Cyanidin-3-O-glucoside and Peonidin-3-O-glucoside-Rich Fraction of Black Rice Germ and Bran Suppresses Inflammatory Responses from SARS-CoV-2 Spike Glycoprotein S1-Induction In Vitro in A549 Lung Cells and THP-1 Macrophages via Inhibition of the NLRP3 Inflammasome Pathway.

Black rice is a functional food that is high in anthocyanin content, primarily C3G and P3G. It possesses nutraceutical properties that exhibit a range of beneficial effects on human health. Currently, the spike glycoprotein S1 subunit of SARS-CoV-2 (SP) has been reported for its contribution to pathological inflammatory responses in targeting lung tissue and innate immune cells during COVID-19 infection and in the long-COVID phenomenon. Our objectives focused on the health benefits of the C3G and P3G-rich fraction of black rice germ and bran (BR extract) on the inhibition of inflammatory responses induced by SP, as well as the inhibition of NF-kB activation and the NLRP3 inflammasome pathway in an in vitro model. In this study, BR extract was identified for its active anthocyanins, C3G and P3G, using the HPLC technique. A549-lung cells and differentiated THP-1 macrophages were treated with BR extract, C3G, or P3G prior to exposure to 100 ng/mL of SP. Their anti-inflammatory properties were then determined. BR extract at concentrations of 12.5-100 µg/mL exhibited anti-inflammation activity for both A549 and THP-1 cells through the significant suppression of NLRP3, IL-1ß, and IL-18 inflammatory gene expressions and IL-6, IL-1ß, and IL-18 cytokine secretions in a dose-dependent manner (p < 0.05). It was determined that both cell lines, C3G and P3G (at 1.25-10 µg/mL), were compatibly responsible for the significant inhibition of SP-induced inflammatory responses for both gene and protein levels (p < 0.05). With regard to the anti-inflammation mechanism, BR extract, C3G, and P3G could attenuate SP-induced inflammation via counteraction with NF-kB activation and downregulation of the inflammasome-dependent inflammatory pathway proteins (NLRP3, ASC, and capase-1). Overall, the protective effects of anthocyanins obtained from black rice germ and bran can be employed in potentially preventive strategies that use pigmented rice against the long-term sequelae of COVID-19 infection.

Case Report: Clinical and Pathological Findings of a Recurrent C3 Glomerulopathy With Superimposed Membranoproliferative Glomerulonephritis Pattern and Cryoglobulinemia Associated With COVID-19.

Coronavirus disease 2019 (COVID-19) may cause a wide spectrum of kidney pathologies. The impact of COVID-19 is unclear in the context of the complement system abnormalities, including C3 glomerulopathy (C3G). In this report, we describe a young adult receiving a kidney transplant for C3 glomerulopathy (C3G), a disorder of the alternative complement pathway. The patient developed a recurrent C3G ~7 months after transplantation. His post-transplant course was complicated by SARS-CoV-2 infection. There was a progression of glomerulonephritis, characterized by de novo immune-complex mediated membranoproliferative glomerulonephritis pattern of injury with crescentic and necrotizing features, along with positive immunoglobulins, persistent IgM staining and the presence of cryoglobulinemia. COVID-19 may have aggravated the inherent complement dysregulation and contributed to cryoglobulinemia observed in this patient. Our study of 5 sequential kidney allograft biopsy series implicates that COVID-19 in this patient promoted a superimposed immune complex-mediated glomerulonephritis with membranoproliferative glomerulonephritis (MPGN) pattern and cryoglobulinemia, which was a potentiating factor in allograft loss. This work represents the first report of cryoglobulinemic GN after COVID-19.