tears of early symptomatic stage COVID-19 patients. The viral load of the tears was lower than the naso-oropharynx. The conjunctival swab method is recommended in tear collection to evaluate the presence of SARS-CoV-2 by RT-PCR analysis in low viral load tears.

Ocular transmissibility of COVID-19: possibilities and perspectives.

Since the initial outbreak of coronavirus disease 2019 (COVID-19), extensive research has emerged from across the globe to understand the pathophysiology of this novel coronavirus. Transmission of this virus is a subject of particular interest as researchers work to understand which protective and preventative measures are most effective. Despite the well understood model of aerosol-respiratory mediated transmission, the exact mechanism underlying the inoculation, infection and spread of COVID-19 is currently unknown. Given anatomical positioning and near constant exposure to aerosolized pathogens, the eye may be a possible gateway for COVID-19 infection. This critical review explores the possibility of an ocular-systemic or ocular-nasal-pulmonic pathway of COVID-19 infection and includes novel insights into the possible immunological mechanisms leading to cytokine surge.

Transcriptomic analysis revealed increased expression of genes involved in keratinization in the tears of COVID-19 patients.

Recent studies have focused their attention on conjunctivitis as one of the symptoms of coronavirus disease 2019 (COVID-19). Therefore, tear samples were taken from COVID-19 patients and the presence of SARS-CoV-2 was evidenced using Real Time reverse transcription polymerase chain reaction. The main aim of this study was to analyze mRNA expression in the tears of patients with COVID-19 compared with healthy subjects using Next Generation Sequencing (NGS). The functional evaluation of the transcriptome highlighted 25 genes that differ statistically between healthy individuals and patients affected by COVID-19. In particular, the NGS analysis identified the presence of several genes involved in B cell signaling and keratinization. In particular, the genes involved in B cell signaling were downregulated in the tears of COVID-19 patients, while those involved in keratinization were upregulated. The results indicated that SARS-CoV-2 may induce a process of ocular keratinization and a defective B cell response.

COVID-19 and the Eye: Ocular Manifestations, Treatment and Protection Measures.

The novel pandemic coronavirus disease 2019 (COVID-19) leading to health and economic problems worldwide is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although COVID-19 mainly occurs as a lower respiratory tract infection, there is multiorgan involvement in infected patients. The disease is transmitted from person to person through air droplets or contact with contaminated surfaces. SARS-CoV-2 leads to this systemic involvement by attaching to angiotensin-converting enzyme 2 (ACE2) receptors located on several human cells. Since SARS-CoV-2 RNA has been found in tears of infected patients, ocular surface may allow the virus to transmit to nasopharynx via the nasolacrimal duct. This narrative review aims to sum up all segmental ocular complications, ocular adverse effects of COVID-19 treatment, and preventive measures suggested to minimize the SARS-CoV-2 transmission between patients and ophthalmologists by reviewing currently available literature.

Suppression of CD80 Expression by ICP22 Affects Herpes Simplex Virus Type 1 Replication and CD8+IFN-γ+ Infiltrates in the Eyes of Infected Mice but Not Latency Reactivation.

Previously, we reported that herpes simplex virus type 1 (HSV-1) ICP22 binds to the CD80 promoter and suppresses its expression in vitro and in vivo. To better understand the impact of ICP22 binding to CD80 on HSV-1 infectivity and pathogenicity, we mapped the region of ICP22 required to bind the CD80 promoter to a 40-amino-acid (aa) region of ICP22. We constructed a recombinant HSV-1 expressing a truncated form of ICP22 that lacks these 40 aa, which does not bind to the CD80 promoter (KOS-ICP22Δ40) and retains the ability to replicate efficiently in rabbit skin cells, in contrast to ICP22-null virus. The replication of this recombinant virus in vitro and in vivo was higher than that of the ICP22-null virus, but virus replication kinetics were lower than those of the wild-type (WT) control virus. Similar to ICP22-null virus, the KOS-ICP22Δ40 mutant virus increased CD80 expression in dendritic cells (DCs) and interferon gamma (IFN-γ) expression in CD8+ T cells but not CD4+ T cells in infected mouse corneas. In contrast to the significantly reduced virus replication in the eyes of ocularly infected mice, the levels of latency reactivation were similar between KOS-ICP22Δ40 virus and WT virus. Thus, blocking ICP22 binding to the CD80 promoter using a recombinant virus expressing a truncated ICP22 that lacks CD80 promoter binding appears to reduce virus replication and enhance CD8+IFN-γ+ infiltrates in corneas of infected mice, with no effect on latency reactivation. IMPORTANCE Direct binding of HSV-1 ICP22 to the CD80 promoter downregulates the expression of the costimulatory molecule CD80 but not CD86. In this study, we fine mapped the region of ICP22 required for binding to the CD80 promoter and constructed a recombinant virus containing a deletion in ICP22 that failed to bind to the CD80 promoter. This recombinant virus replicated less efficiently in vitro and in vivo than did the WT control virus, although CD80-expressing CD11c+ cells and IFN-γ-expressing CD8+ T cells were increased. Interestingly, the levels of latency and reactivation in the two viruses were similar despite lower virus replication in the eyes of infected mice. Therefore, blocking the interaction of ICP22 with the CD80 promoter could be used to temper the immune response.

Identification of SARS-CoV-2 on the ocular surface in a cohort of COVID-19 patients from Brazil.

In this cross-sectional study, we investigate the presence of Severe Acute Respiratory Syndrome Coronavirus 2 Ribonucleic Acid (SARS-CoV-2 RNA) in the tears of hospitalized COVID-19 patients. After laboratory confirmation of SARS-CoV-2 infection by reverse transcription polymerase chain reaction (RT-PCR) analysis, tear samples from both eyes of each patient were collected using conjunctival swab for RT-PCR. Detailed demographic profile, systemic and ocular symptoms, comorbidities, clinical, ancillary, and ocular manifestations were evaluated. Of the 83 patients enrolled in the study, 7 (8.43%) had SARS-CoV-2 RNA detected in the tear samples. Neutrophils' count, C-reactive protein, and D-dimer were higher in patients with SARS-CoV-2 detected in tears than in patients without virus in ocular surface samples. One patient with SARS-CoV-2 in tears showed mild ocular eyelid edema, hyperemia, and chemosis. No relevant ocular manifestations were detected in the other patients. Although the levels of viral RNA on ocular surface samples were low for most patients (5/7), with positivity only for gene N and CT higher than 30, two patients were positive for all viral targets tested (N, E, and RpRd), with viral load near 1 × 105 ePFU/mL, indicating that the ocular transmission of SARS-CoV-2 is a possibility that needs to be considered, especially in the hospital environment. Further studies need to be conducted to demonstrate whether infective viral particles could be isolated from tears.

An Eye on COVID-19: A Meta-analysis of Positive Conjunctival Reverse Transcriptase-Polymerase Chain Reaction and SARS-CoV-2 Conjunctivitis Prevalence.

SIGNIFICANCE: This analysis and review demonstrate that, although emerging data indicate that the prevalence of severe acute respiratory coronavirus 2 (SARS-CoV-2) on the ocular surface and coronavirus disease 2019 (COVID-19) conjunctivitis is rare, the ocular surface remains of interest as a potential inoculation and transmission site for SARS-CoV-2. Continued safety precautions should be taken as more data become available.COVID-19, caused by SARS-CoV-2, is a novel, global pandemic that has infected millions and, up to this point, caused more than two million fatalities worldwide. The ocular surface has become of interest as a possible vector for transmission by acting as a direct inoculation site, being a conduit for the virus into the respiratory system or as a method of transmission from potentially infected conjunctiva or tears. The components necessary for SARS-CoV-2 to theoretically infect ocular tissues are present: binding receptors (angiotensin-converting enzyme 2 and cluster of differentiation 147) and mechanisms for cell entry (transmembrane protease serine 2 and cathepsin L). This meta-analysis of COVID-19 prevalence data indicates that SARS-CoV-2 RNA has been infrequently found in conjunctival samples when tested with reverse transcriptase-polymerase chain reaction. This review estimates the prevalence of SARS-CoV-2 on the ocular surface and prevalence of conjunctivitis in patients with laboratory-confirmed COVID-19. There is much to be learned regarding ocular tropism of SARS-CoV-2.

Comparative Evaluation of Tears and Nasopharyngeal Swab for SARS-CoV-2 in COVID-19 Dedicated Intensive Care Unit Patients.

Purpose: To compare the cycle threshold (Ct) values of tears and nasopharyngeal (NP) swab in severe COVID-19 ICU patients with positive NP swabs.Procedure: A cross-sectional study for the detection of SARS-CoV-2 by real-time RT-PCR on simultaneously collected NP swabs and tears was performed. Detailed demographic profile, including comorbidities, ocular, and systemic features were analyzed.Results: In the 78 cases, the mean tear positivity was 26.92% (21/78), 2 tear samples being positive despite a negative NP swab. The mean Ct value of tears and NP were 28.17 ± 4.76 and 23.71 ± 6.19, respectively (p= .003). None of the cases had ocular findings or relationship between tear positivity and comorbidity.Conclusions: The viral load of tears is less than the NP secretions with the possibility of prolonged shedding in tears. Tears act as an additional source of contact transmission in ICU that can possibly be decreased by frequent hand hygiene by the patient.Abbreviations: SARS-CoV-2: Severe acute respiratory syndrome coronavirus; RT-PCR: Real-time Reverse transcriptase-polymerase chain reaction; COVID-19: Corona virus disease 2019; ICU: Intensive care unit; RdRp: RNA-dependent RNA polymerase; ORF 1b: Open reading frame 1b; AIIR: Airborne infection isolation room; HCW: Health care workers; VTM: viral transport media; NP: Nasopharyngeal swab; PPE: Personal protective equipment.

SARS-CoV-2 on Ocular Surfaces in a Cohort of Patients With COVID-19 From the Lombardy Region, Italy.

Importance: Since February 2020, coronavirus disease 2019 (COVID-19) has spread rapidly all over the world, with an epidemiological cluster in Lombardy, Italy. The viral communicability may be mediated by various body fluids, but insufficient information is available on the presence of the virus in human tears. Objectives: To investigate the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in tears collected from patients with COVID-19 by means of real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) assay and to assess the association of virus presence with concomitant clinical conditions. Design, Setting, and Participants: Cross-sectional study conducted between April 9 and May 5, 2020. The setting was intensive care units at Azienda Socio-Sanitaria Territoriale (ASST) Sette-Laghi Hospital, University of Insubria, in Varese, Lombardy, Italy. A conjunctival swab was performed in 91 patients hospitalized for COVID-19, which was clinically diagnosed by rRT-PCR assay on nasopharyngeal swabs and by radiological imaging. Conjunctival swabs from 17 additional healthy volunteer participants with no symptoms of COVID-19 were examined to evaluate the availability and applicability of the conjunctival swab test. Exposure: SARS-CoV-2 detection by means of rRT-PCR assay performed on the collected samples obtained by conjunctival swabs. Main Outcomes and Measures: Conjunctival swab and nasopharyngeal swab results are reported, as well as demographic and clinical data. Results: A total of 108 participants (mean [SD] age, 58.7 [14.2] years; 55 female and 53 male) were tested for SARS-CoV-2 using rRT-PCR assay, including 91 patients hospitalized with COVID-19 and 17 were healthy volunteers. SARS-CoV-2 was found on the ocular surface in 52 of 91 patients with COVID-19 (57.1%; 95% CI, 46.3%-67.5%), with a wide variability in the mean viral load from both eyes. Among a subset of 41 patients, concordance of 63.0% (95% CI, 41.0%-81.0%) was found between positive conjunctival and nasopharyngeal swab test results when performed within 2 days of each other. In 17 of these patients, nasopharyngeal swab results were negative for SARS-CoV-2. In 10 of these 17 patients, conjunctival swab results were positive for the virus. Conclusions and Relevance: In this study, SARS-CoV-2 RNA was found on the ocular surface in a large part of this cohort of patients with COVID-19, although the infectivity of this material could not be determined. Because patients may have positive test results with a conjunctival swab and negative results with a nasopharyngeal swab, use of the slightly invasive conjunctival swab may be considered as a supplementary diagnostic test.

A review on human body fluids for the diagnosis of viral infections: scope for rapid detection of COVID-19.

Introduction: The unprecedented outbreaks of corona virus disease of 2019 (COVID-19) have highlighted the necessity of readily available, reliable, precise, and faster techniques for its detection. Nasopharyngeal swab has been the gold standard for the diagnosis of COVID-19. However, it is not an ideal screening procedure for massive screening as it implicates the patient's stay in the hospital or at home until diagnosis, thus causing crowding of the specimen at the diagnostic centers. Present study deal with the exploration of potential application of different body fluids using certain highly objective techniques (Optical and e-Nose) for faster detection of molecular markers thereby diagnosing viral infections.Areas covered: This report presents an evaluation of different body fluids, and their advantages for the rapid detection of COVID-19, coupled with highly sensitive optical techniques for the detection of molecular biomarkers.Expert opinion: Tears, saliva, and breath samples can provide valuable information about viral infections. Our brief review strongly recommends the application of saliva/tears and exhaled breath as clinical samples using technics such as high-performance liquid chromatography-laser-induced fluorescence, photoacoustic spectroscopy, and e-Nose, respectively, for the fast diagnosis of viral infections.

Implications of COVID-19 for Ophthalmologists.

PURPOSE: To describe and explain the implications of coronavirus disease 2019 (COVID-19) for ophthalmologists considering the rapid developments in our understanding of the virology, transmission, and ocular involvement. DESIGN: Evidence-based perspective. METHODS: Review and synthesis of pertinent literature. RESULTS: Retrospective studies highlight that <1% of patients display COVID-19-related conjunctivitis. However, prospective studies suggest the rate is higher (~6%). Viral RNA has been identified in tears and conjunctival secretions in patients with active conjunctivitis as well as asymptomatic cases. Overall, conjunctival swabs are positive in 2.5%. Samples taken earlier in the disease course are more likely to demonstrate positive virus. Viral transmission through ocular tissues has not been substantiated. Ophthalmologists are in the high-risk category for COVID-19 infection for several reasons: high-volume clinics, close proximity with patients, equipment-intense clinics, and direct contact with patients' conjunctival mucosal surfaces. COVID-19 is predominantly contracted through direct or airborne transmission by inhalation of respiratory droplets. Evidence that aerosol transmission occurs is increasing in particularly prolonged exposure to high concentrations in a relatively closed environment. Based on the current evidence, ophthalmologists should consider measures that include social distancing, wearing masks, sterilization techniques, and managing clinic volumes. CONCLUSIONS: A major challenge to containing COVID-19 is that many infected people are asymptomatic. Droplet spread, contaminated environmental surfaces, and shared medical devices are areas that require management by ophthalmologists. More studies are required to explore the role of the conjunctiva and ocular tissues in the transmission of disease.

SARS-CoV-2 Presence in the Saliva, Tears, and Cerumen of COVID-19 Patients.

OBJECTIVES/HYPOTHESIS: The emergence of a new coronavirus strain (SARS-CoV-2) in December 2019 from China led to a global pandemic. The lack of herd immunity against this virus and the possibility of viral spread from asymptomatic individuals is still a major challenge for the prevention of viral transmission. The aim of this study was to evaluate the presence of the virus in different bodily secretions as a potential source of viral spread among patients infected with SARS-CoV-2. STUDY DESIGN: Cross Sectional Study. METHODS: The study included 38 COVID-19 patients with a positive real-time polymerase chain reaction (RT-PCR) test result for SARS-CoV-2, obtained from the combined nasopharyngeal-oropharyngeal swab samples. Saliva, tear, and cerumen samples were taken from the patients within 72 hours of the first RT-PCR test. SARS-CoV-2 N1 and N2 gene regions were studied with single-step RT-PCR in all samples. RESULTS: Among the studied samples, the highest positivity rate was in saliva (76.3%) followed by tears (55.3%) and cerumen (39.5%). Viral load in saliva was also significantly higher compared to tears and cerumen (P < .001), while there was no significant difference between tears and cerumen. Higher viral load in combined nasopharyngeal-oropharyngeal swab samples was associated with higher viral load in tears, but not in saliva or cerumen. Half of the saliva, tear, and cerumen samples obtained from asymptomatic patients contained SARS-CoV-2 genome. CONCLUSIONS: The virus was detected in the saliva, tears, and cerumen samples of both symptomatic and asymptomatic patients. The potential role of these bodily fluids on viral spread needs to be studied. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1677-E1682, 2021.

The eye: "An organ that must not be forgotten in coronavirus disease 2019 (COVID-2019) pandemic".

The coronavirus family is a group of zoonotic viruses with some recognized reservoirs particularly some bats. A novel coronavirus emerged in the province of Wuhan (China) in December of 2019.The number of infected patient with serious respiratory infection quickly spread around the world to become a global pandemic. The clinical presentation and viral pathogenesis of the coronavirus disease named COVID-19 indicated that the virus is transmitted from person to person through infected droplets entering the respiratory mucosa. Close contact with infected individuals particularly in crowded environments has characterized the rapid spread of the infection. Clinical manifestations of the viral infection have mentioned the presence of some ocular findings such as conjunctival congestion, conjunctivitis and even corneal injury associated with the classical COVID-19 infection. Some animal models of different coronaviruses eye infections have described the viral pathogenesis through tear and conjunctival sampling. On the other hand, we are recommended protective measure to prevent contagion and limit the spread of the virus in health care professionals and contact lenses wearers.

Ocular Surface and Conjunctival Cytology Findings in Patients With Confirmed COVID-19.

PURPOSE: To assess the effect of severe acute respiratory syndrome coronavirus-2 infection on the conjunctiva and tear film. METHODS: Thirty-eight patients with confirmed COVID-19 and 31 healthy controls were included in this prospective and observational study. Individuals with COVID-19 formed the patient group, and healthy individuals formed the control group. Conjunctival impression cytology (CIC), TBUT, Schirmer II test, and ocular surface disease index were evaluated in all participants. RESULTS: No significant difference was observed regarding the mean age and gender between the groups (P=0.786 and P=0.122, respectively). The mean TBUT and Schirmer II test results did not differ between the two groups (P=0.496 and P=0.447, respectively). The CIC results revealed decreased density and cell size of goblet cells and moderate to high enlargement, squamous changes, and increased nucleocytoplasmic ratio in nongoblet epithelial cells in the COVID-19 group compared with the control group. Based on the Nelson classification in CIC samples, 60.6% of the COVID-19 group and 19.4% of the control group had changes consistent with grade 2 or above. The presence of neutrophils in CIC was significantly higher in the COVID-19 group (P<0.001), whereas the presence of lymphocyte was similar between the two groups (P=0.247). CONCLUSION: This study revealed the pathological conjunctival alterations in patients with COVID-19 and demonstrated that pathological ocular surface alterations may present even at the beginning of COVID-19 without clinically significant ocular manifestation.

Conjunctivitis as sole symptom of COVID-19: A case report and review of literature.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus causing an ongoing pandemic in 2020. Although the symptomatic patients infected by SARS-CoV-2 generally show respiratory distress, atypical manifestations such as conjunctivitis are also observed. A series of cases are reported in which reverse transcriptase polymerase chain reaction (RT-PCR) testing on tears had demonstrated the presence of the virus. However, the transmission of the virus through ocular fluids remains unknown. CASE DESCRIPTION: In this case report, the development of conjunctivitis is presented as the sole symptom of a new coronavirus disease 2019 (COVID-19) in an emergency health care worker. The patient's first application was to the ophthalmology clinic due to redness, stinging, tearing, and photophobia for one day in the right eye. The patient had no symptoms of fever, cough, shortness of breath, or fatigue. Two days later, the RT-PCR test, blood analysis, and chest computed tomography (CT) were applied to the patient for being in contact with a COVID positive patient. Conjunctival swabs did not identify SARS-CoV-2 by RT-PCR. However, nasopharyngeal swab and blood test confirmed the diagnosis of COVID-19. Chest CT did not show pneumonia. CONCLUSION: This phenomenon shows that conjunctivitis may occur as a sole manifestation of COVID-19 which needs to be carefully evaluated by health care workers and eye care professionals during the pandemic.

Detection of Coronavirus in Tear Samples of Hospitalized Patients With Confirmed SARS-CoV-2 From Oropharyngeal Swabs.

PURPOSE: This study was designed to detect CoV-RNA in the tears of polymerase chain reaction (PCR)-confirmed SARS-CoV-2 positive patients. METHODS: We performed a prospective case series study of hospitalized patients who have been confirmed SARS-CoV-2 positive by oropharyngeal swab within the previous 5 days. Tear samples obtained with a laboratory capillary and oropharyngeal swabs were analyzed by real-time PCR using the Altona SARS-CoV-2 Assay or the Roche SARS-CoV-2 LightMix PCR, depending on the availability. Patient history was documented, and ophthalmoscopy was used to assess for ocular surface disease. RESULTS: Of all 18 patients recruited in April 2020, 5 suffered from respiratory failure and were submitted to an intensive care unit. None of our patients had signs of viral conjunctivitis although all patients in intensive care showed chemosis and conjunctival hyperemia because of third-spacing or fluid overload. The presence of coronavirus RNA was confirmed by PCR in 5 of 18 patients (28%) in tears and 72% for oropharyngeal swabs. CONCLUSIONS: Using a tear fluid sampling technique similar to oropharyngeal lavage presents a higher percentage of SARS-CoV-2 positive tears in contrast to earlier reports that used a conjunctival swab. This does not automatically indicate viral shedding in ocular tissue or contagiousness of tear fluid.

Evaluation of SARS-CoV-2 in Tears of Patients with Moderate to Severe COVID-19.

PURPOSE: To investigate the presence of SARS-CoV-2 RNA in tears of patients with moderate to severe coronavirus disease 2019 (COVID-19). DESIGN: Cross-sectional study. PARTICIPANTS: Patients with laboratory-proven moderate to severe COVID-19. METHODS: Tears were collected within 48 hours of laboratory confirmation using 3 methods: conjunctival swab plus Schirmer's test strips (group 1), conjunctival swab (group 2), and Schirmer's test strips (group 3). Samples from both the eyes of each patient were transported in a single viral transport media for real-time RT-PCR. Detailed demographic profiles, systemic symptoms, comorbidities, and ocular manifestations were noted. MAIN OUTCOME MEASURES: Viral load of a sample was determined using cycle threshold (Ct) value of E gene. A specimen was considered to show positive results if the amplification curve for the E gene crossed the threshold line within 35 cycles and if it showed positive results on an RNA-dependent RNA polymerase or open reading frame 1b gene assay. RESULTS: Of the 78 patients enrolled in the study, samples from 3 patients were found to be inadequate for analysis. Thirty-six patients (48%) had moderate disease, whereas 39 patients (52%) had severe disease, with no ocular involvement in any patient. In the 75 patients, RT-PCR analysis of tears showed positive results in 18 patients (24%), and 29 of 225 samples (12.9%) showed positive results. Positive results were found in 11 (14.7%), 11 (14.7%), and 7 (9.3%) patients in groups 1, 2, and 3, respectively (P = 0.3105). Mean Ct values in groups 1, 2, and 3 were 28.36 ± 6.15, 29.00 ± 5.58, and 27.86 ± 6.46 (P = 0.92), respectively. Five patients showed positive RT-PCR results by all 3 methods (mean Ct value, 25.24 ± 6.33), and 12 patients showed positive results by any of the 3 methods (mean Ct value, 32.16 ± 1.94), the difference in Ct values being statistically significant (P = 0.029). The median value of symptomatology in patients with positive RT-PCR results from tears was 5 days (range, 4-9 days). CONCLUSIONS: SARS-CoV-2 RNA was detected in tears of 24% of patients with laboratory-proven moderate to severe COVID-19. Conjunctival swab remains the gold standard of tear collection for RT-PCR assay. A significantly higher possibility of viral transmission exists through tears in patients with moderate to severe COVID-19.