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.

Detection of SARS-CoV-2-RNA in post-mortem samples of human eyes.

PURPOSE: To detect SARS-CoV-2 RNA in post-mortem human eyes. Ocular symptoms are common in patients with COVID-19. In some cases, they can occur before the onset of respiratory and other symptoms. Accordingly, SARS-CoV-2 RNA has been detected in conjunctival samples and tear film of patients suffering from COVID-19. However, the detection and clinical relevance of intravitreal SARS-CoV-2 RNA still remain unclear due to so far contradictory reports in the literature. METHODS: In our study 20 patients with confirmed diagnosis of COVID-19 were evaluated post-mortem to assess the conjunctival and intraocular presence of SARS-CoV-2 RNA using sterile pulmonary and conjunctival swabs as well as intravitreal biopsies (IVB) via needle puncture. SARS-CoV-2 PCR and whole genome sequencing from the samples of the deceased patients were performed. Medical history and comorbidities of all subjects were recorded and analyzed for correlations with viral data. RESULTS: SARS-CoV-2 RNA was detected in 10 conjunctival (50%) and 6 vitreal (30%) samples. SARS-CoV-2 whole genome sequencing showed the distribution of cases largely reflecting the frequency of circulating lineages in the Munich area at the time of examination with no preponderance of specific variants. Especially there was no association between the presence of SARS-CoV-2 RNA in IVBs and infection with the variant of concern (VOC) alpha. Viral load in bronchial samples correlated positively with load in conjunctiva but not the vitreous. CONCLUSION: SARS-CoV-2 RNA can be detected post mortem in conjunctival tissues and IVBs. This is relevant to the planning of ophthalmologic surgical procedures in COVID-19 patients, such as pars plana vitrectomy or corneal transplantation. Furthermore, not only during surgery but also in an outpatient setting it is important to emphasize the need for personal protection in order to avoid infection and spreading of SARS-CoV-2. Prospective studies are needed, especially to determine the clinical relevance of conjunctival and intravitreal SARS-CoV-2 detection concerning intraocular affection in active COVID-19 state and in post-COVID syndrome.

Detection of COVID-19 in tears of ICU-admitted patients with SARS-CoV-2 infection.

PURPOSE: Upon the outbreak of 2019, novel coronavirus (COVID-19) pandemic confirmed the cases surpassed 20 million. Despite a few reports identified the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with ocular manifestations, it may assess the ocular symptoms of patients with the COVID-19 by ophthalmologists facilitate the diagnosis and prevent transmission. METHODS: A total of 60 patients with the COVID-19 admitted to Baghiatallah hospital from March 2020 to May 2020 were retrospectively reviewed and analyzed for the ocular manifestations, blood tests, and reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV-2 using nasopharyngeal and conjunctival swabs. RESULTS: Among 60 included patients with clinically confirmed COVID-19, the median age 58.36 years (IQR: 30-88 years), 27 (45%) were male. Furthermore, 29 (48%) and 5 (8%) patients yielded positive for SARS-CoV-2 on RT-PCR from nasopharyngeal swabs and conjunctival specimens, respectively. Among 60 patients, 10 (16%) and 3 (5%), respectively, had the ocular manifestations and positive results for SARS-CoV-2 on RT-PCR from conjunctival and nasopharyngeal swabs. CONCLUSION: Although the positive rate of tear RT-PCR rate is not noticeable as nasopharyngeal swabs yet, COVID-19 transmission through the eyes is biologically plausible.

Human tear fluid analysis for clinical applications: progress and prospects.

Introduction: Human blood and saliva are increasingly under investigation for the detection of biomarkers for early diagnosis of non-communicable (e.g.cancers) and communicable diseases like COVID-19. Exploring the potential application of human tears, an easily accessible body fluid, for the diagnosis of various diseases is the need of the hour.Areas covered: This review deals with a comprehensive account of applications of tear analysis using different techniques, their comparison and overall progress achieved till now. The techniques used for tear fluid analysis are HPLC/UPLC/SDS-PAGE, CE, etc., together with ELISA, Mass Spectrometry, etc. But, with advances in instrumentation and data processing methods, it has become easy to couple the various separation methods with highly sensitive optical techniques for the analysis of body fluids.Expert opinion: Tear analysis can provide valuable information about the health condition of the eyes since it contains several molecular constituents, and their relative concentrations may alter under abnormal conditions. Tear analysis has the advantage that it is totally non-invasive. This study recommends tear fluid as a reliable clinical sample to be probed by highly sensitive optical techniques to diagnose different health conditions, with special emphasis on eye diseases.

Ocular Surface Impairment After Coronavirus Disease 2019: A Cohort Study.

PURPOSE: This is a cohort study to evaluate the presence of objective signs and subjective symptoms of dry eye disease in postcoronavirus disease 2019 (COVID-19) patients compared with the control. METHODS: Prospective, observational, single-ctenter, cohort study. Sixty-four post-COVID-19 patients and 50 control were recruited. All participants underwent a complete ophthalmological examination including Ocular Surface Disease Index Questionnaire (OSDI), best-corrected visual acuity, slit-lamp biomicroscopy, fundus examination, Schirmer test type 1, tear break-up time test (tBUT), evaluation of conjunctival hyperemia, corneal staining, and tear film osmolarity test. RESULTS: The OSDI score was higher in the post-COVID-19 group in the quantitative and qualitative analysis (P < 0.001 and P =0.012, respectively). The mean tBUT in post-COVID-19 patients was 6.95 ± 4.07 seconds compared with a mean tBUT of 10.12 ± 3.90 seconds in the control group. The post-COVID-19 group showed a higher number of patients with a simultaneous impairment of the OSDI score and tBUT (P = 0.019). The Schirmer test results were strikingly significant both in the quantitative analysis and qualitative analysis (P <0.001 and P = 0.0014, respectively). Both quantitative analysis and qualitative analysis revealed a significant difference in tear osmolarity in the 2 groups. CONCLUSIONS: Comparing the ocular surface assessment of post-COVID-19 patients with heathy control, a statistically significant increase of dry eye disease has emerged both in subjective and objective evaluations. Our clinical results support the findings that suggested a susceptibility of the ocular surface to the virus, and it underlines the importance of the ocular surface assessment in post-COVID-19 patients for a correct diagnosis and therapy.

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.

Effect of Intraocular Pressure on Aerosol Density Generated by Noncontact Tonometer Measurement.

PRECIS: Aerosols generated by a noncontact tonometer (NCT) were quantified. There was a positive correlation between aerosols and intraocular pressure (IOP), and the concentration of aerosols beside the air jet port was the highest. PURPOSE: To investigate the effects of IOP on the aerosol density generated during the use of an NCT and provide references and suggestions for daily protection of ophthalmic medical staff during the coronavirus disease-19 (COVID-19) outbreak. OBJECTIVE AND METHODS: This cross-sectional clinical trial included 214 eyes of 140 patients from a hospital in Wenzhou city, Zhejiang Province. All subjects' IOPs were measured by an NCT (39 eyes with low IOP, 90 eyes with normal IOP, 37 eyes with moderately high IOP, and 48 eyes with very high IOP) between March 7 and June 17, 2020. The density of particulate matter (PM) 2.5 and PM10 generated during the process of IOP measurement with an NCT was analyzed. IOP values were recorded simultaneously. The aerosols generated during different IOP measurements were plotted in scatter plots. RESULTS: PM2.5 was generated more at the air jet port of the tonometer during the process of IOP measurement (H=2.731, P=0.019). Larger quantities of PM2.5 and PM10 were generated when the IOP was higher, and these differences were statistically significant (PM2.5: H=119.476, P<0.001; PM10: H=160.801, P<0.001). Linear correlation analysis with one variable demonstrated that IOP had significantly positive correlations with PM2.5 (r=0.756, P<0.001) and PM10 (r=0.864, P<0.001). CONCLUSIONS: Aerosols can be generated while using an NCT to measure IOP, and aerosols and IOP are positively correlated. Patients with moderately high IOP or very high IOP tend to generate more aerosols during the IOP measurement. The concentration of aerosols beside the air jet port was the highest.

Wearable electrochemical biosensors in North America.

Tremendous research and commercialization efforts around the world are focused on developing novel wearable electrochemical biosensors that can noninvasively and continuously screen for biochemical markers in body fluids for the prognosis, diagnosis and management of diseases, as well as the monitoring of fitness. Researchers in North America are leading the development of innovative wearable platforms that can comfortably comply to the human body and efficiently sample fluids such as sweat, interstitial fluids, tear and saliva for the electrochemical detection of biomarkers through various sensing approaches such as potentiometric ion selective electrodes and amperometric enzymatic sensors. We start this review with a historical timeline overviewing the major milestones in the development of wearable electrochemical sensors by North American institutions. We then describe how such research efforts have led to pioneering developments and are driving the advancement and commercialization of wearable electrochemical sensors: from minimally invasive continuous glucose monitors for chronic disease management to non-invasive sweat electrolyte sensors for dehydration monitoring in fitness applications. While many countries across the globe have contributed significantly to this rapidly emerging field, their contributions are beyond the scope of this review. Furthermore, we share our perspective on the promising future of wearable electrochemical sensors in applications spanning from remote and personalized healthcare to wellness.

Quantitative High-speed Assessment of Droplet and Aerosol From an Eye After Impact With an Air-puff Amid COVID-19 Scenario.

PURPOSE: To quantify aerosol and droplets generated during noncontact tonometry (NCT) and assess the spread distance of the same. METHODOLOGY: This was an experimental study on healthy human volunteers (n=8 eyes). In an experimental setup, NCT was performed on eyes (n=8) of human volunteers under normal settings, with a single and 2 drops of lubricant. High-speed shadowgraphy, frontal lighting technique, and fluorescein analysis were used to detect the possible generation of any droplets and aerosols. Mathematical computation of the spread of the droplets was then performed. RESULTS: In a natural setting, there was no droplet or aerosol production. Minimal splatter along with droplet ejection was observed when 1 drop of lubricant was used before NCT. When 2 drops of lubricant were instilled, a significant amount of fluid ejection in the form of a sheet that broke up into multiple droplets was observed. Some of these droplets traversed back to the tonometer. Droplets ranging from 100 to 500 µm in diameter were measured. CONCLUSIONS: There was no droplet generation during NCT performed in a natural setting. However, NCT should be avoided in conditions with high-tear volume (natural or artificial) as it would lead to droplet spread and tactile contamination.

Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection.

OBJECTIVE: This study aimed to assess the presence of novel coronavirus in tears and conjunctival secretions of SARS-CoV-2-infected patients. METHODS: A prospective interventional case series study was performed, and 30 confirmed novel coronavirus pneumonia (NCP) patients were selected at the First Affiliated Hospital of Zhejiang University from 26 January 2020 to 9 February 2020. At an interval of 2 to 3 days, tear and conjunctival secretions were collected twice with disposable sampling swabs for reverse-transcription polymerase chain reaction (RT-PCR) assay. RESULTS: Twenty-one common-type and nine severe-type NCP patients were enrolled. Two samples of tear and conjunctival secretions were obtained from the only one patient with conjunctivitis yielded positive RT-PCR results. Fifty-eight samples from other patents were all negative. CONCLUSION: We speculate that SARS-CoV-2 may be detected in the tears and conjunctival secretions in NCP patients with conjunctivitis.