Protection against COVID-19 in African population: Immunology, genetics, and malaria clues for therapeutic targets.

BACKGROUND: There is a marked discrepancy between SARS-CoV-2 seroprevalence and COVID-19 cases and deaths in Africa. MAIN: SARS-CoV-2 stimulates humoral and cellular immunity systems, as well as mitogen-activated protein kinase (MAPK) and nuclear NF-kB signalling pathways, which regulate inflammatory gene expression and immune cell differentiation. The result is pro-inflammatory cytokines release, hyperinflammatory condition, and cytokine storm, which provoke severe lung alterations that can lead to multi-organ failure in COVID-19. Multiple genetic and immunologic factors may contribute to the severity of COVID-19 in African individuals when compared to the rest of the global population. In this article, the role of malaria, NF-kB and MAPK pathways, caspase-12 expression, high level of LAIR-1-containing antibodies, and differential glycophorins (GYPA/B) expression in COVID-19 are discussed. CONCLUSION: Understanding pathophysiological mechanisms can help identify target points for drugs and vaccines development against COVID-19. To our knowledge, this is the first study that explores this link and proposes a biological and molecular answer to the epidemiologic discrepancy in COVID-19 in Africa.

Down's syndrome and COVID-19: risk or protection factor against infection? A molecular and genetic approach.

Down syndrome (DS) is the most common genetic cause of learning difficulties and intellectual disabilities. DS patients often present with several congenital defects and chronic diseases, including immunity disorders. Elevated levels of pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) have been seen, which appear to vary with age. At birth, patients present with combined immunodeficiency, with frequent infections that decrease with age. Furthermore, high levels of IL-4 and IL-10 with anti-inflammatory properties and low levels of IL-6 and TNF-α are described in children. The immune system is believed to play an essential role in SARS-CoV-2 pathogenesis, and it has been associated with elevated levels of pro-inflammatory cytokines and an exaggerated cytokine release syndrome (CRS) that may eventually trigger a severe situation called cytokine storm. On the other hand, genetic features seem to be involved in the predisposition to illness and its severity. Overexpression of DSCR1 and ZAKI-4 inhibits the translocation of activated T lymphocyte nuclear factor (NF-AT) to the nucleus, a main step in the inflammatory responsiveness. We discuss here the possible role of immunology and genetic features of DS in the infection and prognosis in COVID-19.

Cerebrovascular disease in COVID-19: Is there a higher risk of stroke?

The presence of stroke has been observed in young adults (under fifty years of age) without cardiovascular risk factors who are suffering from COVID-19. It is speculated that there is really a significant increase, as a few cases have yet to be described, or that the infection favors his development. Cerebrovascular events are more common in older patients with stroke risk factors, such as hypertension and diabetes mellitus, and those who have elevated fibrin D-dimers. Multiple case reports and series about cerebrovascular disease (CVD) in COVID-19 has been informed. The mechanism that causes cerebral ischemia in COVID-19 remains undiscovered. However, progressively there is increasing evidence of hypercoagulability that can be or contribute to the cause. We review the current literature about CVD both epidemiology and etiology. More studies are needed to understand.

PML bodies in reactive sensory ganglion neurons of the Guillain-Barré syndrome.

Acute inflammatory demyelinating polyneuropathy (AIDP) is a type of Guillain-Barré syndrome (GBS) characterized by primary nerve demyelination sometimes with secondary axonal degeneration. Studies on the fine structure of dorsal root ganglia in AIDP are lacking. Our aim was to investigate the cytology and nuclear organization of primary sensory neurons in AIDP with axonal injury using ultrastructural and immunohistochemical analysis. The light cytology of the L5 dorsal ganglion showed the characteristic findings of neuronal axonal reaction. The organization of chromatin, nucleolus, Cajal bodies, and nuclear pores corresponded to transcriptionally active neurons. However, the hallmark of the nuclear response to axonal injury was the formation of numerous nuclear bodies (NBs; 6.37 +/- 0.6, in the AIDP, vs. 2.53 +/- 0.2, in the control, mean +/- SDM), identified as promyelocytic leukemia (PML) bodies by the presence of the protein PML. In addition to PML protein, nuclear bodies contained SUMO-1 and the transcriptional regulators CREB-binding protein (CBP) and glucocorticoid receptor (GR). The presence of proteasome 19S was also detected in some nuclear bodies. We suggest that neuronal PML bodies could regulate the nuclear concentration of active proteins, a process mediated by protein interactions with PML and SUMO-1 proteins. In the AIDP case, the proliferation of PML bodies may result from the overexpression of some nuclear proteins due to changes in gene expression associated with axonal injury.