Cutaneous susceptibility to SARS-CoV-2 infection according to the expression of viral entry factors in the skin / Susceptibilidad cutánea a la infección por SARS-CoV-2 según la expresión de los factores de entrada viral en la piel

Abstract Introduction: Reports of dermatological manifestations in patients with COVID-19 suggest a possible cutaneous tropism of SARS-CoV-2; however, the capacity of this virus to infect the skin is unknown. Objective: To determine the susceptibility of the skin to SARS-CoV-2 infection based on the expression of viral entry factors ACE2 and TMPRSS2 in this organ. Method: A comprehensive analysis of human tissue gene expression databases was carried out looking for the presence of the ACE2 and TMPRSS2 genes in the skin. mRNA expression of these genes in skin-derived human cell lines was also assessed. Results: The analyses showed high co-expression of ACE2 and TMPRSS2 in the gastrointestinal tract and kidney, but not in the skin. Only the human immortalized keratinocyte HaCaT cell line expressed detectable levels of ACE2, and no cell line originating in the skin expressed TMPRSS2. Conclusions: Our results suggest that cutaneous manifestations in patients with COVID-19 cannot be directly attributed to the virus. It is possible that cutaneous blood vessels endothelial damage, as well as the effect of circulating inflammatory mediators produced in response to the virus, are the cause of skin involvement.

Resumen Introducción: Reportes de manifestaciones dermatológicas en pacientes con COVID-19 sugieren un posible tropismo cutáneo del virus SARS-CoV-2; sin embargo, se desconoce la capacidad de este virus para infectar la piel. Objetivo: Determinar la susceptibilidad de la piel a la infección por SARS-CoV-2 con base en la expresión de los factores de entrada viral ACE2 y TMPRSS2 en dicho órgano. Método: Se buscaron los genes ACE2 y TMPRSS2 en la piel, para lo cual se realizó un análisis extenso de las bases de datos de expresión genética en tejidos humanos. Asimismo, se evaluó la expresión de dichos genes en líneas celulares humanas derivadas de la piel. Resultados: Los análisis mostraron alta expresión conjunta de ACE2 y TMPRSS2 en el tracto gastrointestinal y en los riñones, pero no en la piel. Solo la línea celular de queratinocitos humanos inmortalizados HaCaT expresó niveles detectables de ACE2 y ninguna línea celular de origen cutáneo expresó TMPRSS2. Conclusiones: Los resultados sugieren que las manifestaciones dermatológicas en pacientes con COVID-19 no pueden ser atribuidas directamente al virus; es posible que sean originadas por el daño endotelial a los vasos sanguíneos cutáneos y el efecto de los mediadores inflamatorios circulantes producidos en respuesta al virus.

Zika virus damages the human placental barrier and presents marked fetal neurotropism

An unusually high incidence of microcephaly in newborns has recently been observed in Brazil. There is a temporal association between the increase in cases of microcephaly and the Zika virus (ZIKV) epidemic. Viral RNA has been detected in amniotic fluid samples, placental tissues and newborn and fetal brain tissues. However, much remains to be determined concerning the association between ZIKV infection and fetal malformations. In this study, we provide evidence of the transplacental transmission of ZIKV through the detection of viral proteins and viral RNA in placental tissue samples from expectant mothers infected at different stages of gestation. We observed chronic placentitis (TORCH type) with viral protein detection by immunohistochemistry in Hofbauer cells and some histiocytes in the intervillous spaces. We also demonstrated the neurotropism of the virus via the detection of viral proteins in glial cells and in some endothelial cells and the observation of scattered foci of microcalcifications in the brain tissues. Lesions were mainly located in the white matter. ZIKV RNA was also detected in these tissues by real-time-polymerase chain reaction. We believe that these findings will contribute to the body of knowledge of the mechanisms of ZIKV transmission, interactions between the virus and host cells and viral tropism.

Association of X4 tropism with disease progression in antiretroviral-treated children and adolescents living with HIV/AIDS in São Paulo, Brazil

Management of children with HIV/AIDS is specially challenging. Age-related issues do not allow for direct transposition of adult observations to this population. CXCR4 tropism has been associated with disease progression in adults. The geno2pheno web-base is a friendly tool to predict viral tropism on envelope V3 sequences, generating a false positive rate for a CXCR4 prediction. We evaluated the association of HIV-1 tropism prediction with clinical and laboratory outcome of 73 children with HIV/AIDS in São Paulo, Brazil. The CXCR4 tropism was strongly associated with a lower (nadir) CD4 documented during follow-up (p < 0.0001) and with disease severity (clinical event and/or CD4 below 200 cells/mm3) at the last observation, using commonly applied clinical cutoffs, such as10%FPRclonal (p = 0.001). When variables obtained during follow-up are included, both treatment adherence and viral tropism show a significant association with disease severity. As for viremia suppression, 30% (22/73) were undetectable at the last observation, with only adherence strongly associated with suppression after adjustment. The study brings further support to the notion that antiretroviral treatment adherence is pivotal to management of HIV disease, but suggests that tropism prediction may provide an additional prognostic marker to monitor HIV disease in children.