COVID-19 and membranous nephropathy: observational and Mendelian randomization analyses (preprint)

Membranous nephropathy (MN) imposes a substantial burden of illness and death. However, a systematic assessment of the impact of the COVID-19 pandemic on MN incidence has not yet been conducted. This research is an observational cohort study conducted retrospectively. The kidney biopsy results of two medical institutions, including our hospital, were reviewed for the period between January 2016 and May 2023. Relevant statistical analysis of different glomerular diseases was performed based on the corresponding pathological diagnoses. The aim was to compare the incidence changes of different glomerular diseases before and during the COVID-19 pandemic. Our focus was on investigating the changes in the incidence rate of MN and attempting to uncover the causal effects between varying degrees of COVID-19 and MN utilizing bidirectional Mendelian randomization (MR) using GWAS data from European and Asian ancestry. We found that the incidence of MN decreased by 3.6% during the COVID-19 pandemic compared to the period before the onset of the COVID-19 pandemic(P = 0.026). However, after Bonferroni correction, the change in incidence did not reach a significant p-value(P > 0.05/2), and the overall incidence of glomerular diseases did not show a significant change (P = 0.364). Additionally, the Mendelian randomization analysis indicated no significant causality between COVID-19 (critical illness, susceptibility, severe infection, hospitalization, and severity) and MN (no significance, PBonferroni>0.05).The results of this preliminary study suggest that the incidence rate of MN remained relatively stable during the COVID-19 pandemic. Furthermore, our genetic perspective Mendelian randomization analysis has furnished additional evidence contradicting any causal relationship between varying degrees of COVID-19 infection and MN.

Complex Interplay Between COVID-19 Lockdown and Myopic Progression.

Purpose: To compare the myopic progression before and during strict home confinement when coronavirus disease 2019 (COVID-19) outbreak and explore the potential influencing factors. Methods: A cross-sectional study. One hundred and fifteen myopic children (115 right eyes) who replace their frame-glasses from December 2019 to January 2020 and with complete refractive records in our hospital since myopia were involved in the study. At the beginning of the strict home confinement and after a 3-month strict home confinement during the COVID-19 pandemic, they were invited to our hospital to examine the axial length and refractive errors. And visual functions, convergence insufficiency symptom survey (CISS) scale and questionnaires were also performed. Besides, the axial length and refractive errors before the COVID-19 were got from outpatient case files. The effect of strict home confinement on myopia was assessed by comparing monthly axial elongation before COVID-19 and during strict home confinement. Spearman correlation analysis was performed to explore the correlation between potential influencing factors and myopia progression. Results: Axial length's monthly elongation during strict home confinement was 35% higher than normal periods (0.046 vs. 0.033 mm/month, P = 0.003). The proportion of severe asthenopia doubled (P = 0.020). For myopia progression, heredity, close indoor work time and electronic products were risk factors. Besides, the protective factors were age, rest time after continuous eye usage, sleep time and distance from eye to computer screen. Conclusions: During COVID-19, the decline in outdoor activities and increase of exposure time to digital screens accelerated the progression of myopia by 1/3.

Machine learning-based cytokine microarray digital immunoassay analysis.

Serial measurement of a large panel of protein biomarkers near the bedside could provide a promising pathway to transform the critical care of acutely ill patients. However, attaining the combination of high sensitivity and multiplexity with a short assay turnaround poses a formidable technological challenge. Here, the authors develop a rapid, accurate, and highly multiplexed microfluidic digital immunoassay by incorporating machine learning-based autonomous image analysis. The assay has achieved 12-plexed biomarker detection in sample volume <15 µL at concentrations < 5 pg/mL while only requiring a 5-min assay incubation, allowing for all processes from sampling to result to be completed within 40 min. The assay procedure applies both a spatial-spectral microfluidic encoding scheme and an image data analysis algorithm based on machine learning with a convolutional neural network (CNN) for pre-equilibrated single-molecule protein digital counting. This unique approach remarkably reduces errors facing the high-capacity multiplexing of digital immunoassay at low protein concentrations. Longitudinal data obtained for a panel of 12 serum cytokines in human patients receiving chimeric antigen receptor-T (CAR-T) cell therapy reveals the powerful biomarker profiling capability. The assay could also be deployed for near-real-time immune status monitoring of critically ill COVID-19 patients developing cytokine storm syndrome.

A digital protein microarray for COVID-19 cytokine storm monitoring.

Despite widespread concern regarding cytokine storms leading to severe morbidity in COVID-19, rapid cytokine assays are not routinely available for monitoring critically ill patients. We report the clinical application of a digital protein microarray platform for rapid multiplex quantification of cytokines from critically ill COVID-19 patients admitted to the intensive care unit (ICU) at the University of Michigan Hospital. The platform comprises two low-cost modules: (i) a semi-automated fluidic dispensing/mixing module that can be operated inside a biosafety cabinet to minimize the exposure of the technician to the virus infection and (ii) a 12-12-15 inch compact fluorescence optical scanner for the potential near-bedside readout. The platform enabled daily cytokine analysis in clinical practice with high sensitivity (<0.4 pg mL-1), inter-assay repeatability (∼10% CV), and rapid operation providing feedback on the progress of therapy within 4 hours. This test allowed us to perform serial monitoring of two critically ill patients with respiratory failure and to support immunomodulatory therapy using the selective cytopheretic device (SCD). We also observed clear interleukin-6 (IL-6) elevations after receiving tocilizumab (IL-6 inhibitor) while significant cytokine profile variability exists across all critically ill COVID-19 patients and to discover a weak correlation between IL-6 to clinical biomarkers, such as ferritin and C-reactive protein (CRP). Our data revealed large subject-to-subject variability in patients' response to COVID-19, reaffirming the need for a personalized strategy guided by rapid cytokine assays.

Is increased symptom interval associated with advanced stage and poorer outcome? A prospective multicenter study of 220 patients with osteosarcoma around the knee

OBJECTIVE: Osteosarcoma is rare disease and there is a strong controversy about the potential impact of symptom interval on the stage of disease and patients'outcomes. We want to assess whether increased symptom interval (SI) is associated with advanced tumor stage and poor prognosis for patients with osteosarcoma. METHODS: We analyzed prospectively collected data of 220 patients younger than 40 years who had osteosarcoma around the knee. Symptom interval was analyzed to evaluate its impact on metastases at diagnosis, tumor volume, chemotherapy response and overall survival. RESULTS: The median of SI was 64.5 (Q1-Q3: 42-88) days. The 5-year overall survival rate for patients with different length of symptom interval (<42 days, 42-64 days, 65-87 days, >= 88 days) were 0.78 (95 %CI: 0.67-0.89), 0.49 (95 %CI: 0.35-0.63), 0.52 (95 %CI:0.39-0.65), and 0.65 (95 %CI:0.53-0.77) respectively(p = 0.013). Nonparametric test showed increased SI was associated with metastases at diagnosis (p = 0.008), but not associated with large tumor volume or poor chemotherapy response. Cox regression mode test showed that patient with increased SI had higher hazard ratio (42-64 days HR: 2.586 (95 %CI:1.360-4.915);65-87 days, HR: 2.225 (95 %CI:1.170-4.233)) for poor outcomes compared to short SI (<42 days), though it was not significant in multivariate analysis (p = 0.182). CONCLUSION: Increased SI but not the longest SI is associated with higher incidence of metastases at diagnosis;patients can benefit from an earlier diagnosis in terms of survival.