RESUMO
BACKGROUND: Post COVID-19 Condition (PCC), characterized by lingering symptoms post-acute COVID-19, poses clinical challenges, highlighting the need to understand its underlying molecular mechanisms. This meta-analysis aims to shed light on the transcriptomic landscapes and sex-specific molecular dynamics intrinsic to PCC. METHODS: A systematic review identified three studies suitable for comprehensive meta-analysis, encompassing 135 samples (57 PCC subjects and 78 recovered subjects). We performed meta-analysis on differential gene expression, a gene set enrichment analysis of Reactome pathways, and weighted gene co-expression network analysis (WGCNA). We performed a drug and disease enrichment analysis and also assessed sex-specific differences in expression patterns. KEY FINDINGS: A clear difference was observed in the transcriptomic profiles of PCC subjects, with 530 differentially expressed genes (DEGs) identified. Enrichment analysis revealed that the altered pathways were predominantly implicated in cell cycle processes, immune dysregulation and histone modifications. Antioxidant compounds such as hesperitin were predominantly linked to the hub genes of the DEGs. Sex-specific analyses highlighted disparities in DEGs and altered pathways in male and female PCC patients, revealing a difference in the expression of ribosomal proteins. PCC in men was mostly linked to neuro-cardiovascular disorders, while women exhibited more diverse disorders, with a high index of respiratory conditions. CONCLUSION: Our study reveals the intricate molecular processes underlying PCC, highlighting that the differences in molecular dynamics between males and females could be key to understanding and effectively managing the varied symptomatology of this condition.
RESUMO
PURPOSE: To design a randomized clinical trial to assess the efficacy and safety of favipiravir in patients with COVID-19 disease with pneumonia. METHODS: A randomized, double blind, placebo-controlled clinical trial of favipiravir in patients with COVID-19 pneumonia was conducted in three Spanish sites. Randomization 1:1 to favipiravir or placebo (in both groups added to the Standard of Care) was performed to treat the patients with COVID-19 pneumonia. The primary endpoint was "time to clinical improvement," measured as an improvement for ≥ two categories on a 7-point WHO ordinal scale in an up to 28 days' time frame. RESULTS: Forty-four patients were randomized (23 in the favipiravir group and 21 in the placebo group). The median time to clinical improvement was not different between the favipiravir and the placebo arms (10 days for both groups) and none of the secondary endpoints showed significant differences between arms. The proportion of adverse events (both serious and non-serious) was statistically different between the favipiravir group (68.29%) and the placebo group (31.7%) (p = 0.019), but there was insufficient statistical evidence to correlate the degree of severity of the events with the treatment group. CONCLUSIONS: Favipiravir administered for ten days to patients with COVID-19 and pneumonia did not improve outcomes compared with placebo. Although this is an underpowered negative study, efficacy results align with other randomized trials. However, in the present study, the non-serious adverse events were more frequent in the favipiravir group.
