A possibly positive development against severe Covid-19? I guess the importance of the still controversial HCQ is here possibly reestablished in treatment e.g. when used in combination with the now reportedly proven dexamethasone glucocorticoid via a new mechanism (lysosome inhibition):
He Y, Xu Y, Zhang C, et al. Identification of a lysosomal pathway that modulates glucocorticoid signaling and the inflammatory response. Sci Signal. 2011;4(180):ra44.
https://stke.science...4/180/ra44.full
"The antimalaria drug chloroquine has been used as an anti-inflammatory agent for treating systemic lupus erythematosus and rheumatoid arthritis. We report that chloroquine promoted the transrepression of proinflammatory cytokines by the glucocorticoid receptor (GR). In a mouse collagen-induced arthritis model, chloroquine enhanced the therapeutic effects of glucocorticoid treatment. By inhibiting lysosome function, chloroquine synergistically activated glucocorticoid signaling. Lysosomal inhibition by either bafilomycin A1 (an inhibitor of the vacuolar adenosine triphosphatase) or knockdown of transcription factor EB (TFEB, a master activator of lysosomal biogenesis) mimicked the effects of chloroquine. The abundance of the GR, as well as that of the androgen receptor and estrogen receptor, correlated with changes in lysosomal biogenesis. Thus, we showed that glucocorticoid signaling is regulated by lysosomes, which provides a mechanistic basis for treating inflammation and autoimmune diseases with a combination of glucocorticoids and lysosomal inhibitors."
"...Given the widespread clinical use of glucocorticoids for treating inflammatory diseases and cancers, our discovery of the synergism between CQ and glucocorticoids has immediate therapeutic implications. Clinical studies of rheumatoid arthritis have shown that combined treatment of CQ with a low dose of glucocorticoid (for example, prednisolone at <15 mg/day) achieved a better effect, in terms of reducing joint destruction and increasing the remission rate, than either agent alone (44–46). Our results provide mechanistic insight for this treatment strategy and suggest that combined treatment not only will allow a lower dose of glucocorticoid to be effective but may also achieve therapeutic effects in situations when even a maximal dose of glucocorticoid fails to suppress the inflammation. Our study addresses why the combined treatment has better effects and provides a rational basis for developing new therapeutic applications by leveraging the synergy between glucocorticoids and lysosomal inhibitors..."