Case Fatality Rate and Severity of COVID-19 among Patients with Sickle Cell Disease: A Systematic Review and Meta-Analysis.

The sickle cell disease (SCD) population has been considered particularly vulnerable to viral pandemics since the emergence of H1N1 in 2009. In this sense, the advance of the COVID-19 pandemic from 2020 has brought this group of patients to the center of concern. However, scientific knowledge about the susceptibility of patients with SCD to a severe COVID-19 pandemic is still insufficient, and efforts to establish a general profile of the disease in these patients, remain inadequate. The present study, therefore, sought to characterize the case fatality rate and severity of COVID-19 in patients with SCD throughout the world. A systematic review of Pubmed/MEDLINE, Scopus, Cochrane Library, and Virtual Health Library databases through December 2021 was then performed. Subsequently, the primary and secondary outcomes were used in the meta-analysis in RStudio® software. Seventy-two studies were included with 6,011 SCD patients confirmed to have SARS-CoV-2 infection between mid-2020 and early 2022. The mean age of patients was 27 years. During this period, 218 deaths caused by COVID-19 were reported in the studied population, corresponding to an overall case fatality rate of 3%. In addition, 10% of patients with SCD were admitted to the ICU after complications caused by COVID-19, and 4% of them required invasive ventilatory support. In conclusion, the high fatality rate, intensive care unit admission and need for mechanical ventilation due to COVID-19 in young patients with SCD indicate that this population is at high risk for severe disease progression.

LyeTxI-b, a Synthetic Peptide Derived From a Spider Venom, Is Highly Active in Triple-Negative Breast Cancer Cells and Acts Synergistically With Cisplatin.

Breast cancer is the most common cancer that affects women globally and is among the leading cause of women's death. Triple-negative breast cancer is more difficult to treat because hormone therapy is not available for this subset of cancer. The well-established therapy against triple-negative breast cancer is mainly based on surgery, chemotherapy, and immunotherapy. Among the drugs used in the therapy are cisplatin and carboplatin. However, they cause severe toxicity to the kidneys and brain and cause nausea. Therefore, it is urgent to propose new chemotherapy techniques that provide new treatment options to patients affected by this disease. Nowadays, peptide drugs are emerging as a class of promising new anticancer agents due to their lytic nature and, apparently, a minor drug resistance compared to other conventional drugs (reviewed in Jafari et al., 2022). We have recently reported the cytotoxic effect of the antimicrobial peptide LyeTx I-b against glioblastoma cells (Abdel-Salam et al., 2019). In this research, we demonstrated the cytotoxic effect of the peptide LyeTx I-b, alone and combined with cisplatin, against triple-negative cell lines (MDA-MD-231). LyeTx-I-b showed a selectivity index 70-fold higher than cisplatin. The peptide:cisplatin combination (P:C) 1:1 presented a synergistic effect on the cell death and a selective index value 16 times greater than the cisplatin alone treatment. Therefore, an equi-effective reduction of cisplatin can be reached in the presence of LyeTx I-b. Cells treated with P:C combinations were arrested in the G2/M cell cycle phase and showed positive staining for acridine orange, which was inhibited by bafilomycin A1, indicating autophagic cell death (ACD) as a probable cell death mechanism. Furthermore, Western blot experiments indicated a decrease in P21 expression and AKT phosphorylation. The decrease in AKT phosphorylation is indicative of ACD. However, other studies are still necessary to better elucidate the pathways involved in the cell death mechanism induced by the peptide and the drug combinations. These findings confirmed that the peptide LyeTx I-b seems to be a good candidate for combined chemotherapy to treat breast cancer. In addition, in vivo studies are essential to validate the use of LyeTx I-b as a therapeutic drug candidate, alone and/or combined with cisplatin.