SUMMARY The skin is an organ harboring several types of immune cells that participate in innate and adaptive immune responses. The immune system of the skin comprises both skin cells and professional immune cells that together constitute what is designated skin-associated lymphoid tissue (SALT). In this review, I extensively discuss the organization of SALT and the mechanisms involved in its responses to infectious diseases of the skin and mucosa. The nature of these SALT responses, and the cellular mediators involved, often determines the clinical course of such infections. I list and describe the components of innate immunity, such as the roles of the keratinocyte barrier and of inflammatory and natural killer cells. I also examine the mechanisms involved in adaptive immune responses, with emphasis on new cytokine profiles, and the role of cell death phenomena in host-pathogen interactions and control of the immune responses to infectious agents. Finally, I highlight the importance of studying SALT in order to better understand host-pathogen relationships involving the skin and detail future directions in the immunological investigation of this organ, especially in light of recent findings regarding the skin immune system.

The duration and severity of COVID-19 are related to age, comorbidities, and cytokine synthesis. This study evaluated the impact of these factors on patients with clinical presentations of COVID-19 in a Brazilian cohort. A total of 317 patients diagnosed with COVID-19 were included; cases were distributed according to clinical status as severe (n=91), moderate (n=56) and mild (n=170). Of these patients, 92 had acute COVID-19 at sample collection, 90 had already recovered from COVID-19 without sequelae, and 135 had sequelae (long COVID syndrome). In the acute COVID-19 group, patients with the severe form had higher IL-6 levels (p=0.0260). In the post-COVID-19 group, there was no significant difference in cytokine levels between groups with different clinical conditions. In the acute COVID-19 group, younger patients had higher levels of TNF-α, and patients without comorbidities had higher levels of TNF-α, IL-4 and IL-2 (p<0.05). In contrast, patients over age 60 with comorbidities had higher levels of IL-6. In the post-COVID-19 group, subjects with long COVID-19 had higher levels of IL-17 and IL-2 (p<0.05), and subjects without sequelae had higher levels of IL-10, IL-6 and IL- 4 (p<0.05). Our results suggest that advanced age, comorbidities and elevated serum IL-6 levels are associated with severe COVID-19 and are good markers to differentiate severe from mild cases. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 and IL-10 appear to constitute a cytokine profile of long COVID-19, and these markers are potential targets for COVID-19 treatment and prevention strategies.

Lacaziose ou doença de Jorge Lobo é micose crônica, granulomatosa, causada por implantação traumática do fungo Lacazia loboi - patógeno não cultivável até o presente - nos tecidos cutâneo e subcutâneo, manifestando-se clinicamente por lesões nodulares queloidianas predominantes, envolvendo sobretudo pavilhões auriculares, face, membros superiores e inferiores, e não comprometendo as mucosas. A maioria dos casos humanos está registrada em países da América do Sul. Entretanto, a enfermidade apresenta aspectos epidemiológicos destacados, como o aparecimento em tribo Caiabi, no Brasil Central e em mamíferos não humanos, golfinhos de duas espécies (Tursiops truncatus e Sotalia guianensis) capturados na costa da Flórida (EUA), na foz do rio Suriname, na costa de Santa Catarina (Brasil), no golfo de Gasconha (baía de Biscaia-Europa), com manifestações cutâneas e achados histopatológicos muito similares às encontradas no homem. O artigo objetiva abordar características do fungo e sua taxonomia, e aspectos históricos, ecoepidemiológicos, clínicos, imuno-histoquímicos, histopatológicos, ultra-estruturais e terapêuticos.

Although several clinical manifestations of persistent long coronavirus disease (COVID-19) have been documented, their effects on the cardiovascular and autonomic nervous system over the long term remain unclear. Thus, we examined the presence of alterations in cardiac autonomic functioning in individuals with long-term manifestations. The study was conducted from October 2020 to May 2021, and an autonomic assessment was performed to collect heart rate data for the heart rate variability (HRV) analysis. The study participants were divided into the long COVID clinical group, the intragroup, which included patients who were hospitalized, and those who were not hospitalized and were symptomatic for different periods (≤3, >3, ≤6, and >6 months), with and without dyspnoea. The control group, the intergroup, comprised of COVID-free individuals. Our results demonstrated that the long COVID clinical group showed reduced HRV compared with the COVID-19-uninfected control group. Patients aged 23–59 years developed COVID symptoms within 30 days after infection, whose diagnosis was confirmed by serologic or reverse-transcription polymerase chain reaction (swab) tests, were included in the study. A total of 155 patients with long COVID [95 women (61.29%), mean age 43.88 ± 10.88 years and 60 men (38.71%), mean age 43.93 ± 10.11 years] and 94 controls [61 women (64.89%), mean age 40.83 ± 6.31 and 33 men (35.11%), mean age 40.69 ± 6.35 years] were included. The intragroup and intergroup comparisons revealed a reduction in global HRV, increased sympathetic modulation influence, and a decrease in parasympathetic modulation in long COVID. The intragroup showed normal sympathovagal balance, while the intergroup showed reduced sympathovagal balance. Our findings indicate that long COVID leads to sympathetic excitation influence and parasympathetic reduction. The excitation can increase the heart rate and blood pressure and predispose to cardiovascular complications. Short-term HRV analysis showed good reproducibility to verify the cardiac autonomic involvement.

BACKGROUND Non-human primates contribute to the spread of the yellow fever virus (YFV) and the establishment of transmission cycles in endemic areas. OBJECTIVE To describe the severe histopathological aspects of YFV infection, 10 squirrel monkeys were infected with YFV and blood, brain, liver, kidney, spleen, heart, lung, lymph node and stomach were collected at 1-7, 10, 20 and 30 days post-infection (dpi). METHODS Histopathological analysis and detection of the genome and viral antigens and neutralising antibodies were performed by RT-PCR, immunohistochemistry and neutralisation test, respectively. FINDINGS Only one animal died from the experimental infection. The genome and viral antigens were detected in all investigated organs (1-30 dpi) and the neutralising antibodies from seven to 30 dpi. The brain contained perivascular haemorrhage (6 dpi); in the liver, midzonal haemorrhage and lytic necrosis (6 dpi) were observed. The kidney had bleeding in the Bowman’s capsule and tubular necrosis (6 dpi). Pyknotic lymphocytes were observed in the spleen (1-20 dpi), the lung had haemorrhage (2-6 dpi), in the endocardium it contained nuclear pyknosis and necrosis (2-3 dpi) and the stomach contained blood in the lumen (6 dpi). MAIN FINDINGS Squirrel monkeys reliably reproduced the responses observed in human cases of yellow fever and, therefore, constitute an excellent experimental model for studies on the pathophysiology of the disease.

IMPORTANCEDetermining the characteristics, type, and severity of olfactory dysfunction in patients with long COVID is important for the prognosis and potential treatment of the affected population. OBJECTIVE To describe the sociodemographic and clinical features of patients with long COVID who develop persistent olfactory dysfunction. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study, conducted at a rehabilitation center at a public university in the Amazon region of Brazil between September 9, 2020, and October 20, 2021, comprised 219 patients with long COVID and self-reported neurologic symptoms. Of these 219 patients, 139 received a diagnosis of chronic olfactory dysfunction, as confirmed by the Connecticut Chemosensory Clinical Research Center (CCCRC) test. EXPOSURE Clinical diagnosis of long COVID.MAIN OUTCOMES AND MEASURES Electronic case report forms were prepared for the collection of sociodemographic and clinical data. Patients' sense of smell was evaluated via a CCCRC test, and the association of olfactory dysfunction with aspects of daily life was recorded using a questionnaire. RESULTSOf the 219 patients included in the study, 164 (74.9%) were women, 194 (88.6%) were between 18 and 59 years of age (mean [SD] age, 43.2 [12.9] years), 206 (94.1%) had more than 9 years of education, and 115 (52.5%) had a monthly income of up to US $192.00. In the study group, 139 patients (63.5%) had some degree of olfactory dysfunction, whereas 80 patients (36.5%) had normosmia. Patients with olfactory dysfunction had a significantly longer duration of long COVID symptoms than those in the normosmia group (mean [SD], 242.7 [101.9] vs 221.0 [97.5] days; P = .01). Among patients with anosmia, there was a significant association between olfactory dysfunction and daily activities, especially in terms of impairment in hazard detection (21 of 31 patients [67.7%]), personal hygiene (21 of 31 patients [67.7%]), and food intake (21 of 31 patients [67.7%]). Univariable logistic regression analyses found that ageusia symptoms were associated with the occurrence of olfactory dysfunction (odds ratio [OR], 11.14 [95% CI,.07]; P < .001), whereas headache (OR, 0.41 [95% CI, 0.22-0.76]; P < .001) and sleep disorders (OR, 0.48 [95% CI, 0.26-0.92]; P = .02) showed an inverse association with the occurrence of olfactory dysfunction. CONCLUSIONS AND RELEVANCEOlfactory dysfunction is one of the most important long-term neurologic symptoms of COVID-19, with the highest prevalence seen among women, adults, and outpatients. Patients with olfactory dysfunction may experience persistent severe hyposmia or (continued) Key Points Question What are the sociodemographic and clinical characteristics of patients with long COVID and persistent olfactory dysfunction? Findings In this cross-sectional study of 219 patients with long COVID and neurologic symptoms, 64% had olfactory dysfunction, with the highest prevalence among women, adults, and outpatients. Patients with olfactory dysfunction may develop severe olfactory loss (hyposmia or anosm...

Introduction: Dengue is an important mosquito-borne disease in tropical and subtropical regions. Adhesion molecules have not been systematically characterized in the renal tissue of patients with severe dengue (SD). The objective of this study was to detect viral antigens in samples from patients that evolved with SD, correlating with the expression of ICAM-1, VCAM-1, VE-cadherin, and E-selectin to contribute to a better understanding of the pathophysiology of SD. Methods: Kidney specimens from patients with SD were selected according to clinical and laboratorial data and submitted to histological and immunohistochemistry analysis. A semiquantitative evaluation was performed considering positive immunostaining in 20 glomeruli. Results: Viral antigens were mainly detected in distal tubules. The intense immunostaining of VCAM-1 and ICAM-1 was observed. The expression of E-selectin was discrete, and VE-cadherin expression varied from mild to moderate. VCAM-1 was slightly intense in the glomerular capsule; the expression of ICAM-1 was diffuse. E-selectin was diffuse, and VE-cadherin varied from mild to moderate. The most frequent histological findings were glomerular congestion, mild glomerulitis, acute renal injury, and glomerular atrophy. Conclusions: The results appear to demonstrate an imbalance between vascular endothelial permeability regulating events in renal lesions in SD. The increase in the expression of ICAM-1 and VCAM-1 is an in-situ indicator of higher permeability with a consequent influx of cells favoring the inflammation of the endothelium. These molecules are important in the pathophysiology of the disease and provide the possibility of developing new markers for the evaluation, clinical follow-up, and therapeutic response of patients with SD.

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