Tokyo, Japan) and XR Avanti SD-OCT (Optovue, Fremont, CA, USA).All patients showed hyper-reflective lesions at the level of ganglion cell and inner plexiform layers more prominently at the papillomacular bundle in both eyes (figure). Results of OCT-angiography and ganglionar cells complex analysis appeared normal. Furthermore, four patients presented subtle cotton wool spots and microhaemorrhages along the retinal arcade, observed on fundus examination, color fundus photography, and red-free imaging. Visual acuity and pupillary reflexes were normal in all eyes, and we detected no symptoms or signs of intraocular inflammation.Although animal models suggest ocular lesions could include retinitis and optic neuritis, 3,4 this is, to the best of our knowledge, the first report of retinal findings possibly associated with COVID-19 infection in humans. Ganglion cell and plexiform layer findings could be associated with CNS manifestations that have been described in animal studies 4 and in COVID-19 neurological events. 5 We declare no competing interests.

Men experience more severe outcomes from coronavirus disease 2019 (COVID-19) than women. Golden Syrian hamsters were used to explore sex differences in the pathogenesis of a human clinical isolate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

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ARS-CoV-2 is an enveloped positive-sense RNA coronavirus belonging to the Coronaviridae family, and its cellular entry depends mainly on the binding of S protein 1,2 to angiotensin-converting enzyme 2, a specific cellular receptor located at the surface of the host cells. 3,4 The SARS-CoV-2 viral particles' presence in the retina of deceased patients with COVID-19 has been suggested through the real-time polymerase chain reaction (PCR) and immunological methods to detect its main proteins. The eye is affected by COVID-19 infection, 5,6 and retinal changes were attributed to secondary microvascular and immunological changes. The aim of this study was to detect the presence of presumed SARS-CoV-2 viral particles in the retina of individuals who died of COVID-19 using fluorescence microcopy of tissues immunostained for S1 and nucleocapsid proteins and transmission electron microscopy of thin sections. MethodsThis investigational study was approved by the ethical and research committee at the Federal University of São Paulo in São Paulo, Brazil, and all patients' representatives agreed to participate through written consent applied after the patient's death. They were informed of the procedure and potential benefits and risks, and no compensation was received for agreeing to participate. Detailed demographic, medical history, concomitant events, medication history, hospitalization details, IMPORTANCE The presence of the SARS-CoV-2 virus in the retina of deceased patients with COVID-19 has been suggested through real-time reverse polymerase chain reaction and immunological methods to detect its main proteins. The eye has shown abnormalities associated with COVID-19 infection, and retinal changes were presumed to be associated with secondary microvascular and immunological changes.OBJECTIVE To demonstrate the presence of presumed SARS-CoV-2 viral particles and its relevant proteins in the eyes of patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe retina from enucleated eyes of patients with confirmed COVID-19 infection were submitted to immunofluorescence and transmission electron microscopy processing at a hospital in São Paulo, Brazil, from June 23 to July 2, 2020. After obtaining written consent from the patients' families, enucleation was performed in patients deceased with confirmed SARS-CoV-2 infection. All patients were in the intensive care unit, received mechanical ventilation, and had severe pulmonary involvement by COVID-19. MAIN OUTCOMES AND MEASURESPresence of presumed SARS-CoV-2 viral particles by immunofluorescence and transmission electron microscopy processing.RESULTS Three patients who died of COVID-19 were analyzed. Two patients were men, and 1 was a woman. The age at death ranged from 69 to 78 years. Presumed S and N COVID-19 proteins were seen by immunofluorescence microscopy within endothelial cells close to the capillary flame and cells of the inner and the outer nuclear layers. At the perinuclear region of these cells, it was possible to observe by transmission electron microscopy dou...

In the ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more severe outcomes are reported in males compared with females, including hospitalizations and deaths. Animal models can provide an opportunity to mechanistically interrogate causes of sex differences in the pathogenesis of SARS-CoV-2. Adult male and female golden Syrian hamsters (8-10 weeks of age) were inoculated intranasally with 105 TCID50 of SARS-CoV-2/USA-WA1/2020 and euthanized at several time points during the acute (i.e., virus actively replicating) and recovery (i.e., after the infectious virus has been cleared) phases of infection. There was no mortality, but infected male hamsters experienced greater morbidity, losing a greater percentage of body mass, developing more extensive pneumonia as noted on chest computed tomography, and recovering more slowly than females. Treatment of male hamsters with estradiol did not alter pulmonary damage. Virus titers in respiratory tissues, including nasal turbinates, trachea, and lungs, and pulmonary cytokine concentrations, including IFNb and TNFa, were comparable between the sexes. However, during the recovery phase of infection, females mounted two-fold greater IgM, IgG, and IgA responses against the receptor-binding domain of the spike protein (S-RBD) in both plasma and respiratory tissues. Female hamsters also had significantly greater IgG antibodies against whole inactivated SARS-CoV-2 and mutant S-RBDs, as well as virus neutralizing antibodies in plasma. The development of an animal model to study COVID-19 sex differences will allow for a greater mechanistic understanding of the SARS-CoV-2 associated sex differences seen in the human population.

Surveillance for emerging human influenza virus clades is important for identifying changes in viral fitness and assessing antigenic similarity to vaccine strains. While fitness and antigenic structure are both important aspects of virus success, they are distinct characteristics and do not always change in a complementary manner. The 2019-20 Northern Hemisphere influenza season saw the emergence of two H1N1 clades: A5a.1 and A5a.2. While several studies indicated that A5a.2 showed similar or even increased antigenic drift compared with A5a.1, the A5a.1 clade was still the predominant circulating clade that season. Clinical isolates of representative viruses from these clades were collected in Baltimore, Maryland during the 2019-20 season and multiple assays were performed to compare both antigenic drift and viral fitness between clades. Neutralization assays performed on serum from healthcare workers pre- and post-vaccination during the 2019-20 season show a comparable drop in neutralizing titers against both A5a.1 and A5a.2 viruses compared with the vaccine strain, indicating that A5a.1 did not have antigenic advantages over A5a.2 that would explain its predominance in this population. Plaque assays were performed to investigate fitness differences, and the A5a.2 virus produced significantly smaller plaques compared with viruses from A5a.1 or the parental A5a clade. To assess viral replication, low MOI growth curves were performed on both MDCK-SIAT and primary differentiated human nasal epithelial cell cultures. In both cell cultures, A5a.2 yielded significantly reduced viral titers at multiple timepoints post-infection compared with A5a.1 or A5a. Receptor binding was then investigated through glycan array experiments which showed a reduction in receptor binding diversity for A5a.2, with fewer glycans bound and a higher percentage of total binding attributable to the top three highest bound glycans. Together these data indicate that the A5a.2 clade had a reduction in viral fitness, including reductions in receptor binding, that may have contributed to the limited prevalence observed after emergence.

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