Ocular COVID-19: Eyes as a Reservoir to Conceal and Spread SARSCoV- 2.

Ocular tissues can serve as a reservoir for the SARS-CoV-2 virus which can not only cause conjunctivitis but also serve as a source of infection transmission to others. Additionally, the eye and its tear drainage apparatus can track the SARS-CoV-2 from the eye into the respiratory tract of the patient. The potential ocular presence of the SARS-CoV-2 in the eye of a patient can target ACE2 receptors in the endothelium of the conjunctival vessels and use the lacrimal sac a potential space to evade immune detection and clinical isolation. The recently reported case of COVID-19 after the acquisition of SARS-CoV-2 from a COVID-19 patient should alert the healthcare professionals dealing with COVID-19 patients that wearing masks alone cannot guarantee protection against infection transmission. Further studies, like isolation of SARS-CoV-2 from the eyes of patients with COVID-19, are needed to identify the eyes as a potential source of SARS-CoV-2 infection transmission.

The impact of far-UVC radiation (200-230 nm) on pathogens, cells, skin, and eyes - a collection and analysis of a hundred years of data.

Background: The ongoing coronavirus pandemic requires new disinfection approaches, especially for airborne viruses. The 254 nm emission of low-pressure vacuum lamps is known for its antimicrobial effect, but unfortunately, this radiation is also harmful to human cells. Some researchers published reports that short-wavelength ultraviolet light in the spectral region of 200-230 nm (far-UVC) should inactivate pathogens without harming human cells, which might be very helpful in many applications. Methods: A literature search on the impact of far-UVC radiation on pathogens, cells, skin and eyes was performed and median log-reduction doses for different pathogens and wavelengths were calculated. Observed damage to cells, skin and eyes was collected and presented in standardized form. Results: More than 100 papers on far-UVC disinfection, published within the last 100 years, were found. Far-UVC radiation, especially the 222 nm emission of KrCl excimer lamps, exhibits strong antimicrobial properties. The average necessary log-reduction doses are 1.3 times higher than with 254 nm irradiation. A dose of 100 mJ/cm2 reduces all pathogens by several orders of magnitude without harming human cells, if optical filters block emissions above 230 nm. Conclusion: The approach is very promising, especially for temporary applications, but the data is still sparse. Investigations with high far-UVC doses over a longer period of time have not yet been carried out, and there is no positive study on the impact of this radiation on human eyes. Additionally, far-UVC sources are unavailable in larger quantities. Therefore, this is not a short-term solution for the current pandemic, but may be suitable for future technological approaches for decontamination in rooms in the presence of people or for antisepsis.

Severe acute respiratory Syndrome-Coronavirus-2: Can it be detected in the retina?

BACKGROUND/OBJECTIVES: The systemic organ involvement of SARS-CoV-2 needs to be thoroughly investigated including the possibility of an ocular reservoir in humans. To examine retinal tissues and vitreous for histopathology and SARS-CoV-2 presence with regard to possible effects on the human retina and/ or vitreous. We performed histopathological analyses and quantitative (q)RT-PCR-testing for SARS-CoV-2 RNA on retinal tissues and vitreous of COVID-19 postmortem donors. SUBJECTS/METHODS: Included in this study were 10 eyes of 5 deceased COVID-19 patients. The diagnosis of SARS-CoV-2 infection was confirmed via pharyngeal swabs and broncho-alveolar fluids. The highest level of personal protective equipment (PPE) and measures was employed during fluid-tissue procurement and preparation. Histopathological examinations and qRT-PCR-testing were carried out for all retinal tissues and vitreous fluids. RESULTS: The histopathological examinations revealed no signs of morphologically identifiable retinal inflammation or vessel occlusions based on hematoxylin and eosin stains. By qRT-PCRs, we detected no significant level of viral RNA in human retina and vitreous. CONCLUSIONS: In this study, no significant level of SARS-CoV-2-RNA was detected in the human retinal and vitreous fluid samples of deceased COVID-19 patients. Histopathological examinations confirmed no morphological sign of damage to retinal vasculature or tissues. Further studies are needed to confirm or refute the results.

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

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.

Relationship Between Public Mental Health and Immune Status During the COVID-19 Pandemic: Cross-Sectional Data from Saudi Arabia.

PURPOSE: Coronavirus disease 2019 (COVID-19) has evolved into a worldwide pandemic and continues to escalate exponentially in many countries across the globe. Recently, higher rates of psychological distress have been reported in several countries during the pandemic. Accordingly, the study aim was to investigate the relationship between public mental health and immune status during the COVID-19 pandemic. METHODS: Participants of this cross-sectional study were 2252 national and foreign residents of Saudi Arabia. We used a web-based self-rated questionnaire to measure the association between psychological distress (Depression, Anxiety and Stress Scales [DASS-21]) and immune status (Immune Status Questionnaire [ISQ]) during the COVID-19 pandemic. We also investigated predictors of reduced immune status using binary logistic regression analyses. RESULTS: Data from 1721 respondents showed that 17.5% of participants scored below the immune status cutoff (ISQ ˂ 6). Mean (± standard deviation) depression, anxiety, and stress scores in the reduced immune status group (ISQ ˂ 6) indicated moderate depression, anxiety, and stress (19.1 ± 11.4; 15.0 ± 9.6; 21.8 ± 11.2, respectively) and were significantly higher than scores in the normal immune status group (ISQ ≥ 6) (8.6 ± 9.1, P ˂ 0.0001; 5.0 ± 6.7, P ˂ 0.0001; 9.3 ± 9.3, P ˂ 0.0001, respectively). The regression analysis showed that age, anxiety, and stress were the only factors that significantly predicted the presence of reduced immune status. CONCLUSION: There is an association between mental health problems during the COVID-19 pandemic and immune response in the public, especially in elderly people.

Ocular Involvement of SARS-CoV-2 in a Polish Cohort of COVID-19-Positive Patients.

The coronavirus SARS-CoV-2 responsible for the current human COVID-19 pandemic has shown tropism toward different organs with variable efficiency, eyes included. The purpose of this study has been to investigate the presence of detectable SARS-CoV-2 infection in ocular swabs in patients affected by COVID-19. A consecutive series of 74 COVID-19-positive patients (age 21-89) were enrolled at two Polish COVID-19 hospitals for 4 months and were characterized by PCR for the presence of the SARS-CoV-2 genetic material in nasopharyngeal (NP) and ocular swabs, while their respiratory and ocular symptoms were noted. Almost 50% of them presented with severe/critical respiratory involvement, and some degree of eye disease. No tight correlation was observed between the presence of ocular and respiratory symptoms. Three male patients presenting with severe/critical lung disease tested positive in ocular swab, however with mild/moderate ocular symptoms. In conclusion, our study lends further support to the view that overt ocular infection by the SARS-CoV-2 virus is not such a frequent occurrence.

In the eye of the storm: SARS-CoV-2 infection and replication at the ocular surface?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in December 2019 and spread quickly causing the coronavirus disease 2019 (COVID-19) pandemic. Recent single cell RNA-Seq analyses have shown the presence of SARS-CoV-2 entry factors in the human corneal, limbal, and conjunctival superficial epithelium, leading to suggestions that the human ocular surface may serve as an additional entry gateway and infection hub for SARS-CoV-2. In this article, we review the ocular clinical presentations of COVID-19 and the features of the ocular surface that may underline the overall low ocular SARS-CoV-2 infection. We critically evaluate the studies performed in nonhuman primates, ex vivo organ culture ocular models, stem cell derived eye organoids and the differences in infection efficiency observed in different parts of human ocular surface epithelium. Finally, we highlight the additional work that needs to be carried out to understand the immune response of the ocular surface to SARS-CoV-2 infection, which can be translated into prophylactic treatments that may be applied to other organ systems.

Multimodal imaging to aid in diagnosis of uveal effusion syndrome type 3.

A 47-year-old man presented to our retina clinic with gradual onset diminution of vision in his right eye for the last 3 months. Anterior segment evaluation was normal in both eyes. Fundus evaluation showed the presence of leopard spot appearance in the right eye with inferior exudative retinal detachment. Multimodal imaging was done to evaluate retinal pigment epithelium function, choroidal thickness, choroidal vascularity and scleral thickness. Multimodal imaging showed increased choroidal thickness, choroidal congestion on indocyanine green angiography and peripheral choroidal detachment with normal sclera thickness in our patient, thus pointing towards a diagnosis of uveal effusion syndrome type 3.

Catechin and curcumin interact with S protein of SARS-CoV2 and ACE2 of human cell membrane: insights from computational studies.

The recent outbreak of the coronavirus (SARS-CoV2) is an unprecedented threat to human health and society across the globe. In this context, development of suitable interventions is the need of the hour. The viral spike protein (S Protein) and the cognate host cell receptor ACE2 can be considered as effective and appropriate targets for interventions. It is evident from the present computational study, that catechin and curcumin, not only exhibit strong binding affinity to viral S Protein and host receptor ACE2 but also to their complex (receptor-binding domain (RBD) of the spike protein of SARS-CoV2 and ACE2; RBD/ACE2-complex). The binding affinity values of catechin and curcumin for the S protein, ACE2 and RBD/ACE2-complex are - 10.5 and - 7.9 kcal/mol; - 8.9 and - 7.8 kcal/mol; and - 9.1 and - 7.6 kcal/mol, respectively. Curcumin directly binds to the receptor binding domain (RBD) of viral S Protein. Molecular simulation study over a period of 100 ns further substantiates that such interaction within RBD site of S Protein occurs during 40-100 ns out of 100 ns simulation trajectory. Contrary to this, catechin binds with amino acid residues present near the RBD site of S Protein and causes fluctuation in the amino acid residues of the RBD and its near proximity. Both catechin and curcumin bind the interface of 'RBD/ACE2-complex' and intervene in causing fluctuation of the alpha helices and beta-strands of the protein complex. Protein-protein interaction studies in presence of curcumin or catechin also corroborate the above findings suggesting the efficacy of these two polyphenols in hindering the formation of S Protein-ACE2 complex. In conclusion, this computational study for the first time predicts the possibility of above two polyphenols for therapeutic strategy against SARS-CoV2.

Presence of SARS-CoV-2 RNA in the Cornea of Viremic Patients With COVID-19.

Importance: Current recommendations are to avoid tissue for corneal transplant from donors with coronavirus disease 2019 (COVID-19) or those who were recently exposed to COVID-19 owing to the lack of knowledge about the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in corneal tissues. Evidence of SARS-CoV-2 in corneal tissue would seem to have clinical relevance for corneal transplant. Objectives: To investigate the presence of viral SARS-CoV-2 RNA in corneal discs of deceased patients with confirmed COVID-19 and assess viral genomic and subgenomic RNA load, possible infectivity, and histologic abnormalities. Design, Setting, and Participants: A case series was conducted of 11 deceased patients with COVID-19 who underwent autopsy between March 20 and May 14, 2020. Eleven corneal discs (1 corneal disc per patient) were harvested for molecular detection of viral genomic and subgenomic RNA, virus isolation, and immunohistochemistry. The SARS-CoV-2 RNA loads were compared with RNA loads in the conjunctival and throat swab samples and aqueous humor, vitreous humor, and blood samples. Main Outcomes and Measures: Evidence of SARS-CoV-2 RNA in human corneas. Results: This study comprised 11 patients (6 women [55%]; mean [SD] age, 68.5 [18.8] years). In 6 of 11 eyes (55%), SARS-CoV-2 genomic RNA was detected in the cornea; subgenomic RNA was present in 4 of these 6 eyes (67%). Infectivity or the presence of viral structural proteins could not be confirmed in any eye. However, patients whose corneal disc was positive for SARS-CoV-2 RNA also had positive results for SARS-CoV-2 RNA in 4 of 6 conjunctival swab samples, 1 of 3 aqueous humor samples, 3 of 5 vitreous humor samples, and 4 of 5 blood samples. Overall, conjunctival swab samples had positive results for SARS-CoV-2 RNA in 5 of 11 cases. Postmortem SARS-CoV-2 viremia was detected in 5 of 9 patients. Conclusions and Relevance: Viral genomic and subgenomic RNA of SARS-CoV-2 was detected in the cornea of patients with COVID-19 viremia. The risk of COVID-19 infection via corneal transplant is low even in donors with SARS-CoV-2 viremia, but further research is necessary to assess the rate of SARS-CoV-2 transmission via corneal transplant.

SARS-CoV-2/human interactome reveals ACE2 locus crosstalk with the immune regulatory network in the host.

Severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), remains to be a threat across the globe. SARS-CoV-2 entry into the host is mediated by binding of viral spike protein to the Human angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is an essential member of the Renin-Angiotensin system (RAS) involved in maintaining the blood pressure and vascular remodelling. Although ACE2 receptor is the entry point to the host, recent studies show activation of ACE2 to modulate the host to develop a suitable environment for its replication. However, the ACE2 activating the immune signals on SARS-CoV-2 attachment is still under investigation. We have used systems biological approach to construct the host regulatory network upon SARS-CoV-2 attachment to the ACE2 receptor. Since lungs are the primary infection site, we integrate human lung gene expression profile along with the host regulatory network to demonstrate the altered host signalling mechanism in viral infection. Further, the network was functionally enriched to determine immune modulation in the network. We also used the proteomic database to assess the occurrence of similar signalling events in other human tissues that exhibit lineage of infection across different organs. The constructed network contains 133 host proteins with 298 interactions that directly or indirectly connect to the ACE2 receptor. Among 133 proteins, 29 were found to be differentially regulated in the host lungs on SARS-CoV-2 infection. Altered proteins connect multiple proteins in a network that modulates kinase, carboxypeptidase and cytokine activity, leading to changes in the host immune system, cell cycle and signal transduction mechanisms. Further investigation showed the presence of similar signalling events in the kidneys, placenta, pancreas, testis, small intestine and adrenal gland as well. Overall, our results will help in understanding the immune molecular regulatory networks influenced by the ACE2 mediated interaction in other body tissues, which may aid in identifying the secondary health complications associated with SARS-CoV-2 infection.

Unusual cause of acute sinusitis and orbital abscess in COVID-19 positive patient: Case report.

BACKGROUND: Peptoniphilus indolicus is not usually seen in the eye or paranasal sinuses but is a commensal of the human vagina and gut. However, with COVID-19, eye infections and other unusual complications are possible with such unsuspected bacteria. CASE PRESENTATION: The patient is a 76-year-old white male from a nursing home tested positive for COVID-19 and was sent from a nursing facility for left eye drainage and psychiatric evaluation. Upon presentation, the patient was not fully oriented and could not provide a history of the eye drainage. CT scan showed sinusitis with left orbital and periorbital abscess formation, cellulitis, and extensive osteomyelitis. He underwent endoscopic transnasal drainage and orbiotomy. Cultures returned positive for methicillin-resistant Stapholococcus aureus (MRSA), Streptococcus constellatus, and Peptoniphilus indolicus. He was maintained on several days of IV antibiotics and returned to the nursing home. He then presented 2 months later and required enucleation of his globe, due to the presence of multiple scleral perforations in the setting of orbital abscess, as well as removal of necrotic orbital bone. CONCLUSIONS: Given the concomitant infection with COVID-19 and unusual presentation, the patient's sinus cultures support the notion that COVID-19 can affect the presence of bacteria within certain anatomical regions. Specifically, Peptoniphilus indolicus is not normally found outside of the vagina or gut biome. Avascular, pale mucosa and bone of the nasal cavity was noted during surgery of this COVID-19 infected patient, which is in contrast to the friable and edematous tissue typically found in acutely infected sinuses. Our patient's orbital abscess began to drain spontaneously through the skin, which is rare for orbital abscesses. Also uncommon with orbital abscesses is the need for enucleation, which in this case was deemed necessary given that the abscess had perforated the sclera in multiple locations.

Psychological Typhoon Eye Effect During the COVID-19 Outbreak.

Background: The COVID-19 outbreak in Wuhan, Hubei, has brought serious consequences to the lives and mental health of people and has induced psychological stress and affected behavior. Methods: This study used self-designed questionnaires and SPSS to analyze the psychological and behavioral responses of people in different regions during the COVID-19 pandemic and to check for the presence of "psychological typhoon eye" (PTE) effects. The questionnaires adopted three measurement subscales, namely, the risk cognitive subscale, stress response subscale, and behavioral response subscale, and these were administered online (www.wjx.cn) to investigate the psychological and behavioral conduct of respondents from three areas that have been affected by COVID-19 to varying degrees. Exploratory factor analysis and principal component analysis were conducted to explore the factorial structure of these subscales, and confirmatory factor analysis was conducted to explore the structural validity of the questionnaires. The analysis results were used to build a revised 18-item questionnaire which validity was evaluated via ANOVA and LSD. Results: Results confirm the presence of PTE in the research areas during the onset of the COVID-19 outbreak and highlight some significant differences in the cognition and emotions of the residents in these areas. PTE affected the cognition, emotions, and cognitive and emotional responses of the respondents but did not affect their behavioral responses. Conclusion: The findings underscore the urgency of providing sustainable mental health care services across different areas during the COVID-19 outbreak. The residents of those areas worst hit by the pandemic, who may not have taken the situation seriously, require emotional guidance the most. Meanwhile, the residents of other areas, who showed the most negative psychological reactions to the pandemic, require a sense of security, a timely "disconnection" from negative information, an accurate cognition of stress, and an acceptance of self-responses.

Anti-SARS-Cov-2 IgA Response in Tears of COVID-19 Patients.

The pandemic virus SARS-CoV-2 has been reported to be able to enter the body via the eye conjunctiva, but the presence of antiviral response in the eye remains poorly known. Our study was thus aimed to analyze the presence of secretory mucosal anti-SARS-CoV-2 type A immunoglobulins (IgA) in the conjunctival fluid of COVID-19 patients. The tears of 28 COVID-19 patients and 20 uninfected controls were collected by the Schirmer test and analyzed by a specific ELISA assay detecting anti-spike (S1) virus protein IgA. The results showed that 35.7% of COVID-19 subjects have specific antiviral IgA at the ocular level, persisting till 48 days post disease onset. Most of the IgA positive subjects presented mild symptoms. The collected data indicate a prolonged persistence of anti-SARS-CoV-2 IgA at the eye level and suggest that IgA detection may be extremely helpful in clarifying virus pathology and epidemiology.

Ocular surface manifestation of COVID-19 and tear film analysis.

To evaluate the ocular manifestation in patients hospitalized with coronavirus disease 2019 (COVID-19) and to search for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in tears. This study was conducted in 29 hospitalized patients who were admitted to the COVID center at the Policlinic Hospital of the University of Messina, Italy. All patients underwent an ophthalmologic assessment comprising a Standardized Patient Evaluation of Eye Dryness (SPEED) questionnaire, anterior segment, and the ocular surface examination of both eyes using a portable slit lamp. The Schirmer I test was performed, and the filter paper strip was used to search for the presence of SARS-CoV-2 on the ocular surface by real-time quantitative polymerase chain reaction (RT-qPCR). A total of 10 patients reported ocular symptoms; in particular, four reported eye burning, three reported foreign body sensation, and three reported tearing. Moreover, seven patients presented conjunctival hyperemia and/or chemosis, eleven patients presented blepharitis signs such as lid margin hyperemia and/or telangiectasia, crusted eyelashes, and meibomian orifices alterations. Tear analysis did not reveal the presence of SARS-CoV-2. Ocular symptoms are common in patients with COVID-19; although, tear analysis did not reveal the presence of SARS-CoV-2.

Searching for effective antiviral small molecules against influenza A virus: A patent review.

Introduction: Despite the current interest caused by SARS-Cov-2, influenza continues to be one of the most serious health concerns, with an estimated 1 billion cases across the globe, including 3-5 million severe cases and 290,000-650,000 deaths worldwide. Areas covered: This manuscript reviews the efforts made in the development of small molecules for the treatment of influenza virus, primarily focused on patent applications in the last 5 years. Attention is paid to compounds targeting key functional viral proteins, such as the M2 channel, neuraminidase, and hemagglutinin, highlighting the evolution toward new ligands and scaffolds motivated by the emergence of resistant strains. Finally, the discovery of compounds against novel viral targets, such as the RNA-dependent RNA polymerase, is discussed. Expert opinion: The therapeutic potential of antiviral agents is limited by the increasing presence of resistant strains. This should encourage research on novel strategies for therapeutic intervention. In this context, the discovery of arbidol and JNJ7918 against hemagglutinin, and current efforts on RNA-dependent RNA polymerase have disclosed novel opportunities for therapeutic treatment. Studies should attempt to expand the therapeutic arsenal of anti-flu agents, often in combined therapies, to prevent future health challenges caused by influenza virus. Abbreviations: AlphaLISA: amplified luminescent proximity homogeneous assay; HA: hemagglutinin; NA: neuraminidase; RBD: receptor binding domain; RdRp: RNA-dependent RNA polymerase; SA: sialic Acid; TBHQ: tert-butyl hydroquinone; TEVC: two-electrode voltage clamp.

Ocular manifestations of a hospitalised patient with confirmed 2019 novel coronavirus disease.

PURPOSE: To report the ocular characteristics and the presence of viral RNA of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in conjunctival swab specimens in a patient with confirmed 2019 novel coronavirus disease (COVID-19). PARTICIPANT AND METHODS: A 30-year-old man with confirmed COVID-19 and bilateral acute conjunctivitis which occurred 13 days after illness onset. Based on detailed ophthalmic examination, reverse transcription PCR (RT-PCR) was performed to detect SARS-CoV-2 virus in conjunctival swabs. The ocular characteristics, presence of viral RNA and viral dynamics of SARS-CoV-2 in the conjunctival specimens were evaluated. RESULTS: Slit lamp examination showed bilateral acute follicular conjunctivitis. RT-PCR assay demonstrated the presence of viral RNA in conjunctival specimen 13 days after onset (cycle threshold value: 31). The conjunctival swab specimens remained positive for SARS-CoV-2 on 14 and 17 days after onset. On day 19, RT-PCR result was negative for SARS-CoV-2. CONCLUSION: SARS-CoV-2 is capable of causing ocular complications such as viral conjunctivitis in the middle phase of illness. Precautionary measures are recommended when examining infected patients throughout the clinical course of the infection. However, conjunctival sampling might not be useful for early diagnosis because the virus may not appear initially in the conjunctiva.