Serotype-associated immune response and network immunoclusters in children and adults during acute Dengue virus infection.

The present study was designed as an exploratory investigation to characterize the overall profile of chemokines, growth factors, and pro-inflammatory/regulatory cytokines during acute DENV infection according to DENV-1, DENV-2, DENV-4 serotypes and age: children: <1-10-year-old (yo); adolescents:11-20 yo; adults 21-40 yo; and older adults: 41-75 yo. The levels of soluble immunemediators were measured in serum by high-throughput microbeads array in 636 subjects including 317 DENV-infected and 319 age-matching non-infected control (NI). Overall, most soluble mediators were increased in DENV-infected patients as compared to NI group regardless of age and DENV serotype, with high magnitude order of increase for CCL2, CXCL10, IL-1ß, IFN-γ, IL1-Ra (fold change >3x), except PDGF in which no fold change was observed. Moreover, despite the age ranges, DENV-1 and DENV-4 presented increased levels of VEGF, IL-6, and TNF-α in serum but decreased levels of PDGF, while DENV-2 exhibited increased levels of CXCL8, CCL4, and IL-12. Noteworthy was that DENV-2 showed increased levels of IL-12, IL-15, IL-17, IL-4, IL-9, and IL-13, and maintained an unaltered levels of PDGF at younger ages (<1-10 yo and 11-20 yo), whereas in older ages (21-40 yo and 41-75 yo), the results showed increased levels of CCL2, IL-6, and TNF-α, but lower levels of PDGF. In general, DENV infection at younger age groups exhibited more complex network immunoclusters as compared to older age groups. Multivariate analysis revealed a clustering of DENV cases according to age for a set of soluble mediators especially in subjects infected with DENV-2 serotype. Altogether, our findings demonstrate that the profile of circulating soluble mediators differs substantially in acute DENV according to age and DENV serotypes suggesting the participation of serotype-associated immune response, which may represent a potential target for development of therapeutics and could be used to assist medical directive for precise clinical management of severe cases.

Guillain-Barré Syndrome Associated with SARS-CoV-2 Infection in a Pediatric Patient.

We report the case of a 15-year-old male patient presenting frontal headaches with retro-orbital pain accompanied by fever evolving to weakness and pain of the lower limbs, which ascended to upper limbs. A COVID-19 rapid test (IgG and IgM) and nasopharyngeal swab polymerase chain reaction (PCR) was positive for SARS-CoV-2. The blood tests, cerebral spinal fluid (CSF) analysis and CSF aerobic culture revealed no abnormalities. PCR testing of the CSF was negative for the most prevalent etiologies as well as for SARS-CoV-2. Electroneurography study was compatible with the acute motor axonal neuropathy variant of Guillain-Barré syndrome. No cases involving young patients have been presented to date. Therefore, this is the first reported pediatric case of SARS-CoV-2 infection associated with GBS. Evidence reveals that SARS-CoV-2 infection is not limited to the respiratory tract. Neurotropism could explain this important neurologic manifestation of COVID-19 in children.

We report the case of a 15-year-old male patient presenting frontal headaches with retro-orbital pain accompanied by fever evolving to weakness and pain of the lower limbs, which ascended to upper limbs. A COVID-19 rapid test and nasopharyngeal molecular test were positive for the SARS-CoV-2 virus. Neurological examination attested Guillain­Barré syndrome, a condition in which the immune system attacks the nerves and could be triggered by a bacterial or viral infection. The blood tests were normal and cerebral spinal fluid analysis was negative for the most common viruses related to GBS as well as for SARS-CoV-2. Although described in adults, no cases involving young patients have been presented to date. Therefore, this is the first reported case of GBS associated with SARS-CoV-2 in children.

Presence of HPV with overexpression of p16INK4a protein and EBV infection in penile cancer-A series of cases from Brazil Amazon.

BACKGROUND: In Brazil, penile cancer (PC) is not uncommon. The highest incidence of PC is in the North and Northeast of the country. In addition to phimosis, the Human Papillomavirus (HPV) and Epstein-Baar Virus (EBV) infections are also related as risk factors for PC. The overexpression of p16INK4a is a surrogate sensitive marker of HPV infection in PC. OBJECTIVES: To correlate p16INK4a overexpression and HPV infection status with EBV infection in a series of PC patients from the Amazon region. METHODS: Tumor tissues from 47 PC cases were analyzed for the presence of HPV and EBV DNA by PCR. All PC patients were diagnosed between 2013 and 2018 at a public reference cancer center hospital in Manaus, Amazonas-Brazil. HPV was genotyped using E7 HPV16/HPV18 type-specific real-time PCR and the PapilloCheck® HPV-Screening assay. p16INK4a expression was evaluated by immunohistochemistry using the automated Ventana® BenchMark Ultra. RESULTS: The mean age of patients at the time of diagnosis was 57.4 years ±SD 17.8 ranging from 20 to 90 years old. Most of the patients (64%) came from rural areas of the Amazonas State. Thirty patients had phimosis (64%). Among the patients with phimosis, 43% (13/30) underwent circumcision, three during childhood and 10 in adulthood. 60% of the patients were smokers or ex-smokers. HPV infection was observed in 45% (21/47) of cases. HPV16 was detected in 13 patients (61%). Other HPV types detected were HPV 6, 11, 42, 51, 53, 68 and 44/55. EBV infection was observed in 30% (14/47) of the patients with PC. Co-infection with HPV and EBV was observed in 28% (6/21) cases. p16INK4a was only investigated in 26 samples. The p16INK4a overexpression was observed exclusively in HPV 16 positive cases and four HPV negative cases. In the survival analysis, the follow-up time was 35.4 months/patient. The mortality rate during the follow up time was 38%. CONCLUSIONS: p16INK4a positivity presented a high correlation to HPV 16 DNA detection, reinforcing its use as a surrogate marker for HPV-driven cancers. Infection with EBV was quite frequent and its role in epithelial penile oncogenesis needs to be demonstrated.