Desenlaces clínicos de los pacientes con diabetes e hiperglucemia de estrés que presentaron infección por SARS-CoV-2

Introduction. Diabetes and stress hyperglycemia (SH) have been related with poorer clinical outcomes in patients infected by SARS-CoV-2 and at risk for severe disease.Objective. To evaluate clinical outcomes in three groups of patients (with diabetes, without diabetes and stress hyperglycemia [SH]) with SARS-CoV-2 infection.Materials and methods. A retrospective cohort study was conducted in Cali-Colombia. Patients aged ≥18 years with a diagnosis of SARS-CoV-2 infection managed in the emergency room, hospitalization or intensive care unit (ICU) between March 2020 and December 2021 were included. Immunocompromised patients and pregnant women were excluded. Patients were classified in three groups: without diabetes, with diabetes and SH. A comparison between the groups was performed. Results. A total of 945 patients were included (59.6% without diabetes, 27% with diabetes and 13.4% with SH). Fifty-five-point three percent required ICU management, with a higher need in patients with SH (89.8%) and diabetes (67.1%), with no difference between these groups (p=0.249). A higher chance of death was seen in SH vs. without diabetes (adjOR= 8.12, 95% CI 5.12-12.88, p<0.01). Frequency of acute respiratory distress syndrome, need for invasive mechanical ventilation, use of vasopressors and inotropes, the need for de novo renal replacement therapy and mortality was higher in patients with metabolic alterations (diabetes and SH). Conclusions. Diabetes and SH are associated to worse clinical outcomes and mortality in patients with COVID-19. These patients should be identified early and considered as high risk at moment of COVID-19 diagnosis that allow to mitigate adverse outcomes.Introducción. La diabetes y la hiperglucemia de estrés (HE) se han relacionado con peores desenlaces clínicos en pacientes infectados por SARS-CoV-2 y con riesgo de enfermedad grave. Objetivo. Evaluar los resultados clínicos en tres grupos de pacientes (con diabetes, sin diabetes e hiperglucemia de estrés [SH]) con infección por SARS-CoV-2.Materiales y métodos. Se realizó un estudio de cohorte retrospectivo en Cali-Colombia. Se incluyeron pacientes ≥18 años con diagnóstico de infección por SARS-CoV-2 atendidos en urgencias, hospitalización o unidad de cuidados intensivos (UCI) entre marzo de 2020 y diciembre de 2021. Se excluyeron pacientes inmunocomprometidos y mujeres embarazadas. Los pacientes fueron clasificados en tres grupos: sin diabetes, con diabetes e HE. Se realizó una comparación entre los grupos.Resultados. Se incluyeron un total de 945 pacientes (59,6% sin diabetes, 27% con diabetes y 13,4% con HE). El 55,3% requirió manejo en UCI, con mayor necesidad en pacientes con HE (89,8%) y diabetes (67,1%), sin diferencia entre estos grupos (p=0,249). Se observó una mayor probabilidad de muerte en HE vs. sin diabetes (adjOR= 8,12, 95% IC 5,12-12,88, p<0,01). La frecuencia de síndrome de distrés respiratorio agudo, necesidad de ventilación mecánica invasiva, uso de vasopresores e inotrópicos, necesidad de terapia de reemplazo renal de novo y la mortalidad fue mayor en pacientes con alteraciones metabólicas (diabetes e HE).Conclusiones. La diabetes y la HE se asociaron a peores resultados clínicos y mortalidad en pacientes con COVID-19. Estos pacientes deben ser identificados tempranamente y considerados de alto riesgo al momento del diagnóstico de COVID-19 que permitan mitigar los desenlaces adversos

The Synthetic Plasmodium falciparum Circumsporozoite Peptide PfCS102 as a Malaria Vaccine Candidate: A Randomized Controlled Phase I Trial

BACKGROUND: Fully efficient vaccines against malaria pre-erythrocytic stage are still lacking. The objective of this dose/adjuvant-finding study was to evaluate the safety, reactogenicity and immunogenicity of a vaccine candidate based on a peptide spanning the C-terminal region of Plasmodium falciparum circumsporozoite protein (PfCS102) in malaria naive adults. METHODOLOGY AND PRINCIPAL FINDINGS: Thirty-six healthy malaria-naive adults were randomly distributed into three dose blocks (10, 30 and 100 microg) and vaccinated with PfCS102 in combination with either Montanide ISA 720 or GSK proprietary Adjuvant System AS02A at days 0, 60, and 180. Primary end-point (safety and reactogenicity) was based on the frequency of adverse events (AE) and of abnormal biological safety tests; secondary-end point (immunogenicity) on P. falciparum specific cell-mediated immunity and antibody response before and after immunization. The two adjuvant formulations were well tolerated and their safety profile was good. Most AEs were local and, when systemic, involved mainly fatigue and headache. Half the volunteers in AS02A groups experienced severe AEs (mainly erythema). After the third injection, 34 of 35 volunteers developed anti-PfCS102 and anti-sporozoite antibodies, and 28 of 35 demonstrated T-cell proliferative responses and IFN-gamma production. Five of 22 HLA-A2 and HLA-A3 volunteers displayed PfCS102 specific IFN-gamma secreting CD8(+) T cell responses. Responses were only marginally boosted after the 3(rd) vaccination and remained stable for 6 months. For both adjuvants, the dose of 10 microg was less immunogenic in comparison to 30 and 100 microg that induced similar responses. AS02A formulations with 30 microg or 100 microg PfCS102 induced about 10-folds higher antibody and IFN-gamma responses than Montanide formulations. CONCLUSIONS/SIGNIFICANCE: PfCS102 peptide was safe and highly immunogenic, allowing the design of more advanced trials to test its potential for protection. Two or three immunizations with a dose of 30 microg formulated with AS02A appeared the most appropriate choice for such studies. TRIAL REGISTRATION: Swissmedic.ch 2002 DR 1227

Comparison of the diagnostic accuracy of commercial NS1-based diagnostic tests for early dengue infection

<p>Abstract</p> <p>Background</p> <p>We compared the diagnostic accuracy and reproducibility of commercially available NS1-based dengue tests and explored factors influencing their sensitivities.</p> <p>Methods</p> <p>Paired analysis of 310 samples previously characterized as positive (n = 218) and negative (n = 92) for viral isolation and/or RT-PCR and/or IgM seroconversion. Masked samples were tested by two observers with Platelia™ Dengue NS1 Ag, second generation Pan-E™ Dengue Early ELISA, SD Dengue NS1 Ag ELISA, Dengue NS1 Ag STRIP™, and SD BIOLINE™ Dengue Duo (NS1/IgM/IgG).</p> <p>Results</p> <p>SD BIOLINE™ NS1/IgM/IgG had the highest sensitivity (80.7% 95%CI 75-85.7) with likelihood ratios of 7.4 (95%CI 4.1-13.8) and 0.21 (95%CI 0.16-0.28). The ELISA-format tests showed comparable sensitivities; all below 75%. STRIP™ and SD NS1 had even lower sensitivities (<65%). The sensitivities significantly decreased in samples taken after 3 days of fever onset, in secondary infections, viral serotypes 2 and 4, and severe dengue. Adding IgM or IgG to SD NS1 increased its sensitivity in all these situations.</p> <p>Conclusions</p> <p>The simultaneous detection of NS1/IgM/IgG would be potentially useful for dengue diagnosis in both endemic and non endemic areas. A negative result does not rule out dengue. Further studies are required to assess the performance and impact of early laboratory diagnosis of dengue in the routine clinical setting.</p

Plasmodium falciparum CS C-terminal fragment: preclinical evaluation and phase I clinical studies

Preclinical evaluation of synthetic peptides corresponding to the C-terminal regions of the circumsporozoite (CS) protein in various Plasmodia showed that these preparations were immunogenic and safe upon injection in various animal models. Additionally, the corresponding peptide from Plasmodium falciparum was widely recognized by sera and PBL obtained from semi-immune adults living in malaria endemic areas. Moreover, the CS C-terminal peptide derived from P. berghei conferred protection upon challenge with live sporozoites in mice. A GLP preparation of the synthetic peptide corresponding to residues 282-383 of the Pf CS, NF-54 strain is currently evaluated in a open, non-randomized, Phase I human trial. Data obtained after the second antigen injection show that the malaria vaccine Pf CS 282-383 is safe, well tolerated and gives rise to high antibody titre, CD4+ and CD8+ lymphocyte responses

A synthetic malaria vaccine elicits a potent CD8(+) and CD4(+) T lymphocyte immune response in humans. Implications for vaccination strategies

We report the first synthetic peptide vaccine eliciting strong CD8(+) and CD4(+) T lymphocyte responses in humans. The vaccine, representing the C-terminal region of the circumsporozoite protein of Plasmodium falciparum (amino acids 282-383) was well tolerated and strong sporozoite-specific antibodies were elicited. In addition, robust lymphocyte proliferation responses were equally elicited with concomitant in vitro production of IFN-gamma, crucial in the elimination of the parasite. Most importantly, we also observed the development of CD8(+) T lymphocyte responses decisive in the immunity to malaria. The latter finding opens new, possibly safer, avenues for vaccination strategies when a CD8(+) T cell response is needed

Phase I trial of a P.vivax CS protein derived synthetic vaccinecandidate

IP 1106-05-063-97G. Corradin, J.A. Lopez, S. Herrera. -- En: Annals of TropicalMedicine yParasitology. -- Vol. 92, no. 5;(1998) ; p. 539-551. -- Plamodium vivax malaria vaccine development / Myriam Arevalo, Socrates Herrera. -- En:;circumsporozoite protein in individuals naturally exposedto malaria / Myriam Arevalo, Anais Zully Valencia,;Molecular Immunology. -- Vol. 38 (2001) ; p. 443-455. -- Variants of the plasmodium vivax circumsporozoite;protein (VK210 and VK247) in colombian isolates. -- En: MemoriasInst Oswaldo Cruz,Rio de Janeiro. -- Vol. 96,;no. 5 (jul 2001) ; p. 709-712. -- Identification of HLA-A2restricted CD8+T-limphosyte to plasmodium vivax;circumsporozoite protein by immunized Aotus monkeys / Myriam Arevalo, M.A.Roggero, J.M. Gonzalez, J. Vergara,;ARTICULO(S) EN REVISTA: Mapping and comparison of the B-cellepitopes recognized on the plasmodium vivax;Juana Vergara. -- En: Parasity immunology. -- Vol. 24, no.3 (mar 2002) ;p. 161-169

Diversity of the fine specificity displayed by HLA-A*0201-restricted CTL specific for the immunodominant Melan-A/MART-1 antigenic peptide

HLA-A*0201 melanoma patients often develop a CTL response to an immunodominant peptide derived from the melanocyte lineage-specific protein Melan-A/MART-1. We have shown previously that the antigenic peptide most often involved is the decapeptide Melan-A(26-35) (EAAGIGILTV). We also observed some clonal diversity in the fine specificity of Melan-A-specific CTL. To substantiate this observation, we have now tested a series of Melan-A(26-35) variant peptides containing single alanine substitutions for binding to HLA-A*0201 and recognition by polyclonal and monoclonal Melan-A-specific CTL. Substitution of several residues with alanine reduced peptide binding activity by &gt; 10-fold. In contrast, substitution of E26 with alanine (AAAGIGILTV) resulted in a 5-fold higher binding activity as well as in stronger stability of the corresponding HLA-A*0201/peptide complexes. Interestingly, the peptide variant AAAGIGILTV was recognized more efficiently than the natural decapeptide by short term cultured, tumor-infiltrated lymph node cell cultures and a number of Melan-A-specific CTL clones derived from different individuals. Moreover, this analysis revealed that the fine specificity of the CTL response to the Melan-A immunodominant epitope is quite diverse at the clonal level. At least three distinct patterns of fine specificity were identified. This diversity appears to reflect the diversity of the TCR repertoire available for this Ag, since similar results were obtained with a panel of Melan-A-specific CTL clones derived from a single melanoma patient. These findings have important implications for the formulation of Melan-A peptide-based vaccines as well as for the monitoring of Melan-A-specific CTL responses in melanoma patients