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.

Mitochondria modify their function and morphology to satisfice the bioenergetic demand of the cells. Cancer cells take advantage of these features to sustain their metabolic, proliferative, metastatic, and survival necessities. Therefore, the understanding of mitochondrial morphologic changes of the different grades of Triple-Negative Breast Cancer (TNBC) could be relevant for the design of novel treatments. Consequently, this research aimed to explore the mitochondria morphology and gene expression of some proteins related to mitochondrial dynamics as well as proteins related to oxidative and non-oxidative metabolism of metastatic and non-metastatic TNBC. We found that mitochondrial-morphology and metabolism are different between metastatic and non-metastatic TNBC. Metastatic TNBC showed overexpression of genes related to mitochondrial dynamics, fatty acids, and glycolytic metabolism. These features were accompanied by a fused mitochondrial morphology. In contrast, the non-metastatic TNBC presented a stress-associated mitochondrial morphology, hyperfragmented mitochondria accompanied by upregulated expression of mitochondrial biogenesis-related genes, both characteristics related to the higher ROS production observed in this cell line. These differences found between metastatic and non-metastatic TNBC will allow a better understanding of the metastasis process and the improvement of the development of a specific and personalized TNBC therapy.

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Background: Triple negative breast cancer (TNBC) is characterized by heterogeneous metastatic and metabolic properties, which difficult the diagnosis and development of specific treatment. Therefore, the understanding of the mitochondria´s role in the different grades of TNBC could be relevant for the design of novel specific TNBC treatments. This research aimed to explore the mitochondria morphology and gene expression of proteins related to oxidative and non-oxidative metabolism in metastatic and non-metastatic TNBC cell lines. Methods: We performed a gene expression analysis of mitochondrial biogenesis, EMT and principal metabolism-related genes (Integrated DNA Technologies, CA, USA) in three breast cancer cell lines HCC-1395, MDA-MB-231 and MCF-12A. After the gene expression qPCR data mining, in sílico analisis were performed using confocal microscopy (Leica Microsystems,WZL, DE) in the cell lines where mitochondrial distribution, morphology, function and ROS production were measured. Results: The metastatic TNBC-cell line showed a preference for fatty acid biosynthesis and glycolytic metabolism since overexpression of genes related to both pathways was observed. These metabolism features were accompanied by a fused mitochondrial morphology and lower mitochondrial activity since was observed less mitochondrial density accompanied by the downregulated expression of biogenesis-related genes such as PGC1α. In contrast, the non-metastatic TNBC-cell line presented a hyperfragmented mitochondria, a stress associated mitochondrial morphology accompanied by upregulated expression of mitochondrial biogenesis-related genes, both characteristics related to the higher ROS production observed in this cell line. Conclusions: Metastatic TNBC was characterized by a mitochondrial function and morphology similar to control ranges with a metabolic gene program directed to glycolysis and FA usage. While mitochondria of the non-metastatic TNBC cell line was characterized by a higher density and potential, related to an increase of mitochondrial biogenesis, which in turn was associated with higher levels of ROS and with the consequence of a hyperfragmented mitochondrial morphology. These characteristics can provide a better understanding of the metastasis observed in TNBC and contribute to the development of a specific and personalized TNBC therapy. Key words: Triple Negative Breast Cancer, Mitochondria, Cell-metabolism. Citation Format: Claudia D Aguayo-Millán, Perla Perez-Trevino, Sandra Santuario-Facio, Alberto Camacho, Noemí Garcia, Rocio Ortiz-Lopez. Metastatic TNBC is highly associated with a fused mitochondrial morphology and a glycolytic and lipogenic metabolism programmation [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS19-25.