Lucas Sousa Magalhães

Chikungunya virus (CHIKV) poses an enduring public health threat in endemic regions and can progress from acute febrile illness to chronic, disabling rheumatologic disease. We performed an unmatched case–control study of 20 patients sampled during the acute phase (< 14 days) and 20 recruited ≥ 90 days after onset who met criteria for chronic chikungunya disease (CCD). At enrolment we quantified 45 serum cytokines/chemokines by multiplex assay; clinical data were recorded for all, and chronic cases were re-evaluated at 3, 12 and 24 months. CCD participants were older, reported greater initial pain and more often received symptomatic corticosteroids. Acute CHIKV infection showed a focused antiviral signature characterized by higher CCL2, CXCL10, IFN-α and IL-1RA, whereas CCD displayed a broader, non-resolving profile enriched for IL-21, GM-CSF, IL-23, LT-α, IL-4, IL-9, IL-31 and FGF-2. Over follow-up, many CCD cases improved; however, in time-to-discharge analyses, higher IL-23, baseline rheumatoid arthritis, and higher VAS were associated with persistence, whereas higher FGF-2 and IL-4, arthrosis, and anti-CHIKV IgG were associated with earlier resolution. Acute and chronic chikungunya exhibit distinct soluble-mediator signatures. A targeted early antiviral response aligns with recovery, while a broad Th2/Th17-skewed milieu aligns with chronicity. IL-23, for risk, and FGF-2/IL-4, for resolution, emerge as candidate biomarkers for risk stratification and therapeutic trials, alongside clinical factors.

Recurrent COVID-19, defined as two or more distinct episodes, may reflect an impaired immune response to SARS-CoV-2. In this case–control study, we compared three groups: individuals with recurrent COVID-19, those with a single episode, and SARS-CoV-2-naïve controls. We genotyped six immune-related SNPs, including TLR7 rs179008, and measured CD4⁺ and CD8⁺ T cell responses to SARS-CoV-2 antigens using flow cytometry. The T allele of TLR7 rs179008, previously linked to reduced receptor expression, was significantly overrepresented in the recurrent COVID-19 cohort. At baseline, frequencies of IFN-γ⁺, IL-2⁺, and TNF-α⁺ cells among CD4⁺ and CD8⁺ T cells did not differ between groups. However, stratification by the rs179008 genotype revealed that T allele carriers displayed diminished IFN-γ production in both CD4⁺ and CD8⁺ T cells and reduced IL-2 production in CD4⁺ T cells. Following vaccination, T cell responses were comparable across all genotypes. The T allele of TLR7 rs179008 is associated with recurrent COVID-19 and may contribute to impaired T cell-mediated immunity. Further studies are warranted to elucidate the mechanistic role of TLR7 variation in SARS-CoV-2 reinfection risk.

Background: Leprosy remains a significant public health challenge despite diagnostic advances. Methods: This cross-sectional study evaluated the social and clinical characteristics of 302 patients treated at a reference outpatient clinic in northeastern Brazil (2010–2019). Results: Men more frequently presented with multibacillary disease and disabilities than women. These clinical characteristics in men were associated with higher rates of alcohol consumption and hunting. No evidence was found for an association between diagnostic delays and disease severity. Conclusions: This study underscores that social determinants may contribute to worse disease outcomes in men, highlighting the need for targeted policies.

Highlights ■ SARS-CoV-2 infection leads to mild-to-moderate disease in children with cystic fibrosis. ■ No worsening of cystic fibrosis was observed months after infection. ABSTRACT Objective: This study aimed to evaluate the clinical manifestations of SARS-CoV-2 in children and adolescents with cystic fibrosis. Methods: This was a case-control analysis of clinical variables and pulmonary function test results in 43 children with cystic fibrosis, 17 (39.5%) of whom tested positive for SARS-CoV-2. Results: The infected children exhibited a higher frequency of

Chikungunya (CHIKV) and Zika (ZIKV) viruses, both mosquito-borne, often circulate simultaneously, raising concerns about the effects of coinfection. This study evaluated cytokines, chemokines, and growth factors in 12 patients with concurrent CHIKV and ZIKV infections confirmed by RT-qPCR. Clinical data and 45 immune mediators were analyzed. Coinfected and monoinfected patients exhibited similar symptoms, although ZIKV-infected individuals experienced fewer instances of fever. No patients had persistent symptoms or required hospitalization. Chemokines CCL5, CXCL1, and CXCL10 were elevated across all groups. CHIKV-infected patients showed higher levels of CCL2, CCL4, EGF, CXCL12, and IFN-α compared to controls, while IL-1RA, IL-8, and IFN-γ were elevated in both CHIKV and coinfected groups. SCF was elevated only in the ZIKV group. Overall, CHIKV and ZIKV coinfection presented mild clinical symptoms similar to monoinfections and demonstrated a moderate inflammatory response.

: This report documents the first known cases of lepromatous leprosy in patients with chronic mucocutaneous candidiasis (CMC) linked to a gain-of-function mutation in the STAT1 gene. Two related patients, a mother and daughter, who both suffer from CMC and lepromatous leprosy, carry a heterozygous STAT1 mutation (c.821G>A; p.R274Q). Both individuals exhibited similarly high levels of total and phosphorylated STAT1 in CD4⁺ T cells and decreased interleukin 17A transcripts. This mutation underscores a complex relationship between genetic susceptibility to infections and the necessity to evaluate each case individually.

Arthritogenic alphaviruses are positive-strand RNA viruses that cause debilitating musculoskeletal diseases affecting millions worldwide. A recent discovery identified the four-and-a-half-LIM domain protein 1 splice variant A (FHL1A) as a crucial host factor interacting with the hypervariable domain (HVD) of chikungunya virus (CHIKV) nonstructural protein 3 (nsP3). Here, we show that acute and chronic chikungunya disease in humans correlates with elevated levels of FHL1. We generated FHL1^−/− mice, which when infected with CHIKV or o’nyong-nyong virus (ONNV) displayed reduced arthritis and myositis, fewer immune infiltrates, and reduced proinflammatory cytokine/chemokine outputs, compared to infected wild-type (WT) mice. Interestingly, disease signs were comparable in FHL1^−/− and WT mice infected with arthritogenic alphaviruses Ross River virus (RRV) or Mayaro virus (MAYV). This aligns with pull-down assay data, which showed the ability of CHIKV and ONNV nsP3 to interact with FHL1, while RRV and MAYV nsP3s did not. We engineered a CHIKV mutant unable to bind FHL1 (CHIKV-ΔFHL1), which was avirulent in vivo. Following inoculation with CHIKV-ΔFHL1, mice were protected from disease upon challenge with CHIKV and ONNV, and viraemia was significantly reduced in RRV- and MAYV-challenged mice. Targeting FHL1-binding as an approach to vaccine design could lead to breakthroughs in mitigating alphaviral disease.

Obesity alters the capacity of effective immune responses in infections. To further address this phenomenon in the context of COVID-19, this study investigated how the immunophenotype of leukocytes was altered in individuals with obesity in severe COVID-19. This cross-sectional study enrolled 27 ICU COVID-19 patients (67% women, 56.33 ± 19.55 years) that were assigned to obese (BMI ≥ 30 kg/m², n = 9) or non-obese (BMI < 30kg/m², n = 18) groups. Monocytes, NK, and both Low-Density (LD) and High-Density (HD) neutrophils were isolated from peripheral blood samples, and surface receptors’ frequency and expression patterns were analyzed by flow cytometry. Clinical status and biochemical data were additionally evaluated. The frequency of monocytes was negatively correlated with BMI, while NK cells and HD neutrophils were positively associated (p < 0.05). Patients with obesity showed a significant reduction of monocytes, and these cells expressed high levels of PD-L1 (p < 0.05). A higher frequency of NK cells and increased expression of TREM-1+ on HD neutrophils were detected in obese patients (p < 0.05). The expression of receptors related to antigen-presentation, phagocytosis, chemotaxis, inflammation and suppression were strongly correlated with clinical markers only in obese patients (p < 0.05). Collectively, these outcomes revealed that obesity differentially affected, and largely depressed, innate immune response in severe COVID-19.

COVID-19 is caused by SARS-CoV-2 infection and leads from asymptomatic to severe outcomes. The recurrence of the COVID-19 has been described, however, mechanisms involved remains unclear. Thus, the work aimed to investigate the role of multifunctional T cells in patients with recurrent COVID-19. We evaluated clinical characteristics, presence of anti-S1 and anti-Nucleocapsid IgG in patients’ sera, and multifunctional T cells (for IFN-γ, IL-2, and TNF-α) in patients with multiple episodes of COVID-19 and controls. Data demonstrate that patients with recurrent COVID-19 have a T cell pattern predominantly related to IFN-γ production. Also, patients with COVID-19 history and absence of anti-S1 IgG had lower levels of CD4+ IFN + IL-2 + TNF + T cells independently of number of disease episodes. Complementary, vaccination changed the patterns of T cells phenotypes and induced IgG seroconversion, despite not induce higher levels of multifunctional T cells in all patients. In conclusion, the data suggest that recurrent disease is related to early-disease T cell profile and absence of anti-S1 IgG is related to lower multifunctional CD4 T cell response, what suggests possibility of new episodes of COVID-19 in these patients.