Eyewear Significantly Helps Reduce Risk Of COVID-19 Infection


A new study conducted by researchers from University College London (UCL)-UK as part of the Virus Watch prospective community cohort study in England and Wales, has found that eyewear significantly helps reduce risk of COVID-19 infection.

The study findings were published on a preprint server and are currently being peer reviewed.


espiratory viruses infect individuals via the nose, mouth and eyes, through contact with surfaces touched by the individual or via small and larger (i.e. droplet) aerosol particles.1

Recommendations for the protection of the general public in most countries include social distancing, handwashing and face mask use but not eye protection. In the UK eye protection (including full face visors or goggles) is recommended in healthcare settings if blood or body fluid contamination to the eyes or face is anticipated or likely.

Also if caring for patients with a suspected or confirmed infection spread by the droplet or airborne route as deemed necessary by a risk assessment, or during aerosol generating procedures.2 Regular corrective glasses are not considered as eye protection.

The eyes present two routes for SARS-CoV-2 infection, the first through infection of conjunctival cells that contain ACE2 receptors. Several studies have detected SARS-CoV-2 RNA in the tear film, conjunctiva and conjunctival sac with between 1-12% of patients with COVID-19 reported to have ocular manifestations.3–6

The second infection route is via the nasolacrimal duct, which is known to transport pathogens to the nose within minutes and onward to the nasopharynx.7 Supporting the eye as a route of SARS-CoV-2 infection, conjunctival inoculation of the virus in macaques leads to interstitial pneumonia in macaques.8

A small number of hospital based observational studies suggest that eye protection may help prevent COVID-19.9 Amongst these, an observational study of 276 COVID-19 patients admitted to a hospital found the proportion of spectacle wearers was lower than the general population.10

Based on the biological mechanisms and studies in healthcare we hypothesised that glasses wearing in community settings would reduce the risk of COVID-19.

Glasses may provide a barrier to prevent exposure to infectious aerosol particles, particularly the ballistic component of larger particles, and may also reduce contaminated fingers touching the eyes.

We do not expect to see this same protective effect in a counterfactual contact lens analysis. We therefore developed a survey on glasses and contact lenses within the Virus Watch cohort to test these hypotheses. The aim of this study was to test the hypothesis that wearing glasses is associated with a lower risk of COVID-19.

In the middle of the COVID-19 pandemic, various healthcare systems in ophthalmol- ogy including routine patient care and surgeries were greatly affected. Although various ophthalmological societies have issued their statements, there are still no universally agreed upon guidelines [5]. For instance, it is essential for ophthalmologists to know whether donor corneas obtained from COVID-19 patients or asymptomatic patients can be avail- able for corneal transplantation. Therefore, an understanding of the viral replication and transmission is essential for a proper diagnosis and standard precaution.

Our review highlights the viral entry mechanism of the ocular surface as an essential part of the pathogenesis of conjunctivitis. For this, we described the infectious pathway of SARS-CoV-2, which belongs to the family of RNA viruses, and we investigated reports of transmission and disease course in the eye. Although many reports of SARS-CoV-2 have been published, there are still limited data with reports on the eye, and it is controversially debated if SARS-CoV-2 can infect the ocular surface and transmit via the ocular fluid [6]. Napoli et al. suggest that the virus is capable of replicating in the conjunctiva [6]. Therefore, the wearing of eye protection is strongly recommended to prevent transmission. In our review, we discuss the most recent studies on this topic.

Furthermore, we illustrate the viral structure and highlight the known receptor and coreceptors of SARS-CoV-2 to explain the mechanism of the ocular tropism, and trans- mission routes. Finally, we also present the available literature with regard to feasible therapeutic strategies.
Our review shows that the existence of the molecular structures on the ocular surface has been demonstrated. Even when the replication at the ocular surface is described as low, a possible transmission could be expected and a precaution against possible transmissions is strongly recommended.

Ocular Signs of COVID-19 Patients
Viral conjunctivitis causes hyperemia of the bulbar and palpebral conjunctiva due to an inflammation in the conjunctiva, and increases eye discharges, tearing, itchiness, irritation, and gritty feelings on the ocular surface [7]. Severe symptoms lead to conjunctival edema, swelling of the eyelid, or as part of general cold symptoms, with swollen lymph nodes anterior to the ear, fever, a sore throat, and runny nose.
The incubation period of COVID-19 is about 1 to 14 days, and the WHO reports that the average time from infection to the onset of symptoms is about 5 to 6 days. Ocular symptoms usually appear after the onset of respiratory symptoms. However, it should be noted that prodromal ocular symptoms occurred in approximately 10% of COVID-19 patients [8–10], and delayed onset of conjunctivitis after severe COVID-19 infection was observed in some cases [11–13].

Ocular signs in patients with SARS-CoV-2 infection are still not well-described. It has been almost a year since the WHO declared the COVID-19 pandemic, and the evidence of ocular manifestation in COVID-19 patients is gradually accumulating. Our current system- atic review and meta-analysis, with 15 studies involving 1533 patients with SARS-CoV-2, revealed that 11.2% of patients had ocular symptoms, mostly presenting with conjunctivitis (86.4%), followed by ocular pain, dry eye, and floaters [8]. Large retrospective clinical studies regarding SARS-CoV-2 do not include detailed ophthalmic examinations, because patients with SARS-CoV-2 present with life-threatening clinical scenarios [1]. In general, SARS-CoV-2 does not appear to attract significant reactions from the immune system at the ocular surface and is thus rarely associated with inflammatory responses of the ocular surface, unlike with the respiratory system [14]. The natural history of COVID-19 seems to be rapid self-limited conjunctivitis that improves without any treatment and does not affect visual acuity, nor is associated with short-term complications [15]. However, Cheema et al. reported that one patient initially presented with herpes-like pseudodendritic infiltration on the cornea, leading to a decline in vision due to severe keratoconjunctivitis [16], and relapsing viral keratoconjunctivitis and conjunctivitis with pseudomembranous also have been reported [12,17]. The corneal sensitivity testing assessed by the Cochet–Bonnet aesthesiometer did not seem to change in COVID-19 patients, unlike with herpes viruses [18]. Case reports with episcleritis [19,20] have been reported as well, suggesting that SARS- CoV-2 can be involved in the cornea and sclera as well as in the conjunctiva.
Recent reports revealed that the retina might also be affected post SARS-CoV-2 infec- tion [21,22]. Detailed analyses with optical coherence tomography (OCT) demonstrated hyperreflective lesions at the level of ganglion cell and inner plexiform layers more promi- nently at the papillomacular bundle [22]. However, OCT angiography was reportedly normal, suggesting that it can raise some questions as to whether these findings are patho- logical conditions. Another case with retinal vein occlusion (RVO) in a COVID-19 patient has been recently reported [21]. This case is a 52-year-old male and does not have any underlying medical condition to possibly cause RVO, such as diabetes, hypertension, or tuberculosis, indicating RVO occurs secondary to SARS-CoV-2 infection. Recent more papers demonstrated several cases with central RVO [23–26]. However, it is still unclear whether it is caused by the direct SARS-CoV-2 infection to the retina or by thrombosis in the retinal vascular vessels due to the cytokine storm associated with COVID-19. Further, the intense inflammation may drive the severe allograft rejection after corneal transplantation, which required repeat penetrating keratoplasty (PK) [27]. Chorioretinitis from fungal sepsis has also been reported [18]. The severe COVID-19 patients hospitalized in an intensive care unit (ICU) setting may be attributed to secondary fungus endophthalmitis [18]. Case re- ports with acute macular neuroretinopathy [28,29], optic nerve infarction [30], and cerebral venous thrombosis [31,32] have been reported as well. Thus, the inflammatory-associated responses secondary to COVID-19 should be paid careful attention.

Viral Structure of SARS-CoV-2
Viruses are characterized by a simple structure composed of a viral genome and a nucleocapsid. The capsid serves as a protein coat to protect the viral genome, organized in a helical or spherical manner. It is assembled by single protein components, defined as capsomers. However, some viruses are composed of both shapes and are therefore referred to as complex viruses.
The nucleic acids contain either single- or double-stranded RNA or DNA, forming together with the protein-composed capsid the nucleocapsid [33]. An optional structure is a viral envelope, assembled by a phospholipid bilayer with glycoproteins. This structure originates from the nuclear or plasma membrane of the host cell. Within this common microstructure, the particles differ remarkably in size, form, and shape [34]. In our review, we describe Coronaviridae in the following section, particularly focusing on the structures involved in the entry mechanism.

Members of the family Coronaviridae are enveloped, single-stranded RNA-viruses. Despite the vulnerability of enveloped viruses concerning environmental resistance, human coronaviruses (HCoV) are relatively highly resistant to destruction due to temperature and humidity [35]. This characteristic is a major contributor to the current COVID-19 pandemic, the outbreak of SARS-CoV-2, which is expected to have occurred in Wuhan, China in 2019 [36]. The family of Coronaviridae is further classified into the subfamilies Coronavirinae and Torovirinae, revealing the largest known RNA genome (25–32 kb). Characterized by a spherical virion structure, the virus envelope is composed of glycoproteins. Here, the spike (S) protein is the major protein responsible for the typical appearance of the virus.

In total, Coronaviruses encode for 4 proteins. In addition to the S protein, further proteins are involved in the formation of the membrane, named membrane (M) and envelope (E) proteins. The nucleocapsid (N) protein forms the flexible nucleocapsid [37]. In general, infections by HCoV lead to respiratory diseases, with symptoms of the common cold and upper respiratory tract infections. However, since the outbreak of the severe acute respiratory syndrome (SARS) virus in 2002, the fatal potential became evident. However, even case reports of keratoconjunctivitis have been reported, which are likely to be more common and could be an important early detection symptom [17]. The emerging variant SARS-CoV-2 presents a significantly increased infectivity compared

to SARS-CoV. One of the major explanations for this is a mutation of the S protein [38]. Recently detected novel variants of SARS-CoV-2 show mutations at the spike protein leading to higher infectivity of the virus [39]. Independent authors have determined that there is an increased viral load triggered by the D614G mutation [40,41]. Currently, several mutations are identified, and the risk of a further exacerbation of the pandemic due to the increased infectivity is possible.

Figure 1. Overview of SARS-CoV-2 entry molecules, clinical manifestations, and transmission on the ocular surface with references. Figure created with BioRender.com. COVID-19: Coronavirus disease 2019, SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2, OCT: Optical Coherence Tomography, RVO: Retinal Vein Occlusion, qRT-PCR: Quantitative reverse transcription polymerase chain reaction, Ct: Cycle threshold, ACE2: Angiotensin-converting enzyme 2, TMPRSS2: Transmembrane serine protease 2, CTSL: Cathepsin L, DPP4: Dipeptidyl peptidase-4, IFN: Interferon.

Modes of Transmission and Prevention of Viral Infections

In recent years, different transmission pathways of viruses have been proposed [81]. In general, the transmission of enveloped viruses (Coronaviridae) is attributed to direct and indirect contact, respiratory droplets, and airborne transmission [82,83]. Unlike non- enveloped viruses (i.e., Adenoviridae), enveloped viruses are easily inactivated by routine surface cleaning and disinfection. Appropriate personal protection should be taken for those responsible for the decontamination of a room or area. In the subsequent chapter, the transmission routes of coronaviruses are highlighted separately, followed by a discussion of prevention strategies.

Transmission Routes of SARS-CoV-2
The main transmission pathway of SARS-CoV-2 is the respiratory tract. However, extrapulmonary routes for transmission have also been described in the literature. In

addition to respiratory droplets, contact transmissions by touching contaminated surfaces also seem to play a role, as data on the infection of mucous membranes have recently been published [84]. The spread of infection through the hands seems to play a significant role, particularly triggered by fecal infection. An observational study showed that people touched common surfaces and their mouth or nose mucosa at a rate of 3.3–3.6 times per hour [85]. This suggests that, even if the chances of infection are small, the ocular surface may become an entry point for the virus and a reservoir for viral infection. Our previous systematic report indicated that a viral infection is possible through the eye route [8]. Here, the testing of conjunctival swabs was positive in 16 out of 60 cases (27%) [8], and SARS- CoV-2 RNA was detected in tears and conjunctival secretions [45]. In addition, RNA in the tear fluid of patients with moderate to severe COVID-19 was collected with a conjunctival swab or the Schirmer test, and the differences depending on the collection method were examined. However, the collection rate was similar in either method, and the detection rate of viral RNA in the tears reached 24% [47], while no viral RNA was detected in the tear fluid in COVID-19 patients [86,87]. Furthermore, the investigation of human post- mortem ocular tissues in COVID-19 patients found that there was no SARS-CoV-2 RNA in the different parts of ocular tissues and intraocular fluid including corneal epithelium, stroma and endothelium, conjunctival epithelium and fluid, and the anterior chamber [88]. Although we cannot deny if the eye is the transmission route, it suggests that the eye does not seem to be a common transmission route.

However, the majority of COVID-19 studies did not report and investigate the use of eye drops, which could have a potent antiviral effect. In fact, the systematic review by Napoli et al. revealed that many of the eye drops routinely used in ophthalmology, even artificial tears, have antiviral effects, and it is necessary to discuss whether or not the use of anti-glaucoma and anti-allergy eye drops as well as antibiotics eye drops, should be investigated [89]. More recent reports also analyzed donor ocular tissues in COVID-19 patients, and SARS-CoV-2 RNA was detected in 17 out of 132 samples (13%), including cornea and sclera samples, and the SARS-CoV-2 enveloped protein was also detected in the cornea of the COVID-19 donors [90]. Another report also showed SARS-CoV-2 genomic RNA detected in the cornea [91]. Chen et al. described secondary conjunctivitis after 13 days of respiratory illness due to COVID-19 [13].

Here, the occurrence of bilateral con- junctivitis with watery eyes was impressive. The authors strongly suggest the importance of caution when performing an ophthalmic examination. Interestingly, the quantification of SARS-CoV-2 RNA expression was determined with cycle threshold (Ct) values, and RNA in a COVID-19 patient at acute phase was detected at 31 cycles; Ct values were decreasing as their ocular finding improved [13]. Furthermore, RNA obtained from the COVID-19 donors was detected at 29 to 35 cycles [90], which were relatively lower Ct values compared to those of nasal and throat [92], suggesting that viral loads in the ocular surface do not seem to be high. Although only high crossing points were detected in the qRT-PCR of the conjunctival swabs, transmission by this route would be possible.

In addition to the onset of ocular symptoms during a COVID-19 course of infection, primary ocular-triggered infection is also possible. Deng et al. have demonstrated that the conjunctival infection of rhesus macaques leads to pneumonia [93]. Interestingly, this infection route resulted in mild pneumonia with a lower viral load compared to an intratracheal infection. This indicates that the virus can indeed spread from an ocular infection in a generalized manner throughout the entire organism.

These findings correspond to the expression of ACE2 and TMPRSS2 on the conjuncti- val surface [52,66]. The results of Zhou et al. are in contrast to other studies, demonstrating that ACE2 and other entry factors of SARS-CoV-2 including ENPEP, ANPEP, DPP4, and TMPRSS2 are not substantially transcribed in conjunctival tissues [94]. However, since the infection has now been proven, it seems correct that the conjunctiva shows a lower expression rate of essential receptors than does the respiratory tissue. Nevertheless, the drainage of tears through the nasolacrimal gland could be particularly involved in this process [86].

Prevention of Viral Transmission Triggered by Ocular Infections
SARS-CoV2 is a highly contagious virus. Since viruses can be transmitted in various ways, a spread of infection through the eye should not be excluded. Social distancing is the most reliable precaution. Wearing masks by people, including all the time by patients, can help limit the spread of the virus that causes COVID-19. The Centers for Disease Control and Prevention (CDC) recently proposed that wearing a cloth mask on top of a surgical mask helps improve the fit of the surgical mask, a technique called double masking [95]. It is also useful to limit the number of patients in a room who might spread the virus, by an arrangement of their medical appointment schedules, and to screen patients who have any COVID-19 symptoms or potential SARS-CoV2 exposure history, including travel and contact with someone who has been diagnosed with COVID-19 within the previous 14 days. As provided in the guidelines of the American Academy of Ophthalmology and other ophthalmology societies, social distancing in waiting rooms, frequent disinfection, and mandatory mask use have been suggested [5]. However, there is still the lack of universally agreed recommendations on safety systems and legal protection for clinical ophthalmologists, and it is essential to accumulate the further evidence in the future.

The instruments for eye examinations, including slit lamps and their accessory lenses, have also been known to be a source of viral transmission [96]. Among eye examinations, non-contact tonometry may pose a risk for transmission of the SARS-CoV-2 due to air pressure to measure intraocular pressure (IOP), which is one of the most frequent tests in daily practice. Various academic societies have made recommendations on its use and measures to be taken [89]. For instance, the EuroTimes recommends avoiding the use of non-contact tonometers, and using contact tonometers with disposable tips. The American Academy of Ophthalmology allows contact tonometers with reusable tips with 70% ethanol disinfection, but basically recommends the use of disposables.
In the clinical setting, the ophthalmic examination room is limited, and ophthalmol- ogists are quite close to the patients whenever they see the patients. An experimental simulation study revealed that simulated coughing spread droplets throughout the entire examination room. Respiratory droplets were reduced with masking, but were still ob- served on the slit lamp joystick and the slit lamp shields [97,98]. Based on the surface area of the slit lamp, it was found that about half of the area was contaminated by the patient’s exhaled air [99]. Since SARS-CoV-2 RNA in tears and conjunctival secretions of COVID-19 patients was detected [45,47], careful attention should be paid to the spread of viruses via ophthalmic instruments, towels, doorknobs, etc., because large amounts of the virus could be contained in eye discharges and tears during viral infection [100].
In the beginning of the pandemic, corneal transplant surgeries were greatly affected due to a large shortage of donor corneas [101]. In Europe, donor corneas decreased by 38%, 68% and 41%, respectively, during March–May 2020 compared with those in last 2 years [101]. In India, eight out of the 20 eye banks did not collect corneal tissue from April to June 2020, and the number of transplants dropped by two-thirds [102]. In addition, more than half of the surgeons decided not to perform oculoplastic surgeries in consideration of the COVID-19 pandemic, and about 1/4 of the surgeons performed only emergency surgery [103]. Delays in vitreous injections for the treatment of retinal diseases also occurred, with a delay of more than two months and the need for three or more injections in the past being significant poor prognostic factors for visual outcome in diabetic macular edema patients and macular degeneration [104,105]. It has been pointed out that cataract surgeries may also be discontinued or postponed during a pandemic and that this may lead to long-term retention of patients [106], and we need to consider measures to move healthcare appropriately even during a coronavirus pandemic.
There are several experimental reports on the transmission of SARS-CoV2 during cataract surgery. During phacoemulsification and irrigation/aspiration, droplets from the intraocular reflux fluid may adhere to the surgeon’s gloves and gown [107]. However, in a study of visualization of aerosols and droplets during cataract surgery in real-world settings, no visible aerosolization was detected, and droplets were detected but not by an

water indicator, confirming direct contact [108]. This suggests that although droplets do occur, they do not pose a significant infection risk to the surgeon.
The importance of eyeglasses has also been proposed. A member of the national expert panel on pneumonia in Wuhan, China, who was infected by COVID-19, wore an N95 mask but did not wear anything to protect his eyes [109], and the Chinese ophthalmologist who was working on the treatment of COVID-19 patients later passed away. Another report revealed that patients wearing glasses constituted a lower percentage of patients who were hospitalized than did the general population [110], suggesting that a face shield and a proper shield between patients and ophthalmologists can protect people from and help to limit the SARS-CoV2 transmission. However, the wearing of eye protection may not be beneficial only for the treating physicians. Napoli et al. suggest that particularly immunocompromised patients can benefit enormously [6].
The prevention of the spread of SARS-CoV-2 from pre-symptomatic patients is es- sential, especially since tear fluid could be contagious before symptoms arise. In fact, in outpatients with no COVID-19 symptoms who received ophthalmic examinations in the same room as they usually do, the qRT-PCR testing for SARS-CoV-2 on the tables and oph- thalmic instruments revealed two positive samples, which were taken from the slit lamp breath shield and the phoropter, respectively [111]. Since it is challenging to remove viruses from the skin and environmental surfaces, frequent hand hygiene is important for patients and for those who may have come into contact with items to which the virus is attached. Regular handwashing and surface disinfection of instruments for an eye examination with 0.1% of sodium hypochlorite or 70% ethanol reduce the potential risks of transmitting the virus. When in contact with patients, gloves, masks, and glasses should be used to protect against infection. According to infection control practices [112], it is necessary to follow the contact and droplet precautions, environmental cleaning and prompt response, and report clusters of cases. Of course, there is no doubt that telemedicine is effective in reducing the risk of the spread of the virus, and unnecessary eye examinations in diagnosis and management have to be avoided.

Therapy for Conjunctivitis Associated with SARS-CoV-2
There is currently no specific treatment for viral conjunctivitis, although bacterial conjunctivitis can be treated with antibacterial medication for two to three days, and the symptoms will improve. COVID conjunctivitis, like any other viral conjunctivitis, is generally self-limiting and can be managed with lubricants and symptomatic treatment, unless the cornea is involved. However, severe keratoconjunctivitis also has been reported in patients with COVID conjunctivitis [16,17]. Thus, the ocular treatment might need to be investigated.
TMPRSS2, CTSL, CD147, ADAM-17, and DPP4, in addition to ACE2, are involved in the viral entry of SARS-CoV-2. The understanding of viral entry could lead to the development of new therapeutic approaches. Most COVID-19 candidate vaccines express the spike protein or parts of the spike protein, i.e., the receptor-binding domain, as the immunogenic determinant. The vaccines that have been developed by BioNTech/Pfizer and Moderna/NIAID encode the SARS-CoV-2 spike (S) glycoprotein, stabilized in its prefusion conformation [113]. The potential treatment for COVID-19 are summarized in Table 1.
There are many types of ACE2 modulators, including recombinant soluble ACE2 and indirect ACE2 modulators such as angiotensin receptor blockers (ARBs), calmodulin antagonists, and selective estrogen receptor modifiers. Although it is not available for ocular treatment, eye drops can be less difficult for ocular application as there is some evidence that eye drops can be repurposed from systemic treatment [114]. Recombinant soluble ACE2 has already been clinically tested in acute respiratory distress syndrome [115], with phase 1 and 2 clinical trials, and, more recently, APN01 as a recombinant soluble ACE has been conducted for SARS-CoV-2 in a phase 2 clinical trial, and the study was completed as of December in 2020 (NCT04335136). As for ARBs, so far, there are more than

10 ongoing clinical trials [116]. Calmodulin (CALM) antagonists inhibit the CALM–ACE2 interaction and increase the release of the ACE2 ectodomain in a dose- and time-dependent manner [117]. Melatonin, which is known to inhibit calmodulin interaction with its target enzymes, and toremifene, which is a nonsteroidal antiestrogen that blocks the effects of estrogen, have been tested for evaluation of efficacy in several clinical trials (NCT04531748). The randomized elimination and prolongation of ACE inhibitors and ARBs in COVID-19 Trial Protocol is already underway with worldwide collaboration [118]. Similarly, use of an enhancer of ADAM-17, a metalloproteinase involved in the shedding of ACE2, can potentially work as a drug for the treatment of COVID-19 [119].

Another strategy could be the blocking of transmembrane protease TMPRSS2. Hoff- mann et al. have reported that Camostat mesylate blocked the SARS-CoV-2 infection into lung cells [65]. Nafamostat, which is a drug similar to Camostat and has been widely used in clinical practice in Japan, blocked the entry process of the virus at a concentration of less than one-tenth [120]. In parallel, high throughput drug screening found that amantadine hydrochloride, which is approved by the US Food and Drug Administration for influenza and Parkinson’s disease, downregulated CTSL mRNA expression, a protease involved in spike protein activation [121]. Teicoplanin is an antibacterial drug that is already in clinical use, and it may also block SARS-CoV-2 entry through the inhibition of CTSL activ- ity [122,123]. Targeting TMPRSS2 and Cathepsin B/L together may be synergistic against SARS-CoV-2 infection [124].

Apart from the proteases, blocking of CD147, also known as basigin (BSG) or EMM- PRIN, a transmembrane glycoprotein, by the monoclonal antibody meplazumab has been found to inhibit binding of the SARS-CoV-2 spike protein [72]. Azithromycin, which is an antibiotic, induces anti-viral responses in host cells by the activation of an innate immune response via an increase in levels of interferons and interferon-stimulated proteins, and can be effective in the inhibition of SARS-CoV-2 invasion of host cells, possibly interfering with CD147/BSG [125]. A recent report claimed that no supporting evidence for a direct interaction of the SARS-CoV-2 spike protein with CD147/BSG was found [126].

Table 1. Potential drugs for the treatment of SARS-CoV-2.

Name of Potential DrugsTargetsFunction
APN01ACE2Soluble ACE2 [115] [NCT04335136]
Angiotensin receptor blockerACE2ACE2 modulator [116]
MelatoninACE2Calmodulin inhibitor [117]
ToremifeneACE2Nonsteroidal antiestrogen [NCT04531748]
5-fluorouracilADAM-17ADAM-17 enhancer [119]
Camostat mesylateTMPRSSTMPRSS inhibitor [65]
Nafamostat mesylateTMPRSSTMPRSS inhibitor [120]
AmantadineCTSLCTSL inhibitor [121]
TeicoplaninCTSLCTSL inhibitor [122,123]
MeplazumabCD147Anti-CD147 [NCT04275245]
AzithromycinCD147Indirect CD147 inhibition [125]
SitagliptinDPP4DDP4 inhibitor [127]

The primary receptor for MERS and a predicted co-receptor for SARS-CoV-2, DPP4, a serine exopeptidase, can also be targeted for blocking the entry of the virus [79]. It has been reported that soluble DPP4 in the blood is decreased in patients with severe SARS- CoV-2 infection. A study in Italy, where the hospitalized COVID-19 patients were treated with or without the DDP4 inhibitor sitagliptin, revealed that the DPP4 inhibitor treatment improved the mortality and clinical scores, resulting in earlier hospital discharges [127].

In addition, the present topical ophthalmic medications may have potent antiviral effect. Napoli et al. performed a systematic analysis regarding the antiviral effect of topical ophthalmic medications [89]. They found that many ophthalmic eye drops have antiviral effects, including preservatives and disinfectant agents such as benzalkonium chloride and chlorhexidine, artificial tear drops, anti-glaucoma eye drops, and anti-allergy eye drops.

Anti-inflammatory drugs generally have an immunosuppressive effect, but interestingly, non-steroidal anti-inflammatory drugs (NSAIDs) also have an antiviral effect. Thus, existing topical ophthalmic medications may also be effective in treating COVID conjunctivitis as drug repurposing, which is the strategy of identifying new uses for a drug that has already been approved, outside of its original medical indication. This strategy offers a number of advantages over developing an entirely new drug for one indication over an existing ophthalmic drug, and detailed future studies are needed.

reference link : https://doi.org/10.3390/ cells10040796



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