Ophthalmic Manifestations Of Coronavirus (COVID-19)

Authors: Katherine Hu; Jay Patel; Cole Swiston; Bhupendra C. Patel.Author Information Last Update: May 19, 2021.

Several reports of suspected ocular manifestations of coronavirus disease 2019 (COVID-19) have prompted investigations into ocular signs, symptoms, and transmission. This activity reviews the evaluation and management of ocular manifestations of COVID-19 and highlights the interprofessional team’s role in managing patients with this condition.


  • Summarize the epidemiology of ocular manifestations of COVID-19.
  • Describe the typical presentation of a patient with ocular manifestations of COVID-19.
  • Outline management considerations for patients with ocular manifestations of COVID-19, including key patient counseling on disease transmission prevention.
  • Explain the importance of collaboration and communication among the interprofessional team to improve outcomes for patients affected by COVID-19.


Since December 2019, coronavirus disease 2019 (COVID-19) has become a global pandemic caused by the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).[1] Initially, there were several reports of eye redness and irritation in COVID-19 patients, both anecdotal and published, suggesting that conjunctivitis is an ocular manifestation of SARS-CoV-2 infection. Reports continue to emerge on further associations of COVID-19 with uveitic, retinovascular, and neuro-ophthalmic disease.

During the 2003 severe acute respiratory syndrome (SARS) outbreak, a study detected SARS-CoV in tear samples in SARS patients in Singapore.[2] Lack of eye protection was a primary risk factor of SARS-CoV transmission from SARS patients to healthcare workers in Toronto, prompting a concern that respiratory illness could be transmitted through ocular secretions.[3][4] Similar concerns have been raised with SARS-CoV-2, especially among eye care providers and those on the front lines triaging what could be initial symptoms of COVID-19.

As conjunctivitis is a common eye condition, ophthalmologists may be the first medical professionals to evaluate a patient with COVID-19. Indeed, one of the first providers to voice concerns regarding the spread of coronavirus in Chinese patients was Dr. Li Wenliang, MD, an ophthalmologist. He later died from COVID-19 and was believed to have contracted the virus from an asymptomatic glaucoma patient in his clinic.

The authors of this article have attempted to collect the most up-to-date information on ophthalmic manifestations of COVID-19 as a resource for identifying symptoms, providing diagnostic pearls, and mitigating transmission.


SARS-CoV-2 is a novel enveloped, positive single-stranded RNA beta coronavirus that causes COVID-19, originally linked to an outbreak in Wuhan of China’s Hubei province.[1] Direct contact with mucous membranes, including the eye, is a suspected route of transmission.

Coronaviruses can cause severe ocular disease in animals, including anterior uveitis, retinitis, vasculitis, and optic neuritis in feline and murine species. However, ocular manifestations in humans are typically mild and rare, [5] although there are increasing numbers of associated ocular findings in patients positive for the COVID-19. There are no described ocular manifestations of Middle East respiratory syndrome (MERS) or SARS, though, as previously stated, SARS-CoV was isolated in ocular secretions.[2] Other coronaviruses have been found to cause viral conjunctivitis in humans.[6]


At the time of writing the initial article on April 4, 2020, there were 1,272,953 confirmed cases and 69,428 deaths due to COVID-19 worldwide, according to the World Health Organization (WHO), with 79,332 new cases confirmed in the previous 24 hours. At the time, the Center for Disease Control and Prevention (CDC) had reported 337,278 cases and 9,637 deaths in the United States to that date. On April 16, 2021, just over a year since our initial review, the number of deaths worldwide has crossed the 3 million mark. The severity of the pandemic is emphasized by noting the rate of deaths: it took 8.5 months after the first fatality in China to mark the loss of the first 1 million lives, 3.5 months to reach 2 million, and 3 months for the loss to cross 3 million lives. 

As of May 17, 2021, there have been over 164 million confirmed cases globally (the real number is, of course, far in excess of this as the number does not include infected individuals who were not tested or asymptomatic cases) and 3,403,722 deaths. India, Iran, and Brazil are currently experiencing the highest number of infections in a 24 hour period ever with new viral strains being discovered in different parts of the world. The United States has had the most infections (33,745,500) and deaths (600,514), followed by India, Brazil, France, Turkey, Russia and the United Kingdom. Increasing infections are currently being seen in Canada, France, Germany, and other countries, necessitating further shutdowns. In the United States, there is an overall uptick in infections as restrictions are relaxed. 

Viral mutations leading to variants of SARS-CoV-2 have been found around the world: the B.1.525 in the United Kingdom and Nigeria in December 2020, the B.1.526in the United States in November 2020, the B.1.1.7 in the United Kingdom in early 202, the B.1.351 in South Africa in late 2020, and the Indian variant in April 2021. 

Early studies postulated that ocular manifestations of COVID-19 were rare overall. Only 9 (0.8%) out of 1,099 patients from 552 hospitals across 30 provinces in China were reported to have “conjunctival congestion” from December 2019 through January 2020.[7] More recent data, however, have supported a much higher incidence of ocular signs and symptoms. A 2021 meta-analysis by Nasiri et al. reported a pooled prevalence of all ocular manifestations among 7,300 COVID-19 patients as 11.03%, with the most frequent ocular disease being conjunctivitis (88.8%).[8] In the same meta-analysis, dry eye or foreign body sensation (16%), eye redness (13.3%), tearing (12.8%), and itching (12.6%) were among the most frequent symptoms reported. 

A case series reported ocular symptoms in 12 (31.6%) of 38 hospitalized patients with COVID-19 in Hubei province, China.[9] These 12 of 38 patients had conjunctival hyperemia (3 patients), chemosis (7 patients), epiphora (7 patients), or increased secretions (7 patients). Of note is that one patient who had epiphora presented with epiphora as the first symptom of COVID-19. Of those with ocular manifestations, 2 (16.7%) patients had positive results of SARS-CoV-2 on reverse-transcriptase polymerase chain reaction (RT-PCR) by a conjunctival swab, as well as by nasopharyngeal swabs. Only one patient in this study presented with conjunctivitis as the first symptom.[9] The authors noted that patients with ocular symptoms had higher white blood cell and neutrophil counts, C-reactive protein, and higher levels of procalcitonin and lactate dehydrogenase compared to patients without ocular abnormalities. 

Out of 30 hospitalized patients with COVID-19 tested by Xia et al., one patient had conjunctivitis and was also the sole patient in the study to test positive for SARS-CoV-2 in ocular secretions by a conjunctival swab. This patient did not have a severe fever or respiratory symptoms at the time of testing.[10]

For More Information: https://www.ncbi.nlm.nih.gov/books/NBK556093/

COVID-19: A Mitochondrial Perspective

Authors: Pankaj Prasun 1

Coronavirus disease 2019 (COVID-19) is the worst public health crisis of the century. Although we have made tremendous progress in understanding the pathogenesis of this disease, a lot more remains to be learned. Mitochondria appear to be important in COVID-19 pathogenesis because of its role in innate antiviral immunity, as well as inflammation. This article examines pathogenesis of COVID-19 from a mitochondrial perspective and tries to answer some perplexing questions such as why the prognosis is so poor in those with obesity, metabolic syndrome, or type 2 diabetes. Although effective vaccines and antiviral drugs will be the ultimate solution to this crisis, a better understanding of disease mechanisms will open novel avenues for treatment and prevention.

For More Information: https://pubmed.ncbi.nlm.nih.gov/33872068/

COVID-19 Vasculopathy: Mounting Evidence for an Indirect Mechanism of Endothelial Injury

Authors: Roberto F. Nicosia,∗∗ Giovanni Ligresti, Nunzia Caporarello, Shreeram Akilesh, and Domenico Ribatti§

Patients with coronavirus disease 2019 (COVID-19) who are critically ill develop vascular complications characterized by thrombosis of small, medium, and large vessels. Dysfunction of the vascular endothelium due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been implicated in the pathogenesis of the COVID-19 vasculopathy. Although initial reports suggested that endothelial injury was caused directly by the virus, recent studies indicate that endothelial cells do not express angiotensin-converting enzyme 2, the receptor that SARS-CoV-2 uses to gain entry into cells, or express it at low levels and are resistant to the infection. These new findings, together with the observation that COVID-19 triggers a cytokine storm capable of injuring the endothelium and disrupting its antithrombogenic properties, favor an indirect mechanism of endothelial injury mediated locally by an augmented inflammatory reaction to infected nonendothelial cells, such as the bronchial and alveolar epithelium, and systemically by the excessive immune response to infection. Herein we review the vascular pathology of COVID-19 and critically discuss the potential mechanisms of endothelial injury in this disease.

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141344/

Endothelial dysfunction in COVID-19: Current findings and therapeutic implications

Authors: Matthias P Nägele 1Bernhard Haubner 1Felix C Tanner 1Frank Ruschitzka 1Andreas J Flammer 2

Coronavirus disease 2019 (COVID-19) increases the risk of several non-pulmonary complications such as acute myocardial injury, renal failure or thromboembolic events. A possible unifying explanation for these phenomena may be the presence of profound endothelial dysfunction and injury. This review provides an overview on the association of endothelial dysfunction with COVID-19 and its therapeutic implications. Endothelial dysfunction is a common feature of the key comorbidities that increase risk for severe COVID-19 such as hypertension, obesity, diabetes mellitus, coronary artery disease or heart failure. Preliminary studies indicate that vascular endothelial cells can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and evidence of widespread endothelial injury and inflammation is found in advanced cases of COVID-19. Prior evidence has established the crucial role of endothelial cells in maintaining and regulating vascular homeostasis and blood coagulation. Aggravation of endothelial dysfunction in COVID-19 may therefore impair organ perfusion and cause a procoagulatory state resulting in both macro- and microvascular thrombotic events. Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and statins are known to improve endothelial dysfunction. Data from smaller observational studies and other viral infections suggests a possible beneficial effect in COVID-19. Other treatments that are currently under investigation for COVID-19 may also act by improving endothelial dysfunction in patients. Focusing therapies on preventing and improving endothelial dysfunction could improve outcomes in COVID-19. Several clinical trials are currently underway to explore this concept.

For More Information: https://pubmed.ncbi.nlm.nih.gov/33161318/

Mutational Similarities Between SARS-CoV-2 and Its Predecessors

Authors: | Original story from University of Nebraska–Lincoln, Credit: Pete Linforth/ Pixabay

New research from the University of Nebraska-Lincoln has shown that the mutations arising in the COVID-19-causing SARS-CoV-2 virus seem to run in the family — or at least the genus of coronaviruses most dangerous to humans.

After comparing the early evolution of SARS-CoV-2 against that of its closest relatives, the betacoronaviruses, the Nebraska team found that SARS-CoV-2 mutations are occurring in essentially the same locations, both genetically and structurally.

The mutational similarities between SARS-CoV-2 and its predecessors, including the human-infecting SARS-CoV-1 and MERS-CoV, could help inform predictions of how the COVID-causing virus will continue to evolve, the researchers said.

“The problem of looking at only one virus at a time is that you lose the forest for the trees,” said Katherine LaTourrette, a doctoral student in the Complex Biosystems program at Nebraska. “By looking at this big picture, we were able to predict the mutational nature of SARS-CoV-2.

“That gets into these questions of: Are vaccines going to be effective long term? Which variants are going to sneak by? Do we need that booster shot? Are vaccinated people going to be infected a second time?”

For More Information: https://www.technologynetworks.com/genomics/news/mutational-similarities-between-sars-cov-2-and-its-predecessors-350848

Primed” for Infection: Cells Damaged by Chronic Lung Disease Can Result in Severe COVID


Results from a TGen-led international study suggest that SARS-CoV-2 takes advantage of genetic changes among patients with pre-existing lung diseases.

The results of a study by an international scientific team co-led by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, suggest that — like pouring water atop a wellhead before pumping — the airway cells of patients with chronic lung diseases are “primed” for infection by the COVID-19 virus, resulting in more severe symptoms, poorer outcomes and a greater likelihood of death.

The study — published today in Nature Communications — details the genetic changes caused by chronic lung disease in the molecular makeup of a variety of cells, including the epithelial cells that line the lung and airways. The study details how those changes can help enable SARS-CoV-2, the virus that causes COVID-19, to enter the body, replicate and trigger an out-of-control immune response that fills the lungs with fluids and often results in patients needing respirators and lengthy hospitalizations.

For More Information: https://scitechdaily.com/primed-for-infection-cells-damaged-by-chronic-lung-disease-can-result-in-severe-covid/

SARS-CoV-2 viral genomics

Authors: This analysis was performed primarily by Matt Olm (mattolm@stanford.edu) in Justin Sonnenburg’s lab at Stanford University and Alex Crits-Christoph (crits-christoph@berkeley.edu) in Jill Banfield’s lab at University of California, Berkeley

As viruses replicate within their hosts during infection, they mutate and accrue genetic diversity in their populations. These populations are usually shared as a single genome representing the consensus genome from a particular patient, and analysis of inter-patient variation (differences between the consensus genomes from different patients) is useful for understanding how the outbreak spreads, and how the virus evolves globally.

We refer to the variation within a single individual as intra-patient variation, intraspecfic variation, or microdiversity. This genetic variation is less commonly studied, but analysis of this data has the following potential applications:

  • Identification of the genomic loci least likely to mutate during infection, which could be useful for designing universal primers / probes.
  • Comparison of viral evolution within individuals versus global evolution. This can be useful for understanding how the viral evolutionary pressures and functions.
  • Estimation of the number of viral particles acquired at the onset of infection and quantifying genetic diversity transferred during transmission.

Inter-patient SARS-CoV-2 genome variation

To analyze inter-patient variation, we downloaded publicly available SARS-CoV-2 genomes, processed and filtered them, and generated a multiple sequence alignment. Details can be found in the Methods second, and the genomes and alignment can be downloaded from the Data availability section.

After genome alignment, we can visualize genetic diversity across the genome:

For More Information: https://github.com/MrOlm/covid19_population_genomics

Covid-19: links between genes and disease severity

Authors: Bolzano research centre

In March 2020, thousands of scientists around the world joined forces to investigate the questions at the forefront of the medical debate on the pandemic: what genetic factors influence the severity of Covid-19 infections and why do some people develop a serious illness that requires hospitalisation while others have mild or no symptoms?

The results of the research, published in Nature only a few days ago, revealed extraordinary findings 13 loci – points in the human genome – were identified as being strongly associated with severe Covid-19 infection. This discovery comes from one of the world’s largest genetics studies: the group examined the genomes of almost 50,000 patients with Covid-19 and another two million uninfected people. The data findings included participants in the studies conducted by Eurac Research in South Tyrol over the past year.

The Covid-19 Host Genomics Initiative was launched in March 2020 by the Finnish Institute of Molecular Medicine at the University of Helsinki. The initiative has now grown to become one of the most extensive collaborations on human genetics, currently including more than 60 studies from 25 different countries. Thanks to the huge amount of data available, the researchers have been able to produce statistically robust analyses in a relatively short time, achieving results that no research institution could have achieved independently. Of the 13 loci identified, two were found most frequently in East and South Asian populations. The analyses also showed that some of these loci are located in close proximity to genes involved in serious lung diseases such as cancer or pulmonary fibrosis. In these cases, inhibiting the gene could be a therapeutic strategy to be explored further. Researchers have also identified other factors that influence the severity of the disease, such as smoking and a high body mass index.

For More Information: https://www.eurac.edu/en/magazine/covid-19-links-between-genes-disease-severity


Authors: Cleveland Clinic

What is dysautonomia?

Dysautonomia is a general term for a group of disorders that share a common problem – that is, an autonomic nervous system (ANS) that doesn’t function as it should. The ANS is the part of the nervous system that controls involuntary body functions (functions you don’t consciously control) like your heart rate, blood pressure, breathing, digestion, body and skin temperature, hormonal function, bladder function, sexual function and many other functions.

When the ANS doesn’t work the way it should, it can cause heart and blood pressure problems, breathing trouble, loss of bladder control and many other problems.

Who might get dysautonomia?

Dysautonomia, also called autonomic dysfunction or autonomic neuropathy, is relatively common. Worldwide, it affects more than 70 million people. It can be present at birth or appear gradually or suddenly at any age. Dysautonomia can be mild to serious in severity and even fatal (rarely). It affects women and men equally.

Dysautonomia can occur as its own disorder, without the presence of other diseases. This is called primary dysautonomia. It can also occur as a condition of another disease. This is called secondary dysautonomia.

Examples of diseases in which secondary dysautonomia can occur include:

For More Information: https://my.clevelandclinic.org/health/diseases/6004-dysautonomia

What is cytokine release syndrome?

Authors: Medical News Today

Cytokine release syndrome (CRS) can cause a variety of symptoms, including fever, headaches, and nausea. The symptoms can become severe quickly.

CRS occurs when the immune system responds too aggressively to an infection. It can also happen as a result of some types of immunotherapy. Treatments for CRS typically involve reducing the immune response.

This article will discuss what CRS is, its symptoms and treatments, and its link with COVID-19.

What is CRS?

CRS is a collection of symptoms that can vary from fever to vomiting. These symptoms are the result of abnormally high cytokine levels.

Cytokines are small proteins that help cells around the body communicate. When the immune system detects a threat, cells release cytokines to coordinate the body’s response.

In CRS, the immune system is overactive. The elevated cytokines cause harmful levels of inflammation throughout the body, which disrupts normal bodily functions. The inflammation may interfere with organ function and cause severe symptoms.

CRS can occur due to infection or as a result of certain medical treatments.

For More Information: https://www.medicalnewstoday.com/articles/cytokine-release-syndrome