Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity.

Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the "Interferon paradox" previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.

Transcriptomic analysis identifies novel candidates in cardiorenal pathology mediated by chronic peritoneal dialysis.

Peritoneal dialysis (PD) is associated with increased cardiovascular (CV) risk. Studies of PD-related CV pathology in animal models are lacking despite the clinical importance. Here we introduce the phenotypic evaluation of a rat model of cardiorenal syndrome in response to chronic PD, complemented by a rich transcriptomic dataset detailing chronic PD-induced changes in left ventricle (LV) and kidney tissues. This study aims to determine how PD alters CV parameters and risk factors while identifying pathways for potential therapeutic targets. Sprague Dawley rats underwent Sham or 5/6 nephrectomy (5/6Nx) at 10 weeks of age. Six weeks later an abdominal dialysis catheter was placed in all rats before random assignment to Control or PD (3 daily 1-h exchanges) groups for 8 days. Renal and LV pathology and transcriptomic analysis was performed. The PD regimen reduced circulating levels of BUN in 5/6Nx, indicating dialysis efficacy. PD did not alter blood pressure or cardiovascular function in Sham or 5/6Nx rats, though it attenuated cardiac hypertrophy. Importantly PD increased serum triglycerides in 5/6Nx rats. Furthermore, transcriptomic analysis revealed that PD induced numerous changed transcripts involved with inflammatory pathways, including neutrophil activation and atherosclerosis signaling. We have adapted a uremic rat model of chronic PD. Chronic PD induced transcriptomic changes related to inflammatory signaling that occur independent of 5/6Nx and augmented circulating triglycerides and predicted atherosclerosis signaling in 5/6Nx LV tissues. The changes are indicative of increased CV risk due to PD and highlight several pathways for potential therapeutic targets.

Microbial keratitis secondary to unintended poor compliance with scleral gas-permeable contact lenses.

PURPOSE: To report a case of neurotrophic keratitis in which scleral contact lenses improved vision from 20/100 to 20/20, however, due to poor lens care, an incident of microbial keratitis developed. METHODS: A 64-year-old man with an ocular history of neurotrophic keratitis secondary to herpes simplex in each eye was successfully fit with scleral lenses. He subsequently developed microbial keratitis due to a number of risk factors. RESULTS: The lesion was culture negative, yet was very responsive to treatment with moxifloxacin. The lesion fully healed, and the patient did not suffer additional vision loss. CONCLUSIONS: This case demonstrates the ability of scleral lenses to correct visual impairments secondary to poor epithelial integrity and illustrates the importance of the practitioner providing detailed lens care instruction.

Blood levels of vitamin D in teens and young adults with myopia.

PURPOSE: Longitudinal data suggest that time outdoors may be protective against myopia onset. We evaluated the hypothesis that time outdoors might create differences in circulating levels of vitamin D between myopes and non-myopes. METHODS: Subjects provided 200 µl of peripheral blood in addition to survey information about dietary intakes and time spent in indoor or outdoor activity. The 22 subjects ranged in age from 13 to 25 years. Myopes (n = 14) were defined as having at least -0.75 diopter of myopia in each principal meridian and non-myopes (n = 8) had +0.25 diopter or more hyperopia in each principal meridian. Blood level of vitamin D was measured using liquid chromatography/mass spectroscopy. RESULTS: Unadjusted blood levels of vitamin D were not significantly different between myopes (13.95 ± 3.75 ng/ml) and non-myopes (16.02 ± 5.11 ng/ml, p = 0.29) nor were the hours spent outdoors (myopes = 12.9 ± 7.8 h; non-myopes = 13.6 ± 5.8 h; p = 0.83). In a multiple regression model, total sugar and folate from food were negatively associated with blood vitamin D, whereas theobromine and calcium were positively associated with blood vitamin D. Myopes had lower levels of blood vitamin D by an average of 3.4 ng/ml compared with non-myopes when adjusted for age and dietary intakes (p = 0.005 for refractive error group, model R = 0.76). Gender, time outdoors, and dietary intake of vitamin D were not significant in this model. CONCLUSIONS: The hypothesis that time outdoors might create differences in vitamin D could not be evaluated fully because time outdoors was not significantly related to myopia in this small sample. However, adjusted for differences in the intake of dietary variables, myopes appear to have lower average blood levels of vitamin D than non-myopes. Although consistent with the hypothesis above, replication in a larger sample is needed.