RESUMO
SARS-CoV-2 Omicron lineages continue to emerge and evolve into new sublineages, causing infection waves throughout 2022 and 2023, which has been attributed to immune escape. We examined neutralizing antibody responses to the recently emerged SARS-CoV-2 JN.1 variant in comparison to ancestral D614G and Omicron BA.1, BA.2, BA.5, and XBB.1.5 variants. We tested 79 human sera from cohorts with different combinations of vaccinations and infections, including 23 individuals who had been repeatedly exposed to Omicron. Individuals with a monovalent XBB.1.5 vaccine booster or XBB.1.5 breakthrough infection had robust antibody levels against all variants tested; however, JN.1 evaded antibodies in individuals after single Omicron BA.1, BA.2 or BA.5 breakthrough infections. Moreover, in the non-vaccinated cohort, serum antibodies demonstrated almost no cross-neutralization activities against D614G, XBB.1.5 and JN.1. after infections with earlier Omicron variants. These findings show that SARS-CoV-2-immunity is heterogeneous, depending on different combinations of vaccinations and infections, and emphasize the importance of considering different immune-backgrounds when evaluating novel variants.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , SARS-CoV-2 , Humanos , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , Anticorpos Antivirais/sangue , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Vacinação , Testes de Neutralização , IdosoRESUMO
Primary infection with the Omicron variant of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) can be serologically identified with distinct profiles of neutralizing antibodies (nAbs), as indicated by high titers against the Omicron variant and low titers against the ancestral wild-type (WT). Here, we evaluated whether a novel surrogate virus neutralization assay (sVNT) that simultaneously quantifies the binding inhibition of angiotensin-converting enzyme 2 (ACE2) to the proteins of the WT- and Omicron-specific receptor-binding domains (RBDs) can identify nAb profiles after primary Omicron infection with accuracy similar to that of variant-specific live-virus neutralization tests (NTs). Therefore, we comparatively tested 205 samples from individuals after primary infection with the Omicron variant and the WT, and vaccinated subjects with or without Omicron breakthrough infections. Indeed, variant-specific RBD-ACE2 binding inhibition levels significantly correlated with respective NT titers (p < 0.0001, Spearman's r = 0.92 and r = 0.80 for WT and Omicron, respectively). In addition, samples from individuals after primary Omicron infection were securely identified with the sVNT according to their distinctive nAb profiles (area under the curve = 0.99; sensitivity: 97.2%; specificity: 97.84%). Thus, when laborious live-virus NTs are not feasible, the novel sVNT we evaluated in this study may serve as an acceptable substitute for the serological identification of individuals with primary Omicron infection.
RESUMO
The SARS-CoV-2 Omicron variant is characterized by substantial changes in the antigenic structure of the Spike (S) protein. Therefore, antibodies induced by primary Omicron infection lack neutralizing activity against earlier variants. In this study, we analyzed whether these antigenic changes impact the sensitivity of commercial anti-SARS-CoV-2 antibody assays. Sera from 37 unvaccinated, convalescent individuals after putative primary Omicron infection were tested with a panel of 20 commercial anti-SARS-CoV-2 immunoassays. As controls, we used samples from 43 individuals after primary infection with the SARS-CoV-2 ancestral wild-type strain. In addition, variant-specific live-virus neutralization assays were used as a reference for the presence of SARS-CoV-2-specific antibodies in the samples. Notably, in Omicron convalescents, there was a statistically significant reduction in the sensitivity of all antibody assays containing S or its receptor-binding-domain (RBD) as antigens. Furthermore, antibody levels quantified by these assays displayed a weaker correlation with Omicron-specific neutralizing antibody titers than with those against the wild type. In contrast, the sensitivity of nucleocapsid-protein-specific immunoassays was similar in wild-type and Omicron-infected subjects. In summary, the antigenic changes in the Omicron S lead to reduced immunoreactivity in the current commercial S- and RBD-specific antibody assays, impairing their diagnostic performance. IMPORTANCE This study demonstrates that the antigenic changes of the SARS-CoV-2 Omicron variant affect test results from commercial Spike- and RBD-specific antibody assays, significantly diminishing their sensitivities and diagnostic abilities to assess neutralizing antibodies.
Assuntos
COVID-19 , Glicoproteína da Espícula de Coronavírus , Humanos , Testes de Neutralização , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/metabolismo , SARS-CoV-2 , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/metabolismo , COVID-19/diagnóstico , Anticorpos Antivirais , Anticorpos NeutralizantesRESUMO
Background and Methods: The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Omicron (B.1.1.529) variant is the antigenically most distinct variant to date. As the heavily mutated spike protein enables neutralization escape, we studied serum-neutralizing activities of naïve and vaccinated individuals after Omicron BA.1 or BA.2 sub-lineage infections in live virus neutralization tests with Omicron BA.1, Omicron BA.2, wildtype (WT, B1.1), and Delta (B.1.617.2) strains. Serum samples obtained after WT infections and three-dose mRNA vaccinations with and without prior infection were included as controls. Results: Primary BA.1 infections yielded reduced neutralizing antibody levels against WT, Delta, and Omicron BA.2, while samples from BA.2-infected individuals showed almost no cross-neutralization against the other variants. Serum neutralization of Omicron BA.1 and BA.2 variants was detectable after three-dose mRNA vaccinations, but with reduced titers. Vaccination-breakthrough infections with either Omicron BA.1 or BA.2, however, generated equal cross-neutralizing antibody levels against all SARS-CoV-2 variants tested. Conclusions: Our study demonstrates that although Omicron variants are able to enhance cross-neutralizing antibody levels in pre-immune individuals, primary infections with BA.1 or BA.2 induced mostly variant-specific neutralizing antibodies, emphasizing the differently shaped humoral immunity induced by the two Omicron variants. These data thus contribute substantially to the understanding of antibody responses induced by primary Omicron infections or multiple exposures to different SARS-CoV-2 variants and are of particular importance for developing vaccination strategies in the light of future emerging variants.
Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Anticorpos Amplamente Neutralizantes , Humanos , Glicoproteínas de Membrana , Testes de Neutralização , RNA Mensageiro , Glicoproteína da Espícula de Coronavírus/genética , Proteínas do Envelope ViralRESUMO
The treatment of dyspnoea is a considerable challenge in palliative care. Respiratory problems, besides pain, belong to the most common symptoms of terminally ill patients. Invasiveness of diagnostic measures and treatment options demand a critical evaluation of the patient's burden and the expected relief by the therapy. On the basis of a case study of a lung cancer patient, the complexity of different causes of dyspnoea will be discussed. Special consideration will be taken to the psychosocial dimension of dyspnoea.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/psicologia , Dispneia/psicologia , Neoplasias Pulmonares/psicologia , Cuidados Paliativos/psicologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia Combinada , Diagnóstico Diferencial , Progressão da Doença , Dispneia/etiologia , Dispneia/terapia , Feminino , Humanos , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Cuidados Paliativos/métodos , Qualidade de Vida/psicologia , Assistência Terminal/métodos , Assistência Terminal/psicologiaRESUMO
INTRODUCTION: Although several cases of i.v. injection of metallic mercury have been reported, it still remains an uncommon event. CASE REPORT: A 34-year-old male came to hospital because complaining of pleuritic chest pain. X-ray showed radio dense punctate lesions in both lung fields, as well as around both elbows. Mercury concentration in blood (140 microg/L) and urine (320 microg/L) from the patient were significantly elevated, compared with the reference concentrations of < or = 2.0 mug/L mercury in blood and urine. The course of renal elimination of mercury and the mercury concentration in whole blood during 5 months of chelation therapy with sodium 2,3-dimercapto-1-propanesulfonate (Dimaval) were monitored. Furthermore, the time-course of mercury in scalp hair from the patient was determined. CONCLUSION: We report a case of probable consecutive i.v. administration of metallic mercury.
Assuntos
Antídotos/uso terapêutico , Quelantes/uso terapêutico , Intoxicação por Mercúrio , Mercúrio/administração & dosagem , Unitiol/uso terapêutico , Adulto , Dor no Peito/etiologia , Cotovelo , Cabelo/metabolismo , Humanos , Injeções Intravenosas , Pulmão/metabolismo , Masculino , Mercúrio/farmacocinética , Mercúrio/toxicidade , Distribuição Tecidual , Raios XRESUMO
Therapy and the handling of dyspnea in the last period of one's life is described and discussed from a case report. A patient with lung cancer and a distinct chronic obstructive pulmonary disease is presented. His coping with increasing dyspnea and the therapeutic strategies are described. Problems with the side effects of therapy and coping strategies are dealt with, too.