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      Detecting SARS‐CoV‐2 RNA in conjunctival secretions: Is it a valuable diagnostic method of COVID‐19?

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          Abstract

          The main purpose of this study is to evaluate the presence of viral RNA of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) in conjunctival swab specimen of coronavirus disease 2019 (COVID‐19) patients with and without conjunctivitis to establish the diagnostic value of reverse transcription‐polymerase chain reaction (RT‐PCR) in each case and to describe its clinical characteristics. A cross‐sectional study was conducted at the Hospital Clinico San Carlos of Madrid, Spain. Thirty‐six subjects from the COVID admission unit with laboratory‐confirmed SARS‐CoV‐2 infection were included. Conjunctival swabs were collected from 18 patients with conjunctivitis and 18 patients without conjunctivitis and RT‐PCR was performed. Conjunctival swab was collected from both eyes of 36 patients (72 eyes), detecting SARS‐CoV‐2 RNA in conjunctival swab of two patients (5.5%). Among the 18 patients with conjunctivitis, only one of them (5.5%) showed positive results. Likewise, SARS‐CoV‐2 RNA was detected in one patient without conjunctivitis (5.5%). The mean age of the 36 patients was 67.9 years (range, 28‐92 years) and the male‐to‐female ratio was 0.44 (16:20). The mean days since the onset of COVID‐19 symptoms until conjunctivitis manifestation was 8 (range, 1‐24 days). The mean duration of the conjunctivitis was 3 days (range, 1‐7 days). SARS‐CoV‐2 RNA may be detected in conjunctival swabs of both patients with and without conjunctivitis. This study revealed the same rate of positive results amongst the group with and without conjunctivitis, suggesting that detecting SARS‐CoV‐2 in ocular fluids is not conditioned on the presence of conjunctivitis. The presence of SARS‐CoV‐2 RNA in ocular samples highlights the role of the eye as a possible route of transmission of the disease.

          Highlights

          SARS‐CoV‐2 RNA can be detected in conjunctival secretions of both patients with and without conjunctivitis. However, PCR essay of tears and conjunctival secretions appear to have a fairly low potential of detecting the virus.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Conjunctivitis can be the only presenting sign and symptom of COVID-19

            Five cases of non-remitting conjunctivitis turned out to be the sole presenting sign and symptom of COVID-19. These patients tested positive on RT-PCR of naso-pharyngeal swabs and developed no fever, malaise, or respiratory symptoms throughout the course of their illness. They all fully recovered. In the current efforts to fight the spread of this virus, authors want to emphasize that atypical clinical presentations of COVID-19 can occur and a high level of suspicion should be maintained. Ocular involvement and transmission of SARS-CoV-2 should never be overlooked. In fact, conjunctival mucosae are susceptible to respiratory viruses and remain an important point of entry. For this reason, eye protection in the form of goggles or a face shield should be considered essential for all healthcare providers, even when taking care of patients who are not showing typical symptoms of COVID-19.
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              The prevalence of ophthalmic manifestations in COVID-19 and the diagnostic value of ocular tissue/fluid

              Dear Editor, The World Health Organization (WHO) has declared rapid infection of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) across the globe as a pandemic on March 11, 2020. Although the main mode of SARS-CoV-2 transmission is predominantly respiratory, several studies have suggested that exposure of unprotected eyes to the virus may also cause novel coronavirus pneumonia (NCP) [1, 2]. In agreement, a recent animal study also confirmed that macaque’s conjunctiva inoculated with SARS-CoV-2 lead to the development of mild interstitial pneumonia [3], implying that ocular tissues and fluid may be a potential alternative mode of SARS-CoV-2 transmission. So far, there have been varying reports regarding the prevalence of ocular manifestations among COVID-19-infected patients [2, 4–9]. Hence, in order to summarize the current evidence, a meta-analysis was conducted to estimate the prevalence of ocular manifestations among COVID-19-infected patients. In addition, the diagnostic value of ocular tissue/fluid in detecting SARS-CoV-2 was also evaluated. A comprehensive literature search was conducted from PubMed, Scopus, Web of Science, and Google scholar. Keywords such as “ocular/eye/ophthalmology,” “coronavirus 2019/COVID-19,” “2019-nCoV,” and “SARS-CoV-2” were used singularly or in combination without applying language restriction and dated up to April 4, 2020. Criteria of studies included in this meta-analysis were (1) observational studies that reported ocular symptoms among COVID-19-infected patients and (2) comparing diagnostic outcomes between ocular tissue and fluid (conjunctival swab/tears) and nasopharyngeal swab or sputum in detecting SARS-CoV-2 by polymerase chain reaction (PCR) analysis. Seven studies were included in this meta-analysis [2, 4–9]. Prevalence estimates of ocular manifestations were calculated from six studies [2, 4, 5, 7–9] (Table 1). Heterogeneity was evaluated with the I 2 statistic, in which an I 2 value over 50% was considered an indicator of substantial heterogeneity. If heterogeneity existed, the random-effects model was then used; otherwise, the fixed-effects model was applied. A funnel plot and Begg’s test were used to investigate the publication bias if the pooled effect size consisted of 10 or more studies. The value of 0.05 was indicative of the statistical significance. Table 1 Characteristics of included study in this meta-analysis Study Location No. of cases Women (%) Age Ocular symptoms PCR SARS-CoV-2 Yes No CS/tears NP/sputum Chen et al. [8] China 534 NR 40/50 (mean) 25 509 NR 371 Deng et al. [6] China 114 54 61.4 (mean) NR 114 0 90 Jun et al. [4] Singapore 17 NR NR 1 16 0 17 Wu et al. [5] China 38 34 68 (median) 12 26 2 11 Xia et al. [7] China 30 30 54.5 (mean) 1 29 0 29 Xu et al. [9] China 14 50 48 (mean) 1 13 0 14 Zhang et al. [2] China 102 50 57.63 (mean) 2 100 1 72 CS, conjunctival swab; NP, nasopharyngeal swab; NR, not reported; PCR, polymerase chain reaction The prevalence of ocular manifestations among COVID-19-infected patients ranged from 2 to 32%. The random-effects model was used due to heterogeneity (I 2 = 69.62%, p = 0.006). The overall pooled prevalence of ocular manifestations among COVID-19-infected patients was 5.5% (42/735 subjects, 95% CI 1.6–9.4%; Fig. 1). The pooled sensitivity and specificity were calculated from six studies [2, 4–7, 9]. Although the pooled specificity was high (100%, 95% CI 0–100), the pooled sensitivity of ocular tissue/fluid in detecting SARS-CoV-2 was very low (0.6%, 95% CI 0.1–5.1) in comparison with standard sample collection from nasopharyngeal swab/sputum (Table 1). Fig. 1 Forest plot of the 6 studies estimating the pooled prevalence of ocular manifestations among COVID-19-infected patients Therefore, in this current analysis, we emphasize that ocular symptoms have relatively low prevalence among COVID-19-infected patients. Interestingly, it seems that the ophthalmic manifestations appear to be associated with the disease severity of COVID-19 [5, 8]. And although ocular tissue/fluid is useable for SARS-CoV-2 detection, the procedure may not be useful for diagnostic purposes in the clinical setting. Despite the findings, ocular transmission of SARS-CoV-2 remains a crucial issue that requires vigilance of protecting the ocular surface and by wearing protective equipment during ophthalmic examination and handling of ocular fluids by the physician or health care worker.
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                Author and article information

                Contributors
                bburgos171@hotmail.com
                Journal
                J Med Virol
                J. Med. Virol
                10.1002/(ISSN)1096-9071
                JMV
                Journal of Medical Virology
                John Wiley and Sons Inc. (Hoboken )
                0146-6615
                1096-9071
                06 July 2020
                Affiliations
                [ 1 ] Servicio de Oftalmología, Hospital Clínico San Carlos Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC) Madrid Spain
                [ 2 ] Department of Microbiology Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IsISSC) Madrid Spain
                [ 3 ] Servicio de Oftalmología, Departamento de Inmunología, Oftalmología y ORL, Hospital Clínico San Carlos, Facultad de Medicina, Universidad Complutense de Madrid Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC) Madrid Spain
                Author notes
                [* ] Correspondence Barbara Burgos‐Blasco, MD, Department of Ophthalmology, Hospital Clinico San Carlos, Calle del Prof Martín Lagos, s/n, 28040 Madrid, Spain.

                Email: bburgos171@ 123456hotmail.com

                Article
                JMV26219
                10.1002/jmv.26219
                7361904
                32579256
                © 2020 Wiley Periodicals LLC

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

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                Figures: 0, Tables: 3, Pages: 6, Words: 3792
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                Microbiology & Virology

                conjunctivitis, coronavirus, covid, diagnosis, pcr

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