RESUMEN
BACKGROUND: The first case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in Rio Grande do Norte, northeastern Brazil, was diagnosed on March 12, 2020; thereafter, multiple surges of infection occurred, similar to what was seen elsewhere. These surges were mostly due to SARS-CoV-2 mutations leading to emergence of variants of concern (VoC). The introduction of new VoCs in a population previously exposed to SARS-CoV-2 or after vaccination has been a challenge to understanding the kinetics of the protective immune response against this virus. The aim of this study was to investigate the outbreak of SARS-CoV-2 reinfections observed in mid-January 2022 in Rio Grande do Norte state, Brazil. It describes the clinical and genomic characteristics of nine cases of reinfection that occurred coincident with the introduction of the omicron variant. METHODOLOGY/PRINCIPAL FINDINGS: Of a total of 172,965 individuals with upper respiratory symptoms tested for SARS-CoV-2, between March 2020 through mid-February 2022, 58,097 tested positive. Of those, 444 had documented a second SARS-CoV-2 infection and nine reinfection cases were selected for sequencing. Genomic analysis revealed that virus lineages diverged between primary infections and the reinfections, with the latter caused by the Omicron (BA.1) variant among individuals fully vaccinated against SARS-CoV-2. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the Omicron variant is able to evade both natural and vaccine-induced immunity, since all nine cases had prior natural infection and, in addition, were fully vaccinated, emphasizing the need to develop effective blocking vaccines.
Asunto(s)
COVID-19 , Vacunas Virales , Brasil/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Humanos , Reinfección , SARS-CoV-2/genéticaRESUMEN
BACKGROUND: Leprosy is a treatable infectious disease caused by Mycobacterium leprae. However, there is additional morbidity from leprosy-associated pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), which occur in 1 in 3 people with leprosy, even with effective treatment of M. leprae. There is currently no predictive marker in use to indicate which people with leprosy will develop these debilitating immune reactions. Our peripheral blood mononuclear cell (PBMC) transcriptome analysis revealed that activation of the classical complement pathway is common to both RR and ENL. Additionally, differential expression of immunoglobulin receptors and B cell receptors during RR and ENL support a role for the antibody-mediated immune response during both RR and ENL. In this study, we investigated B-cell immunophenotypes, total and M. leprae-specific antibodies, and complement levels in leprosy patients with and without RR or ENL. The objective was to determine the role of these immune mediators in pathogenesis and assess their potential as biomarkers of risk for immune reactions in people with leprosy. METHODOLOGY/FINDINGS: We followed newly diagnosed leprosy cases (n = 96) for two years for development of RR or ENL. They were compared with active RR (n = 35), active ENL (n = 29), and healthy household contacts (n = 14). People with leprosy who subsequently developed ENL had increased IgM, IgG1, and C3d-associated immune complexes with decreased complement 4 (C4) at leprosy diagnosis. People who developed RR also had decreased C4 at leprosy diagnosis. Additionally, elevated anti-M. leprae antibody levels were associated with subsequent RR or ENL. CONCLUSIONS: Differential co-receptor expression and immunoglobulin levels before and during immune reactions intimate a central role for humoral immunity in RR and ENL. Decreased C4 and elevated anti-M. leprae antibodies in people with new diagnosis of leprosy may be risk factors for subsequent development of leprosy immune reactions.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Complemento C3d/análisis , Complemento C4/análisis , Eritema Nudoso/epidemiología , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Lepra Lepromatosa/epidemiología , Mycobacterium leprae/inmunología , Adulto , Anciano , Anticuerpos Antibacterianos/inmunología , Linfocitos B/inmunología , Complemento C3d/inmunología , Complemento C4/inmunología , Eritema Nudoso/sangre , Eritema Nudoso/inmunología , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunidad Activa/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Lepra Lepromatosa/sangre , Lepra Lepromatosa/inmunología , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Type 1 diabetes mellitus (T1DM) and estrogen deficiency are associated with several alterations in bone turnover. Zinc (Zn) is required for growth, development, and overall health. Zinc has been used in complementary therapy against bone loss in several diseases. We hypothesized that Zn supplementation represents a potential therapy against severe bone loss induced by the combined effect of estrogen deficiency and T1DM. We evaluated the protective effect of Zn against bone alterations in a chronic model of these disorders. Female Wistar rats were ramdomized into 3 groups (5 rats each): control, OVX/T1DM (ovariectomized rats with streptozotocin-induced T1DM), and OVX/T1DM+Zn (OVX/T1DM plus daily Zn supplementation). Serum biochemical, bone histomorphometric, and molecular analyses were performed. Histomorphometric parameters were similar between the control and OVX/T1DM+Zn groups, suggesting that Zn prevents bone architecture alterations. In contrast, the OVX/T1DM group showed significantly lower trabecular width and bone area as well as greater trabecular separation than the control. The OVX/T1DM and OVX/T1DM+Zn groups had significantly higher serum alkaline phosphatase activity than the control. The supplemented group had higher levels of serum-ionized calcium and phosphorus than the nonsupplemented group. The RANKL/OPG ratio was similar between the control and OVX/T1DM+Zn groups, whereas it was higher in the OVX/T1DM group. In conclusion, Zn supplementation prevents bone alteration in chronic OVX/T1DM rats, as demonstrated by the reduced RANKL/OPG ratio and preservation of bone architecture. The findings may represent a novel therapeutic approach to preventing OVX/T1DM-induced bone alterations.
Asunto(s)
Densidad Ósea/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Suplementos Dietéticos , Osteoprotegerina/metabolismo , Ligando RANK/metabolismo , Zinc/administración & dosificación , Fosfatasa Alcalina/sangre , Animales , Glucemia/metabolismo , Huesos/efectos de los fármacos , Calcio/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Femenino , Osteoprotegerina/genética , Ovariectomía , Fósforo/sangre , Ligando RANK/genética , Ratas , Ratas WistarRESUMEN
Type 1 diabetes mellitus (T1DM) and estrogen deficiency are associated with several alterations in bone turnover. Zinc (Zn) is required for growth, development, and overall health. Zinc has been used in complementary therapy against bone loss in several diseases. We hypothesized that Zn supplementation represents a potential therapy against severe bone loss induced by the combined effect of estrogen deficiency and T1DM. We evaluated the protective effect of Zn against bone alterations in a chronic model of these disorders. Female Wistar rats were ramdomized into 3 groups (5 rats each): control, OVX/T1DM (ovariectomized rats with streptozotocin-induced T1DM), and OVX/T1DM+Zn (OVX/T1DM plus daily Zn supplementation). Serum biochemical, bone histomorphometric, and molecular analyses were performed. Histomorphometric parameters were similar between the control and OVX/T1DM+Zn groups, suggesting that Zn prevents bone architecture alterations. In contrast, the OVX/T1DM group showed significantly lower trabecular width and bone area as well as greater trabecular separation than the control...