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      Optical Coherence Tomography Angiography Analysis of the Retina in Patients Recovered from COVID19: A Case Control Study

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          Abstract

          Objective

          To quantify the density of the macular microvasculature and the area of the foveal avascular zone (FAZ) in patients recovered from Coronavirus Disease 2019 (COVID-19) using optical coherence tomography angiography (OCTA) analysis.

          Methods

          In a comparative cross-sectional, observational study, patients recovered from COVID-19 were included in this study. All included subjects exhibited a reverse transcription-polymerase chain reaction (RT-PCR) - confirmed diagnosis of COVID-19. Spectral domain macular OCTA was performed at least 2 weeks after recovery from systemic COVID-19. Vessel density (VD) of the superficial (SCP) and deep retinal capillary plexus (DCP) and the area of the FAZ were measured in COVID-19 recovered patients versus age-matched normal controls.

          Results

          Thirty-one recovered COVID-19 patients and 23 healthy normal controls were studied. Mean quality scan index was 7.64±0.66 in the COVID cases and 8.34±0.71 in the normal controls (p=0.001). Mean SCP VD and DCP VD of the COVID cohort was significantly lower than the SCP VD and DCP VD of the control group in the foveal and parafoveal regions. FAZ area was greater in the COVID cohort, but this difference was not statistically significant. In addition, in the COVID cohort, VD of the SCP and DCP were lower in patients with a history of COVID-19 hospitalization versus those without such a history but this did not reach statistical significance.

          Conclusion

          Patients recovered from COVID-19 displayed alterations in the retinal microvasculature including a significantly lower VD in the SCP and DCP. Patients with coronavirus infection may be at risk of retinal vascular complications.

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

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          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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            Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis

            I Hamming, W Timens, MLC Bulthuis … (2004)
            Abstract Severe acute respiratory syndrome (SARS) is an acute infectious disease that spreads mainly via the respiratory route. A distinct coronavirus (SARS‐CoV) has been identified as the aetiological agent of SARS. Recently, a metallopeptidase named angiotensin‐converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS‐CoV. Although ACE2 mRNA is known to be present in virtually all organs, its protein expression is largely unknown. Since identifying the possible route of infection has major implications for understanding the pathogenesis and future treatment strategies for SARS, the present study investigated the localization of ACE2 protein in various human organs (oral and nasal mucosa, nasopharynx, lung, stomach, small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain). The most remarkable finding was the surface expression of ACE2 protein on lung alveolar epithelial cells and enterocytes of the small intestine. Furthermore, ACE2 was present in arterial and venous endothelial cells and arterial smooth muscle cells in all organs studied. In conclusion, ACE2 is abundantly present in humans in the epithelia of the lung and small intestine, which might provide possible routes of entry for the SARS‐CoV. This epithelial expression, together with the presence of ACE2 in vascular endothelium, also provides a first step in understanding the pathogenesis of the main SARS disease manifestations. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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              Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus

              Yushun Wan, Jian Shang, Rachel Graham … (2020)
              The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational, and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.
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                Author and article information

                Contributors
                Mojtaba Abrishami: Role: Conceptualization; Project administration; Funding acquisition; Investigation; Writing - review & editing
                Ramin Daneshvar: Role: Conceptualization; Supervision; Writing - review & editing
                Neda Saeedian: Role: Resources; Investigation
                Saeid Eslami: Role: Conceptualization; Funding acquisition; Resources
                SriniVas Sadda: Role: Supervision; Writing - review & editing
                David Sarraf: Role: Supervision; Writing - review & editing
                Journal
                Journal ID (nlm-ta): Can J Ophthalmol
                Journal ID (iso-abbrev): Can J Ophthalmol
                Title: Canadian Journal of Ophthalmology. Journal Canadien D'Ophtalmologie
                Publisher: Canadian Ophthalmological Society. Published by Elsevier Inc.
                ISSN (Print): 0008-4182
                ISSN (Electronic): 1715-3360
                Publication date PMC-release: 14 November 2020
                Publication date (Electronic): 14 November 2020
                Affiliations
                [1 ]Eye Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
                [2 ]Department of Education and Psychology, Ferdowsi University of Mashhad, Mashhad, Iran
                [3 ]Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
                [4 ]Department of Medical Informatics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
                [5 ]Amsterdam UMC, University of Amsterdam, Department of Medical Informatics, Amsterdam Public Health, Meibergdreef 9, Amsterdam, The Netherlands
                [6 ]Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
                [7 ]Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA
                [8 ]Doheny Eye Institute, UCLA, Los Angeles, CA, USA
                [9 ]Stein Eye Institute, UCLA, Los Angeles, CA, USA
                Author notes
                [* ]Corresponding author: Mojtaba Abrishami MD MSc; Eye Research Center, Khatam-al-Anbia Eye Hospital, Qarani Blvd, Mashhad 9195965919, Iran Tel: +98-51- 37245363, Fax: +98-51- 37285290.
                Article
                Publisher Item ID: S0008-4182(20)30813-9
                DOI: 10.1016/j.jcjo.2020.11.006
                PMC ID: 7666612
                PubMed ID: 33249111
                SO-VID: e0d4fe28-cd0e-4ac4-8a99-4afcbfb13521
                Copyright © © 2020 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 15 October 2020
                Date revision received : 31 October 2020
                Date accepted : 10 November 2020
                Categories
                Subject: Article

                Keywords: severe acute respiratory syndrome corona virus 2 (sars-cov-2),coronavirus disease 2019 (covid-19),optical coherence tomography angiography (octa),macula,retina
                Data availability:
                Keywords: severe acute respiratory syndrome corona virus 2 (sars-cov-2), coronavirus disease 2019 (covid-19), optical coherence tomography angiography (octa), macula, retina

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