ABSTRACT
The SARS-CoV-2 variant of concern Omicron was first detected in Italy in November 2021. Data from three genomic surveys conducted in Italy between December 2021 and January 2022 suggest that Omicron became dominant in less than one month (prevalence on January 3: 78.6%-83.8%) with a doubling time of 2.7-3.1 days. The mean net reproduction number rose from about 1.15 in absence of Omicron to a peak of 1.83 for symptomatic cases and 1.33 for hospitalized cases, while it remained stable for critical cases.
ABSTRACT
Tissue-resident macrophages exert critical but conflicting effects on the progression of coronavirus infections by secreting both anti-viral type I Interferons and tissue-damaging inflammatory cytokines. Steroids, the only class of host-targeting drugs approved for Covid19, indiscriminately suppress both responses, possibly impairing viral clearance, and provide limited clinical benefit. Here we set up a mouse in vitro co-culture system that reproduces the macrophage response to SARS-CoV2 seen in patients and allows quantitation of inflammatory and antiviral activities. We show that the NFKB-dependent inflammatory response can be selectively inhibited by ablating the lysine-demethylase LSD1, which additionally unleashed interferon-independent ISG activation and blocked viral egress through the lysosomal pathway. These results provide a rationale for repurposing LSD1 inhibitors, a class of drugs extensively studied in oncology, for Covid-19 treatment. One-Sentence SummaryTargeting a chromatin-modifying enzyme in coronavirus infections curbs tissue-damage without affecting antiviral response
