Studies with strong scientific evidence have demonstrated that comorbidities are associated with fatal outcomes in patients with SARS‐CoV‐2 infection. To aggregate the findings of these studies and assess the magnitude of the effect of different chronic diseases on COVID‐19 mortality, we conducted a systematic review of reviews and meta‐analysis. Six databases were searched to retrieve systematic reviews with meta‐analysis published during the early years of the pandemic. Statistical analysis was performed using Stata v.12.0 software, and the risk ratio (RR) and odds ratio (OR), with a confidence interval of 95% (95% CI), were calculated. We selected 15 publications with 476 original articles and 2,135,888 patients. Our results indicated the following risk factors for COVID‐19 mortality: diabetes mellitus (RR = 1.95; 95% CI:1.41–2.49); hypertension (RR = 1.88; 95% CI:1.51–2.26); cancer (RR = 1.84; 95% CI:1.24–2.43); cardiovascular (RR = 2.14; 95% CI:1.66–2.63), cerebrovascular (RR = 2.43; 95% CI:2.15–2.72), kidney (RR = 2.39; 95% CI:1.36–3.42), pulmonary (RR = 1.98; 95% CI:1.48–2.47) and liver diseases (OR = 1.56; 95% CI:1.18–1.94); obesity (OR = 1.15; 95% CI:1.04–1.26); smoking habits (OR = 1.18; 95% CI:1.13–1.22); and the male sex (OR = 1.69; 95% CI:1.65–1.73). Evidence has confirmed that underlying chronic conditions, which involve an imbalance in the immune response, significantly increase the risk of COVID‐19 deaths.

Background/Objectives: Neglected tropical diseases (NTDs), such as leishmaniasis, remain a global health challenge due to limited therapeutic options and rising drug resistance. In this study, we developed an advanced nanogel formulation incorporating curcumin (CUR) and Pectis brevipedunculata essential oil (EOPb) within an F127/Carbopol 974P matrix to enhance bioavailability and therapeutic efficacy against Leishmania (Leishmania) amazonensis (LLa) promastigotes. Methods: The chemical profile of EOPb was determined through GC-MS and NMR analyses, confirming the presence of key bioactive monoterpenes such as neral, geranial, $\alpha$-pinene, and limonene. The nanogel formulation (nGPC) was optimized to ensure thermosensitivity, and stability, exhibiting a sol–gel transition at physiological temperatures. Rheological analysis revealed that nGPC exhibited Newtonian behavior at 5 °C, transitioning to shear-thinning and thixotropic characteristics at 25 and 32 °C, respectively. This behavior facilitates its application and controlled drug release, making it ideal for topical formulations. Dynamic light scattering (DLS) analysis demonstrated that nGPC maintained a stable nanoscale structure with hydrodynamic radius below 300 nm, while Fourier-transform infrared spectroscopy (FTIR) confirmed strong molecular interactions between EOPb, CUR, and the polymer matrix. Biological assays demonstrated that nGPC significantly enhanced anti-promastigote activity compared to free CUR and OEPb. Results: At the highest tested concentration (50 μg/mL EOPb and 17.5 μg/mL CUR) nGPC induced over 88% mortality in LLa promastigotes across 24, 48, and 72 h, indicating sustained efficacy. Even at lower concentrations, nGPC retained dose-dependent activity, suggesting a synergistic effect between CUR and EOPb. These findings highlight the potential of nGPC as an innovative nanocarrier for daylight photodynamic therapy (dPDT) in the treatment of leishmaniasis. Future studies will investigate the underlying mechanisms of this synergism and explore the potential application of photodynamic therapy (PDT) to further enhance therapeutic outcomes.

Cutaneous leishmaniasis caused by Leishmania amazonensis is a significant public health issue. This study aimed to evaluate an ecofriendly, thermosensitive nanogel, developed using a low-energy, solvent-free method, incorporating F127 and Carbopol 974P copolymers, and enriched with Pectis brevipedunculata essential oil (EOPb) for its leishmanicidal and anti-inflammatory properties. The nanogel was prepared and characterized through FTIR, DLS, SEM, and AFM to confirm the incorporation of EOPb as well as its stability and rheological properties. In vitro leishmanicidal activity was evaluated on Leishmania amazonensis promastigotes, and in vivo anti-inflammatory effects were assessed using a rat paw edema model. In vitro, nGF3 (EOPb-loaded nanogel) demonstrated significant leishmanicidal activity, with promastigote mortality rates exceeding 80% at 24 h and 90% at 48 h. In vivo, nGF1, nGF2, and nGF3 exhibited anti-inflammatory effects, with nGF2 and nGF3 reducing edema by 62.7% at 2 h post-treatment. The empty nanogel (nGF0) showed minimal anti-inflammatory activity. The ecofriendly EOPb-loaded nanogel (nGF3) demonstrated strong leishmanicidal and anti-inflammatory effects, presenting a promising candidate for cutaneous leishmaniasis treatment. Further studies are necessary to explore its clinical potential.

Leishmaniasis is a neglected disease that affects millions of people worldwide, and special attention should be given to treatment because the available drugs have limitations, which can lead to low therapeutic adherence and parasitic resistance. This study evaluated the activity of the bioactive naphthoquinones, lapachol and β-lapachone, against Leishmania amazonensis. The cell alterations were evaluated in vitro on promastigote and amastigote forms. The lethal dose (LD₅₀) at 24, 48, and 72 h on the promastigote's forms using lapachol was 75.60, 72.82, and 58.85 μg/mL and for β-lapachone was 0.65, 1.24, and 0.71 μg/mL, respectively. The naphthoquinones significantly inhibited the survival rate of L. amazonensis amastigotes at 83.11, 57.59, and 34.95% for lapachol (82.28, 41.14, and 20.57 µg/mL), and 78.49, 83.25, and 80.22% for β-lapachone (3.26, 1.63, and 0.815 µg/mL). The compounds on the promastigote's forms led to the loss of mitochondrial membrane potential, induced changes in the integrity of the membrane, caused damage to cells suggestive of the apoptotic process, and showed inhibition of tumor necrosis factor (TNF)-α and interleukin (IL)-6 production. The results showed that these naphthoquinones are promising candidates for research on new drugs with anti-Leishmania activity derived from natural products.

The outcomes of tegumentary leishmaniasis (TL) rely on a complex interaction between the host immune system and the parasite. This study assessed the influence of polymorphisms in immune-related ge...

Neglected tropical diseases (NTDs), such as leishmaniasis, remain a global health challenge due to limited therapeutic options and rising drug resistance. In this study, we developed an advanced nanogel formulation incorporating curcumin (CUR) and Pectis brevipedunculata essential oil (OEPb) within an F127/Carbopol 974P matrix to enhance bioavailability and therapeutic efficacy against Leishmania (Leishmania) amazonensis (LLa) promastigotes. The chemical composition of OEPb was characterized using GC-MS and NMR, confirming the presence of major bioactive monoterpenes, including neral, geranial, α-pinene, and limonene. The nanogel formulation (nGPC) was optimized to ensure thermosensitivity, and stability, exhibiting a sol-gel transition at physiological temperatures. Rheological analysis revealed that nGPC exhibited Newtonian behavior at 5 ∘C, transitioning to shear-thinning and thixotropic characteristics at 25 and 32 ∘C, respectively. This behavior facilitates application and controlled drug release, making it ideal for topical formulations. Dynamic light scattering (DLS) analysis demonstrated that nGPC maintained a stable nanoscale structure with hydrodynamic diameters below 300 nm, while Fourier-transform infrared spectroscopy (FTIR) confirmed strong molecular interactions between OEPb, CUR, and the polymer matrix. Biological assays demonstrated that nGPC significantly enhanced anti-promastigote activity compared to free CUR and OEPb. At the highest tested concentration (17.5 μg/mL OEPb and 50 μg/mL CUR, nGPC induced over 88% mortality in LLa promastigotes across 24, 48, and 72 h, indicating sustained efficacy. Even at lower concentrations, nGPC retained dose-dependent activity, suggesting a synergistic effect between CUR and OEPb. These findings highlight the potential of nGPC as an innovative nanocarrier for leishmaniasis treatment. Future studies will investigate the underlying mechanisms of this synergism and explore the potential application of photodynamic therapy (PDT) to further enhance therapeutic outcomes.