**2. Viral infections that induce eye damage**

In the last decade, the World Health Organization (WHO) has identified a list of infectious diseases that have the potential to evolve into epidemics resulting in health emergencies and increased economic pressure on healthcare systems worldwide. Moreover, for the viral infections included in the list, there are no effective preventive or curative countermeasures to date. Among the diseases included in the list were coronaviruses, responsible for the pandemic that exploded in 2020, Crimean-Congo hemorrhagic fever, Filovirus diseases (Marburg hemorrhagic fever and EVD), Lassa Fever, Nipah virus infection, Rift Valley fever, and Zika virus [15].

## **2.1 Ocular complications from coronavirus infections**

Coronaviruses include a family of viruses capable of infecting humans discovered for the first time in 1969; the transmission of the virus occurs mainly through respiratory droplets that in contact with the mucous membranes allow the virus to penetrate in the cells. There are seven coronaviruses that infect humans, and in 2002, the virus, named SARS-CoV-1, was isolated that mainly caused benign and mild infections of the upper respiratory tract [https://www.who.int]. Then in 2012, another virus causing respiratory syndrome named MERS-CoV was isolated in the Middle East [16]. The recent pandemic of Coronavirus-19 (COVID-19) due to SARS-CoV-2, which began in December 2019, has resulted in over 108 million cases and 2.3 million deaths. These highly transmissible pathogens cause lower respiratory tract infections that can rapidly progress to severe pneumonia with an estimated mortality rate of <1% for those aged 20–54 years, 1–5% in those aged 55–64 years, and 3–11% in individuals aged 65–84 years [17]. Unlike the other two diseases, COVID-19 symptomatology varies significantly between individuals. Indeed, while many patients develop respiratory

## *Nutraceutical Approach for the Treatment of Retinal Inflammation after Infections DOI: http://dx.doi.org/10.5772/intechopen.105687*

distress and fever, cough, and fatigue, some patients may have no respiratory symptoms at onset and present with extra pulmonary manifestations, including headache, diarrhea, and vomiting.

Ocular complications have not been reported in association with SARS-CoV-1 or MERS-CoV. However, a study of healthcare workers with SARS-CoV showed that three of 36 patients (8%) had traces of SARS-CoV RNA in their tear fluid [18]. Ocular involvement was reported to a greater extent in association with COVID-19. The most common ocular manifestation is conjunctivitis with disease prevalence ranging from 2% to 32% [19]. In addition, several studies have found the presence of viral RNA in lachrymal fluid such that there is a risk of transmission through the tear film [20]. Retinal manifestations have been described through imaging studies. In a study of retinal changes in 12 adults with COVID-19, all patients showed hyperreflective lesions at the level of ganglion cells and inner plexiform layers on OCT, and four had cotton wool and microhemorrhages [21]. Another study showed that six of 27 (22%) of the COVID-19 positive patients with bilateral pneumonia showed cotton wool at an average of 43 days after the onset of COVID-19 symptoms [22].

In addition, the development of optic neuritis, disc edema, vascular tortuosity, acute macular neuroretinopathy (AMN), retinal occlusive vasculopathy (RVO), retinal artery occlusion, intraretinal hemorrhages, cotton wool, uveitis, and endogenous endophthalmitis has been reported in patients who tested positive and had moderate to severe COVID-19 symptoms. Often these diseases affecting the retina and retinal vasculature are the subject of single-case studies so it is necessary to expand these investigations in order to test the incidence of ocular complications of COVID-19 on a large scale [23].

## **2.2 Zika virus**

The Zika virus is a flavivirus transmitted by Aedes mosquitoes and is related to yellow fever virus, dengue virus, and West Nile virus. Flaviviruses are single-stranded RNA viruses contained in capsid and coated with pericapsid. The genome encodes for a total of 10 proteins of which seven are nonstructural and three structural including: glycoprotein E (responsible for host cell infection and antigenic determinant of antibody response), capsid protein C, and membrane protein M (**Figure 1**) [24]. Zika virus was first identified in Uganda in 1947 in macaques and then in humans as early

## **Figure 1.**

*Zika virus 3-D structure (Font: modified https://www.socialnews.xyz/2016/04/01/scientists-revealzika-virus-structure/).*

as 1968. It has also been identified in French Polynesia, where an outbreak has been associated with perinatal transmission and fetal abnormalities. The virus currently present in Brazil appears to have originated from Polynesia. The clinical findings of the primary infection mimic both the dengue virus and the chikungunya virus, also present in Brazil and carried by the same mosquito. Testing for Zika virus is not readily available, making diagnosis challenging; however, serologic testing (IgM quantification) can be performed, and polymerase chain reaction (PCR) is available [25].

In adults, Zika virus infection induces symptoms such as: fever, headache, skin rash, muscle aches, diarrhea, and eye redness (**Figure 2**); but the most serious complications occur if the virus is contracted during pregnancy and especially within the first trimester. Zika virus infection, contracted in the first or second trimester of pregnancy, results in the development of microcephaly and retinal lesions in the fetus. In a study of 29 infants born to mothers who had experienced symptomalogy attributable to Zika virus, ocular abnormalities were present in 35% of the infants examined, and in seven of 10 cases they were bilateral. Characteristic lesions included posterior pole pigment deposits and areas of chorioretinal atrophy [26].
