Introduction: Hospital mortality due to COVID-19 in Mexico is high (32%) and as of today, effective treatment options are limited. More effective treatments that shorten hospital stay and reduce mortality are needed. Initial reports for the use of convalescent plasma (CP) therapy for COVID-19 appear promising. We describe a case series of eight patients with impending respiratory failure, who underwent CP therapy. Methods: Six male and two female (ages 31 to 79) patients that were admitted to the intensive-care unit for severe COVID-19 were transfused with two doses of CP (250 mL per dose, anti-SARS-CoV-2 IgG titers > 1:100). Donors were six SARS-CoV-2 infected males who remained asymptomatic for > 7 days and were negative for two nasopharyngeal RT-PCR tests. Clinical characteristics, inflammatory and cellular injury markers, chest X-ray findings and viral loads were analyzed before and after CP administration. Viral load association to disease severity was further analyzed on a separate cohort of asymptomatic vs hospitalized patients with COVID-19. Results: Eight patients with respiratory failure were successfully discharged with a median length of stay of 22.5 (IQR 18.25-29.00). After CP therapy, we observed a reduction of C-reactive protein (CRP) (median, 22.80 mg/dL vs. 1.63 mg/dL), and of procalcitonin (median, 0.27 ng/mL vs. 0.13 ng/mL). High-Sensitivity Cardiac Troponin I (hs-cTnI), Brain Natriuretic Peptide (BNP) and Lactate Dehydrogenase (LDH) were lower, and a mild reduction of pulmonary infiltrates by chest X-ray was observed. Lastly, a reduction of viral load was after CP therapy was found. (log, median [IQR], 1.2 [0.70-2.20] vs. 0.25 [0.00-1.78]). We observed no adverse effects. Conclusions: CP could potentially be an effective therapeutic option for patients with severe COVID-19. Clinical benefit needs to be studied further through randomized controlled trials.

Chromatin architecture influences transcription by modulating the physical access of regulatory factors to DNA, playing fundamental roles in cell identity. Studies on dopaminergic differentiation have identified coding genes, but the relationship with non-coding genes or chromatin accessibility remains elusive. Using RNA-Seq and ATAC-Seq we profiled differentially expressed transcripts and open chromatin regions during early dopaminergic neuron differentiation. Hierarchical clustering of differentially expressed genes, resulted in 6 groups with unique characteristics. Surprisingly, the abundance of long non-coding RNAs (lncRNAs) was high in the most downregulated transcripts, and depicted positive correlations with target mRNAs. We observed that open chromatin regions decrease upon differentiation. Enrichment analyses of accessibility depict an association between open chromatin regions and specific functional pathways and gene-sets. A bioinformatic search for motifs allowed us to identify transcription factors and structural nuclear proteins that potentially regulate dopaminergic differentiation. Interestingly, we also found changes in protein and mRNA abundance of the CCCTC-binding factor, CTCF, which participates in genome organization and gene expression. Furthermore, assays demonstrated co-localization of CTCF with Polycomb-repressed chromatin marked by H3K27me3 in pluripotent cells, progressively decreasing in neural precursor cells and differentiated neurons. Our work provides a unique resource of transcription factors and regulatory elements, potentially involved in the acquisition of human dopaminergic neuron cell identity.

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