SARS-Cov2 acute and post-active infection in the context of autoimmune and chronic inflammatory diseases.

The clinical and immunological spectrum of acute and post-active COVID-19 syndrome overlaps with criteria used to characterize autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Indeed, following SARS-Cov2 infection, the innate immune response is altered with an initial delayed production of interferon type I (IFN-I), while the NF-kappa B and inflammasome pathways are activated. In lung and digestive tissues, an alternative and extrafollicular immune response against SARS-Cov2 takes place with, consequently, an altered humoral and memory T cell response leading to breakdown of tolerance with the emergence of autoantibodies. However, the risk of developing severe COVID-19 among SLE and RA patients did not exceed the general population except in those having pre-existing neutralizing autoantibodies against IFN-I. Treatment discontinuation rather than COVID-19 infection or vaccination increases the risk of developing flares. Last but not least, a limited number of case reports of individuals having developed SLE or RA following COVID-19 infection/vaccination have been reported. Altogether, the SARS-Cov2 pandemic represents an unique opportunity to investigate the dangerous interplay between the immune response against infectious agents and autoimmunity, and to better understand the triggering role of infection as a risk factor in autoimmune and chronic inflammatory disease development.

Graphene Nanoplatelets: In Vivo and In Vitro Toxicity, Cell Proliferative Activity, and Cell Gene Expression

Multi-layer graphene (2–10 layers), also called graphene nanoplatelets (GNPs), is a carbon-based nanomaterial (CBN) type with excellent properties desirable for many biomedical applications. Despite the promising advantages reported of GNPs, nanoscale materials may also present a potential hazard to humans. Therefore, in this study, the in vivo toxicity of these nanomaterials at a wide range of concentrations from 12.5 to 500 µg/mL was evaluated in the Caenorhabditis elegans model for 24 h (acute toxicity) and 72 h (chronic toxicity). Furthermore, their in vitro toxicity (from 0 to 10 µg/mL for 12 and 24 h), proliferative activity at 72 and 96 h, and their effect on the expression of thirteen genes in human keratinocytes HaCaT cells were studied. The physico-chemical and morphological aspects of the GNPs used in this study were analyzed by Raman scattering spectroscopy, electron microscopy, zeta potential as a function of pH, and particle size measurements by dynamic light scattering. The results of this study showed that GNPs showed in vivo non-toxic concentrations of 25 and 12.5 µg/mL for 24 h, and at 12.5 µg/mL for 72 h. Moreover, GNPs present time-dependent cytotoxicity (EC50 of 1.142 µg/mL and 0.760 µg/mL at 12 h and 24 h, respectively) and significant proliferative activity at the non-toxic concentrations of 0.005 and 0.01 μg/mL in the HaCaT cell line. The gene expression study showed that this multi-layer-graphene is capable of up-regulating six of the thirteen genes of human keratinocytes (SOD1, CAT, TGFB1, FN1, CDH1, and FBN), two more genes than other CBNs in their oxidized form such as multi-layer graphene oxide. Therefore, all these results reinforce the promising use of these CBNs in biomedical fields such as wound healing and skin tissue engineering.

Persistently elevated complement alternative pathway biomarkers in COVID-19 correlate with hypoxemia and predict in-hospital mortality.

Mechanisms underlying the SARS-CoV-2-triggered hyperacute thrombo-inflammatory response that causes multi-organ damage in coronavirus disease 2019 (COVID-19) are poorly understood. Several lines of evidence implicate overactivation of complement. To delineate the involvement of complement in COVID-19, we prospectively studied 25 ICU-hospitalized patients for up to 21 days. Complement biomarkers in patient sera and healthy controls were quantified by enzyme-linked immunosorbent assays. Correlations with respiratory function and mortality were analyzed. Activation of complement via the classical/lectin pathways was variably increased. Strikingly, all patients had increased activation of the alternative pathway (AP) with elevated levels of activation fragments, Ba and Bb. This was associated with a reduction of the AP negative regulator, factor (F) H. Correspondingly, terminal pathway biomarkers of complement activation, C5a and sC5b-9, were significantly elevated in all COVID-19 patient sera. C5a and AP constituents Ba and Bb, were significantly associated with hypoxemia. Ba and FD at the time of ICU admission were strong independent predictors of mortality in the following 30 days. Levels of all complement activation markers were sustained throughout the patients' ICU stays, contrasting with the varying serum levels of IL-6, C-reactive protein, and ferritin. Severely ill COVID-19 patients have increased and persistent activation of complement, mediated strongly via the AP. Complement activation biomarkers may be valuable measures of severity of lung disease and the risk of mortality. Large-scale studies will reveal the relevance of these findings to thrombo-inflammation in acute and post-acute COVID-19.