key: cord-0935915-svk1v86g authors: Tohamy, Dalia; Sharaf, Mohamed; Abdelazeem, Khaled; Saleh, Mohamed G A; Rateb, Mahmoud F; Soliman, Wael; Kedwany, Salma M; Omar Abdelmalek, Mohamed; Medhat, Mohammed A; Tohamy, Amal M; Mahmoud, Hany title: Ocular Manifestations of Post-Acute COVID-19 Syndrome, Upper Egypt Early Report date: 2021-07-23 journal: J Multidiscip Healthc DOI: 10.2147/jmdh.s323582 sha: 5374ee37be2eee462ad678094fa42a2c91588fd3 doc_id: 935915 cord_uid: svk1v86g PURPOSE: To evaluate the ocular manifestations of post-acute COVID-19 syndrome. METHODS: A retrospective, comparative study included 100 patients who had recovered from COVID-19 and 100 controls who were recruited by stratified randomization from hospital registration system and analyzed regarding history, full ophthalmological examination, general examination including internal medicine and neurological evaluation. Laboratory tests were done. RESULTS: Mean±SD of age were 55.5 ± 6.2 in COVID group vs 56.5 ± 5.8 in control group; P value = 0.7. In COVID group, 57 patients (57%) were males vs 51 patients (51%) in control group (P value = 0.39), the other compared parameters including history and risk factors showed non-significant difference except for ESR and D-dimer which were elevated in COVID group. In COVID group, 5 patients (5%) were having retinal vascular occlusion, 2 patients (2%) were having anterior ischemic optic neuropathy AION, 3 patients (3%) were having uveitis and 2 patients (2%) were having central serous chorioretinopathy CSCR. While in control group, 2 patients (2%) were having retinal vascular occlusion, and none had AION, uveitis or CSCR (P value = 0.006). CONCLUSION: Post-acute COVID-19 syndrome could affect the eyes in the form of coagulation problems, neurological morbidities, and other manifestations. This necessitates meticulous follow-up of recovered patients from COVID-19. Since the emergence of the coronavirus in Wuhan china in 2019 many studies have predicted its ocular manifestations including follicular conjunctivitis, subconjunctival hemorrhage, redness, and eye dryness. Exposure keratitis and mucopurulent conjunctivitis (MPC) were found especially in patients admitted to intensive care units which could be due to the exposure of open mask oxygen or eye exposure. Ocular manifestations could be the first symptoms to appear in some infected patients. [1] [2] [3] A new term emerged as a result of lockdown (Quarantine Dry Eye) which was attributed to personal behavior in both developed and developing countries, this necessitates the change in the treatment and follow-up modalities of those patients. 4 The appearance of ocular manifestations, drive the ophthalmologists to give medications in the form of eye drops, Some of them have antiviral activities and their use could raise confusion to the physicians as they could affect the level of the virus in the conjunctival tears and secretions. 5 The presence of the virus in the conjunctival tears and secretions revealed the possibility of its transmission through ocular secretions and could explain the deaths amongst ophthalmologists. Also many researches estimated the immune response to the virus in the eye by estimating immunoglobulin (A IgA). [6] [7] [8] [9] [10] [11] [12] [13] Even with no conjunctival manifestations, the virus could be found in the tears enforcing the need of safety measures during ophthalmology practice which could by using protective goggles, social distances in clinics, and even full personal protective equipment (PPE). Some studies evaluated the safe ophthalmology practice amongst ophthalmologists which was different according to safety protocols in the hospitals or the country protocols. [14] [15] [16] It was a surprise to talk about post-acute COVID-19 syndrome or long COVID syndrome, which was defined by National Institute of Health (NIH), Center of Disease Control (CDC), and the World Health Organization (WHO). It means the presence or appearance of long term effects of coronavirus on different body systems. 17 It is described as causing general fatigue, respiratory, cardiac, or psychological manifestations. The eye could also be affected in post-acute COVID-19 syndrome and some reports have suggested this, but multicenter or worldwide studies are still deficient. [18] [19] [20] [21] [22] In this study we aim to evaluate the ocular manifestations of post-acute COVID-19 or long COVID syndrome in Upper Egypt. Full ethical considerations were followed according to Sohag University Ethical Committee: IBR registration number: Soh-Med-21-05-24, they are adherent to the Helsinki Declaration. Written informed consent was taken from all participants. All investigations were done freely to the patients. Retrospective comparative study COVID group: 100 post-acute COVID-19 patients were recruited randomly by stratified randomization from hospital registrations; they were admitted between September 2020 and March 2021 the recovery is defined by two consecutive negative nasopharyngeal swabs with disappearance of the symptoms. Control group: 100 controls were recruited randomly by stratified randomization from hospital registration system; they were not admitted or diagnosed as COVID-19 patients previously. They were confirmed by nasopharyngeal swab after recruitment and the measurement of immunoglobulin (G IgG) levels. Data were collected from ophthalmological department registration system of both groups showed non-significant difference in past ocular diseases of significant importance related to this study P value >0.05. Both groups were screened ophthalmologically; slit lamp biomicroscopy (Version 1.5.0.0, Nidek Co, Ltd), the visual acuity was measured using Snellen chart, intraocular pressure IOP using Goldmann applanation tonometer Goldmann AT 900 (Haag Streit, Bern, Switzerland), fundus examination, and investigations like fluorescein angiography F/A Deep Range Imaging (DRI) Triton SS-OCT (Topcon Corporation, Tokyo, Japan) and optical coherence tomography OCT Deep Range Imaging (DRI) Triton SS-OCT (Topcon Corporation, Tokyo, Japan) were done for patients with positive findings. COVID-19 manifestations were categorized as mild, moderate, and severe according to guidelines. Patients who underwent assisted ventilation were also registered and stratified. Full general examination was done regarding vascular and endocrine systems, neurological evaluation, and evaluation for autoimmune diseases or coagulation disorders. Laboratory investigations were done for patients with positive findings including: D-dimer, erythrocytes sedimentation rate (ESR), and immunological tests. COVID Group 100 post-acute COVID-19 patients were recruited randomly from hospital registrations; they were admitted between September 2020 and March 2021 the recovery is defined by two consecutive negative nasopharyngeal swabs with disappearance of the symptoms. One-hundred controls were recruited randomly from hospital registration system; they were not admitted or diagnosed as COVID-19 patients previously. They were confirmed by nasopharyngeal swab after recruitment and the measurement of immunoglobulin G IgG levels. They did not receive any type of vaccination. Both groups were matched regarding: age, sex, general condition, chronic diseases, and past ocular diseases. Patients under 18 years of age were excluded. Recovered patients from COVID-19 more than 3 months. The data was collected and analyzed. (Figure 1 ). ESR was elevated in 28 patients (28%) in COVID group vs 11 patients (11%) in control group (P value = 0.002) (Figure 2 ). This is shown in Tables 1 and 2, the change of ESR and D-dimer values are shown in Table 3 showing stratification of patients who developed ocular signs, elevated ESR and D-Dimer at follow-up period with decreased values over the time. In COVID group the patients were classified to mild (30%), moderate (25%), and severe (45%) according to general manifestations and known guidelines ( Table 4 ). The correlation between the severity of COVID-19 clinical manifestations and ocular signs was statistically weak. Moreover, correlation Tohamy et al between assisted ventilation and ocular signs was also weak. In COVID group, 5 patients (5%) were having retinal vascular occlusion either branch retinal vein occlusion (BRVO) or central retinal artery occlusion (CRAO), 2 patients (2%) were having anterior ischemic optic neuropathy (AION), 3 patients (3%) were having uveitis and 2 patients (2%) were having central serous chorioretinopathy (CSCR). While in control group, 2 patients (2%) were having retinal vascular occlusion and none had AION, uveitis or CSCR (P value = 0.006). This is shown in Table 5 and Figures 3-7 . The duration between recovery and occurrence of ocular manifestations in COVID group range from one to three months, the stratification according to duration between recovery and occurrence of ocular manifestation is tabulated in Table 3 with more occurrence in the first month after recovery and least in the third month. Patients were diagnosed and treated according to the guidelines of each case; those with vascular occlusion were investigated by internal medicine specialist to exclude other risk factors for the morbidity. Patients with neurological disorders were examined by a neurologist to exclude or confirm diagnosis. The 3 cases of uveitis were attributed to autoimmune disorders after excluding the infectious causes. Before COVID-19, the incidence of ocular morbidities was as follows: vein occlusion, 1.02 per 1000 patientyears; artery occlusion, 1.3 per 100,000; uveitis (121 cases per 100,000; anterior ischemic optic neuropathy, 10.3 per 100,000; and central serous chorioretinopathy, 10 per 100,000. [23] [24] [25] [26] [27] In this study; those affected with COVID-19 showed ocular morbidities more than control group which did not suffer from COVID-19 infections and more than the incidence in population before the emergence of COVID-19 infection which support the relationship between the infection and the ocular comorbidities. The difference between two groups regarding all other comparative values was insignificant except for the D-dimer and ESR in COVID group; which suggests inflammation. These comorbidities could be attributed to previous COVID-19 infections as we analyzed the other risk factors which showed insignificant difference between both groups. These risk factors include: clinical past history, basic metabolic panel, complete blood count, glycated hemoglobin, antinuclear antibody test, homocysteine levels, antithrombin III, coagulant protein C, functional protein S, resistance to activated C protein (factor V Leiden mutation), prothrombin gene mutation G20210A, anticardiolipin antibodies, prothrombin time, and international normalized ratio along with activated partial thromboplastin time. 1940 ocular diseases occurred after recovery from COVID-19 infection were excluded by examination and investigations. Some reports suggested the occurrence of ocular problems after a COVID-19 infection, especially vascular problems, and explained the elevated possibility of coagulation induced by the infection. 29 The resultants ocular diseases were with higher incidence than in the normal population which focuses the cause on the COVID-19 infection. 30, 31 Some reports suggested the occurrence of endogenous endophthalmitis postcovid. 32 Some reported ocular surface abnormalities after a COVID-19 infection, such as the occurrence of dryness and alternation in the osmolarity of the tears. 33 Some other studies found that there is a correlation between the tear film distribution and the heart rate, which is affected by respiration and could be of importance in such study. 34 The cause of uveitis could be infectious or autoimmune. In this study the cause is most likely to be autoimmune after exclusion of infectious causes in the 3 cases, suggesting immune alternation after COVID-19 infection. 35 The COVID-19 infection could cause post-acute COVID-19 infection or long COVID ocular morbidities which There was a small sample and lack of meticulous follow up, so more longitudinal studies are needed with larger numbers and in many countries. Data related to this research are available upon request from corresponding author. This study was approved by Sohag University ethical committee IBR: Soh-Med-21-05-24 Written informed consent was taken from every participant. 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Ophthalmol Retina Ischemic optic neuropathy A case series of presumed fungal endogenous endophthalmitis in post COVID-19 patients Ocular surface impairment after coronavirus disease 2019: a cohort study The bull's eye pattern of the tear film in humans during visual fixation on en-face optical coherence tomography Visual snow-like symptoms and posterior uveitis following COVID-19 infection We appreciate the efforts of Professor Hatem Ammar, the head of ophthalmology department, Sohag University for his support.We would like to thank Dr Heba Khallaf for her effort in revising the manuscript. All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work. All authors reported no conflicts of interest for this work. This is to certify that: the article has not been presented in a meeting; the authors did not receive any financial support from any public or private sources; The authors have no financial or proprietary interest in the product, method, or material described herein. The Journal of Multidisciplinary Healthcare is an international, peerreviewed open-access journal that aims to represent and publish research in healthcare areas delivered by practitioners of different disciplines. This includes studies and reviews conducted by multidisciplinary teams as well as research which evaluates the results or conduct of such teams or healthcare processes in general. The journal covers a very wide range of areas and welcomes submissions from practitioners at all levels, from all over the world. The manuscript management system is completely online and includes a very quick and fair peer-review system. 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